start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=23 article-no= start-page=3460 end-page=3464 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Remarkable Efficacy of Capmatinib in a Patient with Cancer of Unknown Primary with MET Amplification en-subtitle= kn-subtitle= en-abstract= kn-abstract=This case report describes a 70-year-old female with cancer of unknown primary origin (CUP) who exhibited multiple distant lymph node metastases. Despite conventional chemotherapy (carboplatin and paclitaxel) and immunotherapy (nivolumab), disease progression was noted. Genomic profiling revealed MET amplification, leading to the administration of capmatinib, a selective MET tyrosine kinase inhibitor. The patient experienced substantial tumor reduction with dose adjustments due to adverse effects, indicating the potential efficacy of capmatinib in treating CUP with MET amplification. en-copyright= kn-copyright= en-aut-name=TanakaTakaaki en-aut-sei=Tanaka en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SumiiRyohei en-aut-sei=Sumii en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AndoYayoi en-aut-sei=Ando en-aut-mei=Yayoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Internal Medicine, NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Clinical Research Support Office, National Cancer Center Hospital kn-affil= affil-num=6 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= en-keyword=MET amplification kn-keyword=MET amplification en-keyword=capmatinib kn-keyword=capmatinib en-keyword=MET inhibitors kn-keyword=MET inhibitors en-keyword=cancer of unknown primary kn-keyword=cancer of unknown primary en-keyword=MET exon 14 skipping kn-keyword=MET exon 14 skipping END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=23 article-no= start-page=3413 end-page=3418 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Prompt Diagnosis of Ascites and Dramatic Effect of Alectinib for Advanced Lung Adenocarcinoma Harboring EML4-ALK Fusion en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 75-year-old never-smoker woman presented with dyspnea and loss of appetite. A mass was identified in the left upper lobe of the lung, and the patient was referred to our hospital. Despite the diagnosis of lung adenocarcinoma via bronchoscopy, anaplastic lymphoma kinase (ALK) immunostaining was negative. Rapid weight gain and abdominal distension caused by ascites prompted fluid testing using the AmoyDx® Pan Lung Cancer PCR Panel. EML4-ALK fusion was confirmed, and alectinib therapy was initiated immediately. The tumor size had decreased significantly, and the patient was discharged on day 34. This case highlights the necessity of multiplex genetic testing even when ALK immunostaining is negative. en-copyright= kn-copyright= en-aut-name=BabaTakahiro en-aut-sei=Baba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuokaHiromi en-aut-sei=Matsuoka en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KyakunoMio en-aut-sei=Kyakuno en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshinagaYusuke en-aut-sei=Yoshinaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakeguchiTetsuya en-aut-sei=Takeguchi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraMiho en-aut-sei=Fujiwara en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamadaKotaro en-aut-sei=Yamada en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraEri en-aut-sei=Nakamura en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiMasanori en-aut-sei=Fujii en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Medical Support, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Medical Support, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Geriatric Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=lung adenocarcinoma kn-keyword=lung adenocarcinoma en-keyword=EML4-ALK kn-keyword=EML4-ALK en-keyword=AmoyDxⓇ Pan Lung Cancer PCR Panel kn-keyword=AmoyDxⓇ Pan Lung Cancer PCR Panel en-keyword=alectinib kn-keyword=alectinib END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=JCO-24-02835 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non–Small Cell Lung Cancer: Results From CHRYSALIS-2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose For patients with advanced non–small cell lung cancer (NSCLC) harboring atypical epidermal growth factor receptor (EGFR) mutations (eg, S768I, L861Q, G719X), efficacy of current treatment options is limited.
Patients and Methods CHRYSALIS-2 Cohort C enrolled participants with NSCLC harboring atypical EGFR mutations (G719X, S768I, L861Q, etc) and ≤2 previous lines of therapy. Participants were treatment-naïve or previously received first- or second-generation EGFR tyrosine kinase inhibitors. Coexisting exon 20 insertions, exon 19 deletions, or exon 21 L858R mutations were exclusionary. Participants received 1,050 mg (1,400 mg if ≥80 kg) intravenous amivantamab once weekly for the first 4 weeks and then once every 2 weeks plus 240 mg oral lazertinib once daily. The primary end point was investigator-assessed objective response rate (ORR).
Results As of January 12, 2024, 105 participants received amivantamab-lazertinib. Most common atypical mutations were G719X (56%), L861X (26%), and S768I (23%), including single and compound mutations. In the overall population (median follow-up: 16.1 months), the ORR was 52% (95% CI, 42 to 62). The median duration of response (mDoR) was 14.1 months (95% CI, 9.5 to 26.2). The median progression-free survival (mPFS) was 11.1 months (95% CI, 7.8 to 17.8); median overall survival (mOS) was not estimable (NE; 95% CI, 22.8 to NE). Adverse events were consistent with previous studies and primarily grade 1 and 2. Among treatment-naïve participants, the ORR was 57% (95% CI, 42 to 71). The mPFS was 19.5 months (95% CI, 11.2 to NE), the mDoR was 20.7 months (95% CI, 9.9 to NE), and mOS was NE (95% CI, 26.3 to NE). Solitary or compound EGFR mutations had no major impact on ORR. The ORR in participants with P-loop and αC-helix compressing, classical-like, and T790M-like mutations was 45% (n = 38), 64% (n = 14), and 67% (n = 3), respectively.
Conclusion In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals. en-copyright= kn-copyright= en-aut-name=TomasiniPascale en-aut-sei=Tomasini en-aut-mei=Pascale kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangYongsheng en-aut-sei=Wang en-aut-mei=Yongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiYongsheng en-aut-sei=Li en-aut-mei=Yongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WuLin en-aut-sei=Wu en-aut-mei=Lin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CuiJiuwei en-aut-sei=Cui en-aut-mei=Jiuwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BesseBenjamin en-aut-sei=Besse en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SpiraAlexander I. en-aut-sei=Spira en-aut-mei=Alexander I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NealJoel W. en-aut-sei=Neal en-aut-mei=Joel W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GotoKoichi en-aut-sei=Goto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BaikChristina S. en-aut-sei=Baik en-aut-mei=Christina S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MarmarelisMelina E. en-aut-sei=Marmarelis en-aut-mei=Melina E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ZhangYiping en-aut-sei=Zhang en-aut-mei=Yiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=LeeJong-Seok en-aut-sei=Lee en-aut-mei=Jong-Seok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=LeeSe-Hoon en-aut-sei=Lee en-aut-mei=Se-Hoon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YangJames Chih-Hsin en-aut-sei=Yang en-aut-mei=James Chih-Hsin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MichelsSebastian en-aut-sei=Michels en-aut-mei=Sebastian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AnastasiouZacharias en-aut-sei=Anastasiou en-aut-mei=Zacharias kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=CurtinJoshua C. en-aut-sei=Curtin en-aut-mei=Joshua C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=LyuXuesong en-aut-sei=Lyu en-aut-mei=Xuesong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MahoneyJanine en-aut-sei=Mahoney en-aut-mei=Janine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=DemirdjianLevon en-aut-sei=Demirdjian en-aut-mei=Levon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MeyerCraig S. en-aut-sei=Meyer en-aut-mei=Craig S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ZhangYouyi en-aut-sei=Zhang en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=LeconteIsabelle en-aut-sei=Leconte en-aut-mei=Isabelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=LorenziniPatricia en-aut-sei=Lorenzini en-aut-mei=Patricia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KnoblauchRoland E. en-aut-sei=Knoblauch en-aut-mei=Roland E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=TraniLeonardo en-aut-sei=Trani en-aut-mei=Leonardo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=BaigMahadi en-aut-sei=Baig en-aut-mei=Mahadi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=BaumlJoshua M. en-aut-sei=Bauml en-aut-mei=Joshua M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=ChoByoung Chul en-aut-sei=Cho en-aut-mei=Byoung Chul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Aix Marseille University - CNRS, INSERM, CRCM; CEPCM - AP-HM Hôpital de La Timone kn-affil= affil-num=2 en-affil=Division of Thoracic Tumor Multimodality Treatment, Cancer Center and Clinical Trial Center, West China Hospital, Sichuan University kn-affil= affil-num=3 en-affil=Chongqing University Cancer Hospital kn-affil= affil-num=4 en-affil=Medical Oncology Service, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona kn-affil= affil-num=5 en-affil=Department of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University kn-affil= affil-num=6 en-affil=The First Hospital of Jilin University kn-affil= affil-num=7 en-affil=Paris-Saclay University, Institut Gustave Roussy kn-affil= affil-num=8 en-affil=Virginia Cancer Specialists kn-affil= affil-num=9 en-affil=Stanford Cancer Institute, Stanford University kn-affil= affil-num=10 en-affil=National Cancer Center Hospital East kn-affil= affil-num=11 en-affil=University of Washington Fred Hutchinson Cancer Research Center kn-affil= affil-num=12 en-affil=Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Zhejiang Cancer Hospital kn-affil= affil-num=15 en-affil=Seoul National University College of Medicine and Seoul National University Hospital kn-affil= affil-num=16 en-affil=Samsung Medical Center, Sungkyunkwan University School of Medicine kn-affil= affil-num=17 en-affil=National Taiwan University Cancer Center kn-affil= affil-num=18 en-affil=Department I for Internal Medicine, Faculty of Medicine and University Hospital Cologne, Lung Cancer Group Cologne, Center for Integrated Oncology Aachen Köln Bonn Düsseldorf, University of Cologne kn-affil= affil-num=19 en-affil=Johnson & Johnson kn-affil= affil-num=20 en-affil=Johnson & Johnson kn-affil= affil-num=21 en-affil=Johnson & Johnson kn-affil= affil-num=22 en-affil=Johnson & Johnson kn-affil= affil-num=23 en-affil=Johnson & Johnson kn-affil= affil-num=24 en-affil=Johnson & Johnson kn-affil= affil-num=25 en-affil=Johnson & Johnson kn-affil= affil-num=26 en-affil=Johnson & Johnson kn-affil= affil-num=27 en-affil=Johnson & Johnson kn-affil= affil-num=28 en-affil=Johnson & Johnson kn-affil= affil-num=29 en-affil=Johnson & Johnson kn-affil= affil-num=30 en-affil=Johnson & Johnson kn-affil= affil-num=31 en-affil=Johnson & Johnson kn-affil= affil-num=32 en-affil=Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=5 article-no= start-page=651 end-page=664 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amivantamab Plus Lazertinib in Patients With EGFR-Mutant NSCLC After Progression on Osimertinib and Platinum-Based Chemotherapy: Results From CHRYSALIS-2 Cohort A en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Treatment options for patients with EGFR-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy are limited.
Methods: CHRYSALIS-2 cohort A evaluated amivantamab plus lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy. Primary end point was investigator-assessed objective response rate (ORR). The patients received 1050 mg of intravenous amivantamab (1400 mg if ≥ 80 kg) plus 240 mg of oral lazertinib.
Results: In cohort A (N = 162), the investigator-assessed ORR was 28% (95% confidence interval [CI]: 22–36). The blinded independent central review–assessed ORR was 35% (95% CI: 27–42), with a median duration of response of 8.3 months (95% CI: 6.7–10.9) and a clinical benefit rate of 58% (95% CI: 50–66). At a median follow-up of 12 months, 32 of 56 responders (57%) achieved a duration of response of more than or equal to 6 months. Median progression-free survival by blinded independent central review was 4.5 months (95% CI: 4.1–5.8); median overall survival was 14.8 months (95% CI: 12.2–18.0). Preliminary evidence of central nervous system antitumor activity was reported in seven patients with baseline brain lesions and no previous brain radiation or surgery. Exploratory biomarker analyses using next-generation sequencing of circulating tumor DNA revealed responses in patients with and without EGFR- or MET-dependent resistance. The most frequent adverse events were rash (grouped term; 81%), infusion-related reaction (68%), and paronychia (52%). The most common grade greater than or equal to 3 treatment-related adverse events were rash (grouped term; 10%), infusion-related reaction (9%), and hypoalbuminemia (6%).
Conclusions: For patients with limited treatment options, amivantamab plus lazertinib demonstrated an antitumor activity with a safety profile characterized by EGFR- or MET-related adverse events, which were generally manageable. en-copyright= kn-copyright= en-aut-name=BesseBenjamin en-aut-sei=Besse en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GotoKoichi en-aut-sei=Goto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangYongsheng en-aut-sei=Wang en-aut-mei=Yongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LeeSe-Hoon en-aut-sei=Lee en-aut-mei=Se-Hoon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MarmarelisMelina E. en-aut-sei=Marmarelis en-aut-mei=Melina E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OheYuichiro en-aut-sei=Ohe en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Bernabe CaroReyes en-aut-sei=Bernabe Caro en-aut-mei=Reyes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KimDong-Wan en-aut-sei=Kim en-aut-mei=Dong-Wan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LeeJong-Seok en-aut-sei=Lee en-aut-mei=Jong-Seok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CousinSophie en-aut-sei=Cousin en-aut-mei=Sophie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=LiYongsheng en-aut-sei=Li en-aut-mei=Yongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Paz-AresLuis en-aut-sei=Paz-Ares en-aut-mei=Luis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OnoAkira en-aut-sei=Ono en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SanbornRachel E. en-aut-sei=Sanborn en-aut-mei=Rachel E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=WatanabeNaohiro en-aut-sei=Watanabe en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=de MiguelMaria Jose en-aut-sei=de Miguel en-aut-mei=Maria Jose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HelisseyCarole en-aut-sei=Helissey en-aut-mei=Carole kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShuCatherine A. en-aut-sei=Shu en-aut-mei=Catherine A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SpiraAlexander I. en-aut-sei=Spira en-aut-mei=Alexander I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TomasiniPascale en-aut-sei=Tomasini en-aut-mei=Pascale kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YangJames Chih-Hsin en-aut-sei=Yang en-aut-mei=James Chih-Hsin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ZhangYiping en-aut-sei=Zhang en-aut-mei=Yiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=GriesingerFrank en-aut-sei=Griesinger en-aut-mei=Frank kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=WaqarSaiama N. en-aut-sei=Waqar en-aut-mei=Saiama N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=CallesAntonio en-aut-sei=Calles en-aut-mei=Antonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NealJoel W. en-aut-sei=Neal en-aut-mei=Joel W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=BaikChristina S. en-aut-sei=Baik en-aut-mei=Christina S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=JännePasi A. en-aut-sei=Jänne en-aut-mei=Pasi A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=ShreeveS. Martin en-aut-sei=Shreeve en-aut-mei=S. Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=CurtinJoshua C. en-aut-sei=Curtin en-aut-mei=Joshua C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=PatelBharvin en-aut-sei=Patel en-aut-mei=Bharvin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=GormleyMichael en-aut-sei=Gormley en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=LyuXuesong en-aut-sei=Lyu en-aut-mei=Xuesong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=ChenJun en-aut-sei=Chen en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=ChuPei-Ling en-aut-sei=Chu en-aut-mei=Pei-Ling kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=MahoneyJanine en-aut-sei=Mahoney en-aut-mei=Janine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=TraniLeonardo en-aut-sei=Trani en-aut-mei=Leonardo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=BaumlJoshua M. en-aut-sei=Bauml en-aut-mei=Joshua M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=ThayuMeena en-aut-sei=Thayu en-aut-mei=Meena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=KnoblauchRoland E. en-aut-sei=Knoblauch en-aut-mei=Roland E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=ChoByoung Chul en-aut-sei=Cho en-aut-mei=Byoung Chul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= affil-num=1 en-affil=Paris-Saclay University, Institut Gustave Roussy kn-affil= affil-num=2 en-affil=National Cancer Center Hospital East kn-affil= affil-num=3 en-affil=Institute of Clinical Trial Center and Cancer Center, West China Hospital, Sichuan University kn-affil= affil-num=4 en-affil=Samsung Medical Center, Sungkyunkwan University School of Medicine kn-affil= affil-num=5 en-affil=University of Pennsylvania, Perelman School of Medicine kn-affil= affil-num=6 en-affil=National Cancer Center Hospital kn-affil= affil-num=7 en-affil=Hospital Universitario Virgen Del Rocio kn-affil= affil-num=8 en-affil=Seoul National University College of Medicine and Seoul National University Hospital kn-affil= affil-num=9 en-affil=Seoul National University College of Medicine and Seoul National University Hospital kn-affil= affil-num=10 en-affil=Institut Bergonié kn-affil= affil-num=11 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Chongqing University Cancer Hospital kn-affil= affil-num=13 en-affil=Hospital Universitario 12 de Octubre kn-affil= affil-num=14 en-affil=Shizuoka Cancer Center kn-affil= affil-num=15 en-affil=Earle A. Chiles Research Institute, Providence Cancer Institute kn-affil= affil-num=16 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=17 en-affil=START Madrid-CIOCC, Hospital HM Sanchinarro kn-affil= affil-num=18 en-affil=Clinical Research unit, Military Hospital Begin kn-affil= affil-num=19 en-affil=Columbia University Medical Center kn-affil= affil-num=20 en-affil=Virginia Cancer Specialists kn-affil= affil-num=21 en-affil=Aix Marseille University - CNRS, INSERM, CRCM; CEPCM - AP-HM Hopital de La Timone kn-affil= affil-num=22 en-affil=National Taiwan University Cancer Center kn-affil= affil-num=23 en-affil=Zhejiang Cancer Hospital kn-affil= affil-num=24 en-affil=Medical Oncology Service, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital Campus, Universitat Autonoma de Barcelona kn-affil= affil-num=25 en-affil=Pius-Hospital, University Medicine of Oldenburg kn-affil= affil-num=26 en-affil=Division of Oncology, Washington University School of Medicine kn-affil= affil-num=27 en-affil=Hospital General Universitario Gregorio Marañón kn-affil= affil-num=28 en-affil=Stanford University Medical Center kn-affil= affil-num=29 en-affil=University of Washington, Fred Hutchinson Cancer Center kn-affil= affil-num=30 en-affil=Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute kn-affil= affil-num=31 en-affil=Johnson & Johnson kn-affil= affil-num=32 en-affil=Johnson & Johnson kn-affil= affil-num=33 en-affil=Johnson & Johnson kn-affil= affil-num=34 en-affil=Johnson & Johnson kn-affil= affil-num=35 en-affil=Johnson & Johnson kn-affil= affil-num=36 en-affil=Johnson & Johnson kn-affil= affil-num=37 en-affil=Johnson & Johnson kn-affil= affil-num=38 en-affil=Johnson & Johnson kn-affil= affil-num=39 en-affil=Johnson & Johnson kn-affil= affil-num=40 en-affil=Johnson & Johnson kn-affil= affil-num=41 en-affil=Johnson & Johnson kn-affil= affil-num=42 en-affil=Johnson & Johnson kn-affil= affil-num=43 en-affil=Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine kn-affil= en-keyword=Amivantamab kn-keyword=Amivantamab en-keyword=Biomarker analyses kn-keyword=Biomarker analyses en-keyword=Lazertinib kn-keyword=Lazertinib en-keyword=NSCLC kn-keyword=NSCLC END start-ver=1.4 cd-journal=joma no-vol=51 cd-vols= no-issue=11 article-no= start-page=e70112 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Short‐Term Impacts of Japan's 2024 Physician Working‐Hour Limits on Labor Conditions, Self‐Directed Professional Development, and Happiness Among Obstetrician‐Gynecologists en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: To examine the short-term impacts of Japan's newly implemented physician working-hour limits (April 2024) on working conditions, self-directed professional development (SDPD), defined as activities undertaken outside working hours to enhance one's professional skills, and work-related happiness among obstetrician-gynecologists (OB-GYNs).
Methods: An online survey was conducted between July 8 and July 31, 2024, targeting 867 Japan Society of Obstetrics and Gynecology members. Five hundred and fourteen full-time practitioners who had not changed workplaces around April 2024 and had no missing data were analyzed. Participants were stratified by regulation levels (A, B, C, discretionary labor system, those who don't know their own level), and their working hours, anticipated income, SDPD satisfaction, and happiness (0–10 scale) were assessed. We used multivariate linear regression to evaluate the influence of labor condition changes on happiness and explored interactions involving unpaid overtime, income changes, and SDPD satisfaction.
Results: Compared with level A (up to 960 h of overtime per year), participants at levels B and C (up to 1860 h of overtime per year) reported significantly lower happiness (p < 0.001). Most respondents observed no major shifts in working conditions since March 2024, yet about 40% did not record SDPD hours that meet the working hour requirement as official work time. Adjusted analyses revealed that decreased income and unsatisfactory SDPD significantly lowered happiness, whereas higher SDPD satisfaction increased it (β: −0.64 [−1.07, −0.21], −0.98 [−1.46, −0.50], and 0.90 [0.44, 1.35], respectively). Subgroup analysis indicated that rising unpaid overtime further reduced happiness among those dissatisfied with SDPD (−1.43 [−2.41, −0.45]).
Conclusions: The new working-hour limits had minimal impact on labor conditions in the short run. However, satisfaction with SDPD was positively associated with happiness, whereas anticipated decreases in income were correlated with lower happiness. en-copyright= kn-copyright= en-aut-name=MaedaYuto en-aut-sei=Maeda en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaSatoru en-aut-sei=Nakagawa en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanishiKentaro en-aut-sei=Nakanishi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueEri en-aut-sei=Inoue en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueDaisuke en-aut-sei=Inoue en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KidoSaki en-aut-sei=Kido en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KidoMichiko en-aut-sei=Kido en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KogaKaori en-aut-sei=Koga en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiShunji en-aut-sei=Suzuki en-aut-mei=Shunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SuzukiYukio en-aut-sei=Suzuki en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoEiko en-aut-sei=Yamamoto en-aut-mei=Eiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UmazumeTakeshi en-aut-sei=Umazume en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YokoyamaYoshihito en-aut-sei=Yokoyama en-aut-mei=Yoshihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IwaseAkira en-aut-sei=Iwase en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IkedaTomoaki en-aut-sei=Ikeda en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YoshidaYoshio en-aut-sei=Yoshida en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KudoYoshiki en-aut-sei=Kudo en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SugiyamaTakashi en-aut-sei=Sugiyama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MiuraKiyonori en-aut-sei=Miura en-aut-mei=Kiyonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YahataHideaki en-aut-sei=Yahata en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=UnnoNobuya en-aut-sei=Unno en-aut-mei=Nobuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KurasawaKentaro en-aut-sei=Kurasawa en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=MaenakaTakahide en-aut-sei=Maenaka en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MiyagiEtsuko en-aut-sei=Miyagi en-aut-mei=Etsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KatoKiyoko en-aut-sei=Kato en-aut-mei=Kiyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KatoYasuhito en-aut-sei=Kato en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Public Health, Institute of Science Tokyo kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Osaka University kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Asahikawa Medical University kn-affil= affil-num=4 en-affil=Aiiku Maternal and Child Health Center, Aiiku Hospital kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, University of Fukui kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Japanese Red Cross Medical Center kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Reproductive Medicine Chiba University kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Nippon Medical School kn-affil= affil-num=10 en-affil=Department of Gynecology, Kanagawa Cancer Center kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Healthcare Administration, Nagoya University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Hokkaido University kn-affil= affil-num=15 en-affil=Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Obstetrics and Gynecology, Gunma University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Saiseikai Matsusaka General Hospital kn-affil= affil-num=18 en-affil=Department of Obstetrics and Gynecology, University of Fukui kn-affil= affil-num=19 en-affil=Department of Obstetrics and Gynecology, Hiroshima University kn-affil= affil-num=20 en-affil=Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Obstetrics and Gynecology, Nagasaki University kn-affil= affil-num=22 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=23 en-affil=Center for Perinatal Medicine, JCHO Sagamino Hospital kn-affil= affil-num=24 en-affil=Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine kn-affil= affil-num=25 en-affil=Department of Obstetrics and Gynecology, Higashiosaka City Medical Center kn-affil= affil-num=26 en-affil=Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine kn-affil= affil-num=27 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=28 en-affil=Department of Obstetrics and Gynecology, Asahikawa Medical University kn-affil= en-keyword=gynecologists kn-keyword=gynecologists en-keyword=happiness kn-keyword=happiness en-keyword=obstetrician kn-keyword=obstetrician en-keyword=work style reform kn-keyword=work style reform en-keyword=working-hour limits kn-keyword=working-hour limits END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=12 article-no= start-page=1087 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors associated with period of sick leave after gynecologic cancer treatment: a prospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Gynecologic cancer is one of the most common malignancies in working-age women. This study aimed to investigate factors associated with period of sick leave after gynecologic cancer treatment in Japan.
Methods A prospective cohort study on period of sick leave was conducted among 207 cancer survivors who returned to work at the same workplace. Questionnaires were randomly distributed to patients aged under 65 years and more than one-year post-treatment. Clinical information was extracted from medical records, and the factors influencing the period of sick leave were analyzed using the Mann–Whitney U test and logistic regression analysis.
Results Surgery plus more than six courses of chemotherapy (number (n) = 41, 166.02 ± 146.84 days) led to a significantly longer period of sick leave than surgery without lymph node dissection (n = 64, 31.15 ± 30.47 days), surgery with lymph node dissection (n = 41, 55.56 ± 85.90 days), surgery plus less than six courses of chemotherapy (n = 21, 72.42 ± 56.07 days), and radiotherapy alone (n = 21, 58.85 ± 84.24 days) (OR: 2.63, 2.95, 2.67, and 2.08; 95% CI: 7.71–54.59, 18.17–92.94, 18.22–126.63, and 2.38–115.33; p = 0.009, p = 0.004, p = 0.009, and p = 0.041). gynecologic cancer survivors who experienced adverse effects after treatment had a significantly longer period of sick leave (OR: 8.50; CI: 52.98–84.98; p < 0.001). In univariate and multivariate analyses, patients who received surgery plus more than six courses of chemotherapy were most involved in long period of sick leave than other factors (OR: 11.20, and 16.997; CI: 4.86–25.08, and 5.51–52.35; p < 0.001, and p < 0.001).
Conclusion Patients with gynecologic cancer requiring long-term treatment required the most time to return to work. en-copyright= kn-copyright= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShirakawaShinsuke en-aut-sei=Shirakawa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Period of sick leave kn-keyword=Period of sick leave en-keyword=Surgery plus chemotherapy kn-keyword=Surgery plus chemotherapy en-keyword=Six or more cycles of chemotherapy kn-keyword=Six or more cycles of chemotherapy en-keyword=Gynecologic cancer survivors kn-keyword=Gynecologic cancer survivors END start-ver=1.4 cd-journal=joma no-vol=191 cd-vols= no-issue= article-no= start-page=107586 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Experimental approach of internal dose map visualization during helical CT examinations: importance of X-ray incident direction analysis and central internal dose estimation en-subtitle= kn-subtitle= en-abstract= kn-abstract=During computed tomography (CT) examination, radiation exposures should be appropriately managed taking into considering the effects of bowtie filter, the heel effect and over-beaming effect. Furthermore, the analysis of an X-ray incident direction is important. The purpose of this study is to develop a procedure to obtain two-dimensional (2D) internal dose distributions based on actual measurements of surface dose distribution and central internal dose data. Experiments were conducted using a clinical CT scanner and four cylindrical polyacetal resin (POM) phantoms having diameters of 15–30 cm. The entrance surface doses and the central internal dose were measured by placing the optically stimulated luminescence (OSL) dosimeters on the surface and inner part of the phantom, respectively, during helical CT scans. The X-ray incident direction at the slice containing the dosimeter was estimated based on the noise distribution analysis of the CT image. Then, circumferential surface dose distributions were determined as a function of the X-ray incident direction. Based on these experimental data, we succeeded in visualizing the 2D dose distributions. The obtained dose distribution was inhomogeneous, clearly reflecting the influence of factors such as the heel effect. The uncertainty due to our methodology was estimated to be from 4.3 % to 7.4 %. Our methodology needs central internal dose data, and the absence of this data introduced additional systematic uncertainties of +6.9 % to −11.4 %. In conclusion, correcting for the effect of the X-ray incident directions for entrance surface dose and adding the central inner dose data can improve the reliability of the internal dose distribution. en-copyright= kn-copyright= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakegamiKazuki en-aut-sei=Takegami en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiDaiki en-aut-sei=Kobayashi en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoSota en-aut-sei=Goto en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakemitsuMasaki en-aut-sei=Takemitsu en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiiRin en-aut-sei=Ishii en-aut-mei=Rin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorimotoShinichi en-aut-sei=Morimoto en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MakiMotochika en-aut-sei=Maki en-aut-mei=Motochika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Yamaguchi University Hospital kn-affil= affil-num=3 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=5 en-affil=Faculty of Health Sciences, Kobe Tokiwa University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=8 en-affil=Department of Radiological Technology, Yamaguchi University Hospital kn-affil= affil-num=9 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= affil-num=10 en-affil=Meditec Japan Co., Ltd. kn-affil= affil-num=11 en-affil=Meditec Japan Co., Ltd. kn-affil= en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Medical dosimetry kn-keyword=Medical dosimetry en-keyword=Internal dose distribution kn-keyword=Internal dose distribution en-keyword=X-ray incident direction kn-keyword=X-ray incident direction en-keyword=Optically stimulated luminescence dosimeter kn-keyword=Optically stimulated luminescence dosimeter END start-ver=1.4 cd-journal=joma no-vol=191 cd-vols= no-issue= article-no= start-page=107592 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A novel wearable dosimeter system that can analyze the incident direction of X-rays for medical dosimetry – Improvements to the detector arrangements and analysis algorithm – en-subtitle= kn-subtitle= en-abstract= kn-abstract=When performing real-time dosimetry using an active-type dosimeter during clinical fluoroscopic procedures, angular dependence of dosimeter response should be taken into account. Our research group addressed this issue and proposed a triple-type dosimeter that can determine the incident angle of scattered X-rays. The triple-type detector consists of three active dosimeters. The two side dosimeters have slope filters to enhance the angular dependence and are intentionally tilted. The central dosimeter faces forward. The incident angle of X-rays (θin) is estimated using the signal differences between the central dosimeter and the left and/or right dosimeters. Then, the absolute dose is determined by correcting the angular dependence of the central dosimeter based on the estimated θin. In order to verify the concept of the triple-type dosimeter, we conducted a proof-of-concept experiment using clinical X-ray fluoroscopic equipment. Scattered X-rays were generated by irradiating an elliptical cylindrical water phantom. The response of the triple-type dosimeter was evaluated by rotating it to vary the incident angle of scattered X-rays generated by the water phantom. The proposed dosimetry system could estimate the θin over an angular range of ±80° (with uncertainty of 1.35°), which is 30° wider than the previous version, and successfully determined the absolute doses after correction for the angular dependence of the dosimeter. Although the active-type dosimeter had a systematic uncertainty related to the angular dependence of ±15.2 %, our system succeeded in reducing the systematic uncertainty to ±3.2 %. en-copyright= kn-copyright= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiDaiki en-aut-sei=Kobayashi en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoSota en-aut-sei=Goto en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakegamiKazuki en-aut-sei=Takegami en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshiiRin en-aut-sei=Ishii en-aut-mei=Rin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MitaniMana en-aut-sei=Mitani en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HondaMitsugi en-aut-sei=Honda en-aut-mei=Mitsugi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=3 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=4 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=5 en-affil=Faculty of Health Science, Kobe Tokiwa University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Yamaguchi University Hospital kn-affil= affil-num=7 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= affil-num=8 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=9 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= en-keyword=Wearable active-type dosimeter kn-keyword=Wearable active-type dosimeter en-keyword=X-ray incident direction kn-keyword=X-ray incident direction en-keyword=Occupational dose kn-keyword=Occupational dose en-keyword=Interventional radiology kn-keyword=Interventional radiology END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=2 article-no= start-page=103274 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimization of the reconstruction kernel for temporal bone imaging using photon-counting detector CT: A combined physical and visual evaluation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Photon-counting detector CT (PCD-CT) offers superior spatial resolution and noise characteristics compared to conventional CT. However, optimal reconstruction parameters for temporal bone imaging, especially kernel selection, remain unclear. This study aimed to identify the optimal reconstruction kernel using both objective physical image quality metrics and subjective expert assessments.
Methods: In phantom experiments, the system performance function (SPF) based on the task-based transfer function (TTF) and noise power spectrum (NPS) was calculated across 11 reconstruction kernels (Hr60–Hr98). Based on the results of the physical evaluation and clinical considerations from clinical practice, a subset of kernels was selected for visual assessment. For clinical images, two diagnostic radiologists evaluated three fine anatomical structures (i.e., stapes footplate, incudomalleolar joint, and cochlea) and overall image quality using both a ranking method and a 5-point Likert scale.
Results: TTF analysis indicated that Hr96 had the highest spatial resolution, while Hr60 showed the lowest noise in the NPS. SPF analysis identified Hr72 as providing the optimal balance between resolution and noise. Visual assessment using four reconstruction kernels (Hr60, Hr72, Hr76, and Hr84) showed that Hr76 consistently received the highest preference for overall image quality and visualization of fine structures. Statistically significant differences were observed among the kernels, with Hr60 consistently rated the lowest (p < 0.05).
Conclusion: The kernel Hr76 was found suitable for middle and inner ear diagnoses using PCD-CT, providing a good balance between spatial resolution and image noise. This finding provides a foundation for standardized reconstruction protocols in high-resolution temporal bone imaging.
Implications for practice: These findings support the use of Hr76 as a standard kernel for high-resolution temporal bone imaging and may contribute to protocol optimization in clinical PCD-CT practice. en-copyright= kn-copyright= en-aut-name=NishiiS. en-aut-sei=Nishii en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsaharaT. en-aut-sei=Asahara en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimitsuY. en-aut-sei=Morimitsu en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KajisakiS. en-aut-sei=Kajisaki en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkagiN. en-aut-sei=Akagi en-aut-mei=N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HondaM. en-aut-sei=Honda en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HayashiH. en-aut-sei=Hayashi en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugayaA. en-aut-sei=Sugaya en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MunetomoK. en-aut-sei=Munetomo en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HigakiF. en-aut-sei=Higaki en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirakiT. en-aut-sei=Hiraki en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IguchiT. en-aut-sei=Iguchi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=7 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= affil-num=8 en-affil=Department of Otolaryngology, Head & Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=10 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=11 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= en-keyword=Photon-counting CT kn-keyword=Photon-counting CT en-keyword=Temporal bone imaging kn-keyword=Temporal bone imaging en-keyword=Reconstruction kernel kn-keyword=Reconstruction kernel en-keyword=Image quality kn-keyword=Image quality END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue= article-no= start-page=28 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Airway management during sedation for dental treatment in people with intellectual disabilities: a review en-subtitle= kn-subtitle= en-abstract= kn-abstract=The oral health of people with intellectual disabilities remains poor due to a complex combination of physical and social problems, and often requires invasive dental treatment. However, it can be difficult to obtain their cooperation for dental treatment because they may not fully understand the need for treatment or may experience high levels of anxiety due to lack of understanding and/or sensory aversions to stimuli present in the dental environment, and behavioral management is often necessary during such treatment. Sedation is a very useful patient management method for dental treatment for people with intellectual disabilities; however, the dental treatment-related sedation of people with intellectual disabilities has different characteristics to the dental treatment-related sedation of others or other procedure-related sedation. For example, deep sedation is required for behavioral management; drug interactions between the patient’s regular medications, such as antiepileptic and antipsychotic drugs, and anesthetics may make the depth of sedation deeper; and the prevalence rate of obesity is higher among people with intellectual disabilities. The fact that the patient is in the supine position with their mouth open also makes airway management during sedation for dental treatment more difficult. It is therefore imperative that airway management during dental treatment for people with intellectual disabilities be conducted with the utmost precision and vigilance. Various attempts have been made to improve airway management during such sedation, and new technologies, such as capnography, nasal high-flow systems, and acoustic respiration monitors, may help. The objective of this review is to enhance comprehension of the attributes of airway management in dental sedation for people with intellectual disabilities and to properly understand the usefulness of the techniques that have been attempted thus far to ensure safer and more secure airway management for this population. The ultimate goal is to provide them with safe and secure medical care and improve their health outcomes. en-copyright= kn-copyright= en-aut-name=HiguchiHitoshi en-aut-sei=Higuchi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiokaYukiko en-aut-sei=Nishioka en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyakeSaki en-aut-sei=Miyake en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Dentistry kn-keyword=Dentistry en-keyword=sedation kn-keyword=sedation en-keyword=airway management kn-keyword=airway management en-keyword=people with intellectual disabilities kn-keyword=people with intellectual disabilities END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=40608 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between gestational age and child health and neurodevelopment in twins from a nationwide longitudinal survey in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite previous research, evidence on the relationship between gestational age and long-term health and neurodevelopmental outcomes among twins remains limited. Using data from the Longitudinal Survey of Babies in the 21st Century, we analyzed 549 twins born in Japan in 2010. The twins were grouped by gestational age: <32 weeks (very preterm), 32–36 weeks (moderately and late preterm), and 37–38 weeks (early term). The health status was evaluated by hospitalization between 0.5 and 5.5 years, and behavioral development was assessed using questionnaires at 2.5 and 5.5 years. Binomial log-linear regression with generalized estimating equations accounted for within-pair correlations and adjusted for child and parental variables. Moderately and late preterm children showed a higher risk of all-cause hospitalization during infancy than early-term children (adjusted risk ratio, 1.7; 95% CI, 1.0–2.6). Very preterm children showed a higher point estimate of the risk ratio, but a wide CI (risk ratio, 2.3; 95% CI, 0.8–6.8). Behavioral delays were more common in preterm groups at 2.5 years but not at 5.5 years. Preterm twins have a higher risk of hospitalization during infancy and developmental delay at 2.5 years than early-term twins. These risks show an increasing trend as gestational age decreases. en-copyright= kn-copyright= en-aut-name=TamaiKei en-aut-sei=Tamai en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeuchiAkihito en-aut-sei=Takeuchi en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraMakoto en-aut-sei=Nakamura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KageyamaMisao en-aut-sei=Kageyama en-aut-mei=Misao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Neonatology, NHO Okayama Medical Center kn-affil= affil-num=4 en-affil=Division of Neonatology, NHO Okayama Medical Center kn-affil= affil-num=5 en-affil=Division of Neonatology, NHO Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Behavioral development kn-keyword=Behavioral development en-keyword=Child health kn-keyword=Child health en-keyword=Early term kn-keyword=Early term en-keyword=Gestational age kn-keyword=Gestational age en-keyword=Hospitalization kn-keyword=Hospitalization en-keyword=Multiple births kn-keyword=Multiple births END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e00463-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analysis of the drug target of the anti-tuberculosis compound OCT313: phosphotransacetylase is a potential drug target for anti-mycobacterial agents en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tuberculosis (TB) is one of the most common infectious diseases caused by bacteria worldwide. The increasing prevalence of multidrug-resistant TB (MDR-TB) and latent TB infection (LTBI) has intensified the global TB burden. Therefore, the development of new drugs for MDR-TB and LTBI is urgently required. We have reported that the derivative of dithiocarbamate sugar derivative, 2-acetamido-2-deoxy-β-D-glucopyranosyl N,N-dimethyldithiocarbamate (OCT313), exhibits anti-mycobacterial activity against MDR-MTB. Here, we identified the target of OCT313. In experimentally generated OCT313-resistant bacteria, adenine at position 1,092 in the metabolic enzyme phosphotransacetylase (PTA) gene was replaced with cytosine. This mutation is a nonsynonymous mutation that converts methionine to leucine at position 365 in the PTA protein. OCT313 inhibited the enzymatic activity of recombinant wild-type PTA, but not of the mutant PTA (M365L). PTA is an enzyme that produces acetyl-coenzyme A (acetyl-CoA) from acetyl phosphate and CoA and is involved in metabolic pathways; therefore, it was expected to also be active against dormant Mycobacterium tuberculosis bacilli. OCT313 exhibits antibacterial activity in the Wayne model of dormancy using Mycobacterium bovis BCG, and overexpression of PTA in OCT313-resistant bacilli restored sensitivity to OCT313. Collectively, the target of OCT313 is PTA, and OCT313 is a promising antimicrobial candidate for MDR-TB and LTBI. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaTomohiro en-aut-sei=Hasegawa en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItohSaotomo en-aut-sei=Itoh en-aut-mei=Saotomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaShinji en-aut-sei=Maeda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WadaTakayuki en-aut-sei=Wada en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoritaYasuhiro en-aut-sei=Horita en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiyamaAkihito en-aut-sei=Nishiyama en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoSohkichi en-aut-sei=Matsumoto en-aut-mei=Sohkichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HidaShigeaki en-aut-sei=Hida en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OnozakiKikuo en-aut-sei=Onozaki en-aut-mei=Kikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=3 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=4 en-affil=Graduate School of Pharmaceutical Sciences, Hokkaido University of Sciences kn-affil= affil-num=5 en-affil=Department of Microbiology, Graduate School of Human Life and Ecology, Osaka Metropolitan University kn-affil= affil-num=6 en-affil=Department of Clinical Pharmaceutics, Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=7 en-affil=Department of Bacteriology, Niigata University School of Medicine kn-affil= affil-num=8 en-affil=Department of Bacteriology, Niigata University School of Medicine kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=11 en-affil=Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=12 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=13 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= en-keyword=phosphotransacetylase kn-keyword=phosphotransacetylase en-keyword=acetyl coenzyme A kn-keyword=acetyl coenzyme A en-keyword=dithiocarbamate kn-keyword=dithiocarbamate en-keyword=N-acetyl glucosamine kn-keyword=N-acetyl glucosamine en-keyword=anti-mycobacterial agents kn-keyword=anti-mycobacterial agents en-keyword=latent tuberculosis infection kn-keyword=latent tuberculosis infection END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=40522 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long intervals between repetitive concussions reduce risk of cognitive impairment and limit microglial activation, astrogliosis, and tauopathy in adolescent rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although previous studies have demonstrated the effects of concussions do not accumulate as the time interval between injuries increases, little is known about the relationship between this interval and the effects of repetitive concussions. The objective of this study is to explore the relationship between the time interval and changes in behavior and histology following repetitive concussions. Male adolescent rats received concussions by weight drop and were randomly assigned to one of five experimental groups, receiving concussions three times either daily, every other day, once per week, once every 2 weeks, or receiving sham procedures. Only rats that received daily concussions exhibited cognitive impairment, while the other groups did not. No groups showed motor or anxiety-like impairments. Histological analysis revealed accumulation of microglia, as well as astrogliosis, in the prefrontal cortex, corpus callosum, dentate gyrus, and cornu Ammonis 1 region of the hippocampus in rats subjected to daily concussions. Accumulation of phosphorylated tau was also observed in the prefrontal cortex and cornu Ammonis 1. Longer intervals between concussions may reduce the risk of cognitive impairment and limit microglial activation, astrogliosis, and phosphorylated tau accumulation. These findings may help guide decisions on the appropriate timing for return to play in humans. en-copyright= kn-copyright= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaseTakayuki en-aut-sei=Nagase en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiTatsuya en-aut-sei=Sasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugaharaChiaki en-aut-sei=Sugahara en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiKoji en-aut-sei=Kawai en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanimotoShun en-aut-sei=Tanimoto en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyakeHayato en-aut-sei=Miyake en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaijoTomoya en-aut-sei=Saijo en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Yasuhara Clinic kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= en-keyword=Concussion kn-keyword=Concussion en-keyword=Return to play kn-keyword=Return to play en-keyword=Sports-related head injury kn-keyword=Sports-related head injury en-keyword=Microglia kn-keyword=Microglia en-keyword=Astrocyte kn-keyword=Astrocyte en-keyword=Tauopathy kn-keyword=Tauopathy END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=1 article-no= start-page=219 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Does perioperative discontinuation of anti-rheumatic drugs increase postoperative complications in orthopedic surgery for rheumatoid arthritis? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective This study aimed to investigate whether discontinuation of biological or targeted synthetic antirheumatic disease-modifying drugs (bDMARDs or tsDMARDs) influences the incidence of postoperative complications in patients with rheumatoid arthritis (RA) undergoing orthopedic surgery.
Methods A retrospective multicenter cohort study including patients receiving bDMARDs or tsDMARDs who underwent orthopedic surgery was conducted. Data collected encompassed the duration of drug discontinuation and postoperative adverse events, such as delayed wound healing, surgical site infection (SSI), disease flare-ups, and mortality. The association between drug discontinuation and these outcomes was analyzed. Multivariate analyses were conducted to identify potential risk factors for these events.
Results A total of 2,060 cases were initially enrolled. After applying inclusion and exclusion criteria, data from 1,953 patients were analyzed. No significant differences were observed between the groups regarding delayed wound healing, SSI, or mortality. However, the incidence of disease flare-ups was substantially higher in the drug discontinuation group and in the interleukin (IL)-6 inhibitor group. Multivariate analysis identified that tumor necrosis factor α and IL-6 inhibitor use was associated with a higher risk of delayed wound healing relative to T-cell function modifiers.
Conclusion In orthopedic surgery for patients with RA, maintaining the standard or the half of administration interval of bDMARD appears safe in the preoperative period. However, the drug discontinuation may increase the risk of postoperative flare-ups, particularly with IL-6 inhibitors. In addition, T-cell function modifiers may be associated with a lower risk of delayed wound healing, suggesting their safety profile in this context. en-copyright= kn-copyright= en-aut-name=ItoHiromu en-aut-sei=Ito en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaHajime en-aut-sei=Ishikawa en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiShigeyoshi en-aut-sei=Tsuji en-aut-mei=Shigeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MochizukiTakeshi en-aut-sei=Mochizuki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EbinaKosuke en-aut-sei=Ebina en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KojimaToshihisa en-aut-sei=Kojima en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumotoTakumi en-aut-sei=Matsumoto en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KubotaAyako en-aut-sei=Kubota en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakajimaArata en-aut-sei=Nakajima en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KanekoAtsushi en-aut-sei=Kaneko en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsushitaIsao en-aut-sei=Matsushita en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HaraRyota en-aut-sei=Hara en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakurabaKoji en-aut-sei=Sakuraba en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=AkasakiYukio en-aut-sei=Akasaki en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsubaraTsukasa en-aut-sei=Matsubara en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MochidaYuichi en-aut-sei=Mochida en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KanbeKatsuaki en-aut-sei=Kanbe en-aut-mei=Katsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NakagawaNatsuko en-aut-sei=Nakagawa en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MurataKoichi en-aut-sei=Murata en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MomoharaShigeki en-aut-sei=Momohara en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Kurashiki Central Hospital kn-affil= affil-num=2 en-affil=Department of Rheumatology, Niigata Rheumatic Center kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Osaka Minami Medical Center kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, International University of Health and Welfare kn-affil= affil-num=5 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Kamagaya General Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Osaka University Faculty of Medicine Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Nagoya University Hospital kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, University of Tokyo kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Toho University Omori Medical Center kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery and Rehabilitation, Toho University Sakura Medical Center kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Nagoya Medical Center kn-affil= affil-num=13 en-affil=Department of Rehabilitation Medicine, Kanazawa Medical University kn-affil= affil-num=14 en-affil=The Center for Rheumatic Diseases, Nara Medical University kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery, Kyushu Medical Center kn-affil= affil-num=16 en-affil=Department of Orthopaedic Surgery, Kyushu University kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Matsubara Mayflower Hospital kn-affil= affil-num=18 en-affil=Department of Orthopaedic Surgery, Yokohama City University Medical Center kn-affil= affil-num=19 en-affil=Department of Orthopaedic Surgery, Nippori Orthopaedics and Rheumatic Clinic kn-affil= affil-num=20 en-affil=Department of Orthopaedic Surgery, Kakogawa Medical Center kn-affil= affil-num=21 en-affil=Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Endowed Course for Advanced Therapy for Musculoskeletal Disorders, Keio University School of Medicine kn-affil= en-keyword=Rheumatoid arthritis kn-keyword=Rheumatoid arthritis en-keyword=Orthopaedic surgery kn-keyword=Orthopaedic surgery en-keyword=DMARD kn-keyword=DMARD en-keyword=Perioperative complications kn-keyword=Perioperative complications END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Is Pain Intensity Related to Psychosocial Factors in Chronic Non‐Nociceptive Orofacial Pain Patients? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: In order to understand the psychological aspects of chronic pain, it is important to consider the relationships between pain and psychosocial factors in patients with chronic pain. While psychosocial factors are known to affect pain intensity in temporomandibular disorders, few studies have evaluated them in patients with other types of chronic orofacial pain.
Objective: The purpose of the present study was to evaluate the relationships between pain intensity and patient characteristics, diagnostic categories and psychosocial factors in chronic non-nociceptive orofacial pain patients.
Methods: In a retrospective, cross-sectional study, we collected information from the medical records of 123 patients with chronic non-nociceptive orofacial pain. Pain intensity was measured using the Brief Pain Inventory (BPI) total score. Analysis of the correlations among the variables revealed several strong correlations. Principal component analysis identified two components: the psychological distress and self-efficacy/quality of life (QOL) components. Multiple linear regression analyses of the overall study population and each ICOP pain category were also performed.
Results: In the overall sample, higher BPI scores were significantly associated with a greater psychological distress component and lower self-efficacy/QOL component. The pain category was not a significant predictor of the BPI score. In the subgroup analyses, both components were significant predictors of the BPI score in myofascial orofacial pain; whereas, only the self-efficacy/QOL component was in idiopathic orofacial pain.
Conclusion: The results indicated that pain intensity in chronic non-nociceptive orofacial pain is related to the self-efficacy/QOL psychosocial factor component. These findings suggest that assessing psychosocial factors may be clinically important for the diagnosis and treatment of chronic orofacial pain. en-copyright= kn-copyright= en-aut-name=KawaseAkiko en-aut-sei=Kawase en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiguchiHitoshi en-aut-sei=Higuchi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashimotoFumika en-aut-sei=Hashimoto en-aut-mei=Fumika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeSaki en-aut-sei=Miyake en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiokaYukiko en-aut-sei=Nishioka en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueMidori en-aut-sei=Inoue en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UjitaHitomi en-aut-sei=Ujita en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawauchiAki en-aut-sei=Kawauchi en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaShigeru en-aut-sei=Maeda en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=9 en-affil=Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=10 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=chronic pain kn-keyword=chronic pain en-keyword=International Classification of Orofacial Pain kn-keyword=International Classification of Orofacial Pain en-keyword=orofacial pain kn-keyword=orofacial pain en-keyword=psychological distress component kn-keyword=psychological distress component en-keyword=psychosocial factors kn-keyword=psychosocial factors en-keyword=self-efficacy/ QOL component kn-keyword=self-efficacy/ QOL component END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=5 article-no= start-page=573 end-page=582 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn’s disease activity in the small bowel en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Small bowel (SB) lesions in Crohn’s disease (CD) are often asymptomatic despite being highly active. Fecal calprotectin (FC) is the most widely used biomarker of CD activity, but its drawbacks include a large intra-individual sample variability and the burden of collecting stool samples. Meanwhile, serum leucine-rich alpha-2 glycoprotein (LRG) has recently attracted attention as a biomarker that can address the limitations of FC. This study determined the diagnostic accuracy of LRG and its cut-off values for diagnosing CD activity in SB.
Methods This was a retrospective, multi-center study of CD patients undergoing retrograde balloon-assisted endoscopy. For ileal- and ileocolonic-type patients with a colon SES-CD score of 0, we estimated the receiver operating characteristic curve of LRG and determined the cut-off value to achieve a target sensitivity level of 80%.
Results Among 285 patients with SB lesions, LRG had an area under the curve (AUC) of 0.72 (95% CI 0.67–0.78) with a sensitivity of 80.2% and specificity of 47.2% for a cut-off value of 10.5 when diagnosing endoscopic remission (modified SES-CD ≤ 3), while it had an AUC of 0.72 (95% CI 0.65–0.78) with a sensitivity of 81.2% and specificity of 46.2% for a cut-off value of 10.1 when diagnosing complete ulcer healing (modified SES-CD ≤ 1).
Conclusion LRG was effective for diagnosing CD activity in SB, specifically with cut-off values of 10.5 and 10.1 for endoscopic remission and complete ulcer healing, respectively. A future prospective validation study will assess its clinical utility. en-copyright= kn-copyright= en-aut-name=OkitaMuneyori en-aut-sei=Okita en-aut-mei=Muneyori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakenakaKento en-aut-sei=Takenaka en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraiFumihito en-aut-sei=Hirai en-aut-mei=Fumihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AshizukaShinya en-aut-sei=Ashizuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IijimaHideki en-aut-sei=Iijima en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BambaShigeki en-aut-sei=Bamba en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeKenji en-aut-sei=Watanabe en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimodairaYosuke en-aut-sei=Shimodaira en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShigaHisashi en-aut-sei=Shiga en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamuraTakeshi en-aut-sei=Yamamura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=EmotoRyo en-aut-sei=Emoto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MatsuiShigeyuki en-aut-sei=Matsui en-aut-mei=Shigeyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Biostatistics, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine kn-affil= affil-num=5 en-affil=Osaka International Medical & Science Center, Osaka Keisatsu Hospital kn-affil= affil-num=6 en-affil=Department of Fundamental Nursing, Shiga University of Medical Science kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=8 en-affil=Department of Internal Medicine for Inflammatory Bowel Disease, Toyama University kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Research Center for Intestinal Health Science, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Biostatistics, Nagoya University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Biostatistics, Nagoya University Graduate School of Medicine kn-affil= en-keyword=LRG kn-keyword=LRG en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Crohn’s disease kn-keyword=Crohn’s disease END start-ver=1.4 cd-journal=joma no-vol=1873 cd-vols= no-issue=2 article-no= start-page=120091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SPRED2 controls the severity of cisplatin-induced acute kidney injury by inhibiting ERK activation and TNFα production in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cisplatin is an effective chemotherapeutic agent used to treat solid tumors, but its clinical use is limited by acute kidney injury (AKI), in which ERK signaling plays a crucial role. Here, we investigated whether Sprouty-related EVH1 domain-containing protein 2 (SPRED2), an endogenous inhibitor of the Ras/Raf/ERK pathway, protects against cisplatin-induced AKI. Spred2−/− mice showed more severe renal injury and stronger ERK activation than wild-type (WT) mice, whereas pretreatment with the MEK inhibitor U0126 markedly attenuated the injury. In HK-2 cells (proximal tubular cells), SPRED2 knockdown enhanced cisplatin-induced apoptosis and caspase-3 activation, accompanied by decreased Bcl-2 expression. Spred2−/− kidneys displayed increased macrophage infiltration and elevated Tnfα, Il1b, and Ccl2 expression. Neutralization of TNFα with anti-TNFα antibody ameliorated renal injury and reduced the levels of Il1b and Ccl2 mRNA in Spred2−/− mice. In vitro, TNFα slightly decreased the viability of control and SPRED2 knockdown HK-2 cells without cisplatin treatment, but the decreased viability was augmented in SPRED2 knockdown cells by cisplatin. Immunohistochemistry revealed that macrophages were the predominant TNFα-positive cell population. Bone marrow–derived macrophages from Spred2−/− mice produced higher levels of TNFα in response to cisplatin compared with control cells, and this increase was markedly suppressed by U0126.
These findings indicate that endogenous SPRED2 protects kidneys from cisplatin-induced AKI by limiting ERK activation, tubular apoptosis, and TNFα-mediated inflammation. en-copyright= kn-copyright= en-aut-name=YangXu en-aut-sei=Yang en-aut-mei=Xu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HeJiali en-aut-sei=He en-aut-mei=Jiali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunkelSteven L. en-aut-sei=Kunkel en-aut-mei=Steven L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology, University of Michigan Medical School kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cisplatin kn-keyword=Cisplatin en-keyword=ERK kn-keyword=ERK en-keyword=Macrophage kn-keyword=Macrophage en-keyword=SPRED2 kn-keyword=SPRED2 en-keyword=TNFα kn-keyword=TNFα END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e95808 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk Stratification for the Prediction of Skeletal-Related Events in Patients With Bone Metastases From Non-small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skeletal-related events (SREs) frequently occur in patients with bone metastases from non-small cell lung cancer (NSCLC). This study aimed to identify risk factors for SREs in patients with NSCLC. Based on these factors, we also aimed to stratify patients into subgroups to facilitate the assessment of SRE risk. This retrospective analysis used medical records of 139 patients with NSCLC bone metastases who received treatment at our institution between 2011 and 2014. The incidence of SREs was assessed, and SRE-free survival was analyzed using the Kaplan-Meier method. Clinical information collected at registration was assessed to identify factors associated with the onset of SREs within six months. Univariate analysis was performed using Fisher’s exact test, and multivariate analysis was performed using Cox regression. Of the 139 patients, 36 (26%) developed SREs after registration. The SRE-free survival rates were 80% and 64% at 6 and 12 months, respectively. The univariate and multivariate analyses revealed that the absence of epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangement (hazard ratio (HR): 4.51, 95% confidence interval (CI): 1.32-15.7, p = 0.017) and a lactate dehydrogenase (LDH) level ≥400 U/L (HR: 8.08, 95% CI: 1.78-36.6, p = 0.0067) were risk factors for SRE presentation within six months. Patients were classified into the following three subgroups: with EGFR mutation or ALK rearrangement and LDH level <400 U/L; without EGFR mutation or ALK rearrangement and LDH level <400 U/L; with/without EGFR mutation or ALK rearrangement and LDH level ≥400 U/L. The corresponding six-month SRE-free survival rates were 92%, 69%, and 34%, respectively, showing significant differences (p < 0.001). Close monitoring is recommended for patients with LDH levels ≥400 U/L in daily clinical practice, particularly with the help of the proficiency of orthopedic and radiological experts, to prevent complications such as pathological fractures and paraplegia. en-copyright= kn-copyright= en-aut-name=SakamotoYoshihiro en-aut-sei=Sakamoto en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaYoshimi en-aut-sei=Katayama en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiharaShinsuke en-aut-sei=Sugihara en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anaplastic lymphoma kinase kn-keyword=anaplastic lymphoma kinase en-keyword=bone metastases kn-keyword=bone metastases en-keyword=epidermal growth factor receptor-tyrosine kinase kn-keyword=epidermal growth factor receptor-tyrosine kinase en-keyword=lactate dehydrogenase kn-keyword=lactate dehydrogenase en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=skeletal related events kn-keyword=skeletal related events END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=e77632 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mid-term Clinical and Radiographic Outcomes of the Actis Total Hip System: A Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
Implant technology for total hip arthroplasty (THA) was developed to improve hip function and patient satisfaction. Actis (DePuy Synthes, Warsaw, IN, USA) is a short fit-and-fill titanium stem, with a medial-collared and triple-taper (MCTT) geometry, that is fully coated with hydroxyapatite (HA). We evaluated the radiographic and clinical outcomes of the Actis Total Hip System during a mean follow-up of five years.
Patients and methods
We retrospectively analyzed data from 80 patients (14 male and 66 female, mean age: 65 ± 8.4 years) who underwent primary THA using Actis stems (anterolateral approach, 60 hips; posterior approach, 20 hips). Radiographs were obtained postoperatively and at the time of the final examination. Radiographic assessments included the alignment of the femoral stem, spot welds, stress shielding, cortical hypertrophy, subsidence (>2 mm), radiolucent line, pedestal formation, Dorr type, canal fill ratio (CFR), and stem fixation. Clinical evaluation included the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ) and Harris Hip Score (HHS).
Results
The mean follow-up period was 64.0 ± 6.0 months. No significant differences were observed in the alignment of the femoral components between approaches. Of the 80 hips, 53 (66.3%) showed radiographic signs of stem osseointegration, predominantly in the mid-distal region of the stem at the final follow-up. Multiple logistic regression analysis revealed that younger age and a higher CFR (20 mm proximal to the lesser trochanter) were associated with the presence of spot welds. Mild stress shielding occurred in 25 hips (31.3%), and no patient experienced severe stress shielding. All stems were fixed by bone on growth. The JHEQ and HHS significantly improved at the final assessment.
Conclusion
At the five-year follow-up, patients who received the Actis Total Hip System during THA had good radiographic and clinical outcomes.
en-copyright= kn-copyright= en-aut-name=MasadaYasutaka en-aut-sei=Masada en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KouraTakashi en-aut-sei=Koura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkudaRyuichiro en-aut-sei=Okuda en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TetsunagaTomoko en-aut-sei=Tetsunaga en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YokoyamaYusuke en-aut-sei=Yokoyama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkazakiYuki en-aut-sei=Okazaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=actis kn-keyword=actis en-keyword=hydroxyapatite kn-keyword=hydroxyapatite en-keyword=mid-term outcome kn-keyword=mid-term outcome en-keyword=spot welds kn-keyword=spot welds en-keyword=stem kn-keyword=stem en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue=1 article-no= start-page=373 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Changes in the anatomical positions of the femoral nerve and artery in the lateral and supine positions: a multicenter retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Femoral nerve palsy and femoral artery injury are serious complications of total hip arthroplasty. However, few studies have compared the anatomical positions of these structures in different patient positions. This study aimed to compare the anatomical positions of the femoral nerve and artery in the lateral and supine positions.
Materials and methods This multicenter retrospective study included 111 patients who underwent lateral and supine computed tomography (CT) from 2016 to 2023. CT images were reconstructed in the anterior pelvic plane. The horizontal distance from the anterior margin of the acetabulum to the femoral nerve (Distance N) and femoral artery (Distance A) was measured. The difference in Distance N between the two positions (ΔLateral–supine Distance N) was calculated by subtracting the supine value from the lateral value.
Results The average Distance N was 26.5 ± 5.1 mm in the lateral position and 21.1 ± 4.4 mm in the supine position, with the nerve located significantly closer to the acetabulum in the supine position (P < 0.001). Similarly, the average Distance A was 26.8 ± 5.4 mm in the lateral position and 20.4 ± 4.9 mm in the supine position (P < 0.001). Multiple regression analysis showed that Distance N in the lateral position was significantly shorter in female patients and those with low body weight. In addition, low body weight correlated with a smaller ΔLateral–supine Distance N.
Conclusions The femoral nerve and artery are located closer to the anterior margin of the acetabulum in the supine position than in the lateral position. Low body weight was an independent predictor of shorter Distance N in both positions and a smaller ΔLateral–supine Distance N. These findings underscore the importance of considering patient positioning during total hip arthroplasty, particularly in patients with low body weight, to reduce neurovascular risks. en-copyright= kn-copyright= en-aut-name=OkudaRyuichiro en-aut-sei=Okuda en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TetsunagaTomoko en-aut-sei=Tetsunaga en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KouraTakashi en-aut-sei=Koura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MasadaYasutaka en-aut-sei=Masada en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoTetsuya en-aut-sei=Yamamoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumotoShin en-aut-sei=Matsumoto en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IkumaHisanori en-aut-sei=Ikuma en-aut-mei=Hisanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KomatsubaraTadashi en-aut-sei=Komatsubara en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkazakiYuki en-aut-sei=Okazaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Total hip arthroplasty kn-keyword=Total hip arthroplasty en-keyword=Femoral artery kn-keyword=Femoral artery en-keyword=Femoral nerve kn-keyword=Femoral nerve en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Lateral position kn-keyword=Lateral position en-keyword=Supine position kn-keyword=Supine position END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=原発性鼻腔副鼻腔びまん性大細胞型B細胞リンパ腫におけるMYD88およびCD79B遺伝子変異の解析:MCD様サブタイプの同定 kn-title=High Prevalence of MYD88 and CD79B Mutations in Primary Sinonasal Diffuse Large B-Cell Lymphoma: Identification of an MCD-like Subtype en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=PENGFANGLI en-aut-sei=PENG en-aut-mei=FANGLI kn-aut-name=彭芳丽 kn-aut-sei=彭 kn-aut-mei=芳丽 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=2型糖尿病患者における食後中性脂肪値の変動と腎機能障害、微量アルブミン尿との関連について:後ろ向き観察研究 kn-title=The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UCHIYAMANatsumi en-aut-sei=UCHIYAMA en-aut-mei=Natsumi kn-aut-name=内山奈津実 kn-aut-sei=内山 kn-aut-mei=奈津実 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=豚実験モデルを使ったフォンタン循環における機械的肺循環サポート kn-title=Mechanical Subpulmonary Support in Fontan Circulation: A Juvenile Porcine Experimental Model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SAKODANaoya en-aut-sei=SAKODA en-aut-mei=Naoya kn-aut-name=迫田直也 kn-aut-sei=迫田 kn-aut-mei=直也 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=4 article-no= start-page=313 end-page=326 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review en-subtitle= kn-subtitle= en-abstract= kn-abstract=In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes. en-copyright= kn-copyright= en-aut-name=KubotaYuta en-aut-sei=Kubota en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawanoMasanori en-aut-sei=Kawano en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwasakiTatsuya en-aut-sei=Iwasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItonagaIchiro en-aut-sei=Itonaga en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakuNobuhiro en-aut-sei=Kaku en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaKazuhiro en-aut-sei=Tanaka en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery , Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= en-keyword=NTRK fusion-positive sarcoma kn-keyword=NTRK fusion-positive sarcoma en-keyword=larotrectinib kn-keyword=larotrectinib en-keyword=entrectinib kn-keyword=entrectinib en-keyword=infantile fibrosarcoma kn-keyword=infantile fibrosarcoma en-keyword=NTRK-rearranged spindle cell neoplasms kn-keyword=NTRK-rearranged spindle cell neoplasms END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=19 article-no= start-page=3144 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utility of Same-Modality, Cross-Domain Transfer Learning for Malignant Bone Tumor Detection on Radiographs: A Multi-Faceted Performance Comparison with a Scratch-Trained Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases like malignant bone tumors is limited by scarce annotated data. This study evaluates same-modality cross-domain transfer learning by comparing an AI model pretrained on chest radiographs with a model trained from scratch for detecting malignant bone tumors on knee radiographs. Methods: Two YOLOv5-based detectors differed only in initialization (transfer vs. scratch). Both were trained/validated on institutional data and tested on an independent external set of 743 radiographs (268 malignant, 475 normal). The primary outcome was AUC; prespecified operating points were high-sensitivity (≥0.90), high-specificity (≥0.90), and Youden-optimal. Secondary analyses included PR/F1, calibration (Brier, slope), and decision curve analysis (DCA). Results: AUC was similar (YOLO-TL 0.954 [95% CI 0.937–0.970] vs. YOLO-SC 0.961 [0.948–0.973]; DeLong p = 0.53). At the high-sensitivity point (both sensitivity = 0.903), YOLO-TL achieved higher specificity (0.903 vs. 0.867; McNemar p = 0.037) and PPV (0.840 vs. 0.793; bootstrap p = 0.030), reducing ~17 false positives among 475 negatives. At the high-specificity point (~0.902–0.903 for both), YOLO-TL showed higher sensitivity (0.798 vs. 0.764; p = 0.0077). At the Youden-optimal point, sensitivity favored YOLO-TL (0.914 vs. 0.892; p = 0.041) with a non-significant specificity difference. Conclusions: Transfer learning may not improve overall AUC but can enhance practical performance at clinically crucial thresholds. By maintaining high detection rates while reducing false positives, the transfer learning model offers superior clinical utility. Same-modality cross-domain transfer learning is an efficient strategy for developing robust AI systems for rare diseases, supporting tools more readily acceptable in real-world screening workflows. en-copyright= kn-copyright= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaYujiro en-aut-sei=Otsuka en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeuchiKoichi en-aut-sei=Takeuchi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraYusuke en-aut-sei=Nakamura en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkutaKunihiro en-aut-sei=Ikuta en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OsakiShuhei en-aut-sei=Osaki en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TamiyaHironari en-aut-sei=Tamiya en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiwaShinji en-aut-sei=Miwa en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhshikaShusa en-aut-sei=Ohshika en-aut-mei=Shusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishimuraShunji en-aut-sei=Nishimura en-aut-mei=Shunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KaharaNaoaki en-aut-sei=Kahara en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Medical Informatics and Clinical Support Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Juntendo University School of Medicine kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Plusman LCC kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University kn-affil= affil-num=7 en-affil=Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute, kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Kindai University Hospital kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Mizushima Central Hospital kn-affil= affil-num=13 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=malignant bone tumors kn-keyword=malignant bone tumors en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=transfer learning kn-keyword=transfer learning en-keyword=YOLO kn-keyword=YOLO en-keyword=radiographs kn-keyword=radiographs en-keyword=cross-domain learning kn-keyword=cross-domain learning en-keyword=diagnostic imaging kn-keyword=diagnostic imaging END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=12 article-no= start-page=2351 end-page=2363 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Multicenter, Prospective, Observational, and Single-Arm Interventional Study of Mirogabalin in Diabetic Peripheral Neuropathic Pain: Rationale and Design of Dia-NeP en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: The exact prevalence of and recent changes in diabetic polyneuropathy (DPN) and diabetic peripheral neuropathic pain (DPNP) in Japan are unclear. The oral gabapentinoid, mirogabalin besylate (mirogabalin), is effective with a good safety profile for DPNP with moderate-to-severe pain (numerical rating scale [NRS] scores ≥ 4). However, clinical evidence for mild pain (NRS scores ≤ 3) is unclear. The Dia-NeP study aims to examine: (1) the prevalences of DPN and DPNP and background factors in patients with type 2 diabetes mellitus (T2DM); and (2) the efficacy and safety of mirogabalin in patients with DPNP, including those with mild pain.
Methods: The Dia-NeP study is a multicenter, prospective study consisting of two parts, a baseline survey and an interventional study, to be conducted from March 2025 to August 2026 in patients with T2DM in Japan. The baseline survey is the observational study investigating the epidemiology of DPN and DPNP, and the interventional study is an exploratory, single-arm, open-label study of 12-week mirogabalin treatment. Of patients with T2DM enrolled in the baseline survey, those diagnosed with DPNP who have an NRS score for pain ≥ 1 will be included in the interventional study. The target sample size is 1000 to 3000 patients for the baseline survey and 100 for the interventional study.
Planned Outcomes: The primary endpoint is the change from baseline in the NRS score at week 12 in the interventional study. The safety endpoint is adverse events. This study will not only show the latest prevalence of DPN and DPNP in Japan, but is also the first study to investigate the efficacy and safety of mirogabalin in patients with DPNP having mild pain, as well as moderate-to-severe pain, and is expected to provide useful evidence for future DPN and DPNP treatment.
Trial Registration: Japan Registry of Clinical Trials (jRCTs031240623, registered 20/January/2025, https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031240623). en-copyright= kn-copyright= en-aut-name=KamiyaHideki en-aut-sei=Kamiya en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiRyo en-aut-sei=Suzuki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DeguchiTakahisa en-aut-sei=Deguchi en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HimenoTatsuhito en-aut-sei=Himeno en-aut-mei=Tatsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoShuhei en-aut-sei=Yamamoto en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyamaTaiki en-aut-sei=Toyama en-aut-mei=Taiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraJiro en-aut-sei=Nakamura en-aut-mei=Jiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine kn-affil= affil-num=2 en-affil=Department of Diabetes, Metabolism and Endocrinology, Tokyo Medical University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=4 en-affil=Department of Diabetes, Metabolism and Endocrinology, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine kn-affil= affil-num=6 en-affil=Data Intelligence Department, Daiichi Sankyo Co., Ltd. kn-affil= affil-num=7 en-affil=Primary Medical Science Department, Daiichi Sankyo Co., Ltd. kn-affil= affil-num=8 en-affil=Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine kn-affil= en-keyword=Diabetic peripheral neuropathic pain kn-keyword=Diabetic peripheral neuropathic pain en-keyword=Diabetic polyneuropathy kn-keyword=Diabetic polyneuropathy en-keyword=Epidemiological survey kn-keyword=Epidemiological survey en-keyword=Exploratory study kn-keyword=Exploratory study en-keyword=Mirogabalin kn-keyword=Mirogabalin en-keyword=Quality of life kn-keyword=Quality of life END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=11 article-no= start-page=e13960 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Missing the Target: A Scoping Review of the Use of Percent Weight Loss for Obesity Management en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: To co-create comprehensive targets for obesity management, we need to understand the genesis and current use of percent weight loss targets in research. The goals of our scoping review are to (1) synthesize the literature on percent weight loss targets for adults with obesity and (2) discuss the percent weight loss targets in context with their health benefits.
Methods: We searched Cochrane, MEDLINE, and EMBASE for English language, pharmaceutical, and/or behavioral intervention studies in adults with obesity where the explicit aim of the study was weight reduction defined as a percent of body weight. Reviewers screened citations and extracted data including study characteristics.
Results: From 16,164 abstracts, we included 30 citations which were mostly randomized controlled trials (RCTs) (n = 17) or quasi-experimental studies (n = 12) published between 1992 and 2024. Most of the studies had target weight loss goals between 3% and 10% of body weight (n = 28), while n = 2 had body weight loss goals of 15% or 30%. The proportion of participants who met the percent weight loss target ranged from 5.9% (nutrition only study) to 85% (pharmaceutical study). The studies reported different reasons for targeting a percentage of weight loss such as disease-specific outcomes, reduced risk of disease, or patient-reported outcomes.
Conclusion: Percent weight loss targets were based on similar research and were often not feasible nor sustainable for most participants. The design of these interventions and evaluation of obesity management would benefit from more patient-focused parameters which could help to co-design comprehensive targets for research and practice. en-copyright= kn-copyright= en-aut-name=SherifaliDiana en-aut-sei=Sherifali en-aut-mei=Diana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RaceyMegan en-aut-sei=Racey en-aut-mei=Megan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Fitzpatrick‐LewisDonna en-aut-sei=Fitzpatrick‐Lewis en-aut-mei=Donna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GreenwayMichelle en-aut-sei=Greenway en-aut-mei=Michelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SockalingamSanjeev en-aut-sei=Sockalingam en-aut-mei=Sanjeev kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TeohSoo Huat en-aut-sei=Teoh en-aut-mei=Soo Huat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=PattonIan en-aut-sei=Patton en-aut-mei=Ian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MacklinDavid en-aut-sei=Macklin en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=van RossumElizabeth F. C. en-aut-sei=van Rossum en-aut-mei=Elizabeth F. C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BusettoLuca en-aut-sei=Busetto en-aut-mei=Luca kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HornDeborah Bade en-aut-sei=Horn en-aut-mei=Deborah Bade kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Patricia NeceJ. D. en-aut-sei=Patricia Nece en-aut-mei=J. D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=LeguedeMorgan Emile Gabriel Salmon en-aut-sei=Leguede en-aut-mei=Morgan Emile Gabriel Salmon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=PearceNicole en-aut-sei=Pearce en-aut-mei=Nicole kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Le RouxCarel en-aut-sei=Le Roux en-aut-mei=Carel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ArdJamy en-aut-sei=Ard en-aut-mei=Jamy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AlbergaAngela S. en-aut-sei=Alberga en-aut-mei=Angela S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KaplanLee en-aut-sei=Kaplan en-aut-mei=Lee kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SharmaArya M. en-aut-sei=Sharma en-aut-mei=Arya M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=WhartonSean en-aut-sei=Wharton en-aut-mei=Sean kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University kn-affil= affil-num=2 en-affil=McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University kn-affil= affil-num=3 en-affil=McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University kn-affil= affil-num=4 en-affil=McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University kn-affil= affil-num=5 en-affil=Obesity Canada kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Clinical Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia kn-affil= affil-num=8 en-affil=Obesity Canada kn-affil= affil-num=9 en-affil=Temerty Faculty of Medicine, University of Toronto kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Division of Endocrinology, and Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam kn-affil= affil-num=11 en-affil=Department of Medicine, University of Padova kn-affil= affil-num=12 en-affil=Center of Obesity Medicine and Metabolic Performance, Department of Surgery, University of Texas McGovern Medical School kn-affil= affil-num=13 en-affil=Obesity Action Coalition kn-affil= affil-num=14 en-affil=ABHispalis Spain, Alianza Hispana de Personas con Obesidad Latin America kn-affil= affil-num=15 en-affil=Obesity Canada kn-affil= affil-num=16 en-affil=School of Medicine, University College Dublin kn-affil= affil-num=17 en-affil=School of Medicine, Wake Forest University kn-affil= affil-num=18 en-affil=Department of Health, Kinesiology, and Applied Physiology, Concordia University kn-affil= affil-num=19 en-affil=Obesity, Metabolism and Nutrition Institute Massachusetts General Hospital and Harvard Medical School kn-affil= affil-num=20 en-affil=Department of Medicine, University of Alberta kn-affil= affil-num=21 en-affil=Temerty Faculty of Medicine, University of Toronto kn-affil= en-keyword=obesity management kn-keyword=obesity management en-keyword=percent body weight kn-keyword=percent body weight en-keyword=scoping review kn-keyword=scoping review en-keyword=target kn-keyword=target en-keyword=weight loss kn-keyword=weight loss END start-ver=1.4 cd-journal=joma no-vol=48 cd-vols= no-issue=11 article-no= start-page=2924 end-page=2937 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy and safety of esaxerenone with and without sodium–glucose cotransporter-2 inhibitor use in hypertensive patients with type 2 diabetes mellitus: a pooled analysis of five clinical studies en-subtitle= kn-subtitle= en-abstract= kn-abstract=This pooled subanalysis of five multicenter, prospective, open-label, single-arm studies on esaxerenone aimed to evaluate the efficacy, organ-protective effects, and safety of esaxerenone in hypertensive patients with type 2 diabetes mellitus (T2DM), with and without concomitant sodium–glucose cotransporter-2 inhibitor (SGLT2i) therapy. In total, 283 and 279 patients were included in the safety (with SGLT2i, 148; without, 135) and full analysis sets (with SGLT2i; 145; without, 134), respectively. Significant changes in morning home systolic/diastolic blood pressure (SBP/DBP) from baseline to Week 12 were shown in the overall population (mean change: −11.9/−5.2 mmHg, both P < 0.001) and both SGLT2i and non-SGLT2i subgroups (−11.3/−4.8 and −12.5/−5.7 mmHg, respectively, all P < 0.001). Similar findings were observed in bedtime home and office SBP/DBP. The proportions of patients who achieved target home SBP/DBP < 135/85 mmHg were 71.2% (overall population) and 70.5% and 71.9% in the SGLT2i and non-SGLT2i subgroups, respectively. The urine albumin-to-creatinine ratio significantly improved from baseline to Week 12 in the overall population and SGLT2i subgroups (percentage change in geometric mean from baseline: −42.8%, −43.0%, and −42.6%, respectively, all P < 0.001). N-terminal pro-B-type natriuretic peptide levels improved in all groups. The incidence of serum potassium ≥5.5 mEq/L was 2.0% vs 5.2% in the SGLT2i vs non-SGLT2i subgroups. Esaxerenone demonstrated significant BP-lowering effects, and improved renal and cardiovascular parameters, regardless of SGLT2i use. Safety was consistent across groups, with the numerically lower incidence of serum potassium ≥5.5 mEq/L in the SGLT2i subgroup suggesting a potential mitigating effect of SGLT2is on the risk of hyperkalemia. en-copyright= kn-copyright= en-aut-name=MotokiHirohiko en-aut-sei=Motoki en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuwaharaKoichiro en-aut-sei=Kuwahara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KarioKazuomi en-aut-sei=Kario en-aut-mei=Kazuomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatsuyaTomohiro en-aut-sei=Katsuya en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimosawaTatsuo en-aut-sei=Shimosawa en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsujitaKenichi en-aut-sei=Tsujita en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiShoko en-aut-sei=Suzuki en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SuedomiTomohiro en-aut-sei=Suedomi en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TaguchiTakashi en-aut-sei=Taguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Shinshu University School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Shinshu University School of Medicine kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine kn-affil= affil-num=6 en-affil=Katsuya Clinic kn-affil= affil-num=7 en-affil=Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University kn-affil= affil-num=9 en-affil=Data Intelligence Department, Daiichi Sankyo Co. Ltd. kn-affil= affil-num=10 en-affil=Primary Medical Science Department, Daiichi Sankyo Co. Ltd. kn-affil= affil-num=11 en-affil=Primary Medical Science Department, Daiichi Sankyo Co. Ltd. kn-affil= en-keyword=Esaxerenone kn-keyword=Esaxerenone en-keyword=Hypertension kn-keyword=Hypertension en-keyword=Morning home blood pressure kn-keyword=Morning home blood pressure en-keyword=Sodium–glucose cotransporter-2 inhibitor kn-keyword=Sodium–glucose cotransporter-2 inhibitor en-keyword=Type 2 diabetes mellitus kn-keyword=Type 2 diabetes mellitus END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=10 article-no= start-page=1342 end-page=1353 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=First-time diagnosis and referral practices for individuals with CKD by primary care physicians: a study of electronic medical records across multiple clinics in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Chronic kidney disease (CKD) is a major public health burden in Japan. Japanese primary care physicians (PCPs) are expected to play an important role in the early diagnosis and management of CKD, but comprehensive data on their role are limited.
Methods This observational study examined data from individuals who underwent tests for CKD diagnosis between January 2017 and September 2023 in the Japan Medical Data Survey (JAMDAS) database of primary care clinics in Japan. The primary outcome was the proportion of individuals with CKD without the registration of a CKD-related disease code. Time to CKD diagnosis and referral were also assessed.
Results Among 1,188,543 eligible individuals who underwent kidney-related laboratory tests, 183,473 (15.4%) met CKD diagnosis criteria according to the Japanese Clinical Practice Guideline for CKD. The mean (± SD) age was 77.4 ± 11.0 years, 57.1% were female, and 71.8% had CKD stage 3a. Over 98% of individuals who met CKD diagnosis criteria did not receive an insurance diagnosis code within 90 days after meeting the criteria. Among referrable individuals, 89.7% did not receive a referral within 90 days of meeting the referral criteria.
Conclusion These results suggest CKD may be underdiagnosed and under-referred in Japanese clinics. Measures should be taken to increase detection and diagnosis according to the Japanese Clinical Practice Guideline for CKD. en-copyright= kn-copyright= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaoYuji en-aut-sei=Nagao en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IharaKatsuhito en-aut-sei=Ihara en-aut-mei=Katsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Medicine Division, Nippon Boehringer Ingelheim Co., Ltd. kn-affil= affil-num=4 en-affil=Medicine Division, Nippon Boehringer Ingelheim Co., Ltd. kn-affil= en-keyword=Chronic kidney disease kn-keyword=Chronic kidney disease en-keyword=Electronic medical records kn-keyword=Electronic medical records en-keyword=Japan kn-keyword=Japan en-keyword=Primary care physician kn-keyword=Primary care physician en-keyword=Disease code kn-keyword=Disease code END start-ver=1.4 cd-journal=joma no-vol=48 cd-vols= no-issue=9 article-no= start-page=2413 end-page=2426 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy and safety of esaxerenone in hypertensive patients with chronic kidney disease, with or without type 2 diabetes mellitus: a pooled analysis of five clinical studies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Effective management of blood pressure (BP) and albuminuria are crucial for suppressing chronic kidney disease (CKD) progression and cardiovascular risks in hypertension. This pooled analysis evaluated the antihypertensive effects, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD by integrating five clinical studies of esaxerenone. Patients were divided based on type 2 diabetes mellitus (T2DM) status (with or without T2DM) and creatinine-based estimated glomerular filtration rate (eGFRcreat) (30 to <60 and ≥60 mL/min/1.73 m2). Significant changes in morning home BP from baseline at Week 12 were observed in the overall population (mean change −12.8/ − 5.4 mmHg), T2DM subgroups ( − 12.2/ − 4.5 and −14.5/ − 7.8 mmHg), and eGFRcreat subgroups ( − 12.5/ − 4.7 and −14.0/ − 6.9 mmHg) (all P < 0.001). Bedtime home and office BP showed similar tendencies. Urine albumin-to-creatinine ratio significantly improved from baseline at Week 12 in the overall population (mean change: −55.2%), T2DM subgroups ( − 56.5% and −52.0%), and eGFRcreat subgroups ( − 54.6% and −55.4%) (all P < 0.001). N-terminal pro-B-type natriuretic peptide levels significantly decreased in the overall population (percent change: −14.1%) and subgroup without T2DM ( − 25.3%). The incidence of serum potassium ≥5.5 mEq/L was lower in the subgroup with T2DM vs without T2DM (3.1% and 11.3%), potentially related to the use of sodium–glucose cotransporter 2 inhibitors. These findings highlight the sustained BP-lowering effect of esaxerenone throughout the day in hypertensive patients with CKD, irrespective of T2DM status, and its significant reduction in albuminuria. The data support the safety and efficacy of esaxerenone in this patient population, underscoring its potential as a valuable therapeutic option. en-copyright= kn-copyright= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotokiHirohiko en-aut-sei=Motoki en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwaharaKoichiro en-aut-sei=Kuwahara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KarioKazuomi en-aut-sei=Kario en-aut-mei=Kazuomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatsuyaTomohiro en-aut-sei=Katsuya en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimosawaTatsuo en-aut-sei=Shimosawa en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsujitaKenichi en-aut-sei=Tsujita en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiShoko en-aut-sei=Suzuki en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SuedomiTomohiro en-aut-sei=Suedomi en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TaguchiTakashi en-aut-sei=Taguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Shinshu University School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Shinshu University School of Medicine kn-affil= affil-num=5 en-affil=Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine kn-affil= affil-num=6 en-affil=Katsuya Clinic kn-affil= affil-num=7 en-affil=Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University kn-affil= affil-num=9 en-affil=Data Intelligence Department, Daiichi Sankyo Co., Ltd. kn-affil= affil-num=10 en-affil=Primary Medical Science Department, Daiichi Sankyo Co., Ltd. kn-affil= affil-num=11 en-affil=Primary Medical Science Department, Daiichi Sankyo Co., Ltd. kn-affil= en-keyword=albuminuria kn-keyword=albuminuria en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=esaxerenone kn-keyword=esaxerenone en-keyword=morning hypertension kn-keyword=morning hypertension en-keyword=type 2 diabetes mellitus kn-keyword=type 2 diabetes mellitus END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=5 article-no= start-page=e70057 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of IgA Nephropathy With Membranoproliferative Glomerulonephritis-Like Features Miyu Kanazawa, en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18 years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7 g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5 months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features. en-copyright= kn-copyright= en-aut-name=KanazawaMiyu en-aut-sei=Kanazawa en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokiRyoya en-aut-sei=Aoki en-aut-mei=Ryoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SueMihiro en-aut-sei=Sue en-aut-mei=Mihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeHiromasa en-aut-sei=Miyake en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Okayama University Medical School kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama University Medical School kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Gd-IgA1 kn-keyword=Gd-IgA1 en-keyword=IgA nephropathy kn-keyword=IgA nephropathy en-keyword=membranoproliferative glomerulonephritis kn-keyword=membranoproliferative glomerulonephritis en-keyword=nephrotic syndrome kn-keyword=nephrotic syndrome en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=1100 end-page=1111 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relation between obesity and health disorders as revealed by the J-ORBIT clinical information collection system directly linked to electronic medical records (J-ORBIT 1) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims/Introduction: Obesity triggers various health disorders, but information on these disorders in real-world settings remains limited. To address this knowledge gap, we developed a database directly linked to electronic medical records (EMRs). We here present the baseline data for this database, designated Japan Obesity Research Based on electronIc healTh Records (J-ORBIT).
Materials and Methods: Individuals with obesity disease diagnosed according to the criteria of the Japan Society for the Study of Obesity were registered in J-ORBIT from seven medical centers in Japan. We analyzed the relationship between body mass index (BMI), clinical characteristics, and the prevalence of obesity-related health disorders in this cohort.
Results: Data were obtained from 1,169 individuals, with a mean (±SD) age of 56.9 ± 15.3 years and a BMI of 31.4 ± 6.1 kg/m2. The prevalence of health disorders varied substantially across BMI categories, with a higher BMI being associated with an increased prevalence of hyperuricemia or gout, obstructive sleep apnea syndrome or obesity hypoventilation syndrome, musculoskeletal disorders, and obesity-related kidney disease, as well as with a higher frequency of both a family history of obesity and of a history of childhood obesity. Among individuals with a BMI of ≥25 kg/m2, the prevalence of hypertension and dyslipidemia did not increase with BMI, whereas that of glucose intolerance decreased with increasing BMI.
Conclusions: The J-ORBIT system, which collects clinical data in real time directly from EMRs, has the potential to provide insight into obesity and its associated health conditions, thereby contributing to improved care of affected individuals. en-copyright= kn-copyright= en-aut-name=NishikageSeiji en-aut-sei=Nishikage en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirotaYushi en-aut-sei=Hirota en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakagawaYasushi en-aut-sei=Nakagawa en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiiMasamichi en-aut-sei=Ishii en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhsugiMitsuru en-aut-sei=Ohsugi en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaedaEiichi en-aut-sei=Maeda en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshimuraKai en-aut-sei=Yoshimura en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoAkane en-aut-sei=Yamamoto en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakayoshiTomofumi en-aut-sei=Takayoshi en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatoTakehiro en-aut-sei=Kato en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YabeDaisuke en-aut-sei=Yabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsuhisaMunehide en-aut-sei=Matsuhisa en-aut-mei=Munehide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujitaYukihiro en-aut-sei=Fujita en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KumeShinji en-aut-sei=Kume en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaegawaHiroshi en-aut-sei=Maegawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiyakeKana en-aut-sei=Miyake en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShojimaNobuhiro en-aut-sei=Shojima en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamauchiToshimasa en-aut-sei=Yamauchi en-aut-mei=Toshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YokoteKoutaro en-aut-sei=Yokote en-aut-mei=Koutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=UekiKohjiro en-aut-sei=Ueki en-aut-mei=Kohjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MiyoKengo en-aut-sei=Miyo en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OgawaWataru en-aut-sei=Ogawa en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Center for Medical Informatics Intelligence, National Center for Global Health and Medicine kn-affil= affil-num=5 en-affil=Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine kn-affil= affil-num=6 en-affil=Division of Medical Informatics, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=17 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=18 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=21 en-affil=Chiba University kn-affil= affil-num=22 en-affil=Diabetes Research Center, Research Institute, National Center for Global Health and Medicine kn-affil= affil-num=23 en-affil=Center for Medical Informatics Intelligence, National Center for Global Health and Medicine kn-affil= affil-num=24 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= en-keyword=Body mass index kn-keyword=Body mass index en-keyword=Electronic medical records kn-keyword=Electronic medical records en-keyword=Obesity kn-keyword=Obesity END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=5762 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Patients with end-stage renal disease have lower fasting plasma glucose and HbA1c levels, with significantly higher insulin levels. For a long time, it has been believed that this higher insulin level in renal failure is due to decreased insulin clearance caused by reduced renal function. However, here we reported that accumulation of the gut microbiota-derived uremic toxin, phenyl sulfate (PS) in the renal failure, increased insulin secretion from the pancreas by enhanced glucose-stimulated insulin secretion. Other endogenous sulfides compounds which accumulated as in the renal failure also increased glucose-stimulated insulin secretion from β-cell. With RNA-seq analyses and gene knock down, we demonstrated that insulin secretion evoked by PS was mediated by Ddah2. In addition, we also found that PS increased insulin resistance through lncRNA expression and Erk phosphorylation in the adipocytes. To confirm the relationship between PS and glucose metabolism in human, we recruited 2 clinical cohort studies (DKD and CKD) including 462 patients, and found that there was a weak negative correlation between PS and HbA1c. Because these trials did not measure fasting insulin level, we alternatively used the urinary C-peptide/creatinine ratio (UCPCR) as an indicator of insulin resistance. We found that PS may induce insulin resistance in patients with eGFR < 60 mL/min/1.73 m2. These data suggest that the accumulation of uremic toxins modulates glucose metabolism and induced insulin resistance in CKD and DKD patients. Considering HbA1c as a reflection of chronic hyperglycemia and UCPCR as a reflection of chronic hyperinsulinemia, our findings indicate that PS is negatively associated with hyperglycemia independent of CKD, and positively associated with hyperinsulinemia in DKD patients. en-copyright= kn-copyright= en-aut-name=TonguYoshiyasu en-aut-sei=Tongu en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaTomoko en-aut-sei=Kasahara en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkiyamaYasutoshi en-aut-sei=Akiyama en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiTakehiro en-aut-sei=Suzuki en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoHsin-Jung en-aut-sei=Ho en-aut-mei=Hsin-Jung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoYotaro en-aut-sei=Matsumoto en-aut-mei=Yotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KujiraiRyota en-aut-sei=Kujirai en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KikuchiKoichi en-aut-sei=Kikuchi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NataKoji en-aut-sei=Nata en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KanzakiMakoto en-aut-sei=Kanzaki en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SuzukiKenshin en-aut-sei=Suzuki en-aut-mei=Kenshin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeShun en-aut-sei=Watanabe en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KawabeChiharu en-aut-sei=Kawabe en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyataYui en-aut-sei=Miyata en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItaiShun en-aut-sei=Itai en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ToyoharaTakafumi en-aut-sei=Toyohara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SuzukiChitose en-aut-sei=Suzuki en-aut-mei=Chitose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaTetsuhiro en-aut-sei=Tanaka en-aut-mei=Tetsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TomiokaYoshihisa en-aut-sei=Tomioka en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AbeTakaaki en-aut-sei=Abe en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Tohoku University School of Medicine kn-affil= affil-num=2 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Medical Biochemistry, School of Pharmacy, Iwate Medical University kn-affil= affil-num=10 en-affil=Department of Biomedical Engineering, Tohoku University kn-affil= affil-num=11 en-affil=Tohoku University School of Medicine kn-affil= affil-num=12 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine kn-affil= en-keyword=CKD, DKD, Phenyl sulfate, Uremic toxin, Insulin secretion, Insulin resistance, Gut microbiota kn-keyword=CKD, DKD, Phenyl sulfate, Uremic toxin, Insulin secretion, Insulin resistance, Gut microbiota END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1568338 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250807 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A pilot transcriptomic study of a novel multitargeted BRT regimen for anti–MDA5 antibody-positive dermatomyositis: improving survival over conventional therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5-DM) is associated with severe outcomes, primarily due to rapidly progressive interstitial lung disease (RP-ILD), which is often refractory to standard therapies such as calcineurin inhibitors (e.g., tacrolimus) combined with cyclophosphamide (TC-Tx). This study evaluated the efficacy of a novel multitargeted regimen combining baricitinib, rituximab, and tacrolimus (BRT-Tx) in improving survival outcomes for MDA5-DM patients with poor prognostic factors.
Methods: Fourteen MDA5-DM patients with multiple adverse prognostic factors were studied. Seven received the BRT-Tx regimen, and the remaining seven, previously treated with TC-Tx, served as historical controls. Twelve-month survival was assessed. Transcriptome analysis was performed for six patients (BRT=3, TC=3), beginning with cluster analysis to evaluate whether changes in peripheral blood gene expression varied according to treatment or prognosis. Gene ontology analysis characterized expression profiles in survivors and distinguished treatment effects. Alterations in the type I, II, and III interferon signatures were also assessed.
Results: In the TC-Tx group, four of seven patients succumbed to RP-ILD, whereas all seven BRT-Tx patients survived the 12-month observation period. Only one BRT-Tx patient required combined rescue therapies, including plasma exchange, and one case of unexplained limbic encephalitis (LE) occurred. Cytomegalovirus reactivation was observed in both groups (BRT: 5/7; TC: 6/7). Transcriptomic analysis revealed no treatment-specific clustering of differentially expressed genes (DEGs) before and after therapy. However, survivors and nonsurvivors formed distinct clusters, with survivors showing significant posttreatment suppression of B-cell-related gene expression. Moreover, interferon signature scores were significantly lower after treatment in survivors than in nonsurvivors. BRT-Tx effectively suppressed B-cell-mediated immune responses and maintained a low interferon signature, while TC-Tx resulted in nonspecific gene suppression, and in nonsurvivors, an elevated interferon signature was observed.
Conclusion: BRT-Tx has the potential to improve survival in MDA5-DM patients by effectively targeting hyperactive immune pathways. The combination of rituximab and tacrolimus is expected to disrupt B-cell–T-cell interactions and reduce autoantibody production, whereas baricitinib may suppress both IFN and GM-CSF signaling, regulating excessive autoimmunity mediated by cells such as macrophages. Unlike TC-Tx, BRT-Tx avoids cyclophosphamide-associated risks such as infertility and secondary malignancies. Future randomized controlled trials are warranted to validate its efficacy and safety. en-copyright= kn-copyright= en-aut-name=TokunagaMoe en-aut-sei=Tokunaga en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaiYu en-aut-sei=Nakai en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoYoshiharu en-aut-sei=Sato en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiratsukaMitori en-aut-sei=Hiratsuka en-aut-mei=Mitori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakatsueTakeshi en-aut-sei=Nakatsue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaekiTakako en-aut-sei=Saeki en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmayaharaTakatsune en-aut-sei=Umayahara en-aut-mei=Takatsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KoyamaYoshinobu en-aut-sei=Koyama en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=DNA Chip Research Inc., Medical Laboratory kn-affil= affil-num=4 en-affil=DNA Chip Research Inc., Medical Laboratory kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital kn-affil= affil-num=7 en-affil=Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital kn-affil= affil-num=8 en-affil=Division of Dermatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= en-keyword=anti-MDA5 antibody-positive dermatomyositis (MDA5-DM) kn-keyword=anti-MDA5 antibody-positive dermatomyositis (MDA5-DM) en-keyword=JAK inhibitor kn-keyword=JAK inhibitor en-keyword=baricitinib kn-keyword=baricitinib en-keyword=rituximab kn-keyword=rituximab en-keyword=multitargeted treatment kn-keyword=multitargeted treatment en-keyword=IFN signature kn-keyword=IFN signature en-keyword=transcriptome analysis kn-keyword=transcriptome analysis END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=27481 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between proteinuria and mineral metabolism disorders in chronic kidney disease: the Japan chronic kidney disease database extension (J-CKD-DB-Ex) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR. en-copyright= kn-copyright= en-aut-name=ShimamotoSho en-aut-sei=Shimamoto en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaharaTakako en-aut-sei=Nakahara en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaShunsuke en-aut-sei=Yamada en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagasuHajime en-aut-sei=Nagasu en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KishiSeiji en-aut-sei=Kishi en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakashimaNaoki en-aut-sei=Nakashima en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsuruyaKazuhiko en-aut-sei=Tsuruya en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaHirokazu en-aut-sei=Okada en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamuraKouichi en-aut-sei=Tamura en-aut-mei=Kouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaritaIchiei en-aut-sei=Narita en-aut-mei=Ichiei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaruyamaShoichi en-aut-sei=Maruyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanoYuichiro en-aut-sei=Yano en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YokooTakashi en-aut-sei=Yokoo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WadaTakashi en-aut-sei=Wada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KandaEiichiro en-aut-sei=Kanda en-aut-mei=Eiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KataokaHiromi en-aut-sei=Kataoka en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NangakuMasaomi en-aut-sei=Nangaku en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KashiharaNaoki en-aut-sei=Kashihara en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NakanoToshiaki en-aut-sei=Nakano en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=2 en-affil=Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=3 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Department of Nephrology and Hypertension, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Nephrology and Hypertension, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Medical Informatics, Graduate School of Medical Science, Kyushu University kn-affil= affil-num=7 en-affil=Department of Nephrology, Nara Medical University kn-affil= affil-num=8 en-affil=Department of Nephrology, Faculty of Medicine, Saitama Medical University kn-affil= affil-num=9 en-affil=Department of Medical Science and Cardiorenal Medicine, Graduate School of Medicine, Yokohama City University kn-affil= affil-num=10 en-affil=Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of General Medicine, Juntendo University Faculty of Medicine kn-affil= affil-num=13 en-affil=Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine kn-affil= affil-num=14 en-affil=Department of Nephrology and Rheumatology, Kanazawa University kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Health Data Science, Kawasaki Medical School kn-affil= affil-num=17 en-affil=Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=18 en-affil=Division of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Nephrology and Hypertension, Kawasaki Medical School kn-affil= affil-num=20 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= en-keyword=CKD-MBD kn-keyword=CKD-MBD en-keyword=Proteinuria kn-keyword=Proteinuria en-keyword=Hyperphosphatemia kn-keyword=Hyperphosphatemia en-keyword=Hypocalcemia kn-keyword=Hypocalcemia en-keyword=Hypomagnesemia kn-keyword=Hypomagnesemia en-keyword=J-CKD-DB-Ex kn-keyword=J-CKD-DB-Ex END start-ver=1.4 cd-journal=joma no-vol=786 cd-vols= no-issue= article-no= start-page=152753 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Ischemia-reperfusion (I/R) injury induces oxidative stress, leading to damage in highly susceptible intestinal tissues. Molecular hydrogen (H2) has shown therapeutic potential in I/R injuries, with our prior research showing its efficacy in improving outcomes in rat intestinal transplantation models. However, its impact on mitochondrial function remain insufficiently understood. This study aims to elucidate how H2 modulates mitochondrial function impaired by I/R injury.
Methods: To assess the effects of H2 on I/R injury, cells were divided into three groups: a control group, a hypoxic group (99 % N2, 1 % O2, without H2 for 3, 6, or 24 h), and a hypoxic-H2 group (99 % H2, 1 % O2, for the same durations). After treatment, cells were reoxygenated under normoxic conditions (21 % O2) for 1, 2, 4, or 6 h. Mitochondrial membrane potential, oxygen consumption, and ATP production were measured. Reactive oxygen species production and apoptotic and metabolic regulators were also assessed.
Results: H2 markedly promoting mitochondrial recovery following I/R injury, by enhancing ATP production, restoring mitochondrial membrane potential, and improving oxygen consumption. It also reduced ROS levels and suppressed pro-apoptotic signaling. Notably, H2 suppressed the expression of HIF1α and PDK1, suggesting that H2 may act upstream of hypoxia-driven signaling pathways. These changes promoted oxidative phosphorylation and overall cellular function during reperfusion.
Conclusions: Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions. en-copyright= kn-copyright= en-aut-name=SeyaMizuki en-aut-sei=Seya en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MengYing en-aut-sei=Meng en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinoriKosaki en-aut-sei=Yoshinori en-aut-mei=Kosaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeAkihiro en-aut-sei=Watanabe en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaTaihei en-aut-sei=Yamada en-aut-mei=Taihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=10 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Intestinal ischemia-reperfusion injury kn-keyword=Intestinal ischemia-reperfusion injury en-keyword=Molecular hydrogen kn-keyword=Molecular hydrogen en-keyword=Hydrogen gas therapy kn-keyword=Hydrogen gas therapy en-keyword=Caco-2 cells kn-keyword=Caco-2 cells en-keyword=Mitochondrial function kn-keyword=Mitochondrial function en-keyword=Hypoxia-inducible factor-1α (HIF1α) kn-keyword=Hypoxia-inducible factor-1α (HIF1α) END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=2 article-no= start-page=650 end-page=653 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Transplantation of Multiple Organs from Donor after Helium Asphyxiation: First Case Report in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Helium inhalation has increased, but most cases are either minor injuries or deaths; there have not yet been any reported cases of brain death leading to organ donation. We report a patient who attempted helium inhalation and was declared brain dead and became an organ donor without complications. To the best of our knowledge, this is the first reported case of deceased organ donation following helium asphyxiation in Japan. The patient in cardiac arrest was found with a helium-filled vinyl bag sealed around the neck. During emergency medical transport to the hospital, a spontaneous return of circulation was obtained after 31 minutes of cardiopulmonary resuscitation. Upon hospital arrival, the physical examination revealed dilated pupils with no response to light. Electrocardiography showed widespread ST-segment depression and ST-segment elevation in augmented Vector Right, as well as elevated cardiac enzymes and decreased myocardial contractility. Head computed tomography revealed diffuse cerebral edema and loss of the gray-white matter boundary without signs of air embolism in the cerebral and coronary arteries. Despite comprehensive post-cardiac arrest care with recovery of organ function, brain death was confirmed on day 4 after hospitalization. The family consented to organ donation on the 11th day of hospitalization. The heart, lungs, liver, and two kidneys were successfully transplanted and all organs functioned. All organ grafts were functioning well at the 3-month follow-up. Our case demonstrates that brain death caused by helium inhalation is not a contraindication to organ donation. en-copyright= kn-copyright= en-aut-name=JinnoShunta en-aut-sei=Jinno en-aut-mei=Shunta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=brain death kn-keyword=brain death en-keyword=heart arrest kn-keyword=heart arrest en-keyword=helium kn-keyword=helium END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e64296 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Giant Choledochal Cyst in a Child With Spinocerebellar Ataxia: A Potential Molecular Link Through Aberrant Cytosolic Calcium Signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SumitomoHiromi en-aut-sei=Sumitomo en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanameTadashi en-aut-sei=Kaname en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakenouchiToshiki en-aut-sei=Takenouchi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Genome Medicine, National Center for Child Health and Development kn-affil= affil-num=4 en-affil=Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=calcium signaling kn-keyword=calcium signaling en-keyword=cerebellar ataxia 29 kn-keyword=cerebellar ataxia 29 en-keyword=cerebellar atrophy kn-keyword=cerebellar atrophy en-keyword=choledochal cyst kn-keyword=choledochal cyst en-keyword=congenital biliary dilatation kn-keyword=congenital biliary dilatation en-keyword=inositol 1,4,5-trisphosphate receptors kn-keyword=inositol 1,4,5-trisphosphate receptors en-keyword=ITPR1 kn-keyword=ITPR1 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251019 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of methotrexate-dosing regimens for GVHD prophylaxis on clinical outcomes of HLA-matched allogeneic HSCT en-subtitle= kn-subtitle= en-abstract= kn-abstract=Severe graft-versus-host disease (GVHD) remains a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), necessitating optimal immunosuppressive strategies. This retrospective study used data from the Japanese Transplant Registry Unified Management Program to compare three methotrexate (MTX)-dosing regimens for GVHD prophylaxis in patients undergoing human leucocyte antigen (HLA)-matched allo-HSCT: a low-dose 3-day regimen (Ld3:10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6), a low-dose 4-day regimen (Ld4: Ld3 with an additional 7 mg/m2 on day 11) and an original-dose 3-day regimen (Od3: 15 mg/m2 on day 1, 10 mg/m2 on days 3 and 6). Among 2537 analysed patients, Ld3 was the most commonly used regimen. Multivariate analyses showed no significant differences in the cumulative incidence of grade II–IV acute GVHD among regimens. However, Od3 was associated with an increased risk of grade III–IV acute GVHD, and Ld4 was linked to delayed neutrophil engraftment. This study is the first large-scale retrospective analysis of the impact of different MTX-dosing regimens on the outcomes of HLA-matched allo-HSCT, providing valuable insights into optimal MTX-dosing strategies in clinical practice. en-copyright= kn-copyright= en-aut-name=SuzukiTomotaka en-aut-sei=Suzuki en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JoTomoyasu en-aut-sei=Jo en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshifujiKota en-aut-sei=Yoshifuji en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTadakazu en-aut-sei=Kondo en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishidaTetsuya en-aut-sei=Nishida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OnishiYasushi en-aut-sei=Onishi en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SawaMasashi en-aut-sei=Sawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SerizawaKentaro en-aut-sei=Serizawa en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OtaShuichi en-aut-sei=Ota en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YoshimitsuMakoto en-aut-sei=Yoshimitsu en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=3 en-affil=Department of Hematology, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=5 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital kn-affil= affil-num=6 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Centre kn-affil= affil-num=7 en-affil=Department of Hematology, Japanese Red Cross Aichi Medical Centre Nagoya Daiichi Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Tohoku University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Haematopoietic Stem Cell Transplantation, National Cancer Centre Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Anjo Kosei Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Sapporo Hokuyu Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Kanagawa Cancer Centre kn-affil= affil-num=16 en-affil=Department of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=17 en-affil=Japanese Data Centre for Haematopoietic Cell Transplantation kn-affil= affil-num=18 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=allo-HSCT kn-keyword=allo-HSCT en-keyword=dosing regimens kn-keyword=dosing regimens en-keyword=graft-versus-host disease kn-keyword=graft-versus-host disease en-keyword=GVHD prophylaxis kn-keyword=GVHD prophylaxis en-keyword=methotrexate kn-keyword=methotrexate END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=5 article-no= start-page=e70138 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Late‐Onset Invasive Aspergillosis With Pituitary Involvement and Dysfunction Following CD19 Chimeric Antigen Receptor T‐Cell Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Invasive fungal infection (IFI) after chimeric antigen receptor (CAR) T-cell therapy is less common than bacterial and viral infections, but can be fatal once it develops. As most cases occur within 30 days after CAR T-cell infusion, late-onset IFI—particularly mould infection—appears to be under-recognised.
Discussion: We report an illustrative case of pituitary aspergillosis developing as late as one year after CD19 CAR T-cell therapy, highlighting a persistent risk in certain patients with delayed immune reconstitution.
Conclusion: This case underscores the need for continued vigilance and individualised antifungal strategies to prevent IFI beyond the early post-infusion period.
Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission. en-copyright= kn-copyright= en-aut-name=IkedaDaisuke en-aut-sei=Ikeda en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NawadaTomohiro en-aut-sei=Nawada en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinoharaTakayuki en-aut-sei=Shinohara en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaganoTomohiro en-aut-sei=Nagano en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KubotaSaya en-aut-sei=Kubota en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiyamaRyuichiro en-aut-sei=Hiyama en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoMasaya en-aut-sei=Ueno en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MakitaMasanori en-aut-sei=Makita en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=The Center for Graduate Medical Education, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Fungal Infection, National Institute of Infectious Diseases kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Chugoku Central Hospital kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=aspergillosis kn-keyword=aspergillosis en-keyword=CD19 CAR T kn-keyword=CD19 CAR T en-keyword=invasive fungal infection kn-keyword=invasive fungal infection en-keyword=pituitary kn-keyword=pituitary END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=18 article-no= start-page=4640 end-page=4653 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC en-subtitle= kn-subtitle= en-abstract= kn-abstract=Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials. en-copyright= kn-copyright= en-aut-name=AkahoshiYu en-aut-sei=Akahoshi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InamotoYoshihiro en-aut-sei=Inamoto en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SpyrouNikolaos en-aut-sei=Spyrou en-aut-mei=Nikolaos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakasoneHideki en-aut-sei=Nakasone en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DinizMarcio A. en-aut-sei=Diniz en-aut-mei=Marcio A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AyukFrancis en-aut-sei=Ayuk en-aut-mei=Francis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChoeHannah K. en-aut-sei=Choe en-aut-mei=Hannah K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EtoTetsuya en-aut-sei=Eto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EtraAaron M. en-aut-sei=Etra en-aut-mei=Aaron M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HexnerElizabeth O. en-aut-sei=Hexner en-aut-mei=Elizabeth O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiramotoNobuhiro en-aut-sei=Hiramoto en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HoganWilliam J. en-aut-sei=Hogan en-aut-mei=William J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HollerErnst en-aut-sei=Holler en-aut-mei=Ernst kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KataokaKeisuke en-aut-sei=Kataoka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawakitaToshiro en-aut-sei=Kawakita en-aut-mei=Toshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaTakashi en-aut-sei=Tanaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=UchidaNaoyuki en-aut-sei=Uchida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=VasovaIngrid en-aut-sei=Vasova en-aut-mei=Ingrid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YoshiharaSatoshi en-aut-sei=Yoshihara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=IshimaruFumihiko en-aut-sei=Ishimaru en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ChenYi-Bin en-aut-sei=Chen en-aut-mei=Yi-Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamuraRyotaro en-aut-sei=Nakamura en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=FerraraJames L. M. en-aut-sei=Ferrara en-aut-mei=James L. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=LevineJohn E. en-aut-sei=Levine en-aut-mei=John E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TeshimaTakanori en-aut-sei=Teshima en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=2 en-affil=Department of Blood and Marrow Transplantation and Cellular Therapy, Fujita Health University School of Medicine kn-affil= affil-num=3 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=4 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=5 en-affil=Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf kn-affil= affil-num=8 en-affil=Division of Hematology, Blood and Marrow Transplantation Program, The Ohio State University Comprehensive Cancer Center kn-affil= affil-num=9 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Hamanomachi Hospital kn-affil= affil-num=11 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=12 en-affil=Department of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Department of Hematology, Kobe City Medical Center General Hospital kn-affil= affil-num=14 en-affil=Division of Hematology, Mayo Clinic kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Internal Medicine III, University of Regensburg kn-affil= affil-num=16 en-affil=Division of Molecular Oncology, National Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Department of Hematology, National Hospital Organization Kumamoto Medical Center kn-affil= affil-num=18 en-affil=Department of Hematology, Kanagawa Cancer Center kn-affil= affil-num=19 en-affil=Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital kn-affil= affil-num=21 en-affil=Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen kn-affil= affil-num=22 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=23 en-affil=Technical Department, Japanese Red Cross Blood Service Headquarters kn-affil= affil-num=24 en-affil=Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=25 en-affil=Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital kn-affil= affil-num=26 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=27 en-affil=Department of Hematology and Hematopoietic Cell Transplantation, City of Hope kn-affil= affil-num=28 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=29 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=30 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=31 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=32 en-affil=Department of Hematology, Hokkaido University Faculty of Medicine and Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of ciclosporin monotherapy in non-severe aplastic anaemia not requiring transfusions: Results from a multicentre phase II study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The efficacy of ciclosporin (CsA) to treat transfusion-independent non-severe aplastic anaemia (TI-NSAA) has not yet been systematically evaluated. We conducted a prospective trial in patients with TI-NSAA treated with CsA monotherapy. CsA (3.5 mg/kg/day) was administered to patients with TI-NSAA aged ≥16. The CsA dose was adjusted to maintain a blood CsA level of ≥600 ng/mL at 2 h post-administration. Blood cell counts were assessed after 8, 16 and 52 weeks of therapy. Thirty-two evaluable patients from 21 institutions were enrolled. The median age was 63.5 (range: 16–83) years. At 8 weeks, haematological improvement, with increases in haemoglobin (Hb) ≥1.5 g/dL (haematological improvement in erythrocytes [HI-E]) and platelet count ≥30 × 109/L (haematological improvement in platelets [HI-P]), was observed in 0/25 (0%) and 6/32 (19%) evaluable cases respectively. HI-E and HI-P occurred in 1/25 (4%) and 10/32 (31%) patients at 16 weeks, respectively, and at 52 weeks in 5/25 (20%) and 16/32 (50%) patients respectively. Nine grade 3 adverse events (AEs) occurred in six patients, but there were no grade ≥4 AEs. Ten of the 32 patients experienced grade 2 renal toxicity. Low-dose CsA is effective in TI-NSAA patients and demonstrates minimal renal toxicity. However, at least 16 weeks are necessary to adequately evaluate its efficacy. en-copyright= kn-copyright= en-aut-name=IshiyamaKen en-aut-sei=Ishiyama en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamazakiMasahide en-aut-sei=Yamazaki en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaruyamaHiroyuki en-aut-sei=Maruyama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosonoNaoko en-aut-sei=Hosono en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamaguchiHiroki en-aut-sei=Yamaguchi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanimotoKazuki en-aut-sei=Tanimoto en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UsukiKensuke en-aut-sei=Usuki en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshimuraKenichi en-aut-sei=Yoshimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OgawaSeishi en-aut-sei=Ogawa en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KanakuraYuzuru en-aut-sei=Kanakura en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsumuraItaru en-aut-sei=Matsumura en-aut-mei=Itaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AkashiKoichi en-aut-sei=Akashi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakaoShinji en-aut-sei=Nakao en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Keiju Medical Center kn-affil= affil-num=3 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, University of Fukui Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Nippon Medical School kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Japanese Red Cross Fukuoka Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers kn-affil= affil-num=9 en-affil=Department of Hematology, NTT Medical Center Tokyo kn-affil= affil-num=10 en-affil=Department of Biostatistics and Health Data Science, Graduate School of Medical Science, Nagoya City University kn-affil= affil-num=11 en-affil=Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University kn-affil= affil-num=12 en-affil=Sumitomo Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= en-keyword=ciclosporin kn-keyword=ciclosporin en-keyword=prospective study kn-keyword=prospective study en-keyword=renal toxicity kn-keyword=renal toxicity en-keyword=transfusion-independent non-severe aplastic anaemia kn-keyword=transfusion-independent non-severe aplastic anaemia END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=6 article-no= start-page=e098532 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protocol for a multicentre, open-label, dose-escalation phase I/II study evaluating the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive natural killer cell leukaemia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Aggressive natural killer cell leukaemia (ANKL) is a rare form of NK cell lymphoma with a very low incidence and poor prognosis. While multi-agent chemotherapy including L-asparaginase has been used to treat ANKL patients, they often cannot receive adequate chemotherapy at diagnosis due to liver dysfunction. PPMX-T003, a fully human monoclonal antibody targeting the transferrin receptor 1, shows promise in treating ANKL by helping patients recover from fulminant clinical conditions, potentially enabling a transition to chemotherapy. This study aimed to evaluate the tolerability, safety, efficacy, and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with ANKL.
Methods and analysis This multicentre, open-label, dose-escalation phase I/II study will be conducted at nine hospitals in Japan. Patients diagnosed with ANKL (whether as a primary or recurrent disease) and exhibiting abnormal liver function or hepatomegaly due to the primary disease will be included. The primary endpoint is the tolerability and safety of repeated continuous intravenous administration of PPMX-T003 in the first course, based on adverse events and dose-limiting toxicities. PPMX-T003 will be administered as a continuous intravenous infusion every 24 hours for five consecutive days, followed by a 2-day break. Pretreatment will be provided to minimise the risk of infusion-related reactions. Initial doses of PPMX-T003 will be 0.5, 1.0 or 2.0 mg/kg, with subsequent dose increases determined by the Data and Safety Monitoring Committee. The sample size is set at seven participants, with enrolment increased to up to 12 participants if dose-limiting toxicities occur, based on feasibility due to the rarity of ANKL. Descriptive statistics will summarise data according to initial dose, and pharmacokinetic analysis will be conducted based on administered dose.
Ethics and dissemination This study was approved by the institutional review boards at participating hospitals. The results will be disseminated in peer-reviewed journals.
Trial registration number jRCT2061230008 (jRCT); NCT05863234 (ClinicalTrials.gov). en-copyright= kn-copyright= en-aut-name=FukuharaNoriko en-aut-sei=Fukuhara en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnizukaMakoto en-aut-sei=Onizuka en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoKiyoshi en-aut-sei=Ando en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Hematology, Tohoku University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Tokai University School of Medicine Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=6 en-affil=Department of Hematology, Hiroshima University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=98 cd-vols= no-issue= article-no= start-page=103224 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The vicious cycle between nutrient deficiencies and antibiotic-induced nutrient depletion at the host cell-pathogen interface: Coenzyme Q10 and omega-6 as key molecular players en-subtitle= kn-subtitle= en-abstract= kn-abstract=The increasing prevalence of antibiotic resistance and pathological inflammation underscores the importance of understanding the underlying biochemical and immune processes that govern the host-pathogen interface. Nutrient deficiency, compounded by antibiotic-induced nutrient depletion, forms a vicious cycle of overt inflammation, contributing to bacterial toxin translocation in human inter-organ and intra-organs milieus. Coenzyme Q10 (CoQ10) and omega-6 linoleic acid (LA 18:2ω6) are integral to cellular membrane integrity and immune defense. However, the complex enzymatic steps at the host cell-pathogen interface remain poorly understood. This study is particularly timely, as it explores these knowledge gaps, which can inform the development of nutritional and therapeutic strategies that modulate or target these mechanisms. Using an infectious-inflamed cell co-culture model of the gut-liver axis, we exposed triple cell co-cultures of human intestinal epithelial cells (T84), macrophage-like THP-1 cells, and hepatic cells (Huh7) to linoleic acid-producing Lactobacillus casei (L. casei) and Pseudomonas aeruginosa strain PAO1 (PAO1). The cultures were incubated for 6 h in medium with or without ceftazidime antibiotic. PAO1 and L. casei exerted opposing effects on the secretion of Th1 cytokines IL-1β, IL-6, and the Th 2-type cytokine IL-10. Inoculation with PAO1 decreased CoQ10 and linoleic acid levels compared to uninfected controls. L. casei restored cellular health and biofunctionality impaired by PAO1, indicating its benefit to the host's well-being. The antibiotic ceftazidime exerted dual effects, alleviating PAO1 toxicity while marginally disrupting the beneficial effects of L. casei. Our results show how the vicious cycle of nutrient deficiency and antibiotic-induced nutrient loss reinforces pathological inflammation at the host cell-pathogen interface and highlights the need for more appropriate targeted antibiotic use that preserves essential nutrients like CoQ10 and omega-6 fatty acids. Inflammatory responses driven by opportunistic pathogens and LA-producing bacteria represent opposing immunometabolic pathways that may provide insights into novel approaches for treating infection and reducing antibiotic resistance. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BlömerSophia en-aut-sei=Blömer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Şahi̇n KayaAysel en-aut-sei=Şahi̇n Kaya en-aut-mei=Aysel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KrügerSandra en-aut-sei=Krüger en-aut-mei=Sandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RöckenChristoph en-aut-sei=Röcken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SchäferHeiner en-aut-sei=Schäfer en-aut-mei=Heiner kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Faculty of Medicine, Christian-Albrechts-University of Kiel kn-affil= affil-num=3 en-affil=Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University kn-affil= affil-num=4 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel kn-affil= affil-num=7 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=9 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Antibiotics kn-keyword=Antibiotics en-keyword=Coenzyme Q10 kn-keyword=Coenzyme Q10 en-keyword=Infection kn-keyword=Infection en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Micronutrients kn-keyword=Micronutrients en-keyword=Oxidative stress kn-keyword=Oxidative stress END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome. en-copyright= kn-copyright= en-aut-name=TanakayaKohji en-aut-sei=Tanakaya en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaguchiTatsuro en-aut-sei=Yamaguchi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirataKeiji en-aut-sei=Hirata en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaMasayoshi en-aut-sei=Yamada en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumamotoKensuke en-aut-sei=Kumamoto en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaYasuki en-aut-sei=Akiyama en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshimaruKei en-aut-sei=Ishimaru en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKoichi en-aut-sei=Okamoto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawasakiYuko en-aut-sei=Kawasaki en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KomineKeigo en-aut-sei=Komine en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakamotoAkira en-aut-sei=Sakamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShibataYoshiko en-aut-sei=Shibata en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShimamotoYusaku en-aut-sei=Shimamoto en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShimodairaHideki en-aut-sei=Shimodaira en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SekineShigeki en-aut-sei=Sekine en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakaoAkinari en-aut-sei=Takao en-aut-mei=Akinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakaoMisato en-aut-sei=Takao en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TakamizawaYasuyuki en-aut-sei=Takamizawa en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakeuchiYoji en-aut-sei=Takeuchi en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TanabeNoriko en-aut-sei=Tanabe en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ChinoAkiko en-aut-sei=Chino en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=ChoHourin en-aut-sei=Cho en-aut-mei=Hourin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=DoiSatoru en-aut-sei=Doi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=NakajimaTakeshi en-aut-sei=Nakajima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamoriSakiko en-aut-sei=Nakamori en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakayamaYoshiko en-aut-sei=Nakayama en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NagasakiToshiya en-aut-sei=Nagasaki en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HasumiHisashi en-aut-sei=Hasumi en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=BannoKouji en-aut-sei=Banno en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=HinoiTakao en-aut-sei=Hinoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=FujiyoshiKenji en-aut-sei=Fujiyoshi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HorimatsuTakahiro en-aut-sei=Horimatsu en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=MasudaKenta en-aut-sei=Masuda en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=MiguchiMasashi en-aut-sei=Miguchi en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=MizuuchiYusuke en-aut-sei=Mizuuchi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=MiyakuraYasuyuki en-aut-sei=Miyakura en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=MutohMichihiro en-aut-sei=Mutoh en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=YoshiokaTakahiro en-aut-sei=Yoshioka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=TanakaShinji en-aut-sei=Tanaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SakamotoKazuhiro en-aut-sei=Sakamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SakamakiKentaro en-aut-sei=Sakamaki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ItabashiMichio en-aut-sei=Itabashi en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=IshidaHideyuki en-aut-sei=Ishida en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=TomitaNaohiro en-aut-sei=Tomita en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=SugiharaKenichi en-aut-sei=Sugihara en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=AjiokaYoichi en-aut-sei=Ajioka en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= affil-num=1 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=2 en-affil=Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=3 en-affil=Department of Surgery 1, University of Occupational and Environmental Health kn-affil= affil-num=4 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Genome Medical Science and Medical Genetics, Faculty of Medicine, Kagawa University kn-affil= affil-num=6 en-affil=Department of Surgery 1, University of Occupational and Environmental Health kn-affil= affil-num=7 en-affil=Division of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science kn-affil= affil-num=9 en-affil=College of Nursing, University of Hyogo kn-affil= affil-num=10 en-affil=Department of Medical Oncology, Tohoku University Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Himawari-No-Kai (Sunflower Association), a Patient Advocacy Group for Individuals and Families Affected By Lynch Syndrome kn-affil= affil-num=14 en-affil=Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Division of Medical Oncology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University kn-affil= affil-num=16 en-affil=Department of Pathology, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=19 en-affil=Department of Colorectal Surgery, National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=22 en-affil=Department of Surgery, Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=23 en-affil=Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research kn-affil= affil-num=24 en-affil=Endoscopy Center, Tokyo Medical University Hospital kn-affil= affil-num=25 en-affil=Harmony Line (Association for Patients and Families With Familial Adenomatous Polyposis) kn-affil= affil-num=26 en-affil=Division of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer Institute kn-affil= affil-num=27 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=28 en-affil=Department of Pediatrics, Shinshu University School of Medicine kn-affil= affil-num=29 en-affil=Department of Gastroenterological Surgery, Saitama Cancer Center kn-affil= affil-num=30 en-affil=Department of Urology, Yokohama City University kn-affil= affil-num=31 en-affil=Center of Maternal -Fetal/Neonatal Medicine, Hiroshima University Hospital kn-affil= affil-num=32 en-affil=Department of Clinical and Molecular Genetics, Hiroshima University Hospital kn-affil= affil-num=33 en-affil=Department of Surgery, Kurume University School of Medicine kn-affil= affil-num=34 en-affil=Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital kn-affil= affil-num=35 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=36 en-affil=Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital kn-affil= affil-num=37 en-affil=Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=38 en-affil=Department of Colon and Pelvic Surgery, Cancer Prevention and Genetic Counseling, Tochigi Cancer Center kn-affil= affil-num=39 en-affil=Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=40 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=41 en-affil=JA Onomichi General Hospital kn-affil= affil-num=42 en-affil=Koshigaya Municipal Hospital kn-affil= affil-num=43 en-affil=Faculty of Health Data Science, Juntendo University kn-affil= affil-num=44 en-affil=Saiseikai Kazo Hospital kn-affil= affil-num=45 en-affil=Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=46 en-affil=Division of Cancer Treatment , Toyonaka Municipal Hospital kn-affil= affil-num=47 en-affil=Institute of Science Tokyo kn-affil= affil-num=48 en-affil=Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=Hereditary colorectal cancer kn-keyword=Hereditary colorectal cancer en-keyword=Guidelines kn-keyword=Guidelines en-keyword=Familial adenomatous polyposis kn-keyword=Familial adenomatous polyposis en-keyword=Lynch syndrome kn-keyword=Lynch syndrome END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=11 article-no= start-page=e97797 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-Term Outcome of Xenon-Arc Photocoagulation for Retinopathy of Prematurity in the 1970s in Japan: Eleven Patients With 32- to 49-Year Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Photocoagulation or cryocautery, or their combinations, are the standard of care for retinopathy of prematurity at the recommended timing, which is based on the International Classification of Retinopathy of Prematurity. In Japan, the effectiveness of xenon-arc photocoagulation and cryocautery in retinopathy of prematurity was reported on an empirical basis first in 1968, and became the standard of care in retinopathy of prematurity in the 1970s, 10 years earlier compared with the other countries. In this study, we reported the up to 49 years visual outcome of 11 patients with retinopathy of prematurity who underwent xenon-arc photocoagulation and cryocautery in the 1970s.
Methods: A retrospective review was made on the medical records of 11 consecutive patients who underwent xenon-arc photocoagulation for retinopathy of prematurity in the years 1974 to 1980, and were followed up until the period from 2009 to 2025. The birthweight ranged from 865 g to 2300 g at a median of 1350 g, and the gestational age at birth ranged from 27 weeks to 36 weeks at a median of 30 weeks. The corrected gestational age at the time of photocoagulation ranged from 32 weeks to 53 weeks, with a median of 37 weeks. Oxygen was given to all 11 patients, except for one who was born in the earliest year 1974. The retinopathy of prematurity was at stage 3 in both eyes of seven patients, with plus disease signs in four patients, at stage 2 with and without plus disease in two patients, at stage 2 and stage 3 in each eye of one patient, and at stage 1 with plus disease in both eyes of one patient. The entire 360-degree photocoagulation was given in seven patients, while partial photocoagulation was applied in four patients. Additional cryocautery was applied in six patients.
Results: The age at the last visit ranged from 32 to 49 years with a median of 46 years. At the last visit, seven patients showed the best-corrected visual acuity in decimals of 0.8 or better in both eyes. One dizygotic twin showed no light perception in the phthisic right eye and 0.1 in the left eye with macular degeneration and nystagmus after he underwent cataract surgery at the age of 34 years. The other twin had the best-corrected visual acuity of 0.5 in the right eye and 0.02 in the left eye due to macular degeneration after he underwent cataract surgeries in both eyes at the age of 36 years. Two patients developed rhegmatogenous retinal detachment in one eye at the age of 44 and 41 years, respectively, and underwent vitrectomy with silicone oil tamponade, resulting in visual acuity of 0.1 and 0.3, respectively. Two patients experienced vitreous hemorrhage in one eye, which was absorbed spontaneously at the ages of 37 years and 42 years, respectively. One patient underwent partial scleral buckling for localized rhegmatogenous retinal detachment. No patient used intraocular pressure-lowering eyedrops.
Conclusion: Most patients with xenon-arc photocoagulation for retinopathy of prematurity in the 1970s maintained standard levels of visual acuity up to 49 years in the follow-up. Cataract, retinal detachment, and vitreous hemorrhage were noted as late complications and were coped with on an individual basis. The conclusion would have a meaning, even though not novel, that the patients with retinopathy of prematurity would have benefited from the xenon-arc photocoagulation and cryocautery. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoNobuhiko en-aut-sei=Matsuo en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Ophthalmology, Okayama University Medical School kn-affil= en-keyword=1970s kn-keyword=1970s en-keyword=cataract kn-keyword=cataract en-keyword=cryocautery kn-keyword=cryocautery en-keyword=japan kn-keyword=japan en-keyword=late complications kn-keyword=late complications en-keyword=neonatology kn-keyword=neonatology en-keyword=retinal detachment kn-keyword=retinal detachment en-keyword=retinopathy of prematurity kn-keyword=retinopathy of prematurity en-keyword=vitreous hemorrhage kn-keyword=vitreous hemorrhage en-keyword=xenon-arc photocoagulation kn-keyword=xenon-arc photocoagulation END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=366 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis of thienoacenes by electrochemical double C–S cyclization using a halogen mediator en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thienoacenes are significant compounds as organic materials. One of the most efficient ways to synthesize thienoacenes is to form multiple C–S bonds in a single step. Because unprotected S–H bonds are easily oxidized to S–S bonds, S-Me protected substrates are commonly used for the purpose. However, their reactivity is insufficient, and one-step construction of multiple C–S bonds is still challenging. We herein report the electrochemical synthesis of thienoacenes from S-methoxymethyl (MOM)-protected diarylacetylenes. In the presence of Bu4NBr as a halogen mediator, electrochemical double C–S cyclization of diarylacetylenes bearing two MOM groups proceeded to afford [1]benzothieno[3,2-b][1]benzothiophene (BTBT) derivatives. While S-Me or S-p-methoxybenzyl (PMB)-protected diarylacetylenes did not afford BTBT, BTBT was selectively obtained when a substrate protected with S-MOM groups was used. The S-MOM protection strategy is also effective for the electrochemical synthesis of a more π-expanded thienoacene such as dibenzo[d,d′]thieno[3,2-b,4,5-b′]dithiophene (DBTDT). en-copyright= kn-copyright= en-aut-name=MitsudoKoichi en-aut-sei=Mitsudo en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaharaTakuya en-aut-sei=Nagahara en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatauraNozomi en-aut-sei=Kataura en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkamuraYuka en-aut-sei=Okamura en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YonezawaToki en-aut-sei=Yonezawa en-aut-mei=Toki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TachibanaYuri en-aut-sei=Tachibana en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SouliéNolan en-aut-sei=Soulié en-aut-mei=Nolan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShigemoriKeisuke en-aut-sei=Shigemori en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoEisuke en-aut-sei=Sato en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Science and Engineering, Sorbonne Université kn-affil= affil-num=8 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=11 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Role of the Mylohyoid Line in the Spread of Mandibular Odontogenic Deep Neck Infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Although mandibular odontogenic deep neck infections are occasionally fatal, the transmission pathway has not been elucidated.
Materials and Methods: This multicenter retrospective study was comprised of the patients of both sexes who were over 18 years of age and who had mandibular odontogenic deep neck abscesses. The patients' characteristics, laboratory tests, and radiographic findings were analyzed.
Results: One hundred eighteen patients with mandibular odontogenic deep neck abscesses were included. Bone resorption superior to the mylohyoid line and the related abscess formation in submandibular space or submental space were both significantly associated with the presence of sublingual space abscess. In addition, the type of causative tooth was not a risk factor for abscess formation in both the sublingual space and “submandibular or submental” space.
Conclusions: When an odontogenic lesion is located superior to the mylohyoid line, the abscess tends to initially form in the sublingual space and subsequently spread to the submandibular or submental space. Since any mandibular tooth can lead to abscess formation in these regions, oral and maxillofacial surgeons should carefully assess the anatomical position of the lesion and accurately identify the causative tooth. en-copyright= kn-copyright= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikutaShogo en-aut-sei=Kikuta en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanekoNaoki en-aut-sei=Kaneko en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKotaro en-aut-sei=Sato en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitagawaNorio en-aut-sei=Kitagawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuoKatsuhisa en-aut-sei=Matsuo en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SameshimaJunsei en-aut-sei=Sameshima en-aut-mei=Junsei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TachibanaAkira en-aut-sei=Tachibana en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawanoShintaro en-aut-sei=Kawano en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KusukawaJingo en-aut-sei=Kusukawa en-aut-mei=Jingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AkashiMasaya en-aut-sei=Akashi en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=4 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Nagoya University, Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=9 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital kn-affil= affil-num=11 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=12 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= en-keyword=causative tooth kn-keyword=causative tooth en-keyword=mylohyoid line kn-keyword=mylohyoid line en-keyword=odontogenic deep neck abscesses kn-keyword=odontogenic deep neck abscesses en-keyword=odontogenic deep neck infections kn-keyword=odontogenic deep neck infections en-keyword=transmission pathway kn-keyword=transmission pathway END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=e2025-0034 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimal Virtual-target Definition for Detecting Feeding Arteries of Renal Cell Carcinoma Using Automated Feeder-detection Software en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To determine the optimal virtual-target definition for detecting renal cell carcinoma feeders using transarterial computed tomography angiography with automated feeder-detection software.
Material and Methods: This retrospective study included 17 patients with 17 renal cell carcinomas who underwent transarterial ethiodized-oil marking before cryoablation. Tumor feeders were automatically detected on transarterial renal computed tomography angiography images using the automated feeder-detection software with three virtual-target definitions: small (ellipsoidal area maximized within the tumor contour), medium (ellipsoidal area covering the entire tumor with a minimal peripheral margin), and large (ellipsoidal area including the tumor and a 5-mm peripheral margin). The detected feeders were classified as true or false positives according to the findings of selective renal arteriography, by consensus of two interventional radiologists. Feeder-detection sensitivity and the mean number of false-positive feeders per tumor were calculated for each virtual-target definition.
Results: For 17 tumors, 25 feeding arteries were identified on the arteriography. The feeder-detection sensitivity of the software was 80.0% (20/25), 88.0% (22/25), and 48.0% (12/25) for small, medium, and large virtual targets, respectively. The mean ± standard deviation number of false-positive feeders per tumor was 0.82 ± 1.3, 1.41 ± 1.1, and 2.82 ± 1.6 when using small, medium, and large virtual-target definitions, respectively.
Conclusions: The detection rate of renal cell carcinoma feeders with the automated feeder-detection software varies according to the virtual-target definition. Using a medium virtual target, covering the entire tumor with a minimal peripheral margin, may provide the highest sensitivity and an acceptable number of false-positive feeders. en-copyright= kn-copyright= en-aut-name=OkamotoSoichiro en-aut-sei=Okamoto en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawabataTakahiro en-aut-sei=Kawabata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MunetomoKazuaki en-aut-sei=Munetomo en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Tsuyama Chuo Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=5 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=8 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=computed tomography angiography kn-keyword=computed tomography angiography en-keyword=kidney kn-keyword=kidney en-keyword=software kn-keyword=software en-keyword=therapeutic embolization kn-keyword=therapeutic embolization END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=1 article-no= start-page=95 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case of a large venous ring around the mandibular condyle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anatomical details regarding venous drainage of the head and neck are an important matter for surgeons to avoid unnecessary complications such as hemorrhage. This report describes a case of the large venous ring around the mandibular condyle found in the cadaver. The left maxillofacial region of a latex-injected embalmed male cadaver (82 years of age at death) was dissected. The large two maxillary veins ran lateral to the capsule and superior to the mandibular notch and coursed posteroinferiorly to merge, and one trunk was formed at the posterior border of the ramus. It then received the superficial temporal vein superiorly to form the retromandibular vein (RMV). In addition, three maxillary veins were drained from the pterygoid venous plexus (PVP), medial to the ramus, one maxillary vein drained from the PVP into the RMV trunk, while two maxillary veins drained from the PVP into the anterior division of the RMV. All five large veins lateral and medial to the condyle drained from the PVP into the RMV. The knowledge of such an anatomical variation might prevent intraoperative bleeding in the temporomandibular joint region. en-copyright= kn-copyright= en-aut-name=NishiKeitaro en-aut-sei=Nishi en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkuiTatsuo en-aut-sei=Okui en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KusukawaJingo en-aut-sei=Kusukawa en-aut-mei=Jingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TubbsR. Shane en-aut-sei=Tubbs en-aut-mei=R. Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=2 en-affil=Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=5 en-affil=Department of Neurosurgery, Clinical Neuroscience Research Center, Tulane University School of Medicine kn-affil= affil-num=6 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= en-keyword=Maxillary vein kn-keyword=Maxillary vein en-keyword=Temporomandibular joint kn-keyword=Temporomandibular joint en-keyword=Cadaver kn-keyword=Cadaver en-keyword=Anatomy kn-keyword=Anatomy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250917 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of CT-assessed sarcopenia on the severity of odontogenic deep neck infections: a retrospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sarcopenia is increasingly recognized as a key predictor of adverse health outcomes. This study aimed to evaluate the impact of computed tomography-assessed sarcopenia (CT–SP) on the clinical severity and hospitalization duration of odontogenic deep neck infections (DNIs). Total of 119 patients admitted for odontogenic DNI treatment were included. Patients were divided into two groups by DNI clinical severity (severe or mild) and the patients' characteristics, including CT–SP based on skeletal muscle index (SMI), were compared between two groups. Multivariable logistic regression analysis was performed to identify independent risk factors for severe DNI. The correlation between SMI and hospitalization duration was assessed using Spearman’s rank correlation coefficient. Of the 119 patients, 60 (50.4%) presented with severe DNIs, including deep neck abscesses and necrotizing soft tissue infections. After adjusting for potential confounders, multivariable analysis identified CT–SP as the sole independent risk factor associated with severe DNI (Odds Ratio = 3.04; 95% Confidence Interval, 1.20–7.71; p = 0.019). Furthermore, SMI demonstrated a significant, weak negative correlation with the hospitalization duration (r = − 0.331, p < 0.001). CT–SP is a powerful, independent risk factor associated with severity in patients with odontogenic DNIs. This finding underscores the critical role of systemic host factors in the clinical course of maxillofacial infections and highlights the potential of opportunistic CT screening as a factor to consider in risk stratification in this vulnerable population. en-copyright= kn-copyright= en-aut-name=KikutaShogo en-aut-sei=Kikuta en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiChizuru en-aut-sei=Kobayashi en-aut-mei=Chizuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimuraHiroki en-aut-sei=Kimura en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KinisadaYuki en-aut-sei=Kinisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TachibanaAkira en-aut-sei=Tachibana en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KusukawaJingo en-aut-sei=Kusukawa en-aut-mei=Jingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkashiMasaya en-aut-sei=Akashi en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital kn-affil= affil-num=8 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=CT-assessed sarcopenia kn-keyword=CT-assessed sarcopenia en-keyword=Odontogenic deep neck infections kn-keyword=Odontogenic deep neck infections en-keyword=Severity kn-keyword=Severity en-keyword=Hospitalization duration kn-keyword=Hospitalization duration en-keyword=Skeletal muscle index kn-keyword=Skeletal muscle index END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=127 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical predictors of extubation failure in postoperative critically ill patients: a post-hoc analysis of a multicenter prospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Postoperative patients constitute majority of critically ill patients, although factors predicting extubation failure in this group of patients remain unidentified. Aiming to propose clinical predictors of reintubation in postoperative patients, we conducted a post-hoc analysis of a multicenter prospective observational study.
Methods This study included postoperative critically ill patients who underwent mechanical ventilation for > 24 h and were extubated after a successful 30-min spontaneous breathing trial. The primary outcome was reintubation within 48 h after extubation, and clinical predictors for reintubation were investigated using logistic regression analyses.
Results Among the 355 included patients, 10.7% required reintubation. Multivariable logistic regression identified that the number of endotracheal suctioning episodes during the 24 h before extubation and underlying respiratory disease or pneumonia occurrence were significantly associated with reintubation (adjusted odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05–1.18, p < 0.001; adjusted OR 2.58, 95%CI 1.30–5.13, p = 0.007). The probability of reintubation was increased significantly with the higher frequency of endotracheal suctioning, as indicated by restricted cubic splines. Subgroup analysis showed that these predictors were consistently associated with reintubation regardless of the use of noninvasive respiratory support after extubation.
Conclusions Endotracheal suctioning frequency and respiratory complications were identified as independent predictors of reintubation. These readily obtainable predictors may aid in decision-making regarding the extubation of postoperative patients. en-copyright= kn-copyright= en-aut-name=HattoriJun en-aut-sei=Hattori en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaAiko en-aut-sei=Tanaka en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KosakaJunko en-aut-sei=Kosaka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiraoOsamu en-aut-sei=Hirao en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurushimaNana en-aut-sei=Furushima en-aut-mei=Nana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MakiYuichi en-aut-sei=Maki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KabataDaijiro en-aut-sei=Kabata en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaAkinori en-aut-sei=Uchiyama en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EgiMoritoki en-aut-sei=Egi en-aut-mei=Moritoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MizobuchiSatoshi en-aut-sei=Mizobuchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KotakeYoshifumi en-aut-sei=Kotake en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShintaniAyumi en-aut-sei=Shintani en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KoyamaYukiko en-aut-sei=Koyama en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshidaTakeshi en-aut-sei=Yoshida en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujinoYuji en-aut-sei=Fujino en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Faculty of Medicine, Osaka University kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Anesthesiology, Osaka General Medical Center kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Intensive Care Medicine, Kobe University Hospital kn-affil= affil-num=6 en-affil=Department of Anesthesiology, Toho University Ohashi Medical Center kn-affil= affil-num=7 en-affil=Center for Mathematical and Data Science, Kobe University kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Anesthesia, Kyoto University Hospital kn-affil= affil-num=10 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Anesthesiology and Intensive Care Medicine, Kobe University Hospital kn-affil= affil-num=12 en-affil=Department of Anesthesiology, Toho University Ohashi Medical Center kn-affil= affil-num=13 en-affil=Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=14 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= en-keyword=Reintubation kn-keyword=Reintubation en-keyword=Extubation failure kn-keyword=Extubation failure en-keyword=Endotracheal suctioning kn-keyword=Endotracheal suctioning en-keyword=Postoperative patient kn-keyword=Postoperative patient en-keyword=Clinical predictor kn-keyword=Clinical predictor en-keyword=Critical care kn-keyword=Critical care END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=DSOK-0011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity-Based Anorexia Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Anorexia nervosa (AN) is a metabolic-psychiatric disorder characterized by severe weight loss, hypercortisolemia, and hypothalamic–pituitary–adrenal (HPA) axis activation. In this study, we investigated the effect of inhibiting cortisol regeneration via the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on the pathophysiology of AN.
Method: Female C57BL/6J mice underwent a 7-day activity-based anorexia (ABA) paradigm, involving 3 h daily feeding and free access to wheels, until 25% body weight loss or experiment completion. Mice were orally treated once daily with a potent 11β-HSD1 inhibitor, DSOK-0011, or vehicle. Body weight, food intake, and activity transitions were recorded; plasma corticosterone and cholesterol levels were measured using a fluorometric assay; gut microbiota were analyzed using 16S rRNA sequencing; and hippocampal glial cells were analyzed using immunohistochemistry.
Results: DSOK-0011-treated mice exhibited a modest but significant increase in postprandial wheel-running activity compared to baseline (4–5 p.m., p = 0.018; 5–6 p.m., p = 0.043), whereas vehicle-treated mice showed higher preprandial activity (9–10 a.m., p = 0.0229). Gut microbiota analysis revealed increased alpha diversity in ABA mice, with a specific enrichment of the Lachnospiraceae family in the DSOK-0011 group. However, DSOK-0011 did not significantly affect body weight, food intake, corticosterone, and lipid levels, or hippocampal glial cell populations.
Conclusion: Inhibition of 11β-HSD1 by DSOK-0011 was associated with microbiota alterations and subtle shifts in activity timing under energy-deficient conditions. These findings suggest that peripheral glucocorticoid metabolism may influence microbial and behavioral responses in the ABA model, although its metabolic impact appears limited in the acute phase. en-copyright= kn-copyright= en-aut-name=KawaiHiroki en-aut-sei=Kawai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaNanami en-aut-sei=Wada en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyazakiKenji en-aut-sei=Miyazaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTaro en-aut-sei=Kato en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriuchiYoshihiro en-aut-sei=Horiuchi en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiriiHiroshi en-aut-sei=Kirii en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NguyenHoang Duy en-aut-sei=Nguyen en-aut-mei=Hoang Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HinotsuKenji en-aut-sei=Hinotsu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhyaYoshio en-aut-sei=Ohya en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsadaTakahiro en-aut-sei=Asada en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkahisaYuko en-aut-sei=Okahisa en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=5 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=6 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=7 en-affil=Department of Animal Applied Microbiology, Okayama University Graduate School of Environmental, Life, Natural Science and Technology kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=11β-HSD1 kn-keyword=11β-HSD1 en-keyword=activity-based anorexia kn-keyword=activity-based anorexia en-keyword=anorexia nervosa kn-keyword=anorexia nervosa en-keyword=corticosterone kn-keyword=corticosterone en-keyword=eating disorders kn-keyword=eating disorders en-keyword=microbiota kn-keyword=microbiota END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=1 article-no= start-page=22 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective impact of landiolol against acute lung injury following hemorrhagic shock and resuscitation in rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation, leading to acute lung injury (ALI). Notably, blocking β1 receptors can lead to organ protection through anti‑inflammatory and anti‑apoptotic effects. Additionally, although the β1 receptor pathway is blocked by the β1 blocker, the β2 receptor pathway may be preserved and activate the 5' adenosine monophosphate‑activated protein kinase (AMPK) pathway. The present study aimed to examine whether administration of the β1 blocker landiolol could achieve lung protection in a model of HSR‑ALI, alongside improvements in inflammation and apoptosis. Male Sprague‑Dawley rats underwent hemorrhage keeping their mean arterial pressure at 30 mmHg for 1 h. Resuscitation by reinfusion was initiated to restore blood pressure to pre‑hemorrhage levels for >15 min, followed by a 45‑min stabilization period to create the HSR‑ALI model. Landiolol (100 mg/kg/min) or saline was continuously administered after resuscitation. The lung tissues, which were collected for assessing inflammation and apoptosis‑related damage, underwent analyses, including histological examination, neutrophil count, assessment of lung wet/dry weight ratio, detection of the mRNA levels of tumor necrosis factor‑α (TNF‑α) and inducible nitric oxide synthase (iNOS), identification of terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL)‑positive cells, and evaluation of caspase‑3 expression. In addition, phosphorylated AMPKα (pAMPKα) expression was tested via western blotting. Compared with the HSR/saline group, the HSR/landiolol group demonstrated a reduction in lung tissue damage score, and significant reductions in neutrophil count, lung wet/dry weight ratio, lung TNF‑α and iNOS mRNA levels, TUNEL‑positive cells and cleaved caspase‑3 expression. Furthermore, landiolol administration following HSR treatment increased pAMPKα expression. No significant hypotension occurred between the HSR/landiolol and HSR/saline groups; and blood loss did not differ significantly between the groups. In conclusion, landiolol administration after HSR reduced lung inflammation and apoptosis, suggesting a potential improvement in tissue damage. Furthermore, pAMPKα activation in the HSR/landiolol group may be the mechanism underlying the pulmonary protective effects of landiolol. en-copyright= kn-copyright= en-aut-name=SakamotoRisa en-aut-sei=Sakamoto en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuHiroko en-aut-sei=Shimizu en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraRyu en-aut-sei=Nakamura en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LuYifu en-aut-sei=Lu en-aut-mei=Yifu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiYaqiang en-aut-sei=Li en-aut-mei=Yaqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriEmiko en-aut-sei=Omori en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiToru en-aut-sei=Takahashi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=4 en-affil=Department of Human Anatomy, Shantou University Medical College kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Anesthesiology, Okayama Saidaiji Hospital kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=HSR kn-keyword=HSR en-keyword=lung injury kn-keyword=lung injury en-keyword=landiolol kn-keyword=landiolol en-keyword=β1 blocker kn-keyword=β1 blocker en-keyword=inflammation kn-keyword=inflammation en-keyword=apoptosis kn-keyword=apoptosis END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250909 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Status of Continuous Renal Replacement Therapy in Japanese Intensive Care Units: A Multicenter Retrospective Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Continuous renal replacement therapy (CRRT) is often performed for critically ill patients in intensive care units (ICUs), but its optimal indication and settings have yet to be determined. Thus, we aimed to describe the current status of CRRT in Japan through a multicenter retrospective observational study. Methods: Adult ICU patients receiving CRRT at 18 tertiary hospitals in Japan (up to 100 patients from each hospital over the past year) were retrospectively enrolled. Patients receiving CRRT for <24 h or intermittent renal replacement therapy together with CRRT were excluded. The primary outcomes were the temporal changes in the electrolyte levels, acid-base balance, and uremia-related small solute concentrations. The secondary outcomes included potassium (K) and phosphate (P) supplementations during CRRT. Results: Altogether, 1,045 patients were enrolled. The median CRRT duration and dose were 4.4 days and 17.3 mL/kg/h, respectively. The electrolyte levels, acid-base balance, and uremia-related small solute concentrations returned to normal by day 4 of treatment. A total of 732 (70.0%) patients received K supplementation, and only a few patients had hypokalemia until day 5. Moreover, 414 (39.6%) patients received P supplementation, and approximately 30%–50% of the patients had hypophosphatemia until day 5. Conclusion: The CRRT dose in Japan was lower than that was recommended by the Kidney Disease: Improving Global Outcomes guideline. The electrolyte level abnormalities and acid-base imbalances of the studied patients were improved within 72–96 h of CRRT. Contrarily, K and P supplementations were common, indicating that the current CRRT solutions need to be modified. en-copyright= kn-copyright= en-aut-name=NakanoHidehiko en-aut-sei=Nakano en-aut-mei=Hidehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InokuchiRyota en-aut-sei=Inokuchi en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueYutaro en-aut-sei=Inoue en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekinoMotohiro en-aut-sei=Sekino en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakihanaYasuyuki en-aut-sei=Kakihana en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HattoriNoriyuki en-aut-sei=Hattori en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyazakiMariko en-aut-sei=Miyazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokuhiraNatsuko en-aut-sei=Tokuhira en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujitaniShigeki en-aut-sei=Fujitani en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TodaYuichiro en-aut-sei=Toda en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhchiYoshifumi en-aut-sei=Ohchi en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IchibaShingo en-aut-sei=Ichiba en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MasudaYoshiki en-aut-sei=Masuda en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishidaOsamu en-aut-sei=Nishida en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=AbeTakaya en-aut-sei=Abe en-aut-mei=Takaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MoriguchiTakeshi en-aut-sei=Moriguchi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SatohKasumi en-aut-sei=Satoh en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IdeiMasafumi en-aut-sei=Idei en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NagataHiromasa en-aut-sei=Nagata en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=DoiKent en-aut-sei=Doi en-aut-mei=Kent kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital kn-affil= affil-num=2 en-affil=Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital kn-affil= affil-num=3 en-affil=Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Nephrology, Tohoku University Hospital kn-affil= affil-num=8 en-affil=Department of Intensive Care, Osaka University Hospital kn-affil= affil-num=9 en-affil=Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine kn-affil= affil-num=10 en-affil=Department of Anesthesiology and Intensive Care Medicine, Kawasaki Medical School kn-affil= affil-num=11 en-affil=Department of Anesthesiology and Intensive Care, Oita University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Intensive Care Medicine, Tokyo Women’s Medical University kn-affil= affil-num=14 en-affil=Department of Intensive Care Medicine, Sapporo Medical University School of Medicine kn-affil= affil-num=15 en-affil=Department of Anesthesiology and Critical Care Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=16 en-affil=Department of Urology, Iwate Medical University kn-affil= affil-num=17 en-affil=Department of Emergency and Critical Care Medicine, University of Yamanashi Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Intensive Care Medicine, Yokohama City University kn-affil= affil-num=20 en-affil=Department of Anesthesiology, Keio University School of Medicine kn-affil= affil-num=21 en-affil=Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital kn-affil= en-keyword=Acute kidney injury kn-keyword=Acute kidney injury en-keyword=Renal failure kn-keyword=Renal failure en-keyword=Continuous renal replacement therapy kn-keyword=Continuous renal replacement therapy en-keyword=Electrolytes kn-keyword=Electrolytes END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=2 article-no= start-page=273 end-page=281 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=T2 high-signal-intensity zone of the spinal cord dorsal horn in patients treated with spinal cord stimulation for herpes zoster-associated pain: a retrospective case–control study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose In patients with herpes zoster-associated pain (ZAP), magnetic resonance imaging (MRI) has revealed T2 high-signal intensity zones (MRI T2 HIZ) in the dorsal horn of the spinal cord, associated with postherpetic neuralgia (PHN). We retrospectively analyzed the relationship between PHN and MRI T2 HIZ in patients with refractory ZAP in the subacute phase who underwent temporary spinal cord stimulation therapy (tSCS).
Methods This single-center, case–control study included patients who underwent tSCS for refractory ZAP between 2010 and 2018. MRIs were re-assessed for the presence of T2 HIZ in the dorsal horn of the spinal cord. Patients were divided into T2 HIZ( +) and T2 HIZ(−) groups. Patients with a numerical rating score (NRS) ≥ 3 at the last visit were defined as PHN. The NRS values and the incidence rate of PHN were compared between the two groups.
Results Of the 67 cases extracted, 38 were included in the analysis: 22 in T2 HIZ( +) group and 16 in T2 HIZ(−) group. No significant differences were observed in background factors between the two groups. However, the T2 HIZ( +) group had a significantly higher NRS at the final visit (T2 HIZ( +):3.8 ± 2.1, T2 HIZ(−):1.4 ± 1.5; P < 0.05) and had significantly more patients with PHN than the T2 HIZ(−) group (T2 HIZ( +) vs. T2 HIZ(−), 15/22 (68%) vs. 3/16 (19%); odds ratio = 8.67; 95% confidence interval, 1.7–63.3).
Conclusion T2HIZ is detected in more than half of refractory ZAP, and pain is more likely to remain after tSCS treatment in the T2HIZ( +) group. en-copyright= kn-copyright= en-aut-name=ArakawaKyosuke en-aut-sei=Arakawa en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaMasayuki en-aut-sei=Nakagawa en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AbeYoichiro en-aut-sei=Abe en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pain Management Clinic, NTT Medical Center Tokyo kn-affil= affil-num=3 en-affil=Department of Pain Management Clinic, NTT Medical Center Tokyo kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Herpes zoster kn-keyword=Herpes zoster en-keyword=Magnetic resonance imaging kn-keyword=Magnetic resonance imaging en-keyword=Postherpetic neuralgia kn-keyword=Postherpetic neuralgia en-keyword=Refractory zoster-associated pain kn-keyword=Refractory zoster-associated pain en-keyword=Temporary spinal cord stimulation kn-keyword=Temporary spinal cord stimulation END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=436 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of Pericapsular Nerve Group (PENG) block in preoperative rehabilitation (Prehabilitation) for patients with femoral neck fractures: study protocol for a randomized, placebo-controlled, double-blinded trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Despite surgery intervention for femoral neck fractures is recommended within 48 h of admission, achieving timely surgery presents challenges for patients with severe comorbidities, or in resource-limited settings. Preoperative rehabilitation (prehabilitation) reduces bedridden time, enhances mobility, and improves postoperative outcomes for patients scheduled for hip arthroplasty due to femoral neck fractures. However, prehabilitation is hindered by insufficient pain control. The pericapsular nerve group (PENG) block provides effective analgesia while preserving motor function. We designed a study to assess the efficacy of PENG block in facilitating prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty.
Methods This prospective randomized placebo-controlled double-blinded trial aims to enroll 100 patients with Garden 3 or 4 femoral neck fractures who are scheduled for hip arthroplasty. Participants will be randomly assigned to receive a PENG block with 0.375% ropivacaine (PENG group) or with normal saline (placebo group) before the initial prehabilitation session. The prehabilitation program comprises five items: Bed-sitting, Edge-sitting, Stand-up, Maintaining-standing, and Wheelchair-transfer, performed with the assistance of a single physical therapist. The primary outcome is the percentage of patients completing the entire prehabilitation program. Secondary outcomes during the initial prehabilitation session are the achievement of each program item and the Numerical Rating Scale (NRS) pain score. Other secondary outcomes include intraoperative bleeding amounts, thromboembolic events during postoperative day 0 to 7, postoperative 3-day cumulative Cumulated Ambulation Score (CAS), and discharge destination. The postoperative outcomes will be compared between subgroups of patients undergoing surgery within 48 h of admission and those undergoing surgery more than 48 h of admission.
Discussion This is the first study aiming to assess the efficacy of PENG block in prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. PENG block could be beneficial, especially for patients facing delayed surgery, providing a potential treatment option during the waiting period.
Trial registration Japan Registry of Clinical Trials, jRCT1031220294, registered on August 26, 2022. en-copyright= kn-copyright= en-aut-name=JinZhuan en-aut-sei=Jin en-aut-mei=Zhuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiyamaDaisuke en-aut-sei=Sugiyama en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HigoFumiya en-aut-sei=Higo en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirataTakahiro en-aut-sei=Hirata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiOsamu en-aut-sei=Kobayashi en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UedaKenichi en-aut-sei=Ueda en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=3 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=5 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= en-keyword=Femoral neck fracture kn-keyword=Femoral neck fracture en-keyword=Hip fracture kn-keyword=Hip fracture en-keyword=PENG block kn-keyword=PENG block en-keyword=Pericapsular nerve group block kn-keyword=Pericapsular nerve group block en-keyword=Prehabilitation kn-keyword=Prehabilitation en-keyword=Preoperative mobilization kn-keyword=Preoperative mobilization en-keyword=Preoperative rehabilitation kn-keyword=Preoperative rehabilitation en-keyword=Randomized controlled trial kn-keyword=Randomized controlled trial en-keyword=Study protocol kn-keyword=Study protocol END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=565 end-page=569 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utilization of the pericapsular nerve group block in preoperative rehabilitation of patients with femoral neck fractures -a case series- en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Elderly patients with femoral neck fractures, particularly those with severe comorbidities or living in regions with limited medical resources, may experience delays in surgical treatment. Although the benefits of preoperative rehabilitation (prehabilitation) in hip arthroplasty have been reported, pain management remains a challenge. The pericapsular nerve group (PENG) block, known for its exceptional analgesic effect and motor function preservation, may be a promising intervention during prehabilitation in these patients.
Case: We enrolled ten patients with Garden classification 3–4 femoral neck fractures scheduled for hip arthroplasty. After receiving a PENG block with 20 ml of 0.375% ropivacaine, all patients underwent initial prehabilitation sessions comprising 9 mobility levels, ranging from bed-sitting to walking. One patient was excluded due to experiencing high blood pressure during prehabilitation. Six of the nine remaining patients (66.7%) were successfully transferred from bed to wheelchair.
Conclusions: The PENG block enhanced prehabilitation for patients with femoral neck fractures undergoing hip arthroplasty. en-copyright= kn-copyright= en-aut-name=JinZhuan en-aut-sei=Jin en-aut-mei=Zhuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiyamaDaisuke en-aut-sei=Sugiyama en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HigoFumiya en-aut-sei=Higo en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirataTakahiro en-aut-sei=Hirata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiOsamu en-aut-sei=Kobayashi en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UedaKenichi en-aut-sei=Ueda en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=3 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=5 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= en-keyword=Conduction anesthesia kn-keyword=Conduction anesthesia en-keyword=Femoral neck fractures kn-keyword=Femoral neck fractures en-keyword=Hip fractures kn-keyword=Hip fractures en-keyword=Nerve block kn-keyword=Nerve block en-keyword=Prehabilitation kn-keyword=Prehabilitation en-keyword=Preoperative exercise kn-keyword=Preoperative exercise en-keyword=Preoperative rehabilitation kn-keyword=Preoperative rehabilitation en-keyword=Regional anesthesia kn-keyword=Regional anesthesia END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=8 article-no= start-page=e101809 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurological outcomes with hypothermia versus normothermia in patients with moderate initial illness severity following resuscitation from out-of-hospital cardiac arrest: protocol for a multicentre randomised controlled trial (R-CAST OHCA) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Temperature control is a fundamental intervention for neuroprotection following resuscitation from cardiac arrest. However, evidence regarding the efficacy of hypothermia in post-cardiac arrest syndrome (PCAS) remains unclear. Retrospective studies suggest that the clinical effectiveness of hypothermia may depend on the severity of PCAS. The R-CAST OHCA trial aims to compare the efficacy of hypothermia versus normothermia in improving 30-day neurological outcomes in patients with moderately severe PCAS following out-of-hospital cardiac arrest.
Methods and analysis The multicentre, single-blind, parallel-group, superiority, randomised controlled trial (RCT) is conducted with the participation of 35 emergency and critical care centres and/or intensive care units at academic and non-academic hospitals. The study enrols moderately severe PCAS patients, defined as those with a revised post-Cardiac Arrest Syndrome for induced Therapeutic Hypothermia score of 5.5–15.5. A target number of 380 participants will be enrolled. Participants are randomised to undergo either hypothermia or normothermia within 3 hours after return of spontaneous circulation. Patients in the hypothermia group are cooled and maintained at 34°C until 28 hours post-randomisation, followed by rewarming to 37°C at a rate of 0.25°C/hour. Patients in the normothermia group are maintained at normothermia (36.5°C–37.7°C). Total periods of intervention, including the cooling, maintenance and rewarming phases, will occur 40 hours after randomisation. Other treatments for PCAS can be determined by the treating physicians. The primary outcome is a favourable neurological outcome, defined as Cerebral Performance Category 1 or 2 at 30 days after randomisation and compared using an intention-to-treat analysis.
Ethics and dissemination This study has been approved by the Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital, Ethics Committee (approval number: R2201-001). Written informed consent is obtained from all participants or their authorised surrogates. Results will be disseminated via publications and presentations.
Trial registration number jRCT1062220035. en-copyright= kn-copyright= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishikimiMitsuaki en-aut-sei=Nishikimi en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaYohei en-aut-sei=Okada en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaeyamaHiroki en-aut-sei=Maeyama en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KiguchiTakeyuki en-aut-sei=Kiguchi en-aut-mei=Takeyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishidaKazuki en-aut-sei=Nishida en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuiShigeyuki en-aut-sei=Matsui en-aut-mei=Shigeyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurodaYasuhiro en-aut-sei=Kuroda en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishiyamaKei en-aut-sei=Nishiyama en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwamiTaku en-aut-sei=Iwami en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=JAAM R-CAST OHCA Trial Group en-aut-sei=JAAM R-CAST OHCA Trial Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=3 en-affil=Department of Preventive Services, School of Public Health, Graduate School of Medicine, Kyoto University kn-affil= affil-num=4 en-affil=Department of Emergency and Critical Care Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=5 en-affil=Division of Trauma and Surgical Critical Care, Osaka General Medical Center kn-affil= affil-num=6 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Biostatistics, School of Public Health, Graduate School of Medicine, Kyoto University kn-affil= affil-num=8 en-affil=Department of Biostatistics, School of Public Health, Graduate School of Medicine, Kyoto University kn-affil= affil-num=9 en-affil=Emergency and Critical Care Center, TMG Asaka Medical Center kn-affil= affil-num=10 en-affil=Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science kn-affil= affil-num=11 en-affil=Department of Preventive Services, School of Public Health, Graduate School of Medicine, Kyoto University kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=1 article-no= start-page=e70258 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Early-life exposures and child health outcomes: A narrative review of LSN21 research in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The Longitudinal Survey of Newborns in the 21st Century (LSN21) tracks two Japanese national birth cohorts—2001 (baseline n = 47,010) and 2010 (n = 38,554)—from infancy through young adulthood, capturing parenting practices and family environments. Most studies analyze single exposures or outcomes. We conducted a narrative review summarizing the findings published by the Okayama University group on diverse health and developmental outcomes.
Methods: We reviewed 59 LSN21 papers (2013–2025), extracting data on exposures, outcomes, and methods. Evidence was categorized into four exposure types (infant feeding, sleep, environmental, and perinatal) and three outcome domains (obesity, allergies/respiratory tract infections, and neurobehavioral development), including cohort comparisons.
Results: Exclusive breastfeeding was associated with a lower obesity risk at ages 7 (adjusted odds ratio 0.55, 95% confidence interval 0.39–0.78) and 15, later puberty, and fewer hospitalizations. Short or irregular sleep before age 3 was linked to behavioral problems and injuries. Maternal smoking and prenatal air pollution were associated with respiratory conditions and developmental challenges. Preterm birth and small-for-gestational-age predicted delays, especially without catch-up growth by age 2. Pneumococcal vaccination likely contributed to declining otitis media after 2010. Additional findings included associations between outdoor play and reduced obesity risk, and complex relationships between breastfeeding and food allergies that varied by infantile eczema status.
Conclusions: LSN21 findings highlight modifiable early-life factors (breastfeeding, sleep patterns, and smoke-free environments) and identify preterm and growth-restricted children for priority monitoring. While LSN21's strength lies in longitudinal social assessments, complementary perspectives from other Japanese cohorts could enhance understanding of biological mechanisms and intergenerational effects. en-copyright= kn-copyright= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoRumi en-aut-sei=Matsuo en-aut-mei=Rumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamuraYuka en-aut-sei=Yamamura en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsugeTakahiro en-aut-sei=Tsuge en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KadowakiTomoka en-aut-sei=Kadowaki en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UraguchiKensuke en-aut-sei=Uraguchi en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TamaiKei en-aut-sei=Tamai en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraKazue en-aut-sei=Nakamura en-aut-mei=Kazue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiAkihito en-aut-sei=Takeuchi en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Neonatology, NHO Okayama Medical Center kn-affil= affil-num=10 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=breastfeeding kn-keyword=breastfeeding en-keyword=child health kn-keyword=child health en-keyword=environmental exposure kn-keyword=environmental exposure en-keyword=longitudinal studies kn-keyword=longitudinal studies en-keyword=perinatal kn-keyword=perinatal END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=234 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rotenone targets midbrain astrocytes to produce glial dysfunction-mediated dopaminergic neurodegeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Exposure to pesticides, such as rotenone or paraquat, is an environmental factor that plays an important role in the pathogenesis of Parkinson's disease (PD). Rotenone induces PD-like pathology and is therefore used to develop parkinsonian animal models. Dopaminergic neurotoxicity caused by rotenone has been attributed to the inhibition of mitochondrial complex I, oxidative stress and neuroinflammation; however, the mechanisms underlying selective dopaminergic neurodegeneration by rotenone remain unclear. To resolve this, we focused on glial diversity and examined whether the brain region-specific glial response to rotenone could determine the vulnerability of dopaminergic neurons using primary cultured neurons, astrocytes and microglia from the midbrain and striatum of rat embryos and rotenone-injected PD model mice. Direct neuronal treatment with low-dose rotenone failed to damage dopaminergic neurons. Conversely, rotenone exposure in the presence of midbrain astrocyte and microglia or conditioned media from rotenone-treated midbrain glial cultures containing astrocytes and microglia produced dopaminergic neurotoxicity, but striatal glia did not. Surprisingly, conditioned media from rotenone-treated midbrain astrocytes or microglia monocultures did not affect neuronal survival. We also demonstrated that rotenone targeted midbrain astrocytes prior to microglia to induce dopaminergic neurotoxicity. Rotenone-treated astrocytes produced secreted protein acidic and rich in cysteine (SPARC) extracellularly, which induced microglial proliferation, increase in IL-1β and TNF-α, and NF-κB (p65) nuclear translocation in microglia, resulting in dopaminergic neurodegeneration. In addition, rotenone exposure caused the secretion of NFAT-related inflammatory cytokines and a reduction in the level of an antioxidant metallothionein (MT)-1 from midbrain glia. Furthermore, we observed microglial proliferation and a decrease in the number of MT-positive astrocytes in the substantia nigra, but not the striatum, of low-dose rotenone-injected PD model mice. Our data highlight that rotenone targets midbrain astrocytes, leading to SPARC secretion, which promotes the neurotoxic conversion of microglia and leads to glial dysfunction-mediated dopaminergic neurodegeneration. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImafukuFuminori en-aut-sei=Imafuku en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomimotoKana en-aut-sei=Tomimoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SogawaNorio en-aut-sei=Sogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology kn-affil= affil-num=9 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pharmacotherapy, School of Pharmacy, Shujitsu University kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Rotenone kn-keyword=Rotenone en-keyword=Astrocyte kn-keyword=Astrocyte en-keyword=Microglia kn-keyword=Microglia en-keyword=SPARC kn-keyword=SPARC en-keyword=Parkinson's disease kn-keyword=Parkinson's disease END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue= article-no= start-page=101081 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=AHA’s Life’s Essential-8 cardiovascular health metrics and progression of coronary artery calcification in Japanese men en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and aims: The American Heart Association’s Life’s Essential-8 (LE8) cardiovascular health (CVH) metrics is considered a comprehensive framework for optimal cardiovascular wellbeing. However, its relationship with the progression of subclinical atherosclerosis, like coronary artery calcification (CAC), is not clarified. We investigated the associations of LE8 CVH metrics with the prevalence and progression of CAC in Japanese men.
Methods: We analyzed data from 760 asymptomatic men participating in the Shiga Epidemiological Study of Subclinical Atherosclerosis. We assessed baseline (2006–2008) LE8 CVH (low, 0–49 points; moderate, 50–79 points; high, 80–100 points) using its eight components (diet, physical activity assessed by step count, smoking, sleep, body mass index, blood lipids, blood glucose, blood pressure). We quantified CAC at baseline and follow-up of 5 years employing Agatston’s method and defined its baseline prevalence (CAC >0) and progression (employing Berry’s criteria). Modified Poisson regression analyses were used to estimate risk ratio (RR) and 95 % confidence interval (CI), adjusted for age and family history of cardiovascular disease.
Results: Participants (mean [SD] age, 63.8 [9.4] years) had 63.2 % and 44.9 % prevalence of CAC at baseline and CAC progression at follow-up, respectively. Individuals with moderate and low CVH at baseline had a higher risk of prevalent CAC (RR [95 % CI], 1.42 [1.18–1.71] and 2.07 [1.67–2.57], respectively) at baseline, compared to those with high CVH. Those with moderate and low CVH at baseline had a higher risk of CAC progression (RR [95 % CI], 1.52 [1.17–1.97] and 1.99 [1.42–2.81], respectively), compared to high CVH individuals.
Conclusions: A lower LE8 CVH is significantly associated with a higher risk of prevalence and progression of CAC in general Japanese men. en-copyright= kn-copyright= en-aut-name=MondalRajib en-aut-sei=Mondal en-aut-mei=Rajib kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KadotaAya en-aut-sei=Kadota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoYuichiro en-aut-sei=Yano en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KadowakiSayaka en-aut-sei=Kadowaki en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToriiSayuki en-aut-sei=Torii en-aut-mei=Sayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoKeiko en-aut-sei=Kondo en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaradaAkiko en-aut-sei=Harada en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawashimaMegumi en-aut-sei=Kawashima en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyazawaItsuko en-aut-sei=Miyazawa en-aut-mei=Itsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SegawaHiroyoshi en-aut-sei=Segawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeYoshiyuki en-aut-sei=Watanabe en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakagawaYoshihisa en-aut-sei=Nakagawa en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiyoshiAkira en-aut-sei=Fujiyoshi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=3 en-affil=Department of General Medicine, Faculty of Medicine, Juntendo University kn-affil= affil-num=4 en-affil=Department of Public Health, Shiga University of Medical Science kn-affil= affil-num=5 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=7 en-affil=Department of Medical Statistics, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=9 en-affil=Department of Internal Medicine, Shiga University of Medical Science kn-affil= affil-num=10 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=11 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=14 en-affil=Department of Hygiene, School of Medicine, Okayama Medical University kn-affil= affil-num=15 en-affil=Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= en-keyword=Life’s essential-8 kn-keyword=Life’s essential-8 en-keyword=Cardiovascular health metrics kn-keyword=Cardiovascular health metrics en-keyword=Subclinical atherosclerosis kn-keyword=Subclinical atherosclerosis en-keyword=Coronary artery calcification kn-keyword=Coronary artery calcification en-keyword=CAC progression kn-keyword=CAC progression END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=10 article-no= start-page=e0332595 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship between obesity indices and cognitive function in Japanese men: A cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=We aimed to investigate the associations among various obesity indices, including visceral (VAT) and subcutaneous adipose tissue (SAT), and cognitive function in community-dwelling Japanese men. This population-based cross-sectional study used data of 853 men who participated in the follow-up examinations of the Shiga Epidemiological Study of Subclinical Atherosclerosis. Among them, we analyzed data of 776 men who completed the Cognitive Abilities Screening Instrument (CASI) and had abdominal VAT and SAT areas measured using computed tomography. The VAT-to-SAT ratio (VSR) was calculated; participants were categorized into VSR quartiles. Using analysis of covariance, we computed crude and adjusted means of the CASI total and domain scores across VSR quartiles, adjusting for potential confounders. No significant differences were observed in total CASI scores among body mass index, VAT, or SAT quartiles. However, in the multivariable-adjusted model, participants in the lowest VSR quartile (Q1) had significantly lower CASI total scores than those in the third quartile (Q3) (Q1: 89.5, Q3: 90.9). Low VSR was independently associated with lower cognitive function in a community-based sample of middle-aged and older Japanese men. In summary, VSR may be associated with cognitive function in Japanese men, highlighting the importance of fat distribution in cognitive health and highlighting VSR as a useful indicator. en-copyright= kn-copyright= en-aut-name=MatsunoSatoshi en-aut-sei=Matsuno en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OzekiYuji en-aut-sei=Ozeki en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadowakiSayaka en-aut-sei=Kadowaki en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ToriiSayuki en-aut-sei=Torii en-aut-mei=Sayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoKeiko en-aut-sei=Kondo en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyagawaNaoko en-aut-sei=Miyagawa en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimaAzusa en-aut-sei=Shima en-aut-mei=Azusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhashiMizuki en-aut-sei=Ohashi en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyazawaItsuko en-aut-sei=Miyazawa en-aut-mei=Itsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SegawaHiroyoshi en-aut-sei=Segawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KadotaAya en-aut-sei=Kadota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Psychiatry, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=Department of Psychiatry, Shiga University of Medical Science kn-affil= affil-num=3 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=4 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=5 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Department of Preventive Medicine and Public Health, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Clinical Nursing, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=9 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=10 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=11 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=38590 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies. en-copyright= kn-copyright= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HanzawaShunya en-aut-sei=Hanzawa en-aut-mei=Shunya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KadowakiDaisuke en-aut-sei=Kadowaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamadaYuki en-aut-sei=Hamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhtaniTomoko en-aut-sei=Ohtani en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KumonKento en-aut-sei=Kumon en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=Extracellular vesicle kn-keyword=Extracellular vesicle en-keyword=Liquid biopsy kn-keyword=Liquid biopsy en-keyword=Predictive biomarker kn-keyword=Predictive biomarker en-keyword=Stealth effect kn-keyword=Stealth effect END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=11 article-no= start-page=1677 end-page=1685 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of Cytoreductive Nephrectomy in the Immune Checkpoint Inhibitor Era: A Multicenter Collaborative Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: We aimed to evaluate overall survival (OS) and determine the optimal timing of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI)-based therapy.
Methods: This retrospective study reviewed medical records of 447 patients with mRCC treated with ICI at multiple Japanese institutions between January 2018 and August 2023. From this cohort, 178 patients with lymph node or distant metastases received either cytoreductive nephrectomy (CN group; n = 72) or ICI therapy without cytoreductive nephrectomy (non-CN group; n = 106) as first-line treatment.
Results: Median progression-free survival was 15.7 months, and median overall survival was 58.1 months. CN significantly improved OS, with the CN group's median OS not reached, compared to 29.6 months in the non-CN group (p = 0.01). Deferred CN also showed improved survival outcomes. Poor prognostic factors for immediate CN included International Metastatic Renal Cell Carcinoma Database Consortium poor risk, sarcomatoid differentiation, and a high neutrophil-to-lymphocyte ratio.
Conclusions: We developed a prognostic model to guide patient selection for CN, emphasizing the need for personalized treatment strategies. en-copyright= kn-copyright= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InokiLan en-aut-sei=Inoki en-aut-mei=Lan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujinoTakuya en-aut-sei=Tsujino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirasawaYosuke en-aut-sei=Hirasawa en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HashimotoTakeshi en-aut-sei=Hashimoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OhnoYoshio en-aut-sei=Ohno en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShirokiRyoichi en-aut-sei=Shiroki en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=10 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=11 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=12 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=14 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=17 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=18 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= en-keyword=cytoreductive nephrectomy kn-keyword=cytoreductive nephrectomy en-keyword=IMDC classification kn-keyword=IMDC classification en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=neutrophil-to- lymphocyte ratio kn-keyword=neutrophil-to- lymphocyte ratio en-keyword=sarcomatoid differentiation kn-keyword=sarcomatoid differentiation END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=17 article-no= start-page=6122 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250829 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Potential of Kidney Exchange Programs (KEPs) in Japan for Donor-Specific Antibody-Positive Kidney Transplants: A Questionnaire Survey on KEPs and a Multi-Institutional Study Conducting Virtual Cross-Matching Simulations en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To clarify the need for a kidney exchange program (KEP) in Japan by conducting a questionnaire survey on KEPs and simulated KEPs by virtual cross-matching based on past cases of transplantation avoidance. Methods: In addition to the content regarding KEPs, an electronic survey was conducted to investigate the number of cases of kidney transplant abandonment due to “immunological” reasons over the past 10 years (2012–2021). Virtual cross-matching was conducted to simulate the feasibility of avoiding immunological risks and enabling kidney transplantation in patients who were previously unable to undergo the procedure. Results: The survey received responses from 107 facilities (response rate: 81.7%). In response to the question about the necessity of a KEP in Japan, 71 facilities (66.4%) indicated that KEPs are necessary. In addition, 251 living-donor kidney transplants were abandoned for “immunological” reasons over the past decade (2012–2021). Among the 80 pairs for which detailed information was available, virtual cross-matching simulations showed that 37/80 pairs (46.3%) were donor-specific antibody (DSA)-negative for blood type-matched combinations, and 41/80 pairs (51.3%) were DSA-negative for blood type-incompatible transplants. Conclusions: The need for a KEP in Japan and its potential usefulness were demonstrated. en-copyright= kn-copyright= en-aut-name=ItoTaihei en-aut-sei=Ito en-aut-mei=Taihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoMiki en-aut-sei=Ito en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AidaNaohiro en-aut-sei=Aida en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuriharaKei en-aut-sei=Kurihara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TeraoAkihiro en-aut-sei=Terao en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WataraiYoshihiko en-aut-sei=Watarai en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoMitsuru en-aut-sei=Saito en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KakuKeizo en-aut-sei=Kaku en-aut-mei=Keizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiiDaisuke en-aut-sei=Ishii en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SekiguchiSatoshi en-aut-sei=Sekiguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YonedaTatsuo en-aut-sei=Yoneda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UnagamiKohei en-aut-sei=Unagami en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TasakiMasayuki en-aut-sei=Tasaki en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwamotoHitoshi en-aut-sei=Iwamoto en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakahashiKazuhiro en-aut-sei=Takahashi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamanakaKazuaki en-aut-sei=Yamanaka en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SugimotoMikio en-aut-sei=Sugimoto en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NishikawaKouhei en-aut-sei=Nishikawa en-aut-mei=Kouhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SetoChikashi en-aut-sei=Seto en-aut-mei=Chikashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MuramatsuMasaki en-aut-sei=Muramatsu en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=AsaiToshihiro en-aut-sei=Asai en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=IwamiDaiki en-aut-sei=Iwami en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=YamadaYasutoshi en-aut-sei=Yamada en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YamanagaShigeyoshi en-aut-sei=Yamanaga en-aut-mei=Shigeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KomatsuTomonori en-aut-sei=Komatsu en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MiuraMasayoshi en-aut-sei=Miura en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NoharaTakahiro en-aut-sei=Nohara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=MaruyamaMichihiro en-aut-sei=Maruyama en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=MiyauchiYuki en-aut-sei=Miyauchi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=TanakaToshiaki en-aut-sei=Tanaka en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=NakamuraMichio en-aut-sei=Nakamura en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HottaKiyohiko en-aut-sei=Hotta en-aut-mei=Kiyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KenmochiTakashi en-aut-sei=Kenmochi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=2 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=3 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=4 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=5 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=6 en-affil=Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital kn-affil= affil-num=7 en-affil=Division of Blood Purification, Akita University Hospital kn-affil= affil-num=8 en-affil=Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Urology, Kitasato University of Medicine kn-affil= affil-num=10 en-affil=Transplantation Surgery, Japan Community Healthcare Organization Sendai Hospital kn-affil= affil-num=11 en-affil=Unit of Dialysis, Department of Urology, Nara Medical University kn-affil= affil-num=12 en-affil=Organ Transplant Medicine, Tokyo Women’s Medical University kn-affil= affil-num=13 en-affil=Division of Urology, Department of Regenerative & Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=14 en-affil=Department of Kidney Transplantation Surgery, Tokyo Medical University Hachioji Medical Center kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba kn-affil= affil-num=17 en-affil=Department of Urology, Osaka University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Urology, Faculty of Medicine, Adrenal Surgery and Renal Transplantation, Kagawa University kn-affil= affil-num=19 en-affil=Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Urology, Toyama Prefectural Central Hospital kn-affil= affil-num=21 en-affil=Department of Nephrology, Toho University Faculty of Medicine kn-affil= affil-num=22 en-affil=Department of Kidney Transplant and Dialysis, Osaka City General Hospital kn-affil= affil-num=23 en-affil=Division of Renal Surgery and Transplantation, Department of Urology, Jichi Medical University kn-affil= affil-num=24 en-affil=Department of Blood Purification, Kagoshima University Hospital kn-affil= affil-num=25 en-affil=Department of Transplant Surgery, Japanese Red Cross Kumamoto Hospital kn-affil= affil-num=26 en-affil=Department of Urology, Chukyo Hospital, Japan Community Healthcare Organization kn-affil= affil-num=27 en-affil=Department of Renal Transplantation Surgery and Urology, Sapporo Hokuyu Hospital kn-affil= affil-num=28 en-affil=Department of Urology, Kanazawa University Hospital kn-affil= affil-num=29 en-affil=Department of Frontier Surgery, Chiba University School of Medicine kn-affil= affil-num=30 en-affil=Department of Urology, Ehime University kn-affil= affil-num=31 en-affil=Department of Urology, Sapporo Medical University kn-affil= affil-num=32 en-affil=Department of Transplant Surgery, Tokai University School of Medicine kn-affil= affil-num=33 en-affil=Department of Renal and Genitourinary Surgery, Faculty of Medicine, Hokkaido University kn-affil= affil-num=34 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= en-keyword=kidney transplantation kn-keyword=kidney transplantation en-keyword=donor-specific antibodies kn-keyword=donor-specific antibodies en-keyword=kidney exchange program kn-keyword=kidney exchange program en-keyword=virtual cross-matching kn-keyword=virtual cross-matching END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue= article-no= start-page=1682012 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Maternal circulating GPIHBP1 levels and neonatal outcomes in patients with gestational diabetes mellitus: a pilot study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The prevalence of gestational diabetes mellitus (GDM) is significantly increasing. Hyperglycaemia and dyslipidaemia have been demonstrated to contribute to endothelial dysfunction linked to foetal–placental circulation. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) is crucial for the lipolytic processing of TG-rich lipoproteins through the anchoring of lipoprotein lipase (LPL). In this study, circulating GPIHBP1 levels during pregnancy were evaluated, and their associations with hypertriglyceridaemia and the perinatal outcomes of GDM were evaluated.
Methods: This study included 12 pregnant women with GDM and 21 pregnant women with normal glucose tolerance (NGT).
Results: No significant differences in obstetrical outcomes were detected between the two groups. In participants with NGT, circulating GPIHBP1 levels were markedly lower in the 3rd trimester than in the 2nd trimester and at delivery. In women with GDM, circulating GPIHBP1 levels were unchanged during the 3rd trimester, and circulating GPIHBP1 levels throughout the 3rd trimester were negatively correlated with neonatal birth weight percentile and umbilical venous pO2 (ρ=-0.636, p=0.026; ρ=-0.657, p=0.020).
Discussion: Our findings suggest a possible association between circulating GPIHBP1 levels and perinatal outcomes in patients with GDM. en-copyright= kn-copyright= en-aut-name=WatanabeMayu en-aut-sei=Watanabe en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurookaNaoko en-aut-sei=Kurooka en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) kn-keyword=glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) en-keyword=gestational diabetes mellitus (GDM) kn-keyword=gestational diabetes mellitus (GDM) en-keyword=perinatal outcomes kn-keyword=perinatal outcomes en-keyword=placenta kn-keyword=placenta en-keyword=triglyceride (TG) kn-keyword=triglyceride (TG) END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Admission prognostic nutritional index predicts prolonged hospitalization in severe odontogenic deep neck infections en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives Severe odontogenic deep neck infections (DNIs) can be life threatening. This study investigated the nutritional status of affected patients and evaluated the usefulness of the Prognostic Nutritional Index (PNI) at admission in helping maxillofacial surgeons identify, at presentation, those likely to require extended hospitalization.
Methods A total of 112 patients treated for odontogenic deep neck abscesses and necrotizing soft tissue infections at five hospitals in Japan. Patients were included. Patients were categorized by length of hospitalization duration and factors associated with prolonged hospitalization were analyzed using propensity score matching to minimize bias. Spearman’s rank correlation analysis was also performed to assess the relationship between PNI and hospitalization duration.
Results Fifty patients (44.6%) required hospitalization for more than 14 days. Multivariate analysis identified PNI ≤ 41.2 (odds ratio [OR] = 2.79) and the presence of abscesses in multiple deep neck spaces (OR = 2.76) as significant predictors of prolonged hospitalization. Propensity score analysis confirmed the significant association between PNI and length of hospitalization duration (P = 0.048). In addition, Spearman’s rank correlation coefficient was r = − 0.471 (P < 0.001), indicating a moderate negative correlation.
Conclusion The admission PNI may serve as a useful adjunctive indicator for predicting prolonged hospitalization in patients with severe odontogenic DNIs, as it reflects both nutritional status and systemic inflammation. en-copyright= kn-copyright= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikutaShogo en-aut-sei=Kikuta en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanekoNaoki en-aut-sei=Kaneko en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKotaro en-aut-sei=Sato en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitagawaNorio en-aut-sei=Kitagawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuoKatsuhisa en-aut-sei=Matsuo en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SameshimaJunsei en-aut-sei=Sameshima en-aut-mei=Junsei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TachibanaAkira en-aut-sei=Tachibana en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawanoShintaro en-aut-sei=Kawano en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KusukawaJingo en-aut-sei=Kusukawa en-aut-mei=Jingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AkashiMasaya en-aut-sei=Akashi en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=4 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=9 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital kn-affil= affil-num=11 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=12 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=15 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Odontogenic deep neck infections kn-keyword=Odontogenic deep neck infections en-keyword=Nutrition status kn-keyword=Nutrition status en-keyword=Prognostic nutritional index kn-keyword=Prognostic nutritional index en-keyword=Prolonged hospitalization kn-keyword=Prolonged hospitalization en-keyword=Multiple spaces with abscess kn-keyword=Multiple spaces with abscess END start-ver=1.4 cd-journal=joma no-vol=136 cd-vols= no-issue=10 article-no= start-page=lxaf217 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gut dysbiosis allows foodborne salmonella colonization in edible crickets: a probiotic strategy for enhanced food safety en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Edible insects, including crickets, represent a promising protein source, yet concerns over foodborne pathogens limit consumer acceptance. This study investigated whether gut microbiota modulates colonization by Salmonella enterica subsp. enterica serovar Enteritidis (SE) in the two-spotted cricket (Gryllus bimaculatus).
Methods and Results: Under standard conditions, SE was undetectable in crickets despite prolonged exposure; however, antibiotic-induced dysbiosis enabled stable SE colonization. Long-read 16S rRNA sequencing revealed significant microbiota shifts, notably a reduction in Lactococcus garvieae. In vitro assays showed strong inhibitory effects of L. garvieae against SE, and supplementation of dysbiotic crickets with L. garvieae reduced SE colonization by ∼1000-fold.
Conclusions: The native cricket gut microbiota, especially L. garvieae, plays a protective role against SE colonization. Enhancing beneficial gut bacteria could mitigate pathogen risks and promote edible insects as a sustainable protein. en-copyright= kn-copyright= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokotaKenji en-aut-sei=Yokota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BandoTetsuya en-aut-sei=Bando en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=food safety kn-keyword=food safety en-keyword=edible crickets kn-keyword=edible crickets en-keyword=Salmonella kn-keyword=Salmonella en-keyword=Lactococcus kn-keyword=Lactococcus en-keyword=probiotics kn-keyword=probiotics en-keyword=microbiome kn-keyword=microbiome END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=e92587 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250917 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Intranasal Administration of Semaphorin 3A Inhibitor in a Mouse Model of Olfactory Disorder en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the effects of intranasal administration of a semaphorin 3A inhibitor (Sema3A-I) in a mouse model of olfactory disorder, where olfactory sensory neuron (OSN) axons had been severely damaged. We performed axotomy (transection of OSN axons) of the OSNs in mice and administered Sema3A‑I intranasally to seven mice and saline to another seven mice. Following treatment, we assessed the thickness of the olfactory epithelium and the regeneration ratio of OSN axons. Intranasal administration of Sema3A-I did not significantly promote OSN regeneration, axonal outgrowth, or improve axonal projection compared to saline administration. Although Sema3A-I administration showed some promotion of axonal outgrowth, the difference was not statistically significant. Continuous subcutaneous administration of Sema3A-I in rats after axotomy promotes OSN regeneration and axonal outgrowth. Given that intranasal administration is minimally invasive, we believe that it may still be a feasible route when combined with additional treatment strategies. Further investigation into administration methods and therapeutic combinations is warranted. en-copyright= kn-copyright= en-aut-name=MuraiAya en-aut-sei=Murai en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NodaMinori en-aut-sei=Noda en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimizuAiko en-aut-sei=Shimizu en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaharaJunko en-aut-sei=Takahara en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Technical Support for Medical Science, Department of Comprehensive Technical Solutions, Okayama University kn-affil= affil-num=5 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University kn-affil= en-keyword=axon growth kn-keyword=axon growth en-keyword=intranasal administration kn-keyword=intranasal administration en-keyword=olfactory disorder kn-keyword=olfactory disorder en-keyword=olfactory sensory neurons kn-keyword=olfactory sensory neurons en-keyword=semaphorin3a kn-keyword=semaphorin3a END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=8 article-no= start-page=e89864 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Higher Liver Fibrosis-4 Index Is Associated With More Severe Hearing Loss in Idiopathic Sudden Sensorineural Hearing Loss en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Liver fibrosis is an important medical issue increasing over time in developed countries.
Aims/objectives
This study aimed to investigate whether liver fibrosis, as indicated by routine blood test parameters, influences the risk and severity of idiopathic sudden sensorineural hearing loss (ISSNHL).
Material and methods
Sixty-six patients with ISSNHL and 198 patients with benign parotid gland tumors (BPTs) (controls) were enrolled. Indices for liver fibrosis (Liver Fibrosis-4 index (FIB-4 index) and aspartate aminotransferase-to-platelet ratio index (APRI)) were calculated from the blood laboratory data. The pure tone average (PTA) was calculated as the mean of hearing levels at the six frequencies at the onset of ISSNHL. Severe hearing loss was defined as PTA≥60 decibels Hearing Level (dB HL).
Results
In risk evaluation, the FIB-4 index did not differ significantly between ISSNHL patients and controls. Regarding the severity of ISSNHL, the FIB-4 index was significantly higher in ISSNHL patients with severe hearing loss than in those with PTA<60 dB HL (P<0.05) on univariate comparison. After adjusting for age, sex, and indices of inflammation, both the FIB-4 index and APRI showed a significant association with severe hearing loss (odds ratio (OR): 5.9, 95% confidence interval (CI): 1.3-25.7, and OR: 2.2, 95% CI: 1.1-4.7).
Conclusions and significance
Higher liver fibrosis indices (FIB-4 index and APRI), derived from routine blood laboratory data, are associated with a more severe phenotype of ISSNHL. en-copyright= kn-copyright= en-aut-name=MaedaYukihide en-aut-sei=Maeda en-aut-mei=Yukihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmichiRyotaro en-aut-sei=Omichi en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=aspartate aminotransferase-to-platelet ratio index kn-keyword=aspartate aminotransferase-to-platelet ratio index en-keyword=audiometry kn-keyword=audiometry en-keyword=fatty liver disease kn-keyword=fatty liver disease en-keyword=incidence kn-keyword=incidence en-keyword=liver fibrosis-4 index kn-keyword=liver fibrosis-4 index en-keyword=severity kn-keyword=severity en-keyword=sudden hearing loss kn-keyword=sudden hearing loss END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=10 article-no= start-page=1483 end-page=1493 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biologics and Small‐Molecule Therapies in Netherton Syndrome: A Comprehensive Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Netherton syndrome (NS) is a rare congenital ichthyosis caused by loss-of-function mutations in the SPINK5 gene, leading to defective expression of the serine protease inhibitor LEKTI. Dysregulated epidermal protease activity results in impaired skin barrier function and chronic inflammation, accompanied by complex immune profiles. NS patients commonly show activation of the inflammatory axis, centered on IL-17 and IL-36, in the skin and blood, and show a psoriasis-like shift to Th17. Conversely, the immune profile differs depending on the clinical type, with ichthyosis linearis circumflexa type characterized by complement activation and Th2-type allergic responses, and scaly erythroderma type characterized by a type I IFN signature and Th9-type allergic responses. While symptomatic treatments such as emollients and topical corticosteroids have been the mainstay of care, recent advances have opened new therapeutic avenues involving biologic agents and oral small-molecule immunomodulators. This review provides a comprehensive overview of the current clinical landscape and future directions of biologics (e.g., dupilumab, secukinumab, ustekinumab) and small-molecule therapies (e.g., JAK inhibitors such as tofacitinib, baricitinib, and upadacitinib) in the treatment of NS. Though evidence remains limited to case reports and small series, preliminary data suggest that cytokine-targeted interventions—particularly those inhibiting IL-4, IL-13, IL-17, IL-36, and JAK pathways—may offer tangible clinical benefits. Well-designed clinical trials and mechanistic investigations are crucial to establishing their place in NS management. en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MukaiTomoyuki en-aut-sei=Mukai en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasuiKen‐ichi en-aut-sei=Hasui en-aut-mei=Ken‐ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaAnri en-aut-sei=Morita en-aut-mei=Anri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=27 article-no= start-page=6557 end-page=6563 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fluorescence detection of DNA with a single-base mismatch by a Tm-independent peptide nucleic acid (PNA) twin probe en-subtitle= kn-subtitle= en-abstract= kn-abstract=There is a need to develop efficient methods for detecting target nucleic acids to enable the rapid diagnosis and early treatment of diseases. We previously demonstrated that a peptide nucleic acid (PNA) twin probe, consisting of two PNAs each containing a fluorescent dye, with pyrene at one end, detects target DNA sequence-specifically through pyrene excimer emission. In this study, to advance the development of this probe system, we further investigated the fluorescence properties of the PNA twin probe P1 and P2, and found that the excimer fluorescence was significantly reduced when a mismatched base in the DNA sequence was present at the site of P1 closest to the pyrene. In other words, this probe was found to detect single-base mismatches without taking into account the thermal stability of the PNA/DNA hybrid. The detection limit of this PNA twin probe for the single-base-mismatched DNA was 2.7 nM. In the future, this probe should lead to a method to detect point mutations in endogenous nucleic acids within cells. en-copyright= kn-copyright= en-aut-name=IshiiKoki en-aut-sei=Ishii en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigetoHajime en-aut-sei=Shigeto en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamuraShohei en-aut-sei=Yamamura en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImaiYoshitane en-aut-sei=Imai en-aut-mei=Yoshitane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamatsuMizuki en-aut-sei=Kitamatsu en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=2 en-affil=Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=3 en-affil=Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=4 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Applied Chemistry, Kindai University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=27684 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250729 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The significance of adding posterior decompression to spine stabilization in metastatic spinal surgery: a multicenter prospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The usefulness of spine stabilization for treating metastatic spinal tumors with tumor-induced instability has been reported. However, no reports have prospectively evaluated the effectiveness of adding posterior decompression to stabilization surgery for improving symptoms. This multicenter prospective study aimed to determine whether adding posterior decompression to spine stabilization surgery for metastatic spinal tumors affects postoperative outcomes and complications. A total of 263 patients who underwent spine stabilization with (n = 189) or without (n = 74) decompression were analyzed. Patient demographics, the Spinal Instability Neoplastic Score (SINS), and the Epidural Spinal Cord Compression (ESCC) score were recorded. The outcomes were assessed preoperatively and at 1 and 6 months postoperatively in terms of neurological status, the Barthel Index, the EQ-5D-5 L, and the visual analog scale (VAS). Decompression was primarily performed in patients with severe neurological deficits and high-grade ESCC. Both groups showed postoperative improvement. Propensity score matching was applied to adjust for baseline differences. After matching, there were no significant differences in functional improvement between the decompression and nondecompression groups, and the complication rates were comparable. In matched patients presenting primarily with spinal instability and pain, the addition of decompression did not appear to confer a significant functional benefit within 6 months postoperatively. en-copyright= kn-copyright= en-aut-name=TominagaHiroyuki en-aut-sei=Tominaga en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawamuraIchiro en-aut-sei=Kawamura en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimadaHirofumi en-aut-sei=Shimada en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiHiromi en-aut-sei=Sasaki en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniguchiNoboru en-aut-sei=Taniguchi en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShirataniYuki en-aut-sei=Shiratani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzukiAkinobu en-aut-sei=Suzuki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeraiHidetomi en-aut-sei=Terai en-aut-mei=Hidetomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimizuTakaki en-aut-sei=Shimizu en-aut-mei=Takaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KakutaniKenichiro en-aut-sei=Kakutani en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KandaYutaro en-aut-sei=Kanda en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IshiharaMasayuki en-aut-sei=Ishihara en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=PakuMasaaki en-aut-sei=Paku en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakahashiYohei en-aut-sei=Takahashi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FunayamaToru en-aut-sei=Funayama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiuraKousei en-aut-sei=Miura en-aut-mei=Kousei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShirasawaEiki en-aut-sei=Shirasawa en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=InoueHirokazu en-aut-sei=Inoue en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KimuraAtsushi en-aut-sei=Kimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IimuraTakuya en-aut-sei=Iimura en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MoridairaHiroshi en-aut-sei=Moridaira en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NakajimaHideaki en-aut-sei=Nakajima en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=WatanabeShuji en-aut-sei=Watanabe en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=AkedaKoji en-aut-sei=Akeda en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TakegamiNorihiko en-aut-sei=Takegami en-aut-mei=Norihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=NakanishiKazuo en-aut-sei=Nakanishi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=SawadaHirokatsu en-aut-sei=Sawada en-aut-mei=Hirokatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MatsumotoKoji en-aut-sei=Matsumoto en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=FunabaMasahiro en-aut-sei=Funaba en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SuzukiHidenori en-aut-sei=Suzuki en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=FunaoHaruki en-aut-sei=Funao en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=OshigiriTsutomu en-aut-sei=Oshigiri en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HiraiTakashi en-aut-sei=Hirai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=OtsukiBungo en-aut-sei=Otsuki en-aut-mei=Bungo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=KobayakawaKazu en-aut-sei=Kobayakawa en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=ManabeHiroaki en-aut-sei=Manabe en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=TanishimaShinji en-aut-sei=Tanishima en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=HashimotoKo en-aut-sei=Hashimoto en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=IwaiChizuo en-aut-sei=Iwai en-aut-mei=Chizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=YamabeDaisuke en-aut-sei=Yamabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=HiyamaAkihiko en-aut-sei=Hiyama en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SekiShoji en-aut-sei=Seki en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=GotoYuta en-aut-sei=Goto en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=MiyazakiMasashi en-aut-sei=Miyazaki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=WatanabeKazuyuki en-aut-sei=Watanabe en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=NakamaeToshio en-aut-sei=Nakamae en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=KaitoTakashi en-aut-sei=Kaito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=NakashimaHiroaki en-aut-sei=Nakashima en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=NagoshiNarihito en-aut-sei=Nagoshi en-aut-mei=Narihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=KatoSatoshi en-aut-sei=Kato en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=ImagamaShiro en-aut-sei=Imagama en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=WatanabeKota en-aut-sei=Watanabe en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=InoueGen en-aut-sei=Inoue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=FuruyaTakeo en-aut-sei=Furuya en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Osaka Metropolitan University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Osaka Metropolitan University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Kansai Medical University Hospital kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Kansai Medical University Hospital kn-affil= affil-num=14 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=16 en-affil=Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=18 en-affil=Rehabilitation Center, Jichi Medical University Hospital kn-affil= affil-num=19 en-affil=Department of Orthopaedics, Jichi Medical University kn-affil= affil-num=20 en-affil=Department of Orthopaedic Surgery, Dokkyo Medical University kn-affil= affil-num=21 en-affil=Department of Orthopaedic Surgery, Dokkyo Medical University kn-affil= affil-num=22 en-affil=Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=23 en-affil=Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=24 en-affil=Department of Orthopaedic Surgery, Mie University Graduate School of Medicine kn-affil= affil-num=25 en-affil=Department of Orthopaedic Surgery, Mie University Graduate School of Medicine kn-affil= affil-num=26 en-affil=Department of Orthopaedic Surgery, Kawasaki Medical School kn-affil= affil-num=27 en-affil=Department of Orthopaedic Surgery, Nihon University School of Medicine kn-affil= affil-num=28 en-affil=Department of Orthopaedic Surgery, Nihon University School of Medicine kn-affil= affil-num=29 en-affil=Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine kn-affil= affil-num=30 en-affil=Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine kn-affil= affil-num=31 en-affil=Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=32 en-affil=Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine kn-affil= affil-num=33 en-affil=Department of Orthopedic Surgery, Institute of Science Tokyo kn-affil= affil-num=34 en-affil=Department of Orthopaedic Surgery, Kyoto University Hospital kn-affil= affil-num=35 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=36 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=37 en-affil=Department of Orthopedics, Tokushima University kn-affil= affil-num=38 en-affil=Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=39 en-affil=Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=40 en-affil=Department of Orthopaedic Surgery, Gifu University Hospital kn-affil= affil-num=41 en-affil=Department of Orthopaedic Surgery, Iwate Medical University kn-affil= affil-num=42 en-affil=Department of Orthopaedic Surgery, Tokai University School of Medicine kn-affil= affil-num=43 en-affil=Department of Orthopaedic Surgery, University of Toyama kn-affil= affil-num=44 en-affil=Department of Orthopaedic Surgery, Nagoya City University kn-affil= affil-num=45 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=46 en-affil=Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine kn-affil= affil-num=47 en-affil=Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=48 en-affil=Department of Orthopedic Surgery, Osaka University Graduate School of Medicine kn-affil= affil-num=49 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=50 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=51 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=52 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=53 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=54 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=55 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University kn-affil= en-keyword=Metastatic spinal tumors kn-keyword=Metastatic spinal tumors en-keyword=Spine stabilization kn-keyword=Spine stabilization en-keyword=Decompression kn-keyword=Decompression en-keyword=Propensity score matching kn-keyword=Propensity score matching en-keyword=Multicenter prospective study kn-keyword=Multicenter prospective study en-keyword=The epidural spinal cord compression (ESCC) score kn-keyword=The epidural spinal cord compression (ESCC) score END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=10 article-no= start-page=e70318 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effectiveness of Statins for Oxaliplatin‐Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ≥ 2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (n = 510), statin use was associated with a significantly lower incidence of Grade ≥ 2 OIPN than no statin use (19.8% vs. 28.3%, respectively; p = 0.029). Our findings indicate that statins may protect against OIPN in patients with CRC. en-copyright= kn-copyright= en-aut-name=TakechiKenshi en-aut-sei=Takechi en-aut-mei=Kenshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawashiriTakehiro en-aut-sei=Kawashiri en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MineKeisuke en-aut-sei=Mine en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HidaNoriko en-aut-sei=Hida en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MomoKenji en-aut-sei=Momo en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaMasanobu en-aut-sei=Uchiyama en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaMami en-aut-sei=Uchida en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaMamoru en-aut-sei=Tanaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HidakaNoriaki en-aut-sei=Hidaka en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasuiHideki en-aut-sei=Yasui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UedaMasahiro en-aut-sei=Ueda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiRyohei en-aut-sei=Fujii en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HashimotoMisaki en-aut-sei=Hashimoto en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakamotoYasutaka en-aut-sei=Sakamoto en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UyamaKana en-aut-sei=Uyama en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HanaiYuki en-aut-sei=Hanai en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TsuboyaAyaka en-aut-sei=Tsuboya en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SuzukiKeisuke en-aut-sei=Suzuki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KamiyamaNaoya en-aut-sei=Kamiyama en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HagiwaraHiromi en-aut-sei=Hagiwara en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OkadaNaoto en-aut-sei=Okada en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Research and Development, Graduate School of Pharmacy, SHOWA Medical University kn-affil= affil-num=7 en-affil=Department of Hospital Pharmaceutics, Graduate School of Pharmacy, SHOWA Medical University kn-affil= affil-num=8 en-affil=Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=9 en-affil=Department of Pharmacy, Fukuoka University Hospital kn-affil= affil-num=10 en-affil=Division of Pharmacy, Ehime University Hospital kn-affil= affil-num=11 en-affil=Division of Pharmacy, Ehime University Hospital kn-affil= affil-num=12 en-affil=Center for Clinical Research, Hamamatsu University Hospital kn-affil= affil-num=13 en-affil=Faculty of Pharmaceutical Sciences, Setsunan University kn-affil= affil-num=14 en-affil=Department of Pharmacy, Kansai Medical University Hospital kn-affil= affil-num=15 en-affil=Department of Pharmacy, Kansai Medical University Hospital kn-affil= affil-num=16 en-affil=Department of Pharmacy, Yokohama City University Hospital kn-affil= affil-num=17 en-affil=Department of Pharmacy, Yokohama City University Hospital kn-affil= affil-num=18 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=19 en-affil=Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University kn-affil= affil-num=20 en-affil=Department of Pharmacy, Kawasaki Municipal Tama Hospital kn-affil= affil-num=21 en-affil=Innovation Center for Translational Research, National Center for Geriatrics and Gerontology kn-affil= affil-num=22 en-affil=Asahikawa Medical University Hospital kn-affil= affil-num=23 en-affil=Nagoya City University Hospital kn-affil= affil-num=24 en-affil=Pharmacy Department, Yamaguchi University Hospital kn-affil= affil-num=25 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=26 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= en-keyword=cancer kn-keyword=cancer en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=oxaliplatin kn-keyword=oxaliplatin en-keyword=peripheral neuropathy kn-keyword=peripheral neuropathy en-keyword=statins kn-keyword=statins END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=6 article-no= start-page=836 end-page=849 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251028 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (C1orf50), a gene with a previously uncharacterized function in HCC.
Materials and Methods: We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines.
Results: Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways.
Conclusion: C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer. en-copyright= kn-copyright= en-aut-name=TANAKAATSUSHI en-aut-sei=TANAKA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OTANIYUSUKE en-aut-sei=OTANI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MAEKAWAMASAKI en-aut-sei=MAEKAWA en-aut-mei=MASAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ROGACHEVSKAYAANNA en-aut-sei=ROGACHEVSKAYA en-aut-mei=ANNA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PEÑATIRSO en-aut-sei=PEÑA en-aut-mei=TIRSO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CHINVANESSA D. en-aut-sei=CHIN en-aut-mei=VANESSA D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TOYOOKASHINICHI en-aut-sei=TOYOOKA en-aut-mei=SHINICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ROEHRLMICHAEL H. en-aut-sei=ROEHRL en-aut-mei=MICHAEL H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FUJIMURAATSUSHI en-aut-sei=FUJIMURA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=6 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=stemness kn-keyword=stemness en-keyword=cell cycle kn-keyword=cell cycle en-keyword=epithelial‑mesenchymal transition kn-keyword=epithelial‑mesenchymal transition END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=5 article-no= start-page=e200293 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vanishing White Matter Disease With EIF2B2 c.254T >A Variant en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives
Typical MRI findings of vanishing white matter disease (VWM) include diffuse white matter lesions with cystic degeneration. However, mild cases may lack these typical features, posing diagnostic challenges.
Methods
We describe 2 of 3 individuals carrying the homozygous c.254T >A variant in EIF2B2 identified at our hospital, excluding 1 previously reported case.1 Genetic analyses were performed using whole-genome sequence or whole-exome sequence analysis, and detected variants were confirmed by direct nucleotide sequence analysis. Brain MRI findings and clinical features were reviewed for the 2 individuals along with other cases in the literature with the same variant.
Results
A 69-year-old woman presented with recurrent transient dizziness and secondary amenorrhea. MRI of the brain revealed small T2-hyperintense lesions confined to the subcortical white matter with hyperintensities on diffusion-weighted images and mildly elevated apparent diffusion coefficient values. A 28-year-old woman presented with transient dizziness and secondary amenorrhea. MRI of the brain showed mild T2-hyperintense lesions in the cerebral white matter with frontal predominance.
Discussion
This report highlights the clinically mild cases of VWM with subtle abnormalities on brain MRI who had the homozygous c.254T >A in EIF2B2, further expanding the clinical spectrum of VWM and underscoring the importance of genetic assessments in the diagnosis of individuals with mild clinical and MRI findings. en-copyright= kn-copyright= en-aut-name=KakumotoToshiyuki en-aut-sei=Kakumoto en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokimuraRyo en-aut-sei=Tokimura en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboyamaYoko en-aut-sei=Tsuboyama en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HayashiYasufumi en-aut-sei=Hayashi en-aut-mei=Yasufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataAtsushi en-aut-sei=Iwata en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaMeiko Hashimoto en-aut-sei=Maeda en-aut-mei=Meiko Hashimoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimizuJun en-aut-sei=Shimizu en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GonoiWataru en-aut-sei=Gonoi en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=13 en-affil=Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=478 cd-vols= no-issue= article-no= start-page=123708 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=CST3 (NM_000099.4) encodes cystatin C, whose C-terminal truncating variants in this gene have recently been reported to cause adult-onset leukoencephalopathy, characterized by headaches, transient neurological symptoms, and distinct imaging findings. We present four patients from two Japanese families, including one with a novel variant (c.358-2_395del). Three patients from one family developed chronic headaches around the age of 20, whereas the patient from the other family remained asymptomatic until his fifties. mRNA analysis of the patient with c.358-2_395del revealed a splicing alteration leading to an in-frame deletion (p.Lys120_Gln133del), representing the first CST3 variant that does not result in a truncated protein. These findings broaden our understanding of the clinical and genetic spectra of CST3-related leukoencephalopathy (114 words). en-copyright= kn-copyright= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiomiKazutaka en-aut-sei=Shiomi en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoRyoji en-aut-sei=Goto en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuromiYumiko en-aut-sei=Kuromi en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsudaNozomu en-aut-sei=Matsuda en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanaiKazuaki en-aut-sei=Kanai en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurokawaRyo en-aut-sei=Kurokawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NomotoJunko en-aut-sei=Nomoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TanakaMasaki en-aut-sei=Tanaka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OmaeYosuke en-aut-sei=Omae en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KawaiYosuke en-aut-sei=Kawai en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TokunagaKatsushi en-aut-sei=Tokunaga en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=8 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=9 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=13 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=14 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=15 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=16 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=17 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=CST3 kn-keyword=CST3 en-keyword=Cystatin-C kn-keyword=Cystatin-C en-keyword=Leukodystrophy kn-keyword=Leukodystrophy en-keyword=Leukoencephalopathy kn-keyword=Leukoencephalopathy en-keyword=Middle cerebellar peduncle kn-keyword=Middle cerebellar peduncle en-keyword=MCP kn-keyword=MCP END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=INF2-Related Charcot–Marie–Tooth Disease in a Japanese Cohort: Genetic and Clinical Insights en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: INF2 mutations cause focal segmental glomerulosclerosis (FSGS) and Charcot–Marie–Tooth disease (CMT). Accurate genetic diagnosis is critical, as INF2-related FSGS is typically resistant to immunotherapy yet rarely recurs after transplantation, and its associated neuropathy can mimic treatable immune-mediated disorders such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
Methods: We performed a multicenter study investigating 3329 Japanese patients with inherited peripheral neuropathies/CMT who underwent gene panel sequencing or whole-exome analysis between 2007 and 2024. Clinical data, including electrophysiological assessments, were obtained from the patients' medical records.
Results: We identified six pathogenic INF2 variants in eight patients, all of which were located within the diaphanous inhibitory domain. Structural modeling revealed clustering of variants near the diaphanous autoregulatory domain-binding pocket, which is critical for INF2 autoinhibition. Clinically, all cases were sporadic, with a median age at neurological onset of 9 years. All patients exhibited lower limb weakness, and 6/8 (75%) had sensory disturbances. All patients also developed kidney dysfunction, with 7/8 (88%) progressing to end-stage renal disease at a median age of 15 years. Furthermore, all patients showed demyelinating neuropathy, and 2/8 (25%) received immunotherapy due to suspected immune-mediated neuropathy.
Conclusion: Although INF2 variants are a rare cause of CMT in Japan, they should be considered in pediatric patients with demyelinating neuropathy and early-onset proteinuria, even in the absence of a family history. Blood and urine tests assessing renal dysfunction can provide guidance for appropriate genetic testing. en-copyright= kn-copyright= en-aut-name=YanoChikashi en-aut-sei=Yano en-aut-mei=Chikashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AndoMasahiro en-aut-sei=Ando en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiguchiYujiro en-aut-sei=Higuchi en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YuanJun‐Hui en-aut-sei=Yuan en-aut-mei=Jun‐Hui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimuraAkiko en-aut-sei=Yoshimura en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HobaraTakahiro en-aut-sei=Hobara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatomoRisa en-aut-sei=Nagatomo en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KojimaFumikazu en-aut-sei=Kojima en-aut-mei=Fumikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiramatsuYu en-aut-sei=Hiramatsu en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NozumaSatoshi en-aut-sei=Nozuma en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraTomonori en-aut-sei=Nakamura en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SakiyamaYusuke en-aut-sei=Sakiyama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimuraTakashi en-aut-sei=Kimura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiyazakiAyako en-aut-sei=Miyazaki en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KinjoChinatsu en-aut-sei=Kinjo en-aut-mei=Chinatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YokochiKenji en-aut-sei=Yokochi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamanakaNanami en-aut-sei=Yamanaka en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsudaNozomu en-aut-sei=Matsuda en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SuichiTomoki en-aut-sei=Suichi en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HanaokaYoshiyuki en-aut-sei=Hanaoka en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KojimaHaruka en-aut-sei=Kojima en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TodoKenichi en-aut-sei=Todo en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TakashimaHiroshi en-aut-sei=Takashima en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=2 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=3 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=4 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=8 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=9 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=10 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=11 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=12 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=13 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Neurology, Hyogo Medical University kn-affil= affil-num=16 en-affil=Department of Clinical Genetics, Hyogo Medical University kn-affil= affil-num=17 en-affil=Department of Clinical Genetics, Hyogo Medical University kn-affil= affil-num=18 en-affil=Department of Pediatrics, Toyohashi Municipal Hospital kn-affil= affil-num=19 en-affil=Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Neurology, Fukushima Medical University School of Medicine kn-affil= affil-num=21 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Kurashiki Central Hospital kn-affil= affil-num=23 en-affil=Department of Neurology, Tokyo Women's Medical University kn-affil= affil-num=24 en-affil=Department of Neurology, Tokyo Women's Medical University kn-affil= affil-num=25 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=27 en-affil=Department of Neurology, The University of Tokyo Hospital kn-affil= affil-num=28 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=Charcot-Marie- Tooth disease kn-keyword=Charcot-Marie- Tooth disease en-keyword=focal segmental glomerulosclerosis kn-keyword=focal segmental glomerulosclerosis en-keyword=INF2 kn-keyword=INF2 en-keyword=inherited peripheral neuropathies kn-keyword=inherited peripheral neuropathies en-keyword=neuropathy kn-keyword=neuropathy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ATPase copper transporting beta contributes to cisplatin resistance as a regulatory factor of extracellular vesicles in head and neck squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cisplatin (CDDP) resistance remains a major clinical challenge in the treatment of head and neck squamous cell carcinoma (HNSC). Our group identified ATPase copper transporting beta (ATP7B) as a mediator of CDDP resistance through its role in drug efflux and small extracellular vesicle (sEV) secretion. Herein, we uncovered a novel mechanism by which ATP7B regulates sEV dynamics and the intercellular transmission of CDDP resistance. Using transcriptomic analyses of HNSC datasets, we demonstrate that ATP7B expression correlates with endocytosis- and epithelial-mesenchymal transition (EMT)-related gene sets and with elevated levels of EV-associated proteins. CDDP-resistant HNSC cells exhibited upregulated ATP7B, Rab5/Rab7, and preferentially secreted HSP90- and EpCAM-rich sEVs. These sEVs were leading to increased ATP7B expression and reduced CDDP sensitivity in recipient cells. A pharmacological inhibition of sEV biogenesis with GW4869 suppressed ATP7B and Atox1 expressions, inhibited late endosome maturation, and significantly enhanced CDDP-induced apoptosis in HNSC cells. In vivo, GW4869 reduced the sEV protein content and ATP7B expression in xenograft tumors. These findings establish that ATP7B is a critical modulator of sEV cargo and resistance propagation. Our results highlight a previously unrecognized ATP7B–sEV axis driving chemoresistance and identify sEV inhibition as a promising strategy to overcome therapeutic failure in HNSC. en-copyright= kn-copyright= en-aut-name=OgawaTatsuo en-aut-sei=Ogawa en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RyumonShoji en-aut-sei=Ryumon en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKohei en-aut-sei=Sato en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UmemoriKoki en-aut-sei=Umemori en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaKunihiro en-aut-sei=Yoshida en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkuiTatsuo en-aut-sei=Okui en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Momen-HeraviFatemeh en-aut-sei=Momen-Heravi en-aut-mei=Fatemeh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=11 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Orofacial Sciences, School of Dentistry, University of California San Francisco kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=108 cd-vols= no-issue= article-no= start-page=104508 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Introduction to the “Japanese and Western approaches to psychotrauma” symposium en-subtitle= kn-subtitle= en-abstract= kn-abstract=Understandings of psychotrauma have changed throughout medical history, shaped by cultural and social factors. Reviewing transcultural perspectives of psychotrauma helps understand its complexities and contextual impacts. This paper summarizes the Japan–Netherlands symposium on psychotrauma held on March 1, 2024. Despite experiencing psychological trauma from World War II and numerous natural disasters, Japan did not actively research post-traumatic stress disorder (PTSD) for nearly 50 years after the war. The Great Hanshin-Awaji Earthquake and the Tokyo subway Sarin gas attack (1995) popularized the term PTSD in Japan and triggered related research. The absence of psychotrauma research in Japan may reflect a form of state-level PTSD, characterized by avoidance. Japan’s collectivist culture, stigma against seeking psychological help, view of patience as a virtue, survivor guilt, and moral injury were potential related factors. Additionally, sociocultural factors (e.g., insufficient collective grieving and focusing on post-war reconstruction) were discussed as potential hinderances to discussing war experiences. From a European perspective, we examined how “Konzentrationslager” (KZ) syndrome, a trauma-related disorder, evolved independently into diverse conceptual frameworks, ultimately contributing to the acceptance of PTSD following its introduction in 1980. Beyond state compensation for concentration camp survivors, advocacy by feminist movements and veterans' groups increased awareness of psychotrauma across Europe, fostering scholarly research and public discourse. Both PTSD and KZ syndromes are diagnostic categories shaped by specific historical and cultural contexts and should not be regarded as simple, universally applicable medical conditions. They reflect how trauma is interpreted and responded to differently depending on cultural, political, and historical factors. en-copyright= kn-copyright= en-aut-name=NagamineMasanori en-aut-sei=Nagamine en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaoTomoyo en-aut-sei=Nakao en-aut-mei=Tomoyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=van BergenLeo en-aut-sei=van Bergen en-aut-mei=Leo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShigemuraJun en-aut-sei=Shigemura en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoTaku en-aut-sei=Saito en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=van der DoesFlorentine H.S. en-aut-sei=van der Does en-aut-mei=Florentine H.S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitanoMasato en-aut-sei=Kitano en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GiltayErik J. en-aut-sei=Giltay en-aut-mei=Erik J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=van der WeeNic J. en-aut-sei=van der Wee en-aut-mei=Nic J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=VermettenEric en-aut-sei=Vermetten en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Behavioral Science, National Defense Medical College Research Institute kn-affil= affil-num=2 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= affil-num=3 en-affil=Freelance Medical Historian kn-affil= affil-num=4 en-affil=Faculty of Health Sciences, Mejiro University kn-affil= affil-num=5 en-affil=Division of Behavioral Science, National Defense Medical College Research Institute kn-affil= affil-num=6 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= affil-num=7 en-affil=Division of Behavioral Science, National Defense Medical College Research Institute kn-affil= affil-num=8 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= affil-num=9 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= affil-num=10 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= en-keyword=Psychotrauma kn-keyword=Psychotrauma en-keyword=World War II kn-keyword=World War II en-keyword=Japan kn-keyword=Japan en-keyword=Europe kn-keyword=Europe en-keyword=KZ syndrome kn-keyword=KZ syndrome en-keyword=Post-traumatic stress disorder kn-keyword=Post-traumatic stress disorder END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue= article-no= start-page=57 end-page=65 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rectal Swab–based Targeted Prophylactic Antibiotics Reduce Infectious Complications After Transrectal Prostate Biopsy: A Systematic Review and Meta-analysis of Randomized Controlled Trials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objective: Transperineal ultrasound-guided prostate biopsy is the recommended approach in guidelines, while transrectal ultrasound-guided prostate biopsy (TRUS-PB) is still widely used to diagnose prostate cancer (PCa); however, it is associated with a significant rate of infectious complications. We aimed to assess the efficacy of targeted prophylactic antibiotics (TPAs), based on rectal swabs, in reducing the incidence of infectious complications after TRUS-PB compared with empiric prophylactic antibiotics.
Methods: PubMed, Web of Science, and Scopus were queried in December 2024 for randomized controlled trials (RCTs) comparing infectious complications between patients who received TPAs based on rectal swab culture before TRUS-PB and those who received empiric prophylactic antibiotics before TRUS-PB (PROSPERO: CRD42024523794). The primary outcomes were the incidence rates of febrile urinary tract infection (fUTI) and sepsis.
Key findings and limitations: Overall, nine RCTs (n = 3002) were included in our analyses. The incidence of fUTI was approximately half as high in patients who received TPAs as in those who received empiric prophylactic antibiotics (n = 3002, 2.7% vs 5.2%, risk ratio [RR]: 0.54, 95% confidence interval [CI]: 0.36–0.81, p = 0.003). Based on these pooled incidence rates, the number of patients needed to treat to prevent fUTI after TRUS-PB was 40; however, there was no statistically significant difference in the incidence of sepsis between patients receiving TPAs and those who received empiric antibiotic prophylaxis (n = 2735, 1.3% vs 1.8%, RR: 0.74, 95% CI: 0.31–1.75, p = 0.4).
Conclusions and clinical implications: TPAs based on rectal swab culture significantly reduces the incidence of fUTI in patients who undergo TRUS-PB for PCa diagnosis compared with that in patients who receive empiric prophylactic antibiotics; however, there is insufficient evidence to assess its effect on the risk of sepsis. We recommend, based on the clinically relevant reduction in the incidence of fUTI, performing rectal swab–based TPAs in patients undergoing TRUS-PB.
Patient summary: We reviewed infections occurring after transrectal prostate biopsy in over 3000 patients. The use of antibiotics chosen based on a simple rectal swab decreased the rate of postbiopsy fever and urinary tract infections by half compared with the use of standard antibiotics. More research is needed to understand whether this approach also prevents the rare but serious complication of sepsis. en-copyright= kn-copyright= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Kardoust PariziMehdi en-aut-sei=Kardoust Parizi en-aut-mei=Mehdi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiszczykMarcin en-aut-sei=Miszczyk en-aut-mei=Marcin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FazekasTamás en-aut-sei=Fazekas en-aut-mei=Tamás kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CormioAngelo en-aut-sei=Cormio en-aut-mei=Angelo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KarakiewiczPierre I. en-aut-sei=Karakiewicz en-aut-mei=Pierre I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ChlostaPiotr en-aut-sei=Chlosta en-aut-mei=Piotr kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=BrigantiAlberto en-aut-sei=Briganti en-aut-mei=Alberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=5 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=6 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=12 en-affil=Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre kn-affil= affil-num=13 en-affil=Department of Urology, Jagiellonian University Medical College kn-affil= affil-num=14 en-affil=Unit of Urology/Division of Oncology, Gianfranco Soldera Prostate Cancer Lab, IRCCS San Raffaele Scientific Institute kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= en-keyword=Febrile urinary tract infection kn-keyword=Febrile urinary tract infection en-keyword=Targeted prophylactic antibiotics kn-keyword=Targeted prophylactic antibiotics en-keyword=Transrectal prostate biopsy kn-keyword=Transrectal prostate biopsy en-keyword=Sepsis kn-keyword=Sepsis END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=468 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The safety and efficacy of finasteride for transgender men with androgenetic alopecia: a case series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Testosterone replacement therapy is commonly used in transgender men for masculinization. One of the most common adverse effects of testosterone replacement therapy is androgenetic alopecia. In Japan, finasteride is approved exclusively for cisgender men and is not indicated for transgender men. The aim of this clinical trial was to evaluate the safety and efficacy of finasteride in transgender men with androgenetic alopecia.
Case presentation This study included three transgender men (assigned female at birth, identifying as male), aged 44, 43, and 29 years. All participants were of Asian ethnicity. A clinical trial was conducted from October 2021 to December 2023. Transgender men aged 20–60 years who had not undergone hysterectomy, were undergoing testosterone replacement therapy, and who had been diagnosed with stage ≥ II androgenetic alopecia on the basis of the Norwood–Hamilton scale were recruited. The participants initiated treatment with 0.2 mg of finasteride per day for 3 months (phase 1). If no adverse events above grade 2 occurred, the dose was increased to 1.0 mg per day for an additional 3 months (phase 2). The primary endpoints were the incidence of treatment-related adverse events at 1 week, 1 month, and 3 months, as well as the rate of participants continuing treatment at 3 months. None of the patients experienced serious adverse events at 3 months, and all the patients extended their treatment to a total of 6 months. Improvements of at least one stage on the N–H scale were observed, but two participants experienced resumption of menstruation.
Conclusion Finasteride appears to be a safe and effective treatment for androgenetic alopecia in transgender men undergoing testosterone replacement therapy. However, its potential for reducing some of the effects of testosterone replacement therapy warrants further investigation. Trial registration: jRCT, jRCTs061210040, registered 7 October 2021, https://jrct.mhlw.go.jp/latest-detail/jRCTs061210040. en-copyright= kn-copyright= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoYuko en-aut-sei=Matsumoto en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakoTomoko en-aut-sei=Sako en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriwakeTakatoshi en-aut-sei=Moriwake en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriiSatoshi en-aut-sei=Horii en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=5 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Center for Innovative Clinical Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Finasteride kn-keyword=Finasteride en-keyword=Dihydrotestosterone kn-keyword=Dihydrotestosterone en-keyword=Transgender men kn-keyword=Transgender men en-keyword= Androgenetic alopecia kn-keyword= Androgenetic alopecia en-keyword=Resumption of menstruation kn-keyword=Resumption of menstruation END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=399 end-page=404 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epstein-Barr Virus-Associated Early Gastric Carcinoma with Lymphoid Stroma Mimicking a Submucosal Tumor: A Typical Case Diagnosed by Endoscopic Resection and Treated by Local Resection with Sentinel Node Navigation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastric cancer with lymphoid stroma (GCLS) accounts for 1%-7% of gastric cancers; ~80% are Epstein-Barr virus (EBV)-positive. The rate of lymph node metastasis is relatively low, even when an early GCLS has invaded the submucosa. We report an early GCLS with massive submucosal invasion mimicking a submucosal tumor (SMT), diagnosed by endoscopic submucosal resection (ESD) and treated with local resection and sentinel node navigation surgery (SNNS). The patient was a 40-year-old Japanese man. A protruding lesion on the greater curvature of the middle part of his stomach was detected by X-ray, and an endoscopic examination revealed a 2.5-cm protruding tumor covered with a normal mucosa and small ulcers at the apex. ESD was performed for a diagnosis. The pathological diagnosis was lymphoepithelioma-like gastric cancer (GCLS), pT1b(SM2), Ly0, V0, pHM1, pVM1. EBV infection in the cancer cells was confirmed pathologically by EBV-encoded RNA. The local resection was performed using SNNS. The patient has had no recurrence or post-gastrectomy syndrome 4 years postsurgery. EBV-associated early GCLS resembling an SMT is relatively rare, and clinicians need to be aware of this disease. Local resection using SNNS may be a surgical option for GCLS cases with a low rate of lymphatic metastasis. en-copyright= kn-copyright= en-aut-name=IsozakiHiroshi en-aut-sei=Isozaki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoSasau en-aut-sei=Matsumoto en-aut-mei=Sasau kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakamaTakehiro en-aut-sei=Takama en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IsozakiYuka en-aut-sei=Isozaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShigeki en-aut-sei=Murakami en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Oomoto Hospital kn-affil= en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=gastric cancer with lymphoid stroma kn-keyword=gastric cancer with lymphoid stroma en-keyword=lymphoepithelioma-like carcinoma kn-keyword=lymphoepithelioma-like carcinoma en-keyword=Epstein Barr virus kn-keyword=Epstein Barr virus en-keyword=sentinel node navigation surgery kn-keyword=sentinel node navigation surgery END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=393 end-page=398 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gastroduodenal Artery-Preserving Pancreatoduodenectomy after Esophagectomy with Gastric Conduit Reconstruction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatoduodenectomy (PD) after esophagectomy with gastric conduit reconstruction is technically challenging. Preserving the blood supply of the gastric conduit is crucial in performing PD after esophagectomy. We report the case of a 66-year-old man who underwent gastroduodenal artery-preserving PD after esophagectomy with gastric conduit reconstruction for intraductal papillary mucinous neoplasm. The patient developed pseudoaneurysm rupture postoperatively, but was successfully treated with interventional radiology. Precise assessment is important in developing a surgical strategy depending on the patient’s specific anatomy and tumor characteristics. Moreover, special attention should be paid to avoid accidental injuries of the gastric conduit and gastric vessels during surgery. en-copyright= kn-copyright= en-aut-name=MasunagaAkari en-aut-sei=Masunaga en-aut-mei=Akari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanehiraNoriyuki en-aut-sei=Kanehira en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SotaYumi en-aut-sei=Sota en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=pancreatoduodenectomy kn-keyword=pancreatoduodenectomy en-keyword=esophagectomy kn-keyword=esophagectomy en-keyword=gastric conduit kn-keyword=gastric conduit en-keyword=fluorescence imaging kn-keyword=fluorescence imaging END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=387 end-page=392 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Utility of a Preoperative 3D Imaging Analysis System for Trigonal Meningioma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Trigonal meningiomas are rare and pose surgical challenges due to their deep location and proximity to critical neuroanatomical structures. We present the case of a 67-year-old woman with a growing trigonal meningioma successfully resected with guidance by a preoperative 3D imaging analysis system. Integration of CT and MRI including diffusion tensor imaging (DTI) enabled precise mapping of the optic radiation, guiding a middle temporal gyrus approach. Preoperative embolization reduced tumor vascularity, facilitating gross total resection with minimal blood loss. This case highlights the effectiveness of preoperative 3D imaging systems in optimizing surgical planning and improving outcomes in complex neurosurgical cases. en-copyright= kn-copyright= en-aut-name=MoriYusuke en-aut-sei=Mori en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmaeRyo en-aut-sei=Omae en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiranoShuichiro en-aut-sei=Hirano en-aut-mei=Shuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HarumaJun en-aut-sei=Haruma en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsushitaToshi en-aut-sei=Matsushita en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugiuKenji en-aut-sei=Sugiu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=trigonal meningioma kn-keyword=trigonal meningioma en-keyword=imaging analysis kn-keyword=imaging analysis en-keyword=diffusion tensor imaging kn-keyword=diffusion tensor imaging END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=381 end-page=385 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunoglobulin G4-related Disease Mimicking Portal Vein Tumor Thrombus en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report the case of a 72-year-old Japanese man with an incidental portal vein mass that was surgically resected and diagnosed as immunoglobulin G4 (IgG4)-related disease. The mass was discovered during an atrial fibrillation examination. The patient had a history of gastric cancer and was also diagnosed with rectal cancer, raising concerns about metastasis. Due to technical challenges, a biopsy was not feasible. Imaging findings suggested portal vein tumor thrombosis, complicating the diagnosis. This case highlights a rare presentation of IgG4-related disease mimicking portal vein tumor thrombus. en-copyright= kn-copyright= en-aut-name=SakuraiAtsunobu en-aut-sei=Sakurai en-aut-mei=Atsunobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YabukiTakayuki en-aut-sei=Yabuki en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokiHideki en-aut-sei=Aoki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IsekiAkiko en-aut-sei=Iseki en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Radiology, NHO Iwakuni Clinical Center kn-affil= affil-num=2 en-affil=Department of Radiology, NHO Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, NHO Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Pathology, NHO Iwakuni Clinical Center kn-affil= en-keyword=immunoglobulin G4-related disease kn-keyword=immunoglobulin G4-related disease en-keyword=inflammatory pseudotumor kn-keyword=inflammatory pseudotumor en-keyword=mass kn-keyword=mass en-keyword=portal vein kn-keyword=portal vein en-keyword=pericarditis kn-keyword=pericarditis END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=369 end-page=379 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Blood Pressure and Heart Rate Patterns Identified by Unsupervised Machine Learning and Their Associations with Subclinical Cerebral and Renal Damage in a Japanese Community: The Masuda Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=We applied unsupervised machine learning to analyze blood pressure (BP) and resting heart rate (HR) patterns measured during a 1-year period to assess their cross-sectional relationships with subclinical cerebral and renal target damage. Dimension reduction via uniform manifold approximation and projection, followed by K-means++ clustering, was used to categorize 362 community-dwelling participants (mean age, 56.2 years; 54.9% women) into three groups: Low BP and Low HR (Lo-BP/Lo-HR), High BP and High HR (Hi-BP/Hi-HR), and Low BP and High HR (Lo-BP/Hi-HR). Cerebral vessel lesions were defined as the presence of at least one of the following magnetic resonance imaging findings: lacunar infarcts, white matter hyperintensities, cerebral microbleeds, or intracranial artery stenosis. A high urinary albumin-to-creatinine ratio (UACR) was defined as the top 10% (≥ 12 mg/g) of the mean value from ≥2 measurements. Poisson regression with robust error variance, adjusted for demographics, lifestyle, and medical history, showed that the Hi-BP/Hi-HR group had relative risks of 3.62 (95% confidence interval, 1.75-7.46) for cerebral vessel lesions and 3.58 (1.33-9.67) for high UACR, and the Lo-BP/Hi-HR group had a relative risk of 3.09 (1.12-8.57) for high UACR, compared with the Lo-BP/Lo-HR group. These findings demonstrate the utility of an unsupervised, data-driven approach for identifying physiological patterns associated with subclinical target organ damage. en-copyright= kn-copyright= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinutaMinako en-aut-sei=Kinuta en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MunetomoSosuke en-aut-sei=Munetomo en-aut-mei=Sosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukudaMari en-aut-sei=Fukuda en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KojimaKatsuhide en-aut-sei=Kojima en-aut-mei=Katsuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniguchiKaori en-aut-sei=Taniguchi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakahataNoriko en-aut-sei=Nakahata en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KandaHideyuki en-aut-sei=Kanda en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine kn-affil= affil-num=7 en-affil=Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition kn-affil= affil-num=8 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=blood pressure kn-keyword=blood pressure en-keyword=heart rate kn-keyword=heart rate en-keyword=subclinical disease kn-keyword=subclinical disease en-keyword=uniform manifold approximation and projection kn-keyword=uniform manifold approximation and projection en-keyword=unsupervised machine learning kn-keyword=unsupervised machine learning END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=359 end-page=368 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advantages of Single-Position Surgery over Posterior Fusion for Single-Level Degenerative Lumbar Diseases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Single-position surgery with lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screws (PPSs) is gaining attention for its reduced invasiveness. We developed SPAPS, a technique allowing two surgeons to perform anterior LLIF and posterior PPS insertion simultaneously in a single lateral decubitus position. This retrospective study compared SPAPS (SPAPS-LLIF, Group SL) and minimally invasive posterior/transforaminal lumbar interbody fusion (MIS-PLIF/TLIF, Group PT) in patients treated between 2016 and 2019 with a two-year follow-up. Operative time, estimated blood loss (EBL), length of hospital stay (LOS), JOABPEQ and VAS scores, segmental lordotic angle, lumbar lordotic angle, segmental Cobb’s angle, PPS misplacement, PPS loosening, fusion status, and muscle cross-sectional areas were compared. Fifty-two patients were analyzed (Group SL: 25; Group PT: 27). SPAPS significantly reduced operative time (118.0 vs. 165.3 min, p <0.01) and estimated blood loss (8.6 vs. 164.1 mL, p<0.01). While clinical outcomes and hospital stay were comparable, Group SL had significantly lower PPS loosening (0% vs. 13%, p<0.01) and non-union rates (0% vs. 22.2%, p=0.02). Multifidus muscle atrophy was also less in Group SL (−14.3 vs. −121.5 mm2, p<0.01). SPAPS demonstrated advantages in reducing surgical invasiveness without compromising clinical efficacy, offering a promising alternative to conventional posterior fusion surgery. en-copyright= kn-copyright= en-aut-name=HiroseTomohiko en-aut-sei=Hirose en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkumaHisanori en-aut-sei=Ikuma en-aut-mei=Hisanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaKazutoshi en-aut-sei=Otsuka en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawasakiKeisuke en-aut-sei=Kawasaki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=3 en-affil=Otsuka Orthopedic Clinic kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital kn-affil= en-keyword=single-position surgery kn-keyword=single-position surgery en-keyword=simultaneous kn-keyword=simultaneous en-keyword=lateral decubitus positioning kn-keyword=lateral decubitus positioning en-keyword=lateral lumbar interbody fusion kn-keyword=lateral lumbar interbody fusion en-keyword=posterior lumbar interbody fusion kn-keyword=posterior lumbar interbody fusion END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=353 end-page=358 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of Extraocular Muscles in Patients with Exotropia and Healthy Participants Using Anterior Segment Optical Coherence Tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=To analyze and characterize the medial and lateral rectus muscles in patients with exotropia using anterior segment optical coherence tomography (AS-OCT). This study included 24 patients with exotropia (48 eyes) and 25 healthy individuals (50 eyes). Anterior segment optical coherence tomography was used to construct the en face images. The anterior chamber angle to the extraocular muscle insertion distance, muscle width, and muscle fiber angle from the muscle insertion sites were compared between the exotropia and the control groups. The correlation between these parameters and age or angle of deviation was evaluated. The mean ages were 13.2±4.1 years for the exotropia group and 17.6±7.2 years for the control group. The lateral rectus angle was significantly more inwardly rotated in the exotropia group than in the control group (1.6±6.3°, −1.4±4.0°, p=0.014). With increasing angle of deviation, the width of the lateral rectus increased (p=0.002). Our results indicate that the lateral rectus angle is significantly more inwardly rotated in patients with exotropia. These findings should contribute to a deeper understanding of the extraocular muscles in patients with this condition. en-copyright= kn-copyright= en-aut-name=ChiharaYuki en-aut-sei=Chihara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamasakiIchiro en-aut-sei=Hamasaki en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShibataKiyo en-aut-sei=Shibata en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorisawaShin en-aut-sei=Morisawa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KonoReika en-aut-sei=Kono en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanenagaKeisuke en-aut-sei=Kanenaga en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=exotropia kn-keyword=exotropia en-keyword=AS-OCT kn-keyword=AS-OCT en-keyword=anterior chamber angle to extraocular muscle insertion distance kn-keyword=anterior chamber angle to extraocular muscle insertion distance en-keyword=muscle width kn-keyword=muscle width en-keyword=muscle fiber angle kn-keyword=muscle fiber angle END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=345 end-page=352 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibition of Air-Exposure Stress–Induced Autolysis in Clostridium perfringens by Zn2+ en-subtitle= kn-subtitle= en-abstract= kn-abstract=Clostridium perfringens is a pathogenic anaerobe that causes gas gangrene and food poisoning. Although autolysin-mediated reorganization of the bacterial cell wall is crucial for cell division, excessive autolysin activity induced by stressors can lead to cell lysis. In C. perfringens, air exposure is a significant stressor that causes cell lysis, and Acp (N-acetylglucosaminidase) is known to be a major autolysin. To further facilitate C. perfringens research, a technology to prevent air-induced cell lysis must be developed. This study investigated the role of Acp in air-induced autolysis and explored potential inhibitors that would prevent cell lysis during experimental procedures. Morphological analyses confirmed that Acp functions as an autolysin in C. perfringens, as acpdeficient strains exhibited filamentous growth. The mutants exhibited negligible autolysis under air-exposure stress, confirming the involvement of Acp in the autolytic process. We also evaluated the effects of various divalent cations on Acp activity in vitro and identified Zn2+ as a potent inhibitor. Brief treatment with a Zn2+- containing buffer induced dose-dependent cell elongation and autolysis inhibition in C. perfringens. These findings demonstrate that simple Zn2+ treatment before experiments stabilizes C. perfringens cells, reducing autolysis under aerobic conditions and facilitating various biological studies, except morphological analyses. en-copyright= kn-copyright= en-aut-name=MatsunagaNozomu en-aut-sei=Matsunaga en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EgusaSeira en-aut-sei=Egusa en-aut-mei=Seira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AonoRiyo en-aut-sei=Aono en-aut-mei=Riyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TamaiEiji en-aut-sei=Tamai en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HitusmotoYasuo en-aut-sei=Hitusmoto en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaSeiichi en-aut-sei=Katayama en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=2 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=3 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=4 en-affil=Department of Infectious Disease, College of Pharmaceutical Science, Matsuyama University kn-affil= affil-num=5 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=6 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= en-keyword=Clostridium perfringens kn-keyword=Clostridium perfringens en-keyword=autolysin kn-keyword=autolysin en-keyword=zinc kn-keyword=zinc en-keyword=air-exposure autolysis kn-keyword=air-exposure autolysis END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=339 end-page=343 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Scleral Adjustment Method: A Novel Adjustable Suture Technique in Strabismus Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=To determine whether passing a pole suture through the sclera at two points provides fixation comparable to that of a sliding noose, we measured the tensile strength of the suture‒sclera interface during simulated traction. In this in vitro study, three suture patterns were evaluated in porcine eyeballs, using 6-0 polyglycolic acid sutures. Patterns A (control), B (second suture pass perpendicular), and C (second suture pass in the same direction) were compared. The tensile strength of each pattern was measured 20 times using a KANON TK300CN, and the results were analyzed using the Kruskal‒Wallis test. Pattern A showed a tensile strength of 2±4 gram-force (gf) (range: 0-12). Pattern B showed 112±38 gf (range: 61-184). Pattern C showed 139±31 gf (range: 97-204). Patterns B and C had significantly higher tensile strengths than Pattern A (p<0.001). Although Pattern C was not significantly different from Pattern B (p=0.363), it exhibited the highest tensile strength. Lifting the suture between the first and second suture passes allows for an adjustable suture length, suggesting that adjustability can be achieved using only the sclera. This scleral adjustment method with a second suture pass offers a durable means of securing extraocular muscles and may represent a valuable addition to adjustable suturing techniques. en-copyright= kn-copyright= en-aut-name=HamasakiIchiro en-aut-sei=Hamasaki en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShibataKiyo en-aut-sei=Shibata en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Lino Eye Clinic kn-affil= affil-num=2 en-affil=Lino Eye Clinic kn-affil= en-keyword=scleral adjustment method kn-keyword=scleral adjustment method en-keyword=adjustable suture technique kn-keyword=adjustable suture technique en-keyword=hang-loose method kn-keyword=hang-loose method en-keyword=tensile strength kn-keyword=tensile strength en-keyword=polyglycolic acid sutures kn-keyword=polyglycolic acid sutures END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=329 end-page=337 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Status of Extracorporeal Membrane Oxygenation as a Treatment Strategy for Primary Graft Dysfunction after Lung Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary graft dysfunction (PGD) is one of the major risk factors affecting patients’ short- and long-term survival after lung transplantation. No particular management strategy has been established for PGD; supportive care is the mainstay of PGD treatment. When a supportive strategy fails, the patient may require the introduction of extracorporeal membrane oxygenation (ECMO) as the last-resort measure for severe PGD. A variety of study of ECMO as a PGD treatment was reported and the management of PGD patients developed so far. Early recognition of a patient’s need for ECMO and its prompt initiation are critical to improved outcomes. The use of venovenous-ECMO became the preferred procedure for PGD rather than venoarterial-ECMO. However, the current ECMO strategy has limitations, and using ECMO to manage patients with PGD is not sufficiently effective. Further studies are required to develop this promising technology. en-copyright= kn-copyright= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=primary graft dysfunction kn-keyword=primary graft dysfunction en-keyword=extracorporeal membrane oxygenation kn-keyword=extracorporeal membrane oxygenation en-keyword=ex vivo lung perfusion kn-keyword=ex vivo lung perfusion END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=321 end-page=328 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Review of the Endoscopic Treatment for Bile Leak Following Cholecystectomy and Hepatic Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bile leak occurs in 2-25% of liver transplant, 3-27% of hepatic resection, and 0.1-4% of cholecystectomy cases. The clinical course of bile leak varies depending on the type of surgery that caused the fistula, as well as the type, severity, and timing of bile duct injury. Although infections resulting from bile leak can be life-threatening, the introduction of endoscopic treatment has enabled some patients to avoid reoperation and has reduced the negative impact on quality of life associated with external fistulas for percutaneous drainage. Endoscopic interventions, such as sphincterotomy and stent placement, reduce the pressure gradient between the bile duct and duodenum, facilitating bile drainage through the papilla and promoting the closure of the leak. We reviewed the literature from 2004 to 2024 regarding bile leak following cholecystectomy and liver surgery, examining recommended techniques, timing, and treatment outcomes. In cases of bile leak following cholecystectomy, clinical success was achieved in 72-96% of cases, while success rates for bile leak following liver surgery ranged from 50% to 100%. Although endoscopic treatment is effective, it is not universally applicable, and its limitations must be carefully considered. en-copyright= kn-copyright= en-aut-name=ObataTaisuke en-aut-sei=Obata en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=bile leak kn-keyword=bile leak en-keyword=cholecystectomy kn-keyword=cholecystectomy en-keyword=hepatic surgery kn-keyword=hepatic surgery en-keyword=endoscopic retrograde cholangiography kn-keyword=endoscopic retrograde cholangiography en-keyword=bridging stent placement kn-keyword=bridging stent placement END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=17 article-no= start-page=6102 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk Factors for Perioperative Urinary Tract Infection After Living Donor Kidney Transplantation Characterized by High Prevalence of Desensitization Therapy: A Single-Center Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Limited research exists on risk factors for urinary tract infections (UTIs) in kidney transplant recipients, particularly in high-risk groups such as ABO-incompatible or donor-specific antibody (DSA)-positive cases. Early UTIs, especially within the first month post-transplant, impact on acute rejection and long-term graft outcomes, highlighting the need for risk factor identification and management. Methods: Among 157 living donor kidney transplant cases performed at our institution between 2009 and 2024, 128 patients were included after excluding cases with >72 h of perioperative prophylactic antibiotics or urological complications. UTI was defined as the presence of pyuria and a positive urine culture, accompanied by clinical symptoms requiring antibiotic treatment, occurring within one month post-transplantation. Results: The median onset of UTI was postoperative day 8 (interquartile range, IQR: 6.8–9.3). No subsequent acute rejection episodes were observed. The median serum creatinine at 1 month postoperatively was 1.3 mg/dL (IQR: 1.1–1.7), and this was not significantly different from those who did not develop UTI. In univariate analysis, low or high BMI (<20 or >25), longer dialysis duration (>2.5 years), desensitization therapy (plasmapheresis + rituximab), elevated preoperative neutrophil-to-lymphocyte ratio (NLR) (≥3), and longer warm ischemic time (WIT) (≥7.8 min) were significantly associated with an increased infection risk of UTI (p = 0.010, 0.036, 0.028, 0.015, and 0.038, respectively). Multivariate analyses revealed that abnormal BMI, longer dialysis duration, desensitization therapy, and longer WIT were independent risk factors for UTI (p = 0.012, 0.031, 0.008, and 0.033, respectively). The incidence of UTI increased with the number of risk factors: 0% (0/16) for zero, 10% (5/48) for one, 31% (16/51) for two, 45% (5/11) for three, and 100% (2/2) for four risk factors. Conclusions: Desensitization therapy, BMI, dialysis duration, and WIT were identified as independent risk factors for perioperative UTI. In patients with risk factors, additional preventive strategies should be considered, with extended antibiotic prophylaxis being one potential option. en-copyright= kn-copyright= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueShota en-aut-sei=Inoue en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokunagaMoto en-aut-sei=Tokunaga en-aut-mei=Moto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubotaRisa en-aut-sei=Kubota en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, NHO Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, NHO Okayama Medical Center kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Urology, Shimane University Faculty of Medicine kn-affil= affil-num=19 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=20 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=living donor kidney transplantation kn-keyword=living donor kidney transplantation en-keyword=urinary tract infection kn-keyword=urinary tract infection en-keyword=perioperative kn-keyword=perioperative en-keyword=desensitization kn-keyword=desensitization en-keyword=rituximab kn-keyword=rituximab en-keyword=plasmapheresis kn-keyword=plasmapheresis en-keyword=body mass index kn-keyword=body mass index en-keyword=dialysis duration kn-keyword=dialysis duration en-keyword=warm ischemic time kn-keyword=warm ischemic time en-keyword=prophylactic antimicrobials kn-keyword=prophylactic antimicrobials END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=491 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250826 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk of malignant neoplasms of tacrolimus in kidney transplant patients: a retrospective cohort study conducted using the Japanese National Database of Health Insurance Claims en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although the long-term survival of kidney transplant recipients has significantly improved, malignant neoplasms remain one of the leading causes of death in this population. The recipients face a 1.8-fold increased risk of developing malignant neoplasms compared with the general population. This risk increases with time after transplantation. Tacrolimus (TAC) is preferred over cyclosporine A (CyA) in terms of efficacy against organ rejection, but evidence on the risk of malignant neoplasms is lacking. We aimed to describe the incidence and types of malignant neoplasms in kidney transplant recipients and evaluate the association between malignant neoplasms development and the type of prescribed CNI.
Methods: This retrospective cohort study was conducted using the Japanese National Database of Health Insurance Claims, including data covering 99% of kidney transplant patients in Japan. Patients who underwent kidney transplantation and were prescribed TAC or CyA between April and June 2011 were included. The primary outcome included the incidence of malignant neoplasms, and secondary outcomes included overall survival and graft survival.
Results: A total of 7,590 patients were included, with 11.0% developing malignant neoplasms during the follow-up period. The most common malignant neoplasms were in the digestive organs and urinary tract. No statistically significant difference in malignant neoplasms incidence was observed between TAC and CyA users (hazards ratio: 0.97, 95% CI: 0.84 to 1.12; estimated average treatment effect: −24.05, 95% CI: −184.90 to 136.80). The patient and graft survival rates were also comparable between the groups.
Conclusions: This large study suggests that TAC is not associated with an increased risk of malignant neoplasms compared to CyA in the late post-transplant period. en-copyright= kn-copyright= en-aut-name=KubotaRisa en-aut-sei=Kubota en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokunagaMoto en-aut-sei=Tokunaga en-aut-mei=Moto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakagawaYuki en-aut-sei=Nakagawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IchimaruNaotsugu en-aut-sei=Ichimaru en-aut-mei=Naotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Epidemiology, Kochi Medical School, Kochi University kn-affil= affil-num=3 en-affil=Department of Urology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Urology, Juntendo University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Urology, Kinki Central Hospital kn-affil= affil-num=17 en-affil=Department of Urology, Shimane University Faculty of Medicine kn-affil= affil-num=18 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Calcineurin inhibitors kn-keyword=Calcineurin inhibitors en-keyword=Cyclosporine A kn-keyword=Cyclosporine A en-keyword=Kidney transplant kn-keyword=Kidney transplant en-keyword=Malignant neoplasms kn-keyword=Malignant neoplasms en-keyword=Tacrolimus kn-keyword=Tacrolimus END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=6 article-no= start-page=643 end-page=649 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world clinical usage and efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer: a multi-institutional study in the CsJUC en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: To evaluate the real-world clinical usage and effectiveness of apalutamide in men with nonmetastatic castration-resistant prostate cancer (nmCRPC).
Methods: We retrospectively reviewed the data of 186 men who received apalutamide across 17 institutions. The primary outcomes were the clinical usage of apalutamide for nmCRPC: prior usage of other androgen receptor signaling inhibitors (ARSIs), prior radical treatment, and the distribution of the prostate-specific antigen (PSA) doubling time (PSA-DT) at the initial administration of apalutamide. The secondary outcomes were the efficacy of apalutamide: PSA response (50% or 90% decline), progression-free survival, and skin-adverse events (AEs).
Results: We identified 75 patients with nmCRPC. A total of 31 (41.3%) patients received prior treatment with other ARSIs. A total of 42 men (56%) did not receive any prior radical treatment. The PSA-DT was <3.0, 3.0–5.9, 6.0–10, and > 10 months in 34.7%, 40%, 14.7%, and 10.6% of the patients, respectively. Patients receiving prior treatment with other ARSIs showed a significantly lower PSA response (PSA 50% decline, 88.4% vs. 18.8%; PSA 90% decline, 60.5% vs. 6.2%, P < .001, respectively) and significantly shorter progression-free survival (median: 37 months vs. 4 months; log-rank P < .001) than those without prior ARSI treatment, although cancer status did not differ between the groups. Skin-AEs were observed in 42.7%.
Conclusions: This real-world study revealed that apalutamide was used for the treatment after other ARSIs in >40% of patients with nmCRPC and showed limited efficacy in this context, although the effectiveness of apalutamide without prior other ARSI treatment was comparable with that reported in clinical trial results. en-copyright= kn-copyright= en-aut-name=TohiYoichiro en-aut-sei=Tohi en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiKeita en-aut-sei=Kobayashi en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DaizumotoKei en-aut-sei=Daizumoto en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekinoYohei en-aut-sei=Sekino en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuharaHideo en-aut-sei=Fukuhara en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NiigawaHeima en-aut-sei=Niigawa en-aut-mei=Heima kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuRyutaro en-aut-sei=Shimizu en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakamotoAtsushi en-aut-sei=Takamoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraKenichi en-aut-sei=Nishimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagamiTaichi en-aut-sei=Nagami en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashidaYushi en-aut-sei=Hayashida en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiramaHiromi en-aut-sei=Hirama en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShiraishiKoji en-aut-sei=Shiraishi en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TomidaRyotaro en-aut-sei=Tomida en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KobatakeKohei en-aut-sei=Kobatake en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueKeiji en-aut-sei=Inoue en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiyajiYoshiyuki en-aut-sei=Miyaji en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MorizaneShuichi en-aut-sei=Morizane en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MiuraNoriyoshi en-aut-sei=Miura en-aut-mei=Noriyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SugimotoMikio en-aut-sei=Sugimoto en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=Chu-shikoku Japan Urological Consortium en-aut-sei=Chu-shikoku Japan Urological Consortium en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Department of Urology, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Department of Urology, Graduate School of Medicine, Yamaguchi University kn-affil= affil-num=3 en-affil=Department of Urology, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Urology, Kochi Medical School kn-affil= affil-num=6 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Division of Urology, Department of Surgery, Faculty of Medicine, Tottori University kn-affil= affil-num=9 en-affil=Department of Urology, Fukuyama City Hospital kn-affil= affil-num=10 en-affil=Department of Urology, Ehime University kn-affil= affil-num=11 en-affil=Department of Urology, Shimane University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Sakaide City Hospital kn-affil= affil-num=13 en-affil=Department of Urology, KKR Takamatsu Hospital kn-affil= affil-num=14 en-affil=Department of Urology, Graduate School of Medicine, Yamaguchi University kn-affil= affil-num=15 en-affil=Department of Urology, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=16 en-affil=Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=17 en-affil=Department of Urology, Kochi Medical School kn-affil= affil-num=18 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=19 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Division of Urology, Department of Surgery, Faculty of Medicine, Tottori University kn-affil= affil-num=21 en-affil=Department of Urology, Ehime University kn-affil= affil-num=22 en-affil=Department of Urology, Shimane University Faculty of Medicine kn-affil= affil-num=23 en-affil=Department of Urology, Faculty of Medicine, Kagawa University kn-affil= affil-num=24 en-affil= kn-affil= en-keyword=apalutamide kn-keyword=apalutamide en-keyword=nonmetastatic castration-resistant prostate cancer kn-keyword=nonmetastatic castration-resistant prostate cancer en-keyword=prostate cancer kn-keyword=prostate cancer en-keyword=prostate-specific antigen response kn-keyword=prostate-specific antigen response en-keyword=PSA-doubling time kn-keyword=PSA-doubling time END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=5 article-no= start-page=291 end-page=301 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Systematic Review and Meta-Analysis of Penis Length and Circumference According to WHO Regions: Who has the Biggest One? en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to perform a systematic review and meta-analysis of stretched, erect, and flaccid penis length as well as circumference according to geographic WHO regions. PubMed, Embase, Scopus, and Cochrane Library were searched for articles published until February 2024. Studies in which a healthcare professional evaluated the penis size were considered eligible. After assessing the risk of bias, a systematic review and meta-analyses were performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement, and the outcomes were grouped based on the WHO regions. A total of 33 studies comprising 36 883 patients were included. The risk of bias in the included studies was moderate/low. A comprehensive systematic review was done and meta-analyses performed for flaccid length [n = 28 201, mean (SE) 9.22 (0.24) cm], stretched length [n = 20 814, mean (SE) 12.84 (0.32) cm], erect length [n = 5669, mean (SE) 13.84 (0.94) cm], flaccid circumference [n = 30 117, mean (SE) 9.10 (0.12) cm], and erect circumference [n = 5168, mean (SE) 11.91 (0.18) cm]. The mean length of the stretched penis was largest in Americans [14.47 (0.90) cm]. The mean length of the flaccid penis was the largest in the Americas [10.98 (0.064) cm]. The mean flaccid penile circumference was largest in Americans [n = 29 714, mean (SE) 10.00 (0.04) cm]. Penis sizes vary across WHO regions, suggesting the need to adjust standards according to geography to better understand councilmen and their partners. These data provide a framework for discussing body image expectations and therapeutic strategies in this sensitive and emotional subject matter. en-copyright= kn-copyright= en-aut-name=MostafaeiHadi en-aut-sei=Mostafaei en-aut-mei=Hadi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=QuhalFahad en-aut-sei=Quhal en-aut-mei=Fahad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PradereBenjamin en-aut-sei=Pradere en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LaukhtinaEkaterina en-aut-sei=Laukhtina en-aut-mei=Ekaterina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KönigFrederik en-aut-sei=König en-aut-mei=Frederik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MotlaghReza Sari en-aut-sei=Motlagh en-aut-mei=Reza Sari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RajwaPawel en-aut-sei=Rajwa en-aut-mei=Pawel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Salehi-PourmehrHanieh en-aut-sei=Salehi-Pourmehr en-aut-mei=Hanieh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HajebrahimiSakineh en-aut-sei=Hajebrahimi en-aut-mei=Sakineh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=2 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=3 en-affil=Department of Urology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=5 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=6 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=8 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=9 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=10 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=11 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=12 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=13 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= en-keyword=Penis kn-keyword=Penis en-keyword=length kn-keyword=length en-keyword=circumference kn-keyword=circumference en-keyword=world health organization kn-keyword=world health organization END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=2 article-no= start-page=1 end-page=13 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Context: Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC).
Objective: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs.
Evidence acquisition: Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs).
Evidence synthesis: Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo.
Conclusions: Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings. en-copyright= kn-copyright= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeohJeremy Yuen-Chun en-aut-sei=Teoh en-aut-mei=Jeremy Yuen-Chun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RajwaPaweł en-aut-sei=Rajwa en-aut-mei=Paweł kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=QuhalFahad en-aut-sei=Quhal en-aut-mei=Fahad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PradereBenjamin en-aut-sei=Pradere en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoschiniMarco en-aut-sei=Moschini en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MikiJun en-aut-sei=Miki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=8 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=9 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=10 en-affil=Department of Urology, San Raffaele Hospital and Scientific Institute kn-affil= affil-num=11 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=12 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=urothelial carcinoma kn-keyword=urothelial carcinoma en-keyword=muscle-invasive kn-keyword=muscle-invasive en-keyword=neoadjuvant kn-keyword=neoadjuvant en-keyword=adjuvant kn-keyword=adjuvant END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=20 article-no= start-page=2979 end-page=2984 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Two Cases of Esophageal Mucosal Damage Observed after Peroral Endoscopic Myotomy for Esophageal Motility Disorders en-subtitle= kn-subtitle= en-abstract= kn-abstract=This report presents two cases of esophageal mucosal damage following peroral endoscopic myotomy (POEM) for esophageal motility disorders. In the first case, delayed perforation and mediastinitis occurred on postoperative day 15 and the patient was treated with endoscopic clipping and antibiotics. In the second case, although no perforation was observed, extensive mucosal injury developed the day after POEM which was successfully managed by fasting and antibiotic therapy. These findings highlight the need for careful patient management to minimize the risks associated with POEM, while maximizing its therapeutic benefits. en-copyright= kn-copyright= en-aut-name=HirataShoichiro en-aut-sei=Hirata en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatomiTakuya en-aut-sei=Satomi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaeHiroyuki en-aut-sei=Sakae en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ManabeNoriaki en-aut-sei=Manabe en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=hypercontractile esophagus kn-keyword=hypercontractile esophagus en-keyword=jackhammer esophagus kn-keyword=jackhammer esophagus en-keyword=peroral endoscopic myotomy kn-keyword=peroral endoscopic myotomy END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=34964 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251007 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Periodontitis associated with Porphyromonas gingivalis infection is a risk factor for infertility through uterine hypertrophy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontitis has recently been recognized as a potential risk factor for infertility due to its adverse effect on conception, although the underlying mechanisms remain unclear. This study investigated serum IgG antibody titers against periodontopathogenic bacteria in women with unexplained infertility and investigated how periodontal inflammation affects pregnancy and uterine function using a ligature-induced periodontitis mouse model infected with Porphyromonas gingivalis (Pg). IgG antibody titers against seven periodontopathogenic bacteria strains were measured by ELISA in 76 spontaneously pregnant women and 70 women undergoing infertility treatment. In the in vivo study, periodontitis mice were bred four weeks after periodontitis induction. Birth numbers, newborn weights, and gestation periods were assessed. To evaluate periodontal inflammation, alveolar bone, serum, and uterus was collected before mating. Uterine tissue was evaluated through histological and immunohistochemical staining. Women receiving infertility treatment were significantly older and had higher IgG titers against three Pg strains. Periodontitis mice had fewer births, lower newborn weights, and increased uterine cross-sectional areas. Additionally, elevated estrogen receptor α and progesterone receptor expression levels were observed in endometrial and stromal tissues. These results suggest that periodontitis may cause uterine hypertrophy and hormone receptor changes, potentially impairing pregnancy. en-copyright= kn-copyright= en-aut-name=Kamei-NagataChiaki en-aut-sei=Kamei-Nagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakoHidefumi en-aut-sei=Sako en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaidaKyosuke en-aut-sei=Sakaida en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakayamaMasa-aki en-aut-sei=Nakayama en-aut-mei=Masa-aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Kubota-TakamoriMoyuka en-aut-sei=Kubota-Takamori en-aut-mei=Moyuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KiyamaFumiko en-aut-sei=Kiyama en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraiKimito en-aut-sei=Hirai en-aut-mei=Kimito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IkedaAtsushi en-aut-sei=Ikeda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Takeuchi-HatanakaKazu en-aut-sei=Takeuchi-Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=Tai-TokuzenMasako en-aut-sei=Tai-Tokuzen en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakamotoAi en-aut-sei=Sakamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiyokawaMachiko en-aut-sei=Kiyokawa en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamanishiTomomi en-aut-sei=Yamanishi en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OdaTakashi en-aut-sei=Oda en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakigawaMasayuki en-aut-sei=Takigawa en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MiyakeTakahito en-aut-sei=Miyake en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=16 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=17 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=18 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=19 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=20 en-affil=Miyake Hello Dental Clinic, Pediatric Dentistry and Orthodontics kn-affil= affil-num=21 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=22 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=23 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Infertility kn-keyword=Infertility en-keyword=Periodontitis kn-keyword=Periodontitis en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=Chronic inflammation kn-keyword=Chronic inflammation en-keyword=Uterus kn-keyword=Uterus en-keyword=Sex hormone receptor kn-keyword=Sex hormone receptor END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=34768 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251006 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Continuous glucose monitoring reveals periodontitis-induced glucose variability, insulin resistance, and gut microbiota dysbiosis in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diabetes mellitus (DM) management has advanced from self-monitoring blood glucose (SMBG) to continuous glucose monitoring (CGM), which better prevents complications. However, the influence of periodontitis—a common DM complication—on glucose variability is unclear. This study examined glucose variability in mice with periodontitis using CGM. Periodontitis was induced in 9-week-old male C57BL/6J mice via silk ligatures around the upper second molars. Glucose levels were monitored over 14 days with CGM, validated by SMBG. On day 14, samples were collected to assess alveolar bone resorption and serum levels of tumor necrosis factor-α (TNF-α), insulin, and amyloid A. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted to evaluate insulin resistance. Gut microbiota diversity was also analyzed. By day 10, mice with periodontitis exhibited higher mean glucose levels and time above range than controls. On day 14, serum insulin and amyloid A levels significantly increased, while TNF-α remained unchanged. GTT and ITT indicated insulin resistance. Microbiota analysis showed reduced alpha- and altered beta-diversity, with decreased Coprococcus spp. and increased Prevotella spp., linking dysbiosis to insulin resistance. Periodontitis disrupts glucose regulation by promoting insulin resistance and gut microbiota imbalance, leading to significant glucose variability. en-copyright= kn-copyright= en-aut-name=Kubota-TakamoriMoyuka en-aut-sei=Kubota-Takamori en-aut-mei=Moyuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Kamei-NagataChiaki en-aut-sei=Kamei-Nagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KiyamaFumiko en-aut-sei=Kiyama en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiraiKimito en-aut-sei=Hirai en-aut-mei=Kimito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkuboKeisuke en-aut-sei=Okubo en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraShin en-aut-sei=Nakamura en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IkedaAtsushi en-aut-sei=Ikeda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SaitoTsugumichi en-aut-sei=Saito en-aut-mei=Tsugumichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei University kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Continuous glucose monitoring kn-keyword=Continuous glucose monitoring en-keyword=Periodontal disease kn-keyword=Periodontal disease en-keyword=Insulin resistance kn-keyword=Insulin resistance en-keyword=Chronic inflammation kn-keyword=Chronic inflammation en-keyword=Gut flora kn-keyword=Gut flora END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=5 article-no= start-page=650 end-page=661 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development and validation of an algorithm for identifying patients undergoing dialysis from patients with advanced chronic kidney disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Identifying patients on dialysis among those with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2 remains challenging. To facilitate clinical research in advanced chronic kidney disease (CKD) using electronic health records, we aimed to develop algorithms to identify dialysis patients using laboratory data obtained in routine practice.
Methods We collected clinical data of patients with an eGFR < 15 mL/min/1.73 m2 from six clinical research core hospitals across Japan: four hospitals for the derivation cohort and two for the validation cohort. The candidate factors for the classification models were identified using logistic regression with stepwise backward selection. To ensure transplant patients were not included in the non-dialysis population, we excluded individuals with the disease code Z94.0.
Results We collected data from 1142 patients, with 640 (56%) currently undergoing hemodialysis or peritoneal dialysis (PD), including 426 of 763 patients in the derivation cohort and 214 of 379 patients in the validation cohort. The prescription of PD solutions perfectly identified patients undergoing dialysis. After excluding patients prescribed PD solutions, seven laboratory parameters were included in the algorithm. The areas under the receiver operation characteristic curve were 0.95 and 0.98 and the positive and negative predictive values were 90.9% and 91.4% in the derivation cohort and 96.2% and 94.6% in the validation cohort, respectively. The calibrations were almost linear.
Conclusions We identified patients on dialysis among those with an eGFR < 15 ml/min/1.73 m2. This study paves the way for database research in nephrology, especially for patients with non-dialysis-dependent advanced CKD. en-copyright= kn-copyright= en-aut-name=ImaizumiTakahiro en-aut-sei=Imaizumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokotaTakashi en-aut-sei=Yokota en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FunakoshiKouta en-aut-sei=Funakoshi en-aut-mei=Kouta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasudaKazushi en-aut-sei=Yasuda en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HattoriAkiko en-aut-sei=Hattori en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorohashiAkemi en-aut-sei=Morohashi en-aut-mei=Akemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KusakabeTatsumi en-aut-sei=Kusakabe en-aut-mei=Tatsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShojimaMasumi en-aut-sei=Shojima en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagamineSayoko en-aut-sei=Nagamine en-aut-mei=Sayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanoToshiaki en-aut-sei=Nakano en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HuangYong en-aut-sei=Huang en-aut-mei=Yong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhtaMiki en-aut-sei=Ohta en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagashimaSatomi en-aut-sei=Nagashima en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InoueRyusuke en-aut-sei=Inoue en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraNaoki en-aut-sei=Nakamura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OtaHideki en-aut-sei=Ota en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MaruyamaTatsuya en-aut-sei=Maruyama en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=GobaraHideo en-aut-sei=Gobara en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=EndohAkira en-aut-sei=Endoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AndoMasahiko en-aut-sei=Ando en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShiratoriYoshimune en-aut-sei=Shiratori en-aut-mei=Yoshimune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MaruyamaShoichi en-aut-sei=Maruyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital kn-affil= affil-num=3 en-affil=Kyusyu University Hospital kn-affil= affil-num=4 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Advanced Medicine, Nagoya University Hospital kn-affil= affil-num=7 en-affil=Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital kn-affil= affil-num=8 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=11 en-affil=Division of Medical Informatics, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Comprehensive Therapy for Chronic Kidney Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Clinical Research Promotion Center, The University of Tokyo Hospital kn-affil= affil-num=14 en-affil=Department of Healthcare Information Management, The University of Tokyo Hospital kn-affil= affil-num=15 en-affil=Medical Information Technology Center, Tohoku University Hospital kn-affil= affil-num=16 en-affil=Medical Information Technology Center, Tohoku University Hospital kn-affil= affil-num=17 en-affil=Medical Information Technology Center, Tohoku University Hospital kn-affil= affil-num=18 en-affil=Clinical Research Promotion Center, The University of Tokyo Hospital kn-affil= affil-num=19 en-affil=Division of Medical Informatics, Okayama University Hospital kn-affil= affil-num=20 en-affil=Department of Medical Informatics, Hokkaido University Hospital kn-affil= affil-num=21 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Medical IT Center, Nagoya University Hospital kn-affil= affil-num=23 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= en-keyword=Chronic kidney disease kn-keyword=Chronic kidney disease en-keyword=Algorithm kn-keyword=Algorithm en-keyword=Classification kn-keyword=Classification en-keyword=Dialysis kn-keyword=Dialysis END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=1 article-no= start-page=6 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optical bandgap tuning in SnO2–MoS2 nanocomposites: manipulating the mass of SnO2 and MoS2 using sonochemical solution mixing en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigates controlled optical bandgap tuning through precise adjustment of the SnO2 and MoS2 mass in nanocomposites. A sonochemical solution mixing method, coupled with bath sonication, is employed for the preparation of SnO2–MoS2 nanocomposite. This approach allows for comprehensive characterization using UV–Vis FTIR, XRD, EDX, Raman spectroscopies, and FESEM, providing insights into morphology, chemical, and optical properties. Increasing the SnO2 mass leads to a linear decrease in the optical bandgap energy, from 3.0 to 1.7 eV. Similarly, increasing the MoS2 mass also results in a decrease in the optical bandgap energy, with a limitation of around 2.01 eV. This work demonstrates superior control over optical bandgap by manipulating the SnO2 mass compared to MoS2, highlighting the complexities introduced by MoS2 2D nanosheets during sonication. These findings hold significant value for optoelectronic applications, emphasizing enhanced control of optical bandgap through systematic mass manipulation. en-copyright= kn-copyright= en-aut-name=OngChinkhai en-aut-sei=Ong en-aut-mei=Chinkhai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LeeWeng Nam en-aut-sei=Lee en-aut-mei=Weng Nam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanYee Seng en-aut-sei=Tan en-aut-mei=Yee Seng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhbergPatrik en-aut-sei=Ohberg en-aut-mei=Patrik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HayashiYasuhiko en-aut-sei=Hayashi en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishikawaTakeshi en-aut-sei=Nishikawa en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YapYuenkiat en-aut-sei=Yap en-aut-mei=Yuenkiat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=School of Engineering and Physical Sciences, Heriot-Watt University Malaysia kn-affil= affil-num=2 en-affil=Heriot-Watt Global College, Heriot-Watt University Malaysia kn-affil= affil-num=3 en-affil=Sunway Biofunctional Molecules Discovery Centre, School of Medical and Life Sciences, Sunway University kn-affil= affil-num=4 en-affil=School of Engineering and Physical Sciences, Institute of Photonics and Quantum Sciences, Heriot-Watt University kn-affil= affil-num=5 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Heriot-Watt Global College, Heriot-Watt University Malaysia kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=19 article-no= start-page=9347 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: From Sarcomere to Clinic en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by unexplained left ventricular hypertrophy, often resulting from pathogenic variants of sarcomeric protein genes. Conventional treatments, such as the use of beta blockers or calcium channel blockers, focus on symptomatic control but do not address the underlying hypercontractility at the sarcomere level. Recent advances in molecular understanding have led to the development of cardiac myosin inhibitors that directly modulate sarcomeric function by reducing myosin–actin cross-bridge formation and adenosine triphosphatase (ATPase) activity. Mavacamten and aficamten have shown promising results in phase 2 and 3 clinical trials, improving symptoms, exercise capacity, and left ventricular outflow tract gradients in patients with obstructive HCM. This review summarizes the current understanding of HCM pathophysiology, diagnostic strategies, and conventional treatments with a focus on the mechanisms of action of myosin inhibitors, clinical evidence supporting their use, and future directions for improvement. We also discuss their potential applications in non-obstructive HCM and the importance of precision medicine guided by genetic profiling. en-copyright= kn-copyright= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkumuraTakahiro en-aut-sei=Okumura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoSeiya en-aut-sei=Kato en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoueKenji en-aut-sei=Onoue en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuboToru en-aut-sei=Kubo en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KouzuHidemichi en-aut-sei=Kouzu en-aut-mei=Hidemichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YanoToshiyuki en-aut-sei=Yano en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InomataTakayuki en-aut-sei=Inomata en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Advanced Cardiovascular Therapeutics, Nagoya University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Pathology, Saiseikai Fukuoka General Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Nara Medical University kn-affil= affil-num=5 en-affil=Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University kn-affil= affil-num=6 en-affil=Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=hypertrophic cardiomyopathy kn-keyword=hypertrophic cardiomyopathy en-keyword=myosin inhibitors kn-keyword=myosin inhibitors en-keyword=sarcomere kn-keyword=sarcomere en-keyword=mavacamten kn-keyword=mavacamten en-keyword=aficamten kn-keyword=aficamten en-keyword=heart failure kn-keyword=heart failure END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=1 article-no= start-page=e12658 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Can online interactions reduce loneliness in young adults during university closures in Japan? The directed acyclic graphs approach en-subtitle= kn-subtitle= en-abstract= kn-abstract=As a countermeasure to the increased loneliness induced by the COVID-19 pandemic-related university closures, universities provided students with online interaction opportunities. However, whether these opportunities contributed to reducing loneliness during the university closures remains unclear, as previous studies have produced contradictory findings. We conducted a nationwide cross-sectional survey. Data were collected on demographics, social environment, social support, interactions, health and loneliness from 4949 students from 60 universities across Japan. We used psychological network and Directed Acyclic Graphs (DAGs) to examine the effect of online interactions on loneliness during university closures during COVID-19. The results showed that the frequency of online interactions with friends did not exert a significant influence on loneliness during university closures. A comparative examination of the DAGs further illuminated that the social environment exhibited fewer pathways for interpersonal interactions and social support during these closure periods. The psychosocial pathways influencing young adults' loneliness show variations contingent on the university's closure status. Notably, the impact of heightened online interactions with friends on loneliness appears to be less pronounced among young adults in the context of university closure. en-copyright= kn-copyright= en-aut-name=KambaraKohei en-aut-sei=Kambara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToyaAkihiro en-aut-sei=Toya en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LeeSumin en-aut-sei=Lee en-aut-mei=Sumin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimizuHaruka en-aut-sei=Shimizu en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbeKazuaki en-aut-sei=Abe en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShigematsuJun en-aut-sei=Shigematsu en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangQingyuan en-aut-sei=Zhang en-aut-mei=Qingyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AbeNatsuki en-aut-sei=Abe en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HayaseRyo en-aut-sei=Hayase en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AbeNobuhito en-aut-sei=Abe en-aut-mei=Nobuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakaiRyusuke en-aut-sei=Nakai en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AokiShuntaro en-aut-sei=Aoki en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AsanoKohei en-aut-sei=Asano en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AsanoRyosuke en-aut-sei=Asano en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujimuraMakoto en-aut-sei=Fujimura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FukuiKen’ichiro en-aut-sei=Fukui en-aut-mei=Ken’ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukumotoYoshihiro en-aut-sei=Fukumoto en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FurutaniKaichiro en-aut-sei=Furutani en-aut-mei=Kaichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HasegawaKoji en-aut-sei=Hasegawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HashimotoHirofumi en-aut-sei=Hashimoto en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HashimotoMikoto en-aut-sei=Hashimoto en-aut-mei=Mikoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HosogoshiHiroki en-aut-sei=Hosogoshi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=IkedaHiroshi en-aut-sei=Ikeda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=IshiokaToshiyuki en-aut-sei=Ishioka en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ItoChiharu en-aut-sei=Ito en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IwanoSuguru en-aut-sei=Iwano en-aut-mei=Suguru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KamadaMasafumi en-aut-sei=Kamada en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KanaiYoshihiro en-aut-sei=Kanai en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KaritaTomonori en-aut-sei=Karita en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=KasagiYu en-aut-sei=Kasagi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=KashimaEmiko S. en-aut-sei=Kashima en-aut-mei=Emiko S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=KatoJuri en-aut-sei=Kato en-aut-mei=Juri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawachiYousuke en-aut-sei=Kawachi en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KawaharaJun‐ichiro en-aut-sei=Kawahara en-aut-mei=Jun‐ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=KimuraMasanori en-aut-sei=Kimura en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=KiraYugo en-aut-sei=Kira en-aut-mei=Yugo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=Kiyonaga (Sakoda)Yuko en-aut-sei=Kiyonaga (Sakoda) en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KohguchiHiroshi en-aut-sei=Kohguchi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=KomiyaAsuka en-aut-sei=Komiya en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=MasuiKeita en-aut-sei=Masui en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=MidorikawaAkira en-aut-sei=Midorikawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=MifuneNobuhiro en-aut-sei=Mifune en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=MizukoshiAkimine en-aut-sei=Mizukoshi en-aut-mei=Akimine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=NawataKengo en-aut-sei=Nawata en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=NishimuraTakashi en-aut-sei=Nishimura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=NogiwaDaisuke en-aut-sei=Nogiwa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=OgawaKenji en-aut-sei=Ogawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=OkadaJunko en-aut-sei=Okada en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=OkamotoAki en-aut-sei=Okamoto en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=OkamotoReiko en-aut-sei=Okamoto en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=SasakiKyoko en-aut-sei=Sasaki en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=SatoKosuke en-aut-sei=Sato en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=ShimizuHiroshi en-aut-sei=Shimizu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=SugimuraAtsushi en-aut-sei=Sugimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=SugitaniYoko en-aut-sei=Sugitani en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=SugiuraHitomi en-aut-sei=Sugiura en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=SumiokaKyoko en-aut-sei=Sumioka en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=SunaguchiBumpei en-aut-sei=Sunaguchi en-aut-mei=Bumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=TakebeMasataka en-aut-sei=Takebe en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=TanabeHiroki C. en-aut-sei=Tanabe en-aut-mei=Hiroki C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=TanakaAyumi en-aut-sei=Tanaka en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= en-aut-name=TanakaMasanori en-aut-sei=Tanaka en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=62 ORCID= en-aut-name=TaniguchiJunichi en-aut-sei=Taniguchi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=63 ORCID= en-aut-name=TokunagaNamiji en-aut-sei=Tokunaga en-aut-mei=Namiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=64 ORCID= en-aut-name=TomitaRyozo en-aut-sei=Tomita en-aut-mei=Ryozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=65 ORCID= en-aut-name=UedaYumiko en-aut-sei=Ueda en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=66 ORCID= en-aut-name=YamashitaTomomi en-aut-sei=Yamashita en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=67 ORCID= en-aut-name=YamauraKazuho en-aut-sei=Yamaura en-aut-mei=Kazuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=68 ORCID= en-aut-name=YogoMasao en-aut-sei=Yogo en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=69 ORCID= en-aut-name=YokotaniKenji en-aut-sei=Yokotani en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=70 ORCID= en-aut-name=YoshidaAyano en-aut-sei=Yoshida en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=71 ORCID= en-aut-name=YoshidaHiroaki en-aut-sei=Yoshida en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=72 ORCID= en-aut-name=YoshiharaKatsue en-aut-sei=Yoshihara en-aut-mei=Katsue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=73 ORCID= en-aut-name=YoshikawaAyumi en-aut-sei=Yoshikawa en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=74 ORCID= en-aut-name=YanagisawaKuniaki en-aut-sei=Yanagisawa en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=75 ORCID= en-aut-name=NakashimaKen'ichiro en-aut-sei=Nakashima en-aut-mei=Ken'ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=76 ORCID= affil-num=1 en-affil=Doshisha University kn-affil= affil-num=2 en-affil=Hiroshima University kn-affil= affil-num=3 en-affil=Hiroshima University kn-affil= affil-num=4 en-affil=Nishikyushu Univ. Junior College kn-affil= affil-num=5 en-affil=Hiroshima University kn-affil= affil-num=6 en-affil=Toyama University kn-affil= affil-num=7 en-affil=Hiroshima University kn-affil= affil-num=8 en-affil=Hiroshima Bunkyo University kn-affil= affil-num=9 en-affil=Chubu University kn-affil= affil-num=10 en-affil=Kyoto University kn-affil= affil-num=11 en-affil=Kyoto University kn-affil= affil-num=12 en-affil=Fukushima Medical University kn-affil= affil-num=13 en-affil=Kyoto University kn-affil= affil-num=14 en-affil=Kurume University kn-affil= affil-num=15 en-affil=Fukuoka Jo Gakuin University kn-affil= affil-num=16 en-affil=Kwassui Women's University kn-affil= affil-num=17 en-affil=Kansai Medical University kn-affil= affil-num=18 en-affil=Kansai University kn-affil= affil-num=19 en-affil=Komazawa University kn-affil= affil-num=20 en-affil=Osaka Metropolitan University kn-affil= affil-num=21 en-affil=Chukyo Gakuin University kn-affil= affil-num=22 en-affil=Kansai University kn-affil= affil-num=23 en-affil=Kyushu University kn-affil= affil-num=24 en-affil=Kobe University kn-affil= affil-num=25 en-affil=University of Human Environments kn-affil= affil-num=26 en-affil=Fukushima Medical University kn-affil= affil-num=27 en-affil=Shujitsu Junior College kn-affil= affil-num=28 en-affil=Tohoku Gakuin University kn-affil= affil-num=29 en-affil=Ehime University kn-affil= affil-num=30 en-affil=Rissho University kn-affil= affil-num=31 en-affil=La Trobe University kn-affil= affil-num=32 en-affil=Kanazawa Institute of Technology kn-affil= affil-num=33 en-affil=Tohoku University kn-affil= affil-num=34 en-affil=Hokkaido University kn-affil= affil-num=35 en-affil=Graduate School of Business Administration, Kobe University kn-affil= affil-num=36 en-affil=Kurume University kn-affil= affil-num=37 en-affil=Kyushu Kyoritsu University kn-affil= affil-num=38 en-affil=Ryutsu Keizai University kn-affil= affil-num=39 en-affil=Hiroshima University kn-affil= affil-num=40 en-affil=Otemon Gakuin University kn-affil= affil-num=41 en-affil=Chuo University kn-affil= affil-num=42 en-affil=Kochi University of Technology kn-affil= affil-num=43 en-affil=Asahi University kn-affil= affil-num=44 en-affil=Fukuoka University kn-affil= affil-num=45 en-affil=Hiroshima International University kn-affil= affil-num=46 en-affil=Seikei University kn-affil= affil-num=47 en-affil=Hokkaido University kn-affil= affil-num=48 en-affil=Prefectural University of Hiroshima kn-affil= affil-num=49 en-affil=Okayama University kn-affil= affil-num=50 en-affil=Osaka University kn-affil= affil-num=51 en-affil=Kanagawa University of Human Services kn-affil= affil-num=52 en-affil=Kurume University kn-affil= affil-num=53 en-affil=Kwansei Gakuin University kn-affil= affil-num=54 en-affil=Tokai University kn-affil= affil-num=55 en-affil=Sophia University kn-affil= affil-num=56 en-affil=Kindai University kn-affil= affil-num=57 en-affil=Okayama University kn-affil= affil-num=58 en-affil=Graduate School of Business Administration, Kobe University kn-affil= affil-num=59 en-affil=Otsuma Women's University kn-affil= affil-num=60 en-affil=Nagoya University kn-affil= affil-num=61 en-affil=Doshisha University kn-affil= affil-num=62 en-affil=Hokkai‐Gakuen University kn-affil= affil-num=63 en-affil=Tezukayama University kn-affil= affil-num=64 en-affil=Ehime Prefectural University of Health Sciences kn-affil= affil-num=65 en-affil=Musashino University kn-affil= affil-num=66 en-affil=Asahi University kn-affil= affil-num=67 en-affil=Jumonji University kn-affil= affil-num=68 en-affil=Ritsumeikan University kn-affil= affil-num=69 en-affil=Doshisha University kn-affil= affil-num=70 en-affil=Tokushima University kn-affil= affil-num=71 en-affil=Tohoku Fukushi University kn-affil= affil-num=72 en-affil=Shinshu University kn-affil= affil-num=73 en-affil=Fukuoka Institute of Technology Junior College kn-affil= affil-num=74 en-affil=Osaka Dental University Faculty of Nursing kn-affil= affil-num=75 en-affil=Kobe University kn-affil= affil-num=76 en-affil=Hiroshima University kn-affil= en-keyword=directed acyclic graphs kn-keyword=directed acyclic graphs en-keyword=loneliness kn-keyword=loneliness en-keyword=online interactions kn-keyword=online interactions en-keyword=psychological network kn-keyword=psychological network en-keyword=university closures kn-keyword=university closures en-keyword=university students kn-keyword=university students END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=JE20250409 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect modification and its impact on preventable and attributable fractions in the potential outcomes framework en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Policy decisions should be guided by measures that capture the impact of exposures on outcomes and that explicitly account for present-day exposure distribution. Both the preventable and attributable fractions have been used for this purpose; however, exposure effects can vary across subpopulations, and when this occurs, appropriate interpretation of these measures should be facilitated by a discussion of the contributions of different subpopulations.
Methods: We analyze preventable and attributable fractions in the presence of effect modification. In particular, we use potential outcomes to formally define these quantities and to clarify the weighting of different strata in the total population measures.
Results: Our derivations show that stratum-specific preventable and attributable fractions are weighted in proportion to the relative frequencies of effect modifiers among individuals with the outcome of interest. We also demonstrate that these weights are valid for the related quantities, preventable and attributable proportions. Finally, we present an example that illustrates how effect modification affects interpretation of these measures.
Conclusions: In sum, when effect modification is present, investigators should consider reporting these measures by the relevant population strata, and information that would allow quantification of their implicit weights in the total population estimate. Our study provides a formal justification for this approach. en-copyright= kn-copyright= en-aut-name=GonçalvesBronner P. en-aut-sei=Gonçalves en-aut-mei=Bronner P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Health and Medical Sciences, University of Surrey kn-affil= affil-num=2 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=preventable fraction kn-keyword=preventable fraction en-keyword=attributable fraction kn-keyword=attributable fraction en-keyword=effect modification kn-keyword=effect modification en-keyword=causality kn-keyword=causality END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=6 article-no= start-page=732 end-page=740 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Causal Approaches to Disease Progression Analyses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epidemiologic analyses that aim to quantify exposure effects on disease progression are not uncommon. Understanding the implications of these studies, however, is complicated, in part because different causal estimands could, at least in theory, be the target of such analyses. Here, to facilitate interpretation of these studies, we describe different settings in which causal questions related to disease progression can be asked, and consider possible estimands. For clarity, our discussion is structured around settings defined based on two factors: whether the disease occurrence is manipulable or not, and the type of outcome. We describe relevant causal structures and sets of response types, which consist of joint potential outcomes of disease occurrence and disease progression, and argue that settings where interventions to manipulate disease occurrence are not plausible are more common, and that, in this case, principal stratification might be an appropriate framework to conceptualize the analysis. Further, we suggest that the precise definition of the outcome of interest, in particular of what constitutes its permissible levels, might determine whether potential outcomes linked to disease progression are definable in different strata of the population. Our hope is that this paper will encourage additional methodological work on causal analysis of disease progression, as well as serve as a resource for future applied studies. en-copyright= kn-copyright= en-aut-name=GonçalvesBronner P. en-aut-sei=Gonçalves en-aut-mei=Bronner P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Health and Medical Sciences, University of Surrey kn-affil= affil-num=2 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=disease progression kn-keyword=disease progression en-keyword=causal inference kn-keyword=causal inference en-keyword=principal stratification kn-keyword=principal stratification en-keyword=controlled direct effects kn-keyword=controlled direct effects en-keyword=potential outcomes kn-keyword=potential outcomes END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue=S 01 article-no= start-page=E537 end-page=E538 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic ultrasound-guided ethanol injection with prophylactic pancreatic stenting for a pancreatic neuroendocrine neoplasm en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=20056 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pharmacokinetics and the effectiveness of pyrogen-free bioabsorbable wet adhesives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bioabsorbable materials are essential for advanced therapies, including surgical sealing, cell therapy, and drug delivery. Natural bioabsorbable materials, including collagen and hyaluronic acid, have better biocompatibility than synthetic bioabsorbable polymers; however, they are mainly derived from animals, presenting infection risks. Non-animal origin polymers have a lower molecular weight than those of animal origins. Their viscosity increases with increase in molecular weight, making endotoxin removal difficult. Here, using the phosphoryl chloride disposal method, we present a strategy for synthesizing pyrogen-free bioabsorbable adhesives with controlled molecular weight. Phosphopullulan, a polysaccharide derivative, had less than detectable endotoxin levels and controllable average molecular weight of approximately 300,000 to over 1,400,000. Furthermore, it is important to ensure the safety as well as efficacy of bio-implantable materials. We have evaluated the biosafety of polysaccharide derivatives we are developing, and have examined their cell phagocytosis and pharmacokinetics in vitro and in vivo, and have confirmed that they are safe. We have also evaluated their adhesion to wet tissue adhesions and confirmed that they leak less than existing materials. en-copyright= kn-copyright= en-aut-name=OshimaRisa en-aut-sei=Oshima en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanishiKo en-aut-sei=Nakanishi en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkasakaTsukasa en-aut-sei=Akasaka en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimojiShinji en-aut-sei=Shimoji en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraTeppei en-aut-sei=Nakamura en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkiharaTakumi en-aut-sei=Okihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraMariko en-aut-sei=Nakamura en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TamadaIkkei en-aut-sei=Tamada en-aut-mei=Ikkei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Van MeerbeekBart en-aut-sei=Van Meerbeek en-aut-mei=Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SugayaTsutomu en-aut-sei=Sugaya en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Periodontology, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=4 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=5 en-affil=Department of Periodontology, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Applied Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University kn-affil= affil-num=7 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Department of Clinical Psychology, School of Clinical Psychology, Kyushu University of Medical and Science kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Plastic and Reconstructive Surgery, Tokyo Metropolitan Children’s Medical Center kn-affil= affil-num=11 en-affil=BIOMAT, Department of Oral Health Sciences, & UZ Leuven, Dentistry, KU Leuven kn-affil= affil-num=12 en-affil=Department of Periodontology, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=13 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= en-keyword=Phosphopullulan kn-keyword=Phosphopullulan en-keyword=Polysaccharide kn-keyword=Polysaccharide en-keyword=ADME kn-keyword=ADME en-keyword=Animal study kn-keyword=Animal study en-keyword=Endodontic sealer kn-keyword=Endodontic sealer END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=5 article-no= start-page=257 end-page=267 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=New Catalytic Residues and Catalytic Mechanism of the RNase T1 Family en-subtitle= kn-subtitle= en-abstract= kn-abstract=The ribonuclease T1 family, including RNase Po1 secreted by Pleurotus ostreatus, exhibits antitumor activity. Here, we resolved the Po1/guanosine-3′-monophosphate complex (3′GMP) structure at 1.75 Å. Structure comparison and fragment molecular orbital (FMO) calculation between the apo form and the Po1/3′GMP complex identified Phe38, Phe40, and Glu42 as the key binding residues. Two types of the RNase/3′GMP complex in RNasePo1 and RNase T1 were homologous to Po1, and FMO calculations elucidated that the biprotonated histidine on the β3 sheet (His36) on the β3 sheet and deprotonated Glu54 on the β4 sheet were advantageous to RNase activity. Moreover, tyrosine (Tyr34) on the β3 sheet was elucidated as a crucial catalytic residues. Mutation of Tyr34 with phenylalanine decreased RNase activity and diminished antitumor efficacy compared to that in the wild type. This suggests the importance of RNase activity in antitumor mechanisms. en-copyright= kn-copyright= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiMamoru en-aut-sei=Suzuki en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraYumiko en-aut-sei=Hara en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsutaniTakuya en-aut-sei=Katsutani en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MotoyoshiNaomi en-aut-sei=Motoyoshi en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItagakiTadashi en-aut-sei=Itagaki en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyakawaShuhei en-aut-sei=Miyakawa en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FukuzawaKaori en-aut-sei=Fukuzawa en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KobayashiHiroko en-aut-sei=Kobayashi en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=3 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=4 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=5 en-affil=School of Pharmacy, Nihon University kn-affil= affil-num=6 en-affil=School of Pharmacy, Nihon University kn-affil= affil-num=7 en-affil=Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=8 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=10 en-affil=School of Pharmacy, Nihon University kn-affil= en-keyword=RNase kn-keyword=RNase en-keyword=crystal structure kn-keyword=crystal structure en-keyword=fragment molecular orbital method kn-keyword=fragment molecular orbital method en-keyword=interfragment interaction energy kn-keyword=interfragment interaction energy en-keyword=antitumor activity kn-keyword=antitumor activity en-keyword=RNase activity kn-keyword=RNase activity END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=ycaf092 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Methanol chemoreceptor MtpA- and flagellin protein FliC-dependent methylotaxis contributes to the spatial colonization of PPFM in the phyllosphere en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pink-pigmented facultative methylotrophs (PPFMs) capable of growth on methanol are dominant and versatile phyllosphere bacteria that provide positive effects on plant growth through symbiosis. However, the spatial behavior of PPFMs on plant surfaces and its molecular basis are unknown. Here, we show that Methylobacterium sp. strain OR01 inoculated onto red perilla seeds colonized across the entire plant surface in the phyllosphere concomitant with the plant growth. During its transmission, strain OR01 was found to be present on the entire leaf surface with a preference to sites around the periphery, vein, trichome, and stomata. We found that methanol-sensing chemoreceptor MtpA-dependent chemotaxis (methylotaxis; chemotaxis toward methanol) and flagellin protein FliC-dependent motility facilitated the bacterial entry into the stomatal cavity and their colonization in the phyllosphere. en-copyright= kn-copyright= en-aut-name=KatayamaShiori en-aut-sei=Katayama en-aut-mei=Shiori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiraishiKosuke en-aut-sei=Shiraishi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KajiKanae en-aut-sei=Kaji en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawabataKazuya en-aut-sei=Kawabata en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraNaoki en-aut-sei=Tamura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniAkio en-aut-sei=Tani en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YurimotoHiroya en-aut-sei=Yurimoto en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakaiYasuyoshi en-aut-sei=Sakai en-aut-mei=Yasuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=2 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=3 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Department of Anatomy and Histology, School of Medicine, Fukushima Medical University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= en-keyword=PPFM kn-keyword=PPFM en-keyword=methylotaxis kn-keyword=methylotaxis en-keyword=phyllosphere kn-keyword=phyllosphere en-keyword=fluorescenceimaging kn-keyword=fluorescenceimaging en-keyword=bacterialbehavior kn-keyword=bacterialbehavior en-keyword=plant-microbeinteraction kn-keyword=plant-microbeinteraction END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Applicability of Effective Atomic Number (Z eff) Image Analysis of Coronary Plaques Measured With Photon- Counting Computed Tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Coronary computed tomography (CT) allows the assessment of cardiovascular risk by imaging calcified plaques in coronary arteries. Because photon-counting CT (PC-CT) can analyze the effective atomic number (Zeff) of the subject, it is expected to be applied to the analysis of plaque components. The purpose of this study was to investigate the applicability of plaque analysis based on Zeff images with continuous gradation.
Methods: Zeff images were generated from virtual monoenergetic images (VMIs) obtained by PC-CT. Zeff values were derived from the difference between linear attenuation coefficients (μ) at low and high energies using an in-house program. Coronary CT images of 64 plaques in 10 patients were analyzed. The Zeff score, calculated as the sum of Zeff values within the plaque region, was calculated and compared with the conventional Agatston score and mean coronary artery calcium (CAC) score.
Results: The systematic uncertainty of Zeff images was estimated to be ±0.08. The Zeff score of actual patient data showed strong positive correlations with the conventional Agatston and mean CAC scores. The Zeff score uses all voxel data in the plaque area, whereas conventional scores consider only data from voxels with a CT value >130. We found that the conventional scores excluded 39% of the plaque area, and the Zeff score permitted the analysis of low- and high-density plaques.
Conclusions: Zeff imaging was shown to be applicable to plaque analysis that reflects the entire plaque volume. This study demonstrated its technical feasibility as a compositional analysis method using the Zeff image. en-copyright= kn-copyright= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitaniMana en-aut-sei=Mitani en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakegamiKazuki en-aut-sei=Takegami en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimitsuYusuke en-aut-sei=Morimitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkagiNoriaki en-aut-sei=Akagi en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KanazawaYuki en-aut-sei=Kanazawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Medical Support Department, Division of Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Yamaguchi University Hospital kn-affil= affil-num=6 en-affil=Medical Support Department, Division of Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Medical Support Department, Division of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Faculty of Life Science, Kumamoto University kn-affil= affil-num=10 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= en-keyword=effective atomic number image kn-keyword=effective atomic number image en-keyword=photon-counting computed tomography kn-keyword=photon-counting computed tomography en-keyword=virtual monoenergetic images kn-keyword=virtual monoenergetic images en-keyword=coronary CT kn-keyword=coronary CT en-keyword=coronary plaques kn-keyword=coronary plaques en-keyword=Agatston score kn-keyword=Agatston score END start-ver=1.4 cd-journal=joma no-vol=142 cd-vols= no-issue= article-no= start-page=104967 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu en-subtitle= kn-subtitle= en-abstract= kn-abstract=Under an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive Bifidobacterium bifidum (B. bifidum) and Gram-negative Pseudomonas aeruginosa PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and B. bifidum. In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Fölster-HolstRegina en-aut-sei=Fölster-Holst en-aut-mei=Regina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BlömerSophia en-aut-sei=Blömer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EbsenMichael en-aut-sei=Ebsen en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RöckenChristoph en-aut-sei=Röcken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein kn-affil= affil-num=3 en-affil=Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein kn-affil= affil-num=4 en-affil=Städtisches MVZ Kiel GmbH (Kiel City Hospital), Department of Pathology kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=8 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Bacterial sialidase kn-keyword=Bacterial sialidase en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Cytokines kn-keyword=Cytokines en-keyword=Infection kn-keyword=Infection en-keyword=Bifidobacteria kn-keyword=Bifidobacteria en-keyword=Phages kn-keyword=Phages END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=e93012 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of a Peer-Led International Training Program on Work Motivation Among Early-Career Psychiatrists: A Mixed-Methods Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
The Japan Young Psychiatrists Organization (JYPO) has conducted a Course for Academic Development of Psychiatrists (CADP), a peer-led residential international training program, since 2002 to promote the professional development of early-career psychiatrists. This study aimed to evaluate the impact of CADP on participants' work motivation using a psychometric scale and to identify the factors contributing to these changes.
Methods
We conducted a mixed-method study with 23 Japanese participants of the 21st CADP from March 8 to 10, 2024, in Himeji, Japan. Work motivation was assessed using the abbreviated version of the Measure of Multifaceted Work Motivations (MWM-12) at two time points: two weeks before and three months after the course. The total and subitem scores of the MWM-12 were analyzed using the Wilcoxon signed-rank test. Furthermore, free-text responses collected before and after the course were subjected to qualitative analyses.
Results
Significant improvements were observed in the MWM-12 total score from pre-course to post-course. Significant increases were also identified in specific sub-items: M1 (directionality of achievement-oriented motivation), M4 (directionality of competition-oriented motivation), M6 (sustainability of competition-oriented motivation), and M9 (sustainability of cooperation-oriented motivation). Qualitative analysis revealed changes in key categories, including growth as a psychiatrist, personal networking, personal growth, and increased motivation. The integration of quantitative and qualitative findings suggested that enhanced career perspectives (M1), professional growth and peer interaction (M4), and increased self-confidence and support networks (M6 and M9) contributed to improved motivation.
Conclusion
This study demonstrated that a three-day, two-night peer-led training program positively influenced work motivation among early-career psychiatrists. en-copyright= kn-copyright= en-aut-name=ShimizuToshihiro en-aut-sei=Shimizu en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitaokaJunko en-aut-sei=Kitaoka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuzutaniKen en-aut-sei=Suzutani en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatakeYuto en-aut-sei=Satake en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KodaMasahide en-aut-sei=Koda en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuramochiIzumi en-aut-sei=Kuramochi en-aut-mei=Izumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SartoriusNorman en-aut-sei=Sartorius en-aut-mei=Norman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Psychiatry, Saitama Prefectural Psychiatric Hospital kn-affil= affil-num=2 en-affil=Department of Psychiatry, Fukkoukai Tarumi Hospital kn-affil= affil-num=3 en-affil=Department of Psychiatry, Aizu Medical Center kn-affil= affil-num=4 en-affil=Department of Psychiatry, The University of Osaka kn-affil= affil-num=5 en-affil=Co-learning Community Healthcare Re-innovation Office, Graduate School of Medicine, Okayama University kn-affil= affil-num=6 en-affil=Department of Epileptology and Psychiatry, National Center of Neurology and Psychiatry kn-affil= affil-num=7 en-affil=Psychiatry, Association for the Improvement of Mental Health Programs (AIMHP) kn-affil= en-keyword=cadp kn-keyword=cadp en-keyword=early-career psychiatrists kn-keyword=early-career psychiatrists en-keyword=jypo kn-keyword=jypo en-keyword=peer-led training kn-keyword=peer-led training en-keyword=peer networking kn-keyword=peer networking en-keyword=professional development kn-keyword=professional development en-keyword=professional identity kn-keyword=professional identity en-keyword=work motivation kn-keyword=work motivation END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Disruption of the Enterococcus faecalis–Induced Biofilm on the Intraocular Lens Using Bacteriophages en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To compare the effects of bacteriophages (phages) and vancomycin on Enterococcus faecalis–induced biofilms on the intraocular lens.
Methods: E. faecalis strains EF24, GU02, GU03, and phiEF14H1 were used. The expression of the enterococcus surface protein (esp) gene was analyzed using polymerase chain reaction. Phages or vancomycin was added to the biofilms formed on culture plates or acrylic intraocular lenses. The biofilms were quantified after staining with crystal violet. The structure of the biofilms was analyzed using scanning electron microscopy.
Results: E. faecalis strains EF24, GU02, and GU03 formed biofilms on cell culture plates; however, the esp-negative GU03 strain had a significantly lower biofilm-forming ability than the esp-positive strains EF24 and GU02. The addition of phiEF14H1 resulted in a significant reduction in biofilm mass produced by both EF24 and GU02 compared with the untreated control. However, the addition of vancomycin did not degrade the biofilms. Phages significantly degraded biofilms and reduced the viable EF24 and GU02 bacteria on the intraocular lens.
Conclusions: Phages can degrade biofilms formed on the intraocular lens and destroy the bacteria within it. Thus, phage therapy may be a new treatment option for refractory and recurrent endophthalmitis caused by biofilm-forming bacteria.
Translational Relevance: Phage therapy, a novel treatment option for refractory and recurrent endophthalmitis caused by biofilm-forming bacteria, effectively lyses E. faecalis–induced biofilms. en-copyright= kn-copyright= en-aut-name=KishimotoTatsuma en-aut-sei=Kishimoto en-aut-mei=Tatsuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukudaKen en-aut-sei=Fukuda en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshidaWaka en-aut-sei=Ishida en-aut-mei=Waka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwanaAozora en-aut-sei=Kuwana en-aut-mei=Aozora kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TodokoroDaisuke en-aut-sei=Todokoro en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamashiroKenji en-aut-sei=Yamashiro en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University kn-affil= affil-num=2 en-affil=Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University kn-affil= affil-num=3 en-affil=Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University kn-affil= affil-num=4 en-affil=Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Gunma University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=8 en-affil=Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University kn-affil= en-keyword=biofilm kn-keyword=biofilm en-keyword=bacteriophage kn-keyword=bacteriophage en-keyword=intraocular lens kn-keyword=intraocular lens en-keyword=endophthalmitis kn-keyword=endophthalmitis en-keyword=cataract kn-keyword=cataract en-keyword=enterococcus faecalis kn-keyword=enterococcus faecalis END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=2500368 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250629 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Integration of Cholesterol Oxidase‐Based Biosensors on a Smart Contact Lens for Wireless Cholesterol Monitoring from Tears en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cholesterol plays a critical role in physiological functions, but elevated levels increase the risk of cardiovascular disease. Regular cholesterol monitoring is essential for elderly or obese individuals. Current methods, such as blood tests, are invasive, inconvenient, and require a professional operator. In contrast, tears, as an accessible body fluid, offer a promising alternative for noninvasive monitoring due to their correlation with blood cholesterol levels. Herein, a noninvasive approach for monitoring cholesterol levels in tears using a biosensor integrated into a smart contact lens is reported. The biosensor employs cholesterol oxidases as the biocatalyst, coupled with an osmium-based mediator, to detect cholesterol concentrations ranging from 0.1 mM to 1.2 mM in artificial tears. A key challenge is the extremely low cholesterol concentration in tears, which is addressed using a parity-time (P-T) symmetry-based magnetic resonance coupling system. This system enables wireless signal reading and achieves high sensitivity due to its high-quality (Q) factor, which can achieve a detection limit of 0.061 mM. This portable, high-sensitivity smart contact lens demonstrates significant potential as a wearable device for continuous, noninvasive cholesterol monitoring. The findings contribute to advancing tear-based diagnostic systems and highlight the scientific importance of utilizing tear biomarkers for health monitoring. en-copyright= kn-copyright= en-aut-name=CuiYang en-aut-sei=Cui en-aut-mei=Yang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhuoLin en-aut-sei=Zhuo en-aut-mei=Lin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AzhariSaman en-aut-sei=Azhari en-aut-mei=Saman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeTakeo en-aut-sei=Miyake en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate school of Information, Production and Systems, Waseda University kn-affil= affil-num=2 en-affil=Graduate school of Information, Production and Systems, Waseda University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate school of Information, Production and Systems, Waseda University kn-affil= affil-num=5 en-affil=Graduate school of Information, Production and Systems, Waseda University kn-affil= en-keyword=cholesterol kn-keyword=cholesterol en-keyword=magnetic resonance coupling kn-keyword=magnetic resonance coupling en-keyword=parity-time symmetry kn-keyword=parity-time symmetry en-keyword=smart contact lens kn-keyword=smart contact lens END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=17 article-no= start-page=6049 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250826 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Photon-Counting CT Enhances Diagnostic Accuracy in Stable Coronary Artery Disease: A Comparative Study with Conventional CT en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Coronary CT angiography (CCTA) is a cornerstone in evaluating stable coronary artery disease (CAD), but conventional energy-integrating detector CT (EID-CT) has limitations, including calcium blooming and limited spatial resolution. Photon-counting detector CT (PCD-CT) may overcome these drawbacks through enhanced spatial resolution and improved tissue characterization. Methods: In this retrospective, propensity score–matched study, we compared CCTA findings from 820 patients (410 per group) who underwent either EID-CT or PCD-CT for suspected stable CAD. Primary outcomes included stenosis severity, high-risk plaque features, and downstream invasive coronary angiography (ICA) referral and yield. Results: The matched cohorts were balanced in demographics and cardiovascular risk factors (mean age 67 years, 63% male). PCD-CT showed a favorable shift in stenosis severity distribution (p = 0.03). High-risk plaques were detected less frequently with PCD-CT (22.7% vs. 30.5%, p = 0.01). Median coronary calcium scores did not differ (p = 0.60). Among patients referred for ICA, those initially evaluated with PCD-CT were more likely to undergo revascularization (62.5% vs. 44.1%), and fewer underwent potentially unnecessary ICA without revascularization (3.7% vs. 8.0%, p = 0.001). The specificity in diagnosing significant stenosis requiring revascularization was 0.74 with EID-CT and 0.81 with PCD-CT (p = 0.04). Conclusions: PCD-CT improved diagnostic specificity for CAD, reducing unnecessary ICA referrals while maintaining detection of clinically significant disease. This advanced CT technology holds promise for more accurate, efficient, and patient-centered CAD evaluation. en-copyright= kn-copyright= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraShohei en-aut-sei=Hara en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyagiRyosuke en-aut-sei=Miyagi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Centre kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=photon-counting CT kn-keyword=photon-counting CT en-keyword=coronary CT angiography kn-keyword=coronary CT angiography en-keyword=diagnostic accuracy kn-keyword=diagnostic accuracy en-keyword=invasive coronary angiography kn-keyword=invasive coronary angiography END start-ver=1.4 cd-journal=joma no-vol=1869 cd-vols= no-issue=12 article-no= start-page=130860 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol–disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in Txn-F54L mutant rats; however, the details of why the Txn mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the Txn-F54L rats. en-copyright= kn-copyright= en-aut-name=BabaTakumi en-aut-sei=Baba en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UenoGo en-aut-sei=Ueno en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OheChika en-aut-sei=Ohe en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SajiShuku en-aut-sei=Saji en-aut-mei=Shuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoSachiko en-aut-sei=Yamamoto en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoMasaki en-aut-sei=Yamamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaHiroshi en-aut-sei=Nakagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiNobuo en-aut-sei=Okazaki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Kawasaki-OhmoriIori en-aut-sei=Kawasaki-Ohmori en-aut-mei=Iori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeshitaKohei en-aut-sei=Takeshita en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=2 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=3 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=4 en-affil=Structural Biology Division, Japan Synchrotron Radiation Research Institute kn-affil= affil-num=5 en-affil=Structural Biology Division, Japan Synchrotron Radiation Research Institute kn-affil= affil-num=6 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=7 en-affil=Materials Sciences Research Center, Japan Atomic Energy Agency kn-affil= affil-num=8 en-affil=Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS) kn-affil= affil-num=9 en-affil=Department of Molecular Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University kn-affil= affil-num=11 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= en-keyword=Txn kn-keyword=Txn en-keyword=Thioredoxin kn-keyword=Thioredoxin en-keyword=Protein instability kn-keyword=Protein instability en-keyword=Thermosensitivity kn-keyword=Thermosensitivity en-keyword=Crystal structure kn-keyword=Crystal structure en-keyword=Molecular dynamics simulation kn-keyword=Molecular dynamics simulation END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=9 article-no= start-page=1135 end-page=1151 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Heart failure-specific cardiac fibroblasts contribute to cardiac dysfunction via the MYC–CXCL1–CXCR2 axis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heart failure (HF) is a growing global health issue. While most studies focus on cardiomyocytes, here we highlight the role of cardiac fibroblasts (CFs) in HF. Single-cell RNA sequencing of mouse hearts under pressure overload identified six CF subclusters, with one specific to the HF stage. This HF-specific CF population highly expresses the transcription factor Myc. Deleting Myc in CFs improves cardiac function without reducing fibrosis. MYC directly regulates the expression of the chemokine CXCL1, which is elevated in HF-specific CFs and downregulated in Myc-deficient CFs. The CXCL1 receptor, CXCR2, is expressed in cardiomyocytes, and blocking the CXCL1–CXCR2 axis mitigates HF. CXCL1 impairs contractility in neonatal rat and human iPSC-derived cardiomyocytes. Human CFs from failing hearts also express MYC and CXCL1, unlike those from controls. These findings reveal that HF-specific CFs contribute to HF via the MYC–CXCL1–CXCR2 pathway, offering a promising therapeutic target beyond cardiomyocytes. en-copyright= kn-copyright= en-aut-name=KomuroJin en-aut-sei=Komuro en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashimotoHisayuki en-aut-sei=Hashimoto en-aut-mei=Hisayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsukiToshiomi en-aut-sei=Katsuki en-aut-mei=Toshiomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KusumotoDai en-aut-sei=Kusumoto en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatohManami en-aut-sei=Katoh en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoToshiyuki en-aut-sei=Ko en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoMasamichi en-aut-sei=Ito en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatagiriMikako en-aut-sei=Katagiri en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KubotaMasayuki en-aut-sei=Kubota en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaShintaro en-aut-sei=Yamada en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraTakahiro en-aut-sei=Nakamura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkibaYohei en-aut-sei=Akiba en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KoukaThukaa en-aut-sei=Kouka en-aut-mei=Thukaa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KomuroKaoruko en-aut-sei=Komuro en-aut-mei=Kaoruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimuraMai en-aut-sei=Kimura en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ItoShogo en-aut-sei=Ito en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NomuraSeitaro en-aut-sei=Nomura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KomuroIssei en-aut-sei=Komuro en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaKeiichi en-aut-sei=Fukuda en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IedaMasaki en-aut-sei=Ieda en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Frontier Cardiovascular Science, Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Frontier Cardiovascular Science, Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=12 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=16 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Frontier Cardiovascular Science, Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=20 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=wrae175 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cyanorhodopsin-II represents a yellow-absorbing proton-pumping rhodopsin clade within cyanobacteria en-subtitle= kn-subtitle= en-abstract= kn-abstract=Microbial rhodopsins are prevalent in many cyanobacterial groups as a light-energy-harvesting system in addition to the photosynthetic system. It has been suggested that this dual system allows efficient capture of sunlight energy using complementary ranges of absorption wavelengths. However, the diversity of cyanobacterial rhodopsins, particularly in accumulated metagenomic data, remains underexplored. Here, we used a metagenomic mining approach, which led to the identification of a novel rhodopsin clade unique to cyanobacteria, cyanorhodopsin-II (CyR-II). CyR-IIs function as light-driven outward H+ pumps. CyR-IIs, together with previously identified cyanorhodopsins (CyRs) and cyanobacterial halorhodopsins (CyHRs), constitute cyanobacterial ion-pumping rhodopsins (CyipRs), a phylogenetically distinct family of rhodopsins. The CyR-II clade is further divided into two subclades, YCyR-II and GCyR-II, based on their specific absorption wavelength. YCyR-II absorbed yellow light (λmax = 570 nm), whereas GCyR-II absorbed green light (λmax = 550 nm). X-ray crystallography and mutational analysis revealed that the difference in absorption wavelengths is attributable to slight changes in the side chain structure near the retinal chromophore. The evolutionary trajectory of cyanobacterial rhodopsins suggests that the function and light-absorbing range of these rhodopsins have been adapted to a wide range of habitats with variable light and environmental conditions. Collectively, these findings shed light on the importance of rhodopsins in the evolution and environmental adaptation of cyanobacteria. en-copyright= kn-copyright= en-aut-name=Hasegawa-TakanoMasumi en-aut-sei=Hasegawa-Takano en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosakaToshiaki en-aut-sei=Hosaka en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraYosuke en-aut-sei=Nishimura en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuriharaMarie en-aut-sei=Kurihara en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakajimaYu en-aut-sei=Nakajima en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Ishizuka-KatsuraYoshiko en-aut-sei=Ishizuka-Katsura en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Kimura-SomeyaTomomi en-aut-sei=Kimura-Someya en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShirouzuMikako en-aut-sei=Shirouzu en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshizawaSusumu en-aut-sei=Yoshizawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=2 en-affil=Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=7 en-affil=Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research kn-affil= affil-num=8 en-affil=Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research kn-affil= affil-num=9 en-affil=Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research kn-affil= affil-num=10 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= en-keyword=cyanobacteria kn-keyword=cyanobacteria en-keyword=microbial rhodopsin kn-keyword=microbial rhodopsin en-keyword=ecology kn-keyword=ecology en-keyword=evolution kn-keyword=evolution END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=17 article-no= start-page=8643 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anti-HMGB1 Antibody Therapy Ameliorates Spinal Cord Ischemia–Reperfusion Injury in Rabbits en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spinal cord ischemia–reperfusion (SCI/R) injury remains a major clinical challenge with limited therapeutic options. High-mobility group box 1 (HMGB1), a proinflammatory mediator released during cellular stress, has been implicated in the pathogenesis of ischemia–reperfusion-induced neural damage. In this study, we investigated the neuroprotective potential of the anti-HMGB1 monoclonal antibody (mAb) in a rabbit model of SCI/R injury. Male New Zealand White rabbits were anesthetized and subjected to 11 min of abdominal aortic occlusion using a micro-bulldog clamp following heparinization. Anti-HMGB1 mAb or control IgG was administered intravenously immediately after reperfusion and again at 6 h post-reperfusion. Neurological function was assessed at 6, 24, and 48 h after reperfusion using the modified Tarlov scoring system. The rabbits were euthanized 48 h after reperfusion for spinal cord and blood sampling. Treatment with anti-HMGB1 mAb significantly improved neurological outcomes, reduced the extent of spinal cord infarction, preserved motor neuron viability, and decreased the presence of activated microglia and infiltrating neutrophils. Furthermore, it attenuated apoptosis, oxidative stress, and inflammatory responses in the spinal cord, and helped maintain the integrity of the blood–spinal cord barrier. These findings suggest that anti-HMGB1 mAb may serve as a promising therapeutic agent for SCI/R injury. en-copyright= kn-copyright= en-aut-name=MuraokaGenya en-aut-sei=Muraoka en-aut-mei=Genya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiYasuhiro en-aut-sei=Fujii en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=QiaoHandong en-aut-sei=Qiao en-aut-mei=Handong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OozawaSusumu en-aut-sei=Oozawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Translational Research, Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Medical Technology, Faculty of Science, Okayama University of Science kn-affil= affil-num=7 en-affil=Division of Medical Safety Management, Safety Management Facility, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Translational Research and Drug Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=thoracoabdominal aortic aneurysm kn-keyword=thoracoabdominal aortic aneurysm en-keyword=spinal cord ischemia–reperfusion injury kn-keyword=spinal cord ischemia–reperfusion injury en-keyword=high mobility group box 1 kn-keyword=high mobility group box 1 en-keyword=neuroprotection kn-keyword=neuroprotection en-keyword=blood–spinal cord barrier kn-keyword=blood–spinal cord barrier en-keyword=aortic surgery kn-keyword=aortic surgery END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=6 article-no= start-page=103174 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of a method to predict positioning errors in orthopantomography using cephalography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Various radiographic examinations are used to diagnose diseases and determine treatment plans, and the quality of radiographic images affects diagnostic accuracy. This study assessed the relationship between orthopantomography and cephalometric analysis in predicting positioning errors before orthopantomography.
Methods: This study evaluated four human head phantom types and included 300 patients aged ≥18 years who underwent orthopantomography. The correlation between the Frankfort horizontal plane and occlusal plane angles in the orthopantomogram was analyzed. The occlusal plane angle at a Frankfort horizontal plane of 0° was estimated using a linear approximation formula. Frankfort horizontal plane and occlusal plane angles were measured on the cephalograms, and their differences were analyzed for correlation with the occlusal plane angle at a Frankfort horizontal plane of 0° in the corresponding orthopantomograms. The cephalogram’s condylar plane–corpus line angle was also compared with orthopantomogram measurements.
Results: Frankfort horizontal and occlusal plane angles demonstrated a strong negative correlation (r < −0.9) in phantom studies and moderate negative correlation (r < −0.4) in clinical orthopantomograms. In the phantoms, the occlusal plane at a Frankfort horizontal of 0° in the orthopantomogram strongly correlated with the difference between the Frankfort horizontal and condylar plane–corpus line angles in the cephalogram.
Conclusion: Adjusting patient positioning based on individual skeletal differences and angles may reduce positioning errors and improve image quality. Cephalogram analysis could help determine an appropriate Frankfort plane angle for each patient when acquiring orthopantomograms.
Implications for practice: Integrating cephalometric analysis into positioning protocols enhances radiographic accuracy, reduces retakes, and improves diagnostic reliability in clinical positioning. This research could improve image quality by identifying reference indicators for orthopantomography by incorporating data from images other than cephalograms, such as computed tomography and magnetic resonance imaging. en-copyright= kn-copyright= en-aut-name=ImajoS. en-aut-sei=Imajo en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HondaM. en-aut-sei=Honda en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanabeY. en-aut-sei=Tanabe en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Division of Radiology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Radiology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=3 en-affil=Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=Cephalogram kn-keyword=Cephalogram en-keyword=Orthopantomogram kn-keyword=Orthopantomogram en-keyword=Panoramic radiography kn-keyword=Panoramic radiography en-keyword=Frankfort horizontal plane kn-keyword=Frankfort horizontal plane en-keyword=Occlusal plane angle kn-keyword=Occlusal plane angle en-keyword=Patient positioning kn-keyword=Patient positioning END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=5 article-no= start-page=2810 end-page=2817 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Geriatric Nutritional Risk Index: A Key Indicator of Perioperative Outcome in Oldest-old Patients With Colorectal Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Colorectal cancer (CRC) presents a significant challenge in oldest-old patients (≥85 years), where surgical intervention carries substantial perioperative risks. Nutritional status is a crucial determinant of outcomes, and the Geriatric Nutritional Risk Index (GNRI) has shown promise. This prospective study aimed to validate the GNRI as a key indicator of perioperative outcomes in oldest-old patients undergoing CRC surgery, and to establish its utility in preoperative risk stratification.
Patients and Methods: This prospective study enrolled patients aged ≥85 years undergoing elective surgery for CRC. Preoperative GNRI was calculated using the formula: GNRI=14.89×serum albumin (g/dl)+41.7×[actual body weight/ideal body weight (corresponding to body mass index 22)]. Patients were stratified into two groups: GNRI >98 and GNRI ≤98. Baseline demographics, clinical characteristics, geriatric assessments (including Geriatric-8 and EuroQol 5 dimension), and postoperative complication rates were analyzed.
Results: Twenty-four patients (median age 88 years, interquartile range=86-91) were included: 11 in the GNRI >98 group and 13 in the GNRI ≤98 group. The patients with GNRI >98 demonstrated significantly better G8 scores (median 12 vs. 11, p<0.01) and EQ-5D index values (median 88 vs. 75.0, p<0.01). The postoperative complication rate was significantly higher in the GNRI ≤98 group (p=0.02).
Conclusion: Preoperative GNRI effectively identifies oldest-old patients with CRC at increased risk for postoperative complications. A GNRI ≤98 correlates with poorer nutritional status and impaired geriatric functional parameters. These findings highlight GNRI’s utility as a simple, valuable tool for preoperative risk stratification, potentially guiding interventions to optimize outcomes in this vulnerable population. en-copyright= kn-copyright= en-aut-name=TERAISHIFUMINORI en-aut-sei=TERAISHI en-aut-mei=FUMINORI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UTSUMIMASASHI en-aut-sei=UTSUMI en-aut-mei=MASASHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YOSHIDAYUSUKE en-aut-sei=YOSHIDA en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SHOJIRYOHEI en-aut-sei=SHOJI en-aut-mei=RYOHEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KANAYANOBUHIKO en-aut-sei=KANAYA en-aut-mei=NOBUHIKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MATSUMIYUKI en-aut-sei=MATSUMI en-aut-mei=YUKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SHIGEYASUKUNITOSHI en-aut-sei=SHIGEYASU en-aut-mei=KUNITOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KONDOYOSHITAKA en-aut-sei=KONDO en-aut-mei=YOSHITAKA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ITAGAKISHIORI en-aut-sei=ITAGAKI en-aut-mei=SHIORI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TAMURARIE en-aut-sei=TAMURA en-aut-mei=RIE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MATSUOKAYOSHIKAZU en-aut-sei=MATSUOKA en-aut-mei=YOSHIKAZU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=INAGAKIMASARU en-aut-sei=INAGAKI en-aut-mei=MASARU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=10 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=11 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= en-keyword=Geriatric nutritional risk index kn-keyword=Geriatric nutritional risk index en-keyword=oldest‑old kn-keyword=oldest‑old en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=short‑term outcome kn-keyword=short‑term outcome END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=9 article-no= start-page=396 end-page=406 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250915 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world Experience of Embolization for Intracranial Tumors in Japan: Analysis of 2,756 Cases from Japanese Registry of NeuroEndovascular Therapy 4 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Embolization of intracranial tumors is predominantly performed in Japan, primarily before neurosurgical resection. The Japanese Registry of NeuroEndovascular Therapy (JR-NET) Study Group, established in 2005, aims to clarify the factors influencing the outcomes of neuroendovascular treatment. Japanese Registry of NeuroEndovascular Therapy 4 is a nationwide, multicenter retrospective observational study that evaluates real-world data on intracranial tumor embolization in Japan. Japanese Registry of NeuroEndovascular Therapy 4 is based on data collected from 166 neurosurgical centers in Japan between January 2015 and December 2019. Of 63,230 patients, 2,664 (4.2%) with intracranial tumors underwent embolization. The primary endpoint was the proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 30 days post-procedure. Secondary endpoints included procedure-related complications. Among the 2,664 patients, 61 records lacked sufficient data, leaving 2,603 patients (1,612 females, median age: 61 years [interquartile range 51-71]). The proportion of patients with mRS scores ≤2 at 30 days after the procedure was 86.9%. The overall incidence of procedure-related complications was 4.8%, with 1.8% hemorrhagic, 2.0% ischemic, and 1.0% classified as other complications. In the multivariate analysis, general anesthesia and embolization of vessels other than the external carotid artery were identified as risk factors for the development of complications. Meningioma cases had a complication rate of 4.3%, with major complications occurring in 3.5%. Hemangioblastoma cases had a 14.9% complication rate, with major complications at 9.9%. Japanese Registry of NeuroEndovascular Therapy 4 provides comprehensive real-world data on intracranial tumor embolization in Japan, identifying risk factors to inform and improve the safe practice of intracranial tumor embolization in neuroendovascular therapy. en-copyright= kn-copyright= en-aut-name=HARUMAJun en-aut-sei=HARUMA en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SUGIUKenji en-aut-sei=SUGIU en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HISHIKAWATomohito en-aut-sei=HISHIKAWA en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SOUTOMEYuta en-aut-sei=SOUTOME en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EBISUDANIYuki en-aut-sei=EBISUDANI en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KIMURARyu en-aut-sei=KIMURA en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EDAKIHisanori en-aut-sei=EDAKI en-aut-mei=Hisanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KAWAKAMIMasato en-aut-sei=KAWAKAMI en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MURAISatoshi en-aut-sei=MURAI en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HIRAMATSUMasafumi en-aut-sei=HIRAMATSU en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TANAKAShota en-aut-sei=TANAKA en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SATOWTetsu en-aut-sei=SATOW en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IIHARAKoji en-aut-sei=IIHARA en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IMAMURAHirotoshi en-aut-sei=IMAMURA en-aut-mei=Hirotoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ISHIIAkira en-aut-sei=ISHII en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MATSUMARUYuji en-aut-sei=MATSUMARU en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SAKAIChiaki en-aut-sei=SAKAI en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YOSHIMURAShinichi en-aut-sei=YOSHIMURA en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SAKAINobuyuki en-aut-sei=SAKAI en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Japanese Registry of Neuroendovascular Therapy (JR-NET) Investigators en-aut-sei=Japanese Registry of Neuroendovascular Therapy (JR-NET) Investigators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurosurgery, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurosurgery, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurosurgery, Kindai University kn-affil= affil-num=13 en-affil=Department of Neurosurgery, National Cerebral and Cardiovascular Center kn-affil= affil-num=14 en-affil=Department of Neurosurgery, National Cerebral and Cardiovascular Center kn-affil= affil-num=15 en-affil=Department of Neurosurgery, Juntendo University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Neurosurgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=17 en-affil=Department of Neurosurgery, Kyoto University kn-affil= affil-num=18 en-affil=Department of Neurosurgery, Hyogo Medical University kn-affil= affil-num=19 en-affil=Department of Neurological Surgery, Shimizu Hospital kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=complication kn-keyword=complication en-keyword=intracranial tumor kn-keyword=intracranial tumor en-keyword=embolization kn-keyword=embolization en-keyword=Japanese registry kn-keyword=Japanese registry END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Double-blind randomized noninferiority study of the effect of pharyngeal lidocaine anesthesia on EUS en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objectives: EUS is typically performed under sedation, often with concomitant analgesics to reduce pain. Traditionally used pharyngeal anesthesia, commonly with lidocaine, may cause pharyngeal discomfort and allergic reactions. This study investigated whether lidocaine-based pharyngeal anesthesia is necessary for EUS under sedation with analgesics.
Methods: A double-blind, randomized, noninferiority study was conducted on EUS cases that met the selection criteria. Patients were randomly assigned to receive either 5 sprays of 8% lidocaine (lidocaine group: LG) or saline spray (placebo group: PG) as endoscopy pretreatment. The primary outcome was EUS tolerability, analyzed separately for endoscopists and patients, with a noninferiority margin set at 15%. Secondary outcomes included endoscopist and patient satisfaction, midazolam/pethidine doses, number of gag events, number of esophageal insertion attempts, use of sedative/analgesic antagonists, interruptions due to body movements, throat symptoms after endoscopy, and sedation-related adverse events.
Results: Favorable tolerance was 85% in LG and 88% for PG among endoscopists (percent difference: 3.0 [95% confidence interval, −6.6 to 12.6]) and 90% in LG and 91% in PG among patients (percent difference, 0.94 [95% confidence interval, −7.5 to 9.4]). Both groups exceeded the noninferiority margin (P = 0.0002 for endoscopists and patients). Patient satisfaction was significantly higher in PG (P = 0.0080), but no intergroup differences were found in other secondary outcomes.
Conclusions: PG was noninferior to LG for pharyngeal anesthesia during EUS with sedation and analgesics. These results suggest that pharyngeal anesthesia with lidocaine can be omitted when performing EUS under sedation with concomitant analgesics. Omitting pharyngeal anesthesia with lidocaine may prevent discomfort and complications caused by pharyngeal anesthesia, shorten examination times, and reduce medical costs. en-copyright= kn-copyright= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaKei en-aut-sei=Harada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HattoriNao en-aut-sei=Hattori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ObataTaisuke en-aut-sei=Obata en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=EUS kn-keyword=EUS en-keyword=Lidocaine kn-keyword=Lidocaine en-keyword=Tolerance kn-keyword=Tolerance END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250909 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=S100A8/A9-MCAM signaling promotes gastric cancer cell progression via ERK-c-Jun activation en-subtitle= kn-subtitle= en-abstract= kn-abstract=S100 protein family members S100A8 and S100A9 function primarily as a heterodimer complex (S100A8/A9) in vivo. This complex has been implicated in various cancers, including gastric cancer (GC). Recent studies suggest that these proteins play significant roles in tumor progression, inflammation, and metastasis. However, the exact mechanisms by which S100A8/A9 contributes to GC pathogenesis remain unclear. This study investigates the role of S100A8/A9 and its receptor in GC. Immunohistochemical analysis was performed on GC tissue samples to assess the expression of the S100A8/A9 receptor melanoma cell adhesion molecule (MCAM). In vitro transwell migration and invasion assays were used to evaluate the motility and invasiveness of GC cells. Cell proliferation was assessed using a growth assay, and Western blotting (WB) was employed to examine downstream signaling pathways, including ERK and the transcription factor c-Jun, in response to S100A8/A9–MCAM interaction. S100A8/A9 stimulation enhanced both proliferation and migration through MCAM binding in GC cell lines. These cellular events were accompanied by ERK activation and c-Jun induction. Downregulation of MCAM suppressed both ERK phosphorylation and c-Jun expression, highlighting the importance of the S100A8/A9‒MCAM‒ERK‒c-Jun axis in promoting GC progression. These findings indicate that S100A8/A9 contributes to GC progression via MCAM, which activates the ERK‒c-Jun pathway. The S100A8/A9‒signaling axis may represent a novel therapeutic target in GC. en-copyright= kn-copyright= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YangXu en-aut-sei=Yang en-aut-mei=Xu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PanBo en-aut-sei=Pan en-aut-mei=Bo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WuFangping en-aut-sei=Wu en-aut-mei=Fangping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangXu en-aut-sei=Zhang en-aut-mei=Xu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SagayamaKazumi en-aut-sei=Sagayama en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SunBei en-aut-sei=Sun en-aut-mei=Bei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=2 en-affil=Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=6 en-affil=School of Pharmaceutical Sciences, Zhejiang Chinese Medical University kn-affil= affil-num=7 en-affil=Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=8 en-affil=Faculties of Educational and Research Management Field, Okayama University kn-affil= affil-num=9 en-affil=Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=S100 protein kn-keyword=S100 protein en-keyword=MCAM kn-keyword=MCAM en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Metastasis kn-keyword=Metastasis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=3 article-no= start-page=412 end-page=437 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biophysical regulation of extracellular matrix in systemic lupus erythematosus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by immune dysregulation and multi-organ damage. Recent advances have underscored the critical involvement of extracellular matrix (ECM) biophysical properties in shaping immune cell behavior and metabolic states that contribute to disease progression. This review systematically delineates the pathological remodeling of ECM biophysics in SLE, with a focus on their roles in mechanotransduction, immune-metabolic interplay, and organ-specific tissue injury. By integrating current evidence, we highlight how ECM-derived mechanical cues orchestrate aberrant immune responses and propose new perspectives for targeting ECM-immune crosstalk in the development of organ-specific, mechanism-based therapies for SLE. en-copyright= kn-copyright= en-aut-name=LiQiwei en-aut-sei=Li en-aut-mei=Qiwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiQiang en-aut-sei=Li en-aut-mei=Qiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=XiaoZhaoyang en-aut-sei=Xiao en-aut-mei=Zhaoyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NARUSEKeiji en-aut-sei=NARUSE en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Anesthesiology, The Second Affiliated Hospital of Dalian Medical University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=systemic lupus erythematosus (SLE) kn-keyword=systemic lupus erythematosus (SLE) en-keyword=extracellular matrix (ECM) kn-keyword=extracellular matrix (ECM) en-keyword=mechanotransduction kn-keyword=mechanotransduction en-keyword=mechanism kn-keyword=mechanism en-keyword=immune regulation kn-keyword=immune regulation en-keyword=fibrosis kn-keyword=fibrosis en-keyword=organ-specific damage kn-keyword=organ-specific damage END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=16 article-no= start-page=2634 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic Impact of Gastrointestinal Immune-Related Adverse Events Depends on Nutritional Status in Cancer Patients Treated with Immune Checkpoint Inhibitors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Gastrointestinal immune-related adverse events (GI-irAEs) are recognized complications of immune checkpoint inhibitors (ICIs), but their prognostic relevance and associated risk factors remain unclear. This study aimed to assess whether baseline nutritional status, measured using the prognostic nutritional index (PNI), modifies the prognostic impact of GI-irAEs, and to identify clinical factors associated with their occurrence. Methods: We retrospectively analyzed 1104 cancer patients treated with ICIs at a single institution. GI-irAEs were defined as gastrointestinal symptoms requiring clinical intervention. Patients were stratified by irAE type and PNI (≥40 vs. <40), and differences in survival and treatment response were evaluated. Potential risk factors for developing GI-irAEs were also examined. Results: GI-irAEs occurred in 2.7% of patients and were associated with prolonged overall survival (median: 28.7 vs. 14.0 months) among those with PNI ≥ 40. This survival advantage was not observed in patients with PNI < 40. The PNI-dependent prognostic pattern was specific to GI-irAEs and not observed for non-GI irAEs. Similar trends were confirmed in 4- and 8-week landmark analyses. Differences in objective response rate and disease control rate by PNI status were most pronounced in patients with GI-irAEs. The use of anti-CTLA-4 antibodies was significantly associated with GI-irAE development (odds ratio 4.24; 95% confidence interval 1.73–10.39). Conclusions: GI-irAEs appear to confer a survival benefit primarily in patients with preserved nutritional status. PNI may serve as a useful tool to contextualize the clinical relevance of GI-irAEs and help identify patients most likely to benefit from immune activation during ICI therapy. en-copyright= kn-copyright= en-aut-name=HirataShoichiro en-aut-sei=Hirata en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaEmi en-aut-sei=Tanaka en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SueMasahiko en-aut-sei=Sue en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeuchiYasuto en-aut-sei=Takeuchi en-aut-mei=Yasuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshikawaTomoki en-aut-sei=Yoshikawa en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MakiYoshie en-aut-sei=Maki en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KametakaDaisuke en-aut-sei=Kametaka en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuedaKatsunori en-aut-sei=Matsueda en-aut-mei=Katsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakaguchiChihiro en-aut-sei=Sakaguchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=gastrointestinal immune-related adverse events kn-keyword=gastrointestinal immune-related adverse events en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=prognostic nutrition index kn-keyword=prognostic nutrition index END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250903 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vendor‐Agnostic Vision Transformer‐Based Artificial Intelligence for Peroral Cholangioscopy: Diagnostic Performance in Biliary Strictures Compared With Convolutional Neural Networks and Endoscopists en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Accurate diagnosis of biliary strictures remains challenging. This study aimed to develop an artificial intelligence (AI) system for peroral cholangioscopy (POCS) using a Vision Transformer (ViT) architecture and to evaluate its performance compared to different vendor devices, conventional convolutional neural networks (CNNs), and endoscopists.
Methods: We retrospectively analyzed 125 patients with indeterminate biliary strictures who underwent POCS between 2012 and 2024. AI models including the ViT architecture and two established CNN architectures were developed using images from CHF-B260 or B290 (CHF group; Olympus Medical) and SpyScope DS or DS II (Spy group; Boston Scientific) systems via a patient-level, 3-fold cross-validation. For a direct comparison against endoscopists, a balanced 440-image test set, containing an equal number of images from each vendor, was used for a blinded evaluation.
Results: The 3-fold cross-validation on the entire 2062-image dataset yielded a robust accuracy of 83.9% (95% confidence interval (CI), 80.9–86.7) for the ViT model. The model's accuracy was consistent between CHF (82.7%) and Spy (86.8%, p = 0.198) groups, and its performance was comparable to the evaluated conventional CNNs. On the 440-image test set, the ViT's accuracy of 78.4% (95% CI, 72.5–83.8) was comparable to that of expert endoscopists (82.0%, p = 0.148) and non-experts (73.0%, p = 0.066), with no statistically significant differences observed.
Conclusions: The novel ViT-based AI model demonstrated high vendor-agnostic diagnostic accuracy across multiple POCS systems, achieving performance comparable to conventional CNNs and endoscopists evaluated in this study. en-copyright= kn-copyright= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomiyaMasahiro en-aut-sei=Tomiya en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanimotoTakayoshi en-aut-sei=Tanimoto en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtoAkimitsu en-aut-sei=Ohto en-aut-mei=Akimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkiKentaro en-aut-sei=Oki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KajitaniSatoshi en-aut-sei=Kajitani en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KikuchiTatsuya en-aut-sei=Kikuchi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Healthcare Solutions Division, Ryobi Systems Co., Ltd kn-affil= affil-num=4 en-affil=Healthcare Solutions Division, Ryobi Systems Co., Ltd kn-affil= affil-num=5 en-affil=Healthcare Solutions Division, Ryobi Systems Co., Ltd kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=bile duct neoplasms kn-keyword=bile duct neoplasms en-keyword=cholangioscopy kn-keyword=cholangioscopy en-keyword=computer-assisted diagnosis kn-keyword=computer-assisted diagnosis en-keyword=vision transformer kn-keyword=vision transformer END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Alternative Approach Based on Skin Electrical Impedance to Determine Transepidermal Water Loss for Skin Barrier Function Assessments en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: The transepidermal water loss (TEWL) has long been measured as an indicator to assess the skin barrier function in dermatological research and clinical practice. However, practical limitations such as time requirement, environmental sensitivity, and measurement complexity hinder the widespread uptake of conventional TEWL measurements in clinical settings and routine monitoring. Consequently, there is a growing need for rapid, robust, and clinically applicable alternatives to conventional TEWL measurements. Here, we present a simple, non-invasive, and time-efficient method based on the skin electrical impedance for skin barrier function assessments.
Methods: The skin electrical impedance, TEWL, stratum corneum (SC) thickness, and SC surface water content of 25 healthy adult participants with no history of dermatological diseases were measured at two adjacent forearm sites: intact site with a normal skin barrier and tape-stripped site with an impaired skin barrier. The measured impedance was used to calculate the SC thickness and surface water content, from which the TEWL was estimated and then compared against the TEWL measured using a Tewameter. The estimation accuracy was evaluated by determining the correlation coefficient (R) and root mean square error (RMSE) between estimated and measured TEWL.
Results: A strong correlation (R = 0.891) was observed between estimated and measured TEWL, with an RMSE of 6.05 g/m²/h, indicating high accuracy of the proposed method.
Conclusion: This impedance-based method provides accurate estimations of the TEWL, indicating its potential as a practical alternative to conventional TEWL measurements for skin barrier function assessments, particularly in clinical or high-throughput settings. en-copyright= kn-copyright= en-aut-name=UeharaOsamu en-aut-sei=Uehara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraTakao en-aut-sei=Nakamura en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=Transepidermal water loss kn-keyword=Transepidermal water loss en-keyword=Electrical impedance kn-keyword=Electrical impedance en-keyword=Stratum corneum kn-keyword=Stratum corneum en-keyword=Skin barrier kn-keyword=Skin barrier END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=8 article-no= start-page=e70325 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cardiotoxicity Assessment of EGFR Tyrosine Kinase Inhibitors Using Human iPS Cell‐Derived Cardiomyocytes and FDA Adverse Events Reporting System en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent advances in the development of anti-cancer drugs have contributed to prolonged survival of cancer patients. In contrast, drug-induced cardiotoxicity, particularly cardiac contractile dysfunction, is of growing concern in cancer treatment. Therefore, it is important to understand the risks of anti-cancer drug-induced cardiac contractile dysfunction in drug development. We have previously developed image-based motion analysis using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to assess the effect of drugs on contractility. However, the utility and predictive potential of image-based motion analysis using hiPSC-CMs for anti-cancer drug-induced cardiac contractile dysfunction have not been well understood. Here we focused on epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and investigated the correlation between the hiPSC-CMs data and clinical signals of adverse events related to cardiac contractile dysfunction. We examined the effects of the four EGFR-TKIs, osimertinib, gefitinib, afatinib, and erlotinib, on the contractility of hiPSC-CMs using image-based motion analysis. We found that osimertinib decreased contraction velocity and deformation distance in a dose- and time-dependent manner, whereas gefitinib, afatinib, and erlotinib had little effect on these parameters. Next, we examined the real-world data of the EGFR-TKIs using FDA Adverse Event Reporting System (FAERS; JAPIC AERS). Only osimertinib showed significant clinical signals of adverse events related to cardiac contractile dysfunction. These data suggest that hiPSC-CM data correlate with clinical signals in FAERS analysis for four EGFR-TKIs. Thus, image-based motion analysis using hiPSC-CMs can be a useful platform for predicting the risk of anti-cancer drug-induced cardiac contractile dysfunction in patients. en-copyright= kn-copyright= en-aut-name=YanagidaShota en-aut-sei=Yanagida en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawagishiHiroyuki en-aut-sei=Kawagishi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoMitsuo en-aut-sei=Saito en-aut-mei=Mitsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandaYasunari en-aut-sei=Kanda en-aut-mei=Yasunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Pharmacology, National Institute of Health Sciences (NIHS) kn-affil= affil-num=2 en-affil=Division of Pharmacology, National Institute of Health Sciences (NIHS) kn-affil= affil-num=3 en-affil=Japan Pharmaceutical Information Center (JAPIC) kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Pharmacology, National Institute of Health Sciences (NIHS) kn-affil= en-keyword=cardiomyocytes kn-keyword=cardiomyocytes en-keyword=cardiotoxicity kn-keyword=cardiotoxicity en-keyword=contractility kn-keyword=contractility en-keyword=EGFR-tyrosine kinase inhibitor kn-keyword=EGFR-tyrosine kinase inhibitor en-keyword=FAERS kn-keyword=FAERS en-keyword=human iPS cell kn-keyword=human iPS cell END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=40 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Time dependent predictors of cardiac inflammatory adverse events in cancer patients receiving immune checkpoint inhibitors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Cardio-inflammatory immune related adverse events (irAEs) while receiving immune checkpoint inhibitor (ICI) therapy are particularly consequential due to their associations with poorer treatment outcomes. Evaluation of predictive factors of these serious irAEs with a time dependent approach allows better understanding of patients most at risk.
Objective: To identify different elements of patient data that are significant predictors of early and late-onset or delayed cardio-inflammatory irAEs through various predictive modeling strategies.
Methods: A cohort of patients receiving ICI therapy from January 1, 2010 to May 1, 2022 was identified from TriNetX meeting inclusion/exclusion criteria. Patient data collected included occurrence of early and later cardio-inflammatory irAEs, patient survival time, patient demographic information, ICI therapies, comorbidities, and medication histories. Predictive and statistical modeling approaches identified unique risk factors for early and later developing cardio-inflammatory irAEs.
Results: A cohort of 66,068 patients on ICI therapy were identified in the TriNetX platform; 193 (0.30%) experienced early cardio-inflammatory irAEs and 175 (0.26%) experienced later cardio-inflammatory irAEs. Significant predictors for early irAEs included: anti-PD-1 therapy at index, combination ICI therapy at index, and history of peripheral vascular disease. Significant predictors for later irAEs included: a history of myocarditis and/or pericarditis, cerebrovascular disease, and history of non-steroidal anti-inflammatory medication use.
Conclusions: Cardio-inflammatory irAEs can be divided into clinically meaningful categories of early and late based on time since initiation of ICI therapy. Considering distinct risk factors for early-onset and late-onset events may allow for more effective patient monitoring and risk assessment. en-copyright= kn-copyright= en-aut-name=SayerMichael en-aut-sei=Sayer en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagasakaMisako en-aut-sei=Nagasaka en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LeeBenjamin J. en-aut-sei=Lee en-aut-mei=Benjamin J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DohJean en-aut-sei=Doh en-aut-mei=Jean kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PatelPranav M. en-aut-sei=Patel en-aut-mei=Pranav M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OzakiAya F. en-aut-sei=Ozaki en-aut-mei=Aya F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=2 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Hematology and Oncology, University of California kn-affil= affil-num=4 en-affil=Department of Pharmacy, University of California Irvine Health kn-affil= affil-num=5 en-affil=Department of Pharmacy, University of California Irvine Health kn-affil= affil-num=6 en-affil=Division of Cardiology, Department of Medicine, University of California kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Immune-Related adverse events kn-keyword=Immune-Related adverse events en-keyword=Myocarditis kn-keyword=Myocarditis en-keyword=Pericarditis kn-keyword=Pericarditis en-keyword=Predictive modeling kn-keyword=Predictive modeling en-keyword=TriNetx kn-keyword=TriNetx END start-ver=1.4 cd-journal=joma no-vol=239 cd-vols= no-issue= article-no= start-page=113260 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Helical X-ray tube trajectory estimation via image noise analysis for enhanced CT dosimetry en-subtitle= kn-subtitle= en-abstract= kn-abstract=Information on the helical trajectory of the X-ray tube is necessary for accurate dose evaluation during computed tomography (CT). We aimed to propose a methodology for analyzing the trajectory of the X-ray tube. The novelty of this paper is that the incident direction of X-rays is estimated from the standard deviation (SD) distribution. The X-ray incident direction for each slice was analyzed using a distribution function of SD values, in which the analysis regions were placed in the air region. Then, the helical trajectory of the CT scan was estimated by fitting a three-dimensional helical function to the analyzed data. The robustness of our algorithm was verified through phantom studies: the analyzed X-ray incident directions were compared with instrumental log data, in which cylindrical polyoxymethylene resin phantoms and a whole-body phantom were scanned. Chest CT scanning was mimicked, in which the field of view (FOV) was set at the lung region. The procedure for analyzing the X-ray incident direction was applicable to cylindrical phantoms regardless of the phantom size. In contrast, in the case of the whole-body phantom, although it was possible to apply our procedure to the chest and abdomen regions, the shoulder slices were inappropriate to analyze. Therefore, the helical trajectory was determined based on chest and abdominal CT images. The accuracy in X-ray incident direction analysis was evaluated to be 7.5°. In conclusion, we have developed an algorithm to estimate a three-dimensional helical trajectory that can be used for dose measurements and simulations. en-copyright= kn-copyright= en-aut-name=MaedaTatsuya en-aut-sei=Maeda en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakegamiKazuki en-aut-sei=Takegami en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotoSota en-aut-sei=Goto en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiDaiki en-aut-sei=Kobayashi en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamashitaKazuta en-aut-sei=Yamashita en-aut-mei=Kazuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HigashinoKosaku en-aut-sei=Higashino en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorimotoShinichi en-aut-sei=Morimoto en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KonishiTakeshi en-aut-sei=Konishi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MakiMotochika en-aut-sei=Maki en-aut-mei=Motochika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Yamaguchi University Hospital kn-affil= affil-num=3 en-affil=Faculty of Health Sciences, Kobe Tokiwa University kn-affil= affil-num=4 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=6 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=7 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=8 en-affil=Department of Orthopedics, School of Medicine, Tokushima University kn-affil= affil-num=9 en-affil=Shikoku Medical Center for Children and Adults kn-affil= affil-num=10 en-affil=MEDITEC JAPAN Co., Ltd., Yamaguchi Kosan Bld. kn-affil= affil-num=11 en-affil=MEDITEC JAPAN Co., Ltd., Yamaguchi Kosan Bld. kn-affil= affil-num=12 en-affil=MEDITEC JAPAN Co., Ltd., Yamaguchi Kosan Bld. kn-affil= affil-num=13 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= en-keyword=X-ray medical diagnosis kn-keyword=X-ray medical diagnosis en-keyword=Helical CT scan kn-keyword=Helical CT scan en-keyword=CT image kn-keyword=CT image en-keyword=X-ray incident direction kn-keyword=X-ray incident direction en-keyword=Helical trajectory kn-keyword=Helical trajectory en-keyword=Radiation dose measurement kn-keyword=Radiation dose measurement END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=24040 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250705 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lactose fermenting enteroinvasive Escherichia coli from diarrhoeal cases confers enhanced virulence en-subtitle= kn-subtitle= en-abstract= kn-abstract=Enteroinvasive Escherichia coli (EIEC), known for causing bacillary dysentery akin to Shigella species, comprises both lactose-fermenting (LF) and non-lactose-fermenting (NLF) isolates. While NLF-EIEC is a well-established pathogen associated with acute dysentery and harbours classical Shigella-like virulence factors, the role of LF-EIEC in human disease remains underexplored. In this study, we sought to characterize LF-EIEC clinical isolates and assessed their pathogenic potential in comparison to NLF-EIEC. Among 13,682 diarrhoeal stool specimens, six LF and nine NLF-EIEC were isolated, predominantly belonging to serogroups O28ac, O125, O136, and O152. Unlike other E. coli, all the EIEC isolates were non-motile. Both the types of EIEC had multiple plasmids harbouring several virulence encoding genes (ipaBCD, ial, virF, sig, sepA and ipaH). Resistance to recent generation antibiotics were mostly confined to NLF-EIEC but some of the LF-EIEC were resistant only to ceftriaxone. Higher invasion ability and significant increase in the expression of virulence encoding genes by the LF-EIEC (p < 0.05) were noted during infection to Int407 cell-line. Additionally, LF-EIEC exhibited extensive colonization of the mouse intestine and expressed severe keratoconjunctivitis in guinea pigs. Together, our findings highlight LF-EIEC as an emerging pathogenic variant warranting heightened surveillance and comprehensive investigation to better understand its epidemiological and clinical significance. en-copyright= kn-copyright= en-aut-name=GhoshDebjani en-aut-sei=Ghosh en-aut-mei=Debjani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HalderProlay en-aut-sei=Halder en-aut-mei=Prolay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SamantaProsenjit en-aut-sei=Samanta en-aut-mei=Prosenjit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShawSreeja en-aut-sei=Shaw en-aut-mei=Sreeja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BosePuja en-aut-sei=Bose en-aut-mei=Puja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RoyDeboleena en-aut-sei=Roy en-aut-mei=Deboleena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=RoyNivedita en-aut-sei=Roy en-aut-mei=Nivedita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RamamurthyThandavarayan en-aut-sei=Ramamurthy en-aut-mei=Thandavarayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoleyHemanta en-aut-sei=Koley en-aut-mei=Hemanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MukhopadhyayAsish Kumar en-aut-sei=Mukhopadhyay en-aut-mei=Asish Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=2 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=3 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=4 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=5 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=6 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=7 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=8 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=9 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=10 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=11 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=12 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= affil-num=14 en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI) kn-affil= en-keyword=Antibiotic resistance kn-keyword=Antibiotic resistance en-keyword=Bacterial infections kn-keyword=Bacterial infections en-keyword=Diarrhoea kn-keyword=Diarrhoea en-keyword=Enteroinvasive Escherichia coli kn-keyword=Enteroinvasive Escherichia coli en-keyword=Keratoconjunctivitis kn-keyword=Keratoconjunctivitis en-keyword=Pathogenesis kn-keyword=Pathogenesis END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bioengineered chondrocyte-products from human induced pluripotent stem cells are useful for repairing articular cartilage injury in minipig model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The capacity of articular cartilage for self-repair is limited. Therefore, wide-ranging cartilage damage rarely resolves spontaneously, leading to the development of osteoarthritis. Previously, we developed human-induced pluripotent stem cell (hiPSC)-derived expandable human limb-bud-like mesenchymal (ExpLBM) cells with stable expansion and high chondrogenic capacity. In this study, various forms of articular cartilage-like tissue were fabricated using ExpLBM technology and evaluated to examine their potential as biomaterials. ExpLBM cells derived from hiPSCs were used to produce particle-like cartilage tissue and plate-like cartilage tissue. The cartilaginous particles and cartilaginous plates were transplanted into a minipig osteochondral defect model, and cartilage engraftment was histologically evaluated. For both transplanted cartilaginous particles and cartilaginous plates, good Safranin O staining and integration with the surrounding tissue were observed. Cartilaginous particles and cartilaginous plates made using hiPSCs-derived ExpLBM cells are effective for the regeneration of cartilage after injury. en-copyright= kn-copyright= en-aut-name=TakihiraShota en-aut-sei=Takihira en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaoTomoka en-aut-sei=Takao en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujisawaYuki en-aut-sei=Fujisawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaDaisuke en-aut-sei=Yamada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HanakiShojiro en-aut-sei=Hanaki en-aut-mei=Shojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtakeShigeo en-aut-sei=Otake en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyazawaShinichi en-aut-sei=Miyazawa en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=83 end-page=88 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 124th General Assembly of the Okayama Medical Association kn-title=第124回 岡山医学会総会 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=82 end-page=82 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 16th Annual Meeting of the Japanese Society of Recklinghausen Disease kn-title=第16回日本レックリングハウゼン病学会学術大会 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakenouchiToshiki en-aut-sei=Takenouchi en-aut-mei=Toshiki kn-aut-name=武内俊樹 kn-aut-sei=武内 kn-aut-mei=俊樹 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Pediatric Neurology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 小児発達病因病態学 END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=80 end-page=81 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Anatomy-Physiology-Pharmacology Week in 2025 kn-title=第130回日本解剖学会/第102回日本生理学会/第98回日本薬理学会合同大会 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name=成瀬恵治 kn-aut-sei=成瀬 kn-aut-mei=恵治 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 システム生理学 END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=76 end-page=79 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=What acute care hospitals should do in light of the 2024 revision of medical fees kn-title=令和6年度診療報酬改定を踏まえ急性期病院に今求められること en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=InoueTakahiro en-aut-sei=Inoue en-aut-mei=Takahiro kn-aut-name=井上貴裕 kn-aut-sei=井上 kn-aut-mei=貴裕 aut-affil-num=1 ORCID= affil-num=1 en-affil=Okayama University Hospital kn-affil=岡山大学病院 END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=72 end-page=75 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Drug interaction (63. Precautions for the use of antifungal agents from the perspective of drug–drug interactions) kn-title=薬物相互作用(63―薬物相互作用の観点からみた抗真菌薬の使用上の注意点) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name=菊岡亮 kn-aut-sei=菊岡 kn-aut-mei=亮 aut-affil-num=1 ORCID= en-aut-name=HigashionnaTsukasa en-aut-sei=Higashionna en-aut-mei=Tsukasa kn-aut-name=東恩納司 kn-aut-sei=東恩納 kn-aut-mei=司 aut-affil-num=2 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name=濱野裕章 kn-aut-sei=濱野 kn-aut-mei=裕章 aut-affil-num=3 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name=座間味義人 kn-aut-sei=座間味 kn-aut-mei=義人 aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil=岡山大学病院 薬剤部 affil-num=2 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil=岡山大学病院 薬剤部 affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil=岡山大学病院 薬剤部 affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil=岡山大学病院 薬剤部 END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=65 end-page=71 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Robotic surgery in gastrointestinal surgery: Current trends and future directions kn-title=消化器外科領域におけるロボット支援手術の現状と今後の展望 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name=黒田新士 kn-aut-sei=黒田 kn-aut-mei=新士 aut-affil-num=1 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name=藤原俊義 kn-aut-sei=藤原 kn-aut-mei=俊義 aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 消化器外科学 affil-num=2 en-affil=Department of Gastroenterological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 消化器外科学 en-keyword=ロボット支援手術 kn-keyword=ロボット支援手術 en-keyword=遠隔手術 kn-keyword=遠隔手術 en-keyword=人工知能 kn-keyword=人工知能 en-keyword=内視鏡外科手術 kn-keyword=内視鏡外科手術 en-keyword=消化器外科 kn-keyword=消化器外科 END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=58 end-page=64 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The process of left-hand writing improvement in patients with right hemiplegic stroke: Occupational therapists' observations kn-title=脳卒中右片麻痺者における左手書字の上達過程を捉える作業療法士の観察内容 en-subtitle= kn-subtitle= en-abstract= kn-abstract= This study explored the observations of occupational therapists regarding the early stages of left-hand writing improvement in patients with right hemiplegic stroke. Semi-structured interviews using interview guides were conducted with 12 occupational therapists, and the qualitative data were analyzed inductively. From 79 descriptive codes, 33 interpretive codes were generated and grouped into 12 subcategories. These were further classified into five main categories : ‘letter neatness,’ ‘tool operability, postural optimization,’ ‘practical utility of writing,’ and ‘autonomy in writing.’ These results revealed that the occupational therapists observed improvements in handwriting from a multifaceted perspective, including not only the patients' motor skills but also psychological and behavioral aspects. The findings of this study capture the contents of occupational therapists' observations regarding the process of the early improvement of left-hand writing, and the insights suggest that, in supporting left-hand writing for stroke patients with right hemiplegia — among whom it is necessary to grasp changes within a limited intervention period — these observations are potentially useful for occupational therapists to assess handwriting improvement and provide support, regardless of their years of experience. en-copyright= kn-copyright= en-aut-name=DaitoMaki en-aut-sei=Daito en-aut-mei=Maki kn-aut-name=大東真紀 kn-aut-sei=大東 kn-aut-mei=真紀 aut-affil-num=1 ORCID= en-aut-name=MorimotoMichiko en-aut-sei=Morimoto en-aut-mei=Michiko kn-aut-name=森本美智子 kn-aut-sei=森本 kn-aut-mei=美智子 aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil=岡山大学大学院保健学研究科 affil-num=2 en-affil=Division of Nursing, Faculty of Health Sciences, Okayama University kn-affil=岡山大学学術研究院保健学域 看護学 en-keyword=書字 (handwriting) kn-keyword=書字 (handwriting) en-keyword=脳卒中患者 (stroke patient) kn-keyword=脳卒中患者 (stroke patient) en-keyword=作業療法士 (occupational therapist) kn-keyword=作業療法士 (occupational therapist) en-keyword=観察 (observation) kn-keyword=観察 (observation) en-keyword=質的研究 (qualitative study) kn-keyword=質的研究 (qualitative study) END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=52 end-page=57 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Challenges in reconstructive surgery: Focus on the head and neck area kn-title=再建外科の挑戦(頭頸部領域を中心に) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakanariKeisuke en-aut-sei=Takanari en-aut-mei=Keisuke kn-aut-name=高成啓介 kn-aut-sei=高成 kn-aut-mei=啓介 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 形成再建外科学 en-keyword=頭頸部再建 kn-keyword=頭頸部再建 en-keyword=遊離皮弁移植 kn-keyword=遊離皮弁移植 en-keyword=動的再建 kn-keyword=動的再建 en-keyword=神経再建 kn-keyword=神経再建 END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=49 end-page=51 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2024 Incentive Award of the Okayama Medical Association in Cancer Research (2024 Hayashibara Prize and Yamada Prize) kn-title=令和6年度岡山医学会賞 がん研究奨励賞(林原賞・山田賞) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name=直井勇人 kn-aut-sei=直井 kn-aut-mei=勇人 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科 腫瘍微小環境学 END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=46 end-page=48 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2024 Incentive Award of the Okayama Medical Association in General Medical Science (2024 Yuuki Prize) kn-title=令和6年度岡山医学会賞 総合研究奨励賞(結城賞) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UrakamiHitoshi en-aut-sei=Urakami en-aut-mei=Hitoshi kn-aut-name=浦上仁志 kn-aut-sei=浦上 kn-aut-mei=仁志 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科 皮膚科学 END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=2 article-no= start-page=43 end-page=45 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2024 Incentive Award of the Okayama Medical Association in Cardiovascular and Pulmonary Research (2024 Sunada Prize) kn-title=令和6年度岡山医学会賞 胸部・循環研究奨励賞(砂田賞) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name=西原大裕 kn-aut-sei=西原 kn-aut-mei=大裕 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科 循環器内科学 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neutrophil-to-lymphocyte ratio affects the impact of proton pump inhibitors on efficacy of immune checkpoint inhibitors in patients with non‑small-cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The neutrophil-to-lymphocyte ratio (NLR) at the initiation of immune checkpoint inhibitor (ICI) therapy is a known predictor of prognosis. Proton pump inhibitors (PPIs) reportedly attenuate the therapeutic efficacy of ICIs. However, the attenuation effects are not consistently observed across all patients. This study aimed to evaluate whether NLR serves as a stratification factor to determine the impact of PPI on the efficacy of ICI.
Methods This retrospective study was conducted in patients with NSCLC treated with ICI monotherapy. Patients were stratified into two groups (higher NLR (≥ 4) and lower NLR (< 4)). PPI use was defined as the administration of PPIs within 30 days before or after ICI initiation. The primary outcome was progression-free survival (PFS) and the secondary outcome was overall survival (OS).
Results Among the 132 patients included, PPI users exhibited significantly shorter median PFS and OS than non-PPI users. In the higher NLR group (n = 61), PPI users had a markedly shorter PFS and OS than non-PPI users (median PFS: 1.6 vs. 8.2 months; p < 0.01, median OS: 3.3 vs. 19.6 months; p = 0.015). Conversely, in the lower NLR group (n = 71), no significant difference in PFS and OS was observed between PPI users and non-PPI users (median PFS: 2.8 vs. 7.3 months, p = 0.83, median OS: 17.6 vs. 24.4 months, p = 0.40).
Conclusion NLR may be a significant stratification factor for evaluating the impact of PPI on PFS and OS in patients with NSCLC undergoing ICI monotherapy. en-copyright= kn-copyright= en-aut-name=HoriTomoki en-aut-sei=Hori en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoTakefumi en-aut-sei=Ito en-aut-mei=Takefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkushimaShigeki en-aut-sei=Ikushima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Nara Prefecture General Medical Center kn-affil= affil-num=4 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=5 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor en-keyword=Neutrophil-to-lymphocyte ratio kn-keyword=Neutrophil-to-lymphocyte ratio en-keyword=Non-small-cell lung cancer kn-keyword=Non-small-cell lung cancer en-keyword=Proton pump inhibitor kn-keyword=Proton pump inhibitor END start-ver=1.4 cd-journal=joma no-vol=149 cd-vols= no-issue=1 article-no= start-page=36 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250426 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cerebral Braak stage and amygdala granular fuzzy astrocyte status have independent effects on neuronal 3R-tau and 4R-tau accumulations in the olfactory bulb, respectively, in cases with low to intermediate AD neuropathologic change en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YokotaOsamu en-aut-sei=Yokota en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MikiTomoko en-aut-sei=Miki en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Nakashima-YasudaHanae en-aut-sei=Nakashima-Yasuda en-aut-mei=Hanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshizuHideki en-aut-sei=Ishizu en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiTakashi en-aut-sei=Haraguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyashitaAkinori en-aut-sei=Miyashita en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkeuchiTakeshi en-aut-sei=Ikeuchi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaMasato en-aut-sei=Hasegawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishikawaNaoto en-aut-sei=Nishikawa en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakenoshitaShintaro en-aut-sei=Takenoshita en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TeradaSeishi en-aut-sei=Terada en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama University Medical School kn-affil= affil-num=4 en-affil=Okayama University Medical School kn-affil= affil-num=5 en-affil=Department of Neurology, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Molecular Genetics, Brain Research Institute, Niigata University kn-affil= affil-num=7 en-affil=Department of Molecular Genetics, Brain Research Institute, Niigata University kn-affil= affil-num=8 en-affil=Dementia Research Project, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=9 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Asymptomatic intracranial vascular lesions and cognitive function in a general population of Japanese men: Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Intracranial subclinical vessel diseases are considered important indicators of cognitive impairment. However, a comprehensive assessment of various types of vessel disease, particularly in Asian populations, is lacking. We aimed to compare multiple types of intracranial vessel disease in association with cognitive function among a community-based Japanese male population. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited and examined a community-based cohort of Japanese men from Shiga, Japan. We analyzed those who underwent the Cognitive Abilities Screening Instrument (CASI) assessment and cranial magnetic resonance imaging/angiogram (MRI/MRA) in 2010–2015. Using MRI/MRA, we assessed lacunar infarction, microbleeds, periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), and intracranial artery stenosis (ICAS). We divided these subclinical cerebrovascular diseases (SCDs) into three categories according to severity. Using linear regression, we calculated the CASI score according to the grade of each vessel disease, adjusted for age and years of education. Results: In the adjusted models, CASI scores were significantly associated with both PVH and DSWMH. Specifically, multivariable-adjusted CASI scores declined across increasing severity categories of DSWMH (91.7, 91.2, and 90.4; p for trend = 0.011) and PVH (91.5, 90.4, and 89.7; p for trend = 0.006). Other SCDs did not show significant associations. In stratified analyses based on the presence or absence of each SCD, both DSWMH and PVH demonstrated significant inverse trends with CASI scores in the absence of lacunar infarcts and microbleeds and in the presence of ICAS. Additionally, among participants with PVH (+), ≥moderate ICAS was significantly associated with lower CASI scores. Conclusion: PVH and DSWMH showed significant dose-response relationships with cognitive function among community-based Japanese men. These findings suggest that white matter lesions may be an important indicator of early cognitive impairment, and severe ICAS may also play a role in those with PVH. en-copyright= kn-copyright= en-aut-name=ItoTakahiro en-aut-sei=Ito en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiyoshiAkira en-aut-sei=Fujiyoshi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhkuboTakayoshi en-aut-sei=Ohkubo en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShiinoAkihiko en-aut-sei=Shiino en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShitaraSatoshi en-aut-sei=Shitara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyagawaNaoko en-aut-sei=Miyagawa en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToriiSayuki en-aut-sei=Torii en-aut-mei=Sayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SegawaHiroyoshi en-aut-sei=Segawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KondoKeiko en-aut-sei=Kondo en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KadotaAya en-aut-sei=Kadota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TooyamaIkuo en-aut-sei=Tooyama en-aut-mei=Ikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WatanabeYoshiyuki en-aut-sei=Watanabe en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YoshidaKazumichi en-aut-sei=Yoshida en-aut-mei=Kazumichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NozakiKazuhiko en-aut-sei=Nozaki en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=The SESSA Research Group en-aut-sei=The SESSA Research Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=3 en-affil=Department of Hygiene and Public Health, Teikyo University School of Medicine kn-affil= affil-num=4 en-affil=Molecular Neuroscience Research Center, Shiga University of Medical Science kn-affil= affil-num=5 en-affil=Department of Neurosurgery, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Department of Preventive Medicine and Public Health, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=10 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=11 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=12 en-affil=Molecular Neuroscience Research Center, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=14 en-affil=Department of Neurosurgery, Shiga University of Medical Science kn-affil= affil-num=15 en-affil=Department of Neurosurgery, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=17 en-affil= kn-affil= en-keyword=Cognitive impairment kn-keyword=Cognitive impairment en-keyword=Cerebrovascular disease kn-keyword=Cerebrovascular disease en-keyword=Brain magnetic resonance imaging kn-keyword=Brain magnetic resonance imaging en-keyword=White matter lesion kn-keyword=White matter lesion en-keyword=Community-based population study kn-keyword=Community-based population study END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=e70104 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adequacy evaluation of 22‐gauge needle endoscopic ultrasound‐guided tissue acquisition samples and glass slides preparation for successful comprehensive genomic profiling testing: A single institute experience en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: This study aimed to evaluate the successful sequencing rate of Foundation One CDx (F1CDx) using small tissue samples obtained with a 22-gauge needle (22G) through endoscopic ultrasound-guided fine needle acquisition (EUS-TA) and to propose guidelines for tissue quantity evaluation criteria and proper slide preparation in clinical practice.
Methods: Between June 2019 and April 2024, 119 samples of 22G EUS-TA collected for F1CDx testing at Himeji Red Cross Hospital were retrospectively reviewed. Tissue adequacy was only assessed based on tumor cell percentage (≥20%). The procedure stopped when white tissue fragments reached 20 mm during macroscopic on-site evaluation. The specimens were prepared using both ‘tissue preserving sectioning’ to retain tissue within formalin-fixed paraffin-embedded blocks and the ‘thin sectioning matched needle gauge and tissue length’ method with calculation to ensure minimal unstained slides for the 1 mm3 sample volume criterion. Tissue area from HE slides and sample volume were measured, and F1CDx reports were analyzed.
Results: Of 119 samples, 108 (90.8%) were suitable for F1CDx. Excluding the cases not submitted for testing, in the 45 cases where F1CDx was done using 22G EUS-TA samples, eight (17.8%) had a sum of tissue area tissue of 25 mm2 or greater in the HE-stained sample. However, all cases met the F1CDx 1 mm3 volume criterion by submitting > 30 unstained slides per sample. As a result, 43 of 45 cases (95.6%) were successfully analyzable.
Conclusions: The 22G EUS-TA needle is an effective tool for providing the sufficient tissue volume required for F1CDx. en-copyright= kn-copyright= en-aut-name=NagataniTami en-aut-sei=Nagatani en-aut-mei=Tami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WaniYoji en-aut-sei=Wani en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakataniMasahiro en-aut-sei=Takatani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FushimiSoichiro en-aut-sei=Fushimi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriShinichiro en-aut-sei=Hori en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KaiKyohei en-aut-sei=Kai en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkazakiTetsuya en-aut-sei=Okazaki en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TaniokaMaki en-aut-sei=Tanioka en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=5 en-affil=Division of Medical Support, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=7 en-affil=Department of Genetic Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=8 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=12 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=biliary tract cancer kn-keyword=biliary tract cancer en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=endoscopic ultrasound-guided fine needle aspiration kn-keyword=endoscopic ultrasound-guided fine needle aspiration en-keyword=endoscopic ultrasound-guided fine needle biopsy kn-keyword=endoscopic ultrasound-guided fine needle biopsy en-keyword=pancreatic cancer kn-keyword=pancreatic cancer END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=10 article-no= start-page=2373 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development and Characterization of a Three-Dimensional Organotypic In Vitro Oral Cancer Model with Four Co-Cultured Cell Types, Including Patient-Derived Cancer-Associated Fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Cancer organoids have emerged as a valuable tool of three-dimensional (3D) cell cultures to investigate tumor heterogeneity and predict tumor behavior and treatment response. We developed a 3D organotypic culture model of oral squamous cell carcinoma (OSCC) to recapitulate the tumor–stromal interface by co-culturing four cell types, including patient-derived cancer-associated fibroblasts (PD-CAFs). Methods: A stainless-steel ring was used twice to create the horizontal positioning of the cancer stroma (adjoining normal oral mucosa connective tissue) and the OSCC layer (surrounding normal oral mucosa epithelial layer). Combined with a structured bi-layered model of the epithelial component and the underlying stroma, this protocol enabled us to construct four distinct portions mimicking the oral cancer tissue arising in the oral mucosa. Results: In this model, α-smooth muscle actin-positive PD-CAFs were localized in close proximity to the OSCC layer, suggesting a crosstalk between them. Furthermore, a linear laminin-γ2 expression was lacking at the interface between the OSCC layer and the underlying stromal layer, indicating the loss of the basement membrane-like structure. Conclusions: Since the specific 3D architecture and polarity mimicking oral cancer in vivo provides a more accurate milieu of the tumor microenvironment (TME), it could be crucial in elucidating oral cancer TME. en-copyright= kn-copyright= en-aut-name=AizawaYuka en-aut-sei=Aizawa en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagaKenta en-aut-sei=Haga en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshibaNagako en-aut-sei=Yoshiba en-aut-mei=Nagako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YortchanWitsanu en-aut-sei=Yortchan en-aut-mei=Witsanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakadaSho en-aut-sei=Takada en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaRintaro en-aut-sei=Tanaka en-aut-mei=Rintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaitoEriko en-aut-sei=Naito en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AbéTatsuya en-aut-sei=Abé en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaruyamaSatoshi en-aut-sei=Maruyama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamazakiManabu en-aut-sei=Yamazaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanumaJun-ichi en-aut-sei=Tanuma en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TomiharaKei en-aut-sei=Tomihara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TogoShinsaku en-aut-sei=Togo en-aut-mei=Shinsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IzumiKenji en-aut-sei=Izumi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=2 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=3 en-affil=Department of Oral Health and Welfare, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=4 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=5 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=6 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=7 en-affil=Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=8 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=9 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=10 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=11 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=12 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=13 en-affil=Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University kn-affil= affil-num=15 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=oral cancer kn-keyword=oral cancer en-keyword=cancer-associated fibroblasts kn-keyword=cancer-associated fibroblasts en-keyword=oral mucosa kn-keyword=oral mucosa en-keyword=patient-derived kn-keyword=patient-derived en-keyword=organotypic culture kn-keyword=organotypic culture en-keyword=3D in vitro model kn-keyword=3D in vitro model en-keyword=polarity kn-keyword=polarity END start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue=2 article-no= start-page=473 end-page=479.e1 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dried blood spot proteome identifies subclinical interferon signature in neonates with type I interferonopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.
Objective: This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples. The aim was to evaluate the usefulness of the interferon signature for neonatal screening and to gain insight into presymptomatic state of neonates with inborn errors of immunity (IEIs).
Methods: DBS samples from healthy newborns/adults, patients with type I interferonopathy or other IEIs as well as from neonates with viral infections, including some samples obtained during the presymptomatic neonatal period, were examined by nontargeted proteome analyses. Expression of interferon-stimulated genes (ISGs) was evaluated and a DBS-interferon signature was defined. Differential expression/pathway analysis was also performed.
Results: The ISG products IFIT5, ISG15, and OAS2 were detected. Expression of IFIT5 and ISG15 was upregulated significantly in individuals with type I interferonopathy. We defined the sum of the z scores for these as the DBS-interferon signature, and found that patients with IEIs other than type I interferonopathy, such as chronic granulomatous disease (CGD), also showed significant elevation. Additionally, neonatal samples of type I interferonopathy and CGD patients showed high interferon signatures. Pathway analysis of neonatal CGD samples revealed upregulation of systemic lupus erythematosus–like pathways.
Conclusion: Upregulation of the interferon pathway exists already at birth—not only in neonates with type I interferonopathy but also in other IEIs, including CGD. en-copyright= kn-copyright= en-aut-name=NihiraHiroshi en-aut-sei=Nihira en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaDaisuke en-aut-sei=Nakajima en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IzawaKazushi en-aut-sei=Izawa en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawashimaYusuke en-aut-sei=Kawashima en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShibataHirofumi en-aut-sei=Shibata en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonnoRyo en-aut-sei=Konno en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashiguchiMotoko en-aut-sei=Higashiguchi en-aut-mei=Motoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoTakayuki en-aut-sei=Miyamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nishitani-IsaMasahiko en-aut-sei=Nishitani-Isa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiejimaEitaro en-aut-sei=Hiejima en-aut-mei=Eitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HondaYoshitaka en-aut-sei=Honda en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsubayashiTadashi en-aut-sei=Matsubayashi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaTakashi en-aut-sei=Ishihara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwataNaomi en-aut-sei=Iwata en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OhwadaYoko en-aut-sei=Ohwada en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomotakiSeiichi en-aut-sei=Tomotaki en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawaiMasahiko en-aut-sei=Kawai en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MurakamiKosaku en-aut-sei=Murakami en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhnishiHidenori en-aut-sei=Ohnishi en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshimuraMasataka en-aut-sei=Ishimura en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OkadaSatoshi en-aut-sei=Okada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YamashitaMotoi en-aut-sei=Yamashita en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MorioTomohiro en-aut-sei=Morio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HoshinoAkihiro en-aut-sei=Hoshino en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KaneganeHirokazu en-aut-sei=Kanegane en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ImaiKohsuke en-aut-sei=Imai en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakamuraYasuko en-aut-sei=Nakamura en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NonoyamaShigeaki en-aut-sei=Nonoyama en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UchiyamaToru en-aut-sei=Uchiyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=OnoderaMasafumi en-aut-sei=Onodera en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=IshikawaTakashi en-aut-sei=Ishikawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawaiToshinao en-aut-sei=Kawai en-aut-mei=Toshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=TakitaJunko en-aut-sei=Takita en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NishikomoriRyuta en-aut-sei=Nishikomori en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OharaOsamu en-aut-sei=Ohara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=YasumiTakahiro en-aut-sei=Yasumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= affil-num=1 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=7 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Seirei Hamamatsu General Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Nara Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University kn-affil= affil-num=15 en-affil=Department of Infection and Immunology, Aichi Children’s Health and Medical Center kn-affil= affil-num=16 en-affil=Department of Pediatrics, Dokkyo Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neonatology, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Pediatrics, Gifu University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences kn-affil= affil-num=23 en-affil=Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=24 en-affil=Laboratory of Immunology and Molecular Medicine, Advanced Research Initiative, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=25 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=26 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=27 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=28 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=29 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=30 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=31 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=32 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=33 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=34 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=35 en-affil=Department of Pediatrics and Child Health, Kurume University School of Medicine kn-affil= affil-num=36 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=37 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= en-keyword=Inborn errors of immunity kn-keyword=Inborn errors of immunity en-keyword=interferonopathy kn-keyword=interferonopathy en-keyword=signature kn-keyword=signature en-keyword=proteome kn-keyword=proteome en-keyword=dried blood spot kn-keyword=dried blood spot en-keyword=CGD kn-keyword=CGD en-keyword=WAS kn-keyword=WAS en-keyword=newborn kn-keyword=newborn en-keyword=neonate kn-keyword=neonate END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=roaf042 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recommendations for the treatment of juvenile idiopathic arthritis with oligoarthritis or polyarthritis from the 2024 update of the Japan College of Rheumatology Clinical Practice Guidelines for the management of rheumatoid arthritis including juvenile idiopathic arthritis with oligoarthritis or polyarthritis – secondary publication en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To conduct systematic reviews (SRs) and develop clinical practice guidelines (CPGs) for managing juvenile idiopathic arthritis (JIA) with oligoarthritis or polyarthritis.
Methods: The Grading of Recommendations, Assessment, Development, and Evaluation methodology was employed to carry out SRs and formulate the CPGs. An expert panel, including patients, paediatric and nonpaediatric rheumatologists, guideline specialists, and patient representatives, used the Delphi method to discuss and agree on the recommendations.
Results: Six clinical questions (CQs) on the efficacy and safety of medical treatments were evaluated. These included CQ1 on methotrexate (MTX), CQ2 on non-MTX conventional synthetic disease-modifying antirheumatic drugs, CQ3 on glucocorticoids, CQ4 on tumour necrosis factor inhibitors, CQ5 on interleukin-6 inhibitors, and CQ6 on Janus kinase inhibitors. Two randomized controlled trials were identified for CQ1, three for CQ2, two for CQ3, eight for CQ4, two for CQ5, and two for CQ6. Based on these evaluations, three strong and three conditional recommendations were established. The CPGs have been endorsed by the Japan College of Rheumatology and the Pediatric Rheumatology Association of Japan.
Conclusions: The SRs provided the necessary evidence to develop the CPGs, which are intended to guide not only paediatric but also nonpaediatric rheumatologists, caregivers, patients, and their families in treatment decision-making. en-copyright= kn-copyright= en-aut-name=MiyamaeTakako en-aut-sei=Miyamae en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamotoNami en-aut-sei=Okamoto en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueYuzaburo en-aut-sei=Inoue en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaTomohiro en-aut-sei=Kubota en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EbatoTakasuke en-aut-sei=Ebato en-aut-mei=Takasuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IrabuHitoshi en-aut-sei=Irabu en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamedaHideto en-aut-sei=Kameda en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanekoYuko en-aut-sei=Kaneko en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboHiroshi en-aut-sei=Kubo en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MitsunagaKanako en-aut-sei=Mitsunaga en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MoriMasaaki en-aut-sei=Mori en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakajimaAyako en-aut-sei=Nakajima en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimuraKenichi en-aut-sei=Nishimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OhkuboNaoaki en-aut-sei=Ohkubo en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SatoTomomi en-aut-sei=Sato en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugitaYuko en-aut-sei=Sugita en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakanashiSatoshi en-aut-sei=Takanashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaTakayuki en-aut-sei=Tanaka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UmebayashiHiroaki en-aut-sei=Umebayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamanishiShingo en-aut-sei=Yamanishi en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FusamaMie en-aut-sei=Fusama en-aut-mei=Mie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HirataShintaro en-aut-sei=Hirata en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KishimotoMitsumasa en-aut-sei=Kishimoto en-aut-mei=Mitsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KohnoMasataka en-aut-sei=Kohno en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KojimaMasayo en-aut-sei=Kojima en-aut-mei=Masayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KojimaToshihisa en-aut-sei=Kojima en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MorinobuAkio en-aut-sei=Morinobu en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=SugiharaTakahiko en-aut-sei=Sugihara en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=TanakaEiichi en-aut-sei=Tanaka en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=YajimaNobuyuki en-aut-sei=Yajima en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=YanaiRyo en-aut-sei=Yanai en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawahitoYutaka en-aut-sei=Kawahito en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HarigaiMasayoshi en-aut-sei=Harigai en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Department of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety kn-affil= affil-num=3 en-affil=Department of General Medical Science, Graduate School of Medicine, Chiba University kn-affil= affil-num=4 en-affil=Department of Pediatrics, Kagoshima Prefectural Satsunan Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kitasato University kn-affil= affil-num=6 en-affil=Department of Pediatrics and Development Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=7 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University kn-affil= affil-num=8 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=10 en-affil=Department of Allergy and Rheumatology, Chiba Children's Hospital kn-affil= affil-num=11 en-affil=Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University kn-affil= affil-num=12 en-affil=Center for Rheumatic Diseases, Mie University Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Yokohama City University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Iizuka Hospital kn-affil= affil-num=15 en-affil=Clinical Education Center For Physicians, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Pediatrics, School of Medicine, Osaka Medical and Pharmaceutical University kn-affil= affil-num=17 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Department of Pediatrics, Japanese Red Cross Otsu Hospital kn-affil= affil-num=19 en-affil=Department of Rheumatology and Infectious Diseases, Miyagi Children’s Hospital kn-affil= affil-num=20 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Pediatrics, Nippon Medical School kn-affil= affil-num=22 en-affil=Health Sciences Department of Nursing, Kansai University of International Studies kn-affil= affil-num=23 en-affil=Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital kn-affil= affil-num=24 en-affil=Department of Nephrology and Rheumatology, Kyorin University School of Medicine kn-affil= affil-num=25 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=26 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=27 en-affil=Department of Orthopedic Surgery, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=28 en-affil=Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=29 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine kn-affil= affil-num=30 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= affil-num=31 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=32 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=33 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=34 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= en-keyword=Clinical practice guidelines kn-keyword=Clinical practice guidelines en-keyword=baricitinib kn-keyword=baricitinib en-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) kn-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) en-keyword=juvenile idiopathic arthritis kn-keyword=juvenile idiopathic arthritis en-keyword=systematic review kn-keyword=systematic review END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue= article-no= start-page=244 end-page=256 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Postnatal expression of Cat-315-positive perineuronal nets in the SAMP10 mouse primary somatosensory cortex en-subtitle= kn-subtitle= en-abstract= kn-abstract=Perineuronal nets (PNNs) form at the end of the critical period of plasticity in the mouse primary somatosensory cortex. PNNs are said to have functions that control neuroplasticity and provide neuroprotection. However, it is not clear which molecules in PNNs have these functions. We have previously reported that Cat-315-positive molecules were not expressed in the PNNs of the senescence-accelerated model (SAM)P10 strain model mice at 12 months of age. To confirm whether the loss of Cat-315-positive molecules occurred early in life in SAMP10 mice, we examined Cat-315-positive PNNs in the primary somatosensory cortex during postnatal development. This research helps to elucidate the function of PNNs and the mechanism of cognitive decline associated with ageing. To confirm whether Cat-315-positive PNNs changed in an age-dependent manner in SAMP10 mice, we examined the primary somatosensory cortex at 21, 28, and 56 days after birth. We compared these results with those of senescence-accelerated mouse-resistant (SAMR) mice. In SAMP10 mice, Cat-315-positive PNNs were expressed in the primary somatosensory cortex early after birth, but their expression was significantly lower than that in SAMR1 mice. Many other molecules that calibrated the PNN were unchanged between SAMP10 and SAMR1 mice. This study revealed that the expression of the Cat-315 epitope was decreased in the primary somatosensory cortex of SAMP10 mice during postnatal development. SAMP10 mice have had histological abnormalities in their brains since early life. Furthermore, using SAMP10 will be useful in elucidating the mechanism of age-related abnormalities in brain function as well as in elucidating the function and structure of PNNs. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=Ageing kn-keyword=Ageing en-keyword=Brain function kn-keyword=Brain function en-keyword=Neuroplasticity kn-keyword=Neuroplasticity en-keyword=Neuroprotection kn-keyword=Neuroprotection en-keyword=Cognitive decline kn-keyword=Cognitive decline END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Age-related behavioural abnormalities in C57BL/6.KOR–Apoe shl mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spontaneously hyperlipidaemic (Apoeshl) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the Apoe gene. However, age-related behavioural changes in commercially available Apoeshl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimer’s disease (AD). To understand whether Apoeshl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoeshl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoeshl mice to investigate the behavioural abnormalities associated with ageing in Apoeshl mice. In this study, 7-month-old Apoeshl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoeshl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoeshl mice showed decreased anxiety-like behaviour. Moreover, Apoeshl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoeshl mice changes with age. However, 11-month-old Apoeshl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoeshl mice can be used to investigate the function of ApoE in the central nervous system. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyazakiTetsuji en-aut-sei=Miyazaki en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=age kn-keyword=age en-keyword=apolipoprotein kn-keyword=apolipoprotein en-keyword=behavioural test kn-keyword=behavioural test en-keyword=central nervous system kn-keyword=central nervous system en-keyword=mouse kn-keyword=mouse END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rearing in an envy-like environment increases anxiety-like behaviour in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Interest in the societal and psychological harm caused by widespread envy and social comparison is increasing. Envy is associated with anxiety and depression, though the mechanism by which envy affects neuropsychiatric disorders, such as depression, remains unclear. Clarifying the neurobiological basis of envy’s effects on behaviour and emotion regulation in experimental mice is essential for developing disease-prevention and treatment strategies. As mice recognize other mice in neighbouring cages, this study investigated whether they recognize neighbouring cages housed in environmentally enriched cages and suffer psychological stress due to envy. After being raised in an envy-like environment for 3 weeks, we revealed changes in the behaviour of the mice through a series of behavioural experiments. Mice raised in an envious environment showed increased body weight and anxiety-like behaviour but decreased social behaviour and serum corticosterone levels compared to control mice. Thus, mice recognize their neighbouring cages and experience psychological stress due to envy. This study revealed a part of the scientific basis for why envy increased anxiety. Using this novel experimental breeding environment, it may be possible to create an experimental animal model of anxiety disorders. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=behaviour kn-keyword=behaviour en-keyword=anxiety kn-keyword=anxiety en-keyword=mouse kn-keyword=mouse en-keyword=envy kn-keyword=envy en-keyword=rodent kn-keyword=rodent END start-ver=1.4 cd-journal=joma no-vol=2024 cd-vols= no-issue= article-no= start-page=9215607 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mice Recognise Mice in Neighbouring Rearing Cages and Change Their Social Behaviour en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mice are social animals that change their behaviour primarily in response to visual, olfactory, and auditory information from conspecifics. Rearing conditions such as cage size and colour are important factors influencing mouse behaviour. In recent years, transparent plastic cages have become standard breeding cages. The advantage of using a transparent cage is that the experimenter can observe the mouse from outside the cage without touching the cage. However, mice may recognise the environment outside the cage and change their behaviour. We speculated that mice housed in transparent cages might recognise mice in neighbouring cages. We used only male mice in this experiment. C57BL/6 mice were kept in transparent rearing cages with open lids, and the cage positions were maintained for 3 weeks. Subsequently, we examined how mice behaved toward cagemate mice, mice from neighbouring cages, and mice from distant cages. We compared the level of interest in mice using a social preference test. Similar to previous reports, subject mice showed a high degree of interest in unfamiliar mice from distant cages. By contrast, subject mice reacted to mice from neighbouring cages as familiar mice, similar to cagemate mice. This suggests that mice housed in transparent cages with open lids perceive the external environment and identify mice in neighbouring cages. Researchers should pay attention to the environment outside the mouse cage, especially for the social preference test. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=1399 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association Between Chewing Status and Steatotic Liver Disease in Japanese People Aged ≥50 Years: A Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: In this longitudinal study, the relationship between chewing status and steatotic liver disease (SLD) was examined in 3775 people aged ≥50 years who underwent medical checkups at Junpukai Health Maintenance Center in Okayama, Japan. Methods: Participants without SLD at the time of a baseline survey in 2018 were followed until 2022. Chewing status was assessed by a self-administered questionnaire. The presence or absence of SLD was ascertained from the medical records of Junpukai Health Maintenance Center. Results: A total of 541 participants (14%) were diagnosed as having a poor chewing status at baseline. Furthermore, 318 (8%) participants were newly diagnosed with SLD at follow-up. In multivariate logistic regression analyses, the presence or absence of SLD was found to be associated with the following characteristics at baseline: sex (male: odds ratio [ORs] = 1.806; 95% confidence interval [CIs]: 1.399–2.351), age (ORs = 0.969; 95% CIs: 0.948–0.991), body mass index (≥25.0 kg/m2; ORs = 1.934; 95% CIs: 1.467–2.549), diastolic blood pressure (ORs = 1.017; 95% CIs: 1.002–1.032), and chewing status (poor: ORs = 1.472; 95% CIs: 1.087–1.994). Conclusions: The results indicate that a poor chewing status was associated with SLD development after 4 years. Aggressively recommending dental visits to participants with poor chewing status may not only improve their ability to chew well but may also reduce the incidence of SLD. en-copyright= kn-copyright= en-aut-name=IwaiKomei en-aut-sei=Iwai en-aut-mei=Komei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AzumaTetsuji en-aut-sei=Azuma en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YonenagaTakatoshi en-aut-sei=Yonenaga en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TabataKoichiro en-aut-sei=Tabata en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KataokaKota en-aut-sei=Kataoka en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TomofujiTakaaki en-aut-sei=Tomofuji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= affil-num=4 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= affil-num=5 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= en-keyword=oral health kn-keyword=oral health en-keyword=liver diseases kn-keyword=liver diseases en-keyword=longitudinal studies kn-keyword=longitudinal studies en-keyword=mastication kn-keyword=mastication en-keyword=physical examination kn-keyword=physical examination en-keyword=surveys and questionnaires kn-keyword=surveys and questionnaires END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=cr.25-0141 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Obese Patient with Gastric Diverticulum Undergoing Laparoscopic Sleeve Gastrectomy Guided by Preoperative Endoscopic Measurement: A Case Report and Literature Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=INTRODUCTION: Gastric diverticulum is a rare condition, often asymptomatic and incidentally detected. Laparoscopic sleeve gastrectomy (LSG) is a widely performed bariatric procedure, but a gastric diverticulum complicates surgical planning. In this case, careful preoperative assessment allowed safe execution of LSG despite the diverticulum’s proximity to the esophagogastric junction.
CASE PRESENTATION: A 45-year-old woman (BMI: 46.8 kg/m2) with hypertension, dyslipidemia, and glucose intolerance was referred for bariatric surgery after unsuccessful weight loss with conservative management. Preoperative endoscopy revealed an 18 × 14 mm gastric diverticulum on the posterior wall of the gastric fundus, 40 mm from the esophagogastric junction. LSG was performed using a surgical stapler, ensuring complete diverticulum resection while preserving gastric tube integrity. The surgery was uneventful, with minimal blood loss and a duration of 2 hours and 52 minutes. The patient had an uneventful postoperative course and was discharged on day 9. Her BMI decreased to 39.3 kg/m2 at the 1-year follow-up, with improved metabolic parameters.
CONCLUSIONS: This case highlights the importance of thorough preoperative evaluation when performing LSG in patients with gastric diverticulum. Accurate endoscopic measurement of the diverticulum’s location aids in determining the optimal resection line, ensuring surgical safety and efficacy. Surgeons should remain vigilant when encountering such anatomical variations to optimize outcomes in bariatric surgery. en-copyright= kn-copyright= en-aut-name=HirosunaKensuke en-aut-sei=Hirosuna en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Center for Graduate Medical Education, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=obese patient kn-keyword=obese patient en-keyword=gastric diverticulum kn-keyword=gastric diverticulum en-keyword=sleeve gastrectomy kn-keyword=sleeve gastrectomy en-keyword=metabolic surgery kn-keyword=metabolic surgery en-keyword=bariatric surgery kn-keyword=bariatric surgery en-keyword=endoscopic measurement kn-keyword=endoscopic measurement END start-ver=1.4 cd-journal=joma no-vol=2892 cd-vols= no-issue= article-no= start-page=012002 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Crystal Grain Rotation during Tensile Test of Polycrystalline Pure Titanium Thin Sheet Based on Surface Height and Crystal Orientation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thin sheets and wires of polycrystalline pure titanium are important materials for various devices used in electrical, mechanical, dental, and medical fields. Since pure titanium shows strong anisotropy in elastic and plastic deformation, and the individual grains comprising a polycrystalline body have different orientations and geometries, inhomogeneous deformation always occurs on the microscopic scale. This inhomogeneity is more significant in thin films than in bulk materials. It is therefore important to investigate the inhomogeneous deformation of pure titanium thin sheets to ensure the reliability of various titanium devices. In this study, thin-sheet specimens made of polycrystalline pure titanium were subjected to tensile testing. Inhomogeneous deformation was evaluated on the basis of two kinds of crystal grain rotations based on surface height and crystal orientation. The results under elastic and plastic tensile conditions were compared. en-copyright= kn-copyright= en-aut-name=TadaNaoya en-aut-sei=Tada en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiHiroaki en-aut-sei=Ohashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UemoriTakeshi en-aut-sei=Uemori en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoJunji en-aut-sei=Sakamoto en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= affil-num=4 en-affil=Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Activated Clotting Time Requires Adaptation Across Altered Measurement Devices: Determination of Appropriate Range During Atrial Fibrillation Ablation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Methods for measuring activated clotting time (ACT) are not yet standardized.
Objectives: To adjust and compare values between two measurement systems and to optimize ACT during atrial fibrillation (AF) ablation.
Methods: Two systems were compared: electromagnetic detection using a rotating tube (EM system; Hemochron Response) and photo-optical detection using a cartridge immersed in blood (PO system; ACT CA-300TM).
Results: ACT was measured simultaneously in 124 instances in 53 patients before and during AF ablations using both methods. A linear regression analysis showed ACT (EM system) = 1.19 × ACT (PO system) + 9.03 (p < .001, r = 0.90). Bland–Altman plots indicated an average difference of 50 s between the two systems. In 3364 ACT measurements from 1161 ablations, the EM system recorded a mean ACT of 320 ± 44 s (range 156-487 s). Estimating the target range as mean ± 1 SD range, the EM system's range was 275-365 s, in 5-s increments. The pre-ablation ACT measured on the EM system was 143 ± 28 s (115-170 s). Cardiac tamponade occurred in 4 out of 2085 ablations (0.19%) over 5 years, with ACT values ranging from 330 to 391 s on the EM system. Based on these findings, the estimated optimal ACT range for the PO system was adjusted to 225-300 s to align with the EM system's range of 275-365 s.
Conclusions: ACT target ranges should be system-specific, and direct extrapolation between devices is not recommended. Adjustment is clinically necessary when switching systems. en-copyright= kn-copyright= en-aut-name=SakanoueHaruna en-aut-sei=Sakanoue en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamajiHirosuke en-aut-sei=Yamaji en-aut-mei=Hirosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkamotoSayaka en-aut-sei=Okamoto en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkanoKumi en-aut-sei=Okano en-aut-mei=Kumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujitaYuka en-aut-sei=Fujita en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigashiyaShunichi en-aut-sei=Higashiya en-aut-mei=Shunichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurakamiTakashi en-aut-sei=Murakami en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KusachiShozo en-aut-sei=Kusachi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Nursing, Okayama Heart Clinic kn-affil= affil-num=2 en-affil=Heart Rhythm Center, Okayama Heart Clinic kn-affil= affil-num=3 en-affil=Department of Nursing, Okayama Heart Clinic kn-affil= affil-num=4 en-affil=Department of Nursing, Okayama Heart Clinic kn-affil= affil-num=5 en-affil=Department of Nursing, Okayama Heart Clinic kn-affil= affil-num=6 en-affil=Heart Rhythm Center, Okayama Heart Clinic kn-affil= affil-num=7 en-affil=Heart Rhythm Center, Okayama Heart Clinic kn-affil= affil-num=8 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=9 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=anticoagulation kn-keyword=anticoagulation en-keyword=heparin kn-keyword=heparin en-keyword=catheter kn-keyword=catheter en-keyword=supraventricular arrhythmia kn-keyword=supraventricular arrhythmia en-keyword=point-of-care testing kn-keyword=point-of-care testing END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1561628 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250321 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histidine-rich glycoprotein inhibits TNF-α–induced tube formation in human vascular endothelial cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Tumor necrosis factor-α (TNF-α)-induced angiogenesis plays a critical role in tumor progression and metastasis, making it an important therapeutic target in cancer treatment. Suppressing angiogenesis can effectively limit tumor growth and metastasis. However, despite advancements in understanding angiogenic pathways, effective strategies to inhibit TNF-α-mediated angiogenesis remain limited.
Methods: This study investigates the antiangiogenic effects of histidine-rich glycoprotein (HRG), a multifunctional plasma protein with potent antiangiogenic properties, on TNF-α-stimulated human endothelial cells (EA.hy926). Tube formation assays were performed to assess angiogenesis, and gene/protein expression analyses were conducted to evaluate HRG’s effects on integrins αV and β8. The role of nuclear factor erythroid 2-related factor 2 (NRF2) in HRG-mediated antiangiogenic activity was also examined through nuclear translocation assays and NRF2 activation studies.
Results: At physiological concentrations, HRG effectively suppressed TNF-α-induced tube formation in vitro and downregulated TNF-α-induced expression of integrins αV and β8 at both the mRNA and protein levels. HRG treatment promoted NRF2 nuclear translocation in a time-dependent manner. Furthermore, activation of NRF2 significantly reduced TNF-α-induced tube formation and integrin expression, suggesting that NRF2 plays a key role in HRG-mediated antiangiogenic effects.
Discussion and Conclusion: Our findings indicate that HRG suppresses TNF-α-induced angiogenesis by promoting NRF2 nuclear translocation and transcriptional activation, which in turn inhibits integrin αV and β8 expression. Given the essential role of angiogenesis in tumor progression, HRG’s ability to regulate this process presents a promising therapeutic strategy for cancer treatment. en-copyright= kn-copyright= en-aut-name=HatipogluOmer Faruk en-aut-sei=Hatipoglu en-aut-mei=Omer Faruk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishinakaTakashi en-aut-sei=Nishinaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaykasliKursat Oguz en-aut-sei=Yaykasli en-aut-mei=Kursat Oguz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeMasahiro en-aut-sei=Watanabe en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToyomuraTakao en-aut-sei=Toyomura en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakahashiHideo en-aut-sei=Takahashi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pharmacology, Kindai University Faculty of Medicine kn-affil= affil-num=2 en-affil=Department of Pharmacology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen kn-affil= affil-num=4 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=5 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=6 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=7 en-affil=Department of Translational Research and Dug Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacology, Kindai University Faculty of Medicine kn-affil= affil-num=10 en-affil=Department of Pharmacology, Kindai University Faculty of Medicine kn-affil= en-keyword=histidine-rich glycoprotein kn-keyword=histidine-rich glycoprotein en-keyword=tumor necrosis factor-α kn-keyword=tumor necrosis factor-α en-keyword=integrin kn-keyword=integrin en-keyword=tube formation kn-keyword=tube formation en-keyword=angiogenesis kn-keyword=angiogenesis en-keyword=factor erythroid 2-related factor 2 kn-keyword=factor erythroid 2-related factor 2 END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=8 article-no= start-page=1261 end-page=1268 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overview of task shifting guidelines in Japan: from radiologists to radiological technologists en-subtitle= kn-subtitle= en-abstract= kn-abstract=As one of the key pillars of work style reform for physicians, task shifting and sharing from radiologists to radiological technologists has been considered. In May 2021, the Radiological Technologists Act was amended, allowing for the expansion of several duties. Alongside these legal and regulatory changes, a notice from Ministry of Health, Labour and Welfare was issued, highlighting tasks to be particularly promoted under the current system prior to the amendment of the Radiological Technologists Act. These amendments authorize radiological technologists to perform advanced and specialized tasks, such as securing venous access for contrast agent administration, which require significantly higher skill levels than their traditional roles. However, the amended legislation did not include specific guidelines, rules, or considerations for the practical implementation of these new duties in daily medical practice, especially from the perspectives of patient safety and quality of care. To address this, the Japan Radiological Society, the Japanese College of Radiology, and the Japan Association of Radiological Technologists collaborated with other related societies to develop guidelines on five key topics:-Guidelines for Safe Conduct of CT/MRI Contrast-Enhanced Examinations: Considering the expanded scope of practice for radiological technologists. -Guidelines for Safe Conduct of Nuclear Medicine Examinations: Aligned with the expanded responsibilities of radiological technologists. -Guidelines for Clinical application of Image-Guided Radiation Therapy (IGRT). -Guidelines for Safe Conduct of Angiography and Interventional Radiology (IR): Adapted for the expanded roles of radiological technologists. -Guidelines for Reporting Findings of STAT Imaging: Addressing urgent conditions with potential impact on life prognosis. en-copyright= kn-copyright= en-aut-name=KidoAki en-aut-sei=Kido en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhnoKazuko en-aut-sei=Ohno en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKei en-aut-sei=Yamada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamakadoKoichiro en-aut-sei=Yamakado en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MizowakiTakashi en-aut-sei=Mizowaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AidaNoriko en-aut-sei=Aida en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Oyama-ManabeNoriko en-aut-sei=Oyama-Manabe en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KodamaNaoki en-aut-sei=Kodama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UedaKatsuhiko en-aut-sei=Ueda en-aut-mei=Katsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AokiShigeki en-aut-sei=Aoki en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TomiyamaNoriyuki en-aut-sei=Tomiyama en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Radiology, Toyama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Kyoto University of Medial Science kn-affil= affil-num=3 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=4 en-affil=Department of Radiology, The Hospital of Hyogo College of Medicine kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University kn-affil= affil-num=7 en-affil=Department of Diagnostic Radiology, Yokohama City University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Radiology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Faculty of Medical Technology, Niigata University of Health and Welfare kn-affil= affil-num=10 en-affil=Department of Radiological Sciences, School of Health Sciences at Narita, International University of Health and Welfare kn-affil= affil-num=11 en-affil=Health Data Science, Department of Radiology/Data Science, Graduate School of Medicine, Juntendo University kn-affil= affil-num=12 en-affil=Department of Radiology, Osaka University Graduate School of Medicine kn-affil= en-keyword=Task shifting and sharing kn-keyword=Task shifting and sharing en-keyword=Radiological technologists kn-keyword=Radiological technologists en-keyword=Guideline kn-keyword=Guideline en-keyword=IGRT kn-keyword=IGRT en-keyword=STAT kn-keyword=STAT END start-ver=1.4 cd-journal=joma no-vol=1863 cd-vols= no-issue= article-no= start-page=149752 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spearmint extract Neumentix downregulates amyloid-β accumulation by promoting phagocytosis in APP23 mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=In recent years, many researchers have focused on natural compounds that can effectively delay symptoms of Alzheimer’s disease (AD). The spearmint extract Neumentix, which is rich in phenolic compounds, has been shown to reduce inflammatory responses and oxidative stress in mice. However, the effect of Neumentix on AD has not been thoroughly studied. In this study, APP23 transgenic female and male mice were administered Neumentix orally from 4 to 18 months of age at a dosage of 2.65 g/kg/day (containing 0.41 g/kg/day of rosmarinic acid). The impact was evaluated by behavioral tests and histological analyses and compared with APP23 mice to which Neumentix was not administered. The results showed that Neumentix administration increased the survival rate of APP23 mice and effectively reduced Aβ accumulation by enhancing its phagocytosis by microglial cells. These findings suggest that Neumentix is a potential natural nutritional treatment for improving the progression of AD. en-copyright= kn-copyright= en-aut-name=HuXinran en-aut-sei=Hu en-aut-mei=Xinran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BianYuting en-aut-sei=Bian en-aut-mei=Yuting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SunHongming en-aut-sei=Sun en-aut-mei=Hongming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Ota-ElliottRicardo Satoshi en-aut-sei=Ota-Elliott en-aut-mei=Ricardo Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=National Center Hospital, National Center of Neurology and Psychiatry kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Alzheimer's disease kn-keyword=Alzheimer's disease en-keyword=Amyloid-beta kn-keyword=Amyloid-beta en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Neumentix kn-keyword=Neumentix en-keyword=Phagocytosis kn-keyword=Phagocytosis en-keyword=Survival rate kn-keyword=Survival rate END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=1 article-no= start-page=144 end-page=156 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241109 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lymphadenectomy and chemotherapy are effective treatments for patients with 2023 international federation of gynecology and obstetrics stage IIC-high risk endometrial cancer in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background In early-stage endometrial cancer (EC), the treatment of aggressive histological subtypes (endometrioid carcinoma grade 3, serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed carcinoma, and carcinosarcoma) is controversial. We aimed to investigate the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage IIC EC according to the 2023 classification.
Methods We retrospectively identified patients with FIGO 2023 stage IC, IIC-intermediate risk (IIC-I), and IIC-high risk (IIC-H) EC who underwent adjuvant therapy or observation after surgery at eight medical institutions from 2004 to 2023. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier estimates and univariate and multivariate analyses.
Results The PFS and OS were significantly worse in patients with FIGO 2023 stage IIC-H EC than in those with FIGO 2023 stage IIC-I EC (PFS: p = 0.008 and OS: p = 0.006). According to the FIGO 2023 stage IIC-H classification, lymphadenectomy and chemotherapy resulted in better prognoses regarding both PFS and OS (p < 0.001 for both) than other treatments. Our findings suggest that lymphadenectomy and chemotherapy effectively reduced vaginal stump and lymph node metastases in FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.008, respectively). Furthermore, in the multivariate analysis, not undergoing lymphadenectomy or chemotherapy were independent predictors of recurrence and poor prognoses in patients with FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.031, respectively).
Conclusion Lymphadenectomy and chemotherapy resulted in better prognoses regarding both recurrence and survival in patients with FIGO 2023 stage IIC high-risk EC. en-copyright= kn-copyright= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YorimitsuMasae en-aut-sei=Yorimitsu en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekiNoriko en-aut-sei=Seki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanishiMie en-aut-sei=Nakanishi en-aut-mei=Mie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItouHironori en-aut-sei=Itou en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimizuMiyuki en-aut-sei=Shimizu en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoDan en-aut-sei=Yamamoto en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakaharaEtsuko en-aut-sei=Takahara en-aut-mei=Etsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Kagawa Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, National Organization Fukuyama Medical Center kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Fukuyama City Hospital kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Endometrial cancer kn-keyword=Endometrial cancer en-keyword=FIGO 2023 kn-keyword=FIGO 2023 en-keyword=Stage IIC high risk kn-keyword=Stage IIC high risk en-keyword=Lymphadenectomy kn-keyword=Lymphadenectomy en-keyword=Chemotherapy kn-keyword=Chemotherapy END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=1 article-no= start-page=43 end-page=53 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fan-Shaped Pneumatic Soft Actuator that Can Operate Bending Motion for Ankle-Joint Rehabilitation Device en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, owing to declining birthrates and an aging population, patients and the elderly requiring rehabilitation are not getting enough physical activity. In addressing this issue, devices for rehabilitating them have been researched and developed. However, rehabilitation devices are almost exclusively used for patients who can get up, rather than those who are bedridden. In this study, we aim to develop a rehabilitation device that can provide passive exercise for bedridden patients. The ankle joint was selected as the target joint because the patients who have undergone surgery for cerebrovascular disease remain bedridden, and early recovery in the acute stage is highly desirable. We proposed and tested a fan-shaped pneumatic soft actuator (FPSA) that can expand and bend stably at angles when supply pressure is applied as an actuator for a rehabilitation device to encourage patient exercise. However, the previous FPSA’s movement deviates from the arch of the foot owing to increased supply pressure. In the ideal case, FPSA should push the arch of the foot in an arc motion. This study proposes and tests the FPSA that can operate a bending motion to provide passive exercise to the ankle joint using tensile springs and a winding mechanism powered by a servo motor. The proposed FPSA has a significant advantage of exhibiting no hysteresis in its pressure-displacement characteristics. The configuration and static analytical model of the improved FPSA are described. en-copyright= kn-copyright= en-aut-name=ShimookaSo en-aut-sei=Shimooka en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyaHirosato en-aut-sei=Yokoya en-aut-mei=Hirosato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShiomiShun en-aut-sei=Shiomi en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UeharaTakenori en-aut-sei=Uehara en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamegawaTetsushi en-aut-sei=Kamegawa en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, NHO Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=fan-shaped pneumatic soft actuator kn-keyword=fan-shaped pneumatic soft actuator en-keyword=ankle-joint rehabilitation device kn-keyword=ankle-joint rehabilitation device en-keyword=hysteresis kn-keyword=hysteresis en-keyword=range of motion kn-keyword=range of motion END start-ver=1.4 cd-journal=joma no-vol=329 cd-vols= no-issue=1 article-no= start-page=L183 end-page=L196 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Activated factor X inhibition ameliorates NF-κB-IL-6-mediated perivascular inflammation and pulmonary hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=Activated factor X (FXa) induces inflammatory response and cell proliferation in various cell types via activation of proteinase-activated receptor-1 (PAR1) and/or PAR2. We thus aimed to investigate the impact of FXa on the development of pulmonary arterial hypertension (PAH) and the mechanisms involved. The effects of edoxaban, a selective FXa inhibitor, on hemodynamic, right ventricular (RV) hypertrophy, and vascular remodeling were evaluated in a monocrotaline (MCT)-exposed pulmonary hypertension (PH) rat model. At 21 days after a single subcutaneous injection of MCT of 60 mg/kg, right ventricular systolic pressure (RVSP) and total pulmonary vascular resistance index (TPRI) were elevated concomitant with the increased plasma FXa and lung interleukin-6 (IL-6) mRNA. Daily administration of edoxaban (10 mg/kg/day, by gavage) starting from the day of MCT injection for 21 days ameliorated RVSP, TPRI, RV hypertrophy, pulmonary vascular remodeling, and macrophage accumulation. Edoxaban reduced nuclear factor-kappa B (NF-κB) activity and IL-6 mRNA level in the lungs of MCT-exposed rats. mRNA levels of FXa, PAR1, and PAR2 in cultured pulmonary arterial smooth muscle cells (PASMCs) isolated from patients with PAH were higher than those seen in normal PASMCs. FXa stimulation increased cell proliferation and mRNA level of IL-6 in normal PASMCs, both of which were blunted by edoxaban and PAR1 antagonist. Moreover, FXa stimulation activated extracellularly regulated kinases 1/2 in a PAR1-dependent manner. Inhibition of FXa ameliorates NF-κB-IL-6-mediated perivascular inflammation, pulmonary vascular remodeling, and the development of PH in MCT-exposed rats, suggesting that FXa may be a potential target for the treatment of PAH.
NEW & NOTEWORTHY This study demonstrated that chronic treatment with activated factor X (FXa) inhibitor ameliorated NF-κB-IL-6-mediated perivascular inflammation in a rat model with pulmonary arterial hypertension, which is associated with elevated FXa activity. FXa may act on pulmonary arterial smooth muscle cells, inducing cell proliferation and inflammatory response via upregulated PAR1, thereby contributing to pulmonary vascular remodeling. Understanding the patient-specific pathophysiology is a prerequisite for applying FXa-targeted therapy to the treatment of pulmonary arterial hypertension. en-copyright= kn-copyright= en-aut-name=ImakiireSatomi en-aut-sei=Imakiire en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuroKeiji en-aut-sei=Kimuro en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaKeimei en-aut-sei=Yoshida en-aut-mei=Keimei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasakiKohei en-aut-sei=Masaki en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IzumiRyo en-aut-sei=Izumi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImabayashiMisaki en-aut-sei=Imabayashi en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeTakanori en-aut-sei=Watanabe en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshikawaTomohito en-aut-sei=Ishikawa en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HosokawaKazuya en-aut-sei=Hosokawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsushimaShouji en-aut-sei=Matsushima en-aut-mei=Shouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HashimotoToru en-aut-sei=Hashimoto en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShinoharaKeisuke en-aut-sei=Shinohara en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatsukiShunsuke en-aut-sei=Katsuki en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatobaTetsuya en-aut-sei=Matoba en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HiranoKatsuya en-aut-sei=Hirano en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsutsuiHiroyuki en-aut-sei=Tsutsui en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AbeKohtaro en-aut-sei=Abe en-aut-mei=Kohtaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Okayama University kn-affil= affil-num=16 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= en-keyword=factor Xa kn-keyword=factor Xa en-keyword=IL-6 kn-keyword=IL-6 en-keyword=proteinase-activated receptor kn-keyword=proteinase-activated receptor en-keyword=pulmonary arterial hypertension kn-keyword=pulmonary arterial hypertension en-keyword=pulmonary hypertension kn-keyword=pulmonary hypertension END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=1 article-no= start-page=e70090 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Changes in body mass index during early childhood on school‐age asthma prevalence classified by phenotypes and sex en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Few studies have explored the relationship between changes in body mass index(BMI) during early childhood and asthma prevalence divided by phenotypes and sex, and the limited results are conflicting. This study assessed the impact of BMI changes during early childhood on school-age asthma, classified by phenotypes and sex, using a nationwide longitudinal survey in Japan.
Methods: From children born in 2001 (n = 47,015), we divided participants into BMI quartiles (Q1, Q2, Q3, and Q4) and the following BMI categories: Q1Q1 (i.e., Q1 at birth and Q1 at age 7), Q1Q4, Q4Q1, Q4Q4, and others. Asthma history from ages 7 to 8 was analyzed, with bronchial asthma (BA) further categorized as allergic asthma (AA) or nonallergic asthma (NA) based on the presence of other allergic diseases. Using logistic regression, we estimated the asthma odds ratio (OR) and 95% confidence intervals (CIs) for each BMI category.
Results: Q1Q4 showed significantly higher risks of BA, AA, and NA. In boys, BA and NA risks were significantly higher in Q1Q4 (adjusted OR: 1.47 [95% CI: 1.17–1.85], at 1.56 [95% CI: 1.16–2.1]), with no significant difference in AA risk. In girls, no increased asthma risk was observed in Q1Q4, but AA risk was significantly higher in Q4Q4 (adjusted OR: 1.78 [95% CI: 1.21–2.6]).
Conclusion: Our results demonstrated that BMI changes during early childhood impact asthma risks, particularly that the risk of NA in boys increases with BMI changes during early childhood, and the risk of AA in girls increases with consistently high BMI. en-copyright= kn-copyright= en-aut-name=YabuuchiToshihiko en-aut-sei=Yabuuchi en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=asthma kn-keyword=asthma en-keyword=body mass index kn-keyword=body mass index en-keyword=child kn-keyword=child en-keyword=phenotypes kn-keyword=phenotypes en-keyword=sex kn-keyword=sex END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=2 article-no= start-page=282 end-page=289 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240917 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of a novel central venous access port for direct catheter insertion without a peel-away sheath en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose This study retrospectively evaluated the feasibility and safety of implanting a newly developed central venous access port (CV-port) that allows catheter insertion into a vein without the use of a peel-away sheath, with a focus on its potential to minimize risks associated with conventional implantation methods.
Materials and methods All procedures were performed using a new device (P-U CelSite Port™ MS; Toray Medical, Tokyo, Japan) under ultrasound guidance. The primary endpoint was the implantation success rate. The secondary endpoints were the safety and risk factors for infection in the early postprocedural period (< 30 days).
Results We assessed 523 CV-port implantations performed in a cumulative total of 523 patients (240 men and 283 women; mean age, 61.6 ± 13.1 years; range, 18–85 years). All implantations were successfully performed using an inner guide tube and over-the-wire technique through 522 internal jugular veins and one subclavian vein. The mean procedural time was 33.2 ± 10.9 min (range 15–112 min). Air embolism, rupture/perforation of the superior vena cava, or hemothorax did not occur during catheter insertion. Eleven (2.1%) intraprocedural complications occurred, including Grade I arrhythmia (n = 8) and subcutaneous bleeding (n = 1), Grade II arrhythmia (n = 1), and Grade IIIa pneumothorax (n = 1). Furthermore, 496 patients were followed up for ≥ 30 days. Six early postprocedural complications were encountered (1.1%), including Grade IIIa infection (n = 4), catheter occlusion (n = 1), and skin necrosis due to subcutaneous leakage of trabectedin (n = 1). These six CV-ports were withdrawn, and no significant risk factors for infection in the early postprocedural period were identified.
Conclusion The implantation of this CV-port device demonstrated comparable success and complication rates to conventional devices, with the added potential benefit of eliminating complications associated with the use of a peel-away sheath. en-copyright= kn-copyright= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawabataTakahiro en-aut-sei=Kawabata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkamotoSoichiro en-aut-sei=Okamoto en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MunetomoKazuaki en-aut-sei=Munetomo en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Central venous catheters kn-keyword=Central venous catheters en-keyword=Vascular access device kn-keyword=Vascular access device en-keyword=Treatment outcome kn-keyword=Treatment outcome en-keyword=Safety kn-keyword=Safety END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=7661 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240916 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurotransmitter recognition by human vesicular monoamine transporter 2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Human vesicular monoamine transporter 2 (VMAT2), a member of the SLC18 family, plays a crucial role in regulating neurotransmitters in the brain by facilitating their uptake and storage within vesicles, preparing them for exocytotic release. Because of its central role in neurotransmitter signalling and neuroprotection, VMAT2 is a target for neurodegenerative diseases and movement disorders, with its inhibitor being used as therapeutics. Despite the importance of VMAT2 in pharmacophysiology, the molecular basis of VMAT2-mediated neurotransmitter transport and its inhibition remains unclear. Here we show the cryo-electron microscopy structure of VMAT2 in the substrate-free state, in complex with the neurotransmitter dopamine, and in complex with the inhibitor tetrabenazine. In addition to these structural determinations, monoamine uptake assays, mutational studies, and pKa value predictions were performed to characterize the dynamic changes in VMAT2 structure. These results provide a structural basis for understanding VMAT2-mediated vesicular transport of neurotransmitters and a platform for modulation of current inhibitor design. en-copyright= kn-copyright= en-aut-name=ImDohyun en-aut-sei=Im en-aut-mei=Dohyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JormakkaMika en-aut-sei=Jormakka en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JugeNarinobu en-aut-sei=Juge en-aut-mei=Narinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KishikawaJun-ichi en-aut-sei=Kishikawa en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTakayuki en-aut-sei=Kato en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugitaYukihiko en-aut-sei=Sugita en-aut-mei=Yukihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NodaTakeshi en-aut-sei=Noda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UemuraTomoko en-aut-sei=Uemura en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShiimuraYuki en-aut-sei=Shiimura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsadaHidetsugu en-aut-sei=Asada en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IwataSo en-aut-sei=Iwata en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=3 en-affil=Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University kn-affil= affil-num=4 en-affil=Department of Applied Biology, Kyoto Institute of Technology kn-affil= affil-num=5 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=6 en-affil=Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University kn-affil= affil-num=7 en-affil=Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University kn-affil= affil-num=8 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=9 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=10 en-affil=Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University kn-affil= affil-num=11 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=12 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=5 article-no= start-page=567 end-page=579 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ChatGPT Responses to Clinical Questions in the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Disease 2022 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Artificial intelligence is increasingly used in the medical field. We assessed the accuracy and reproducibility of responses by ChatGPT to clinical questions (CQs) in the Japan Atherosclerosis Society Guidelines for Prevention Atherosclerotic Cardiovascular Diseases 2022 (JAS Guidelines 2022).
Methods: In June 2024, we assessed responses by ChatGPT (version 3.5) to CQs, including background questions (BQs) and foreground questions (FQs). Accuracy was assessed independently by three researchers using six-point Likert scales ranging from 1 (“completely incorrect”) to 6 (“completely correct”) by evaluating responses to CQs in Japanese or translated into English. For reproducibility assessment, responses to each CQ asked five times separately in a new chat were scored using six-point Likert scales, and Fleiss kappa coefficients were calculated.
Results: The median (25th–75th percentile) score for ChatGPT’s responses to BQs and FQs was 4 (3–5) and 5 (5–6) for Japanese CQs and 5 (3–6) and 6 (5–6) for English CQs, respectively. Response scores were higher for FQs than those for BQs (P values <0.001 for Japanese and English). Similar response accuracy levels were observed between Japanese and English CQs (P value 0.139 for BQs and 0.586 for FQs). Kappa coefficients for reproducibility were 0.76 for BQs and 0.90 for FQs.
Conclusions: ChatGPT showed high accuracy and reproducibility in responding to JAS Guidelines 2022 CQs, especially FQs. While ChatGPT primarily reflects existing guidelines, its strength could lie in rapidly organizing and presenting relevant information, thus supporting instant and more efficient guideline interpretation and aiding in medical decision-making. en-copyright= kn-copyright= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukudaMari en-aut-sei=Fukuda en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KinutaMinako en-aut-sei=Kinuta en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KandaHideyuki en-aut-sei=Kanda en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Autonomic intelligence kn-keyword=Autonomic intelligence en-keyword=ChatGPT kn-keyword=ChatGPT en-keyword=Accuracy kn-keyword=Accuracy en-keyword=Reproducibility kn-keyword=Reproducibility en-keyword=Guidelines kn-keyword=Guidelines END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Several prospective studies have evaluated the benefit of primary tumour resection (PTR) in de novo Stage IV breast cancer (BC) patients, but it remains controversial. We aimed to investigate whether PTR improves the survival of de novo stage IV BC patients.
Methods: De novo stage IV BC patients were enrolled in the first registration and received systemic therapies according to clinical subtypes. Patients without progression after primary systemic therapy for 3 months were randomly assigned 1:1 to systemic therapy alone (arm A) or PTR plus systemic therapy (arm B). The primary endpoint was overall survival (OS), and the secondary endpoints included local relapse-free survival (LRFS).
Results: Five hundred seventy patients were enrolled between May 5, 2011, and May 31, 2018. Of these, 407 were randomised to arm A (N = 205) or arm B (N = 202). The median follow-up time of all randomised patients was 60 months. The difference in OS was not statistically significant (HR 0.86 90% CI 0.69–1.07, one-sided p = 0.13). Median OS was 69 months (arm A) and 75 months (arm B). In the subgroup analysis, PTR was associated with improved OS in pre-menopausal patients, or those with single-organ metastasis. LRFS in arm B was significantly longer than that in arm A (median LRFS 20 vs. 63 months: HR 0.42, 95% CI 0.33–0.53, p < 0.0001). There were no treatment-related deaths.
Conclusions: PTR did not prolong OS. However, it improved local control and might benefit a subset of patients, such as those with premenopausal status or with single-organ metastasis. It also improved local relapse-free survival (LRFS), which is a clinically meaningful outcome in trials of systemic therapy.
Clinical trial registration: UMIN Clinical Trials Registry (UMIN000005586); Japan Registry of Clinical Trials (jRCTs031180151). en-copyright= kn-copyright= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AogiKenjiro en-aut-sei=Aogi en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanagidaYasuhiro en-aut-sei=Yanagida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuneizumiMichiko en-aut-sei=Tsuneizumi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoNaohito en-aut-sei=Yamamoto en-aut-mei=Naohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SutoAkihiko en-aut-sei=Suto en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeKenichi en-aut-sei=Watanabe en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraoMichiko en-aut-sei=Harao en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanbayashiChizuko en-aut-sei=Kanbayashi en-aut-mei=Chizuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ItohMitsuya en-aut-sei=Itoh en-aut-mei=Mitsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KadoyaTakayuki en-aut-sei=Kadoya en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AnanKeisei en-aut-sei=Anan en-aut-mei=Keisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaShigeto en-aut-sei=Maeda en-aut-mei=Shigeto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OgawaGakuto en-aut-sei=Ogawa en-aut-mei=Gakuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SajiShigehira en-aut-sei=Saji en-aut-mei=Shigehira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaHaruhiko en-aut-sei=Fukuda en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Okayama University Hospital kn-affil= affil-num=2 en-affil=Cancer Institute Hospital kn-affil= affil-num=3 en-affil=National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Shizuoka General Hospital kn-affil= affil-num=5 en-affil=Gunma Prefectural Cancer Center kn-affil= affil-num=6 en-affil=Chiba Prefectural Cancer Center kn-affil= affil-num=7 en-affil=Saitama Prefectural Cancer Center kn-affil= affil-num=8 en-affil=National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Hokkaido Cancer Center kn-affil= affil-num=10 en-affil=Jichi Medical University Hospital kn-affil= affil-num=11 en-affil=Niigata Prefectural Cancer Center kn-affil= affil-num=12 en-affil=Hiroshima City Hiroshima Citizen’s Hospital kn-affil= affil-num=13 en-affil=Hiroshima University Hospital kn-affil= affil-num=14 en-affil=Kitakyushu Municipal Medical Center kn-affil= affil-num=15 en-affil=Nagasaki Municipal Medical Center kn-affil= affil-num=16 en-affil=National Cancer Center Hospital kn-affil= affil-num=17 en-affil=National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Fukushima Medical University kn-affil= affil-num=19 en-affil=National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Aichi Cancer Center Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=4 article-no= start-page=630 end-page=637 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250526 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immediate breast reconstruction surgery for breast cancer: current status and future directions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Immediate breast reconstruction (IBR) has become increasingly recognized in Japan as an important component of breast cancer care, improving patients’ quality of life after mastectomy. While the adoption of IBR is growing, the reconstruction rate in Japan remains lower than in Western countries. To clarify the current practice and challenges, the Japanese Breast Cancer Society (JBCS) conducted a nationwide survey.
Methods We conducted a comprehensive web-based questionnaire survey among all JBCS-certified institutions between December 2020 and February 2021. The survey assessed institutional capabilities, surgical techniques, decision-making criteria for BR, and the integration of adjuvant therapy.
Results A total of 429 institutions responded, with 72.5% offering BR and 61.7% capable of providing immediate reconstruction. Nipple-sparing mastectomy (NSM) was performed at 73.7% of institutions offering reconstruction. Multidisciplinary conferences with plastic surgeons were held at 70.5% of institutions. Approximately 30% of institutions discontinued IBR if sentinel lymph node metastases were detected intraoperatively, and 62.8% avoided recommending IBR for patients likely to require postoperative radiation therapy. In 94% of institutions, BR did not cause delays in the administration of adjuvant chemotherapy. However, 15% of institutions modified their radiation therapy approach in reconstructed patients. Additionally, 27% of physicians still believed that BR could negatively affect prognosis.
Conclusions The survey confirmed that IBR is widely performed and feasible in Japan. However, institutional differences, limited access to plastic surgeons, and persistent misconceptions remain significant barriers. Strengthening multidisciplinary collaboration and establishing standardized guidelines will help improve BR rates and patient outcomes in Japan. en-copyright= kn-copyright= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NogiHiroko en-aut-sei=Nogi en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgiyaAkiko en-aut-sei=Ogiya en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshitobiMakoto en-aut-sei=Ishitobi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamauchiChikako en-aut-sei=Yamauchi en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimoAyaka en-aut-sei=Shimo en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaruiKazutaka en-aut-sei=Narui en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NaguraNaomi en-aut-sei=Nagura en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SekiHirohito en-aut-sei=Seki en-aut-mei=Hirohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaigaMiho en-aut-sei=Saiga en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UchidaTatsuya en-aut-sei=Uchida en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SasadaShinsuke en-aut-sei=Sasada en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SakuraiTeruhisa en-aut-sei=Sakurai en-aut-mei=Teruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NiikuraNaoki en-aut-sei=Niikura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MoriHiroki en-aut-sei=Mori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Breast and Endocrine Surgery, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Japanese Red Cross Medical Center kn-affil= affil-num=4 en-affil=Department of Breast Surgery, Mie University School of Medicine kn-affil= affil-num=5 en-affil=Department of Radiation Oncology, Shiga General Hospital kn-affil= affil-num=6 en-affil=Department of Breast and Endocrine Surgery, St. Marianna University School of Medicine kn-affil= affil-num=7 en-affil=Department of Breast and Thyroid Surgery, Medical Center, Yokohama City University kn-affil= affil-num=8 en-affil=Department of Breast Surgical Oncology, St Luke’s International Hospital kn-affil= affil-num=9 en-affil=Department of Breast Surgery, Kyorin University School of Medicine kn-affil= affil-num=10 en-affil=Department of Breast and Endocrine Surgery, Akita University Hospital kn-affil= affil-num=11 en-affil=Department of Plastic Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Plastic Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=14 en-affil=Sakurai Breast Clinic kn-affil= affil-num=15 en-affil=Department of Breast Oncology, Tokai University School of Medicine kn-affil= affil-num=16 en-affil=Department of Plastic and Reconstructive Surgery, Tokyo Medical and Dental University kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Immediate reconstruction surgery kn-keyword=Immediate reconstruction surgery en-keyword=Prognosis kn-keyword=Prognosis en-keyword=Complications kn-keyword=Complications END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=2 article-no= start-page=53 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bisphenol A diglycidyl ether (BADGE) is the main component of epoxy resin and is used for the inner coating of canned foods and plastic food containers. BADGE can easily migrate from containers and result in food contamination; the compound is known as an endocrine-disrupting chemical. We previously reported that maternal exposure to bisphenol A bis (2,3-dihydroxypropyl) ether (BADGE·2H2O), which is the most detected BADGE derivative not only in canned foods but also in human specimens, during gestation and lactation, could accelerate neuronal differentiation in the cortex of fetuses and induce anxiety-like behavior in juvenile mice. In this study, we investigated the effects of low-dose BADGE·2H2O (1–100 pM) treatment on neurites and the mechanism of neurite outgrowth in cortical neurons. BADGE·2H2O exposure significantly increased the number of dendrites and neurite length in cortical neurons; these accelerating effects were inhibited by estrogen receptor (ER) antagonist ICI 182,780 and G-protein-coupled estrogen receptor (GPER) antagonist G15. BADGE·2H2O down-regulated Hes1 expression, which is a transcriptional repressor, and increased levels of neuritogenic factor neurogenin-3 (Ngn3) in the cortical neurons; the changes were significantly blocked by G15. These data suggest that direct BADGE·2H2O exposure can accelerate neuritogenesis and outgrowth in cortical neurons through down-regulation of Hes1 and by increasing Ngn3 levels through ERs, particularly GPER. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiyamaChiharu en-aut-sei=Nishiyama en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagoshiTakeru en-aut-sei=Nagoshi en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakoAkane en-aut-sei=Miyako en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OnoSuzuka en-aut-sei=Ono en-aut-mei=Suzuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MisawaIchika en-aut-sei=Misawa en-aut-mei=Ichika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IsseAika en-aut-sei=Isse en-aut-mei=Aika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TomimotoKana en-aut-sei=Tomimoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ZenshoKazumasa en-aut-sei=Zensho en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=7 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=8 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=BADGE kn-keyword=BADGE en-keyword=neurite outgrowth kn-keyword=neurite outgrowth en-keyword=estrogen receptor kn-keyword=estrogen receptor en-keyword=GPER kn-keyword=GPER en-keyword=Hes1 kn-keyword=Hes1 en-keyword=neurogenin-3 kn-keyword=neurogenin-3 END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=e003250 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical impact of combined assessment of myocardial inflammation and fibrosis using myocardial biopsy in patients with dilated cardiomyopathy: a multicentre, retrospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Among patients with dilated cardiomyopathy (DCM), myocardial inflammation and fibrosis are risk factors for poor clinical outcomes. Here, we investigated the combined prognostic value of these two factors, as evaluated using myocardial biopsy samples.
Methods This retrospective and multicentre study included patients with DCM—defined as LVEF of ≤45% and left diastolic diameter of >112% of predicted value, without evidence of secondary or ischaemic cardiomyopathy. In myocardial biopsy samples, inflammatory cells were counted using immunohistochemistry, and Masson’s Trichrome staining was performed to quantify the myocardial fibrosis as collagen area fraction (CAF). Higher myocardial inflammation was defined as leucocytes of ≥14/mm², including ≤4 monocytes/mm², with CD3+ T lymphocytes of≥7/mm². Greater myocardial fibrosis was defined as CAF of>5.9% by the Youden’s index. The primary endpoint was cardiac death or left ventricular assist device implantation.
Results A total of 255 DCM patients were enrolled (average age, 53.1 years; 78% males). Within this cohort, the mean LVEF was 28.0%, mean CAF was 10.7% and median CD3+ cell count was 8.3/mm2. During the median follow-up period of 2688 days, 46 patients met the primary endpoint. Multivariable Cox proportional hazard analyses revealed that CD3+ cell count and CAF were independent determinants of the primary endpoint. Kaplan–Meier analysis showed that patients with both higher myocardial inflammation and greater fibrosis had the worst prognosis (log-rank p<0.001). When myocardial inflammation was graded as one of three degrees: T lymphocytes of <13/mm² (low); 13 of 13.1–23.9/mm² (moderate); and T lymphocytes of ≥24 /mm² (high), patients with moderate inflammation exhibited a superior survival rate when CAF was ≤5.9%, but a worse survival rate when CAF was >5.9%.
Conclusions Having both biopsy-proven higher myocardial inflammation and greater fibrosis predicted the worst clinical prognosis in patients with DCM. en-copyright= kn-copyright= en-aut-name=NakayamaTakafumi en-aut-sei=Nakayama en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgoKeiko Ohta en-aut-sei=Ogo en-aut-mei=Keiko Ohta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuganoYasuo en-aut-sei=Sugano en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokokawaTetsuro en-aut-sei=Yokokawa en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanamoriHiromitsu en-aut-sei=Kanamori en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkedaYoshihiko en-aut-sei=Ikeda en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiroeMichiaki en-aut-sei=Hiroe en-aut-mei=Michiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HatakeyamaKinta en-aut-sei=Hatakeyama en-aut-mei=Kinta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Ishibashi-UedaHatsue en-aut-sei=Ishibashi-Ueda en-aut-mei=Hatsue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DohiKaoru en-aut-sei=Dohi en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AnzaiToshihisa en-aut-sei=Anzai en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SeoYoshihiro en-aut-sei=Seo en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Imanaka-YoshidaKyoko en-aut-sei=Imanaka-Yoshida en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Cardiology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=3 en-affil=Department of Cardiology, Keiyu Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Fukushima Medical University kn-affil= affil-num=5 en-affil=Department of Cardiology, Gifu University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=7 en-affil=Department of Cardiology, National Center for Global Health and Medicine kn-affil= affil-num=8 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=9 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=10 en-affil=Center for Advanced Heart Failure, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Cardiology and Nephrology, Mie University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Cardiology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=14 en-affil=Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=1 article-no= start-page=64 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluating a discretized data acquisition method for couch modeling to streamline the commissioning process of radiological instruments en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The commissioning of radiotherapy treatment planning system (RTPS) involves many time-consuming tests to maintain consistency between actual and planned dose. As the number of new technologies and peripheral devices increases year by year, there is a need for time-efficient and accurate commissioning of radiation therapy equipment. Couch modeling is one type of commissioning, and there are no recommended values for CT due to differences in equipment calibration between facilities. This study evaluated the optimal electron density (ED) for the couch using discretized gantry angles.
Results All discrete-angle groups showed a high correlation between the surface ED and dose difference between the actual and planned doses (|r|> 0.9). AcurosXB did not demonstrate a significant correlation between dose differences and each energy. For a small number of discretized gantry groups, the optimal couch modeling results revealed several combinations of surface and interior ED with the same score. Upon adding all couch thickness scores, all energy scores, and both algorithm scores, the optimal surface and interior EDs with the highest score across all couch thicknesses were 0.4 and 0.07, respectively.
Conclusions The optimal couch surface ED dose difference trend was identified, and the effectiveness indicated using the dose difference score from discrete-angle couch modeling. Using this method, couch modeling can be evaluated in a highly precise and quick manner, which helps in the commissioning of complicated linear accelerator and radiological treatment plans. en-copyright= kn-copyright= en-aut-name=TomimotoSyouta en-aut-sei=Tomimoto en-aut-mei=Syouta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaekiYusuke en-aut-sei=Saeki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotodaOkihiro en-aut-sei=Motoda en-aut-mei=Okihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaMasato en-aut-sei=Tanaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsumotoSyouki en-aut-sei=Tsumoto en-aut-mei=Syouki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishikawaHana en-aut-sei=Nishikawa en-aut-mei=Hana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyashimaYuki en-aut-sei=Miyashima en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiguchiMakiko en-aut-sei=Higuchi en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TaniTadashi en-aut-sei=Tani en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=4 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=8 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=10 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=11 en-affil=Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=Couch modeling kn-keyword=Couch modeling en-keyword=Commissioning kn-keyword=Commissioning en-keyword=Attenuation of couch kn-keyword=Attenuation of couch en-keyword=Linear accelerator kn-keyword=Linear accelerator en-keyword=Radiotherapy planning system kn-keyword=Radiotherapy planning system END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=2 article-no= start-page=606 end-page=617 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanistic Insights Into Oxidative Response of Heat Shock Factor 1 Condensates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heat shock factor 1 (Hsf1), a hub protein in the stress response and cell fate decisions, senses the strength, type, and duration of stress to balance cell survival and death through an unknown mechanism. Recently, changes in the physical property of Hsf1 condensates due to persistent stress have been suggested to trigger apoptosis, highlighting the importance of biological phase separation and transition in cell fate decisions. In this study, the mechanism underlying Hsf1 droplet formation and oxidative response was investigated through 3D refractive index imaging of the internal architecture, corroborated by molecular dynamics simulations and biophysical/biochemical experiments. We found that, in response to oxidative conditions, Hsf1 formed liquid condensates that suppressed its internal mobility. Furthermore, these conditions triggered the hyper-oligomerization of Hsf1, mediated by disulfide bonds and secondary structure stabilization, leading to the formation of dense core particles in the Hsf1 droplet. Collectively, these data demonstrate how the physical property of Hsf1 condensates undergoes an oxidative transition by sensing redox conditions to potentially drive cell fate decisions. en-copyright= kn-copyright= en-aut-name=KawagoeSoichiro en-aut-sei=Kawagoe en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsusakiMotonori en-aut-sei=Matsusaki en-aut-mei=Motonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MabuchiTakuya en-aut-sei=Mabuchi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgasawaraYuto en-aut-sei=Ogasawara en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshimoriKoichiro en-aut-sei=Ishimori en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaioTomohide en-aut-sei=Saio en-aut-mei=Tomohide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=2 en-affil=Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=3 en-affil=Frontier Research Institute for Interdisciplinary Sciences, Tohoku University kn-affil= affil-num=4 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Chemistry, Faculty of Science, Hokkaido University kn-affil= affil-num=7 en-affil=Institute of Advanced Medical Sciences, Tokushima University kn-affil= en-keyword=heat shock factor 1 kn-keyword=heat shock factor 1 en-keyword=oxidative hyper-oligomerization kn-keyword=oxidative hyper-oligomerization en-keyword=biological phase transition kn-keyword=biological phase transition en-keyword=stress response kn-keyword=stress response en-keyword=biophysics kn-keyword=biophysics END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=15 article-no= start-page=2290 end-page=2294 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and Genetic Analyses of SPG7 in Japanese Patients with Undiagnosed Ataxia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Spastic paraplegia 7 (SPG7) is an autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in SPG7. It is predominantly characterized by adult-onset slowly progressive spastic paraparesis. While SPG7 presenting with ataxia with or without spasticity is relatively common in Europe and North America, it is considered rare in Japan. This study aimed to identify SPG7 patients among those with undiagnosed ataxia within the Japanese population.
Methods We retrospectively selected 351 patients with undiagnosed ataxia, excluding those with secondary and common spinocerebellar ataxia. Whole-exome sequence analysis was conducted, and homozygosity of the identified variants was confirmed using droplet digital polymerase chain reaction (ddPCR).
Results Among the 351 patients, 2 were diagnosed with SPG7, and homozygosity was confirmed by ddPCR. Both patients carried homozygous pathogenic variants in SPG7: c.1948G>A, p.Asp650Asn, and c.1192C>T, p.Arg398Ter (NM_003119.4). Clinically, both patients presented with progressive ataxia. In addition, Patient 1 exhibited partial ophthalmoplegia and spastic paraparesis, whereas Patient 2 demonstrated cerebellar ataxia without spasticity.
Conclusion The rarity of SPG7 in Japan may be attributed to variation in the minor allele frequency of the c.1529C>T, p.Ala510Val variant, which is more prevalent in Europe and North America than in other areas. en-copyright= kn-copyright= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HinoRimi en-aut-sei=Hino en-aut-mei=Rimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujinoGo en-aut-sei=Fujino en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaiYuto en-aut-sei=Sakai en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=K. IwataNobue en-aut-sei=K. Iwata en-aut-mei=Nobue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, International University of Health and Welfare Mita Hospital kn-affil= affil-num=6 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, International University of Health and Welfare Mita Hospital kn-affil= affil-num=9 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=cerebellar ataxia kn-keyword=cerebellar ataxia en-keyword=spastic paraparesis kn-keyword=spastic paraparesis en-keyword=whole-exome sequence analysis kn-keyword=whole-exome sequence analysis en-keyword=SPG7 kn-keyword=SPG7 END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=10 article-no= start-page=1151 end-page=1159 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=NCF-1 plays a pivotal role in the survival of adenocarcinoma cells of pancreatic and gastric origins en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reactive oxygen species (ROS) play a pivotal biological role in cells, with ROS function differing depending on cellular conditions and the extracellular environment. Notably, ROS act as cytotoxic factors to eliminate infectious pathogens or promote cell death under cellular stress, while also facilitating cell growth (via ROS-sensing pathways) by modifying gene expression. Among ROS-related genes, neutrophil cytosolic factor-1 (NCF-1; p47phox) was identified as a ROS generator in neutrophils. This product is a subunit of a cytosolic NADPH oxidase complex activated in response to pathogens such as bacteria and viruses. NCF-1 has been examined primarily in terms of ROS-production pathways in macrophages and neutrophils; however, the expression of this protein and its biological role in cancer cells remain unclear. Here, we report expression of NCF-1 in pancreatic and gastric cancers, and demonstrate its biological significance in these tumor cells. Abundant expression of NCF-1 was observed in pancreatic adenocarcinoma (PDAC) lines and in patient tissues, as well as in gastric adenocarcinomas. Accumulation of the protein was also detected in the invasive/metastatic foci of these tumors. Unexpectedly, BxPC-3 underwent apoptotic cell death when transfected with a small interfering RNA (siRNA) specific to NCF-1, whereas the cells treated with a control siRNA proliferated in a time-dependent manner. A similar phenomenon was observed in HSC-58, a poorly differentiated gastric adenocarcinoma line. Consequently, the tumor cells highly expressing NCF-1 obtained coincident accumulation of ROS and reduced glutathione (GSH) with expression of glutathione peroxidase 4 (GPX4), a quencher involved in ferroptosis. Unlike the conventional role of ROS as a representative cytotoxic factor, these findings suggest that NCF-1-mediated ROS generation may be required for expansive growth of PDAC and gastric cancers. en-copyright= kn-copyright= en-aut-name=Furuya-IkudeChiemi en-aut-sei=Furuya-Ikude en-aut-mei=Chiemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KittaAkane en-aut-sei=Kitta en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomonobuNaoko en-aut-sei=Tomonobu en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawasakiYoshihiro en-aut-sei=Kawasaki en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=2 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= en-keyword=NCF-1 (p47phox) kn-keyword=NCF-1 (p47phox) en-keyword=ROS kn-keyword=ROS en-keyword=Cancer kn-keyword=Cancer en-keyword=Tumor growth kn-keyword=Tumor growth en-keyword=Apoptosis kn-keyword=Apoptosis END start-ver=1.4 cd-journal=joma no-vol=472 cd-vols= no-issue= article-no= start-page=123486 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical, neuroimaging and genetic findings in the Japanese case series of CLCN2-related leukoencephalopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Biallelic loss-of-function variants in CLCN2 lead to CLCN2-related leukoencephalopathy (CC2L), also called leukoencephalopathy with ataxia (LKPAT). CC2L is characterized clinically by a spectrum of clinical presentations including childhood- to adult-onset mild ataxia, spasticity, cognitive decline, and vision loss as well as typical MRI findings of symmetrical high signal intensities on the DWIs/T2WIs of the middle cerebellar peduncles (MCPs). We searched for pathogenic variants of CLCN2 in a case series of undiagnosed leukoencephalopathy accompanied by MCP signs, which led to the identification of four Japanese patients with CC2L. All the patients carried at least one allele of c.61dupC (p.Leu21Profs*27) in CLCN2, including compound heterozygosity with either the novel pathogenic variant c.983 + 2 T > A or the previously reported pathogenic variant c.1828C > T (p.Arg610*). Of note, all the four previously reported cases from Japan also harbored c.61dupC, and no reports of this variant have been documented from outside Japan. The allele frequency of c.61dupC in the Japanese population is 0.002152, raising the possibility of a relatively high prevalence of CC2L in Japan. Patients in this study developed symptoms after the age of 30, and demonstrated neurological signs including cerebellar ataxia, pyramidal signs, and mild cognitive impairment, consistent with previous reports. One male patient had two children, supporting preserved fertility, and another patient had calcifications in the cerebral and cerebellar surfaces. These findings provide valuable insights into the broader clinical and genetic spectra of CC2L in the Japanese population, and emphasize the importance of considering this disease in the differential diagnoses of leukoencephalopathy with MCP signs. en-copyright= kn-copyright= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChoTakusei en-aut-sei=Cho en-aut-mei=Takusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaruseHiroya en-aut-sei=Naruse en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakiyamaYoshio en-aut-sei=Sakiyama en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SumiKensho en-aut-sei=Sumi en-aut-mei=Kensho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchioNaohiro en-aut-sei=Uchio en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatakeAkane en-aut-sei=Satake en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakiyamaYoshihisa en-aut-sei=Takiyama en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsushitaTakuya en-aut-sei=Matsushita en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OmaeYosuke en-aut-sei=Omae en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KawaiYosuke en-aut-sei=Kawai en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TokunagaKatsushi en-aut-sei=Tokunaga en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Division of Neurology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, Mitsui Memorial Hospital kn-affil= affil-num=8 en-affil=Department of Neurology, Mitsui Memorial Hospital kn-affil= affil-num=9 en-affil=Department of Neurology, Fuefuki Central Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Fuefuki Central Hospital kn-affil= affil-num=11 en-affil=Department of Neurology, Kochi Medical School, Kochi University kn-affil= affil-num=12 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=13 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=14 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=15 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=16 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=17 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=Leukodystrophy kn-keyword=Leukodystrophy en-keyword=CC2L kn-keyword=CC2L en-keyword=CLCN2 kn-keyword=CLCN2 en-keyword=MCP sign kn-keyword=MCP sign END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=e261 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alcohol consumption, multiple Lugol‐voiding lesions, and field cancerization en-subtitle= kn-subtitle= en-abstract= kn-abstract=The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol-voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol-voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol-voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC. en-copyright= kn-copyright= en-aut-name=KatadaChikatoshi en-aut-sei=Katada en-aut-mei=Chikatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyamaTetsuji en-aut-sei=Yokoyama en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoTomonori en-aut-sei=Yano en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHaruhisa en-aut-sei=Suzuki en-aut-mei=Haruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurueYasuaki en-aut-sei=Furue en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoKeiko en-aut-sei=Yamamoto en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoyamaHisashi en-aut-sei=Doyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoikeTomoyuki en-aut-sei=Koike en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamaokiMasashi en-aut-sei=Tamaoki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawataNoboru en-aut-sei=Kawata en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraoMotohiro en-aut-sei=Hirao en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OgataTakashi en-aut-sei=Ogata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatagiriAtsushi en-aut-sei=Katagiri en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamanouchiTakenori en-aut-sei=Yamanouchi en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KiyokawaHirofumi en-aut-sei=Kiyokawa en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawakuboHirofumi en-aut-sei=Kawakubo en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KonnoMaki en-aut-sei=Konno en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhashiShinya en-aut-sei=Ohashi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KondoYuki en-aut-sei=Kondo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KishimotoYo en-aut-sei=Kishimoto en-aut-mei=Yo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KanoKoichi en-aut-sei=Kano en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MureKanae en-aut-sei=Mure en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HayashiRyuichi en-aut-sei=Hayashi en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IshikawaHideki en-aut-sei=Ishikawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MutoManabu en-aut-sei=Muto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Health and Promotion, National Institute of Public Health kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=6 en-affil=Division of Endoscopy, Hokkaido University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Ishikawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=10 en-affil=Division of Endoscopy, Shizuoka Cancer Center kn-affil= affil-num=11 en-affil=Department of Surgery, National Hospital Organization Osaka National Hospital kn-affil= affil-num=12 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=14 en-affil=Department of Medicine, Division of Gastroenterology, Showa University Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Kumamoto Regional Medical Center kn-affil= affil-num=16 en-affil=Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= affil-num=17 en-affil=Department of Surgery, Kawasaki Municipal Kawasaki Hospital kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Tochigi Cancer Center kn-affil= affil-num=19 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=20 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=22 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital kn-affil= affil-num=23 en-affil=Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine kn-affil= affil-num=24 en-affil=Department of Public Health, Wakayama Medical University School of Medicine kn-affil= affil-num=25 en-affil=Department of Head and Neck Surgery, National Cancer Center Hospital East kn-affil= affil-num=26 en-affil=Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine kn-affil= affil-num=27 en-affil=Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=28 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=alcohol kn-keyword=alcohol en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=field cancerization kn-keyword=field cancerization en-keyword=head and neck cancer kn-keyword=head and neck cancer en-keyword=JEC study kn-keyword=JEC study END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=8 article-no= start-page=e18026 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Commissioning of respiratory‐gated 4D dynamic dose calculations for various gating widths without spot timestamp in proton pencil beam scanning en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Proton pencil beam scanning (PBS) is susceptible to dose degradation because of interplay effects on moving targets. For cases of unacceptable motion, respiratory-gated (RG) irradiation is an effective alternative to free breathing (FB) irradiation. However, the introduction of RG irradiation with larger gate widths (GW) is hindered by interplay effects, which are analogous to those observed with FB irradiation. Accurate estimation of interplay effects can be performed by recording spot timestamps. However, our machine lacks this feature, making it imperative to find an alternative approach. Thus, we developed an RG 4-dimensional dynamic dose (RG-4DDD) system without spot timestamps.
Purpose: This study aimed to investigate the accuracy of calculated doses from the RG-4DDD system for PBS plans with varying breathing curves, amplitudes, and periods for 10%–50% GW.
Methods: RG-4DDDs were reconstructed using in-house developed software that assigned timestamps to individual spots, integrated start times for spills with breathing curves, and utilized deformable registrations for dose accumulation. Three cubic verification plans were created using a heterogeneous phantom. Additionally, typical liver and lung cases were employed for patient plan validation. Single- and multi-field-optimized (SFO and IMPT) plans (ten beams in total) were created for the liver and lung cases in a homogeneous phantom. Lateral profile measurements were obtained under both motion and no-motion conditions using a 2D ionization chamber array (2D-array) and EBT3 Gafchromic films on the CIRS dynamic platform. Breathing curves from the cubic plans were used to assess nine patterns of sine curves, with amplitudes of 5.0–10.0 mm (10.0–20.0 mm target motions) and periods of 3–6 sec. Patient field verifications were conducted using a representative patient curve with an average amplitude of 6.4 mm and period of 3.2 sec. Additional simulations were performed assuming a ± 10% change in assigned timestamps for the dose rate (DR), spot spill (0.08-s), and gate time delay (0.1-s) to evaluate the effect of parameter selection on our 4DDD models. The 4DDDs were compared with measured values using the 2D gamma index and absolute doses over that required for dosing 95% of the target.
Results: The 2D-array measurements showed that average gamma scores for the reference (no motion) and 4DDD plans for all GWs were at least 99.9 ± 0.2% and 98.2 ± 2.4% at 3%/3 mm, respectively. The gamma scores of the 4DDDs in film measurements exceeded 95.4% and 92.9% at 2%/2 mm for the cubic and patient plans, respectively. The 4DDD calculations were acceptable under DR changes of ±10% and both spill and gate time delays of ±0.18 sec. For the 4DDD plan using all GWs for all measurement points, the absolute point differences for all validation plans were within ±5.0% for 99.1% of the points.
Conclusions: The RG-4DDD calculations (less than 50% GW) of the heterogeneous and actual patient plans showed good agreement with measurements for various breathing curves in the amplitudes and periods described above. The proposed system allows us to evaluate actual RG irradiation without requiring the ability to record spot timestamps. en-copyright= kn-copyright= en-aut-name=TominagaYuki en-aut-sei=Tominaga en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakisakaYushi en-aut-sei=Wakisaka en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoTakahiro en-aut-sei=Kato en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchiharaMasaya en-aut-sei=Ichihara en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasuiKeisuke en-aut-sei=Yasui en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SasakiMotoharu en-aut-sei=Sasaki en-aut-mei=Motoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OitaMasataka en-aut-sei=Oita en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishioTeiji en-aut-sei=Nishio en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic kn-affil= affil-num=2 en-affil=Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic kn-affil= affil-num=3 en-affil=Department of Radiological Sciences, School of Health Sciences, Fukushima Medical University kn-affil= affil-num=4 en-affil=Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka kn-affil= affil-num=5 en-affil=School of Medical Sciences, Fujita Health University kn-affil= affil-num=6 en-affil=Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=7 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka kn-affil= en-keyword=4D dynamic dose kn-keyword=4D dynamic dose en-keyword=interplay effect kn-keyword=interplay effect en-keyword=pencil beam scanning kn-keyword=pencil beam scanning en-keyword=proton therapy kn-keyword=proton therapy en-keyword=respiratory gating kn-keyword=respiratory gating END start-ver=1.4 cd-journal=joma no-vol=238 cd-vols= no-issue= article-no= start-page=113243 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bone-enhanced high contrast X-ray images derived from attenuation estimation related to ultra-low energy X-rays – An application of an energy-resolving photon-counting detector (ERPCD) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: X-ray diagnosis in medicine is often used for bone diagnosis based on qualitative observation analysis. However, there are often cases where the contrast of bones is reduced because of the existence of soft-tissues, making it difficult to accurately diagnose the bone conditions. Although the algorithm for bone extraction images was proposed using an energy-resolving photon-counting detector (ERPCD), this algorithm can depict “one” bone material (such as hydroxyapatite under the assumption), and it is difficult to adequately depict other components. The purpose of this study is to develop an algorithm for bone-enhanced high-contrast images that can be virtually represented by the attenuation of extremely low-energy X-rays without making any special assumptions.
Methods: High-contrast images were virtually generated based on the attenuation rate of ultra-low energy X-rays. It was determined by fitting the mass attenuation coefficient (μ/ρ) curve to the X-ray attenuation values (μt values) measured at middle (30–40 keV) and high (40–60 keV) energy windows, and extrapolating the μt values to those for the low energy region (E = 5–20 keV). When performing the extrapolation, the effective atomic number (Zeff ) of the object was taken into consideration. The methodology was validated by simulating X-ray projections using a digital human body phantom. The frequency of correspondence between the pixel values in the high-contrast image and the Zeff image was analyzed for each pixel.
Results: We succeeded in creating virtual high-contrast X-ray images that reflect the image contrast of monochromatic X-rays of 5–20 keV. It was confirmed that the pixel values in the high-contrast image corresponding to an Zeff = 7.5 (soft-tissue) were completely separated from those corresponding to an Zeff = 9 (bone). The optimization of the energy related to the high contrast images was performed based on the contrast-to-noise ratio (CNR) analysis. The high contrast image with 10 keV showed a good CNR value.
Conclusions: Based on the analysis of the attenuation information of middle and high-energy X-rays measured by ERPCDs, we succeeded in creating a novel algorithm that can generate a virtual monochromatic image with high contrast. en-copyright= kn-copyright= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaTatsuya en-aut-sei=Maeda en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiDaiki en-aut-sei=Kobayashi en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GotoSota en-aut-sei=Goto en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HabaTomonobu en-aut-sei=Haba en-aut-mei=Tomonobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanazawaYuki en-aut-sei=Kanazawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoShuichiro en-aut-sei=Yamamoto en-aut-mei=Shuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=2 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=3 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=5 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=6 en-affil=Faculty of Health Sciences, Kobe Tokiwa University kn-affil= affil-num=7 en-affil=Faculty of Radiological Technology, School of Medical Science, Fujita Health University kn-affil= affil-num=8 en-affil=Faculty of Life Science, Kumamoto University kn-affil= affil-num=9 en-affil=JOB CORPORATION kn-affil= affil-num=10 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= en-keyword=Medical X-ray diagnosis kn-keyword=Medical X-ray diagnosis en-keyword=Photon-counting detector kn-keyword=Photon-counting detector en-keyword=High contrast image kn-keyword=High contrast image en-keyword=Virtual monochromatic image kn-keyword=Virtual monochromatic image en-keyword=Effective atomic number kn-keyword=Effective atomic number en-keyword=Ultra-low energy image kn-keyword=Ultra-low energy image END start-ver=1.4 cd-journal=joma no-vol=239 cd-vols= no-issue= article-no= start-page=113237 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Counting-loss correction procedure of X-ray imaging detectors with consideration for the effective atomic number of biological objects en-subtitle= kn-subtitle= en-abstract= kn-abstract=It is necessary to correct counting loss caused by the pulse pile-up effect and dead time when using energy-resolving photon-counting detectors (ERPCDs) under “high-counting-rate” conditions in medical and/or industrial settings. We aimed to develop a novel counting-loss correction procedure in which biological objects having effective atomic numbers (Zeff values) of 6.5–13.0 are measured with polychromatic X-rays. To correct for counting loss, such a procedure must theoretically estimate the count value of an ideal X-ray spectrum without counting loss. In this study, we estimated the ideal X-ray spectrum by focusing on the following two points: (1) the X-ray attenuation in an object (Zeff values of 6.5–13.0) and (2) the detector response. Virtual materials having intermediate atomic numbers between 6.5 and 13.0 were generated by using a mixture of polymethylmethacrylate (PMMA, Zeff = 6.5) and aluminum (Al, Zeff = 13.0). We then constructed an algorithm that can perform the counting-loss correction based on the object’s true Zeff value. To demonstrate the applicability of our procedure, we analyzed investigational objects consisting of PMMA and Al using a prototype ERPCD system. A fresh fish sample was also analyzed. The Zeff values agree with the theoretical values within an accuracy of Zeff ±1. In conclusion, we have developed a highly accurate procedure for correcting counting losses for the quantitative X-ray imaging of biological objects. en-copyright= kn-copyright= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiDaiki en-aut-sei=Kobayashi en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaTatsuya en-aut-sei=Maeda en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GotoSota en-aut-sei=Goto en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanazawaYuki en-aut-sei=Kanazawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatsumataAkitoshi en-aut-sei=Katsumata en-aut-mei=Akitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoShuichiro en-aut-sei=Yamamoto en-aut-mei=Shuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=2 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=3 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Health Science, Kobe Tokiwa University kn-affil= affil-num=7 en-affil=Faculty of Life Science, Kumamoto University kn-affil= affil-num=8 en-affil=Oral Radiology and Artificial Intelligence, Asahi University kn-affil= affil-num=9 en-affil=JOB CORPORATION kn-affil= affil-num=10 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= en-keyword=Photon-counting detector kn-keyword=Photon-counting detector en-keyword=Pulse pile-up kn-keyword=Pulse pile-up en-keyword=Dead time kn-keyword=Dead time en-keyword=Counting-loss correction kn-keyword=Counting-loss correction en-keyword=Charge-sharing effect kn-keyword=Charge-sharing effect en-keyword=Effective atomic number kn-keyword=Effective atomic number END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=8 article-no= start-page=afaf224 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oestrogen replacement combined with resistance exercise in older women with knee osteoarthritis: a randomised, double-blind, placebo-controlled clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Interventions targeting physical function decline in older women with knee osteoarthritis (KOA) are vital for healthy ageing. The additive benefits of combining oestrogen replacement therapy (ERT) with resistance exercise remain unclear.
Objective: To evaluate the additive effect of low-dose ERT on physical performance when combined with a muscle resistance exercise programme (MREP) in older women with KOA.
Design: This is a placebo-controlled, double-blind, randomised clinical trial.
Subjects: The subjects were community-dwelling women aged ≥65 years with chronic knee pain and KOA diagnosis.
Methods: Participants completed a 3-month MREP and were randomised to receive daily low-dose transdermal ERT (oestradiol 0.54 mg/day) or placebo. Outcomes were assessed at baseline, postintervention and 12 months later. The primary outcome was change in 30-second chair stand test (CS-30) score. Secondary outcomes included muscle mass, knee extension strength, walking performance, metabolic indicators, knee pain scale and 12-item short-form health survey (SF-12). Between-group differences in CS-30 changes were analysed using a linear regression model based on the intention-to-treat principle.
Results: Among 168 individuals screened, 75 participants (mean age 73.8 years, SD 5.8) were enrolled and randomised into an ERT group (n = 37) or a placebo group (n = 38). Baseline CS-30 scores were 14.81 (SD 3.95) in the ERT group and 15.58 (SD 3.48) in the placebo group. At 3 months, mean changes were 2.59 (SD 2.58) and 1.79 (SD 2.28) repetitions, respectively. The primary analysis showed no statistically significant between-group difference [regression coefficient: 0.81 (95% CI: −0.31, 1.92); P = .16]. Post hoc subgroup and sensitivity analyses suggested that benefits may exist among early-stage KOA participants. SF-12 mental health scores also improved significantly in the ERT group. No serious adverse events occurred.
Conclusions: ERT did not confer significant additive benefits to resistance exercise overall but may improve outcomes in early-stage KOA and mental health domains. These exploratory findings warrant further investigation. en-copyright= kn-copyright= en-aut-name=MitomaTomohiro en-aut-sei=Mitoma en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OobaHikaru en-aut-sei=Ooba en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiKasumi en-aut-sei=Takahashi en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTsunemasa en-aut-sei=Kondo en-aut-mei=Tsunemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaTomohiro en-aut-sei=Ikeda en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakamotoYoko en-aut-sei=Sakamoto en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=2 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=3 en-affil=Obstetrics and Gynecology, Ochiai Hospital kn-affil= affil-num=4 en-affil=Obstetrics and Gynecology, Ochiai Hospital kn-affil= affil-num=5 en-affil=Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=7 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=8 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= en-keyword=oestrogen replacement therapy kn-keyword=oestrogen replacement therapy en-keyword=muscle resistance exercise kn-keyword=muscle resistance exercise en-keyword=knee osteoarthritis kn-keyword=knee osteoarthritis en-keyword=physical performance kn-keyword=physical performance en-keyword=randomised controlled trial kn-keyword=randomised controlled trial en-keyword=older people kn-keyword=older people END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=77 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Individuals on the preclinical Alzheimer's continuum, particularly those with both amyloid and tau positivity (A + T +), display a rapid cognitive decline and elevated disease progression risk. However, limited studies exist on brain atrophy trajectories within this continuum over extended periods.
Methods This study involved 367 ADNI participants grouped based on combinations of amyloid and tau statuses determined through cerebrospinal fluid tests. Using longitudinal MRI scans, brain atrophy was determined according to the whole brain, lateral ventricle, and hippocampal volumes and cortical thickness in AD-signature regions. Cognitive performance was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). A generalized linear mixed-effects model was used to examine group × time interactions for these measures. In addition, progression risks to mild cognitive impairment (MCI) or dementia were compared among the groups using Cox proportional hazards models.
Results A total of 367 participants (48 A + T + , 86 A + T − , 63 A − T + , and 170 A − T − ; mean age 73.8 years, mean follow-up 5.1 years, and 47.4% men) were included. For the lateral ventricle and PACC score, the A + T − and A + T + groups demonstrated statistically significantly greater volume expansion and cognitive decline over time than the A − T − group (lateral ventricle: β = 0.757 cm3/year [95% confidence interval 0.463 to 1.050], P < .001 for A + T − , and β = 0.889 cm3/year [0.523 to 1.255], P < .001 for A + T + ; PACC: β =  − 0.19 /year [− 0.36 to − 0.02], P = .029 for A + T − , and β =  − 0.59 /year [− 0.80 to − 0.37], P < .001 for A + T +). Notably, the A + T + group exhibited additional brain atrophy including the whole brain (β =  − 2.782 cm3/year [− 4.060 to − 1.504], P < .001), hippocampus (β =  − 0.057 cm3/year [− 0.085 to − 0.029], P < .001), and AD-signature regions (β =  − 0.02 mm/year [− 0.03 to − 0.01], P < .001). Cox proportional hazards models suggested an increased risk of progressing to MCI or dementia in the A + T + group versus the A − T − group (adjusted hazard ratio = 3.35 [1.76 to 6.39]).
Conclusions In cognitively normal individuals, A + T + compounds brain atrophy and cognitive deterioration, amplifying the likelihood of disease progression. Therapeutic interventions targeting A + T + individuals could be pivotal in curbing brain atrophy, cognitive decline, and disease progression. en-copyright= kn-copyright= en-aut-name=FujishimaMotonobu en-aut-sei=Fujishima en-aut-mei=Motonobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawasakiYohei en-aut-sei=Kawasaki en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsudaHiroshi en-aut-sei=Matsuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Radiology, Kumagaya General Hospital kn-affil= affil-num=2 en-affil=Department of Biostatistics, Graduate School of Medicine, Saitama Medical University kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Biofunctional Imaging, Fukushima Medical University kn-affil= en-keyword=Preclinical kn-keyword=Preclinical en-keyword=Alzheimer’s disease kn-keyword=Alzheimer’s disease en-keyword=Longitudinal MRI kn-keyword=Longitudinal MRI en-keyword=Tau kn-keyword=Tau en-keyword=Amyloid-β kn-keyword=Amyloid-β END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year= dt-pub= dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title= en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=207 cd-vols= no-issue= article-no= start-page=108683 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Intracranial activity of sotorasib vs docetaxel in pretreated KRAS G12C-mutated advanced non-small cell lung cancer from a global, phase 3, randomized controlled trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To assess the efficacy and safety of sotorasib in patients with brain metastases using data from the phase 3 CodeBreaK 200 study, which evaluated sotorasib in adults with pretreated advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC).
Materials and methods: Patients with KRAS G12C-mutated NSCLC who progressed after platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1:1 to sotorasib or docetaxel. An exploratory post-hoc analysis evaluated central nervous system (CNS) progression-free survival (PFS) and time to CNS progression in patients with treated and stable brain metastases at baseline. Measures were assessed by blinded independent central review per study-modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
Results: Of the patients randomly assigned to receive sotorasib (n=171) or docetaxel (n=174), baseline CNS metastases were present in 40 (23%) and 29 (17%) patients, respectively. With a median follow-up of 20.0 months for this patient subgroup, median CNS PFS was longer with sotorasib compared with docetaxel (9.6 vs 4.5 months; hazard ratio, 0.43 [95% CI, 0.20–0.92]; P=0.02). Among patients with baseline treated CNS lesions of ≥10 mm, the percentage of patients who achieved CNS tumor shrinkage of ≥30% was two-fold higher with sotorasib than docetaxel (33.3% vs 15.4%). Treatment-related adverse events among patients with CNS lesions at baseline were consistent with those of the overall study population.
Conclusions: These results suggest intracranial activity with sotorasib complements the overall PFS benefit observed with sotorasib vs docetaxel, with safety outcomes similar to those in the general CodeBreaK 200 population.
Clinical trials registration number: NCT04303780. en-copyright= kn-copyright= en-aut-name=DingemansAnne-Marie C. en-aut-sei=Dingemans en-aut-mei=Anne-Marie C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SyrigosKonstantinos en-aut-sei=Syrigos en-aut-mei=Konstantinos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiviLorenzo en-aut-sei=Livi en-aut-mei=Lorenzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PaulusAstrid en-aut-sei=Paulus en-aut-mei=Astrid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimSang-We en-aut-sei=Kim en-aut-mei=Sang-We kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChenYuanbin en-aut-sei=Chen en-aut-mei=Yuanbin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GriesingerFrank en-aut-sei=Griesinger en-aut-mei=Frank kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ZalcmanGerard en-aut-sei=Zalcman en-aut-mei=Gerard kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HughesBrett G.M. en-aut-sei=Hughes en-aut-mei=Brett G.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SørensenJens Benn en-aut-sei=Sørensen en-aut-mei=Jens Benn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=BlaisNormand en-aut-sei=Blais en-aut-mei=Normand kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FerreiraCarlos G.M. en-aut-sei=Ferreira en-aut-mei=Carlos G.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=LindsayColin R. en-aut-sei=Lindsay en-aut-mei=Colin R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DziadziuszkoRafal en-aut-sei=Dziadziuszko en-aut-mei=Rafal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WardPatrick J. en-aut-sei=Ward en-aut-mei=Patrick J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ObiozorCynthia Chinedu en-aut-sei=Obiozor en-aut-mei=Cynthia Chinedu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=WangYang en-aut-sei=Wang en-aut-mei=Yang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=PetersSolange en-aut-sei=Peters en-aut-mei=Solange kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Erasmus MC Cancer Institute, University Medical Center kn-affil= affil-num=2 en-affil=Sotiria General Hospital kn-affil= affil-num=3 en-affil=Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence kn-affil= affil-num=4 en-affil=Centre Hospitalier Universitaire de Liège kn-affil= affil-num=5 en-affil=Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine kn-affil= affil-num=6 en-affil=The Cancer & Hematology Centers of Western Michigan kn-affil= affil-num=7 en-affil=Medical Oncology Department, Vall d’Hebron University Hospital kn-affil= affil-num=8 en-affil=Pius-Hospital Oldenburg kn-affil= affil-num=9 en-affil=Okayama University Hospital kn-affil= affil-num=10 en-affil=Hospital Bichat-Claude Bernard kn-affil= affil-num=11 en-affil=The Prince Charles Hospital, University of Queensland kn-affil= affil-num=12 en-affil=Rigshospitalet kn-affil= affil-num=13 en-affil=Department of Medicine, Centre Hospitalier de l’Université de Montréal kn-affil= affil-num=14 en-affil=Oncoclinicas kn-affil= affil-num=15 en-affil=Division of Cancer Sciences, University of Manchester and The Christie NHS Foundation Trust kn-affil= affil-num=16 en-affil=University Clinical Centre, Medical University of Gdansk kn-affil= affil-num=17 en-affil=SCRI at OHC kn-affil= affil-num=18 en-affil=Amgen Inc. kn-affil= affil-num=19 en-affil=Amgen Inc. kn-affil= affil-num=20 en-affil=Lausanne University Hospital kn-affil= en-keyword=Brain metastases kn-keyword=Brain metastases en-keyword=KRAS G12C-mutated kn-keyword=KRAS G12C-mutated en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=NSCLC kn-keyword=NSCLC en-keyword=Randomized controlled trial kn-keyword=Randomized controlled trial en-keyword=Sotorasib kn-keyword=Sotorasib en-keyword=Survival kn-keyword=Survival END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250714 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Week 2 remission with vedolizumab as a predictor of long-term remission in patients with ulcerative colitis: a multicenter, retrospective, observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Vedolizumab (VDZ), a gut-selective monoclonal antibody for ulcerative colitis (UC) treatment, has no established biomarkers or clinical features that predict long-term remission. Week 2 remission, a potential predictor of long-term remission, could inform maintenance treatment strategy.
Methods This retrospective, observational chart review included patients with UC in Japan who initiated VDZ between December 2018 and February 2020. Outcome measures included 14- and 54-week remission rates in patients with week 2 and non-week 2 remission (remission by week 14), 54-week remission rates in patients with week 14 remission and primary nonresponse, and predictive factors of week 2 and week 54 remission (logistic regression).
Results Overall, 332 patients with UC (176 biologic-naïve and 156 biologic-non-naïve) were included. Significantly more biologic-naïve than biologic-non-naïve patients achieved week 2 remission (36.9% vs. 28.2%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.05–1.94; P=0.0224). Week 54 remission rates were significantly different between week 14 remission and primary nonresponse (both groups: P<0.0001), and between week 2 and non-week 2 remission (all patients: OR, 2.41; 95% CI, 1.30–4.48; P=0.0052; biologic-naïve patients: OR, 2.40; 95% CI, 1.10–5.24; P=0.0280). Week 2 remission predictors were male sex, no anti-tumor necrosis factor alpha exposure, and normal/mild endoscopic findings. Week 54 remission was significantly associated with week 2 remission and no tacrolimus use.
Conclusions Week 2 remission with VDZ is a predictor of week 54 remission in patients with UC. Week 2 may be used as an evaluation point for UC treatment decisions. (Japanese Registry of Clinical Trials: jRCT-1080225363) en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FernandezJovelle L en-aut-sei=Fernandez en-aut-mei=Jovelle L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Colitis, ulcerative kn-keyword=Colitis, ulcerative en-keyword=Inflammatory bowel diseases kn-keyword=Inflammatory bowel diseases en-keyword=Japan kn-keyword=Japan en-keyword=Vedolizumab kn-keyword=Vedolizumab END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The duration of prior anti-tumor necrosis factor agents is associated with the effectiveness of vedolizumab in patients with ulcerative colitis: a real-world multicenter retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Previous literature suggests that the response of patients with ulcerative colitis to vedolizumab may be affected by previous biologic therapy exposure. This real-world study evaluated vedolizumab treatment effectiveness in biologicnon-naïve patients.
Methods This was a multicenter, retrospective, observational chart review of records from 16 hospitals in Japan (December 1, 2018, to February 29, 2020). Included patients who had ulcerative colitis, were aged ≥ 20 years, and received at least 1 dose of vedolizumab. Outcomes included clinical remission rates from weeks 2 to 54 according to prior biologic exposure status and factors associated with clinical remission up to week 54.
Results A total of 370 eligible patients were included. Clinical remission rates were significantly higher in biologic-naïve (n=197) than in biologic-non-naïve (n=173) patients for weeks 2 to 54 of vedolizumab treatment. Higher clinical remission rates up to week 54 were significantly associated with lower disease severity (partial Mayo score ≤ 4, P= 0.001; albumin ≥ 3.0, P= 0.019) and the duration of prior anti-tumor necrosis factor α (anti-TNFα) therapy (P= 0.026). Patients with anti-TNFα therapy durations of < 3 months, 3 to < 12 months, and ≥ 12 months had clinical remission rates of 28.1%, 32.7%, and 60.0%, respectively (P= 0.001 across groups).
Conclusions The effectiveness of vedolizumab in biologic-non-naïve patients was significantly influenced by duration of prior anti-TNFα therapy. (Japanese Registry of Clinical Trials: jRCT-1080225363) en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FernandezJovelle L en-aut-sei=Fernandez en-aut-mei=Jovelle L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=6 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Tumor necrosis factor-alpha kn-keyword=Tumor necrosis factor-alpha en-keyword=Real-world evidence kn-keyword=Real-world evidence en-keyword=Colitis kn-keyword=Colitis en-keyword=ulcerative kn-keyword=ulcerative en-keyword=Vedolizumab kn-keyword=Vedolizumab en-keyword=Sequencing kn-keyword=Sequencing END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=6 article-no= start-page=1435 end-page=1445 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250515 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-World Effectiveness and Safety of Vedolizumab in Patients ≥ 70 Versus < 70 Years With Ulcerative Colitis: Multicenter Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Vedolizumab (VDZ) is often used in older patients with ulcerative colitis (UC) in clinical practice; however, real-world evidence is still limited, including in those with late-onset UC.
Methods: This post hoc analysis of a multicenter, retrospective, observational chart review, enrolling 370 patients with UC receiving VDZ between December 2018 and February 2020, compared effectiveness and safety of VDZ among patients ≥ 70 (n = 40) versus < 70 years (n = 330), and among patients ≥ 70 years with and without late-onset UC (age at disease onset: ≥ 70 [n = 13] versus < 70 years [n = 26]).
Results: There were no differences between patients ≥ 70 and < 70 years in clinical remission rates (week 6: 57.5% vs. 47.6%, p = 0.9174; week 14: 62.5% vs. 54.8%, p = 0.1317; week 54: 47.5% vs. 46.4%, p = 0.8149), primary nonresponse (10.0% vs. 15.5%, p = 0.6248), loss of response (12.5% vs. 9.4%, p = 0.5675), or overall safety. Among patients ≥ 70 years, the incidence of adverse drug reactions was numerically greater in those with concomitant corticosteroids than in those without. For older patients with and without late-onset UC, week 54 remission rates were 23.1% versus 57.7% (p = 0.0544); surgery was reported in 3/13 versus 2/26 patients and hospitalization in 5/13 versus 6/26 patients. One death was reported in patients with late-onset UC.
Conclusions: VDZ effectiveness and safety were similar in patients ≥ 70 and < 70 years; VDZ may be a suitable treatment option for patients ≥ 70 years with UC. Patients with late-onset UC tended to have more frequent surgery/hospitalization and lower effectiveness than those without, possibly necessitating greater caution when using VDZ.
Trial Registration: Japanese Registry of Clinical Trials registration number: jRCT-1080225363 en-copyright= kn-copyright= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FernandezJovelle L. en-aut-sei=Fernandez en-aut-mei=Jovelle L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HiroseLisa en-aut-sei=Hirose en-aut-mei=Lisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=2 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=22 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=elderly kn-keyword=elderly en-keyword=inflammatory bowel diseases kn-keyword=inflammatory bowel diseases en-keyword=onset age kn-keyword=onset age en-keyword=vedolizumab kn-keyword=vedolizumab END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors affecting 1-year persistence with vedolizumab for ulcerative colitis: a multicenter, retrospective real-world study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response.
Methods In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled.
Results Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response.
Conclusions Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence. en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FernandezJovelle L. en-aut-sei=Fernandez en-aut-mei=Jovelle L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=DeguchiHisato en-aut-sei=Deguchi en-aut-mei=Hisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=22 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Colitis, ulcerative kn-keyword=Colitis, ulcerative en-keyword=Inflammatory bowel diseases kn-keyword=Inflammatory bowel diseases en-keyword=Japan kn-keyword=Japan en-keyword=Vedolizumab kn-keyword=Vedolizumab en-keyword=Medication persistence kn-keyword=Medication persistence END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Health-related quality of life, work productivity, and persisting challenges in treated ulcerative colitis patients: a Japanese National Health and Wellness Survey en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Despite available treatments for ulcerative colitis (UC), unmet needs persist among patients in Japan. This study explored the health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), indirect cost, and unmet needs among treated UC patients in Japan.
Methods This cross-sectional, observational study utilized data from the online 2017, 2019, and 2021 Japan National Health and Wellness Survey. Respondents were aged ≥ 18 years and had undergone or were on UC treatment (5-aminosalicylic acid, steroids, immunomodulators/immunosuppressants, biologics/Janus kinase inhibitors [JAKi]). Demographic, general health, and clinical characteristics, medication adherence, HRQoL, WPAI, and indirect cost were collected and analyzed.
Results Among 293 treated UC patients, 83.6% were non-biologic/JAKi users, 29.0% had UC ≥ 15 years, 34.8% had moderate-to-severe disease severity, 55.3% experienced ≥ 1 persisting UC symptom, and 91.5% reported UC as bothersome to an extent. Patients reported EuroQoL visual analog scale score of 68.1 and ≥ 35% reported anxiety and depression. Mean work productivity loss was 29.3%, resulting in an annual mean indirect loss of 1.1 million JPY (45.3 thousand USD) per person. Higher WPAI (impairment) was associated with being male, moderate-to-severe disease severity, and low treatment adherence (P<0.05). Biologics/JAKi users had higher work impairment, and IM/IS users had higher activity impairment than 5-aminosalicylic acid users (P<0.05).
Conclusions Despite treatment, Japanese UC patients experienced high disease burden and persistent disease-related challenges. Overall HRQoL were lower than the mean healthy population and work productivity impairment led to high indirect costs. The findings suggest the importance of new interventions for optimizing UC outcomes. en-copyright= kn-copyright= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuangZhezhou en-aut-sei=Huang en-aut-mei=Zhezhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=QinFei en-aut-sei=Qin en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Nathan ArokianathanFatima Megala en-aut-sei=Nathan Arokianathan en-aut-mei=Fatima Megala kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DavéKiran en-aut-sei=Davé en-aut-mei=Kiran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShahShweta en-aut-sei=Shah en-aut-mei=Shweta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimHyunchung en-aut-sei=Kim en-aut-mei=Hyunchung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Okayama University kn-affil= affil-num=2 en-affil=Cerner Enviza kn-affil= affil-num=3 en-affil=Cerner Enviza kn-affil= affil-num=4 en-affil=Oracle Life Sciences kn-affil= affil-num=5 en-affil=Bristol Myers Squibb kn-affil= affil-num=6 en-affil=Bristol Myers Squibb kn-affil= affil-num=7 en-affil=Bristol Myers Squibb kn-affil= en-keyword=Quality of life kn-keyword=Quality of life en-keyword=Presenteeism kn-keyword=Presenteeism en-keyword=Absenteeism kn-keyword=Absenteeism en-keyword=Ulcerative colitis kn-keyword=Ulcerative colitis en-keyword=Japan kn-keyword=Japan END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=7 article-no= start-page=920 end-page=927 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The association of fasting triglyceride variability with renal dysfunction and proteinuria in medical checkup participants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The association between the variability of triglyceride (TG) and chronic kidney disease (CKD) progression remains unclear. We examined whether intraindividual variability in fasting TG was associated with the exacerbation of CKD.
Methods We conducted a retrospective and observational study. 18,339 participants, who went through medical checkups and had checked their estimated glomerular filtration rate (eGFR) and semi-quantitative proteinuria by urine dipstick every year since 2017 for 4 years were registered. Variability in fasting TG was determined using the standard deviation (SD), and maximum minus minimum difference (MMD) between 2017 and 2021. The primary end point for the analysis of eGFR decline was eGFR < 60 mL/min/1.73 m2. The secondary end point for the analysis of proteinuria was the incidence of proteinuria ≥ ( ±) by urine dipstick.
Results The renal survival was lower in the higher-SD, and higher-MMD groups than in the lower-SD, and lower-MMD groups, respectively (log-rank test p < 0.001, and < 0.001, respectively). Lower SD and lower MMD were significantly associated with renal survival in the adjusted model (hazard ratio (HR), 1.12; 95% confidence intervals (CI), 1.04–1.21, and HR, 1.13; 95% CI 1.05–1.23, respectively). The non-incidence of proteinuria was lower in the higher-SD, and higher-MMD groups than in the lower-SD, and lower-MMD groups, respectively (log-rank test p < 0.001 and < 0.001, respectively).
Conclusion Fasting TG variability was associated with CKD progression in participants who went through medical checkups. en-copyright= kn-copyright= en-aut-name=Matsuoka-UchiyamaNatsumi en-aut-sei=Matsuoka-Uchiyama en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsakawaTomohiko en-aut-sei=Asakawa en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakurabuYoshimasa en-aut-sei=Sakurabu en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaKatsuyoshi en-aut-sei=Katayama en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoShugo en-aut-sei=Okamoto en-aut-mei=Shugo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakemotoRika en-aut-sei=Takemoto en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UmebayashiRyoko en-aut-sei=Umebayashi en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=eGFR decline kn-keyword=eGFR decline en-keyword=Proteinuria kn-keyword=Proteinuria en-keyword=Renal dysfunction kn-keyword=Renal dysfunction en-keyword=Triglyceride variability kn-keyword=Triglyceride variability en-keyword=Fasting triglyceride kn-keyword=Fasting triglyceride END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=2 article-no= start-page=e70276 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Occupational motions such as kneeling and squatting are associated with the increased development of medial meniscus posterior root tears, regardless of the medial posterior tibial slope angle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: The relationship between occupational motions and the medial posterior tibial slope (MPTS) with the development of medial meniscus posterior root tears (MMPRTs) has not been investigated. The development of non-traumatic degenerative MMPRTs may be influenced by repetitive occupational motions and bone morphological characteristics. Herein, we examined the association between occupational motions and MPTS in patients with MMPRT development.
Methods: During the first medical examination, MPTS was measured using lateral knee radiographic images, and occupational motions were investigated in 559 patients (591 knees). Occupational motions were classified as kneeling and squatting, standing and walking, sitting, lifting heavy weights, and housework. Mann–Whitney U test was used to compare patient characteristics between male and female patients and MPTS relative to occupational motion.
Results: The most frequent occupational motion was housework (160/559 patients, 28.6%), followed by kneeling and squatting (140/559, 25.0%), standing and walking (128/559, 22.9%), sitting (82/559, 14.7%), and lifting heavy weights (49/559, 8.8%). Furthermore, housework (10.0 ± 2.6°) involved significantly greater MPTS than kneeling and squatting (9.3 ± 2.7°; p = 0.012). However, the MPTS associated with other occupational motions was not significantly different from that associated with housework.
Conclusion: The most frequent occupational motion among patients with MMPRTs was housework, followed by kneeling and squatting. Patients who performed housework tended to have a higher MPTS. Occupational motions such as kneeling and squatting potentially increase the development of MMPRTs, even without a high MPTS.
Level of Evidence: Level IV. en-copyright= kn-copyright= en-aut-name=KawadaKoki en-aut-sei=Kawada en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyamaYusuke en-aut-sei=Yokoyama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TamuraMasanori en-aut-sei=Tamura en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkazakiYuki en-aut-sei=Okazaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurumatsuTakayuki en-aut-sei=Furumatsu en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=kneeling kn-keyword=kneeling en-keyword=meniscus kn-keyword=meniscus en-keyword=occupational motion kn-keyword=occupational motion en-keyword=posterior root tear kn-keyword=posterior root tear en-keyword=posterior tibial slope kn-keyword=posterior tibial slope END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=317 end-page=320 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Surgical Treatment for a Large Pulmonary Artery Aneurysm with a Quadricuspid Pulmonary Valve en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 65-year-old man was referred to our hospital for the annual assessment of the diameter and dilation of a pulmonary artery (PA) aneurysm. He had a small ventricular septal defect (VSD) that had closed naturally. Echocardiography revealed a dilated main PA, mild pulmonary regurgitation and no VSD. Computed tomography confirmed the dilation of the main PA (66.7×47.8 mm), right PA (37.1×32.9 mm), and left PA (36.7×34.0 mm). The patient underwent pulmonary artery replacement using a prosthetic vascular graft. A quadricuspid pulmonary valve was identified intraoperatively. Early surgical intervention could help to prevent rupture and dissection of PA aneurysms. en-copyright= kn-copyright= en-aut-name=MoriokaKei en-aut-sei=Morioka en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurokoYosuke en-aut-sei=Kuroko en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadowakiSachiko en-aut-sei=Kadowaki en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiJunko en-aut-sei=Kobayashi en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KotaniYasuhiro en-aut-sei=Kotani en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= en-keyword=pulmonary artery aneurysm kn-keyword=pulmonary artery aneurysm en-keyword=quadricuspid pulmonary valve kn-keyword=quadricuspid pulmonary valve en-keyword=pulmonary valve regurgitation and stenosis kn-keyword=pulmonary valve regurgitation and stenosis en-keyword=congenital heart disease kn-keyword=congenital heart disease en-keyword=pulmonary artery graft replacement kn-keyword=pulmonary artery graft replacement END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=311 end-page=315 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mimicking Contralateral Pneumothorax during Thoracoscopic Bullectomy Associated with Intraoperative Hyperinflation of a Large Bulla in an Obese Patient en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 55-year-old obese Japanese male with left pneumothorax presented to our hospital. Bilateral pulmonary emphysema was confirmed. Persistent air leakage was observed, and a thoracoscopic bullectomy was performed. Although the thoracoscopic bullectomy was completed uneventfully, pre-extubation chest X-ray imaging indicated hyper-lucency occupying the right upper part of the thoracic cavity, suggesting right-sided pneumothorax. CT imaging indicated a right-upper-lobe expanded bulla. Extubation was performed, and the hyperinflated bulla gradually deflated. Careful management of bulla expansion and respiratory status may be necessary for patients with obesity and large bullae, especially in one-lung ventilation cases. en-copyright= kn-copyright= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiranoYutaka en-aut-sei=Hirano en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= en-keyword=giant bulla kn-keyword=giant bulla en-keyword=pneumothorax kn-keyword=pneumothorax en-keyword=obesity kn-keyword=obesity en-keyword=positive pressure ventilation kn-keyword=positive pressure ventilation en-keyword=one lung ventilation kn-keyword=one lung ventilation END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=305 end-page=309 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Rare Presentation of Pneumonic-Type Adenocarcinoma Hidden behind Empyema en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pneumonic-type adenocarcinoma (P-ADC) can closely mimic pneumonia. We report a P-ADC initially diagnosed as pneumonia which developed into a pulmonary abscess and empyema. A 50-year-old Japanese male diagnosed with pneumonia, pulmonary abscess, and empyema was administered antibiotics and a chest tube for drainage, which improved his symptoms and blood test results. However, chest computed tomography showed an enlarged infiltrative shadow. The patient underwent bronchoscopy and was diagnosed with an adenocarcinoma. This case highlights the importance of considering P-ADC in differential diagnoses when a pneumonia-like shadow enlarges post-empyema treatment. Diagnostic and clinical tests, e.g., bronchoscopy, should be performed in such cases. en-copyright= kn-copyright= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NimanEito en-aut-sei=Niman en-aut-mei=Eito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiRyoko en-aut-sei=Tsuji en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakataKohei en-aut-sei=Takata en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumoriShunsuke en-aut-sei=Matsumori en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MuranoFumika en-aut-sei=Murano en-aut-mei=Fumika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugisakiYuka en-aut-sei=Sugisaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OmoriHiroki en-aut-sei=Omori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakahashiKenji en-aut-sei=Takahashi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkadaToshiaki en-aut-sei=Okada en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=10 en-affil=Department of Diagnostic Pathology, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=12 en-affil=Department of General Thoracic Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= en-keyword=pneumonic type adenocarcinoma kn-keyword=pneumonic type adenocarcinoma en-keyword=empyema kn-keyword=empyema en-keyword=bronchoscopy kn-keyword=bronchoscopy en-keyword=lung cancer diagnosis kn-keyword=lung cancer diagnosis en-keyword=cavity formation kn-keyword=cavity formation END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=299 end-page=303 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pulmonary Calcium Phosphate Cement Embolism After Percutaneous Vertebroplasty for Thoracic Vertebrae Fractures en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary cement embolism (PCE) is a rare but severe complication following percutaneous vertebroplasty (PVP). Calcium phosphate cement (CPC) has emerged as an alternative to traditional materials for vertebral augmentation. There appear to be no established guidelines for managing symptomatic PCE, and there is scarce literature on CPC embolisms. This is a first report of a case of pulmonary CPC embolism following PVP. The patient, a 63-year-old Chinese female, was administered anticoagulant treatment and achieved a satisfactory outcome. Her case highlights the severe potential morbidity associated with CPC leakage and emphasizes the efficacy of anticoagulant treatment for managing pulmonary CPC embolisms. en-copyright= kn-copyright= en-aut-name=FengRuibin en-aut-sei=Feng en-aut-mei=Ruibin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhuBikang en-aut-sei=Zhu en-aut-mei=Bikang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WeiDanyun en-aut-sei=Wei en-aut-mei=Danyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhuDingjiao en-aut-sei=Zhu en-aut-mei=Dingjiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChenCairu en-aut-sei=Chen en-aut-mei=Cairu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=2 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=3 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=4 en-affil=Department of Radiology, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=5 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= en-keyword=percutaneous vertebroplasty kn-keyword=percutaneous vertebroplasty en-keyword=thoracic vertebrae fracture kn-keyword=thoracic vertebrae fracture en-keyword=calcium phosphate cement kn-keyword=calcium phosphate cement en-keyword=pulmonary embolism kn-keyword=pulmonary embolism END