Okayama University Medical School Acta Medica Okayama 0386-300X 80 5 2026 Transient Atrioventricular Conduction Disturbances in a Case of Severe Fever with Thrombocytopenia Syndrome 333 337 EN Masahiro Yamamoto Department of General Medicine, Kochi Health Sciences Center Ken-ei Sada Department of Clinical Epidemiology, Kochi Medical School, Kochi University Satoshi Kawada Department of Cardiology, Kochi Health Sciences Center Taeko Furihata Department of Emergency and Critical Care Center, Kochi Health Sciences Center Sachiko Muramatsu Department of General Medicine, Kochi Health Sciences Center Daichi Miyamoto Department of General Medicine, Kochi Health Sciences Center Akihiko Yano Department of General Medicine, Kochi Health Sciences Center Kohei Miyashita Department of Emergency and Critical Care Center, Kochi Health Sciences Center Yuichi Saisaka Department of Emergency and Critical Care Center, Kochi Health Sciences Center Takayuki Ishii Department of General Medicine, Kochi Health Sciences Center Case Report 10.18926/AMO/71343 A 79-year-old woman with severe fever with thrombocytopenia syndrome (SFTS) developed progressive atrioventricular (AV) conduction disturbances during hospitalization. On hospital day 6, first-degree AV block progressed to transient complete AV block, causing syncope and a 15-sec asystolic pause. Echocardiography showed preserved ventricular function, and cardiac magnetic resonance imaging did not support clinically overt myocarditis. A temporary transvenous pacemaker was inserted, and AV conduction recovered spontaneously; pacing was discontinued by day 9 without permanent pacemaker implantation. This case suggests that SFTS can cause reversible high-degree AV block and may warrant continuous twelve-lead electrocardiography (ECG) monitoring and timely temporary pacing. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 5 2026 Ruptured Intrahepatic Arterial Aneurysm due to Segmental Arterial Mediolysis Treated with Coil Embolization 327 332 EN Yurika Hata Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Shuta Tamura Department of Gastroenterological Surgery, Kochi Health Sciences Center Sunao Uemura Department of Gastroenterological Surgery, Kochi Health Sciences Center Teppei Tokumaru Department of Gastroenterological Surgery, Kochi Health Sciences Center Rika Yoshimatu Department of Radiology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/71342 A 67-year-old man presented with sudden-onset abdominal pain and hemorrhagic shock. Contrast-enhanced CT revealed a large hematoma in hepatic segments VI-VII with capsular rupture and hemoperitoneum. CT angiography demonstrated a saccular pseudoaneurysm in a posterior segmental branch of the right hepatic artery and a beaded appearance with irregular dilatation and segmental narrowing of the right hepatic artery branches, without inflammatory or atherosclerotic findings, supporting a diagnosis of segmental arterial mediolysis (SAM). Emergency angiography followed by coil embolization achieved hemostasis. Follow-up CT at 5 months showed complete exclusion of the aneurysmal lesions, with no evidence of recurrence or new vascular lesions. Coil embolization may be an effective, minimally invasive option for ruptured intrahepatic SAM lesions. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 5 2026 Radiogenomic Analysis of Contrast-Enhanced MRI for Predicting Pathogenic BRCA Variants in Ovarian Cancer 317 325 EN Hayato Saito Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Ryohei Fukui Department of Radiological Technology, Faculty of Health Sciences, Okayama University Hanako Sugihara Department of Obstetrics and Gynecology, Okayama University Akihiro Tada Okayama Diagnostic Imaging Center Shoji Nagao Department of Obstetrics and Gynecology, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/71341 This study evaluated the feasibility of predicting pathogenic BRCA1/2 variants in ovarian cancer using radiogenomic analysis of contrast-enhanced MRI. Twenty six patients were analyzed, including 14 with pathogenic BRCA1/2 variants and 12 without. Contrast enhanced MRI was used to generate two dimensional (2D) and three dimensional (3D) tumor segmentations. Radiomic features extracted with PyRadiomics were reduced using least absolute shrinkage and selection operator (LASSO) regression, yielding two selected features. Linear discriminant analysis (LDA) models were trained on 18 patients and tested on 8, with performance assessed using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve. The DeLong test compared AUCs between segmentation methods. Automated machine learning (AutoML) was performed with a training set of 20 patients and a test set of 6, with multiple performance metrics calculated. LDA achieved approximately 60% accuracy in both 2D and 3D test datasets. AUCs were 0.80 (3D) and 0.77 (2D), with no significant difference (p=0.85). AutoML identified CatBoost_BAG_L2_FULL as the optimal model, achieving accuracy above 80%. MRI-based radiogenomic analysis demonstrated moderate classification performance for identifying pathogenic BRCA1/2 variants in ovarian cancer. These preliminary findings suggest a potential role for noninvasive prediction, warranting further validation in larger cohorts. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 5 2026 Dynamics of Serum Amyloid A Levels in the Blood, Brain and Liver in a Mouse Model of Focal Cerebral Ischemia 309 316 EN Saki Egashira Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Takafumi Nakano Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Keiichi Irie Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Soichiro Ushio Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Akiko Manabe Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Ayuko Masaki Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Rie Mukai Department of Microbiology Laboratory, Faculty of Pharmaceutical Sciences, Fukuoka University Yoshihiko Nakamura Department of Emergency and Critical Care Medicine, Fukuoka University Hospital Masato Hosokawa Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Tomomitsu Satho Department of Microbiology Laboratory, Faculty of Pharmaceutical Sciences, Fukuoka University Kazunori Sano Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Kenichi Mishima Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Original Article 10.18926/AMO/71340 This study examined the dynamics of serum amyloid A (SAA) levels in the blood, brain, and liver over time using a mouse model of focal cerebral ischemia induced by occlusion of the middle cerebral artery (MCA) for 4 h followed by reperfusion. Blood SAA concentrations increased transiently after cerebral infarction, coinciding with changes in brain and liver SAA gene expression and protein levels. SAA concentrations in the brain, liver, and blood increased at similar time points after cerebral infarction, suggesting that SAA may serve as an important indicator of the associated pathological condition. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 5 2026 Prognostic Value of Combined Preoperative CALLY and SII Assessment in Patients Undergoing Resection for Esophageal Squamous Cell Carcinoma 299 308 EN Tao Xu Department of Oncology, The General Hospital of Western Theater Command Ying Zheng Department of Oncology, The General Hospital of Western Theater Command Xuemei Huang Department of Oncology, The General Hospital of Western Theater Command Hong Luo Department of Oncology, The General Hospital of Western Theater Command Original Article 10.18926/AMO/71339 This study evaluated the prognostic significance of the C-reactive protein–albumin–lymphocyte (CALLY) index and systemic immune-inflammation (SII) index in predicting postoperative outcomes in patients with esophageal squamous cell carcinoma (ESCC). A retrospective analysis was performed on clinical data from 102 patients with ESCC who underwent surgical resection at Western Theater General Hospital of China between January 2020 and July 2023. The associations between preoperative CALLY and SII indices and relapse-free survival (RFS) and overall survival (OS) were examined. Survival curves were generated using the Kaplan–Meier method, and prognostic factors were identified using Cox proportional hazards regression analysis. Patients with a high CALLY index had significantly longer RFS (HR=0.30, 95% CI: 0.13-0.71), and those with a low SII index also had significantly longer RFS (HR=2.23, 95% CI: 1.12-4.41). Similarly, patients with a high CALLY index had significantly longer OS (HR=0.27, 95% CI: 0.13-0.55), and those with a low SII index had significantly longer OS (HR=2.27, 95% CI: 1.09-4.71). When patients were stratified into four groups, the low-CALLY–high-SII group showed significantly shorter RFS than the high-CALLY–low-SII group (HR=0.26, 95% CI: 0.11-0.61; p=0.013), and OS was also significantly worse in the low-CALLY–high-SII group (HR=0.22, 95% CI: 0.09-0.54; p=0.016). Univariate Cox regression analysis identified both CALLY and SII as significant prognostic factors. In multivariate analysis, the CALLY index and N stage were independently associated with RFS, whereas only tumor size remained independently associated with OS. The combined assessment of preoperative CALLY and SII indices may be useful for prognostic stratification in patients with ESCC undergoing upfront surgical resection. It may help identify high-risk patient subgroups with distinct survival outcomes, thereby providing a potential rationale for stratifying postoperative surveillance and tailoring individualized adjuvant strategies, although validation in larger prospective cohorts is warranted. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 5 2026 High Accuracy of Pelvic Tilt Measurement Using Three-Dimensional Planning Software: A Validation Study Using Dry Bone Models 289 298 EN Yuki Komuta Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University Norio Imai Division of Comprehensive Musculoskeletal Medicine, Graduate School of Medical and Dental Sciences, Niigata University Daisuke Homma Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University Kazuhisa Funayama Division of Legal Medicine, Graduate School of Medical and Dental Sciences, Niigata University Yuki Hirano Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University Yoji Horigome Division of Comprehensive Musculoskeletal Medicine, Graduate School of Medical and Dental Sciences, Niigata University Izumi Minato Department of Orthopedic Surgery, Niigata Rinko Hospital Hiroyuki Kawashima Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University Original Article 10.18926/AMO/71338 The �gCR Alignment�h function was recently introduced in ZedHip®, the hip joint module of ZedView®, to evaluate pelvic tilt in non-supine positions via two-dimensional (2D)‒3D matching using radiographs. However, its ccuracy has not been validated. This study therefore evaluated the accuracy of pelvic tilt measurements using the CR Alignment function in dry pelvic bone specimens. Two cadaveric pelvic bone models were placed in nine orientations (anterior/posterior tilt and left/right rotation). Both radiographic and CT images were acquired in each position. In Study 1, pelvic tilt measured directly from CT images was defined as the �gtrue value.�h Three observers used the CR Alignment function to calculate pelvic tilt on radiographs, and measurement errors were determined relative to the true values. In Study 2, measurement errors were compared between matched (same position) and mismatched (different position) imaging. In Study 1, the mean measurement error was 1.28�}0.64�‹. Intra- and interobserver intraclass correlation coefficients were 0.996-0.998 and 0.997, respectively. In Study 2, the mean errors were 1.20�}0.88�‹ (matched) and 1.32�}1.03�‹ (mismatched). This software exhibited high accuracy and reproducibility in 2D‒3D matching of pelvic tilt, with lower variability under matched acquisition, demonstrating its utility for pre- and postoperative assessment in joint arthroplasty. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 5 2026 Diabetes Mellitus as a Risk Factor for Severe COVID-19 and Pneumonia: A Comparison Between the Pre-Omicron and Omicron-Dominant Periods in Okayama City, Japan 279 288 EN Satoshi Miyamoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Soshi Takao Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/71337 Diabetes mellitus is a well-established risk factor for severe COVID-19; however, few studies have examined this association during the Omicron-dominant period. We conducted a population-based study using surveillance data from the Okayama City Public Health Center in Japan to compare the risk of severe COVID-19 and pneumonia among patients with diabetes mellitus between the pre-Omicron (March 2020–December 2021) and Omicron-dominant (January–September 2022) periods. Among 98,905 COVID-19 patients aged 10 years or older, we calculated adjusted odds ratios (aORs) controlling for age, sex, smoking status, comorbidities, obesity, and the number of COVID-19 vaccine doses received. In the pre-Omicron period, diabetes mellitus was significantly associated with severe COVID-19 (aOR: 1.36; 95% CI: 1.03-1.78), and this association persisted in the Omicron-dominant period (aOR: 1.54; 95% CI: 1.10-2.17). Similar findings were observed for pneumonia. The association was more pronounced among patients aged 40-69 years than among those aged 70 years or older. These findings suggest that diabetes mellitus remains an important risk factor for severe COVID-19 even during the Omicron-dominant period, highlighting the need for continued clinical vigilance and early intervention in patients with diabetes mellitus. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 5 2026 Artificial Intelligence-Assisted Peroral Cholangioscopy for the Diagnosis and Management of Biliary Strictures: Current Evidence and Future Directions 271 277 EN Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Review 10.18926/AMO/71336 Peroral cholangioscopy (POCS) enables direct intraductal visualization and targeted biopsies for indeterminate biliary strictures. However, its diagnostic performance remains operator-dependent and is limited by sampling error. As artificial intelligence (AI) has rapidly advanced in gastrointestinal endoscopy, AI-assisted cholangioscopy has progressed from proof-of-concept image classification to multicenter validation, feature detection, and real-time application. Recent studies using digital single-operator cholangioscopy have reported diagnostic accuracy comparable to that of experts in differentiating malignant from benign strictures, and feature-based approaches can automatically detect tumor vessels and other key visual characteristics. Beyond classification, generative models may enhance mucosal and margin visualization through virtual chromoendoscopy, potentially improving lesion-margin assessment. Furthermore, new models compatible with multiple systems are emerging to address device heterogeneity, which is a key barrier to routine practice. This review summarizes the current evidence on AI-assisted POCS, discusses practical considerations for clinical translation, and highlights future directions, including real-time integration and multimodal decision support. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 3 2026 Bioinformatic Prediction of Activation States in Molecular Network Pathways of Eukaryotic Initiation Factor 2 (EIF2) Signaling and Coronavirus Pathogenesis 1525 EN Shihori Tanabe Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences Sabina Quader Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion Ryuichi Ono Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Horacio Cabral Department of Bioengineering, Graduate School of Engineering, The University of Tokyo Eukaryotic initiation factor 2 (EIF2) signaling plays a crucial role in regulating mRNA translation and initiating eukaryotic protein synthesis. Computational molecular network pathway analysis of the canonical pathways of the coronaviral infection revealed that EIF2 signaling is inactivated when the coronavirus pathogenesis pathway is activated and vice versa. Our computational analyses indicated that the coronavirus pathogenesis pathway and EIF2 signaling had inverse activation states. Computational investigation of upstream or downstream microRNA (miRNA) revealed that EIF2 signaling directly interacted with miRNAs, including let-7, miR-1292-3p (miRNAs with the seed CGCGCCC), miR-15, miR-34, miR-378, miR-493, miR-497, miR-7, miR-8, and MIRLET7. A total of 36 nodes, including 8 molecules (ATF4, BCL2, CCND1, DDIT3, EIF2A, EIF2AK3, EIF4E, and ERK1/2), 1 complex (the ribosomal 40s subunit), and 1 function (apoptosis) in the coronavirus pathogenesis pathway, overlapped with EIF2 signaling. Alterations in EIF2 signaling may play a role in the pathogenesis of coronavirus. No potential conflict of interest relevant to this article was reported.

Japanese Circulation Society Acta Medica Okayama 1346-9843 89 6 2025 Clinical Impact of Genetic Testing for Long QT Syndrome�@�\ Evidence From a Nationwide LQTS Registry in Japan �\ 835 844 EN Takeshi Aiba Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Seiko Ohno Medical Genome Center, National Cerebral and Cardiovascular Center (NCVC) Misa Takegami Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center (NCVC) Yoshiaki Kato Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center (NCVC) Heima Sakaguchi Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center (NCVC) Keiko Shimamoto Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Keiko Sonoda Medical Genome Center, National Cerebral and Cardiovascular Center (NCVC) Kazufumi Ida Division of Counseling for Medical Genetics, National Cerebral and Cardiovascular Center (NCVC) Naokata Sumitomo Department of Pediatric Cardiology, Saitama Medical University International Medical Center Taisuke Nabeshima Department of Pediatric Cardiology, Saitama Medical University International Medical Center Takashi Murakami Department of Child Health, Institution of Medicine, University of Tsukuba Yumiko Ninomiya Department of Pediatrics, National Hospital Organization Kagoshima Medical Center Koichi Kato Department of Cardiovascular Medicine, Shiga University of Medical Science Megumi Fukuyama Department of Cardiovascular Medicine, Shiga University of Medical Science Takeru Makiyama Department of Cardiology, Kyoto University Kenshi Hayashi Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences Kunio Ohta Department of Medical Education, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University Graduate School of Medical Sciences Hiroshi Morita Okayama University Graduate School of Medicine Tadashi Nakajima Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine Yoshiaki Kaneko Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine Nobue Yagihara Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences Sou Otsuki Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences Tomoki Kosho Department of Medical Genetics, Shinshu University School of Medicine Yoko Yoshida Osaka City General Hospital Motoki Takamuro Hokkaido Children�fs Hospital Michihiko Ueno Department of Pediatrics, Teine-Keijinkai Hospital Tatsunori Takahashi Department of Pediatrics, Yamagata University Faculty of Medicine Yasuya Inden Department of Cardiology, Nagoya University Graduate School of Medicine Yasunobu Hayabuchi Department of Pediatrics, Tokushima University Shota Muraji Fukuoka Children�fs Hospital Shigeo Watanabe Yokohama City University Kunihiro Nishimura Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center (NCVC) Yoshihiro Asano Department of Genomic Medicine, National Cerebral and Cardiovascular Center (NCVC) Hitoshi Horigome Department of Child Health, Institution of Medicine, University of Tsukuba Masao Yoshinaga Department of Pediatrics, National Hospital Organization Kagoshima Medical Center Minoru Horie Department of Cardiovascular Medicine, Shiga University of Medical Science Wataru Shimizu Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Kengo Kusano Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Background: Genetic testing for long QT syndrome (LQTS) is useful for diagnosis, risk stratification, and therapeutic strategies. This study investigated the clinical impact of genetic testing for LQTS patients.<br> Methods and Results: Total 3,851 patients (proband: 2,316 [60%]; female: 2,283 [59%]; median age: 14 years [interquartile range 9–36 years]) diagnosed with LQTS (LQTS score ≥3.5, QTc ≥500 ms, pathogenic variants in LQTS-associated genes, or unexplored syncope with QTc 480–499 ms) were enrolled in this study. Of these patients, 1,146 (29.8%) experienced syncope and 322 (8.5%) experienced ventricular fibrillation (VF) or cardiopulmonary arrest (CPA) at ≤70 years of age. Genetic testing using a next-generation sequencing panel and/or Sanger sequencing was performed for 3,770 (98%) patients, genotype was then identified in the following LQTS-associated genes: KCNQ1 (45%), KCNH2 (34%), SCN5A (8%), KCNE1 (0.1%), KCNE2 (0.03%), KCNJ2 (2.7%), CACNA1C (1.2%), and CALM1,2 (0.3%). Forty-seven (1.2%) patients had double or compound heterozygous variants in LQTS-associated genes, whereas the genotype remained unknown in 220 (5.8%) patients. When comparing phenotype with genotype, QTc was significantly longer in CALM1,2 patients than in others except for CACNA1C, whereas QTc was almost normal in KCNJ2 patients. The incidence of the first cardiac event (syncope, VF/CPA) differed among the genotypes, and prognosis was significantly worse for CALM1,2 patients.<br> Conclusions: Comprehensive genetic testing, including non-major LQTS genes, is important for diagnosis and risk stratification of LQTS. No potential conflict of interest relevant to this article was reported.

American Association for Cancer Research (AACR) Acta Medica Okayama 1078-0432 32 17 2026 Sequential Immune Activation of Effector T Cells as Biomarkers of Response to Durvalumab in Patients with Locally Advanced NSCLC 3880 3890 EN Atsuto Mouri Department of Respiratory Medicine, International Medical Center, Saitama Medical University Hirotsugu Kenmotsu Division of Thoracic Oncology, Shizuoka Cancer Center Hiroshi Kagamu Department of Respiratory Medicine, International Medical Center, Saitama Medical University Koichi Azuma Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine Ryota Saito Department of Respiratory Medicine, Tohoku University Graduate School of Medicine Hiroaki Akamatsu Internal Medicine III, Wakayama Medical University Kimio Yonesaka Department of Medical Oncology, Kindai University Faculty of Medicine Mikiko Kakegawa Department of Respiratory Medicine, Kitasato University School of Medicine Hiromi Nagashima Department of Respiratory Medicine, Iwate Medical University School of Medicine Satoshi Takahashi Department of Thoracic Surgery, Tokyo Medical University Hospital Masaki Fujita Department of Respiratory Medicine, Fukuoka University Hospital Noriko Yanagitani Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasuhiko Nishioka Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University Keita Mori Department of Biostatistics, Clinical Research Support Center, Shizuoka Cancer Center Shigehisa Kitano Department of Advanced Medical Development, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Koji Tamada Department of Immunology, Yamaguchi University Graduate School of Medicine Nobuyuki Yamamoto Internal Medicine III, Wakayama Medical University Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Tetsuya Mitsudomi Division of Thoracic Surgery, Izumi City General Hospital Purpose: Durvalumab therapy following concurrent chemoradiotherapy (cCRT) improves progression-free survival (PFS) in patients with unresectable locally advanced non–small cell lung cancer. In this prospective observational study, we evaluated the changes in peripheral blood immune cell counts to elucidate the immunologic mechanisms underlying cCRT and durvalumab therapy.<br> Experimental Design: Peripheral blood mononuclear cell (PBMC) samples were collected at four time points: before cCRT, after cCRT, at the start of durvalumab, and 8 weeks after the start of durvalumab, and analyzed by multicolor flow cytometry.<br> Results: Of the 149 enrolled patients, 115 received durvalumab consolidation therapy after cCRT. The median PFS in the overall population was 24.2 months, and the 3-year PFS rate was 38.9%. PBMC analysis showed an increased effector fraction of CD4+ T cells before and after cCRT but no change in CD8+ T cells. Following durvalumab therapy, the effector fraction ratio of CD8+ T cells (CD62Llow CD8+ T cells) increased and positively correlated with increased CD62Llow CD4+ T cells during cCRT. Patients whose proportion of CD62Llow CD4+ T cells exceeded the threshold for cCRT had better PFS than those below the threshold. Patients whose CD62Llow CD8+ T-cell proportion exceeded the threshold after durvalumab therapy showed prolonged PFS compared with those below the threshold.<br> Conclusions: cCRT promotes an increase in effector CD4+ T cells, and the subsequent increase in CD8+ T cells following durvalumab therapy prolongs PFS. Peripheral blood effector–type CD4+ and CD8+ T cells are potential biomarkers for evaluating the immune status of patients and predicting treatment efficacy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-5002 218 2026 ULK1, a novel therapeutic target to delay drug tolerance to EGFR–TKIs in an EGFR-mutant non-small cell lung cancer model 109516 EN Ayako Morita Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kammei Rai Center for Innovative Clinical Medicine, Okayama University Hospital Tadahiro Kuribayashi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Tatsuya Nishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naofumi Hara Department of Allergy and Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Allergy and Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Toshio Kubo Center for Innovative Clinical Medicine, Okayama University Hospital Kadoaki Ohashi Center for Innovative Clinical Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Nobuaki Ochi Department of General Internal Medicine 4, Kawasaki Medical School Yosuke Togashi Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Background: The presence of drug-tolerant persister (DTP) cells reduces the effectiveness of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC). Although autophagy is a potential target for eliminating DTP cells, clinical trials targeting autophagy in EGFR-mutant NSCLC have been unsuccessful�\likely because most trials have utilized chloroquine, non-specifically inhibiting autophagy targeting lysosomes with dose limitations. This study focused on unc-51-like autophagy activating kinase 1 (ULK1), a more specific target for autophagy inhibition, to assess whether ULK1 inhibition delays the emergence of tolerance to EGFR-tyrosine kinase inhibitors in EGFR-mutant NSCLC cells.<br> Methods: DTP cells were generated by treating EGFR-mutant NSCLC cell lines with osimertinib. Autophagy status and ULK1 expression were evaluated using immunofluorescence, western blotting, and quantitative real-time PCR. The effects of both pharmacological and genetic inhibition of ULK1 were examined in vitro and in vivo.<br> Results: ULK1 and LC3-II, markers of autophagy, were upregulated in DTP cells. Inhibition of ULK1, either pharmacologically or genetically, suppressed autophagy, prevented the formation of DTP cells, and enhanced the antitumor activity of osimertinib in both in vitro and in vivo models. Furthermore, upregulation of ULK1 expression through serum starvation conferred tolerance to osimertinib, reinforcing ULK1�Œs role in drug tolerance. Notably, ULK1 inhibition showed modest efficacy even after cells transitioned to the DTP or acquired resistance states.<br> Conclusion: ULK1 plays a critical role in mediating drug tolerance in EGFR-mutant NSCLC. Targeting ULK1 represents a promising therapeutic approach to enhance the efficacy of EGFR-TKIs and to delay the development of drug tolerance. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1759-7706 17 10 2026 Interstitial Lung Disease in Patients With Unresectable Stage III NSCLC Treated With Chemoradiotherapy Followed by Durvalumab in Japan: Analysis From the Multicenter Prospective AYAME Study e70299 EN Nobuyuki Yamamoto Internal Medicine III, Wakayama Medical University Hirotsugu Kenmotsu Division of Thoracic Oncology, Shizuoka Cancer Center Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Burak Akdemir Oncology Medical, AstraZeneca K.K Shinya Uematsu Oncology Medical, AstraZeneca K.K Ayako Fukui Evidence and Observational Research, Medical, AstraZeneca K.K Ryo Koto Evidence and Observational Research, Medical, AstraZeneca K.K Masakazu Fujiwara Evidence and Observational Research, Medical, AstraZeneca K.K Chikako Iwao Oncology Medical, AstraZeneca K.K Hiroshi Kitagawa Oncology Medical, AstraZeneca K.K Ichiro Yoshino Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Tetsuya Mitsudomi Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine Yoshinobu Saito Department of Pulmonary Medicine, Nippon Medical School Musashi Kosugi Hospital Introduction: Interstitial lung disease (ILD) is a concerning adverse event associated with immune checkpoint inhibitors, including durvalumab. This analysis of the multicenter AYAME study assessed the longterm safety of durvalumab, focusing on ILD.<br> Methods: AYAME enrolled patients prescribed durvalumab for unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) from July 2019 to December 2020 in Japan. Patients received durvalumab for ≤ 12 months and were prospectively followed for 3 years. Incidence, severity, and management of ILD were examined. Multivariable logistic regression analysis was conducted to investigate the association of patient characteristics with grade ≥ 2 ILD occurrence.<br> Results: Of 511 patients in the safety analysis population, ILD occurred in 383 patients (75.0%) from durvalumab initiation to subsequent treatment start; median time to occurrence was 44.0 days. ILD led to permanent durvalumab discontinuation in 121/383 patients (31.6%), dose interruption in 111/383 (29.0%), and corticosteroid intervention in 168/383 (43.9%). Grade ≥ 2 ILD occurrence was higher in patients with volume of lung parenchyma that received 20 Gy (V20) ≥ 25% versus < 25% (60.3% vs. 29.4%; adjusted odds ratio 2.20, 95% confidence interval 1.08–4.48), 5 Gy (V5) ≥ median (37.85%) versus < median (51.5% vs. 27.2%; 1.79, 1.07–3.00), and grade 1 ILD before durvalumab administration versus no ILD (50.0% vs. 37.6%; 2.11, 1.07–4.17).<br> Conclusions: This study of durvalumab for NSCLC after CRT in a real-world setting indicated factors associated with grade ≥ 2 ILD and provided valuable insights into ILD management strategies. These findings may contribute to establishing effective approaches to minimize ILD risk in practice.<br> Trial Registration: UMIN000037090/NCT03995875 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1556-0864 21 1 2026 Long-Term Safety and Effectiveness of Durvalumab in Unresectable Stage III NSCLC in Japan: A Multicenter Prospective Study (AYAME) 160 173 EN Hirotsugu Kenmotsu Division of Thoracic Oncology, Shizuoka Cancer Center Yoshinobu Saito Department of Respiratory Medicine, Nippon Medical School, Musashi Kosugi Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinya Uematsu Oncology Medical, AstraZeneca K.K. Burak Akdemir Oncology Medical, AstraZeneca K.K. Ayako Fukui Evidence and Observational Research, Medical, AstraZeneca K.K. Ryo Koto Evidence and Observational Research, Medical, AstraZeneca K.K. Masakazu Fujiwara Evidence and Observational Research, Medical, AstraZeneca K.K. Chikako Iwao Oncology Medical, AstraZeneca K.K. Hiroshi Kitagawa Oncology Medical, AstraZeneca K.K. Ichiro Yoshino Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Tetsuya Mitsudomi Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine and Faculty of Medicine & Hospital Nobuyuki Yamamoto Internal Medicine III, Wakayama Medical University Introduction: Based on the PACIFIC trial results, durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III NSCLC. However, few large-scale studies have prospectively evaluated its long-term effectiveness and safety, including subsequent treatment.<br> Methods: This multicenter, noninterventional study (AYAME) enrolled patients who were prescribed durvalumab for unresectable stage III NSCLC after CRT (July 2019–December 2020; 52 sites; Japan). Patients received durvalumab for a maximum of 12 months and were prospectively followed up for 3 years, including the post-durvalumab treatment period. Primary end points were real-world progression-free survival (rwPFS), the incidence of interstitial lung disease (ILD), and adverse events of special interest (AESIs).<br> Results: Of the 529 enrolled patients, 512 received durvalumab and 511 comprised the safety analysis population. The median time to onset of the first presentation or occurrence of ILD was 45.0 days. ILD of any grade occurred in 387 patients (75.7%) over the 3-year study period: grade 3, 57 (11.2%); grade 4, none (0.0%); and grade 5, 9 (1.8%). The most common AESIs of any grade during durvalumab treatment were thyroid dysfunction (12.5%), hepatic dysfunction (7.2%), and colitis (2.0%). No durvalumab treatment-related ILD or AESIs occurred during the post-treatment period. The median [95% confidence interval] rwPFS was 23.2 [18.2, 27.2] months in the effectiveness analysis population (n = 495). rwPFS rates were 62.5%, 54.6%, 49.4%, and 40.4% at 12, 18, 24, and 36 months, respectively.<br> Conclusions: This first and largest prospective, observational study demonstrated the long-term safety and effectiveness of durvalumab for unresectable stage III NSCLC after CRT in a real-world clinical setting.<br> Clinical Trial Registration: UMIN000037090 and NCT03995875 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 5 2025 Phase II Study of Platinum Re-administration in Non-small Cell Lung Cancer Following Chemoimmunotherapy Resistance e84709 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinobu Hosokawa Respiratory Medicine, Japanese Red Cross Okayama Hospital Toshihide Yokoyama Respiratory Medicine, Kurashiki Central Hospital Masaaki Inoue Chest Surgery, Shimonoseki City Hospital Keisuke Sugimoto Respiratory Medicine, Japanese Red Cross Kobe Hospital Kenichiro Kudo Respiratory Medicine, National Hospital Organization Okayama Medical Center Toshiaki Okada Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Tadashi Maeda Respiratory Medicine, National Hospital Organization Yamaguchi Ube Medical Center Haruyuki Kawai Internal Medicine, Okayama Saiseikai General Hospital Masayuki Yasugi Respiratory Medicine, Chugoku Central Hospital Koji Inoue Respiratory Medicine, Ehime Prefectural Central Hospital Shoichi Kuyama Respiratory Medicine, Iwakuni Medical Center Takashi Ninomiya Respiratory Medicine, National Hospital Organization Shikoku Cancer Center Isao Oze Division of Molecular Medicine, Aichi Cancer Center Research Institute Yoshinobu Maeda Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Platinum compounds represent standard treatments for various cancers. However, the efficacy of re-administrating platinum compounds has been demonstrated only in ovarian cancer and small cell lung cancer (SCLC), with its utility in non-small cell lung cancer (NSCLC) remaining unclear. Given that the prognosis of NSCLC has improved with effective treatments such as immune checkpoint inhibitors (ICIs), we propose a multicenter, single-arm, prospective phase II trial of re-administrating platinum-based combination therapy for NSCLC. Patients with NSCLC who have progressed after chemoimmunotherapy and exhibit a platinum-free interval of 85 days or more will receive carboplatin combination therapy. The drugs combined with carboplatin - pemetrexed, nab-paclitaxel, or gemcitabine - must not have been administered previously. The primary endpoint is progression-free survival (PFS), assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Assuming a threshold PFS of 4.2 months and an expected hazard ratio of 0.60, the required sample size is calculated as 40 patients to achieve 70% power with a 5% alpha error. Secondary endpoints included objective response rate, toxicity, and overall survival. This study will clarify the efficacy of re-administrating platinum compounds to patients with NSCLC who have developed resistance to chemoimmunotherapy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0047-6374 234 2026 The eukaryotic host–microbe–phage–nutrition interplay determines the bacterial effectors of supplemental lysine�fs health benefits: An experimental cellular senescence model of digestive conditions in older adults 112260 EN Darab Ghadimi Department of Microbiology and Biotechnology, Max Rubner-Institut Sophia Blömer Faculty of Medicine, Christian-Albrechts-University of Kiel Aysel ŞAHİN KAYA Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University Sandra Krüger Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Christoph Röcken Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Heiner Schäfer Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel Geraldine de Heer University Center for Nutritional Medicine, University Medical Centre Hamburg-Eppendorf Dominik Jarczak University Center for Nutritional Medicine, University Medical Centre Hamburg-Eppendorf Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University Wilhelm Bockelmann Department of Microbiology and Biotechnology, Max Rubner-Institut Recently, the consumption of various forms of the nutritive amino acid lysine (e.g., nutraceuticals and dietary supplements) has increased, particularly among the elderly, as it cannot be synthesized by the human body and plays a crucial role in several cellular physiological processes, including intestinal calcium and iron absorption, proteinogenesis, and fatty acid metabolism. However, the biochemical and immunological events that occur within the eukaryotic host-microbe-phage-nutrition interaction, especially when high amounts of lysine are consumed in nutraceutical or dietary supplement form by the elderly due to age-related requirements, as well as the impact on gut bacteria-derived metabolites, have not yet been fully studied. We hypothesized that (1) within an infectious-inflamed digestive milieu, the metabolism of excess extracellular lysine differs between young and senescent digestive cells, and (2) phages within the milieu exhibit alterations in host-microbe cometabolite signal profiles. To address this, we examined how gut microbes and phages, key regulators of eukaryotic host physiology, influence the immunometabolism of excess lysine. By combining two models of young and senescent digestive cells, the pathogenic P. aeruginosa PAO1, the Pseudomonas phage KPP22, and the anti-inflammatory bacterium Intestinimonas butyriciproducens, and simulating the pathogenesis of the interactive process of excessive lysine ingestion, we developed a five-way screening approach to explore key cell readouts, including viability, integrity, and function of the epithelial barrier, as well as cellular immunometabolic responses to exogenous lysine supplementation in cultures under infectious inflammation. Our findings are consistent with the possibility that host–microbe–microbe interactions involving lysine utilization and cross-feeding may influence the effects of lysine supplementation. These effects, whether beneficial or detrimental, can depend on the bacterial community, including the presence of pathogenic or potentially beneficial bacteria, interactions with intestinal phages, and the physiological conditions and metabolic requirements of the host and individual microbial taxa. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 19 2026 Impaired Myostatin Function Alters Body Composition Without Detectable Attenuation of Imiquimod-Induced Psoriasiform Dermatitis 8518 EN Yoshihiro Matsuda Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Morizane Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuma Sakamoto Department of Immunology and Molecular Genetics, Kawasaki Medical School Nobuyasu Baba Department of Immunology and Molecular Genetics, Kawasaki Medical School Masanori Iseki Department of Immunology and Molecular Genetics, Kawasaki Medical School Daiki Takezaki Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Kawakami Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-Ichiro Nishimatsu Department of Natural Sciences, Kawasaki Medical School Yutaka Ohsawa Department of Neurology, Kawasaki Medical School Yoshihide Sunada Department of Neurology, Kawasaki Medical School Tomoyuki Mukai Department of Immunology and Molecular Genetics, Kawasaki Medical School Psoriasis is a chronic inflammatory skin disease closely associated with obesity and metabolic dysfunction. While excess adiposity is considered a key risk factor, the independent contribution of body composition to psoriatic inflammation remains unclear. Myostatin negatively regulates skeletal muscle growth, and its inhibition leads to muscle hypertrophy and reduced adiposity. In this study, we investigated whether altered body composition due to impaired myostatin function affects imiquimod (IMQ)-induced psoriasiform dermatitis. Wild-type (WT) and dominant-negative myostatin transgenic mice were fed either a normal diet or a high-fat diet (HFD) for 10 weeks, followed by topical IMQ treatment to induce dermatitis. Mutant mice exhibited increased skeletal muscle mass and reduced visceral fat compared with WT controls, indicating marked changes in body composition. In WT mice, HFD feeding increased fat mass and tended to aggravate IMQ-induced ear swelling. In contrast, no significant effect of impaired myostatin function on ear thickness, epidermal hyperplasia, or the expression of psoriasis-associated genes was detected, despite reduced visceral fat. Under the present experimental conditions, these changes in body composition were not associated with a detectable attenuation of psoriasiform skin inflammation. Our results suggest that obesity-related psoriasis is influenced by metabolic and immunological factors beyond body composition. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 2026 The Geriatric Nutritional Risk Index Predicts Short�] and Long�]Term Outcomes in the Oldest�]Old With Colorectal Cancer: A Multi�]Institutional Analysis of 225 Nonagenarians EN Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Hospital Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Ryo Inada Department of Surgery, Kochi Health Sciences Center Tsuyoshi Ohtani Department of Surgery, Saiseikai Okayama Hospital Ryosuke Yoshida Department of Surgery, Okayama Rosai Hospital Naoto Hori Department of Surgery, Tottori Municipal Hospital Kaoru Shigemitsu Department of Surgery, Tsuyama Chuo Hospital Sumiharu Yamamoto Department of Surgery, Okayama City Hospital Tetsushi Kubota Department of Surgery, Kobe Red Cross Hospital Yuka Okano Department of Surgery, Onomichi City Hospital Tetsuji Nobuhisa Department of Surgery, Himeji Red Cross Hospital Fumitaka Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center Wataru Ishikawa Department of Surgery, Fukuyama City Hospital Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Hospital Tatsuo Matsuda Department of Surgery, Matsuda Hospital Tatsuo Umeoka Department of Surgery, Matsuyama City Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital The Setouchi Colorectal Neoplasm Registration Study Group Aim: Surgical outcomes for colorectal cancer (CRC) in nonagenarians remain uncertain due to frailty, comorbidities, and malnutrition. The Geriatric Nutritional Risk Index (GNRI) is associated with surgical outcomes in older patients with CRC, but its prognostic value in nonagenarians is unclear. This study evaluated the GNRI's predictive value for short- and long-term surgical outcomes in this population.<br> Methods: We retrospectively analyzed 225 nonagenarians undergoing surgical resection of CRC at 15 institutions between 2011 and 2022. Patients were stratified by GNRI-high/low status using two cutoffs: 98 (Cohort 1) and 86 (Cohort 2). Outcomes included postoperative complications, length of hospital stay, and overall survival (OS). Stabilized inverse-probability-of-treatment weighting (IPTW) was used to adjust for measured confounding.<br> Results: The median age was 92 years (female, 64.9%; colon cancer, 79.6%). GNRI-high patients had higher body mass index and albumin levels. Complication rates did not differ between the groups. After adjustment, GNRI-high patients in Cohort 1 had a shorter expected hospital stay (ratio 0.70, 95% CI 0.51–0.96; p = 0.025) but no significant OS difference. In Cohort 2, GNRI-high patients had better OS (p < 0.01), confirmed by adjusted Cox models (HR 0.54, 95% CI 0.35–0.82; p < 0.01).<br> Conclusions: Preoperative GNRI was associated with hospital stay and OS in nonagenarians undergoing CRC surgery, although the OS association was significant only with the cohort-derived cutoff of 86, which requires external validation, and not with the literature-based cutoff of 98. The GNRI is a simple tool to stratify surgical risk and optimize perioperative nutritional status in this vulnerable population. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-2392 16 2025 Efficacy in Japanese adults with growth hormone deficiency receiving weekly somapacitan or daily growth hormone: results from phase 3 REAL 1 trial 1534891 EN Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michael Højby Rasmussen Clinical Drug Development, Novo Nordisk A/S Takaaki Endo Medical Affairs Department, Novo Nordisk Pharma Ltd. Claus Sværke Clinical Drug Development, Novo Nordisk A/S Shigeyuki Tahara Department of Neurological Surgery, Nippon Medical School, Musashikosugi Hospital Gudmundur Johannsson Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and Department of Endocrinology, Diabetology, and Metabolism, Sahlgrenska University Hospital Introduction: Somapacitan is a long-acting growth hormone (GH) derivative approved for once-weekly treatment of adult GH deficiency (AGHD). This study aimed to evaluate the efficacy and safety of somapacitan and daily GH in Japanese individuals with AGHD.<br> Methods: This subgroup study included the 34-week main period of the multinational, randomized, parallel-group, phase 3 trial, REAL 1 (NCT02229851). Participants received once-weekly somapacitan or daily GH (Norditropin®), both administered subcutaneously. Investigators and trial sites were blinded. A total of 36 Japanese GH-naïve individuals with AGHD were allocated to somapacitan or daily GH (excluding the placebo group of the global trial). Endpoints included change in truncal fat percentage to week 34 measured using dual-energy x-ray absorptiometry, as well as other body composition measures. Insulin-like growth factor I standard deviation score values were used for dose titration.<br> Results: In total, 36 Japanese individuals were included (18 and 18 in the somapacitan and daily GH group, respectively). 35 completed the main period (34 weeks). Mean (SD) change from baseline to week 34 in truncal fat percentage was -2.23 (2.50) %-points in the somapacitan group and -2.12 (4.21) %-points in the daily GH group. Other body composition measures also improved in both groups, including reduced visceral fat and increased lean body mass. Somapacitan was well tolerated, with a safety profile similar to daily GH.<br> Conclusions: In Japanese treatment-naïve individuals with AGHD, once-weekly somapacitan demonstrated similar efficacy and safety to daily GH after 34 weeks of treatment. Somapacitan provides an effective alternative to daily GH in AGHD. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 74 3 2025 Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis 76 EN Takafumi Yanagisawa Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Keiichiro Mori Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Akihiro Matsukawa Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ekaterina Laukhtina Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Pawel Rajwa Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Fahad Quhal Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Benjamin Pradere Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Kosuke Iwatani Department of Urology, The Jikei University School of Medicine Renate Pichler Department of Urology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck Jeremy Yuen-Chun Teoh S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong Marco Moschini Department of Urology, San Raffaele Hospital and Scientific Institute Wojciech Krajewski Department of Minimally Invasive and Robotic Urology, Wrocław Medical University Jun Miki Department of Urology, The Jikei University School of Medicine Shahrokh F. Shariat Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Takahiro Kimura Department of Urology, The Jikei University School of Medicine European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47–0.99) and PFS (HR: 0.67, 95%CI 0.49–0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1556-0864 20 6 2025 A Single-Arm Phase 2 Study of Sotorasib Plus Carboplatin and Pemetrexed in Patients With Advanced Nonsquamous NSCLC With KRAS G12C Mutation (WJOG14821L, SCARLET) 775 785 EN Hiroaki Akamatsu Internal Medicine III, Wakayama Medical University Shinya Sakata Department of Respiratory Medicine, Kumamoto University Hospital Koichi Azuma Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Takehiro Uemura Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences Yuko Tsuchiya-Kawano Department of Respiratory Medicine, Kitakyushu Municipal Medical Center Seiya Esumi Respiratory Center, Matsusaka Municipal Hospital Takashi Kurosaki Department of Medical Oncology, Kindai University Faculty of Medicine Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Tomohiro Sakamoto Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Ryo Toyozawa Department of Thoracic Oncology, NHO Kyushu Cancer Center Yasuto Yoneshima Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Takehito Shukuya Department of Respiratory Medicine, Juntendo University Graduate School of Medicine Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Haruko Daga Department of Medical Oncology, Osaka City General Hospital Terufumi Kato Department of Thoracic Oncology, Kanagawa Cancer Center Toshiaki Takahashi Division of Thoracic Oncology, Shizuoka Cancer Center Mitsuo Osuga Center for Biomedical Sciences, Wakayama Medical University Yasuhiro Koh Internal Medicine III, Wakayama Medical University Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Nobuyuki Yamamoto Internal Medicine III, Wakayama Medical University Introduction: The efficacy and safety of sotorasib plus platinum doublet chemotherapy in KRAS G12C-mutated nonsquamous NSCLC (nonsq NSCLC) have been previously reported with a limited follow-up period.<br> Methods: SCARLET is a single-arm phase 2 study involving chemotherapy-naive patients with KRAS G12C–mutated nonsq NSCLC. The participants received 960 mg daily plus four cycles of carboplatin (area under the curve = 5)/pemetrexed 500 mg/m2, followed by sotorasib/pemetrexed until disease progression. The primary end point was the overall response rate (ORR) and the secondary end points were progression-free survival (PFS), overall survival, and safety. Using plasma samples, next-generation sequencing was performed at baseline, 3 weeks, and during disease progression (the Japan Registry of Clinical Trials number 2051210086).<br> Results: Thirty patients were enrolled between October 2021 and July 2022 with a median follow-up of 14.8 months. ORR was 88.9% (80% confidence interval [CI]: 78.5%–94.8%, 95% CI: 70.8%–97.6%), median PFS was 6.6 months (95% CI: 5.3–16.7 mo), and median overall survival was 20.6 months (95% CI: 8.1 mo–not estimated). Among patients with programmed death-ligand 1 expression levels of 1% or higher and less than 1%, the ORRs were 82.3 and 100%, respectively, and the median PFS was 7.6 and 9.7 months, respectively. Using plasma samples, patients without KRAS G12C at baseline, without KRAS-related pathway co-alterations, or who cleared KRAS G12C at 3 weeks had better median PFS (16.7, 13.9, 8.7 mo, respectively). Tumor protein 53 mutations and EGFR and MET amplification were detected as acquired resistance.<br> Conclusions: In patients with KRAS G12C-mutated nonsq NSCLC, sotorasib plus carboplatin/pemetrexed reported favorable efficacy, particularly for patients with less than 1% programmed death-ligand 1, with manageable toxicity. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study 1 16 EN Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Takatoshi Fujishita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Akito Hata Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Nobuhisa Ishikawa Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Go Saito Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Department of Respiratory Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Kazuya Nishii Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen�fs Hospital Hiroshi Kuraishi Department of Pulmonary Medicine, Nagano Red Cross Hospital Ken Yoshihara Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear.<br> Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy.<br> Design: This was a sub-analysis of the retrospective multicenter NINJA study.<br> Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations.<br> Results: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r = 0.389, p < 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN (n = 12) had significantly poorer progression-free survival (PFS) than those without the condition (n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021).<br> Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patient�fs baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2624-5175 7 1 2025 Association Between Alcohol Use Patterns and Insomnia Symptoms or Poor Sleep Quality Among Adult Women: An Internet Cross-Sectional Survey in Japan 5 EN Suguru Nakajima Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Yuichiro Otsuka Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Yoshitaka Kaneita Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Osamu Itani Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Yuki Kuwabara Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Aya Kinjo Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Ruriko Minobe National Hospital Organization Kurihama Medical and Addiction Center Hitoshi Maesato National Hospital Organization, Ryukyu Hospital Susumu Higuchi National Hospital Organization Kurihama Medical and Addiction Center Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Yoshimoto Department of Family Medicine, General Practice and Community Health, Faculty of Medicine, University of Tsukuba Maki Jike Department of Food Science and Nutrition, Faculty of Life and Environmental Science, Showa Women�fs University Hideaki Kasuga Department of Hygiene and Preventive Medicine, Fukushima Medical University Teruna Ito Department of Food and Nutrition, Koriyama Women�fs University Yoneatsu Osaki Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University It is unclear whether patterns of alcohol consumption are associated with sleep disturbance. We aimed to investigate the relationship between comprehensive alcohol-related factors and insomnia symptoms, as well as sleep quality, among adult women in Japan. Responses to an online cross-sectional survey were gathered from 12,000 women. The survey items included demographic characteristics, alcohol consumption (Alcohol Use Disorders Identification Test, nightcaps, years of drinking), sleep-related factors (sleep duration, insomnia symptoms, sleep quality), lifestyle-related factors, and mental health. Binary logistic regression was used to investigate the relationship between alcohol consumption and both insomnia symptoms and sleep quality. A total of 10,233 women were included in the final analysis. The results revealed that several alcohol-related behaviors, including the consumption of nightcaps and years of drinking, were significantly associated with insomnia symptoms and poor sleep quality. Specifically, nightcaps were significantly associated with all types of insomnia symptoms and poor sleep quality, with a higher odds ratio than other alcohol-related items. Our findings suggest that specific alcohol-related behaviors, particularly the consumption of nightcaps, are associated with insomnia symptoms and poor sleep quality among women. Intervention programs for alcohol consumption should be provided to prevent sleep problems among women. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-6382 14 3 2025 Influence of Educational Films on Antiviral Prescription for COVID-19: Insights from Web-Based Survey in Japan 276 EN Kosaku Komiya Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine Akihiko Hagiwara Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine Yuichiro Shindo Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Kazufumi Takamatsu Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Naoki Nishimura Department of Respiratory Medicine, National Center for Global Health and Medicine Yukako Takechi Iki-iki Clinic Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Takahiro Takazono Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences Shinyu Izumi Department of Respiratory Medicine, National Center for Global Health and Medicine Shimpei Gotoh Department of Clinical Application, Center for iPS Cell, Research and Application, Kyoto University Seiichiro Sakao Department of Pulmonary Medicine, School of Medicine, International University of Health and Welfare Takehiro Izumo Department of Respiratory Medicine, Japanese Red Cross Medical Center Kazuko Yamamoto Division of Infectious, Respiratory, and Digestive Medicine, First Department of Internal Medicine, University of the Ryukyus Graduate School of Medicine Kazuhiro Yatera Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Japan Hiroshi Kakeya Department of Infection Control Science, Osaka Metropolitan University Graduate School of Medicine Yoko Shibata Department of Pulmonary Medicine, Fukushima Medical University School of Medicine Keisuke Tomii Department of Respiratory Medicine, Kobe City Medical Center General Hospital Hironori Sagara Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine Yuka Sasaki Center for Pulmonary Disease, National Hospital Organization Tokyo Hospital Toyohiro Hirai Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University Akihito Yokoyama Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Hiroshi Mukae Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences Takashi Ogura Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center Background: Prescribing antiviral agents for severe acute respiratory syndrome coronavirus 2 requires careful consideration based on the patient�fs risk factors for severe disease progression and their vaccination status. However, effective interventions ensuring the appropriate use of antiviral agents by physicians have yet to be fully established. Thus, this study evaluated the impact of an educational film on antiviral prescription rates for coronavirus disease 2019 (COVID-19). Methods: This prospective, nationwide, web-based survey enrolled 1500 physicians. They were instructed to view a short educational film and assess the necessity of prescribing antiviral agents in 16 fictitious scenarios featuring adult patients with COVID-19 with varying risk factors for severe disease and vaccination statuses. We compared the antiviral prescription rates before and after viewing the educational film. Results: There was a significant increase in the antiviral prescription rates after viewing the educational film, particularly nirmatrelvir/ritonavir prescribed in cases involving immunocompromised patients (from 31.3% to 49.4%) and those with obesity (from 15.1% to 33.7%) who were unvaccinated and had no risk of drug interactions. However, viewing the educational film made little to no impact on the prescription rates for the patients with hypertension and hyperlipidemia or those with no underlying conditions. Conclusions: Short educational films may promote the appropriate use of antiviral agents for COVID-19. However, their impact on altering prescription behavior appears limited and varies according to the clinical context. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study 1 13 EN Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Ken Yamamoto Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Ken Masuda Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Takuji Suzuki Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Shoichi Kuyama Department of Respiratory medicine, NHO Iwakuni Clinical Center Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen�fs Hospital Hiroshi Kuraishi Department of Respiratory Medicine, Nagano Red Cross Hospital Ken Yoshihara Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci + GC) administration. However, the prognostic effect of skin disorders in patients with lung squamous cell carcinoma (LSCC) administered Neci + GC is unclear.<br> Objectives: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration.<br> Design: This was a sub-analysis of the retrospective multicenter NINJA study.<br> Methods: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders.<br> Results: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278 days, p = 0.0201; median PFS: 148 vs 82 days, p = 0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p = 0.0044) and PFS (p = 0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101 days, p = 0.0495).<br> Conclusion: A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0961-8368 35 10 2026 Conformational stability and domain�]specific structural features of tumor autoantigens regulate autoantibody epitope propensity e70808 EN Ai Miyamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rika Yamamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryui Sakaguchi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rikako Kutsuma Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takeru Mori Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mirei Masui Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomoko Honjo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Midori Futami Department of Bioscience, Faculty of Life Science, Okayama University of Science Mariko Morii Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hiromi Watanabe Department of Respiratory Medicine, Okayama University Hospital Tadahiro Kuribayashi Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Junichiro Futami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Autoantibodies against tumor-associated autoantigens are clinically valuable biomarkers for cancer diagnosis; however, the structural determinants governing epitope selectivity remain unknown. Here, we investigated whether the intrinsic conformational stability of target autoantigens regulates the epitope propensity of tumor-associated autoantibodies in non-small cell lung cancer. Using a dual-antigen Luminex bead-based assay that presents each autoantigen in both native and S-cationized denatured forms, we directly compared IgG autoantibody reactivity toward conformational and linear epitopes across 11 autoantigens. Intrinsically disordered aggregation-prone autoantigens, including cancer/testis antigens, NY-ESO-1, and XAGE-1b, predominantly elicit linear epitope-directed responses, whereas thermodynamically stable soluble autoantigens generally drive conformational epitope recognition. Intriguingly, for autoantigens harboring both ordered and disordered segments, the immune response is strictly guided by domain-specific biophysics: while p53-specific antibodies preferentially target their flanking disordered regions, the Wilms' tumor protein 1 exceptionally drives conformational recognition directed toward its structured zinc-finger domains. Recombinant solubility in Escherichia coli broadly correlated with epitope class across all 11 autoantigens, confirming that prokaryotic folding efficiency generally reflects intrinsic conformational stability in vivo for autonomously folding monomeric cytosolic proteins. Independent computational validation was provided by the concordance between the experimental solubility ratios and AlphaFold3-derived Rosetta energy unit/solvent-accessible surface area values, demonstrating the convergence of thermodynamic estimates and patient-derived immune data within a unifying biophysical framework. These findings establish that the autoantibody epitope propensity is closely associated with the thermodynamic stability of the target autoantigen and provide a rational basis for tailoring antigen preparation strategies for autoantibody-based cancer diagnosis. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-2615 75 3 2026 Investigation of carbapenem-hydrolysing Klebsiella oxytoca strains lacking detectable carbapenemase genes 002139 EN Hiroshi Teraguchi Department of Clinical Laboratory, Kindai University Nara Hospital Ayaka Oda Dental School, Okayama University Satoyo Wakai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Sayoko Kawakami Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Koki Yoshida Department of Clinical Laboratory, Kindai University Nara Hospital Wataru Hayashi Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Norikazu Kitamura Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Yo Sugawara Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Naoya Ohara Dental School, Okayama University Motoyuki Sugai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Koji Yahara Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Aki Hirabayashi Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Introduction. Carbapenemase-producing Enterobacterales (CPE) pose a clinical concern due to limited treatment options and plasmid-mediated spread of carbapenemase genes. The modified carbapenem inactivation method (mCIM) is increasingly used in clinical settings to detect CPE.<br> Gap Statement. Interpretation of mCIM results for isolates with reduced carbapenem susceptibility remains challenging.<br> Aim. To assess the interpretation of positive mCIM results in Klebsiella oxytoca isolates lacking detectable carbapenemase genes and exhibiting reduced carbapenem susceptibility and to propose a phenotypic testing strategy for accurate evaluation.<br> Methodology. Antimicrobial susceptibility testing with clavulanic or dipicolinic acid supplementation, phenotypic carbapenemase assays, carbapenem hydrolysis assays and whole-genome sequencing (WGS) were conducted on K. oxytoca strains.<br> Results. K. oxytoca strains were isolated from both blood and urine samples of a patient in a Japanese hospital. Although classified as susceptible by clinical breakpoints, these isolates exhibited reduced susceptibility to carbapenems. Although these strains were mCIM-positive, the zinc-supplemented carbapenem inactivation method did not support the presence of metallo-ƒÀ-lactamase (MBL) activity. MIC reductions in the presence of CVA were consistent with inhibition of a class A ƒÀ-lactamase. In contrast, dipicolinic acid supplementation did not reduce the meropenem MIC, ruling out MBL production. Furthermore, WGS revealed that both K. oxytoca strains lacked known carbapenemase genes, with blaOXY-2-4 being the only identifiable ƒÀ-lactamase gene encoding a class A enzyme. No novel ƒÀ-lactamase genes were identified; however, an enhanced blaOXY-2-4 expression-associated point mutation was found in the promoter region. Both K. oxytoca strains exhibited carbapenem-hydrolysing activity, although to a lesser extent than that of the MBL-producing strain.<br> Conclusion. We identified K. oxytoca strains that lacked known carbapenemase genes but that yielded positive mCIM results, possibly due to OXY-2 overproduction. Our study findings emphasize the need for cautious mCIM result interpretation for K. oxytoca and highlight the diagnostic value of combined susceptibility testing with clavulanic and dipicolinic acids to distinguish the underlying resistance mechanisms. Combining complementary clinical laboratory tests will enable clarification of the factors underlying mCIM positivity and guide clinical decision-making. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-8609 100 4 2025 Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns 592 605 EN Mizuna Otsuka Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Tomohiro Koga Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Remi Sumiyoshi Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Shoichi Fukui Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Yuko Kaneko Division of Rheumatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan Takayuki Shimizu Division of Hematology, Department of Medicine, Keio University School of Medicine Atsushi Katsube Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine Shingo Yano Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine Yasufumi Masaki Department of Hematology and Immunology, Kanazawa Medical University Makoto Ide Department of Hematology, Takamatsu Red Cross Hospital Hajime Yoshifuji DDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University Masayasu Kitano Department of Collagen Disease and Rheumatology, Sumitomo Hospital Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Naoki Sawa Nephrology Center and Department of Rheumatology, Toranomon Hospital Kajigaya Hiroaki Niiro Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital Naoya Nakamura Department of Pathology, Tokai University School of Medicine David C. Fajgenbaum Center for Cytokine Storm Treatment & Laboratory, University of Pennsylvania Frits van Rhee Myeloma Center, University of Arkansas for Medical Sciences Atsushi Kawakami Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Individuals diagnosed with Castleman disease (CD) and TAFRO syndrome (characterized by thrombocytopenia, anasarca, fever, bone marrow fibrosis, and organomegaly) displays a wide range of clinical symptoms, including varying patterns of lymph node enlargement, systemic inflammation, and impaired organ function. Some patients may present with both CD and TAFRO syndrome concurrently. A retrospective study conducted across multiple centers in Japan examined 321 cases to determine if the quantity and position of swollen lymph nodes could forecast the clinical progression and intensity of these conditions. Interestingly, the study revealed that patients with TAFRO syndrome exhibited lymphadenopathy across all ranges of lymph node region counts. Moreover, no specific clinical patterns were associated with the number of affected lymph node regions in CD patients, regardless of whether they also had TAFRO syndrome. These results enhance our understanding of the clinical variability in CD and TAFRO syndrome, suggesting that a comprehensive clinical evaluation, rather than relying solely on lymph node count, is crucial for effectively managing these conditions. Additional studies are required to establish reliable diagnostic markers and to predict disease severity at the time of diagnosis, ultimately improving patient outcomes. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2212-5345 63 3 2025 Practical Guidelines for Asthma Management (PGAM): Digest edition 405 421 EN Jun Tamaoki Department of Respiratory Medicine, Tokyo Women's Medical University Hiroyuki Nagase Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine Hiroyuki Sano Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Takeshi Kaneko Department of Pulmonology, Yokohama City University Graduate School of Medicine Yasuhiro Gon Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Hironori Sagara Department of Medicine, Division of Allergology and Respiratory Medicine, School of Medicine, Showa University Akihiko Tanaka Department of Medicine, Division of Allergology and Respiratory Medicine, School of Medicine, Showa University Takahiko Horiguchi Department of Respiratory Medicine, Toyota Regional Medical Center Etsuko Tagaya Department of Respiratory Medicine, Tokyo Women's Medical University Tomohiro Akaba Department of Respiratory Medicine, Tokyo Women's Medical University Yuji Tohda Kindai University Hospital The international and national guidelines for asthma management are typically comprehensive and designed for respiratory specialists, making them less practical for primary care physicians who handle most asthma cases. Recognizing the need for more accessible guidelines, the Japan Asthma Society developed the Practical Guidelines for Asthma Management (PGAM). PGAM aims to provide a concise summary of key asthma management principles, increasing awareness, education, and support among nonspecialists and patients alike. It includes user-friendly tables and lists outlining common symptoms, triggers, diagnostic criteria, and basic management strategies, along with frequently encountered treatable traits and comorbidities. These elements are presented through simple, clinically relevant algorithms. A notable feature of PGAM is the �gBasic Roadmap for Asthma Management,�h which outlines a clear sequence for patient assessment, diagnosis, and treatment from initial consultation onward, offering an easy-to-follow visual guide. Additionally, the guidelines include methods for assessing airway inflammation, enabling patient phenotyping and endotyping. This supports a personalized treatment approach, particularly with biologics, aimed at achieving clinical remission. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 8 2 2025 Unraveling Causality: Innovations in Epidemiologic Methods 323 337 EN Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University For several decades, the counterfactual model and the sufficient cause model have shaped our understanding of causation in biomedical science and, more recently, the link between these two models has enabled us to obtain a deeper understanding of causality. In this article, I provide a brief overview of these fundamental causal models using a simple example. The counterfactual model focuses on one particular cause or intervention and gives an account of the various effects of that cause. By contrast, the sufficient cause model considers sets of actions, events, or states of nature which together inevitably bring about the outcome under consideration. In other words, the counterfactual framework addresses the question �gwhat if?�h while the sufficient cause framework addresses the question �gwhy does it happen?�h Although these two models are distinct and address different causal questions, they are closely related and used to elucidate the same cause-effect relationships. Importantly, the sufficient cause model makes clear that causation is a multifactorial phenomenon, and it is a �gfiner�h model than the counterfactual model; an individual is of one and only one response type in the counterfactual framework, whereas an individual may be at risk of none, one, or several sufficient causes. Understanding the link between the two causal models can provide greater insight into causality and can facilitate the use of each model in appropriate contexts, highlighting their respective strengths. I will briefly present three topics of interest from our research: the relationship between the concepts of confounding and of covariate balance; distinctions between attributable fractions and etiologic fractions; and the identification of operating mediation and mechanism. It is important to scrutinize observed associations in a complementary manner, using both the counterfactual model and the sufficient cause model, employing both inductive and deductive reasoning. This holistic approach will better help us to unravel causality. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0929-1903 32 5 2025 Tob negatively regulates NF-ƒÈB activation in breast cancer through its association with the TNF receptor complex 573 583 EN Miho Tokumasu Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsuko Sato Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University Taku Ito-Kureha Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University Mizuki Yamamoto Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo Nao Ohmine Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University Kentaro Semba Department of Life Science and Medical Bioscience, Waseda University Jun-ichiro Inoue The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA) Tadashi Yamamoto Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University NF-ƒÈB mediates transcriptional regulation crucial to many biological functions, and elevated NF-ƒÈB activity leads to autoimmune and inflammatory diseases, as well as cancer. Since highly aggressive breast cancers have few therapeutic molecular targets, clarification of key molecular mechanisms of NF-ƒÈB signaling would facilitate the development of more effective therapy. In this report, we show that Tob, a member of the Tob/BTG family of antiproliferative proteins, acts as a negative regulator of the NF-ƒÈB signal in breast cancer. Studies with 35 human breast cancer cell lines reveal that Tob expression is negatively correlated with NF-ƒÈB activity. Analysis of The Cancer Genome Atlas (TCGA) database of clinical samples reveals an inverse correlation between Tob expression and NF-ƒÈB activity. Tob knockdown in human breast cancer cells promoted overactivation of NF-ƒÈB upon TNF-ƒ¿ treatment, whereas overexpression of Tob inhibited TNF-ƒ¿ stimulation-dependent NF-ƒÈB activation. Mechanistically, Tob associates with the TNF receptor complex I and consequently inhibits RIPK1 polyubiquitylation, leading to possible prevention of overwhelming activation of NF-ƒÈB. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-3751 604 18 2026 Integrative simulation analysis of myocardial ischaemia–reperfusion injury 7640 7662 EN Takao Shimayoshi Center for Artificial Intelligence and Mathematical Data Science, Okayama University Ayako Takeuchi Department of Physiology and Biophysics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Matsuoka Department of Integrative and Systems Physiology, Faculty of Medical Sciences, University of Fukui Cardiac ischaemia, reduced coronary blood flow, causes significant damages to the heart, and paradoxically reperfusion, restored flow after ischaemia, often results in more severe injury. Although the mechanisms underlying cardiac ischaemia–reperfusion injury have been intensively investigated, effective therapeutic strategies applicable during reperfusion to mitigate this damage have not been established yet. To obtain more insights into the mechanisms underlying ischaemia–reperfusion injury, and to explore effective methods to relieve reperfusion injury, we developed a comprehensive mathematical model of ventricular myocyte, implementing excitation–contraction (E–C) coupling, cytosolic and mitochondrial pH regulation, pH dependence of major components of E–C coupling and cellular energy metabolism, including mitochondrial oxidative phosphorylation. The mathematical model successfully reproduced experimentally observed findings on cardiac ischaemia–reperfusion injury, such as intracellular and extracellular acidosis, cytosolic Na+ overload, cytosolic Ca2+ overload, mitochondrial dysfunction, action potential shortening and contraction failure. It was found that the reperfusion-induced exacerbation of Na+i, Ca2+i overloads was mainly caused by insufficient production of NADH, which is used in mitochondrial oxidative phosphorylation to synthesize ATP for Na+/K+ pump and sarcoplasmic/endoplasmic reticulum Ca2+ pump (SERCA) to expel accumulated cytosolic Na+ and Ca2+, respectively. It was suggested that the preservation of mitochondrial NADH production, attenuation of ATP consumption via SERCA or contraction for a short period or activation of the Na+/K+ pump during reperfusion mitigates reperfusion injury. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 16 6 2026 Association between venous access-site closure device use and postoperative nausea and vomiting after atrial fibrillation ablation under propofol sedation: a single-centre retrospective observational study in Okayama, Japan e117719 EN Haruna Sakanoue Department of Nursing, Okayama Heart Clinic Hirosuke Yamaji Heart Rhythm Centre, Okayama Heart Clinic Sayaka Okamoto Department of Nursing, Okayama Heart Clinic Kumi Okano Department of Nursing, Okayama Heart Clinic Yuka Fujita Department of Nursing, Okayama Heart Clinic Shunichi Higashiya Heart Rhythm Centre, Okayama Heart Clinic Takashia Murakami Heart Rhythm Centre, Okayama Heart Clinic Satoshi Hirohata Graduate School of Health Sciences, Department of Medical Technology, Okayama University Shozo Kusachi Heart Rhythm Centre, Okayama Heart Clinic Objectives To examine whether the use of a venous access-site closure device is associated with the occurrence of postoperative nausea and vomiting (PONV) after atrial fibrillation (AF) ablation under propofol sedation.<br> Design Observational study.<br> Setting A single-centre retrospective observational study in Okayama, Japan.<br> Participants We retrospectively analysed consecutive patients who underwent AF ablation under deep propofol sedation with adaptive servo-ventilation. A total of 686 patients were included. Patients were managed using a standardised sedation protocol with or without low-dose pentazocine. Patients treated with conventional manual compression for haemostasis (n=383) were compared with those treated using a venous access-site closure device (n=303).<br> Interventions Postprocedural bed rest duration and the incidence and timing of PONV were compared between groups. Associations between closure device use and PONV were evaluated using logistic regression analysis.<br> Primary outcome measure The primary outcome was the occurrence of PONV following AF ablation.<br> Results All procedures were completed under propofol sedation without conversion to general anaesthesia. The duration of postprocedural bed rest was shorter in the device group than in the conventional-compression group (mean difference �|14.7 hours, 95% CI �|15.2 to �|14.0).<br> PONV occurred in 6/303 patients (2.0%) in the device group and 20/383 patients (5.2%) in the conventional-compression group, corresponding to a relative risk of 0.38 (95% CI 0.15 to 0.93), an OR 0.25 (95% CI 0.10 to 0.62) and a risk difference of �|3.2% (95% CI �|6.0% to �|0.5%).<br> In multivariable analysis, use of a venous closure device was associated with a lower likelihood of PONV.<br> Conclusions In this single-centre observational study, use of a venous access-site closure device was associated with a lower occurrence of PONV after AF ablation under propofol sedation. These findings suggest that postprocedural management strategies enabling earlier mobilisation may be associated with improved patient comfort; however, causal inference is limited by the observational design. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 16 8 2026 Study protocol for a phase II clinical trial evaluating the safety and efficacy of favipiravir injection combined with oseltamivir in influenza treatment e106715 EN Sayaka Hikida Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Hidetoshi Nomoto Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Yukari Uemura Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Tadaki Suzuki Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security Koichi Izumikawa Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences Hiroki Ohge Project Research Center for Nosocomial Infectious Diseases, Hiroshima University Masaya Yamato Infectious Diseases Center, Rinku General Medical Center Yasuyuki Kato Department of Infectious Diseases, International University of Health and Welfare Narita Hospital Ryota Hase Department of Infectious Diseases, Japanese Red Cross Narita Hospital Tetsuji Aoyagi Department of Clinical Microbiology and Infection, Tohoku University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoko Nukui Department of Infection Control & Laboratory Medicine, Kyoto Prefectural University of Medicine Kazuko Yamamoto First Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus Graduate School of Medicine Yoshio Takesue Chita Peninsula General Medical Organization, Rinku Hospital Kota Sawada Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Yosuke Shimizu Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Sho Miyamoto Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security Namiko Tamura Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Kozue Takahashi Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Sho Saito Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Kazuki Miyazaki Center for Clinical Sciences, Japan Institute for Health Security Eriko Morino Center for Clinical Sciences, Japan Institute for Health Security Daisuke Tokita Center for Clinical Sciences, Japan Institute for Health Security Norio Ohmagari Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Introduction Older adults are at an increased risk of influenza-related hospitalisation and mortality due to a combination of risk factors. Severe influenza and excess mortality in this population remain major public health concerns, underscoring the need for novel treatment strategies.<br> Methods and analysis This multicentre, investigator-initiated, randomised, double-blind clinical trial evaluated the efficacy and safety of the investigational drug favipiravir injection (T-705IV) in combination with oseltamivir phosphate, compared with oseltamivir monotherapy in hospitalised patients with influenza aged ≥65 years. Both T-705IV and oseltamivir phosphate will be administered for 5 days. The primary endpoint is time from randomisation to recovery within 15 days. Recovery is defined as either actual hospital discharge or sustained clinical status permitting discharge for 3 consecutive days. Clinical status will be assessed using a 7-point ordinal scale based on hospitalisation status and oxygen requirement. The primary analysis employs a Bayesian Cox proportional hazards model with a non-informative prior to estimate the posterior probability that the HR exceeds 1.0. The secondary endpoints include the distribution of 7-point scale scores over a 29-day period; rates of clinical worsening at days 15 and 29; duration of fever; all-cause mortality; intensive care unit admission within 29 days; pneumonia complication rate at 15 days; and changes in viral titre and viral RNA load on days 1, 2, 3 and 7. Safety will be assessed through the collection of adverse events (AEs) up to day 29. Pharmacokinetic evaluation will include measurement of plasma favipiravir concentrations on day 3. The planned sample size is 80 patients (40 per group).<br> Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by the Center Hospital of the National Center for Global Health and Medicine Institutional Review Board (approval number: NCGM-I-022-24a) and registered in the Japan Registry of Clinical Trials. Study findings will be disseminated through peer-reviewed publications and/or presentations at academic conferences.<br> Trial registration number jRCT2031240586, No potential conflict of interest relevant to this article was reported.

Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, Japan Society of Gynecologic Oncology Acta Medica Okayama 2005-0380 37 5 2026 Examining the relationship between cesarean section scar and endometrial cancer e96 EN Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Tani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironori Itou Department of Obstetrics and Gynecology, National Hospital Organization Iwakuni Clinical Center Miyuki Shimizu Department of Obstetrics and Gynecology, Kagawa Rosai Hospital Thi Hai Ly Dao Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikari Nakato Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Okamoto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Ogawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: The incidence of endometrial cancer (EC) has been increasing annually. Studies have reported that cesarean section (CS) is associated with a higher risk of developing EC than vaginal delivery (VD). However, few studies have examined the relationship between CS and EC development.<br> Methods: Data were extracted from the medical records of patients with EC and a history of childbirth who underwent EC treatment at 3 institutions. Factors contributing to EC development were analyzed between April 2010 and December 2024.<br> Results: Among patients EC and a history of childbirth, 8.7% (69/794) had undergone CS, and 50.7% (35/69) developed a CS scar. Compared with patients who had a VD or those without a CS scar, patients with a CS scar showed significantly shorter intervals from delivery to EC onset (VD: p=0.013; non-CS scar: p=0.031). A narrower residual myometrial thickness/adjacent myometrial thickness (RMT/AMT) ratio of the CS scar was significantly associated with a shorter interval from the last delivery to EC onset (p=0.034) and was independently associated with earlier EC onset after the last delivery in both univariate and multivariate analyses (p<0.001 and p=0.030, respectively).<br> Conclusion: A narrower RMT/AMT ratio in the CS scar was considerably associated with a shorter interval from the last delivery to EC onset. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2576-098X 2026 Complete genome sequence of Helicobacter pylori strain NY43 harboring bacteriophage KHP30 e00747-26 EN Michiko Takahashi Department of Surgery, Kochi Medical School, Kochi University Hiromichi Maeda Department of Surgery, Kochi Medical School, Kochi University Satoru Seo Department of Surgery, Kochi Medical School, Kochi University Hiroaki Takeuchi Department of Medical Laboratory Sciences, Health and Science, International University of Health and Welfare Graduate School Jumpei Uchiyama Department of Infectious Diseases, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Surgery, Kochi Medical School, Kochi University The Helicobacter pylori NY43 strain spontaneously releases the bacteriophage (phage) KHP30. Here, we report the complete genome sequence of H. pylori NY43. In addition to the chromosome of H. pylori NY43, we successfully obtained the complete sequence of the episomal prophage KHP30. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 17 1 2026 RNase-mediated defence and its association with SCCmec in Staphylococcus aureus 9986 EN Kohei Kondo Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Aa Haeruman Azam Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Junzo Hisatsune Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Shinjiro Ojima Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Kotaro Chihara Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Tomohiro Nakamura Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Azumi Tamura Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Wakana Yamashita Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Satoshi Nakano Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Shoko Kutsuno Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Yo Sugawara Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Masayuki Amagai Department of Dermatology, Keio University School of Medicine Tetsuo Yamaguchi Department of Microbiology and Infectious Diseases, Toho University School of Medicine Yoshikazu Ishii Department of Microbiology and Infectious Diseases, Toho University School of Medicine Koichi Watashi Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Yoshimasa Takahashi Research Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security Kotaro Kiga Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Motoyuki Sugai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security The rise of antibiotic resistance in Staphylococcus aureus is a major threat to global health. Resistance often emerges when bacteria acquire foreign DNA elements, such as the SCCmec cassette that makes strains resistant to nearly all ƒÀ-lactam antibiotics. Yet, not all S. aureus lineages take up these elements equally, raising the question of what prevents some strains from becoming drug-resistant. Here we identify a previously unknown defence factor that explains this mystery in a common skin lineage (ST188), frequently isolated from patients with atopic dermatitis. Such defence factor is encoded by a gene, which we name sadR, that is present in methicillin-susceptible ST188 strains but absent from resistant counterparts. SadR exhibits RNase activity that provides anti-bacteriophage and anti-plasmid defence, thus acting as a barrier to the uptake of mobile genetic elements. Gene sadR is found in methicillin-susceptible strains in S. aureus lineages other than ST188, and is consistently located adjacent to rlmH, the canonical SCCmec integration site. Moreover, SadR homologues are widespread across staphylococci and other bacteria suggesting a previously unrecognised family of RNase-based defence systems. No potential conflict of interest relevant to this article was reported.

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 21 3 2026 Incidence of pelvic fractures after definitive radiotherapy for cervical cancer: A retrospective multicenter cohort study (The IPFAR study) e0344384 EN Shinsuke Shirakawa Department of Obstetrics and Gynecology, Okayama University Shoji Nagao Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kotaro Yoshio Department of Radiology, Okayama University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Noriaki Imafuku Department of Obstetrics and Gynecology, Fukuyama Medical Center Dan Yamamoto Department of Obstetrics and Gynecology, Fukuyama Medical Center Masae Yorimitsu Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital Junichi Kodama Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital Hisako Nagasaka Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Yoshie Nakanishi Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Objective<br> This multicenter study aimed to identify the risk factors for pelvic insufficiency fractures (PIFs) in women who received definitive radiotherapy (RT) as the initial treatment for cervical cancer and to examine the differences in the incidence of PIFs across institutions.<br> Patients and Methods The medical records of 208 women were reviewed. These women received definitive RT as an initial treatment for cervical cancer at four institutions between January 2016 and December 2018.<br> Results<br> The median age was 61.5 years (range: 29–93 years). Overall, 59 patients (28.4%) developed PIF, with 48 (81.4%) of them developing it within two years after completion of RT. Multivariate analysis identified postmenopausal status and treating institution as independent risk factors. The incidence of PIF varied significantly among institutions, ranging from 18.9% to 50.0%, despite no significant differences in patient demographics or RT protocols.<br> Conclusion<br> Substantial inter-institutional variation in PIF incidence was observed, even under standardized treatment conditions. These findings underscore the need for individualized risk assessment and institutional quality control in the long-term management of cervical cancer survivors. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2328-8957 12 3 2025 Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory Mycobacterium avium Complex Pulmonary Disease ofaf118 EN Yu Kurahara Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Shiomi Yoshida Clinical Research Center, NHO Kinki Chuo Chest Medical Center , Osaka , Asami Osugi Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Yuya Tanaka Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Takehiko Kobayashi Clinical Research Center, NHO Kinki Chuo Chest Medical Center Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Yohei Kawasaki Department of Biostatistics, Graduate School of Medicine, Saitama Medical University Satoshi Mitarai Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Kazunari Tsuyuguchi Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Background. Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear.<br> Methods. We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance.<br> Results. We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype (P = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ≥1 mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66–70.40) compared with those with CRP <1 mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ≥128 µg/mL), and of these 71.4% (5/7) had rrs mutations.<br> Conclusions. Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 8 2026 Impact of Adjusted Creatinine Clearance on Carboplatin Dosing in Endometrial Cancer: A Retrospective Study 1285 1290 EN Kentaro Katayama Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Makio Imamura Department of Clinical Support, Kurashiki Medical Center Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Carboplatin (CBDCA) dosing is commonly determined using the Calvert formula, with creatinine clearance (Ccr) estimated by the Cockcroft–Gault formula. In Japan, where serum creatinine (sCr) is usually measured enzymatically, unadjusted Ccr may overestimate glomerular filtration rate and lead to CBDCA overdosing. We retrospectively compared treatment exposure, hematologic toxicity, and exploratory oncologic outcomes in patients with endometrial cancer who received postoperative paclitaxel plus CBDCA therapy. Patients were grouped according to whether CBDCA dosing was based on the conventional Cockcroft–Gault formula (CG group) or on adjusted Ccr calculated by adding 0.2 mg/dL to sCr (adjusted group). The incidence of Grade ≥3 neutropenia was significantly lower in the adjusted group than in the CG group. The 5-year progression-free survival (PFS) rate was numerically lower in the adjusted group than in the CG group, although no statistically significant difference was observed between the groups. Because the number of PFS events was limited, the effect of adjusted Ccr-based dosing on oncologic outcomes remains uncertain. These findings suggest that adjusted Ccr-based dosing may reduce hematologic toxicity in routine clinical practice. However, given the limited number of PFS events and the wide uncertainty in survival estimates, further studies are needed to clarify its impact on oncologic outcomes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 6 2026 Routine Generative AI Use and Acceptance of Medical AI: A Cross-Sectional Survey of Healthcare Workers and the Public in Japan e110118 EN Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Background<br> Acceptance of medical artificial intelligence (AI) is critical for successful implementation, yet its acceptance may vary by clinical application and stakeholder group. Whether routine use of generative AI (GAI) is associated with acceptance of medical AI remains unclear.<br> Methods<br> A cross-sectional web survey was conducted in Japan in November 2025 using web-panel convenience sampling from an online research panel. The small analytic sample comprised 200 participants aged 20-69 years, including 100 healthcare workers and 100 non-healthcare workers. GAI use was assessed using two five-point items (GAI use at work and in daily life) and dichotomized as at least monthly use in either daily life or work versus less than monthly use in both settings, based on prespecified criteria. Acceptance of medical AI was measured for five scenario-based applications - AI-assisted imaging interpretation, AI-based health risk prediction, AI-based treatment recommendations, AI-enabled triage guidance, and AI-assisted robotic surgery - using a four-point acceptability scale; responses were dichotomized as acceptable versus not acceptable. Calibration weights were constructed to approximate Japanese internet users by raking on sex-by-age group and household income, normalized to the analytic sample size, and truncated at prespecified bounds. Adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression with robust standard errors, stratified by occupation; covariates were selected a priori using a modified disjunctive cause criterion. This study was exploratory; therefore, adjustments for multiple comparisons were not performed.<br> Results<br> Among healthcare workers, the lower-use group had a higher prevalence of non-acceptance of AI-based health risk prediction (aPR 6.980, 95% CI 1.412-34.506) and AI-based treatment recommendations (aPR 4.364, 95% CI 1.331-14.305), whereas estimates for imaging interpretation, triage guidance, and robotic surgery remained statistically uncertain. Among non-healthcare workers, the lower-use group had a higher prevalence of non-acceptance of AI-assisted imaging interpretation (aPR 13.906, 95% CI 1.624-119.052), AI-based health risk prediction (aPR 4.861, 95% CI 1.133-20.862), AI-based treatment recommendations (aPR 6.288, 95% CI 1.386-28.530), and AI-assisted robotic surgery (aPR 6.173, 95% CI 1.435-26.561); the adjusted estimate for AI-enabled triage guidance was not statistically supported (aPR 1.840, 95% CI 0.521-6.505). Several estimates had wide confidence intervals, indicating substantial imprecision.<br> Conclusions<br> In this small exploratory web-panel convenience sample, lower-frequency GAI use was associated with higher non-acceptance of several medical AI applications. Associations were observed across more applications among non-healthcare workers than among healthcare workers. Because the study was cross-sectional, used convenience sampling, and included imprecise estimates with wide confidence intervals, the findings should not be interpreted causally. Larger studies using longitudinal or interventional designs are needed to clarify temporality and mechanisms. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-806X 251 2027 A rule-based calculation approach to derive bone-suppressed chest X-ray images using photon-counting techniques 114493 EN Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Mana Mitani Division of Radiology, Medical Support Department, Okayama University Hospital Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Noriaki Akagi Division of Radiology, Medical Support Department, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Improving the visibility of lung nodules, which are often hidden by bone shadows and difficult to identify, remains a challenge in chest radiography. This study aims to develop an algorithm for generating novel bone-suppressed images using photon-counting techniques. The core idea of our algorithm is to fit photon interaction cross-sections to X-ray attenuation data measured with photon-counting detectors. Based on further calculations using the derived fitting coefficients, both density (ƒÏ) and amount-of-substance concentration (mol) were determined. The product of these values produced a ƒÏ�~mol image exhibiting a clear bone-suppression effect. We conducted a virtual chest imaging simulation using 10 patient datasets acquired via clinical photon-counting computed tomography (PC-CT). The CT images were converted into ƒÏ�~mol images following the proposed processing procedure, and two-dimensional chest images were generated through projection. Quantitative evaluations confirmed that the proposed images achieved sufficient bone suppression. Furthermore, commercial software provided by a vendor was used to generate bone-suppressed images from conventional images projected from CT data. A comparable bone-suppression effect on the ribs was observed between the vendor-generated images and our proposed images, while lesion visibility (e.g., lung nodules) was preserved. Additionally, bone-suppression effects in our images were observed in the vertebrae and clavicles located outside the lung fields. Our research demonstrates the value of constructing general X-ray imaging systems using photon-counting detectors. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 3050-5976 2 1 2026 Older patients with LBCL show comparable outcomes to younger patients and product-specific profiles in CAR-T therapy 100037 EN Sho Shibata Department of Hematology, Kyoto University Hospital Yasuyuki Arai Department of Hematology, Kyoto University Hospital Junya Kanda Department of Hematology, Kyoto University Hospital Daisuke Kaji Department of Hematology, Toranomon Hospital Daisuke Minakata Division of Hematology, Department of Medicine, Jichi Medical University Toshio Kitawaki Department of Hematology, Kyoto University Hospital Kazuyuki Shimada Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Tatsu Shimoyama Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Shinichi Makita Department of Hematology, National Cancer Center Hospital, Tokyo Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Go Yamamoto Department of Hematology, Toranomon Hospital Emiko Sakaida Department of Hematology, Chiba University Hospital Yasuhiro Nakashima Department of Hematology, Osaka Metropolitan University Hospital Akiyo Yoshida Division of Transfusion Medicine, Kanazawa University Hospital Yoshihiro Umezawa Department of Hematology, Institute of Science Tokyo Hospital Jun Kato Division of Hematology, Department of Medicine, Keio University School of Medicine Haryoon Kim Division of Hematology, Department of Medicine, Keio University School of Medicine Keisuke Kataoka Division of Hematology, Department of Medicine, Keio University School of Medicine Hideki Goto Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Koji Kato Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a key treatment option for patients with relapsed or refractory large B-cell lymphoma (LBCL). However, data on its effectiveness and safety in older populations remain limited, particularly in real-world clinical practice. Moreover, comparative outcomes among different CAR-T products across age groups have not yet been fully characterized. We conducted a nationwide retrospective cohort study using data from the Japanese Society for Transplantation and Cellular Therapy. A total of 908 patients who received CAR-T therapy between January 2019 and September 2024 were included. Patients were categorized as younger (aged <65 years) or older (aged ≥65 years). Subgroup analyses were performed by CAR-T product (tisagenlecleucel [tisa-cel], lisocabtagene maraleucel [liso-cel], and axicabtagene ciloleucel [axi-cel]). In univariate analysis, 1-year overall survival (OS) and progression-free survival (PFS) were comparable between younger and older patients (OS, 69.4% vs 65.7% [P = .40]; PFS, 47.9% vs 54.1% [P = .17]). In multivariate analysis, age ≥65 years showed no significant association with OS (hazard ratio, 0.88; 95% confidence interval, 0.65-1.21; P = .44). The incidence of immune effector cell–associated neurotoxicity syndrome was significantly higher in older patients (12.7% vs 7.0%; P = .005). Compared with tisa-cel, axi-cel and liso-cel were associated with superior PFS, predominantly in younger patients. Among older patients, axi-cel was associated with higher nonrelapse mortality rate than tisa-cel. CAR-T therapy is feasible and effective for older patients with LBCL. These findings support age-adapted treatment strategies that consider both the efficacy and toxicity of each product. No potential conflict of interest relevant to this article was reported.

XMLink Acta Medica Okayama 2005-0380 37 2026 Nationwide survey of hereditary breast and ovarian cancer–related clinical practice in gynecologic oncology in Japan: a joint study by the Japan Society of Gynecologic Oncology (JSGO) and the Japan Society of Obstetrics and Gynecology (JSOG) e122 EN Kenta Masuda Department of Obstetrics and Gynecology, Keio University School of Medicine Katsutoshi Oda Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo Hidemichi Watari Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine and Faculty of Medicine Akira Hirasawa Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinya Sato Department of Obstetrics and Gynecology, Tottori University School of Medicine Kenichi Harano Department of Medical Oncology, National Cancer Center Hospital East Satoru Nagase Department of Obstetrics and Gynecology, Faculty of Medicine, Yamagata University Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Masaki Mandai Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University Yuko Sasajima Department of Pathology, Teikyo University Hospital Tamotsu Sudo Department of Cancer Genetics & Genomics, Fujita Health University, School of Medicine Hiroyuki Yanai Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hitoshi Tsuda Department of Basic Pathology, National Defense Medical College Yusuke Kobayashi Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba Kei Kawana Department of Obstetrics and Gynecology, Nihon University School of Medicine Mikio Mikami Department of Medical Science, Shonan University of Medical Science Kiyoko Kato Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Daisuke Aoki International University of Health and Welfare Graduate School Aikou Okamoto Department of Obstetrics and Gynecology, The Jikei University School of Medicine Objective: To evaluate the current status of hereditary breast and ovarian cancer (HBOC)–related clinical practice in Japan, including genetic testing, risk-reducing surgery, and surveillance systems, and to identify institutional gaps and unmet needs.<br> Methods: A nationwide questionnaire survey was conducted between February and April 2024 targeting 647 Japan Society of Obstetrics and Gynecology–affiliated training facilities and gynecologic oncology centers. Institutional-level data on genetic testing, homologous recombination deficiency (HRD) testing, risk-reducing salpingo-oophorectomy (RRSO), postoperative management, surveillance practices, and healthcare infrastructure were collected. Responses from 248 institutions (response rate, 38.3%) were analyzed descriptively.<br> Results: BRCA1/2 genetic testing was performed in 83% of institutions, and HRD testing using the myChoice® CDx system in 87%. However, only 30% offered universal BRCA1/2 testing for ovarian, fallopian tube, or peritoneal cancer, and testing indications varied widely. Genetic counseling resources were uneven, with 29% lacking on-site genetic specialists, driven mainly by institutional characteristics rather than geographic location. RRSO was performed in 50% of institutions, predominantly laparoscopically. While management of occult carcinoma after RRSO was largely consistent, postoperative management of serous tubal intraepithelial carcinoma (STIC) and positive peritoneal cytology varied substantially. Over 70% of institutions reported a need for expanded insurance coverage for genetic services and preventive care.<br> Conclusion: Although HBOC-related genetic testing and preventive strategies are widely implemented in Japan, this nationwide survey revealed critical structural and evidence gaps, particularly in institutional capacity and the management of evidence-limited scenarios such as STIC, underscoring the need for system-level improvement. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 6 2026 Effect of Deuterated Drugs on Safety: Insights from Pharmacovigilance Data Analysis 983 988 EN Kohei Kitagawa Department of Neuropsychiatry, Okayama Psychiatric Medical Center Hideki Nawa Department of Pharmacy, Faculty of Pharmacy, Shujitsu University Shota Asai Department of Pharmacy, Faculty of Pharmacy, Shujitsu University Naohiro Iwata Department of Pharmacy, Okayama University Hospital Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Mitsuhiro Goda Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Huntington�fs disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Tetrabenazine (TBZ), a vesicular monoamine transporter 2 inhibitor, is commonly used to manage chorea; however, it may exhibit fluctuating plasma levels and elicit frequent adverse events. In this study, we aimed to clarify the effects of TBZ deuteration on its safety profile. We compared the safety profiles of TBZ and deutetrabenazine (DTBZ) in real-world clinical practice using disproportionality analysis and the large-scale pharmacovigilance database, VigiBase�\the WHO�fs global database of adverse drug reactions. Adverse event signals were assessed using the information component (IC). Seriousness was classified according to clinical outcome, and time to onset (TTO) was analyzed for selected events. TBZ showed signals for disorientation, dystonia, and sleep disorders (IC025 > 0), whereas DTBZ did not. Serious adverse events were reported in 54.7% of TBZ cases and 37.9% of DTBZ cases. The TTO of sleep disorder was also evaluated; however, the number of cases with available TTO information was limited. DTBZ showed fewer adverse event signals and a lower proportion of serious adverse events than TBZ. These findings suggest potential differences in the safety profiles of the two drugs, which may influence tolerability in the treatment of HD. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0941-4355 34 8 2026 Machine learning approaches to predict early cardiac immune-related adverse events in patients receiving immune checkpoint inhibitors 809 EN Michael Sayer School of Pharmacy & Pharmaceutical Sciences, University of California Peter D. Chang School of Medicine, Pathology & Laboratory Medicine, University of California Hirofumi Hamano Department of Pharmacy, Medical Development Field, Okayama University Reina Yamamoto Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Misako Nagasaka Division of Hematology and Oncology, University of California Ali A. Naqvi Mary & Steve Wen Cardiovascular Division, Department of Medicine, University of California Pranav M. Patel Mary & Steve Wen Cardiovascular Division, Department of Medicine, University of California Yoshito Zamami Department of Pharmacy, Medical Development Field, Okayama University Aya F. Ozaki School of Pharmacy & Pharmaceutical Sciences, University of California Purpose Immune checkpoint inhibitor (ICI)–induced cardiac immune-related adverse events (cardiac irAEs) are rare yet serious complications. Clinical assessment tools to identify at-risk patients would allow for more effective prevention strategies, thus improving clinical outcomes. We constructed various machine learning (ML) models to predict these events among patients receiving ICI therapy.<br> Methods A cohort of patients receiving ICI therapy from 2010 to 2023 was identified from the TriNetX database. Cardiac irAEs were defined as the occurrence of relevant diagnosis codes within 90 days of ICI initiation, with corresponding hospital visits. We created ML models to predict these events, including elastic net logistic regression and multiple tree-based approaches (gradient boosted trees and random forest). We evaluated model performance with different performance measures and utilized assigned risk scores to stratify risk of cardiac irAEs into low, medium, and high-risk tiers.<br> Results We identified 61,117 patients receiving ICI therapy, with nearly 2% of patients experiencing cardiac irAEs. Model performance on testing data was comparable with all approaches (AUC = 0.71–0.72, balanced accuracy = 65–66%). Each model emphasized distinct features to make classifications, as observed with feature importance and SHAP values. Comparing cardiac irAE rates among assigned risk strata, patients identified as high risk were significantly more likely to experience cardiac irAEs compared to lower tiers.<br> Conclusion Our preliminary exploration of ML methods demonstrated the potential for risk assessment tools to predict rare cardiac irAEs in patients receiving ICI therapy. Follow-up studies can implement time series approaches to harness longitudinal data that incorporates real-time labs, new diagnoses, and new therapy, to refine predictions further. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2045-1253 16 2026 Seizures associated with clozapine augmentation by other antipsychotics: a pharmacovigilance–pharmacodynamic analysis using VigiBase EN Masakazu Hatano Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Masaya Kanda Department of Pharmacy, Asahikawa Medical University Hospital Takenao Koseki Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Tsuyoshi Nakai Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Rina Horii Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Nozomi Yoshihara Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Takeo Saito Department of Psychiatry, Fujita Health University School of Medicine Kenshi Takechi Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University Satoru Esumi The Faculty of Pharmaceutical Sciences, Kobe Gakuin University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Shigeki Yamada Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Background: Clozapine is associated with a high risk of central nervous system abnormalities. However, seizure risk related to interactions between clozapine and other antipsychotics remains poorly characterized, and the pharmacological mechanisms underlying these seizures are unclear. Objectives: We aimed to evaluate safety signals for seizures associated with clozapine augmentation by other antipsychotics and analyze the relationship between these signals and neurotransmitter receptor occupancy profiles.<br> Design: A pharmacovigilance–pharmacodynamic analysis using a spontaneous reporting system.<br> Methods: This pharmacovigilance study used VigiBase, an adverse drug reaction database maintained by the World Health Organization. Drug–drug interactions (DDIs) between clozapine and other antipsychotics were assessed using the ƒ¶ shrinkage measure model. The association between DDI signals and neurotransmitter receptor occupancy was evaluated using linear regression. Robustness was tested using four frequency statistical models: additive, multiplicative, combination risk ratio, and chi-square statistic models. Results: Of 38,758,077 reports in VigiBase between 1990 and 2024, 230,371 involved clozapine. Among antipsychotics classified under ATC code N05A, DDIs with clozapine were detected for amisulpride, chlorpromazine, haloperidol, lurasidone, olanzapine, penfluridol, risperidone, sulpiride, zotepine, and zuclopenthixol. A significant association between dopamine D4 receptor occupancy and the point estimates of signal values was observed in the ƒ¶ shrinkage measure model (ƒÀ = 0.295, 95% confidence interval: 0.119–0.471, p = 0.002) and replicated across all frequency statistical models.<br> Conclusions: These findings suggest a potential role of dopamine D4 receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 2026 Biological Resectability in Colorectal Liver Metastases: A Nomogram�]Based Continuous Risk Model to Define Borderline Disease EN Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Kojima Department of Surgery, Okayama Saiseikai General Hospital Takeshi Koujima Department of Surgery, Himeji Red Cross Hospital Tatsuo Matsuda Department of Surgery, Tenwakai Matsuda Hospital Daisuke Satoh Department of Surgery, Hiroshima Citizens Hospital Masaru Inagaki Department of Surgery, National Hospital Organization Fukuyama Medical Center Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Resectability in colorectal liver metastases (CRLM) is traditionally defined by technical feasibility; however, a biologically based definition of borderline resectable disease has not been established. We evaluated the prognostic impact of KRAS mutation and developed a model for biological risk stratification.<br> Methods: This multi-institutional retrospective study included 584 patients undergoing initial hepatectomy for CRLM. The impact of KRAS mutation was assessed according to primary tumor sidedness and tumor burden score (TBS). A nomogram predicting overall survival (OS) was constructed using independent prognostic factors and compared with established clinical risk scores.<br> Results: KRAS mutation was identified in 36.8% of patients and was associated with worse OS (median survival: 47.3 vs. 70.6 months, p = 0.0006) and recurrence-free survival. This adverse impact was observed in left-sided tumors but not in right-sided tumors. TBS stratified prognosis in KRAS wild-type but not in mutant cases, suggesting that tumor biology may outweigh morphology. A nomogram incorporating KRAS status, TBS, CA19-9, primary nodal status, and extrahepatic disease demonstrated improved discriminatory ability compared with conventional models and stratified recurrence patterns, including extrahepatic recurrence.<br> Conclusions: The prognostic impact of KRAS mutation depends on tumor sidedness and is independent of tumor morphology. Our nomogram provides a continuous biological risk assessment and may facilitate biological risk stratification and support future refinement of the concept of biologically borderline resectable CRLM. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2165-0497 14 8 2026 High-throughput screening system for antimycobacterial compounds using in vitro infected cells: construction and application to compounds in the Ōmura Natural Compound Library e00484-26 EN Takemasa Takii Department of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Aoi Kimishima Ōmura Satoshi Memorial Institute, Kitasato University Masato Iwatsuki Ōmura Satoshi Memorial Institute, Kitasato University Yoshihiro Watanabe Ōmura Satoshi Memorial Institute, Kitasato University Naoya Ohara Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University Yukihiro Asami Ōmura Satoshi Memorial Institute, Kitasato University The global increase in multidrug-resistant tuberculosis strains poses a major threat; consequently, there is an urgent need to identify and develop novel drugs. We have previously presented a simple fibroblast assay (SFA) screening method that enables the simultaneous assessment of antibacterial activity and cytotoxicity toward host cells. This method was developed based on our finding that live (but not dead) Mycobacterium tuberculosis bacilli exhibit cytotoxic activity against human lung fibroblasts, and that this cytotoxicity, which is proportional to the number of viable bacterial cells, is inhibited by known antimycobacterial drugs. While conventional methods to measure M. tuberculosis growth require 2–4 weeks to detect antibacterial activity; the SFA method enables detection within 2–3 days and can detect compounds that are active within host cells. Here, we applied high-throughput screening, based on assessment of cytotoxicity, to identify candidate antimycobacterial agents. In parallel, by comparing the direct antibacterial activity of compounds in liquid medium (using the broth dilution test) with that observed via SFA, we developed a new SFA-based screening system to select compounds with low cytotoxicity that are active outside or inside the host cells. Using this dual system, we screened 742 compounds from the Ōmura Natural Compound Library (Kitasato University, Japan), with 62 hits. Of these, 19 were excluded owing to their toxicity, and six exhibited antibacterial activity only via SFA screening. Four promising antimycobacterial candidates with no cytotoxicity at the 10 ƒÊg/mL threshold�\aridicin A, lankamycin, streptovaricin, and lariatin A�\were identified. identified.This novel system supports the rapid identification of low-cytotoxicity antimycobacterial compounds that are active inside or outside the host cells. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2471-254X 10 3 2026 Hepatocellular carcinoma in Fontan-associated liver disease: Incidence, risk stratification, and surveillance implications e0910 EN Hideki Onishi Department of Gastroenterology and Hepatology, Medical Development Field, Okayama University Norihisa Toh Department of Cardiovascular Medicine, Medical Development Field, Okayama University, Okayama, Japan Kenji Baba Department of Pediatric Cardiology, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Kotani Department of Cardiovascular Surgery, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Kasahara Department of Cardiovascular Surgery, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoyuki Otsuka Department of Gastroenterology and Hepatology, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Hepatocellular carcinoma (HCC) is a serious complication of Fontan-associated liver disease (FALD). However, data on its incidence, risk factors, and outcomes in this rare population are limited. We aimed to assess the incidence and predictors of HCC and evaluate the utility of surveillance in patients with FALD.<br> Methods: We conducted a retrospective cohort study on patients with FALD who were referred to our gastroenterology department. The cumulative incidence of HCC after FALD diagnosis was calculated, and multivariate analysis was used to identify independent risk factors. Overall survival after FALD diagnosis was compared between patients who developed HCC and those who did not.<br> Results: A total of 120 patients with FALD were followed up for a median period of 50.0 months. The cumulative incidence rates of HCC at 1, 2, and 3 years after FALD diagnosis were 0.9%, 2.7%, and 3.9%, respectively. Elevated alpha-fetoprotein (AFP) at FALD diagnosis was independently associated with HCC development (hazard ratio, 1.29; 95% confidence interval, 1.04–1.60; p=0.01). There was no significant difference in overall survival between patients with and without HCC in this cohort (log-rank test, p=0.50).<br> Conclusions: Patients with FALD face a non-negligible risk of developing HCC, thus supporting the need for surveillance. Elevated AFP levels at the time of FALD diagnosis may aid in risk stratification, which enables the targeted monitoring and early detection of HCC. Furthermore, routine surveillance contributes to the excellent prognosis of patients with FALD who develop HCC, thus making their prognosis comparable to that of patients without HCC. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2047-9980 15 3 2026 Long�]Term Outcomes and Risk Factors for Mortality After Single Ventricle Palliation for Asplenia Syndrome e044756 EN Yasuyuki Kobayashi Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital Shunji Sano Department of Pediatric Cardiac Surgery Showa Medical University Toyosu Hospital Yuhei Tokuda Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital Ayari Kimura Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital Steven J. Staffa Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children�fs Hospital, Boston Harvard Medical School David Zurakowski Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children�fs Hospital, Boston Harvard Medical School Shingo Kasahara Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital Background: This study evaluated the long�]term outcomes of asplenia syndrome with single ventricle palliation, hypothesizing that total anomalous pulmonary vein connection (TAPVC), pulmonary atresia (PA), and greater than or equal to moderate atrioventricular valve regurgitation increase mortality risk.<br> Methods: This retrospective review analyzed 151 patients with asplenia syndrome who underwent single ventricle palliation between 1990 and 2024. The primary end point was mortality, with risk factors assessed by Cox regression analysis over a mean follow�]up of 9.3 years.<br> Results: The median age at initial operation was 35 days, including 70 neonates (46%). Overall, 62 (41%) patients died, whereas 66 (44%) patients are alive post�]Fontan completion. Survival probabilities at 1 and 20 years were 75.7% (95% CI, 67.9–81.8) and 53.7% (95% CI, 44.5–62.0), respectively. TAPVC (P=0.014), PA (P=0.007), and greater than or equal to moderate atrioventricular valve regurgitation (P=0.040) emerged as independent risk factors for mortality in the overall cohort. In the TAPVC cohort, independent risk factors for mortality included PA (P=0.019), infracardiac TAPVC (P=0.045), and neonatal TAPVC repair (P=0.018). When stratified by the risk factors of TAPVC, PA, or greater than or equal to moderate atrioventricular valve regurgitation, survival probabilities did not differ between patients with none or 1 of these conditions (P=0.181) but were significantly lower in those with ≥2 risk factors (P<0.001, at 15 years: 0, 72.9%; 1, 59.1%; ≥2, 32.8%).<br> Conclusions: Survival after single ventricle palliation for asplenia syndrome remains suboptimal, particularly when TAPVC, PA, and greater than or equal to moderate atrioventricular valve regurgitation are present in combination rather than in isolation. Improved strategies or surgical techniques are required for this complex asplenia syndrome cohort. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2052-8817 13 1 2026 Clinical and Microbiological Characteristics of Invasive Group A Streptococcus Infection: Four Case Series of Re�]Emerging Pathogens e70160 EN Shuji Okahara Department of Intensive Care, Okayama University Hospital Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuto Hamaguchi Department of Anesthesiology and Resuscitology, Okayama University Hospital Masanobu Hishiike Department of Anesthesiology and Resuscitology, Okayama University Hospital Yohei Motoi Department of Anesthesiology and Resuscitology, Okayama University Hospital Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Introduction: Group A Streptococcus (GAS), particularly the M1UK lineage, has re-emerged as a major global public health concern following the COVID-19 pandemic, with a rise in invasive GAS (iGAS) and streptococcal toxic shock syndrome (STSS). Although STSS is under national surveillance in Japan, comprehensive molecular monitoring of iGAS infections remains limited, and the clinical characteristics of M1UK-associated iGAS have not been fully elucidated.<br> Methods: We retrospectively reviewed four consecutive iGAS cases requiring intensive care between March and May 2024. Detailed clinical, microbiological, and genomic investigations were performed to characterize the causative strains and their associated virulence profiles.<br> Results: All patients required respiratory and/or circulatory support with surgical debridement. Three cases involved necrotizing fasciitis, and one involved intra-abdominal infection secondary to ovarian tumor rupture. All four patients received penicillin G and clindamycin as definitive antimicrobial therapy, with two developing severe drug-related adverse events. Genotypic analysis identified three isolates as emm1 strains, including two M1UK lineage strains. The two M1UK isolates commonly harbored multiple superantigen genes. All isolates remained susceptible to ƒÀ-lactam, clindamycin, and macrolide antibiotics.<br> Conclusion: This case series documents the identification of the M1UK lineage among critically ill patients with iGAS infections in Japan. Our findings support the need for continued molecular surveillance while reinforcing the importance of prompt surgical source control and appropriate antimicrobial therapy in the management of severe iGAS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 33 5 2026 Breast ultrasound screening in young adult women undergoing infertility treatment at an infertility clinic: a retrospective observational study 1093 1101 EN Kanako Nakano Department of Radiology, Okayama Couple�fs Clinic Women�fs Health Checkup Center Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Reina Maeda Department of Breast and Endocrine Surgery, Okayama University Hospital Marie Saji Department of Breast and Endocrine Surgery, Okayama University Hospital Rei Hirata Department of Senior Embryologist, Okayama Couple�fs Clinic Motomi Yukawa Department of Radiology, Okayama Couple�fs Clinic Women�fs Health Checkup Center Shizuka Okuda Department of Radiology, Okayama Couple�fs Clinic Women�fs Health Checkup Center Miyu Hirano Department of Medical Technology, Okayama Couple�fs Clinic Toshihiro Habara Department of Reproductive Medicine, Okayama Couple�fs Clinic Nobuyoshi Hayashi Department of Reproductive Medicine, Okayama Couple�fs Clinic Background Young adult women are increasingly undergoing infertility treatment; however, evidence regarding breast cancer screening in this population remains limited. Given that most women in this age group have dense breast tissue, for which mammography has limited sensitivity, breast ultrasound (US) is often used as a screening modality. A diagnosis of breast cancer during infertility treatment may affect both oncologic management and reproductive planning. This study aimed to examine the clinical relevance of breast US in women in their 30s undergoing infertility treatment at an infertility clinic.<br> Methods We retrospectively analyzed 1,336 women aged 30–39 years who underwent screening breast US between November 1, 2018, and June 30, 2025. Analyses were performed on a per-woman basis, including only the first screening examination for each participant. Breast composition was categorized according to the BI-RADS 5th edition Atlas. Screening outcomes�\including recall rate, positive predictive value (PPV), cancer detection rate, and US findings (mass and non-mass findings)�\were assessed using medical records. The continuation of infertility treatment, defined as ongoing or resumed treatment during the diagnostic evaluation period, was descriptively evaluated as part of the clinical context.<br> Results Of the 1,336 women, 1,277 (95.6%) were classified as having dense breasts. A total of 140 (10.5%) women were recalled for further evaluation. In these recalled cases, 147 findings were identified, comprising 113 mass lesions (76.8%) and 34 non-mass findings (23.1%). Four breast cancers were identified, corresponding to a cancer detection rate of 0.30% and a PPV of 2.86%. Histological diagnoses included one mucinous carcinoma, two invasive carcinomas of no special type (NST), and one ductal carcinoma in situ (DCIS). Following diagnostic evaluation, 124 recalled women (88.6%) continued infertility treatment.<br> Conclusions Breast US screening in women in their 30s undergoing infertility treatment provides descriptive findings within a specific clinical setting. The observed cancer detection rate appears to be within the range reported in previous studies; however, direct comparisons are limited due to differences in study populations and clinical contexts. The clinical course following recall was described as part of the screening pathway. Further prospective and multicenter studies are required to clarify the clinical significance of breast US screening in this population. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2667-2421 19 2025 Chronic fluoxetine modulates perineuronal nets and inhibitory neuronal function in relation to behavioral outcomes 781 791 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Eriko Kitano Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Chronic fluoxetine administration has been reported to enhance neural plasticity in the adult brain, but the underlying structural correlates remain incompletely understood. In particular, the impact of fluoxetine on aggrecan-positive perineuronal nets (PNNs)�\critical regulators of plasticity�\is largely unknown. We investigated whether chronic fluoxetine treatment (20 mg/kg/day, i.p., 21 days) alters behavior and PNN expression in adult male C57BL/6 N mice. Behavioral assessments included grip strength, hot plate, light/dark transition, elevated plus-maze, open field, Y-maze, social interaction, tail suspension, Porsolt forced swim, and passive avoidance tests. To evaluate structural plasticity, we performed immunohistochemical analyses of parvalbumin (PV)-positive neurons and PNNs using aggrecan-specific antibodies (Cat-315, AB1031) in the primary somatosensory cortex and hippocampus. Fluoxetine-treated mice exhibited increased exploration and reduced anxiety-like behavior in light/dark transition and elevated plus-maze tests, with no significant changes in grip strength or nociception. They also showed increased locomotor activity (distance and entries) in the Y-maze, but did not significantly alter spontaneous alternation performance, and increased social interaction, the latter possibly reflecting abnormal social behavior. No significant differences were observed in depression-like behavior as assessed by tail suspension and forced swim tests. Passive avoidance performance was impaired, suggesting a decline in cognitive function. Immunohistochemical analysis revealed a significant reduction in aggrecan-positive PNN density, particularly in layer 4 of the primary somatosensory cortex and in the CA1 and CA3 regions of the hippocampus. Our results indicate that chronic fluoxetine administration induces behavioral and structural changes indicative of reactivated neuroplasticity. Importantly, these changes are associated with a region- and layer-specific reduction of aggrecan-positive PNNs, underscoring their critical role in modulating adult cortical plasticity. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 30 7 2025 Guidance on the short hydration method for cisplatin administration 1287 1293 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Kei Kunimasa Department of Thoracic Oncology, Osaka International Cancer Institute Yasuko Kurata Department of Pharmacy, Okayama University Hospital Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Yasuhito Fujisaka Department of Medical Oncology, Osaka Medical and Pharmaceutical University Hitoshi Ishikawa QST Hospital, National Institutes for Quantum Science and Technology Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Cisplatin is currently used as the central agent in several cancer chemotherapy protocols because of its broad antitumor spectrum and potent antitumor effects; however, preventing cisplatin-induced renal damage and other adverse events is challenging. Recently, several clinical studies have shown that a short hydration method could prevent cisplatin-induced renal damage. In addition, appropriate magnesium supplementation and administration of forced diuretics have been shown to be renoprotective. The Japanese Lung Cancer Society Guidelines Committee has summarized the evidence of renal protection regarding cisplatin administration to provide optimal administration guidance for the cisplatin short hydration method. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0028-3940 2026 Angioarchitectural characterization of transdural supply in brain arteriovenous malformations: a multicenter retrospective study EN Yasuyuki Kaku Department of Neurosurgery, Kumamoto University Hospital Tetsu Satow Department of Neurosurgery/Stroke Center, Kindai University Hospital Shuichi Tanoue Department of Radiology, Kurume University School of Medicine Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiko Ozaki Department of Neurosurgery, University of Osaka Graduate School of Medicine Wataro Tsuruta Department of Endovascular Neurosurgery, Toranomon Hospital Yushin Takemoto Department of Neurosurgery, Kumamoto University Hospital Timo Krings Division of Neurointerventional Radiology, Lahey Hospital & Medical Center – Beth Israel Lahey Health, UMass Chan Medical School Hiro Kiyosue Department of Radiology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto University Purpose Transdural supply (TDS) is a recognized angioarchitectural feature of brain arteriovenous malformations (bAVMs). We aimed to systematically characterize the angioarchitecture of TDS in bAVMs, focusing on whether transdural feeders terminated within the nidus or connected directly to the draining vein. TDS prevalence and its associated clinical features were also investigated.<br> Methods This retrospective study enrolled 521 patients (524 bAVMs) from 16 centers who underwent systematic six-vessel digital subtraction angiography. bAVMs were classified as nidus- or fistula-dominant. Angiography was evaluated with specific focus on the presence of TDS and the termination site of transdural feeders. TDS was classified as TDS-Nidus (fistulous point within the nidus) or TDS-DV (fistulous point at the draining vein wall).<br> Results TDS was identified in 88 bAVMs (16.8%). The fistula-dominant type was more frequent in bAVMs with TDS (P < 0.01). Among TDS cases, 25 (28.4%) demonstrated TDS-DV. Fistula-dominant morphology was the only independent predictor of TDS-DV (P < 0.01). No significant differences in complete occlusion rates or modified Rankin Scale score after treatment were observed between the TDS-Nidus and TDS-DV groups. Older age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02–1.06), larger nidus size (OR: 1.95; 95% CI: 1.60–2.42), occipital location (OR: 3.12; 95% CI: 1.28–7.62), eloquent area involvement (OR: 3.23; 95% CI: 1.61–6.50), and headache (OR: 2.85; 95% CI: 1.26–6.44) were independently associated with TDS.<br> Conclusion TDS-DV was identified in 28% of bAVMs with TDS and was strongly associated with fistula-dominant morphology. Recognition of this angioarchitectural pattern may facilitate angiographic characterization of bAVMs with TDS. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1738-5733 59 1 2027 Impact of correcting beam hardening and detector response function in photon-counting X-ray imaging when using anti-coincidence mode 104678 EN Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Takuya Kasue Graduate School of Medical Sciences, Kanazawa University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University X-ray imaging using photon-counting detectors (PCDs) allows for the calculation of quantitative images such as the effective atomic number (𝑍eff). However, physical phenomena such as characteristic X-ray emission and charge sharing can cause incomplete total absorption events during signal generation, which reduces the accuracy of X-ray penetration analysis. To solve the problem, an anti-coincidence mode (ACM) has been developed, but complete correction has not been established. We aimed to investigate the accuracy of 𝑍eff image when the proposed software-based corrections, namely beam hardening and response function corrections, are added to the hardware-based correction of the ACM. The response function was calculated using the Monte-Carlo simulation code. In a simulation study, we analyzed a phantom composed of virtual materials with 𝑍eff values of 4–16. While sufficient accuracy cannot be achieved by applying only the ACM, it was demonstrated that low-noise 𝑍eff images can be obtained by applying our correction. Furthermore, it was demonstrated that 𝑍eff images of food samples can be generated by using actual non-destructive testing equipment with a 10 m/min transportation speed. In conclusion, our correction procedure can maximize the performance of PCDs, and our findings are essential for promoting imaging techniques concerning quantitative images. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 9 2026 Antiproteinuric Effect of SGLT2 Inhibitors in Patients With Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab 5141 5154 EN TOMOKI HORI Department of Pharmacy, Nara Prefecture General Medical Center KAZUHIRO YAMAMOTO Department of Integrated Clinical and Basic Pharmaceutical Science, Okayama University HIROSHI AOI Department of Pharmacy, Nara Medical University Hospital YUSUKE KOIZUMI Department of Pharmacy, Nara Medical University Hospital MAKOTO KUROMATSU Department of Pharmacy, Tenri Hospital AIKO FUKUI Department of Pharmacy, Kindai University Nara Hospital HIROYO OKAMOTO Department of Pharmacy, Kindai University Nara Hospital ATSUSHI HIRATA Department of Pharmacy, Kindai University Nara Hospital KENTARO SHINMORI Department of Pharmacy, Yamatotakada Municipal Hospital YUKI IMANAKA Department of Pharmacy, Yamatotakada Municipal Hospital MIYU NAMBA Department of Pharmacy, Nara Prefecture General Medical Center SYUNSUKE KITAMURA Department of Nephrology, Nara Medical University Hospital KEISUKE NAKANISHI Department of Gastroenterology, Nara Prefecture General Medical Center HIDEO TSUSHIMA Department of Nephrology, Nara Prefecture General Medical Center IKUKO YANO Department of Pharmacy, Kobe University Hospital KEI MORIYA Department of Gastroenterology, Nara Prefecture General Medical Center MASARU MATSUI Department of Nephrology, Nara Medical University Hospital SHIGEKI IKUSHIMA Department of Pharmacy, Nara Prefecture General Medical Center Background/Aim: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce proteinuria in patients with diabetes mellitus and chronic kidney disease. However, their effect on vascular endothelial growth factor inhibitor-induced proteinuria remains unclear. This study evaluated the prophylactic effect of SGLT2i on bevacizumab-induced proteinuria in patients with hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab.<br> Patients and Methods: This multicenter retrospective study included patients with HCC who started therapy with atezolizumab plus bevacizumab between September 2020 and December 2023. The primary outcome was the time to exacerbation of proteinuria from baseline within 6 months after treatment initiation according to SGLT2i use. Secondary outcomes included the development of grade ≥2 proteinuria.<br> Results: A total of 188 patients were included, of whom 29 received SGLT2i. No significant difference in the time to exacerbation of proteinuria was observed between the SGLT2i and non-SGLT2i groups considering the overall population (median: 157 vs. 116 days, p=0.95). Multivariate analysis identified diabetes with systolic blood pressure ≥130 mmHg as an independent risk factor for proteinuria exacerbation (hazard ratio=2.19, 95% confidence interval=1.18-4.06, p=0.013), whereas SGLT2i use was not significantly associated with proteinuria exacerbation. In patients with both diabetes and systolic blood pressure ≥130 mmHg, SGLT2i significantly prolonged the time to proteinuria exacerbation.<br> Conclusion: SGLT2i may suppress proteinuria progression only in high-risk patients with HCC complicated by diabetes and hypertension. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2198-4034 12 1 2026 Development of a preoperative accuracy prediction model using machine learning for implant placement in static-guided surgery: retrospective observational study 44 EN Takuya Mino Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Yurina Matsuoka Department of Semiconductor, Computer Science and Applied Mathematics, Graduate School of Science and Technology, Kumamoto University Ken�fichi Morooka Division of Biomedical Engineering, Faculty of Advanced Science and Technology, Kumamoto University Kana Tokumoto Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University Hiroaki Shimizu Shimizu Dental Clinic Yoko Kurosaki Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Aya Kimura-Ono Center for Innovative Clinical Medicine, Okayama University Hospital Hiromitsu Kishimoto Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Maekawa Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Purpose This study aimed to develop a machine learning model capable of preoperatively predicting three-dimensional implant placement errors at the implant apex in static-guided surgery and to identify the clinical features associated with placement accuracy.<br> Methods Clinical data partially derived from a previous observational study were analyzed. In total, 181 patients and 480 implants placed using fully static-guided surgery were included in this study. The outcome variable was defined as three-dimensional implant placement error at the implant apex relative to the preoperative simulation, dichotomized as less than 0.5 mm or ≥ 0.5 mm. Twenty-one clinical and radiographic factors previously suggested to influence the placement accuracy were used as explanatory variables. The feature importance was evaluated using three gradient boosting decision tree models. Furthermore, a stacking model combining multiple classifiers was constructed, and the classification performance was assessed using ten-fold cross-validation.<br> Results The feature importance analysis identified 12 features associated with implant placement errors. The stacking model demonstrated superior classification performance compared to individual classifiers. The true positive rate was 0.73, false negative rate was 0.27, false positive rate was 0.14, and true negative rate was 0.86.<br> Conclusions The proposed stacking model correctly classified 86% of cases with implant placement error less than 0.5 mm and 73% of cases with implant placement error of ≥ 0.5 mm. These findings suggest that the proposed model may support the preoperative evaluation of implant placement accuracy in static-guided surgeries. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2212-8778 112 2026 Adaptive oligodendrogenesis regulates blood-hypothalamus barrier permeability, hypothalamic glucose sensing and systemic glucose homeostasis in male mice 102428 EN Sophie Buller Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Emily O. Staricoff Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Christine Riches Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Anthony Tsang Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Giada Giavara Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Masa Josipovic Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Kentaro Ikemura Department of Medical Technology, Graduate School of Health Sciences, Okayama University Gabriel Opoku Department of Medical Technology, Graduate School of Health Sciences, Okayama University Ikumi Sato Department of Medical Technology, Graduate School of Health Sciences, Okayama University Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Saskia Stenzel Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Stuart G. Nayar Wolfson Institute for Biomedical Research, University College London Marta Ramos Vega GUBRA Jacob Hecksher-Sørensen GUBRA Sebastian Timmler Cambridge Stem Cell Institute, University of Cambridge Georgina K.C. Dowsett Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Brian Y.H. Lam Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Giles S.H. Yeo Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Kimberly M. Alonge Diabetes Institute, University of Washington Huiliang Li Wolfson Institute for Biomedical Research, University College London William D. Richardson Wolfson Institute for Biomedical Research, University College London Mark L. Evans Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Clemence Blouet Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Objective: Brain glucose sensing is critical for survival during hypoglycaemia, yet how glucose-sensing neurons access circulating glucose concentrations to maintain glucose homeostasis remains poorly understood. Here we tested the hypothesis that adult oligodendrogenesis in the median eminence (ME) is responsive to changes in blood glucose levels and contributes to hypothalamic glucose sensing through regulation of the blood-hypothalamus barrier.<br> Methods: We used glycemic challenges and hypoinsulinaemic clamp studies to identify the effect of systemic changes in glycaemia on hypothalamic oligodendrocyte lineage cells. We used conditional knockout mouse models to dissect the respective contributions of adult oligodendrogenesis and new myelin formation to glucose homeostasis in adult male mice. Analyses combined immunofluorescence, serial electron microscopy, whole-brain tissue clearing, and transcriptomic analyses.<br> Results: We found that adult oligodendrogenesis in the median eminence (ME) is modulated by changes in circulating glucose levels and rapidly upregulated by hypoglycaemia. Genetic blockade of new oligodendrocyte production in adult male mice impairs the regulation of glucose homeostasis, the integrity of the ME blood-hypothalamus barrier, and hypothalamic glucose sensing. Unexpectedly, functional integrity of adult-formed myelin is not required for the maintenance of glucose homeostasis. Instead, we show that blockade of adult oligodendrogenesis disrupts hypothalamic expression of A disintegrin and metallopeptidase with thrombospondin motifs 4 (ADAMTS4), a metallopeptidase whose brain expression is restricted to the oligodendrocyte lineage and whose ME expression requires ongoing adult oligodendrogenesis. We show that ADAMTS4 regulates hypothalamic perineuronal net deposition, vascular permeability and glucose sensing. Finally, we show that ME ADAMTS4 expression is regulated by changes in peripheral glycaemia and is dysregulated in diabetes, providing a mechanism by which ME oligodendrocytes contribute to the regulation of glucose homeostasis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1474-9718 25 5 2026 UNC45B Reduction With Aging: A Myofiber-Intrinsic Promoting Factor for Sarcopenia e70502 EN Taiga Mishima Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Taiga Nagamune Department of Life Science and Applied Chemistry, Nagoya Institute of Technology Saori Tada Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Daiki Watanabe Graduate School of Sport and Health Sciences, Osaka University of Health and Sport Sciences Nao Tokuda Graduate School of Health Sciences, Sapporo Medical University Takashi Yamada Graduate School of Health Sciences, Sapporo Medical University Akiko Hashimoto�]Hachiya Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Sayaka Higo�]Yamamoto Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Kohei Kido Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University Aoi Ikedo Division of Integrative Pathophysiology, Proteo�]Science Center, PIAS, Ehime University Yuuki Imai Division of Integrative Pathophysiology, Proteo�]Science Center, PIAS, Ehime University Ryo Fujita Division of Regenerative Medicine, Transborder Medical Research Center, Institute of Medicine, University of Tsukuba Seiya Mizuno Laboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of Tsukuba Satoru Takahashi Laboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of Tsukuba Katsutaka Oishi Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Satoru Ato Faculty of Medical Science, Nippon Sport Science University Riki Ogasawara Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Skeletal muscle mass and force decline with age, and the loss of muscle force precedes muscle atrophy. However, the underlying mechanisms remain unclear. Here, we investigated the role of the myosin co-chaperone, uncoordinated mutant number-45 myosin chaperone B (UNC45B), in regulating muscle mass and force. UNC45B expression decreased in mouse gastrocnemius muscle with age, particularly at 24 months old, and adeno-associated virus vector-mediated knockdown of Unc45b in 3-month-old mouse triceps surae muscle first reduced plantar flexor torque and then decreased gastrocnemius muscle mass. In addition, Unc45b knockdown in the triceps surae muscle resulted in lower bone mineral density. While maximum Ca2+-activated force in mechanically skinned fibers was not affected by Unc45b knockdown, Unc45b knockdown decreased the ratio of depolarization-induced force to the maximum Ca2+-activated force. We established tamoxifen-inducible skeletal muscle-specific Unc45b knockout (Unc45b imKO) mice to investigate whether the muscle atrophy and weakness due to the loss of Unc45b impacts metabolism and behavior. We found that Unc45b imKO reduced muscle mass and force at a whole-body level, but did not influence systemic glucose tolerance, insulin sensitivity, or the respiratory exchange ratio. However, Unc45b imKO mice reduced the amount of deeper non-rapid eye movement sleep, locomotor activity, and body temperature during the sleep phase. We conclude that UNC45B is essential for maintaining fast-twitch muscle mass and muscle force. In addition, Unc45b deficiency-mediated muscle loss is also associated with bone fragility, decreased body temperature, and impaired sleep quality. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1873-9601 20 2 2026 Species�]specific roles of cellular communication network proteins in cartilage development: A comparative study using in vitro chondrogenic models e70089 EN Zhangzheng Wang Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Judit Vágó Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Roland Takács Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Szilárd Póliska Genomic Medicine and Bioinformatics Core Facility Department of Biochemistry and Molecular Biology Faculty of Medicine, University of Debrecen Ee Hyun Kim Department of Biomedical Materials Science Graduate School of JABA, Wonkwang University Eun�]Jung Jin Department of Biomedical Materials Science Graduate School of JABA, Wonkwang University Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University, Faculty of Medicine, Dentistry and Pharmaceutical Science Celina G Kleer Department of Pathology, University of Michigan Medical School Bernard Perbal International CCN Society Csaba Matta Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Cellular communication network (CCN) proteins are key matricellular regulators of cartilage development, yet their species-specific roles and network-level context remain unclear. This study integrated bulk RNA sequencing from chicken and mouse embryonic limb bud micromass cultures and human mesenchymal stem cell chondrogenesis with co-expression, protein–protein interaction, and ortholog analyses to construct CCN-centered regulatory networks across models. CCN1 and CCN2 emerged as dominant, conserved hubs enriched in collagen-containing extracellular matrix, cartilage development, and growth factor signaling modules, whereas CCN3–CCN6 showed lower context-dependent expression and connectivity. Functional and ortholog analyses revealed moderate pathway conservation, with high conservation of IGF, EGFR, and HIF-1 signaling, but reduced overlap in hypoxia and mechanosensing/Hippo categories, indicating species-specific tuning of environmental sensing. A focused ortholog screen identified multifunctional conserved hubs, including COL2A1, TGFBR1, SMAD3, RUNX2, HIF1A, IGF1, SPP1, and CD44. Single-cell RNA-seq meta-analysis of human iPSC-derived chondrogenesis and embryonic limb datasets showed CCN1/2 expression and homologous network activity peaking in mesenchymal and early chondrocyte populations, consistent with model-dependent persistence into hypertrophic and ossification stages in vivo. Overall, this work defines a conserved CCN1/2-centered axis integrating extracellular matrix formation with growth factor and mechanical cues, providing a framework for model selection and CCN-targeted cartilage regeneration strategies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0934-9723 2026 Streptococcal toxic shock syndrome caused by ST525 Streptococcus dysgalactiae subsp. equisimilis with genomic characterization of virulence and antimicrobial resistance EN Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Maki Tanioka Clinical Oncology Center, Okayama University Hospital Hideharu Hagiya Research Center for Intestinal Health Science, Okayama University Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of severe invasive infections. We describe the clinical course of an immunocompromised patient with advanced breast cancer who developed streptococcal toxic shock syndrome, necrotizing fasciitis, and disseminated intramuscular abscesses caused by a multidrug-resistant Lancefield group G SDSE isolate, alongside a comprehensive genomic characterization of its virulence and antimicrobial resistance profiles. Genomic analysis identified the isolate as emm subtype stG840.0 and sequence type 525 (ST525), harboring genes encoding several virulence-associated factors, including an emm-like gene encoding an M-like surface protein, streptokinase, streptolysin O, streptolysin S, and SpeG. Through comprehensive genomic analysis of the highly virulent SDSE isolate, we provided insights into its underlying genetic background. Further accumulation of genomic data is expected to fully elucidate the mechanisms of virulence and antimicrobial resistance in SDSE. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0924-8579 67 10 2026 Clinical characteristics and therapeutic dilemmas in nocardiosis: Insights from a case series 107906 EN Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Tomoyuki Miyahara Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Sakura Ogawa Microbiology Division, Clinical Laboratory, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Objectives: Nocardiosis often requires prolonged antimicrobial therapy, and trimethoprim–sulfamethoxazole (TMP–SMX) is considered the cornerstone of treatment. However, TMP–SMX–related adverse events frequently complicate long-term therapy, and real-world data regarding treatment continuity and outcomes remain limited.<br.> Methods: We conducted a retrospective observational study of patients with Nocardia species isolated from clinical specimens at a tertiary-care academic hospital in Japan between January 2015 and April 2025. Clinical characteristics, antimicrobial therapy, adverse events, and outcomes were reviewed.<br> Results: Eleven cases were enrolled, with a median age of 65 years. The cohort comprised seven patients with severe nocardiosis (disseminated disease, brain abscess, and pneumonia in transplant recipients) and four patients with mild nocardiosis (cutaneous infection and pneumonia). Nine patients received TMP–SMX as part of the initial regimen, of whom seven required modification of therapy within 1 day to 3 months because of adverse events. Following modification of TMP–SMX, patients were treated with alternative regimens, including fluoroquinolone�\and minocycline-based therapies, as well as ƒÀ-lactam–containing combinations. Importantly, no cases of treatment failure or death were observed, and no relapses were identified during the available follow-up period, even among patients with those clinically complex diseases.<br> Conclusions: Although TMP–SMX is the first-line therapy for nocardiosis, the majority of our patients did not tolerate the drug. Nevertheless, favorable outcomes were observed with alternative regimens, even in patients with clinically complex disease, suggesting that alternative regimens may be reasonable options when TMP–SMX is not tolerated. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 17 2026 Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer�fs Disease in a Mouse Model 7542 EN Momoko Nakahara Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Kataoka Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mohammad Nurhamim Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yixuan Zhang Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Daiki Fukuhara Department of Preventive Dentistry, Dental School, Okayama University Yoko Uchida-Fukuhara Laboratory of Biological Anthropology, Research Center for Integrative Evolutionary Science, The Graduate University for Advanced Studies, SOKENDAI Md Monirul Islam Centre for Policy Studies, University College Cork Manabu Morita Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care Takashi Saito Department of Neuropathology, Graduate School of Medicine, The University of Tokyo Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The purpose of the present study was to investigate how periodontitis and diabetes mellitus (DM) are associated with Alzheimer�fs disease (AD) through microRNA (miRNA) using AD model mice. The experimental period was 8 weeks. Twenty-four male knock-in mice (B6-AppNL-G-F/NL-G-F/J) were divided into four groups: control group fed a normal diet (C), DM group fed a high-fat/sucrose diet (DM), periodontitis (P) group, and DM + periodontitis (DM+P) group. Memory performance was compared using the Y-maze test. Next-generation sequencing was performed on brain samples, and fold changes in miRNA expression were calculated by comparing the DM+P and C groups. Integrated miRNA–mRNA analysis identified putative miRNA-targeted mRNAs, and protein expression of the top candidate gene was assessed. Memory function in the DM+P group was significantly lower than in the C group. Among the seven mRNAs identified by the integrated analysis, Neurod1 showed the greatest decrease in expression, and it was predicted to be regulated by miR-693-3p. Neurod1 protein expression in the hippocampus was significantly lower in the DM+P group than the C group. Our results suggest that the combined exposure to periodontitis and DM was associated with AD-like pathological changes and identified the miR-693-3p/Neurod1 pair as a candidate regulatory axis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0172-0643 2026 Fenestration Re-creation for Early Fontan Deterioration: Long-Term Hemodynamic and Clinical Outcomes EN Thi Hai Yen Tran Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshihiko Kurita Department of Pediatrics, Kochi Health Sciences Center Maiko Kondo Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yosuke Fukushima Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yusuke Shigemitsu Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuya Kawamoto Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mayuko Hara Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hirokazu Tsukahara Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tatsuo Iwasaki Department of Pediatric anesthesiology, Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Hospital Kenji Baba Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Spontaneous closure of a Fontan fenestration may precipitate early hemodynamic deterioration in vulnerable patients. In such situations, fenestration re-creation may be considered as a rescue strategy when medical therapy is insufficient. However, the long-term hemodynamic consequences of this intervention remain poorly defined. We retrospectively reviewed 62 patients who underwent the Fontan procedure between January 2011 and December 2020 and subsequently experienced spontaneous fenestration closure. Patients were divided into two groups according to management strategy: those who underwent fenestration re-creation (Group 1, n = 19) and those managed without re-creation (Group 2, n = 43). Longitudinal hemodynamic data were analyzed using linear mixed models over a median follow-up of 10.2 years. Fenestration closed spontaneously at a median of 12 days (IQR 2.5–26.5) and initial re-creation was performed at the median of 42 days (IQR 11–213) postoperatively. Early and mide-term hemodynamic trends were broadly similar between groups, however, clear divergence emerged in the late follow-up. fenestration re-created patients demonstrated persistently higher central venous pressure and pulmonary vascular resistance, lower systemic vascular resistance, progressive increases in cardiac index, and declining oxygen saturation. Survival in this group remained above 80% during the mid-term follow-up but declined substantially in the late phase compared with patients without re-creation (52% vs. 85%, p = 0.043). This was accompanied by higher incidences of protein-losing enteropathy/plastic bronchitis, thromboembolism, and severe cyanosis. Fenestration re-creation may provide temporary hemodynamic stabilization in early Fontan deterioration; however, its benefits appear to diminish in the late phase. These findings highlight the need for hemodynamically tailored management strategies and alternative therapeutic options for patients with deteriorating Fontan circulation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Microstructural changes in irradiated teeth revealed by swept-source optical coherence tomography 22258 EN Kumiko Matsuzaki Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Hidenobu Matsuzaki Department of Oral Diagnosis and Dentomaxillofacial Radiology, Okayama University Hospital Tomoko Tabata Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Hideki Aoyama Central Division of Radiology, Okayama University Hospital Kotaro Yoshio Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirotaka Kosaki Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Naoko Ohara Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Alireza Sadr Biomimetics Biomaterials Biophotonics Biomechanics & Technology Laboratory, Department of Restorative Dentistry, Magnuson Health Sciences Center, University of Washington Yoshihiko Soga Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Yasushi Shimada Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Radiation-induced caries is a late complication of radiotherapy for head and neck cancers. Although direct irradiation-induced changes in tooth structure may contribute to its development, these changes have not been fully characterized. This study evaluated irradiation-associated microstructural alterations and tissue density changes in human teeth using swept-source optical coherence tomography (SS-OCT). Eight extracted fully impacted human third molars were assigned to irradiated and non-irradiated groups (n = 4 each). The irradiated group received X-rays at a total dose of 70 Gy, a clinically relevant dose in definitive radiotherapy for head and neck cancer. A total of 64 SS-OCT cross-sectional images were obtained and analyzed, with 32 images from each group, including 16 from the coronal area on the occlusal side and 16 from the cervical area. Microcrack-like features were observed in 100% (16/16) of irradiated and 31.3% (5/16) of non-irradiated images in the coronal area on the occlusal side, and in 43.8% (7/16) and 0% (0/16) of images in the cervical area, respectively. Attenuation coefficients were significantly higher in irradiated enamel and dentin. These findings suggest that irradiation-induced microstructural changes in extracted human teeth in vitro may contribute to increased susceptibility to radiation-induced caries. No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 ‘æ125‰ñ�@‰ªŽRˆãŠw‰ï‘�‰ï 80 86 EN No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 ‘æ33‰ñ“ú–{ƒXƒeƒ�ƒCƒhƒzƒ‹ƒ‚ƒ“Šw‰ïŠw�p�W‰ï 78 79 EN Fumio Otsuka Department of General Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 ‘æ‚T‰ñ“ú–{ŽüŽYŠú–ƒ�Œ‰ÈŠw‰ïŠw�p�W‰ïŠJ�Õñ�� 76 77 EN Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 •a—��f’f‚Ì�‘�Û“I•W�€‰» 71 73 EN Hidetaka Yamamoto Department of Pathology and Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 –ò•¨‘ŠŒÝ�ì—p�i66�\ƒIƒŒƒLƒVƒ“Žó—e‘Ì�h�R–ò‚Ì–ò•¨‘ŠŒÝ�ì—p�j 68 70 EN Yuka Narumoto Department of Pharmacy, Okayama University Hospital Hirofumi Hamano Department of Pharmacy, Medical Development Field, Okayama University Yoshito Zamami Department of Pharmacy, Medical Development Field, Okayama University No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 ”xŠà‚É‚¨‚¯‚镪Žq•W“IŽ¡—ÂÌ�V“WŠJ�\�R‘̈ã–òŽž‘ã‚Ì“ž—ˆ�\ 62 67 EN Tomoka Nishimura Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 Ž©‘R’E—Ž‚µ‚½Žq‹{Œ´”­ DLBCL ‚ɑ΂µ‚Ä Pola-R-CHP —Ö@‚Æ CNS �Ä”­—\–h‚ð�s‚Á‚½‚P—á 58 61 EN Hikaru Osada Department of Hematology, Japanese Red Cross Okayama Hospital Maiko Kimura Department of Hematology, Japanese Red Cross Okayama Hospital Manaka Muneishi Department of Hematology, Japanese Red Cross Okayama Hospital Kozo Murayama Department of Hematology, Japanese Red Cross Okayama Hospital Daigo Niiya Department of Hematology, Japanese Red Cross Okayama Hospital Makoto Takeuchi Department of Hematology, Japanese Red Cross Okayama Hospital Soichiro Fujii Department of Hematology, Japanese Red Cross Okayama Hospital �@A 55-year-old woman presented to her local physician with the chief complaint of genital bleeding. A 22�~19-mm mass was noted on the patient's cervix, and during the internal examination the mass auto-amputated. The pathological examination of the auto-amputated mass revealed diffuse large B-cell lymphoma (DLBCL). An examination by F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) showed FDG uptake at physiological levels in the cervix, with no abnormal uptake in other organs. Cervical tissue was sampled after the spontaneous detachment of the cervical mass, and the biopsy of the cervical mass did not reveal findings suggestive of lymphoma. Six courses of chemotherapy with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone (Pola-R-CHP) plus an intramedually injection of methotrexate, cytarabine, and predonisolone (IT-triple), followed by two courses of high-dose intrathecal methotrexate (HD-MTX) were adiministered, and the patient has remained recurrence-free for the more than 8 months since the completion of this treatment. Primary uterine DLBCL is an extremely rare disease with a high rate of recurrence in the central nervous system and a poor prognosis. Our search of the relevant literature identified very few reports describing the prognoses of cases with spontaneous tumor detachment. No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 �׋Û�«ƒRƒ‰ƒQƒi�[ƒ[‚Ì�\‘¢Šˆ�«‘ŠŠÖ‚ƈã—Éž—p 50 57 EN Osamu Matsushita Professor Emeritus, Okayama University No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 Š´�õ�ÇŠw•ª–ì‘n�݃}ƒjƒtƒFƒXƒg�\“ú–{‹üŽw‚ÌŠ´�õ�ÇŒ¤‹†‹’“_‚ð–ÚŽw‚µ‚Ä�\ 45 49 EN Hideharu Hagiya Department of Infectious Diseases, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 ‚RŒ^–Ɖu‰ž“š‚É‚æ‚é’°ŠÇ�P�í�«ˆÛŽ�‚¨‚æ‚ÑŽ©ŒÈ–Ɖu�«ŠÖ�߉Š—U“±‹@�\ 40 44 EN Keiji Hirota Department of Immunology and Inflammation, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 —ߘa‚V”N“x‰ªŽRˆãŠw‰ï�Ü�@‚ª‚ñŒ¤‹†�§—ã�Ü�i—ÑŒ´�Ü�EŽR“c�Ü�j 38 39 EN Hibiki Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 —ߘa‚V”N“x‰ªŽRˆãŠw‰ï�Ü�@‹¹•”�E�zŠÂŒ¤‹†�§—ã�Ü�i�»“c�Ü�j 35 37 EN Yoshihiko Itoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

‰ªŽRˆãŠw‰ï Acta Medica Okayama 0030-1558 138 2 2026 —ߘa‚V”N“x‰ªŽRˆãŠw‰ï�Ü�@‘��‡Œ¤‹†�§—ã�Ü�iŒ‹�é�Ü�j 31 34 EN Yui Kambara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1662-5110 20 2026 New mechanistic insight into SARM1 activation: TRIM32-mediated ubiquitination is a key lever that actuates SARM1�fs catalytic action, leading to axon degeneration and cell death 1842408 EN Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sterile alpha and TIR motif-containing protein 1 (SARM1) is an enzyme that cleaves nicotinamide adenine dinucleotide (NAD+) and plays a role in disrupting neural circuits through axon degeneration and cell death. SARM1 is activated by changes in the nicotinamide mononucleotide (NMN)/NAD+ ratio and by various post-translational modifications, but its complete regulatory mechanism remains poorly understood. Here, we report that tripartite motif-containing protein 32 (TRIM32) activates SARM1 through specific ubiquitination triggered by anticancer drug treatment. TRIM32 promotes the attachment of Lys27-linked ubiquitin chains to Lys173 and Lys375 within the ARM domain, which is an autoinhibitory region of SARM1. This ubiquitination by TRIM32 increases SARM1�fs NAD+-cleaving catalytic activity and enhances its ability to induce neurite degeneration and cell death. A mutant form of TRIM32 lacking the enzymatically active RING domain fails to promote SARM1 ubiquitination, and reducing TRIM32 levels decreases SARM1 ubiquitination. Additionally, ubiquitin-specific peptidase 13 (USP13), a known negative regulator of SARM1, can deubiquitinate SARM1. These findings suggest that TRIM32 is a key regulator of axon degeneration and cell death through its ubiquitination of SARM1. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 6 2026 Efficacy of bepotastine compared with hydroxyzine in preventing rituximab-induced infusion-related reactions in non-hodgkin lymphoma patients: a phase II, double-blind, multicenter, and randomized trial 979 988 EN Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Hironobu Minami Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimikazu Yakushijin Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Keiji Kurata Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Rina Sakai Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Miki Saeki Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Yuri Okazoe-Hirakawa Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Kotaro Iida Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Natsuko Murase Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Isamu Harima Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Naoko Kitamura Department of Pharmacy, Kobe University Hospital Kotaro Itohara Department of Pharmacy, Kobe University Hospital Tomohiro Omura Department of Pharmacy, Kobe University Hospital Takeshi Sugimoto Department of Hematology and Oncology, Kita-Harima Medical Center Hidetomo Takakura Department of Hematology and Oncology, Kita-Harima Medical Center Akihito Kitao Department of Hematology and Oncology, Kita-Harima Medical Center Masako Takahashi Department of Pharmacy, Kita-Harima Medical Center Manabu Shimoyama Department of Hematology and Oncology, Kohnan Medical Center Mamoru Okuno Department of Pharmacy, Kohnan Medical Center Ikuko Yano Department of Pharmacy, Kobe University Hospital Background This study evaluated the efficacy of hydroxyzine and bepotastine, first- and second-generation H1 receptor antagonists (H1RA), as pretreatments to prevent infusion-related reactions (IRRs) during the initial rituximab infusion in patients with non-Hodgkin lymphoma.<br> Methods In this double-blind, multicenter, randomized phase II study, 40 patients received hydroxyzine or bepotastine with acetaminophen 30 min before rituximab infusion. Primary endpoint was incidence of ≥ grade 2 IRRs based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Secondary endpoints included IRRs severity, time to IRR onset, and H1RA-induced drowsiness.<br> Results Incidence of ≥ grade 2 IRRs was 52.4% and 31.6% for the hydroxyzine (n = 21) and bepotastine (n = 19) groups, respectively (P = 0.184). Distribution of initial and maximum IRR grades in the two groups was not statistically significant (P = 0.846 and 0.555). Median time (range) to IRR onset in the two groups was 67 (12–112) and 62 (10–119) min, respectively (P = 0.981). Median visual analog scale score (range and 75th percentile) for drowsiness was 37 (0–100, 46) and 12 (0–100, 29) mm in the two groups, respectively (P = 0.138). Incidence of ≥ grade 2 IRRs in the absence of bone marrow infiltration was 43.8% and 14.3% in the two groups, respectively (P = 0.118), and no group differences were observed with bone marrow infiltration.<br> Conclusions Bepotastine did not show significant superiority over hydroxyzine in preventing rituximab-induced IRRs due to the small sample size. Nevertheless, this exploratory study provides insight for further confirmatory studies.<br> Trial registration number and date of registration jRCTs051220169; February 14, 2023. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2328-8957 13 6 2026 Digital Tattoos in Infectious Diseases Management ofag338 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital The widespread adoption of electronic medical records (EMRs) has improved continuity and efficiency in healthcare; however, the permanence of digital documentation may unknowingly and unintentionally disadvantage patients. Certain infectious disease–related labels, particularly those denoting colonization of antimicrobial-resistant organisms, status of stigmatized diseases, or antibiotic drug allergy, frequently persist long after their clinical relevance has expired. These Digital Tattoos silently influence clinical decision-making and impose multifaceted burdens, leading to unnecessary isolation, excessive use of broad-spectrum antimicrobials, psychological distress, higher healthcare costs, and reinforcement of stigma. A critical mismatch exists between static (unchanged) EMRs and the dynamic (changeable) nature of clinical conditions. To mitigate the harms of Digital Tattoos, we must urgently move beyond passive documentation toward proactive management of healthcare data. Decoupling the permanence of digital records from systemic inequities in patient care hinges on the robust synthesis of Digital Humility and patient-oriented risk evaluation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2059-1381 12 1 2026 Potential effects of intradialytic exercise therapy on physical performance in hemodialysis patients based on the intervention period: a systematic review and meta-analysis 19 EN Daisuke Uchida Department of Internal Medicine, Teikyo University Hospital Mizonokuchi Yu Honda Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine Shigeki Kojima Kojima Kidney and Dialysis Clinic Hiromasa Miyake Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Masatoshi Nishimoto Department of Nephrology, Nara Medical University Akihito Hishikawa Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine Shun Tonomura Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine Tadashi Sofue Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University Naohiko Fujii Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital Masakazu Saitoh Department of Physical Therapy, Faculty of Health Science, Juntendo University Ichiei Narita Niigata Institute for Health and Sports Medicine, Niigata Sports Association Kunihiro Yamagata Department of Nephrology, Institute of Medicine, University of Tsukuba Junichi Hoshino Division of Preventive and Sports Nephrology, Graduate School of Comprehensive Human Sciences, Tokyo Women�fs Medical University Hiroo Kawarazaki Department of Internal Medicine, Teikyo University Hospital Mizonokuchi Tsutomu Sakurada Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine Background Intradialytic exercise during hemodialysis (HD) improves physical function and shows high adherence. In Japan, the 2018 guideline by the Japanese Society of Renal Rehabilitation supports intradialytic exercise, but medical insurance only covers the first 90 days. As new studies have emerged since the guideline was published, we conducted a systematic review and meta-analysis to evaluate the impact and optimal duration of exercise interventions beyond 12 weeks.<br> Methods We followed a preregistered protocol (PROSPERO CRD42025642273) and PRISMA-P guidelines. Randomized controlled trials of adult patients undergoing HD performing structured exercise were identified via MEDLINE database (PubMed, March 2017–November 2024) and ICHUSHI-Web database. Two independent reviewers screened studies, extracted data, and assessed risk of bias using Cochrane RoB 2.0. Outcomes included peak oxygen uptake (VO2peak), maximal oxygen uptake (VO2max), 6 min walk distance, timed up and go (TUG) test, handgrip strength, sit-to-stand (STS) performance, and biochemical measures (hemoglobin, standard weekly urea Kt/V [std Kt/V]). Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a mixed-effects model (Hartung–Knapp–Sidik–Jonkman method).<br> Results A total of 71 studies, including 43 newly identified studies, were included. Risk of bias was moderate-to-high. Interventions > 12 weeks significantly improved 6 min walking distance (MD 52.4 m [95% CI 35.4–69.3], p < 0.01), VO2peak (MD 3.5 mL/kg/min [95% CI 1.96–5.04], p < 0.01), VO2max (MD 5.29 mL/kg/min [95% CI 2.36–8.22], p < 0.01), hemoglobin (MD 0.94 g/dL [95% CI 0.09–1.78], p = 0.03), and std Kt/V (MD 0.16 [95% CI 0.12–0.20], p < 0.01). TUG (MD �|1.68 s [95% CI �|2.96 to �|0.41], p = 0.02), handgrip strength (MD 4.08 kg [95% CI 1.95–6.22], p < 0.01), and STS performance (MD �|2.75 s [95% CI �|4.45 to �|1.05], p < 0.01) significantly improved in the integrated results of undefined study periods, with nonsignificant trends in studies of > 12 weeks of exercise.<br> Conclusions Our findings suggest that exercise interventions lasting more than 12 weeks can enhance physical performance. Nevertheless, the applicability of these results to older patients remains uncertain, as most evidence is derived from middle-aged cohorts.<br> Trial registration Registered in the PROSPERO database (CRD42025642273). No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2059-1381 12 1 2026 Duration-stratified effects of exercise therapy on health-related quality of life in hemodialysis patients: a systematic review and meta-analysis 13 EN Yu Honda Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine Daisuke Uchida Department of Internal Medicine, Teikyo University Hospital Mizonokuchi Shigeki Kojima Kojima Kidney and Dialysis Clinic Hiromasa Miyake Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Masatoshi Nishimoto Department of Nephrology, Nara Medical University Akihito Hishikawa Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine Shun Tonomura Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine Tadashi Sofue Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University Naohiko Fujii Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital Masakazu Saitoh Department of Physical Therapy, Faculty of Health Science, Juntendo University Ichiei Narita Niigata Institute for Health and Sports Medicine, Niigata Sports Association Kunihiro Yamagata Department of Nephrology, Institute of Medicine, University of Tsukuba Junichi Hoshino Department of Nephrology, Tokyo Women�fs Medical University Hiroo Kawarazaki Department of Internal Medicine, Teikyo University Hospital Mizonokuchi Tsutomu Sakurada Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine Background: Patients on maintenance hemodialysis (HD) have reduced health-related quality of life (HRQoL). Structured exercise therapy is recommended, but domain-specific effects and the influence of intervention duration remain uncertain. This study evaluated the impact of structured exercise therapy on multiple HRQoL domains, including fatigue and depression, stratified by intervention duration.<br> Methods: We conducted a systematic review and meta-analysis, searching MEDLINE (PubMed) through November 2024. The protocol was registered in PROSPERO (CRD42025642273). We included trials comparing structured exercise with non-exercise controls in adult HD patients. Primary outcomes were Short Form (SF)-36 Physical and Mental Component Summaries (PCS, MCS), fatigue, pain, general health, and depression (Beck Depression Inventory). Data were synthesized using random-effects models, stratified by intervention duration (≤ 3 versus > 3 months). Risk of bias was assessed using the Cochrane RoB 2 tool.<br> Results: We identified 94 randomized controlled trials (5228 participants); 22 reported HRQoL outcomes and were meta-analyzed. Exercise significantly improved fatigue (mean difference [MD] + 7.27, 95% confidence interval [CI] 4.75–9.80) and reduced depressive symptoms in > 3-month trials (MD �|7.62, 95% CI �|8.34 to �|6.90); no ≤ 3-month depression data were available. In overall analyses, general health (MD + 11.59, 95% CI 6.98–16.21) and PCS (MD + 5.83, 95% CI 0.71–10.94) improved, whereas MCS (MD + 7.60, 95% CI �|3.75 to 18.94) and pain (MD + 2.19, 95% CI �|4.41 to 8.79) showed no clear benefit. Short-term interventions (≤ 3 months) yielded significant improvements in pain and general health. In longer-term interventions (> 3 months), general health estimates were similar in magnitude but statistically nonsignificant, and pain effects were also nonsignificant with substantial heterogeneity. Fatigue improved in both duration strata.<br> Conclusions: Structured exercise therapy appears to improve fatigue in patients on maintenance HD and may provide additional gains in PCS and general health with interventions longer than 3 months. Improvements in depressive symptoms were observed from limited evidence, and duration-specific effects remain uncertain because no trials assessed depression at ≤ 3 months. Effects on pain and MCS remain uncertain owing to substantial heterogeneity. Larger long-term trials are needed to clarify the sustainability of HRQoL benefits beyond 3 months. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2699-9307 6 6 2026 NUAK2 Inhibition Enhances Macromolecular Drug Delivery in a 3D Fibrotic Model of the Pancreatic Tumor Microenvironment e202500237 EN Misaki Nakamura Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Mayu Ohira Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Haruko Ohta�]Okano Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Reika Nakamura Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yu Seno Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Saaya Yara Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Sakura Fujita Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Daichi Shibata Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Masaya Yamamoto Department of Materials Processing Graduate School of Engineering, Tohoku University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Osada Department of Molecular Imaging and Theranostics Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) Horacio Cabral Department of Bioengineering Graduate School of Engineering, The University of Tokyo Atsushi Masamune Division of Gastroenterology Graduate School of Medicine, Tohoku University Mitsunobu R. Kano Department of Pharmaceutical Biomedicine Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Pancreatic ductal adenocarcinoma (PDAC) features a fibrotic tumor microenvironment that impedes drug delivery and significantly limits the successful clinical application of nanomedicines. Targeting signaling in pancreatic stellate cells (PSCs), which drive fibrosis via excessive secretion of extracellular matrix proteins such as collagen I, may be useful in overcoming this fibrotic barrier. The AMPK-related kinases NUAK1/2 have recently gained interest as promoters of fibrosis, but whether they play a profibrotic role in PSCs remains unknown. Here, patient PSCs are used to assess NUAK1/2 involvement in the PDAC fibrotic barrier. Leveraging a 3D cell culture model of PDAC fibrosis, the effect of targeting NUAK1/2 on the permeability of macromolecular dextrans of various sizes, as well as physiologically relevant macromolecules, albumin and IgG, and clinical nanomedicines, Doxil and Abraxane, is investigated. NUAK1/2 inhibition is shown to diminish collagen I to enhance macromolecular permeability, via a mechanism independent of established pathways involving transforming growth factor-ƒÀ (TGFƒÀ) and yes-associated protein (YAP). Through isoform-specific knockdown, predominant NUAK2 involvement is demonstrated. Mechanistically, actin stress fiber regulation by NUAK2 is shown to be important. Altogether, these results show in vitro that NUAK2 promotes fibrotic signaling in PSCs and may be targeted to enhance macromolecular drug delivery in PDAC. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2056-306X 12 1 2026 Knockout analysis of period and timeless and EGFP-based visualization of per-expressing clock cells in the cricket circadian clock 12 EN Kenji Tomioka Graduate School of Natural Science and Technology, Okayama University Shintaro Inoue Bio-Innovation Research Center, Tokushima University Taro Mito Bio-Innovation Research Center, Tokushima University Yoshiyuki Moriyama Department of Natural Sciences, Kawasaki Medical School Taishi Yoshii Graduate School of Environmental, Life, Natural Science and Technology, Okayama University In the present study, we generated crickets with knockout of either period (per) or timeless (tim) gene by CRISPR/Cas9-based genome editing. We also identified a naturally occurring per- mutant lacking a large coding region including PAS domains. To examine possible synergistic effects, a per- and timKO double mutant was generated by applying genome editing to the per- crickets. Under constant darkness (DD), timKO crickets exhibited a locomotor rhythm with a free-running period of 23.06 �} 0.20 h (mean �} SD), which was significantly shorter than that of the parental strain (23.78 �} 0.12 h). By contrast, perKO and per- crickets showed basically similar phenotype of locomotor rhythm: they exhibited an arrhythmic pattern during the first two to three weeks after transfer to DD but subsequently showed a complex rhythmic pattern with one or multiple components with significantly longer free-running periods (33.35 �} 10.72 h). In the per-;timKO double mutants, approximately 60% of individuals became arrhythmic, while the remaining 40% exhibited complex rhythms with extremely longer free-running periods (37.0 �} 9.17 h) under DD. These results suggest the existence of an underlying oscillatory mechanism that is responsible for regulating locomotor rhythms independently of the canonical per/tim feedback loop. Furthermore, we generated a reporter line on a per�| background by knocking egfp into exon 1 of the per gene, allowing egfp expression to report per transcription. EGFP expression was detected in three distinct clusters of cells within the optic lobe: two located along the dorsal and ventral boundaries between the lamina and medulla neuropils, and one situated near the accessory medulla. These findings raise the possibility that these form part of the circadian clock network that governs circadian locomotor rhythms. No potential conflict of interest relevant to this article was reported.

Œö‰vŽÐ’c–@�l “ú–{•úŽË�ü‹Z�pŠw‰ï Acta Medica Okayama 0369-4305 82 10 2026 ƒxƒCƒY�„’è‚ð—p‚¢‚½ƒ‰ƒWƒIƒNƒ�ƒ~ƒbƒNƒtƒBƒ‹ƒ€‚ÌADC’l–�ü—Ê•ÏŠ·–@ 26-1707 EN Yuki Tanimoto Department of Radiology, NHO Iwakuni Clinical Center Kohei Sugimoto Department of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Masahide Tamori Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Miho Yatsuki Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Shohei Yoshida Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Kazuma Sugahara Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Masataka Oita Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University �y–Ú“I�zƒ‰ƒWƒIƒNƒ�ƒ~ƒbƒNƒtƒBƒ‹ƒ€‚Í�‚‚¢‹óŠÔ•ª‰ð”\‚ð—L‚·‚邱‚Æ‚©‚ç�CŠ³ŽÒ•ÊIMRT•iŽ¿•Û�Ø�iIMRT QA�j‚É�L‚­—˜—p‚³‚ê‚Ä‚¢‚é�Dˆê•û�CƒsƒNƒZƒ‹’l‚ð�ü—Ê‚Ö•ÏŠ·‚·‚邽‚߂̃LƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“‚É‚Í�C•¡�”‚ÌŠù’m�ü—Ê‚Å�ÆŽË‚µ‚½ƒtƒBƒ‹ƒ€‚ª•K—v‚Å‚ ‚è�C�ì‹Æ•‰’S‚ª‘å‚«‚¢‚±‚Æ‚©‚ç�CŽ{�Ý‚É‚æ‚Á‚Ă̓tƒBƒ‹ƒ€ƒ�ƒbƒg•Ï�XŽž‚È‚Ç‚ÉŒÀ’肵‚ÄŽÀŽ{‚³‚ê‚é�ê�‡‚ª‚ ‚é�D–{Œ¤‹†‚Å‚Í�C‰ß‹Ž‚̃LƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“ƒf�[ƒ^ƒZƒbƒg‚Æ‘Î�ÛƒtƒBƒ‹ƒ€‚Ì–¢�ÆŽËŽžƒsƒNƒZƒ‹’l‚ð—p‚¢‚ăLƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“‹È�ü‚ð�„’è‚·‚éƒxƒCƒY�„’胂ƒfƒ‹‚ð�\’z‚µ�CƒLƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“�ì‹Æ‚ÌŒø—¦‰»‚ð–Ú“I‚Æ‚µ‚Ä‚»‚Ì—L—p�«‚ðŒŸ�Ø‚µ‚½�D�y•û–@�zTomoHD‚ð—p‚¢‚Ď擾‚µ‚½93‘g‚̃LƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“ƒf�[ƒ^ƒZƒbƒg‚ð‰ð�Í‘Î�Û‚Æ‚µ‚½�D�ü—Ê‚¨‚æ‚Ñ�ÆŽË‚©‚çƒXƒLƒƒƒ“‚Ü‚Å‚ÌŒo‰ßŽžŠÔ‚ð�à–¾•Ï�”‚Æ‚·‚é“ñŽŸ‘½�€Ž®‰ñ‹Aƒ‚ƒfƒ‹‚ð�\’z‚µ‚½�Dƒ‚ƒfƒ‹‚̓XƒLƒƒƒi‚Ì“Ç‚ÝŽæ‚è•ûŒü�i�c•ûŒü�E‰¡•ûŒü�j‚²‚Æ‚É�ì�¬‚µ�C‘Î�ÛƒtƒBƒ‹ƒ€‚Ì–¢�ÆŽËŽžƒsƒNƒZƒ‹’l‚ð�Ø•Ð�€‚Æ‚µ‚Ä�„’肵‚½�DƒxƒCƒY�„’è‚É‚ÍStan‚ð—p‚¢�CƒgƒŒ�[ƒXƒvƒ�ƒbƒg‚¨‚æ‚ÑRhat“�Œv—Ê‚É‚æ‚èŽû‘©�«‚ð•]‰¿‚µ‚½�D�X‚Ƀ‚ƒfƒ‹�«”\‚Ì•]‰¿‚É‚Í�CˆÙ‚È‚éƒ�ƒbƒg‚ÌEBT4ƒtƒBƒ‹ƒ€10–‡‚ð—p‚¢‚Ä—\‘ªƒsƒNƒZƒ‹’l‚ÆŽÀ‘ª’l‚ð”äŠr‚·‚é‚Æ‚Æ‚à‚É�C�ü—ÊŒë�·‚ð•]‰¿‚µ‚½�D�yŒ‹‰Ê�z‚·‚ׂẴ‚ƒfƒ‹‚ÅRhat‚Í1.01–¢–ž‚ðŽ¦‚µ�C—Ç�D‚ÈŽû‘©�«‚ªŠm”F‚³‚ꂽ�DŒŸ�Ø—pƒtƒBƒ‹ƒ€‚Å‚Í�CƒsƒNƒZƒ‹’l‚ÌŒë�·‚Í3.6%–¢–ž�CŒˆ’èŒW�”�iR2�j‚Í0.99ˆÈ�ã‚Å‚ ‚Á‚½�D‚Ü‚½�C�ü—ÊŒë�·‚Í24 cGy‚Å•½‹Ï2.7 cGy�iSD 1.3�j�C868.2 cGy‚Å•½‹Ï37.5 cGy�iSD 12.8�j‚Å‚ ‚è�C�Å‘å�ü—ÊŒë�·‚Í710.6 cGy‚É‚¨‚¢‚Ä66.6 cGy‚Å‚ ‚Á‚½�D�yŒ‹Œê�z–{Žè–@‚Í�C‰ß‹Ž‚̃LƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“ƒf�[ƒ^ƒZƒbƒg‚Æ‘Î�ÛƒtƒBƒ‹ƒ€‚Ì–¢�ÆŽËŽžƒsƒNƒZƒ‹’l‚ð—p‚¢‚ăLƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“‹È�ü‚ð�„’è‚Å‚«‚é‰Â”\�«‚ðŽ¦‚µ‚½�D‚Ü‚½�Cƒ‰ƒWƒIƒNƒ�ƒ~ƒbƒNƒtƒBƒ‹ƒ€‚̃LƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“�ì‹Æ‚ÌŒø—¦‰»‚ÉŠñ—^‚·‚é‰Â”\�«‚ªŽ¦�´‚³‚ꂽ�D�¡Œã‚ÍŠ³ŽÒ•ÊIMRT QA‚É“K—p‚µ�C�ü—Ê•ª•z•]‰¿‚ւ̉e‹¿‚ðŒŸ�Ø‚·‚é•K—v‚ª‚ ‚é�D No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2399-3642 8 1 2025 Structural insights into tRNA recognition of the human FTSJ1-THADA complex 893 EN Kensuke Ishiguro Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mikako Shirouzu Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research tRNA undergoes various post-transcriptional modifications in the anticodon loop. FTSJ1, a protein conserved among most eukaryotes, mediates 2�f-O-methylations at position 32 (Nm32) or position 34 (Nm34), complexed with THADA or WDR6, respectively. These methylations are crucial for accurate translation and cellular growth. FTSJ1 mutations are associated with non-syndromic X-linked intellectual disability. Although the structure of the FTSJ1-WDR6 complex in yeast has been solved, the structural details of the FTSJ1-THADA complex formation and substrate recognition remain unclear. Herein, using cryo-electron microscopy, we solve the high-resolution structure of FTSJ1-THADA with or without a tRNA substrate. FTSJ1 binds to THADA via its C-terminal region, with a unique interaction mode distinct from the FTSJ1-WDR6 complex. The tRNA substrate is anchored inside THADA, and key THADA residues for THADA-tRNA interaction are identified via structural and biochemical analyses. These findings demonstrate how FTSJ1 and THADA form a complex to mediate Nm32 modification in various tRNAs. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 0732-183X 43 11 2025 Trastuzumab-Pertuzumab Plus Eribulin or Taxane as First-Line Chemotherapy for Human Epidermal Growth Factor 2–Positive Locally Advanced/Metastatic Breast Cancer: The Randomized Noninferiority Phase III EMERALD Trial 1302 1313 EN Toshinari Yamashita Department of Breast Surgery and Oncology, Kanagawa Cancer Center Shigehira Saji Department of Medical Oncology, Fukushima Medical University Toshimi Takano Department of Breast Medical Oncology, The Cancer Institute Hospital of JFCR Yoichi Naito Department of General Internal Medicine, National Cancer Center Hospital East Michiko Tsuneizumi Department of Breast Surgery, Shizuoka General Hospital Akiyo Yoshimura Department of Breast Oncology, Aichi Cancer Center Hospital Masato Takahashi Department of Breast Surgery, Hokkaido University Hospital Junji Tsurutani Advanced Cancer Translational Research Institute, Showa University Tsuguo Iwatani Breast and Endocrine Surgery, Okayama University Hospital Masahiro Kitada Department of Breast Disease Center, Asahikawa Medical University Hospital Hiroshi Tada Department of Surgery, Division of Breast and Endocrine Surgery, Tohoku University Hospital Natsuko Mori Department of Breast Surgery, Seirei Hamamatsu General Hospital Toru Higuchi Department of Breast Unit, Japanese Red Cross Saitama Hospital Tsutomu Iwasa Department of Medical Oncology, Kindai University Hospital Kazuhiro Araki Department of Breast Medical Oncology, Gunma Prefectural Cancer Center Kei Koizumi Department of Surgery 1, Division of Breast Surgery, Hamamatsu University School of Medicine Hiroki Hasegawa Medical HQs, Eisai Co, Ltd Yohei Uchida Medical HQs, Eisai Co, Ltd Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University Norikazu Masuda Department of Breast Surgery, Graduate School of Medicine, Kyoto University Purpose Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC.<br> Methods In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.gov identifier: NCT03264547/UMIN000027938), patients were randomly assigned (1:1) to receive eribulin 1.4 mg/m2 once daily on days 1 and 8 (eribulin group) or a taxane (docetaxel 75 mg/m2 once on day 1 or paclitaxel 80 mg/m2 once daily on days 1, 8, and 15; taxane group) intravenously in a 21-day cycle, each with HP on day 1. The primary end point was progression-free survival (PFS; intention-to-treat population). Secondary end points included objective response rate, overall survival (OS), patient-reported quality of life (QoL), and safety. Noninferiority was tested using the stratified Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events, with a noninferiority HR margin of 1.33.<br> Results Between August 2017 and June 2021, 446 patients (median age, 56.0 years) were enrolled. The median PFS was 14.0 and 12.9 months in the eribulin group (n = 224) and taxane group (n = 222 [docetaxel/paclitaxel, n = 186/36]), respectively (HR, 0.95 [95% CI, 0.76 to 1.19]), which confirmed the noninferiority of the study regimen. The median OS was 65.3 months in the taxane group but has not been reached in the eribulin group. Median time to QoL deterioration was numerically longer with eribulin than with taxane. Adverse event (AE) rates were similar, despite the longer duration of eribulin use. Infusion reaction, skin-related AEs, diarrhea, and edema were more common with taxane, whereas neutropenia was more common with eribulin.<br> Conclusion The results suggested that eribulin + HP is an option for first-line treatment of locally advanced/metastatic HER2+ BC. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2226-7190 13 3 2024 Hormonal changes revealed by selective arterial calcium injection tests in patients with insulinoma treated with EUS–guided ethanol injection 193 195 EN Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Motoshi Komatsubara Department of Endocrinology, Okayama City Hospital Kenichi Inagaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otuka Department of Gastroenterology and Hepatology, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0911-6028 2026 Performance of generative artificial intelligence in oral and maxillofacial radiology based on the board-certification examination of Japan EN Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kawazu Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Hisatomi Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University Mamiko Fujikura Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University Shunsuke Okada Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University Akira Shibanuma Department of Community and Global Health, Graduate School of Medicine, The University of Tokyo Yuri Namba Department of Oral and Maxillofacial Radiology, Division of Dentistry, Okayama University Hospital Suzuka Yoshida Department of Oral and Maxillofacial Radiology, Division of Dentistry, Okayama University Hospital Saori Yoshida Preliminary Examination Room, Medical Development Field, Okayama University Yoshihide Nakamura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Yanagi Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective To evaluate the performance and potential utility of generative artificial intelligence (AI) in oral and maxillofacial radiology using the board-certification examination administered by the Japanese Society for Oral and Maxillofacial Radiology (JSOMR).<br> Methods The responses generated by ChatGPT for multiple-choice questions from the board-certification examination of the JSOMR over the three-year period from 2020 to 2022 were assessed. The questions were manually entered individually as prompts for GPT-3.5, GPT-4, and GPT-5, which are the models available from ChatGPT. The accuracy was calculated according to examination year, question format, and level of taxonomy.<br> Results GPT-3.5 achieved an accuracy of 40.3% for the three years (42.9%, 42.0%, and 36.0% for 2020, 2021, and 2022, respectively), that of GPT-4 was 67.8% (67.3%, 74.0%, and 62.0%, respectively), and that of GPT-5 was 76.5% (79.6%, 78.0%, and 72.0%, respectively). GPT-5�fs results exceeded the passing score for each year with the accuracy significantly outperformed that of GPT-3.5 and GPT-4. Regarding performance according to the question format, GPT-5 performed significantly superior to the earlier models, especially on two-answer questions.<br> Conclusions On the board-certification examination of the JSOMR, the performance of GPT-5 was significantly superior to that of GPT-3.5 and GPT-4. This suggests that, given the rapid development of generative AI, GPT-5 has reached a level of text-based knowledge equivalent to that assessed in the board-certification examination of the JSOMR. No potential conflict of interest relevant to this article was reported.

S. Karger AG Acta Medica Okayama 2296-9403 10 1 2025 Efficacy and Safety of Three Janus Kinase Inhibitors in Ulcerative Colitis Patients over and under 65 Years of Age: A Real-World Comparative Analysis 180 186 EN Shintaro Akiyama Department of Gastroenterology, Institute of Medicine, University of Tsukuba Hiromichi Shimizu Department of Gastroenterology and Hepatology, Institute of Science Tokyo Akiko Tamura Department of Gastroenterology and Hepatology, Institute of Science Tokyo Kaoru Yokoyama Department of Gastroenterology, Kitasato University School of Medicine Toshiyuki Sakurai Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine Mariko Kobayashi Department of Gastroenterology, Institute of Medicine, University of Tsukuba Makoto Eizuka Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University Shunichi Yanai Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University Kei Nomura Department of Gastroenterology, Juntendo University School of Medicine Tomoyoshi Shibuya Department of Gastroenterology, Juntendo University School of Medicine Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Sako Center for Inflammatory Bowel Disease, Tokyo Yamate Medical Center, Japan Community Healthcare Organization Atsushi Yoshida Center for Gastroenterology and Inflammatory Bowel Disease, Ofuna Chuo Hospital Kozo Tsuruta Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine Shinichiro Yoshioka Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine Miki Koroku Institute of Gastroenterology, Tokyo Women�fs Medical University Teppei Omori Institute of Gastroenterology, Tokyo Women�fs Medical University Masayuki Saruta Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine Takayuki Matsumoto Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University Ryuichi Okamoto Department of Gastroenterology and Hepatology, Institute of Science Tokyo Kiichiro Tsuchiya Department of Gastroenterology, Institute of Medicine, University of Tsukuba Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Introduction: It remains unclear whether Janus kinase (JAK) inhibitors differ in efficacy and safety between elderly and non-elderly patients with ulcerative colitis. Methods: We retrospectively compared outcomes between patients who started a JAK inhibitor at ≥65 years (elderly group) and those <65 years (non-elderly group). Results: Among 228, 215, and 159 patients treated with upadacitinib, filgotinib, and tofacitinib, we identified 14, 36, and 13 elderly patients, respectively. There were no significant differences in efficacy between elderly and non-elderly patients for any of the three JAK inhibitors. The elderly group had a 3-fold higher risk of herpes zoster infection with upadacitinib or tofacitinib compared to the non-elderly group, whereas the risk with filgotinib was less than 3% in both groups. The non-elderly group had a 3-fold higher risk of acne with upadacitinib. Conclusion: Adverse event risks with JAK inhibitors should be considered by age. Given the limitations of this study, including its retrospective design and small sample size, further studies with larger sample sizes are needed to validate our findings. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2452-302X 10 10 2025 Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression 101308 EN Toshiomi Katsuki Department of Cardiology, Keio University School of Medicine Dai Kusumoto Department of Cardiology, Keio University School of Medicine Yohei Akiba Department of Cardiology, Keio University School of Medicine Mai Kimura Department of Cardiology, Keio University School of Medicine Jin Komuro Department of Cardiology, Keio University School of Medicine Takahiro Nakamura Department of Cardiology, Keio University School of Medicine Hisayuki Hashimoto Department of Cardiology, Keio University School of Medicine Thukaa Kouka Department of Cardiology, Keio University School of Medicine Kazuhisa Sugai Institute for Integrated Sports Medicine, School of Medicine, Keio University Yoshinori Katsumata Department of Cardiology, Keio University School of Medicine Masaki Miyasaka Department of Computational Biology and Medical Sciences, the University of Tokyo Yutaka Suzuki Department of Computational Biology and Medical Sciences, the University of Tokyo Junko Kuramoto Department of Pathology, Keio University School of Medicine Yoshiaki Kubota Department of Anatomy, Keio University School of Medicine Keiichi Fukuda Department of Cardiology, Keio University School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaki Ieda Department of Cardiology, Keio University School of Medicine Inappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression. EC-specific Scarb1 knockout and systemic SCARB1 inhibition attenuated heart failure progression. In vitro and spatial omics analyses confirmed the role of SCARB1 in ECs and cell-cell interaction during heart failure progression. These findings highlight SCARB1 as a promising therapeutic target for EC-focused interventions. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1439-7595 36 1 2025 Vaccination in paediatric, adolescent, and transitional-age rheumatic diseases: a systematic review 97 112 EN Takuma Ohnishi Department of Pediatrics, Keio University School of Medicine Hiroyuki Wakiguchi Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine Shingo Ishimori Department of Pediatrics, Kobe University Graduate School of Medicine Naohiro Itoh Faculty of Medical Sciences, Department of Pediatrics, University of Fukui Masato Yashiro Department of Pediatrics, Okayama University Hospital Susumu Yamazaki Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine Ikuo Okafuji Department of Pediatrics, Kobe City Medical Center General Hospital Yoshiyuki Ohtomo Department of Pediatrics, Juntendo University Nerima Hospital Ichiro Kobayashi Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center Objectives: This systematic review evaluated the efficacy and safety of vaccination in patients with paediatric, adolescent, and transitional-age rheumatic diseases as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement.<br> Methods: An independent investigator systematically searched PubMed to identify relevant studies published by September 2022. The search results were divided into vaccines or toxoids for diphtheria, pertussis, tetanus, pneumococcus, influenza virus, hepatitis A virus, hepatitis B virus, human papillomavirus, poliovirus, measles virus, mumps virus, rubella virus, varicella zoster virus, and tuberculosis.<br> Results: A meta-analysis was not feasible due to the lack of randomized controlled trials with standardized patient backgrounds and conditions. Non-live vaccines are generally immunogenic and safe for patients with rheumatic diseases. In contrast, live attenuated vaccines should usually be withheld in patients on immunosuppressants, corticosteroids, biologics, or Janus kinase inhibitors. However, for necessary immunizations against measles, rubella, mumps, or varicella, live attenuated vaccines may be considered for patients receiving low-dose corticosteroids, methotrexate, or tumour necrosis factor inhibitors.<br> Conclusions This review highlights the significant gap in evidence for paediatric populations compared with adults, particularly concerning new biological therapies and Janus kinase inhibitors. Further evidence is needed regarding vaccination in paediatric patients with rheumatic diseases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Transcanal Cochlear Implantation Under Endoscopic Guidance with Canal Closure in a Pediatric Patient with CHARGE Syndrome: A Case Report and Surgical Technique 265 270 EN Takuto Yamasaki Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuto Naoi Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Kariya Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medical School Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Case Report 10.18926/AMO/71071 Cochlear implantation (CI) in patients with CHARGE syndrome presents unique surgical challenges due to complex external, middle, and inner ear malformations. We describe the case of a 3-year-old Japanese boy for whom simultaneous transcanal CI under endoscopic guidance and external auditory canal closure were performed. This approach enabled safe electrode placement and resulted in favorable auditory outcomes, representing a potential novel surgical option for CI in patients with CHARGE syndrome. There are few reports of this type of surgical intervention, and the present case highlights the feasibility and clinical benefits of individualized surgical planning for CI in anatomically complex patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Spinous Process Plate Fixation Alone for an AO Spine Osteoporotic Fracture (OF) 5 Diffuse Idiopathic Skeletal Hyperostosis (DISH)-Associated Thoracolumbar Fracture in a Nonagenarian 259 264 EN Satoru Yabuno Department of Neurosurgery, Kagawa Rosai Hospital Masatoshi Yunoki Department of Neurosurgery, Kagawa Rosai Hospital Saori Takeuchi Department of Neurosurgery, Kagawa Rosai Hospital Koji Hirashita Department of Neurosurgery, Kagawa Rosai Hospital Case Report 10.18926/AMO/71070 Diffuse idiopathic skeletal hyperostosis (DISH) predisposes the spine to highly unstable fractures because of long lever-arm biomechanics. Unstable injuries, including AO Spine Osteoporotic Fracture (OF) type 5, are typically treated with long-segment posterior instrumentation; however, pedicle-screw fixation may be infeasible in very elderly patients with severe osteoporosis, critically narrow pedicles, and/or significant comorbidities. A 93-year-old Japanese woman presented with severe back pain without apparent trauma. Computed tomography (CT) revealed a T12 fracture with DISH, classified as OF5. The pedicles were critically narrow (3.7-4.1 mm), and dual-energy X-ray absorptiometry confirmed severe osteoporosis. Because conventional pedicle-screw fixation was considered technically unsafe and excessively invasive, limited posterior stabilization was performed using a single spinous process plate spanning T10-L1. The operative time was 48 min and the estimated blood loss was 10 ml. Immediate postoperative CT confirmed appropriate implant positioning and maintained alignment. At the 1-year follow-up, CT demonstrated solid bony union with preserved alignment and no implant failure; the patient had remained pain-free and ambulatory. This case demonstrates that spinous process-plate fixation can be a minimally invasive salvage option for carefully selected very-elderly patients with DISH when pedicle-screw instrumentation is not feasible. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Hemorrhage from a Jejunal Lymphangioma 253 257 EN Sachiko Ishikami Department of Gastroenterological Surgery, Kochi Health Sciences Center Shuta Tamura Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Nao Yamamoto Department of General Medicine, Kochi Health Sciences Center Yuki Okamoto Department of Gastroenterology and Hepatology, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, Kochi Health Sciences Center Manabu Matsumoto Department of Diagnostic Pathology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/71069 Lymphangioma is a benign tumor arising from lymphatic vessel proliferation and most commonly occurs in the head, neck, or axilla. Involvement of the small intestine is rare and is often overlooked as a source of obscure gastrointestinal bleeding. Because jejunal lymphangiomas frequently present with nonspecific symptoms and may escape detection by conventional upper and lower gastrointestinal endoscopy or cross-sectional imaging, diagnosis is often delayed. Advances in balloon-assisted enteroscopy have enabled direct visualization of small intestinal lesions, facilitating accurate diagnosis and appropriate therapeutic decision-making. Here, we report a case of jejunal lymphangioma presenting with severe anemia due to active bleeding, which was detected by double-balloon endoscopy and successfully managed by laparoscopic-assisted resection. This case highlights the importance of considering small intestinal lymphangioma in the differential diagnosis of unexplained gastrointestinal bleeding and underscores the clinical utility of deep enteroscopy in identifying rare but clinically significant small bowel tumors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Post-Tracheostomy Fistula Formation Between the Trachea and Left Common Carotid Artery in a Pediatric Patient with Trisomy 18 247 252 EN Tsuyoshi Shiina Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Watanabe Department of Pediatrics, Fukuyama City Hospital Junko Yoshimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takeshi Sato Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisaku Morimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Okamura Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Terutaka Tanimoto Department of Pediatric Surgery, Okayama University Hospital Yosuke Washio Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Oyama Department of Pediatric Surgery, Fukuyama City Hospital Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuo Noda Department of Pediatric Surgery, Japanese Red Cross Society Himeji Hospital Case Report 10.18926/AMO/71068 The long-term survival of individuals with trisomy 18 has improved, and the need for tracheostomy in this population has thus increased. We describe the case of a 3-year-old Japanese boy with trisomy 18 who developed a tracheoarterial fistula involving the left common carotid artery (LCCA). He underwent an emergency tracheostomy for respiratory failure secondary to pneumonia. Massive hemorrhage from the tracheostoma occurred on postoperative day 31, leading to his death. The autopsy revealed that the LCCA originated from the brachiocephalic trunk and coursed medially, forming a fistulous connection with the trachea. This case highlights the clinical importance of preoperative vascular mapping in patients with chromosomal abnormalities. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Video-Assisted Thoracoscopic Resection of an Upper Mediastinal Ectopic Parathyroid Adenoma 241 246 EN Yuta Hasegawa Department of Surgery, National Defense Medical College Hospital Hironori Tsujimoto Department of Surgery, National Defense Medical College Hospital Naoyuki Uehata Department of Surgery, National Defense Medical College Hospital Risa Kariya Department of Surgery, National Defense Medical College Hospital Asuma Ide Department of Surgery, National Defense Medical College Hospital Takafumi Suzuki Department of Surgery, National Defense Medical College Hospital Seiichiro Fujishima Department of Surgery, National Defense Medical College Hospital Keita Kouzu Department of Surgery, National Defense Medical College Hospital Yoshihisa Yaguchi Department of Surgery, National Defense Medical College Hospital Kosuke Miyai Department of Laboratory Medicine, National Defense Medical College Hospital Ayumu Kurihara Department of Laboratory Medicine, National Defense Medical College Hospital Sho Ogata Department of Laboratory Medicine, National Defense Medical College Hospital Susumu Matsukuma Department of Laboratory Medicine, National Defense Medical College Hospital Hideki Ueno Department of Surgery, National Defense Medical College Hospital Case Report 10.18926/AMO/71067 Primary hyperparathyroidism (pHPT) is typically caused by a parathyroid adenoma, although some cases arise from ectopic glands. Accurate preoperative localization is essential for guiding surgical strategy, particularly for mediastinal lesions. We report successful video-assisted thoracoscopic surgery (VATS) for an upper mediastinal parathyroid adenoma. A 68-year-old woman was referred for hypercalcemia during evaluation for recurrent ureteral stones. Laboratory tests revealed elevated serum calcium (13.2 mg/dl) and intact parathyroid hormone (iPTH) levels (266 pg/ml). Contrast-enhanced computed tomography, magnetic resonance imaging, and 99mTc-methoxyisobutylisonitrile scintigraphy identified a 20-mm mass adjacent to the right esophageal wall. VATS was performed due to the tumor�fs mediastinal location. The lesion was resected with intraoperative nerve monitoring (IONM) to avoid recurrent laryngeal nerve damage. Postoperatively, iPTH and calcium levels rapidly normalized. Transient hypocalcemia and mild hoarseness occurred but resolved with calcium supplementation and conservative management. Pathological examination confirmed a parathyroid adenoma without malignancy. VATS offers a safe and minimally invasive approach for upper mediastinal parathyroid adenomas. IONM and vigilant calcium management are crucial for minimizing these complications. This case highlights the importance of comprehensive imaging, surgical planning, and postoperative care in managing upper mediastinal pHPT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Regional Prevalence of Carbapenemase-Producing Enterobacterales and Extended-Spectrum Beta-Lactamase-Producing Enterobacterales in Okayama and Neighboring Prefectures, Japan 233 240 EN Sakura Ogawa Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidemasa Akazawa Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sachie Namba Department of Laboratory Testing, Okayama Medical Laboratory Center Chiyoko Hirota Department of Laboratory Testing, Okayama Medical Laboratory Center Tomoyoshi Kishiue Department of Laboratory Testing, Okayama Medical Laboratory Center Shohei Ibara Department of Laboratory Testing, Okayama Medical Laboratory Center Takayuki Kondo Department of Laboratory Testing, Okayama Medical Laboratory Center Genshi Fukuda Department of Sales Promotion, Okayama Medical Laboratory Center Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/71066 Carbapenemase-producing Enterobacterales (CPE) and extended-spectrum ƒÀ-lactamase (ESBL)-producing Enterobacterales (ESBL-E) are representative antimicrobial-resistant pathogens. We investigated the prevalence of CPE and ESBL-E in Okayama, Japan to clarify their current epidemiology and potential clinical burden. Active surveillance for CPE and ESBL-E was performed first, using stool samples submitted to the Okayama Medical Laboratory (Japan) in the years 2024-2025. Screening was performed using a selective agar (CHROMagar mSuper CARBA/ESBL). Phenotypic identification was conducted with the use of a modified carbapenem inactivation method and double-disk phenotypic confirmatory tests. Clinical information including patient age, sex, sampling date, and hospital address were collected, and the data were analyzed according to specimen origin (hospitals, clinics, and health checkups). A total of 2,000 stool samples were screened, of which two CPE isolates (0.1%) and 285 ESBL-E isolates (14.3%) were identified. By specimen origin, the ESBL-E positivity rate was significantly higher in hospitals (17.4%) than in clinics (11.8%). By age category, the late elderly (> 75 years) exhibited the highest ESBL-E positivity rate (22.6%) compared to other age groups. In the clinics and health checkups, infants (0 years) demonstrated high ESBL-E positivity rates (18.2% and 14.3%, respectively). Escherichia coli was the most common ESBL-E organism in the hospitals (77.2%), clinics (88.8%), and health checkups (87.5%). Our active screening demonstrated that the prevalences of CPE and ESBL-E were within the reported ranges; however, in this era of increasing internationalization, continuous surveillance of these notifiable pathogens is warranted. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 The Impact of Migraine on Cerebral Artery Dissection 227 231 EN Kenichi Kashihara Okayama Neurology Clinic Toshikazu Hamaguchi Department of Neurology, Okayama Kyokuto Hospital Yasuko Takeda Okayama Neurology Clinic Original Article 10.18926/AMO/71065 The impact of migraines as a risk factor for cervicocerebral artery dissection was retrospectively investigated in patients who had a cervicocerebral artery dissection. We first evaluated the patients�f medical records and history of migraine and then calculated the proportion of patients with migraine as well as the relevant vascular risk factors. The prevalence of migraine with respect to the location of the cervicocerebral artery dissection was also identified. Sixty-two patients (37 men, 25 women) had both a cerebral artery dissection and a record of migraine. Among them, 93.5% presented with an isolated headache, and 6.5% presented with a related stroke. Regarding the locations of the artery dissection, 56 (90.3%) were in the intracranial vertebral artery (VA), three (4.8%) were in the internal carotid artery, and one case each (1.6%) was in an anterior cerebral artery, basilar artery (BA), and both the VA and BA. Among the patients with VA dissection, 42 (73.7%) presented with migraines. Among the four patients with dissection of an artery of anterior circulation, only one (25%) had a migraine history. The frequency of migraines tended to be higher in the patients with VA dissection compared to those with a dissection of arteries of anterior circulation. These data suggest that (i) migraine is a potent risk factor for cerebral artery dissection, especially intracranial VA dissection, and (ii) the intracranial VA may be more susceptible to dissection compared to arteries of anterior circulation. No potential conflict of interest relevant to this article was reported.

Japanese Society of Veterinary Science Acta Medica Okayama 0916-7250 88 8 2026 Comparison of three irradiation ways with Monte Carlo calculation for the feline lymphoma with orthovoltage radiation therapy 1239 1245 EN Yuki NEMOTO Department of Veterinary Radiology, Joint Faculty of Veterinary Medicine, Yamaguchi University Yoshinori TANABE Faculty of Medicine, Graduate School of Health Sciences, Okayama University Ryouta ONIZUKA Department of Radiology, Kokura Memorial Hospital Munekazu NAKAICHI Department of Veterinary Radiology, Joint Faculty of Veterinary Medicine, Yamaguchi University Although orthovoltage radiation therapy remains widely used in veterinary medicine in Japan due to its affordability and operational simplicity, accurate calculation of dose distribution is challenging. Treatment planning varies between practitioners and tends to rely on empirical methods. This study aimed to compare the effects of three different orthovoltage beam directions on dose distribution in feline nasal lymphoma using Monte Carlo simulations. CT images from five clinical cases were analyzed using three irradiation plans: Plan A (beam directed perpendicularly to the hard palate), Plan B (perpendicularly to the nasal bridge), and Plan C (from the oral cavity). Each plan used a 4 �~ 4 cm field and delivered a 10 Gy dose at 280 kVp. Doses to the tumor, brain, and both eyes were calculated. Mean dose for the tumor did not significantly differ among the three plans. Plan B resulted in significantly higher doses to the ipsilateral eye compared to Plan C, but delivered the lowest brain dose. Depth-dose analysis revealed a peak just above the bone at the beam entrance, followed by a sharp attenuation in all plans. These findings suggest that beam direction substantially affects dose distribution in orthovoltage therapy, particularly for organs at risk including superficial bones and overlying skin. Meticulous planning is essential to ensure sufficient tumor dose coverage while mitigating and distributing adverse effects, especially in complex regions like the feline nasal cavity. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 8 2026 Incidence and Time to Onset of Pseudophakic Cystoid Macular Edema (Irvine-Gass Syndrome) After 1,325 Consecutive Cataract Surgeries Performed by a Single Surgeon Over Four Years e114802 EN Toshihiko Matsuo Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems Chie Nakago-Matsuo Orthodontics, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Objectives<br> Macular edema after cataract surgery is known as pseudophakic cystoid macular edema or Irvine-Gass syndrome. The aim of this study was to determine the incidence and time to onset of cystoid macular edema after uncomplicated cataract surgery.<br> Methods <br> A retrospective review was conducted of 1,325 consecutive cataract surgeries performed by a single surgeon at a single institution over four years, from January 2022 to December 2025.<br> Results<br> Among 1,325 eyes, one or more macular cysts were detected by optical coherence tomography in 27 eyes (2.0%) of 22 patients who complained of blurred vision or decreased visual acuity after having no symptoms immediately after surgery. The 22 patients (27 eyes: 12 right and 15 left) comprised 12 men and 10 women. Their ages at the time of surgery ranged from 57 to 82 years, with a median of 75.5 years. Of the 27 eyes that developed macular cysts, 13 eyes with no preoperative or intraoperative risk factors for inflammation received topical 0.1% bromfenac twice daily as the only postoperative anti-inflammatory treatment, together with topical antibacterial 0.5% moxifloxacin four times daily. In contrast, the remaining 14 eyes, which had risk factors for inflammation, such as exfoliation, floppy iris, poor mydriasis, extracapsular cataract extraction, or diabetes mellitus, received topical bromfenac twice daily and 0.1% betamethasone (or 0.1% fluorometholone in two eyes) four times daily, as well as topical moxifloxacin. The time from surgery to the diagnosis of macular cysts ranged from one week to eight months, with a median of two weeks, in the 13 eyes treated with topical bromfenac only. In the 14 eyes treated with the combination of topical bromfenac and betamethasone, the time to diagnosis ranged from two weeks to 13 months, with a median of two months. In 26 of the 27 eyes, the macular cysts disappeared and visual acuity returned to normal without residual symptoms within two weeks to seven months, with a median of one month, after topical betamethasone four times daily was initiated or resumed.<br> Conclusions <br> Pseudophakic macular cysts developed during the postoperative course in eyes with no preoperative or intraoperative risk factors that received topical bromfenac alone. They also developed later in the postoperative course after the combination of topical bromfenac and betamethasone was discontinued in eyes with risk factors for inflammation. The macular cysts disappeared following the initiation or resumption of topical betamethasone, accompanied by recovery of visual acuity and resolution of symptoms. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Workforce and institutional factors associated with comprehensive genomic profiling utilization in gynecologic oncology: a nationwide questionnaire survey in Japan EN Tamotsu Sudo Department of Cancer Genetics and Genomics, School of Medicine, Fujita Health University Kenta Masuda Department of Obstetrics and Gynecology, Keio University School of Medicine Katsutoshi Oda Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo Hidemichi Watari Department of Obstetrics and Gynecology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University Akira Hirasawa Department of Clinical Genomic Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinya Sato Department of Obstetrics and Gynecology, Tottori University School of Medicine Kenichi Harano Department of Medical Oncology, National Cancer Center Hospital East Satoru Nagase Department of Obstetrics and Gynecology, Faculty of Medicine, Yamagata University Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Masaki Mandai Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine Yuko Sasajima Department of Pathology, Teikyo University Hospital Hirouki Yanai Department of Pathology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitoshi Tsuda Department of Basic Pathology, National Defense Medical College Yusuke Kobayashi Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba Kei Kawana Department of Obstetrics and Gynecology, Nihon University School of Medicine Mikio Mikami Department of Medical Science, Shonan University of Medical Science Kiyoko Kato Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Daisuke Aoki International University of Health and Welfare Graduate School Aikou Okamoto Department of Obstetrics and Gynecology, The Jikei University School of Medicine Background Comprehensive genomic profiling (CGP) has been widely introduced into precision oncology; however, its real-world implementation in gynecologic oncology remains unclear. This study evaluated nationwide CGP utilization, treatment translation, and management of secondary germline findings in Japanese gynecologic oncology.<br> Methods A nationwide survey was conducted across 98 institutions participating in gynecologic oncology training and/or Japan�fs cancer genomic medicine network. Institutional characteristics, workforce composition, treatment translation, and management of germline findings were assessed. Associations between institutional factors and CGP utilization or trial-related treatment translation were analyzed using incidence rate ratios (IRRs) with 95% confidence intervals.<br> Results Among 68 institutions with complete CGP volume data, 6,964 CGP tests were performed, including 922 for gynecologic malignancies. The median number of gynecologic CGP tests per institution was 10. In multivariate analysis, the number of board-certified obstetrician–gynecologists was associated with CGP utilization (IRR, 1.05; 95% CI 1.01–1.08). CGP-guided therapy was delivered to 80 patients (8.7%). Trial-related treatment translation was associated with the number of board-certified obstetrician–gynecologists (IRR, 1.09; 95% CI 1.02–1.16) and the presence of a medical oncology department (IRR, 7.93; 95% CI 1.41–44.72). Presumed germline pathogenic variants were identified in 100 cases (10.8%); however, confirmatory germline testing was performed in only 38 cases.<br> Conclusion CGP utilization in Japanese gynecologic oncology was associated with gynecologic workforce capacity and multidisciplinary genomic infrastructure. Collaboration between gynecologic oncology and medical oncology may facilitate treatment translation. CGP may also serve as an entry point for hereditary cancer evaluation despite incomplete downstream germline evaluation. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 0022-2593 2026 Updated ENIGMA recommendations for reporting germline variants in cancer susceptibility genes and their translation into twenty languages EN Arcangela De Nicolo Department of Experimental Oncology, Unit of Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei Tumori Diana M Eccles Faculty of Medicine, University of Southampton Kirsimari Aaltonen Duodecim Medical Publications Ltd Pia Alhopuro HUS Diagnostic Center, Laboratory of Genetics, Helsinki University Hospital and University of Helsinki Sarah Louise Ariansen Department of Medical Genetics, Oslo University Hospital Michela Biancolella Department of Biology, University of Rome Tor Vergata Sandrine M Caputo Department of Genetics, Institut Curie Olivier Caron Département de Médecine Oncologique, Gustave Roussy Pietro Cavalli Medical Genetics, IRCCS Humanitas Research Hospital Jianbang Chiang Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore Kathleen B M Claes Center for Medical Genetics, Ghent University Hospital Edgar Christian S Cuaresma St. Luke�fs Medical Center Miguel de la Hoya Hospital Clínico San Carlos, Molecular Oncology Laboratory, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos Antoine De Pauw Department of Genetics, Institut Curie Orland Díez Vall d�fHebron Hospital Universitari, Area of Clinical and Molecular Genetics, Vall d�fHebron Barcelona Hospital Campus Mev Domínguez-Valentin Institute of Cancer Research, Department of Tumor Biology, The Norwegian Radium Hospital Hans Ehrencrona Department of Clinical Genetics, Pathology and Molecular Diagnostics, Skåne University Hospital Magnhild K Fjeldvær Department of Medical Genetics, Oslo University Hospital Florentia Fostira INRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-Demokritos Marie Belle D Francia St. Luke�fs Medical Center Javier Galego-Carro Fundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de Compostela Encarna B Gómez García Department of Clinical Genetics, Maastricht University Medical Centre Nur Tiara Hassan Cancer Research Malaysia Jan Hauke Faculty of Medicine and Center for Familial Breast and Ovarian Cancer, University of Cologne, University Hospital Cologne Akira Hirasawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Clinical Genomic Medicine, Okayama University Xin Huang Department of Breast Surgery, Peking Union Medical College Hospital Elaine Marisse H Ilagan-Cargullo St. Luke�fs Medical Center Issei Imoto Aichi Cancer Center Research Institute Sowmya Jonnagadla Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore, Si Manasadevi Karthikeyan Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore Petra Kleiblova Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Irene Konstantopoulou INRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-Demokritos Artur Kowalik Department of Molecular Diagnostics, Holy Cross Cancer Centre Anders Kvist Department of Clinical Sciences Lund, Division of Oncology, Lund University Fabienne Lesueur PSL Research University Shao-Tzu Li Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore Adrià López-Fernández Hereditary Cancer Genetics Group, Vall d�fHebron Barcelona Hospital Campus, Vall d�fHebron Institute of Oncology (VHIO) Eva Machackova Center for Medical Genetics, Masaryk Memorial Cancer Institute Alexandra Martins Univ Rouen Normandie, Inserm U1245 Arjen R Mensenkamp Department of Human Genetics, Radboud University Medical Center Yukihide Momozawa Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences Gemma Montalban Department of Oncogenetics, MRC Holland Alvaro N A Monteiro Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute Heli Nevanlinna HUS Diagnostic Center, Laboratory of Genetics, Helsinki University Hospital and University of Helsinki Joanne Ngeow Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore Edenir Inez Palmero Molecular Oncology Research Center, Barretos Cancer Hospital Inge Sokilde Pedersen Molecular Diagnostics and Clinical Cancer Research Centre, Aalborg University Hospital Frances Victoria F Que St. Luke�fs Medical Center Marta Santamariña Fundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de Compostela Elizabeth Santana dos Santos Department of Medical Oncology, A.C. Camargo Cancer Center Christian F Singer Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Medical University of Vienna Monika Siołek Genetic Clinic, Holy Cross Cancer Centre Angela R Solano Departmento de Analisis Clinicos, Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" (CEMIC) Jana Soukupova Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Priyadharshini d/o Suresh Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore Magdalena Szczepaniak Department of Molecular Diagnostics, Holy Cross Cancer Centre Yen Y Tan Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Medical University of Vienna Soo Hwang Teo Cancer Research Malaysia Emma Tham Department of Clinical Genetics and Genomics, Karolinska University Hospital Mads Thomassen Department of Clinical Genetics, Odense University Hospital Georgios Tsaousis Genekor Medical S.A Thomas van Overeem Hansen Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet Ana Vega Fundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de Compostela Eladio A Velasco-Sampedro Instituto de Biología y Genética Molecular, Splicing and Genetic Susceptibility to Cancer, Consejo Superior de Investigaciones Científicas - Universidad de Valladolid (CSIC-UVa) Teresia Wangensteen Department of Medical Genetics, Oslo University Hospital Barbara Wappenschmidt Faculty of Medicine and Center for Familial Breast and Ovarian Cancer, University of Cologne, University Hospital Cologne Drakoulis Yannoukakos INRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-Demokritos Sook-Yee Yoon Cancer Research Malaysia Amanda B Spurdle Population Health Program, QIMR Berghofer Medical Research Institute Paolo Radice Department of Experimental Oncology, Unit of Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei Tumori Genetic testing for cancer susceptibility underpins precision cancer prevention and care. Gaps in the healthcare providers�f genetic literacy and an ambiguous lexicon for variant description may hinder proper delivery and clinical application of consistently trustworthy test results. The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) international consortium supports controlled terminology and recommends a framework for reporting germline variants in cancer susceptibility genes, using breast cancer as an exemplar. Moving forward towards terminological coherence across disciplines and borders, the ENIGMA Clinical Working Group launched a multinational effort to release consortium-approved translations of the published recommendations. The herein reported Vocabulary Translation Project offered an opportunity to reappraise and align the reference text to the recent BRCA1 and BRCA2 specifications to the American College of Medical Genetics and Genomics/Association for Molecular Pathology rules by the ENIGMA Variant Curation Expert Panel and to highlight country-specific differences in breast cancer risk assessment and management. The updated recommendations and their 20 translations are now provided as easy to handle documents, covering 11 of the most widely spoken languages in the world. They will contribute to minimised erroneous inferences, more informed decision-making, improved health outcomes and equity in the use of genetic testing for cancer predisposition and in translational oncology. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Clinical utility of diagnosing Lynch syndrome in gynecologic oncology: a joint statement from four Japanese academic societies EN Shinya Sato Department of Obstetrics and Gynecology, Faculty of Medicine, Tottori University Kenta Masuda Department of Obstetrics and Gynecology, Keio University School of Medicine Katsutoshi Oda Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo Takeshi Kuwata Department of Genetic Medicine and Services, National Cancer Center Hospital East Takeshi Nakajima Division of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer Institute Masayoshi Yamada Endoscopy Division, National Cancer Center Hospital Tatsuro Yamaguchi Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Akira Hirasawa Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaki Mandai Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine Kohji Tanakaya Department of Surgery, National Hospital Organization Iwakuni Medical Center Hideyuki Ishida Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University Takayuki Yoshino Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East Aikou Okamoto Department of Obstetrics and Gynecology, Sanno Hospital, International University of Health and Welfare Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome, associated with substantially increased risks of colorectal and gynecologic malignancies. Endometrial cancer may serve as a sentinel cancer for LS, placing gynecologists and gynecologic oncologists in a key position for early recognition and long-term management. This joint statement was developed through a multidisciplinary process involving the Japan Society of Gynecologic Oncology, the Japan Society of Clinical Oncology, the Japanese Society of Hereditary Tumors, and the Japanese Society for Cancer of the Colon and Rectum. It aims to clarify the clinical utility of diagnosing LS in gynecologic oncology within the Japanese healthcare system. We outline a tumor-first paradigm in which universal mismatch repair immunohistochemistry and/or microsatellite instability testing for endometrial cancer facilitates LS detection and provides actionable biomarkers for systemic therapy. This statement summarizes the clinical impact of LS diagnosis across gynecologic oncology. We highlight patterns of synchronous and metachronous malignancies and the prevalence of LS in ovarian cancer, particularly in endometrioid and clear–cell subtypes. We discuss surgical implications, including risk-reducing hysterectomy with bilateral salpingo-oophorectomy, consideration of concomitant gynecologic risk-reducing surgery during colorectal cancer resection, and individualized ovarian preservation in selected early-stage endometrial cancer or atypical endometrial hyperplasia. We also review the treatment relevance of deficient mismatch repair/microsatellite instability-high status for immune checkpoint inhibitors and emerging fertility-preserving approaches, and address surveillance, cascade testing for relatives, implementation barriers, and the need for multidisciplinary pathways and healthcare system–level support to ensure equitable access to genetic counseling and testing. No potential conflict of interest relevant to this article was reported.

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 21 8 2026 Study protocol: Effect of inulin supplementation on gut microbiota in patients with oral lichen planus �\ A double-blind, randomised, placebo-controlled parallel-group trial e0356180 EN Koki Nambu Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Naoki Kaneko Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Shiho Yokomizo Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Hu Chen Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Lijing Yan Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Wang Shiyao Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Ryusei Shizuma Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Eiji Iwata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yukiko Ohyama Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Shohei Akagawa Department of Pediatrics, Kansai Medical University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shintaro Kawano Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Masafumi Moriyama Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Oral lichen planus is a chronic inflammatory disease of the oral mucosa characterised by immune dysregulation, but its pathogenesis remains incompletely understood and no curative treatment has been established. Our previous work showed that patients with oral lichen planus exhibit gut dysbiosis, including reduced microbial diversity and depletion of butyrate-producing bacteria. Because butyrate promotes regulatory T-cell differentiation and supports immune homeostasis, targeting this dysbiosis may represent a microbiota-directed approach for immune modulation in oral lichen planus. This study aims to investigate the effects of inulin supplementation on the gut microbiota and related immune markers in patients with oral lichen planus. This multicentre, double-blind, randomised, placebo-controlled parallel-group trial will enrol 80 patients with oral lichen planus. Participants will be randomly assigned in a 1:1 ratio to receive either inulin (8 g/day) or a maltose placebo for 4 weeks, in addition to standard care. The primary outcome is the change in the relative abundance of prespecified butyrate-producing gut bacteria from baseline to the end of intervention at Week 6. Secondary outcomes include changes in gut microbiota diversity, salivary microbiota composition, faecal short-chain fatty acid concentrations, peripheral blood regulatory T-cell counts, blood test parameters, and clinical symptoms of oral lichen planus. Analyses will follow the intention-to-treat principle, and between-group differences will be assessed using appropriate statistical methods. This trial is designed to evaluate, in a randomised placebo-controlled setting, whether a microbiota-directed intervention can modify gut microbial profiles and related immune markers in patients with oral lichen planus. The findings are expected to clarify whether inulin supplementation can modify gut microbial profiles and related immunological markers in patients with oral lichen planus. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000060840, registered on 1 April 2026 (https://rctportal.mhlw.go.jp/detail/um?trial_id=UMIN000060840#). No potential conflict of interest relevant to this article was reported.

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 66 2 2026 RHOA G17V mutation analysis redirecting diagnosis: nodal T-follicular helper cell lymphoma with classic Hodgkin lymphoma feature 122 129 EN Rio Yamada Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Takuya Fukumi Department of Hematology, Okayama City Hospital Kumiko Ohsawa Department of Pathology, Saitama Medical Center, Saitama Medical University Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Nodal T-follicular helper cell lymphoma (nTFHL) may present with Hodgkin/Reed–Sternberg (HRS)-like cells and can morphologically mimic classic Hodgkin lymphoma (CHL), although these entities are usually distinguishable. We report an unusual case showing marked morphologic and molecular overlap with CHL, creating a diagnostic challenge but ultimately considered biologically consistent with nTFHL.<br> An 81-year-old woman presented with stage IV disease involving the bone marrow and markedly elevated serum soluble interleukin-2 receptor levels. Excisional lymph node biopsy revealed scattered HRS cells in a T-cell–rich background, with strong CD30 and PD-L1 expression and weak PAX5 positivity, findings consistent with CHL. Fluorescence in situ hybridization demonstrated copy-number alterations at the 9p24.1 locus in HRS cells, further supporting molecular features characteristic of CHL.<br> However, the presence of two T-follicular helper markers, detection of the RHOA p.Gly17Val (G17V) mutation, and oligoclonal T-cell receptor rearrangements with shared peaks in lymph node and bone marrow indicated an underlying nTFHL. The differential therapeutic response also supported a diagnosis of nTFHL, which could not have been established on morphology alone.<br> In this case, although the HRS cells displayed morphological, immunophenotypic, and molecular features highly suggestive of CHL, the biological nature of the lesion was consistent with nTFHL. Compared with previously reported cases of nTFHL with HRS-like cells, this case more closely resembled CHL and may represent a distinct subset best described as �gnTFHL with CHL features,�h a concept warranting greater recognition among pathologists and clinicians. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 2 2025 Durable Response to Nivolumab Combined With Metformin in Advanced Pancreatic Cancer: A Case Report With Seven Years of Follow-Up e79001 EN Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Toshio Kubo Department of Allergy and Respiratory Medicine, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology, Okayama City Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Toshiyuki Kozuki Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Heiichiro Udono Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital We report a case of poorly differentiated pancreatic cancer that showed an exceptional response to combination therapy with nivolumab and metformin. A 58-year-old man presented with epigastric pain and was diagnosed with locally advanced pancreatic cancer with para-aortic lymph node metastasis. After disease progression following modified FOLFIRINOX therapy (a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin), the patient was enrolled in a phase Ib clinical trial of nivolumab (3 mg/kg biweekly) combined with metformin (750 mg/day). Post-treatment imaging showed marked tumor shrinkage with normalization of the tumor markers. During treatment, the patient was diagnosed with early-stage lung cancer and underwent successful left S1+S2 segmentectomy with temporary suspension of immunotherapy. The therapeutic response of pancreatic cancer has been sustained for seven years, with minimal residual disease. This unprecedented response duration is particularly noteworthy considering his microsatellite stability, which typically predicts a limited response to immune checkpoint inhibition.<br> This case demonstrates an exceptional response to nivolumab and metformin combination therapy in poorly differentiated pancreatic cancer. The remarkable durability of the response suggests the need for further investigation to identify patients most likely to benefit from this therapeutic approach. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 2 2025 A Rare Course of Chiari Malformation With Large Syringomyelia Presenting at 54 Years Old e78399 EN Masato Tanaka Orthopedic Surgery, Okayama University Hospital Sneha Sharma Orthopedics, North Delhi Municipal Corporation (DMC) Medical College Kushal H Gori Orthopedic Surgery, Okayama Rosai Hospital Md Shohidullah Orthopedic Surgery, Okayama Rosai Hospital Koji Uotani Orthopedic Surgery, Okayama University Hospital Chiari malformation type 1 (CM1) is considered a congenital condition. The symptoms include severe headache, hypalgesia, and loss of temperature sensation. It constitutes a significant burden among children and young adults. The onset of symptoms of CM1 is more commonly observed in relatively young children and is very rare in those over 50 years old. This study aims to present a rare surgical case of CM1 associated with a large syringomyelia in a 54-year-old man.<br> A 54-year-old man with low back pain was introduced to our department. He had slight hyperreflexia of the extremities, slight muscle weakness in both legs, and numbness in the right leg (3/10). He also had urinary and bowel incontinence and spastic gait. Cervical magnetic resonance imaging (MRI) showed CM1 with large syringomyelia extending from C1 to T11. The cervical canal was widened because of a long history of spinal cord expansion.<br> The patient was successfully treated surgically by foramen magnum decompression and syringosubarachnoid shunting under the guidance of O-arm navigation. The muscle weakness and sensory function recovered almost entirely on the one-year follow-up. The patient's cervical Japanese Orthopedic Association (JOA) score had improved from 11/17 to 16/17.<br> Gradually enlarging syringomyelia with slight CM1 is rare, but surgeons should consider this condition's possibility. Foramen magnum decompression achieves good results even in cases with a long history of syringomyelia. This new navigation technique provides an excellent result for a large syringomyelia with CM1. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 16 11 2024 Accuracy of Cup Alignment in Total Hip Arthroplasty: A Comparison Between Portable Navigation and Goniometer e74176 EN Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Tetsunaga Department of Orthopaedic Surgery, Okayama University Hospital Kazuki Yamada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Koura Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichiro Okuda Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasutaka Masada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Muguruma Department of Orthopaedics, Okayama Medical Center Yuki Okazaki Department of Orthopaedics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Navigation systems, including portable navigation systems, used for total hip arthroplasty (THA) are useful for achieving higher cup alignment accuracy. NAVBIT, a newly available portable navigation system, uses a unique registration method, the table tilt registration. However, its accuracy is unclear. This retrospective study aimed to investigate whether THA with a portable navigation system in the lateral position with the flip technique is more accurate than THA with a cup goniometer in the supine or lateral positions.<br> Methodology This study included 96 consecutive patients (77 women, 19 men) who underwent primary cementless THA using either a portable navigation system in the lateral position with the flip technique or a cup goniometer in the supine or lateral positions. The average age of the patients was 66.8 years (range = 29-91) and the average body mass index was 24.6 kg/m2 (range = 17.5-39.9). The accuracy of cup orientation was compared among the three groups.<br> Results The absolute values of the difference in cup inclination and anteversion with the NAVBIT (2.1 �} 1.7�‹, 2.0 �} 1.4�‹) were smaller than that with the cup goniometer in the supine (3.4 �} 2.4�‹, 3.4 �} 2.2�‹) and lateral decubitus positions (3.4 �} 2.5�‹, 5.0 �} 3.5�‹). Overall, 91%, 64.5%, and 56.3% were within 5�‹ of the target angles in the navigation, supine goniometer, and lateral goniometer groups, respectively.<br> Conclusions The accuracy of cup alignment with the portable navigation system using the flip technique was significantly higher than that with the cup goniometer in the supine and lateral decubitus positions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 5 2025 Association Between Initial Symptoms and Clinical Outcomes in COVID-19 e84919 EN Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Mitsuru Tsuge Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Yasushi Tanimoto Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Sho Mitsumune Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Goro Kimura Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Haruto Yamada Department of Infectious Diseases, Okayama City Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akihiko Taniguchi Department of Internal Medicine, Fukuyama City Hospital Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Aokage Department of Emergency Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: The clinical presentation of coronavirus disease 2019 (COVID-19) ranges from localized respiratory symptoms such as cough and sore throat to systemic symptoms such as fever and fatigue. To our knowledge, no study has assessed severe disease risk by dividing onset symptoms into localized respiratory and other symptoms. We aimed to determine whether the risk of severe COVID-19 differs depending on whether the symptoms at onset are limited to local respiratory symptoms.<br> Method: This was a multicenter prospective cohort study. The patients were classified into localized respiratory or systemic symptom groups based on the symptoms at onset. Demographic data, blood biomarkers, and clinical outcomes, including mortality, intubation, admission to the intensive care unit, and time to discharge, were compared. This study included 100 adult patients diagnosed with COVID-19 between July 2020 and August 2021.<br> Result: Twelve patients were classified into the localized respiratory symptom group and the remaining 88 into the systemic symptom group. No significant differences between the groups were observed in the baseline characteristics, blood biomarkers, or clinical outcomes. The mortality rates were 0.0% and 4.6%, respectively. The median durations to discharge were 11 and 10 days, respectively (p=0.512). The levels of inflammatory and oxidative stress biomarkers, including interleukin-6 and hydroperoxides, were similar between the groups.<br> Conclusion: The symptom type at disease onset was not significantly associated with differences in clinical outcomes. Comprehensive assessments beyond initial symptoms are crucial for predicting disease progression and optimizing management strategies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 14 8 2026 Black Hairy Tongue in a 54�]Day�]Old Infant: A Case Report e73170 EN Masanori Masui Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumi Sakamoto Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Black hairy tongue is a benign condition caused by elongation and defective desquamation of the filiform papillae, and it is uncommon in neonates and infants. We report a case in a 54-day-old girl who presented with a black lesion on the tongue dorsum. The lesion had first been noted at the 1-month medical checkup and persisted despite observation. At presentation, a localized blackish-brown lesion with accentuated filiform papillae was observed on the tongue dorsum and could not be wiped off with gauze. Oral candidiasis was considered in the differential diagnosis, but microbiological examination detected no Candida species. A clinical diagnosis of black hairy tongue was made, and the parents were instructed to gently clean the tongue dorsum with gauze and a sponge brush. The lesion resolved within 2 weeks without recurrence. Recognition of this benign entity may help avoid unnecessary treatment in infants. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1936-0568 20 1 2026 Early-Stage Oral Squamous Cell Carcinoma in Adolescents and Young Adults Compared with Older Patients Exhibits Distinct Clinicopathological Features 88 EN Sawako Ono Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsutoshi Hirose Department of Oral and Maxillofacial Pathology, Osaka University Graduate School of Dentistry Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuya Abe Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Shintaro Sukegawa Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Masanori Masui Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chihoko Ikeda Department of Oral Pathology, Osaka Dental University Madoka Isomura Department of Diagnostic Pathology, School of Medicine, Fujita Health University Yuri Tachibana Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Faculty of Medicine Junya Ono Department of Pathology, The Nippon Dental University School of Life Dentistry at Niigata Katsumitsu Shimada Department of Clinical Pathophysiology, School of Dentistry, Matsumoto Dental University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose This study aimed to compare the clinicopathological features of stage I–II oral squamous cell carcinoma (OSCC) between adolescents and young adults (AYAs) and older patients, and to identify prognostic factors in AYA OSCC.<br> Methods Forty-eight AYA patients aged 15–39 years and 69 older patients aged ≥ 65 years with surgically treated stage I–II OSCC were retrospectively analyzed. Histological evaluation, survival analysis, immunohistochemistry for p53, p16, and MTAP, high-risk HPV RNA in situ hybridization, and fluorescence in situ hybridization for CDKN2A and MTAP were performed.<br> Results Compared with older patients, OSCCs in AYAs were more frequently located on the tongue (93.7% vs. 47.8%) and more often exhibited a superficial spreading growth pattern (60.4% vs. 31.8%). AYA tumors more frequently showed modified WPOI-1, high tumor budding, and abnormal p53 immunophenotypes (85.4% vs. 68.1%). AYA patients showed significantly better overall and disease-free survival than older patients. Within the AYA group, depth of invasion (DOI) > 5 mm was associated with distant metastasis and poorer overall and disease-free survival. Postoperative lymph node metastasis occurred in 31.2% of AYAs. Univariable analysis suggested that clinical stage II, tumor thickness > 5 mm, DOI > 5 mm, and tumor budding scores 1–2 were associated with postoperative lymph node metastasis. Molecular status, including p53, p16/CDKN2A, and MTAP, did not provide robust prognostic stratification.<br> Conclusion Early-stage AYA OSCC exhibits distinct clinicopathological features. DOI was the strongest prognostic indicator, whereas clinical stage, tumor thickness, and tumor budding may provide additional prognostic information regarding the risk of late nodal metastasis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1526-9914 27 7 2026 Potential of quantitative X�]ray imaging from photon�]counting CT: A novel analysis based on effective atomic number and physical density e70673 EN Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Mana Mitani Division of Radiological Technology, Medical Support Department, Okayama University Hospital Yusuke Morimitsu Division of Radiological Technology, Medical Support Department, Okayama University Hospital Noriaki Akagi Division of Radiological Technology, Medical Support Department, Okayama University Hospital Fumiyo Higaki Department of Radiology, Medical Development Field, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation Kanazawa University Kanazawa Ishikawa Japan Background: Conventional CT assessment of lung lesions is based mainly on morphological features. CT values represent relative X-ray attenuation that does not directly reflect tissue composition and/or physical density. Quantitative imaging using photon-counting CT (PC-CT) has the potential to provide quantitative parameters, such as effective atomic number (Zeff) and effective physical density (ƒÏeff).<br> Purpose: The purpose is to develop and demonstrate the potential of an algorithm that generates both the Zeff and ƒÏeff images, derived directly from virtual monoenergetic images (VMIs) acquired with a clinical PC-CT system.<br> Methods: The ƒÏeff image was generated by fitting a database of mass attenuation coefficients (ƒÊ/ƒÏ) to the measured linear attenuation coefficients (ƒÊ), which were obtained from two VMIs at 70 and 100 keV. As an effective material, Zeff information was also determined and fed back into the ƒÏeff calculation. An in-house low-density phantom was scanned for quantitative evaluation of ƒÏeff. In addition, to demonstrate the applicability of our procedure to actual clinical imaging, representative chest PC-CT images from patients were analyzed.<br> Results: In experiments using low-density phantoms, the CT values did not necessarily correlate with Zeff values, but they showed a very good correlation with the ƒÏeff values. The ƒÏeff values calculated using our procedure correlated well with the correct values of ƒÏ. A relative root mean square error of ƒÏeff calculation was 5.5%. Furthermore, we found that in pulmonary diagnosis, image contrast information from ƒÏeff makes it easier to identify and distinguish lesions compared to that from Zeff.<br> Conclusions: The proposed procedure directly generated Zeff and ƒÏeff images from PC-CT data and enabled quantitative interpretation of CT value in terms of elemental composition and physical density. In this study, the feasibility of generating Zeff and ƒÏeff images was demonstrated. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0305-1846 52 4 2026 Frontotemporal Lobar Degeneration�]TDP Type C With Striatal Glial Cytoplasmic Inclusions and Motor Neuron Degeneration e70090 EN Akiko Uchino Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Kazutomi Kanemaru Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Airi Tarutani Department of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical Science Masato Hasegawa Department of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical Science Hiroya Naruse Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shigeo Murayama Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Yuko Saito Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-0102 229 2026 Enhanced calcium activity and transcriptomic alterations in iPSC-derived neurons from BAFME patients with repeat expansions 105080 EN Yuki Nagasako Department of Neurology, Graduate School of Medicine, The University of Tokyo Mitsuru Ishikawa Department of Physiology, Keio University School of Medicine Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sopak Supakul Department of Physiology, Keio University School of Medicine Sumihiro Maeda Department of Physiology, Keio University School of Medicine Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Hideyuki Okano Department of Physiology, Keio University School of Medicine Benign adult familial myoclonus epilepsy (BAFME) is caused by intronic TTTCA and TTTTA repeat expansions in SAMD12 and other genes; the neuronal basis of cortical hyperexcitability, however, remains unclear. We generated induced pluripotent stem cell (iPSC)-derived glutamatergic and GABAergic neurons from three BAFME1 patients and examined functional and transcriptomic phenotypes. Patient-derived neurons retained the pathogenic repeat expansions and showed a tendency toward upstream intronic RNA accumulation. Calcium imaging revealed increased spontaneous Ca2 + transient frequency in both neuronal subtypes, indicating heightened activity. Pharmacological profiling demonstrated attenuated responses to calcium-permeable ƒ¿-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor (CP-AMPAR) blockade and GABAA receptor antagonism in GABAergic neurons, suggesting altered inhibitory signaling. RNA sequencing revealed transcriptomic alterations without differential expression of ion channels and neurotransmitter receptors. In glutamatergic neurons, ATF4-regulated genes, including SLC7A5 encoding LAT1, a Kv1.2 channel modulator, were downregulated. Reduced SLC7A5 expression was validated at both mRNA and protein levels. In GABAergic neurons, synapse-associated genes PTPRD and GPC6 were upregulated. TCERG1L and NLRP2 were suppressed across both neuronal subtypes. These findings suggest subtype-specific alterations may contribute to neuronal hyperexcitability in BAFME and provide a platform for mechanistic studies of repeat expansion-associated epilepsies. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2607 14 7 2026 Upregulation of the Outer Membrane Protein OmpV and Its Role in Polymyxin B Stress Adaptation in Vibrio mimicus 1527 EN Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Onodera Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunki Annoi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Basilua Andre Muzembo Research Center for Intestinal Health Science, Okayama University Daisuke Imamura Research Institute of Nursing Care for People and Community, University of Hyogo OmpV is an outer membrane protein found in a variety of Gram-negative bacteria. In this study, we demonstrated that V. mimicus strain CS-66, isolated from a patient with diarrhea, was resistant to polymyxin B (PL-B) and colistin (CL) but susceptible to chloramphenicol and ciprofloxacin. When strain CS-66 was cultured in Luria–Bertani broth containing a sub-minimal inhibitory concentration of each antibiotic used for the susceptibility tests, ompV expression as assayed by reverse transcription-qPCR, significantly increased regardless of the antibiotic tested. In contrast, cell aggregation during the early log phase was observed only when the strain was grown in the broth supplemented with PL-B or CL. A space-filling model of V. mimicus OmpV was generated. The model showed that, although OmpV adopted a ƒÀ-barrel conformation, it had closed top and bottom ends and possessed a lateral cavity. Structural analysis further indicated that the interior of this lateral cavity was negatively charged and sufficiently large to accommodate PL-B. These results suggest that V. mimicus may adapt to PL-B stress through physical sequestration within the negatively charged cavity of OmpV. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0022-1759 541 2025 Development of a novel histidine-rich glycoprotein measurement system as a biomarker for sepsis 113868 EN Takaoki Uchiumi Diagnostic Drug Office, Shionogi & Co., Ltd. Masahiro Nishibori Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoko Inoue Diagnostic Drug Office, Shionogi & Co., Ltd. Hiroshi Nishi Diagnostic Drug Office, Shionogi & Co., Ltd. Norio Ota Diagnostic Drug Office, Shionogi & Co., Ltd. The plasma histidine-rich glycoprotein concentration is a marker of sepsis severity. In this study, we generated selective and specific monoclonal antibodies against histidine-rich glycoprotein for use in a prototype enzyme-linked immunosorbent assay-based in vitro diagnostic system. First, we investigated the properties of monoclonal antibodies produced by 21 hybridomas that we developed using immunized mice, and we identified monoclonal antibodies 69-1A and 75-2D to be the most suitable combination for use in the sandwich enzyme-linked immunosorbent assay. Wild-type histidine-rich glycoprotein (Form-1, 75 kDa) with a proline residue at amino acid position 204 is the most common isoform of the protein in humans, followed by its variant (Form-2, 77 kDa), which has a serine residue at position 204.<br> The epitope mapping was examined for the HRG amino acid sequence with 69-1A and 75-2D mAbs to achieve the identification of respective specific binding domains, though the other kinds of mAbs showed considerably complex domains. The identified epitopes recognized by 69-1A and 75-2D monoclonal antibodies did not span position 204. Furthermore, immunoprecipitation-immunoblotting analysis showed that the 69-1A and 75-2D monoclonal antibodies could bind to both Form-1 and Form-2 in human plasma samples. Thus, these two new antibodies can be used to clearly detect both forms of histidine-rich glycoproteins in human plasma samples. In our analysis of clinical samples by enzyme-linked immunosorbent assays using various combinations of our newly synthesized antibodies, we found that the histidine-rich glycoprotein concentration was significantly lower in plasma samples from septic patients than in those from healthy volunteers (p < 0.01). Thus, our novel analysis system using the new antibodies is expected to be a useful tool for sepsis research, and it may be adapted as an in vitro diagnostic tool for many other kinds of diseases in the future. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1746-8094 127 2026 Outcome-aware and interpretable subtyping of chronic kidney disease: an analysis of the FROM-J study 111090 EN Tianyi Shi Department of Computer Science, University of Tsukuba Xiucai Ye Department of Computer Science, University of Tsukuba Wenyu Xi Department of Computer Science, University of Tsukuba Akira Imakura Department of Computer Science, University of Tsukuba Kaori Mase Department of Nephrology, Faculty of Medicine, University of Tsukuba Ryoya Tsunoda Department of Nephrology, Faculty of Medicine, University of Tsukuba Chie Saito Department of Nephrology, Faculty of Medicine, University of Tsukuba Akihiko Kato Blood Purification Unit, Hamamatsu University School of Medicine Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoichi Maruyama Department of Nephrology, Nagoya University Graduate School of Medicine Takashi Wada Department of Nephrology and Rheumatology, Kanazawa University Ichiei Narita Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences Kunihiro Yamagata Department of Nephrology, Faculty of Medicine, University of Tsukuba Tetsuya Sakurai Department of Computer Science, University of Tsukuba Chronic kidney disease (CKD) affects approximately 10% of the global population and exhibits substantial heterogeneity in disease progression and clinical outcomes. Despite ongoing efforts to develop new therapeutic strategies, the number of patients progressing to end-stage kidney disease (ESKD) and the incidence of cardiovascular disease (CVD) continue to rise. Although severity classification systems for CKD are well established and refined, they remain insufficient to capture prognostically relevant patient subtypes. In this study, we developed an outcome-aware and interpretable clustering framework for CKD subtyping using data from the FROM-J cohort with prognostic follow-up. A supervised XGBoost model was first trained to predict a ≥ 30% decline in estimated glomerular filtration rate (eGFR), a surrogate marker of CKD progression. SHAP (SHapley Additive exPlanations) values derived from this model were then used to quantify outcome-relevant feature contributions. Based on these feature attributions, a similarity graph was constructed, and spectral clustering was performed to identify patient subtypes driven by prognostic relevance. The proposed framework identified four CKD subtypes with distinct baseline clinical characteristics and significantly different risks of renal replacement therapy (RRT) and cardiovascular disease (CVD) events. Serum albumin, blood urea nitrogen (BUN), and smoking status consistently emerged as key features defining subtype structure and prognosis. Robust risk stratification was preserved even when clustering was restricted to these three routinely measured variables. Overall, our findings demonstrate that integrating outcome-driven feature attribution into clustering enables interpretable and clinically relevant CKD subtyping, providing a practical approach for characterizing disease heterogeneity and supporting risk stratification and personalized management. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2165-0497 2026 Escalation of CTX-M-producing extensively drug-resistant Shigella spp. in Kolkata, India, following the COVID-19 pandemic e02824-25 EN Puja Bose Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Gourab Halder Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Pratanu Kayet Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections Goutam Chowdhury Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Surajit Basak Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections Deboleena Roy Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Daisuke Imamura Research Center for Intestinal Health Science, Okayama University Shin-ichi Miyoshi Research Center for Intestinal Health Science, Okayama University Masatomo Morita Department of Bacteriology I, National Institute of Infectious Diseases Thandavarayan Ramamurthy Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Hemanta Koley Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Santasabuj Das Division of Clinical Medicine, ICMR-National Institute for Research in Bacterial Infections Asish Kumar Mukhopadhyay Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Shigella spp. is recognized by the World Health Organization as a high-priority pathogen due to its global prevalence, unique pathogenic mechanisms, and growing antimicrobial resistance (AMR). Nearly half of all Shigella strains worldwide are now multidrug-resistant (MDR), and the emergence of extensively drug-resistant (XDR) variants�\resistant to ciprofloxacin, ceftriaxone, and azithromycin�\has severely limited effective treatment options. The present study is based on prospective laboratory surveillance involving 323 Shigella isolates collected during 2021–2023, with pre-COVID-19 pandemic data included from a previously published study solely for historical comparison. The presence of antibiotic resistance genes (ARGs) was investigated, and whole-genome sequencing (WGS) was performed on representative isolates to assess phylogenetic relatedness with global isolates. Approximately 10% of isolates exhibited resistance to third-generation cephalosporins. While only 3% of Shigella isolates carried the blaCTX-M-15 gene from 2013 to 2019, its prevalence increased to 26% by 2022–2023. Among 38 ceftriaxone-resistant S. sonnei isolates, 33 were also resistant to azithromycin, categorizing them as XDR. These isolates showed 48% clonal similarity and high phylogenetic resemblance to the isolates reported from England. Hybrid genome assembly revealed a plasmid harboring both the blaCTX-M-15 and mphA ARGs. Conjugation experiments and plasmid profiling confirmed the plasmid�fs transferability. We report a rising trend in third-generation cephalosporin resistance among Shigella spp., primarily driven by the spread of extended-spectrum ƒÀ-lactamase-producing S. flexneri and the emergence of XDR S. sonnei. These findings underscore the urgent need for strengthened national AMR containment strategies and enhanced international surveillance of cephalosporin-resistant Shigella to mitigate this growing public health threat. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0916-9636 49 7 2026 Effect of population-approach programs promoting salt reduction and potassium intake in Japan: the Population-based Sodium/Potassium Improvement Program (PoSPIP) 1992 2003 EN Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayoshi Ohkubo Department of Hygiene and Public Health, Teikyo University School of Medicine Takuya Tsuchihashi Cardiovascular Center, Steel Memorial Yawata Hospital Katsushi Yoshita Department of Public Health, Nutrition, School of Human Life and Ecology, Osaka Metropolitan University Yukari Takemi Faculty of Nutrition, Kagawa Nutrition University Hitomi Hayabuchi Graduate School of Health and Environmental Sciences, Fukuoka Women�fs University Yukiko Okami Gunma University Center for Food Science and Wellness Kaori Kitaoka NCD Epidemiology Research Center, Shiga University of Medical Science Keiko Sakaguchi Faculty of Nursing and Nutrition, Shukutoku University Atsushi Hozawa Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine Tomonori Okamura Department of Preventive Medicine and Public Health, Keio University School of Medicine Hiroshi Itoh Japanese Society of Hypertension Hiromi Rakugi Japanese Society of Hypertension Koichi Node Japanese Society of Hypertension Katsuyuki Miura NCD Epidemiology Research Center, Shiga University of Medical Science Reducing sodium intake in populations is essential, but insufficient for preventing and managing high blood pressure, while the importance of increasing potassium intake is overlooked. We investigated the effects of 1-year population-approach programs (2021–2022) promoting salt reduction and potassium intake using urinalysis feedback and food environment improvement. This retrospective observational study included 7649 participants (mean age, 54.0 years; 45.3% women) from 11 municipalities and 4 workplaces. Outcomes in intensive support programs�\including urinary sodium, potassium, and sodium-to-potassium (Na/K) ratio measurements with feedback, dietary promotion, and food environment improvement�\were compared with standard support programs providing usual health guidance. In linear regression adjusted for demographics, lifestyle factors, and medical history, the reduction in urinary Na/K ratio was greater in the intensive support group (n = 4064) than in the standard support group (n = 3585) (mean difference �|0.14 [95% confidence interval, �|0.27 to �|0.01]). Although estimated potassium intake decreased in both groups, the decline was smaller in the intensive support group (mean difference 31 [12 to 51] mg/day). Estimated salt intake did not differ between the groups. The intensive support group showed greater increases in diastolic blood pressure and high-density lipoprotein cholesterol and smaller increases in blood glucose, as well as greater reductions in hemoglobin A1c and Salt Check Sheet scores. Mean differences between the groups for endpoints were not heterogeneous across intensive support program types. Our findings support the development of hypertension prevention and management strategies that promote healthier dietary behaviors and can be implemented in community and workplace settings, with broad public health applicability. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0721-832X 2026 Dissociation between globe shape-induced rectus muscle pulley displacement and abduction limitation in patients aged 40 years and older with high myopic strabismus EN Reika Kono Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Ichiro Hamasaki Lino Eye Clinic Fumiko Kishimoto Division of Ophthalmology, Ibara City Hospital Kiyo Shibata Lino Eye Clinic Shin Morisawa Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Purpose We hypothesized that high myopia (HM)-induced globe deformation displaces rectus muscle (RM) pulleys, contributing to mild ocular motility restriction. This study investigated the effects of globe shape on RM pulley positions in older Japanese patients with acquired strabismus (AS) and mild motility restriction�\defined as the ability to abduct both eyes beyond the midline.<br> Methods In this retrospective case series, 28 patients (mean age �} standard deviation: 61.2 �} 9.0 years) with adult-onset AS were included: 6 patients with (LAB group) and 22 patients without abduction limitation (NLAB group). In each subject, the eye with the longer axial length (AL ≥ 26 mm), measured using an AL measurement apparatus, was analyzed using magnetic resonance imaging (MRI). RM pulley positions relative to the globe center and equatorial diameter (ED) were measured; the ED-to-AL ratio (EAR) was calculated. We compared these parameters between groups and analyzed correlations of globe-shape factors (EAR, AL, and ED) with pulley positions and age.<br> Results No significant differences in EAR, AL, ED, or pulley positions were detected between LAB and NLAB groups, possibly owing to the limited sample size and group imbalance, in the analyzed eyes. However, as EAR decreased (prolate deformation), the superior rectus (SR) pulley (r = 0.68, P < 0.01) and inferior rectus (IR) pulley (r = 0.40, P = 0.03) significantly displaced nasally. AL (r = -0.52, P < 0.01) correlated with the horizontal SR pulley position. Furthermore, age significantly correlated with AL (r = 0.45, P = 0.02) and decrease in EAR (r = -0.41, P = 0.03).<br> Conclusions In older Japanese patients with HM and AS, prolate globe deformation was associated with age and significantly correlated with SR and IR pulley positions. While the direct relationship between these structural changes and the clinical degree of mild abduction limitation requires further investigation in larger cohorts, EAR sensitively reflected age-related morphological shifts; thus, when used in conjunction with AL, EAR may represent a readily measurable MRI-based parameter associated with restrictive motility tendencies in strabismus with high myopia. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1078-8174 32 6 2026 Students�f perceptions of an electronic one-minute paper in a radiography training programme: An exploratory cross-sectional questionnaire study 103486 EN Y. Komatsu Division of Radiological Technology, Graduate School of Health Sciences, Okayama University S. Abe Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences S. Tsudou Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences Y. Yamamoto Division of Radiological Technology, Graduate School of Health Sciences, Okayama University Y. Tanabe Faculty of Health Sciences, Department of Radiological Technology, Okayama University Medical School, Okayama University Introduction: Formative assessment can support health professions education; however, reports on electronic 1-min papers as classroom feedback and engagement tools in radiography programmes remain limited. This study explored radiography students�f perceptions of an electronic 1-min paper, focusing on in-class reflection, ease of asking questions, and instructor feedback.<br> Methods: An electronic 1-min paper was used in a radiotherapy course across 45 class sessions in the 2024 academic year for third-year students enrolled in a 4-year radiography programme. Each 90-min class comprised a 60-min lecture, 10-min completion of the paper, and 20-min instructor feedback. After the course, a de-identified online questionnaire was administered. Eleven 5-point Likert-scale items were analysed using descriptive statistics and Spearman's rank correlations. Free-text responses were analysed using inductive qualitative content analysis.<br> Results: Of the 77 eligible students, 74 responded (96.1%). Ease of use received the highest rating (mean, 4.76; standard deviation [SD], 0.52), followed by ease of asking questions (mean, 4.32), question resolution (mean, 4.16), and usefulness of instructor feedback (mean, 4.08). Motivation to review after class was lowest (mean, 3.04; SD, 1.16). Active participation showed a strong positive association with in-class concentration (rs = 0.815; P < 0.001). Free-text responses indicated reflection and improved understanding, anonymous sharing of questions, active listening and concentration, and suggestions for improvement.<br> Conclusion: The electronic 1-min paper was widely accepted and perceived to support in-class reflection, question expression, and immediate feedback. However, students�f perceptions of its influence on out-of-class review motivation were limited. The findings indicate perceived value and engagement rather than demonstrated educational effectiveness.<br> Implications for practice: Electronic 1-min papers may help instructors identify students�f questions and respond during class, providing a practical approach to in-class feedback. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0941-4355 34 8 2026 Incidence and impact of odontogenic infection-related febrile episodes during perioperative doxorubicin-cyclophosphamide or docetaxel-cyclophosphamide chemotherapy for breast cancer 747 EN Yoshihiko Soga Division of Hospital Dentistry, Okayama University Hospital Kumiko Matsuzaki Division of Hospital Dentistry, Okayama University Hospital Hirotaka Kosaki Division of Hospital Dentistry, Okayama University Hospital Tomoko Kishimoto Division of Hospital Dentistry, Okayama University Hospital Aiko Yoshitomi Division of Hospital Dentistry, Okayama University Hospital Makoto Kajizono Department of Pharmacy, Okayama University Hospital Takashi Makita Department of Pharmacy, Okayama University Hospital Yuta Tanaka Department of Pharmacy, Okayama University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Surgery, Kawasaki Medical School General Medical Center Background Doxorubicin-cyclophosphamide (AC) and docetaxel-cyclophosphamide (TC) are standard perioperative chemotherapy regimens for breast cancer. Febrile neutropenia (FN) is a common adverse event, and odontogenic infections may contribute to febrile episodes. This study was performed to investigate the incidence and impact of febrile episodes clinically associated with odontogenic infections during AC and TC chemotherapy.<br> Methods A total of 408 patients with breast cancer receiving 4 cycles of AC (n = 285) or TC (n = 123) between 2015 and 2020 were included in this single-center retrospective study. Patients recorded daily axillary temperatures and oral symptoms. Dental evaluations were performed when oral infection was suspected. Febrile episodes (≥ 37.5 �‹C) were assessed, and their clinical association with odontogenic infections was determined based on dental records and the documented clinical course. Relative dose intensity (RDI) was calculated to assess chemotherapy delivery.<br> Results Overall, 40.2% of patients experienced febrile episodes, and the frequency was higher in the TC group (48.8%) than the AC group (36.5%, P = 0.02). Febrile episodes associated with oral infections occurred in 9.1% of patients, of which 78.4% were clinically associated with odontogenic infections (7.1% of all patients). Most such episodes occurred during the first chemotherapy cycle (79.3%, P < 0.01). Chemotherapy RDI was reduced in three patients with febrile episodes clinically associated with odontogenic infection, but remained ≥ 85%.<br> Conclusions Febrile episodes clinically associated with odontogenic infections occurred in approximately 7%–8% of patients with breast cancer receiving perioperative AC or TC chemotherapy, predominantly during the first cycle. Odontogenic infections should be considered one possible source of febrile episodes during treatment. No potential conflict of interest relevant to this article was reported.

Japan Atherosclerosis Society Acta Medica Okayama 1340-3478 33 2 2026 A Case of Acquired LCAT Deficiency with the Discrepancy between Spontaneous Resolution of Proteinuria and Continually Low HDL Cholesterol Levels 228 236 EN Miki Matsuo Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center Masatsune Ogura Department of Clinical Laboratory Technology, Faculty of Medical Science, Juntendo University Masayuki Kuroda Center for Advanced Medicine, Chiba University Hospital, Chiba University Tetsuya Arisato Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center Masatsugu Kishida Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center Mariko Harada-Shiba Cardiovascular Center, Osaka Medical and Pharmaceutical University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koutaro Yokote Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine Fumiki Yoshihara Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center A 79-year-old Chinese man was referred for nephrotic syndrome (proteinuria 4.4 g/day). In blood tests, serum high-density lipoprotein (HDL) cholesterol was undetectable, and the esterified cholesterol to total cholesterol ratio was very low. Lecithin: cholesterol acyltransferase (LCAT) activity was also undetectable. Since he had neither corneal opacity nor pathological mutations in the LCAT gene and anti-LCAT antibodies were detected in serum, a diagnosis of acquired LCAT deficiency was made. Renal biopsy revealed glomerulopathy associated with LCAT deficiency and membranous nephropathy (MN). Since the patient�fs proteinuria did not improve despite prescribing an angiotensin II receptor blocker (ARB), we suggested the prescription of prednisolone, but he returned to China due to the expiration of his residence visa for Japan. One year after the initial visit, his proteinuria had improved to 0.9 g/day without immunosuppressive therapy. However, his HDL cholesterol level was still low at around 3 mg/dL, indicating a discrepancy between remission of nephrotic syndrome and lack of improvement in lipid levels.<br> Of the 11 patients with acquired LCAT deficiency reported to date, 4 with undetectable LCAT activity and MN on renal biopsy required immunosuppressive therapy to alleviate proteinuria. The present patient was prescribed only an ARB according to his preference, which happened to be consistent with the MN treatment guideline that states, �gWait 6 months for spontaneous remission while using maximal antiproteinuric therapy.�h The clinical course of acquired LCAT deficiency varies, and further case reports are needed to determine the necessity of immunosuppressive therapy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1323-8930 75 3 2026 Outcomes following the discontinuation of biologic therapy in patients with severe asthma 400 408 EN Tadao Nagasaki Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital Hisako Matsumoto Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Takashi Iwanaga Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Kazuto Matsunaga Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University Kiyoshi Sekiya Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Tomoya Harada Department of Multidisciplinary Internal Medicine, Division of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University Shogo Sakurai Department of Respiratory Medicine, Shizuoka General Hospital Norihiro Harada Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine Toshiyuki Koya Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Koichi Fukunaga Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine Takeshi Kaneko Department of Pulmonology, Yokohama City University Graduate School of Medicine Kazuhisa Asai Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University Yuko Komase Department of Respiratory Medicine, St.Marianna University School of Medicine, Yokohama Seibu Hospital Yasuhiro Gon Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine Akihiko Tanaka Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine Hironori Sagara Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine Hironobu Sunadome Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University Tatsuya Nagano Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Yoichi Nakamura Medical Center for Allergic and Immune Diseases, Yokohama City Minato Red Cross Hospital Akio Niimi Department of Respiratory Medicine, Allergy, and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences Noboru Hattori Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University Takashi Hajiro Department of Respiratory Medicine, Tenri Hospital Hajime Fujimoto Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine Masayuki Hojo Division of Respiratory Medicine, National Center for Global Health and Medicine Nobuaki Miyahara Department of Medical Technology, Okayama University Graduate School of Health Sciences Masafumi Yamaguchi Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science Kimiko Tsuji Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Akiko Sano Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Ryuta Haraguchi Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Hiroyuki Sano Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Masato Muraki Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital Yuji Tohda Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Background: Biologic therapies are pivotal in managing severe asthma. Despite their efficacy, some patients discontinue biologics, with varying outcomes. Predictors of successful versus unsuccessful discontinuation remain poorly defined. This study aimed to identify clinical factors associated with post-discontinuation outcomes in a real-world practice.<br> Methods: This retrospective cohort included adults with severe asthma who had received biologics for at least 12 months and subsequently discontinued therapy for a minimum of three consecutive months. We assessed the effects of baseline blood eosinophilia (≥300 cells/ƒÊL), residual sputum symptoms during biologic therapy, treatment responsiveness, biologic class, and discontinuation reasons on post-discontinuation asthma exacerbation rates using multivariable Cox models.<br> Results: A total of 118 patients were analyzed. The Kaplan–Meier analysis estimated a 65 % exacerbation-free probability at 12 months after discontinuation. Factors associated with successful discontinuation included a robust clinical response and absence of exacerbations before cessation. Conversely, baseline eosinophilia, residual sputum symptoms during biologics, and discontinuation due to inadequate therapeutic response or financial burden were associated with post-discontinuation exacerbations. In class-stratified restricted models, persistent sputum remained significantly associated with post-discontinuation exacerbations after stopping anti-IL-5 therapies, while baseline eosinophilia was associated with post-discontinuation exacerbations after stopping anti-IgE or anti-IL-4Rƒ¿. Among patients with sputum symptoms or poor-response discontinuation, the overall frequency of exacerbations declined after discontinuation.<br> Conclusions: Baseline eosinophilia, persistent sputum during therapy, and discontinuation prompted by poor response or cost may serve as risk factors for post-discontinuation exacerbations; however, risk is phenotype- and class-dependent. Careful patient selection and monitoring are essential when considering the discontinuation of biologic treatment. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1745-6215 27 1 2025 Oral health care during pregnancy to prevent preterm birth and low birth weight: study protocol for a randomized controlled trial 35 EN Junko Yasuoka Division of Global Health Sciences, Graduate School of Public Health, St. Luke�fs International University Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Okada Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University Prodhan MD Rubayet Alam Department of Orthodontics, Dental Unit, TMSS Medical College & Rafatullah Community Hospital Akira Shibanuma Department of Community and Global Health, Graduate School of Medicine, The University of Tokyo Keiko Nanishi Office of International Academic Affairs, Graduate School of Medicine, The University of Tokyo Yoko Sato Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University Md. Zahid Hossain Department of Periodontology and Oral Pathology, Holy Family Red Crescent Medical College Hospital Musfiqa Aman Department of Periodontology, Dental Unit, TMSS Medical College & Rafatullah Community Hospital Fahmida Karim Department of Obstetrics & Gynecology, Holy Family Red Crescent Medical College Hospital Sultana Razia Department of Obstetrics & Gynecology, TMSS Medical College & Rafatullah Community Hospital Rifat Rezwana Department of Molecular and Cellular Biochemistry, Division of Oral Health, Brain Health and Total Health, Faculty of Dental Science, Kyushu University Md Mahmudur Rahman Global Communication Center, Grameen Communications Nusrat Jahan Khan Global Communication Center, Grameen Communications Naoki Nakashima Department of Medical Informatics, Graduate School of Medical Sciences, Kyushu University Rafiqul Islam Division of Healthcare Digital Transformation, Kyushu University Kimiyo Kikuchi Department of Research Promotion, Institute for Asian and Oceanian Studies, Kyushu University Background Periodontal disease during pregnancy has been associated with an increased risk of preterm birth (PTB) and low birth weight (LBW). However, most previous interventional studies have reported that scaling and root planing (SRP), a form of basic periodontal treatment, is insufficient to effectively prevent PTB and LBW. Recent systematic reviews and meta-analyses suggest that combining SRP with routine use of chlorhexidine gluconate (CHG) mouthwash may reduce the risk of these adverse birth outcomes by approximately half. This study will be among the first randomized controlled trials (RCTs) to evaluate the potential synergistic effects of this combined approach on improving birth outcomes.<br> Methods This multi-center, three-arm RCT will be conducted at two hospitals in Dhaka and Bogura, Bangladesh, between April 2025 and September 2026. A total of 480 pregnant women less than 20 weeks�f gestation attending antenatal checkups will be recruited. Participants diagnosed with periodontal disease will be randomly assigned to either an intervention group or a positive control group. Participants without periodontal disease will be assigned to a negative control group. The intervention consists of SRP combined with continued use of CHG mouthwash throughout pregnancy. The primary outcome will be the rate of PTB. Secondary outcomes include the birth weight of the newborn baby, maternal periodontal status, and oral health-related quality of life (OHRQoL). Effectiveness will be assessed by comparing outcomes across the study groups.<br> Discussion The oral health intervention is expected to improve both birth outcomes and maternal oral health. Demonstrating its effectiveness in a real-world setting may support the integration of oral health care into broader maternal, neonatal, and child health strategies, particularly in resource-limited settings.<br> Trial registration UMIN Clinical Trials Registry. UMIN000057519. Registered on April 4, 2025. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000065719. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0914-5087 87 5 2026 Cardio-ankle vascular index as a screening tool for coronary artery disease in patients with metabolic dysfunction-associated steatotic liver disease 429 433 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Ueki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Nishihara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Hara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Centre Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common hepatic disorder that significantly increases cardiovascular risk. However, no established screening method exists for detecting subclinical coronary artery disease (CAD) in this high-risk population. The cardio-ankle vascular index (CAVI), a blood pressure–independent measure of arterial stiffness, may offer a non-invasive tool for early detection of coronary atherosclerosis.<br> Methods: We retrospectively analyzed 295 patients with MASLD who underwent both CAVI measurement and coronary computed tomography angiography at a single center. Significant CAD was defined as ≥50 % luminal stenosis. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic performance. Multivariable logistic regression was performed to identify independent associations between elevated CAVI and CAD. The incremental predictive value of CAVI was assessed using net reclassification improvement (NRI).<br> Results: Of the 295 patients, 110 (37.3 %) had significant CAD. Patients with CAD had significantly higher CAVI values (9.0 vs. 8.7, p = 0.007). The area under the ROC curve for CAVI predicting CAD was 0.614. A CAVI cut-off of 8.6 provided a sensitivity of 66.4 % and a specificity of 56.8 %. CAVI ≥8.0 was independently associated with CAD (OR 3.44, 95 % CI: 1.06–11.2, p = 0.040). Adding CAVI to a conventional risk model improved risk reclassification (NRI 0.4236, p < 0.001), although the C-statistic change was not significant (from 0.724 to 0.725, p = 0.835).<br> Conclusions: CAVI is independently associated with significant coronary stenosis in MASLD patients and may serve as a non-invasive screening tool to enhance cardiovascular risk stratification. Its moderate diagnostic accuracy suggests utility as a component of a multifactorial risk assessment strategy. No potential conflict of interest relevant to this article was reported.

Japan Neurosurgical Society Acta Medica Okayama 0470-8105 66 3 2026 Full-endoscopic Laminotomy Is Effective for Lumbar Spinal Stenosis with Low-grade Spondylolisthesis: A Comparative Cohort Study 107 115 EN Kyohei KIN Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryoji TOMINAGA Department of Orthopaedics, Iwai Orthopaedic Medical Hospital Kento TAKEBAYASHI Department of Orthopaedics, Iwai Orthopaedic Medical Hospital Hiroki IWAI Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirohiko INANAMI Department of Orthopaedics, Iwai Orthopaedic Medical Hospital Hisashi KOGA Department of Orthopaedics, Iwai Orthopaedic Medical Hospital The optimal management of lumbar spinal canal stenosis with spondylolisthesremains controversial, particularly when choosing between decompression alone or decompression with fusion. Current evidence is based on conventional open or endoscopy-assisted surgeries, with limited data on full-endoscopic decompression. This study aimed to assess the impact of spondylolisthesis on outcomes after full-endoscopic laminotomy by evaluating back pain-related disability scores in patients with lumbar spinal canal stenosis, with and without spondylolisthesis. A retrospective analysis was conducted at Iwai Orthopaedic Hospital, Japan. Patients with lumbar spinal canal stenosis who underwent full-endoscopic laminotomy between January 2021 and December 2022 were included and categorized into those without spondylolisthesis and those with spondylolisthesis. Postoperative Oswestry Disability Index scores at 2 years were compared in the groups using multivariable linear regression, adjusting for confounding factors. Exploratory analyses were also conducted to identify factors affecting the Oswestry Disability Index in the patients with lumbar spinal canal stenosis with spondylolisthesis group. Statistical significance was set at p < 0.05. The study included 80 patients, with 40 in each group. Both groups showed improved postoperative Oswestry Disability Index. There was no significant association between spondylolisthesis and postoperative Oswestry Disability Index. However, cauda equina redundancy negatively affected postoperative Oswestry Disability Index improvement in the patients with lumbar spinal canal stenosis with spondylolisthesis group. Full-endoscopic laminotomy is an effective surgical option for lumbar spinal canal stenosis, leading to significant alleviation of disability and improvements in quality of life, regardless of spondylolisthesis. Full-endoscopic laminotomy may offer similar functional improvements regardless of the presence of low-grade spondylolisthesis, supporting its role as a less invasive alternative to fusion. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 65 11 2026 Endotracheal and Endobronchial Metastases in Epidermal Growth Factor Receptor Exon 19 Deletion Lung Adenocarcinoma: A Case Successfully Managed with Bronchoscopic Therapy and Sequential Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors 1520 1523 EN Miho Fujiwara Department of Respiratory Medicine, Okayama University Hospital Takahiro Baba Department of Respiratory Medicine, Okayama University Hospital Kotaro Yamada Department of Respiratory Medicine, Okayama University Hospital Eri Nakamura Department of Respiratory Medicine, Okayama University Hospital Tetsuya Takeguchi Department of Respiratory Medicine, Okayama University Hospital Yuki Takigawa Department of Respiratory Medicine, NHO Okayama Medical Center Ayako Morita Center for Clinical Oncology, Okayama University Hospital Naofumi Hara Department of Respiratory Medicine, Okayama University Hospital Hiromi Watanabe Department of Respiratory Medicine, NHO Okayama Medical Center Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Kammei Rai Center for Innovative Clinical Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Ken Sato Department of Respiratory Medicine, NHO Okayama Medical Center Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Endotracheal and endobronchial metastases from peripheral lung adenocarcinoma are rare, and optimal clinical management remains unclear. We herein report a 60-year-old woman with epidermal growth factor receptor (EGFR) exon 19 deletion-positive early-stage lung adenocarcinoma who underwent surgical resection followed by osimertinib treatment for recurrence. She later developed oligoprogressive disease with airway metastases. Bronchoscopic tumor removal was performed, and next-generation sequencing of the resected specimen revealed an acquired EGFR C797S mutation, along with exon 19 deletion. Gefitinib treatment was initiated, which led to a partial response. This case underscores the utility of repeated molecular profiling and local intervention in managing acquired resistance in EGFR-mutant non-small-cell lung cancer. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1877-0568 112 3 2026 Relationship between the Hounsfield Unit value of the greater trochanter and the risk of greater trochanteric fractures in anterolateral muscle-sparing minimally invasive total hip arthroplasty 104642 EN Ryuichiro Okuda Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University Tomoko Tetsunaga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yasutaka Masada Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Tetsuya Yamamoto Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Shin Matsumoto Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yuki Okazaki Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Background: No previous studies have investigated the association between the risk of greater trochanteric fractures and the Hounsfield Unit (HU) of the greater trochanter in muscle-sparing minimally invasive total hip arthroplasty (MIS-THA). This study aimed to investigate the risk factors for greater trochanteric fractures in anterolateral MIS-THA.<br> Hypothesis: Lower HU values of the greater trochanter are associated with a higher risk of intraoperative and early postoperative greater trochanteric fractures.<br> Patients and methods: This single-center retrospective observational study included 223 patients (257 hips) who underwent primary THA for osteoarthritis or osteonecrosis between January 2010 and August 2024 using a minimally invasive anterolateral approach in the lateral position. All surgeries were performed by four surgeons. Preoperative CT was used to reconstruct coronal sections including the femoral head center and proximal femoral axis, and cancellous HU values of the greater trochanter were measured. Postoperative CT (1 week) with metal artifact reduction was routinely performed; fractures were defined as cortical fracture lines on 3D-reconstructed CT and assessed by two independent orthopedic surgeons. Patients were divided into two groups according to the presence or absence of fractures.<br> Results: The incidence of greater trochanteric fractures was 6.6% (17/257 hips). Twelve of these fractures (70.6%) were recognized intraoperatively or immediately postoperatively. Full hydroxyapatite (HA)-coated stems were associated with an increased fracture risk compared with other designs (relative risk [RR], 2.68; 95% CI, 1.07–6.68). Age, sex, BMI, ASA physical status, and diagnosis were not significantly associated with fractures. Multivariate analysis identified lower HU values (odds ratio [OR], 0.973; p < 0.0001) and full HA-coated stems (OR, 13.3; p = 0.04) as independent predictors. Receiver operating characteristic (ROC) analysis determined an optimal cut-off of 72.0 HU (sensitivity, 0.941; specificity, 0.742), with a value ≤72.0 HU demonstrating high predictive power (RR, 36.7; p < 0.0001).<br> Conclusion: Preoperative measurement of HU values in the greater trochanter is a useful screening tool for identifying patients at increased risk of fractures in anterolateral MIS-THA. While an HU value of ≤ 72.0 necessitates careful intraoperative management and increased vigilance, it should be interpreted as an indicator of risk rather than a definitive predictor of fracture due to its moderate specificity.<br> Level of evidence: IV; retrospective study. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Asthma-like bronchodilator responsiveness in patients with neuronal intranuclear inclusion disease 16760 EN Daisuke Tahara Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Nao Tahara Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Chisato Tamai Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Akio Akagi Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Yuichi Riku Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Hiroaki Miyahara Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Rei Kobayashi Department of Neurology, NHO Nagoya Medical Center Hisashi Okada Department of Neurology, NHO Nagoya Medical Center Michi Kawamoto Department of Neurology, Kobe City Medical Center General Hospital Junko Ishii Department of Neurology, Kobe City Medical Center General Hospital Hiroki Yamazaki Department of Neurology, Tokushima University Graduate School of Biomedical Science Takashi Kurashige Department of Neurology, NHO Kure Medical Center and Chugoku Cancer Center Atsuhiko Sugiyama Department of Neurology, Chiba University Akiko Nagaishi Department of Neurology, NHO Nagasaki Kawatana Medical Center Katsuya Nishida Department of Neurology, NHO Hyogo Chuo National Hospital Kazuma Sugie Department of Neurology, Nara Medical University Hospital Takayasu Fukudome Department of Neurology, NHO Nagasaki Kawatana Medical Center Kazuko Hasegawa Department of Neurology, NHO Sagamihara National Hospital Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruki Koike Department of Neurology, Saga University Takashi Kasai Department of Neurology, Kyoto Prefectural University of Medicine Toshiki Mizuno Department of Neurology, Kyoto Prefectural University of Medicine Masahiro Ando Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yujiro Higuchi Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Fumiaki Tanaka Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine Yuishin Izumi Department of Neurology, Tokushima University Graduate School of Biomedical Science Gen Sobue Aichi Medical University Yasushi Iwasaki Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Satoru Ito Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University Jun Sone Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative condition characterized by the presence of intranuclear inclusions in neuronal and visceral cells. Patients with NIID can present respiratory symptoms; however, data on pulmonary functions in NIID are lacking. This study investigated the respiratory conditions in NIID patients diagnosed with histopathological and genetic studies. We conducted two spirometries before and after administrating the bronchodilator in NIID patients with asthmatic histories or symptoms. We statistically compared pre- and post-measured values including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Before two spirometries, we also measured fractional concentration of exhaled nitric oxide (FeNO), if possible. Of the 51finally enrolled patients, 17 (33.3%, 95% CI 20.8% to 47.9%) patients had asthmatic histories or symptoms, and 14 patients received two spirometries. After administrating the bronchodilator, FEV1 and PEF significantly increased by 150 mL (6.01%, p = 0.002) and 260 mL/s (6.72%, p = 0.017), respectively. The median (interquartile range) of FeNO measured in nine patients was 15 (10–21) ppb. Patients with NIID have airflow reversibility like asthma. This condition appears to be less associated with airway inflammation and may be related to autonomic dysfunction. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0584 105 7 2026 WT1 mRNA in peripheral blood enables early prognostic stratification in AML patients receiving venetoclax and azacitidine therapy 105 EN Hiroyuki Sugiura Division of Internal Medicine, Fukuyama City Hospital Noboru Asada Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takeru Asano Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Yasushi Hiramatsu Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Tomohiro Urata Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Makoto Nakamura Department of Hematology, Okayama City Hospital Kazuhiko Yamamoto Department of Hematology, Okayama City Hospital Tatsunori Ishikawa Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers Masanori Makita Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers Takanori Yoshioka Department of Hematology, NHO Okayama Medical Center Kazutaka Sunami Department of Hematology, NHO Okayama Medical Center Kyosuke Saeki Division of Hematology, Ehime Prefectural Central Hospital Yuichiro Nawa Division of Hematology, Ehime Prefectural Central Hospital Maiko Kimura Department of Hematology, Japanese Red Cross Okayama Hospital Makoto Takeuchi Department of Hematology, Japanese Red Cross Okayama Hospital Masaya Abe Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shoji Asakura Department of Internal Medicine, Okayama Rosai Hospital Tomofumi Yano Department of Internal Medicine, Okayama Rosai Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Venetoclax and azacitidine (VEN/AZA), which target BCL-2 and DNA methylation, have demonstrated substantial efficacy, particularly in older or unfit patients with acute myeloid leukemia (AML). Wilms�f Tumor-1 (WT1) mRNA, measurable in peripheral blood (PB), is an established biomarker for monitoring treatment response and predicting AML prognosis. We conducted a retrospective analysis of patients with AML treated with VEN/AZA within the Okayama Hematology Study Group (OHSG). Patients who showed a marked reduction in PB WT1 mRNA levels from baseline after the first or second treatment cycle had significantly improved overall survival (OS) and progression-free survival (PFS). Moreover, achieving PB WT1 mRNA negativity-regardless of whether this occurred early or later in the therapy།was consistently associated with superior OS and PFS. These findings suggest that PB WT1 mRNA is a sensitive and reliable biomarker for predicting treatment response and long-term outcomes in patients with AML receiving VEN/AZA. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1022-5536 34 1 2026 Similar functional outcomes but different remodeling patterns: A minimum 5-years radiographic comparison of short fit-and-fill stem and quadrangular taper stem 1 10 EN Yasutaka Masada Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuo Fujiwara Department of Orthopaedic Surgery, Okayama City General Medical Center, Okayama City Hospital Kazuki Yamada Department of Orthopaedic Surgery, Okayama University Hospital Tomohiro Inoue Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichiro Okuda Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Tetsunaga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Okazaki Center for Education in Medicine and Health Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose: ACTIS and CORAIL are cementless titanium femoral stems with hydroxyapatite (HA) coating but differing macro-geometries: ACTIS features a variable triple-taper with a medial collar, whereas CORAIL is a straight double-tapered design available with or without a collar. We compared mid-term clinical and radiographic outcomes of these stems with a minimum 5-years follow-up.<br> Methods: We retrospectively reviewed 114 primary total hip arthroplasties using ACTIS (63 hips) or CORAIL (51 hips). Clinical outcomes and standardized radiographic parameters were assessed and compared between groups.<br> Results: The canal-fill ratio (CFR) was significantly greater at the proximal, middle, and distal levels in the ACTIS group. Spot-weld formation was more frequent with ACTIS than with CORAIL (58.7% vs 35.3%). In logistic regression, proximal CFR significantly predicted spot-weld formation for ACTIS, with an optimal cutoff of 66.2% (sensitivity 91.9%, specificity 72.0%). Rates of subsidence, radiolucent lines, and pedestal formation did not differ significantly between groups. No severe stress shielding was observed with ACTIS, whereas three CORAIL hips demonstrated severe stress shielding (0% vs 5.9%). Clinical scores improved significantly in both groups, with no significant between-group differences at final follow-up.<br> Conclusions: Both stems yielded favorable radiographic and clinical mid-term outcomes. In ACTIS, greater proximal canal fill was associated with radiographic osseointegration, suggesting proximal CFR as a probabilistic radiographic marker of stem ingrowth. No potential conflict of interest relevant to this article was reported.

American Society of Hematology Acta Medica Okayama 2473-9529 10 13 2026 Drivers of temporal improvement in CAR T-cell therapy for large B-cell lymphoma: a Japanese nationwide registry analysis 4427 4438 EN Yu Yagi Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Yusuke Kanemasa Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Toshiki Terao 2Department of Hematology, Okayama University Hospital, Okayama, Japan Motohiro Kato Department of Pediatrics, The University of Tokyo Tomoyasu Jo Department of Hematology, Kyoto University Hospital Tatsu Shimoyama Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Toshio Kitawaki Department of Hematology, Kyoto University Hospital Ryo Hanajiri Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Noriko Iwaki Department of Hematology, National Cancer Center Hospital Go Yamamoto Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital Masatoshi Sakurai Division of Hematology, Department of Medicine, Keio University School of Medicine Toshihiro Matsukawa Department of Hematology, Hokkaido University Hospital Emiko Sakaida Department of Hematology, Chiba University Hospital Yasuhiro Nakashima Hematology and Hematopoietic Cell Transplantation, Osaka Metropolitan University Hospital Akiyo Yoshida Division of Transfusion Medicine, Kanazawa University Hospital Yoshihiro Umezawa Department of Hematology, Institute of Science Tokyo Hospital Haryoon Kim Division of Hematology, Department of Medicine, Keio University School of Medicine Keisuke Kataoka Division of Hematology, Department of Medicine, Keio University School of Medicine Hideki Goto 11Department of Hematology, Hokkaido University Hospital, Sapporo, Japan Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Koji Kato Department of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital Real-world CD19 chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is characterized by expanded eligibility and evolving management practices. However, the prognostic impact of these changes remains inconsistent, and the specific drivers of outcomes remain unclear. This study analyzed 913 patients with relapsed/refractory (R/R) LBCL from a Japanese registry and compared the outcomes between 2 calendar periods (2019-2021 vs 2022-2024). The 2022-2024 cohort was older, had more adverse baseline features, and was less pretreated. Treatment patterns have shifted toward higher utilization of second-line therapy, a growing preference for axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), and improved disease control before infusion. Accordingly, the 2022-2024 cohort achieved a longer progression-free survival (PFS; 6-month PFS, 63.2% vs 55.2%; P = .005), which persisted after adjusting for baseline characteristics using propensity score matching. Multivariable analysis identified second-line therapy, improved preinfusion disease control, and a shift in product selection from tisagenlecleucel to axi-cel or liso-cel as the primary drivers of this improvement. This benefit was pronounced in high-risk populations, including patients with stable or progressive disease at infusion (6-month PFS, 54.6% vs 43.8%; P = .012) and those who were refractory to first-line therapy (6-month PFS, 51.7% vs 40.3%; P = .013). Despite broader use in higher-risk populations and greater axi-cel exposure, 6-month nonrelapse mortality remained low (2.1% vs 1.5%). Real-world outcomes of CD19 CAR T-cell therapy for R/R LBCL have improved, predominantly driven by second-line therapy, enhanced preinfusion disease control, and increased use of more potent CAR T products. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 17 1 2026 The role of Pth1r in posterior cranium cartilage regulation and craniosynostosis 5862 EN Katsuhiko Amano Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Okuzaki Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of Osaka Yuji Fujimoto Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of Osaka Yu-Chen Liu Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of Osaka Mikihiko Kogo The First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Craniosynostosis is a major craniofacial congenital disorder that causes developmental complications. During normal cranial development, intramembranous ossification forms the flat bones and sutures, while cartilage appears transiently in the posterior calvarial region. However, in craniosynostosis, premature suture fusion disturbs normal calvarial morphogenesis. To clarify the role of transient cartilage in this morphogenetic disruption, we investigated its molecular regulation and pathology in mice, focusing on parathyroid hormone 1 receptor (Pth1r) signaling. Conditional deletion of Pth1r in the cranial mesenchyme unexpectedly caused acrocephalic dysmorphology and craniosynostosis, with altered cartilage differentiation. Occipito–interparietal synostosis consistently occurred in Pth1r-ablated Gli1+ and Acan+ lineages, but not after adult Gli1-CreERT2 deletion, indicating a developmental role. Bulk and single-cell RNA-seq analysis revealed nine mesenchymal subsets, with mutant cells showing abnormal chondrocyte differentiation and upregulated Indian hedgehog (Ihh) signaling. These findings indicate that Pth1r maintains proper chondrogenic regulation during calvarial development, and its loss induces craniosynostosis through Ihh overactivation. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 2026 Impact of pre-existing schizophrenia spectrum disorder on the receipt of invasive and systemic therapy for gastric cancer: a multicenter nationwide cohort study in Japan hyag102 EN Myo Min Khant Department of Psychiatry, Faculty of Medicine, Shimane University Masaki Fujiwara Department of Neuropsychiatry, Medical Development Field, Okayama University Yuto Yamada Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Taisuke Ishii Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Tomone Watanabe Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Takashi Fukao Department of Neuropsychiatry, Medical Development Field, Okayama University Maiko Fujimori Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Naoki Nakaya Tohoku Medical Megabank Organization, Tohoku University Toshihiko Kawamura Department of Medical Informatics, Shimane University Hospital Koji Otsuki Department of Psychiatry, Faculty of Medicine, Shimane University Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Taichi Shimazu Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University Yosuke Uchitomi Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine Masatoshi Inagaki Department of Psychiatry, Faculty of Medicine, Shimane University Background: Patients with schizophrenia spectrum disorders (SSD) experience higher cancer mortality, partly because of later-stage diagnosis and lower rates of recommended treatments. While treatment disparities have been reported across several cancer types, no study has specifically examined stage-appropriate treatment for gastric cancer among patients with SSD.<br> Methods: We conducted a retrospective cohort study using a nationwide Hospital-Based Cancer Registry linked to administrative data in Japan. Patients who received initial treatment for gastric cancer between 2018 and 2021 were included. Multivariable logistic regression models examined the association between SSD and the receipt of stage-appropriate cancer treatments, adjusting for age, sex, clinical stage, Charlson Comorbidity Index, and Barthel Index.<br> Results: Among 189 447 patients from 709 hospitals, 1312 had SSD. Patients with SSD were more likely to be diagnosed at advanced stages. In crude analysis, SSD was associated with lower rates of surgical or endoscopic treatment; however, this association was not statistically significant after adjustment (adjusted odds ratio [aOR], 0.90; 95% confidence interval [CI], 0.75–1.08). In contrast, SSD was independently associated with lower rates of postoperative adjuvant chemotherapy for pathological stage II/III disease (aOR, 0.64; 95% CI, 0.45–0.91) and systemic therapy for stage IV disease (aOR, 0.36; 95% CI, 0.28–0.47).<br> Conclusions: Among patients with gastric cancer, SSD was associated with reduced receipt of systemic therapy but not surgical or endoscopic treatment. Efforts to improve early detection among patients with SSD may be important for reducing treatment disparities, alongside strengthened support for systemic therapy to ensure equitable access to guideline-recommended gastric cancer care. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1478-6362 27 1 2025 Performance of the modified 2022 ACR/EULAR giant cell arteritis classification criteria without age restriction for discriminating from Takayasu arteritis 19 EN Takahiko Sugihara Department of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Masayoshi Harigai Division of Rheumatology, Department of Internal Medicine, Tokyo Women�fs Medical University School of Medicine Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hajime Yoshifuji Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University Yasuhiro Maejima Department of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Jun Ishizaki Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine Yoshiko Watanabe Department of General Medicine, Kawasaki Medical School Hiroaki Dobashi Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University Yoshinori Komagata Department of Nephrology and Rheumatology, Kyorin University School of Medicine Naoto Tamura Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Yoshikazu Nakaoka Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS) Objective To evaluate the ability to discriminate giant cell arteritis (GCA) from Takayasu arteritis (TAK) according to the modified 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) GCA classification criteria.<br> Methods Patients enrolled in the Japanese nationwide retrospective registry were evaluated using the criteria with partial modification; wall thickening of descending thoracic-abdominal aorta were mainly diagnosed by contrast-enhanced computed tomography (CT) or magnetic resonance imaging instead of evaluating with positron emission tomography (PET)-CT. The discriminability of the criteria was evaluated using C-statistic (> 0.7: good ability).<br> Results Newly diagnosed patients with GCA (n = 139) and TAK (n = 129) were assessed, and 23.3% of TAK were aged 50 years or older at onset. The sensitivity of the modified 2022 ACR/EULAR GCA classification criteria with a score ≥ 6 was 82.0%, 68.5%, and 32.1% in all GCA, GCA with large-vessel involvement, and GCA without cranial arteritis, respectively. The specificity of the modified criteria was 96.1% for the 129 TAK as controls. Five patients with late-onset TAK met the modified criteria, and four had cranial signs and symptoms, two had bilateral axillary artery involvement, and four had descending thoracic-abdominal aorta involvement. The discriminability of the criteria was good (C-statistic: 0.986, 95% confidence interval [CI]: 0.976–0.996) and remained good after excluding age (C-statistic: 0.927, 95% CI: 0.894–0.961). The discriminability of a set of large-vessel lesions (bilateral axillary artery and descending thoracic-abdominal aorta) and inflammatory markers was markedly decreased with poor C-statistic value (C-statistic: 0.598, 95% CI: 0.530–0.667). Discriminability was improved after adding polymyalgia rheumatica (PMR) (C-statistic: 0.757, 95% CI: 0.700–0.813) or age (C-statistic: 0.913, 95%CI: 0.874–0.951) to the set of large-vessel lesions. In GCA patients with a score ≤ 5, 52% had bilateral subclavian and/or axillary artery involvement.<br> Conclusion The modified 2022 ACR/EULAR GCA classification criteria well performed in classifying GCA and TAK without PET-CT in routine clinical practice. A set of items included in the modified GCA classification criteria had good discriminative ability for GCA and TAK, even when age was excluded. However, age restriction or PMR was required to distinguish GCA without cranial lesions from TAK. No potential conflict of interest relevant to this article was reported.

American Society for Clinical Investigation Acta Medica Okayama 1558-8238 136 10 2026 Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLC e195021 EN Kohsuke Isomoto Department of Medical Oncology, Kindai University Faculty of Medicine Koji Haratani Department of Medical Oncology, Kindai University Faculty of Medicine Takahiro Tsujikawa Department of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Yusuke Makutani Department of Surgery, Kindai University Faculty of Medicine Masayuki Takeda Department of Medical Oncology, Kindai University Faculty of Medicine Kimio Yonesaka Department of Medical Oncology, Kindai University Faculty of Medicine Kaoru Tanaka Department of Medical Oncology, Kindai University Faculty of Medicine Tsutomu Iwasa Department of Medical Oncology, Kindai University Faculty of Medicine Kazuko Sakai Department of Genome Biology, Kindai University Faculty of Medicine Kazuto Nishio Department of Genome Biology, Kindai University Faculty of Medicine Akihiko Ito Department of Pathology, Kindai University Faculty of Medicine Kazuhiko Nakagawa Department of Medical Oncology, Kindai University Faculty of Medicine Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine BACKGROUND. Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 axis have revolutionized metastatic non–small cell lung cancer (mNSCLC) treatment. However, disease progression remains a concern, and the role of the complex tumor microenvironment (TME) in treatment failure is not fully understood.<br> METHODS. In this biomarker study involving 103 patients with mNSCLC, including 81 patients who received ICI treatment, we evaluated the association between heterogeneous immune cell subsets and ICI efficacy through single-cell spatial profiling of pretreatment tumor tissue, using a 29-marker multiplex IHC platform built for in-depth dissection of the TME.<br> RESULTS. Among various types of intratumoral lymphocytes, including Th1, Treg, and NK cells, only CD8+ T cells (tumor-infiltrating lymphocytes [TILs]) were associated with ICI efficacy. Computational tissue segmentation underscored the importance of direct physical interactions between CD8+ TILs and cancer cells for ICI efficacy. TIL phenotyping identified CD39/CD103/Ki-67 positivity as a hallmark of exhausted yet functional tumor-reactive CD8+ TILs. Immunosuppressive tumor-associated macrophages (TAMs) and cancer-associated fibroblasts were independent unfavorable adversaries. High CD73 expression on cancer cells was suggested to confer tolerance to ICI in EGFR/ALK-oncogene+ NSCLC, potentially through M2-TAM accumulation and aberrant angiogenesis.<br> CONCLUSION. Our study delineates the clinical relevance of heterogeneous immune cell subsets in ICI-treated mNSCLC, aiding the development of targeted therapeutic strategies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 17 1 2026 Bacterial collagenase harnesses collagen geometry for processive cleavage 5485 EN Hiroya Oki Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, The University of Osaka Katsuki Takebe Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Adjoa Bonsu Department of Chemistry and Biochemistry, University of Arkansas Kazunori Fujii Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University Ryo Masuda Waseda Research Institute for Science and Engineering, Waseda University Nicholas Henderson Department of Chemistry and Biochemistry, University of Arkansas Takehiko Mima Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences Takaki Koide Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University Mahmoud Moradi Department of Chemistry and Biochemistry, University of Arkansas Osamu Matsushita Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joshua Sakon Department of Chemistry and Biochemistry, University of Arkansas Kazuki Kawahara Graduate School of Pharmaceutical Sciences, The University of Osaka Collagen, the major structural protein in the animal extracellular matrix, forms a triple helix that resists proteolysis and requires specialised enzymes for degradation. Flesh-eating bacteria secrete collagenases that unwind the collagen triple helix and processively trim Gly–X–Y triplet repeats, yet the molecular basis of this process has remained obscure. Here, cryo-electron microscopy reveals how Hathewaya histolytica collagenase ColH engages its substrate and exploits the helix�fs architecture for catalysis. ColH encircles a single collagen triple helix in a closed-ring conformation and, through dynamic domain motions, dehydrates and destabilises it. The enzyme undergoes substrate-assisted twisting to adopt a rigid ratcheted conformation, in which one chain is bent into a tripeptide-long �ebight�f and threaded into the active site for cleavage, while two uncut strands are partitioned to non-catalytic sites. Release of the bight appears to reset the enzyme, with the uncut strands serving as guiding tracks. Repeated cycling between dynamic and rigid states likely enables triplet-by-triplet translocation, allowing ColH to harness collagen�fs geometry for processive degradation. These findings reveal a bacterial strategy for collagen unwinding and cleavage distinct from that of mammalian collagenases, highlighting divergent evolutionary solutions for degrading one of nature�fs most intractable substrates. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2977-0548 2 3 2026 Truncation by death in the sufficient-cause framework uuag021 EN Bronner P Gonçalves Faculty of Health and Medical Sciences, University of Surrey Eiji Yamamoto Okayama University of Science Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The sufficient-cause framework has been used for decades to improve our understanding of both basic and complex causal concepts in epidemiology, such as mediation and interaction. Here, we make use of this framework to provide a description of truncation by death, in which the outcome of interest is undefined for individuals who die before the assessment time at the end of follow-up. We explain the noncausal nature of the crude estimand that compares outcomes by treatment levels conditional on observed survival by showing that it corresponds to a comparison of distinct risk-status types, which are defined based on their susceptibility to sufficient causes. Further, expressions for the crude estimand and for the survivor average causal effect (SACE)�\a causal estimand defined under the principal stratification approach�\are provided in terms of population-level joint frequencies of the background factors of sufficient causes. Finally, we also describe conditions, based on background factors of sufficient causes, under which the SACE is null. Our description of this problem, which studies truncation by death from a new perspective, might encourage further analyses of principal stratification-based estimands using sufficient causes. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0066-4804 69 1 2025 Genomic epidemiology and genetic characteristics of clinical Campylobacter species cocirculating in West Bengal, India, 2019, using whole genome analysis e01108-24 EN Daichi Morita Department of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima University Asish Kumar Mukhopadhyay Division of Bacteriology, ICMR - National Institute of Cholera and Enteric Diseases Goutam Chowdhury Division of Bacteriology, ICMR - National Institute of Cholera and Enteric Diseases Fumito Maruyama Section of Microbial Genomics and Ecology, The IDEC Institute, Hiroshima University Miyuki Kanda Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University Yuki Yamamoto Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hidetoshi Tahara Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University Piyali Mukherjee Division of Bacteriology, ICMR - National Institute of Cholera and Enteric Diseases Mainak Bardhan Division of Bacteriology, ICMR - National Institute of Cholera and Enteric Diseases Takanori Kumagai Department of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima University Kei Kitahara Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR-NICED Shin-Ichi Miyoshi Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR-NICED Shanta Dutta Division of Bacteriology, ICMR - National Institute of Cholera and Enteric Diseases Teruo Kuroda Department of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima University Campylobacter species are the most common pathogens responsible for foodborne gastroenteritis worldwide. India is a region with frequent diarrheal infections and a high level of Campylobacter infection incidence, but the detailed genomic information is limited. This study aimed to characterize 112 isolates of Campylobacter from diarrhea patients at two hospitals in Kolkata, West Bengal, by whole genome analysis. The Campylobacter isolates consisted of 90 C. jejuni, 20 C. coli, and 2 C. lari isolates. Multilocus sequence typing analysis revealed that the largest sequence type (ST) populations were ST-2131 in C. jejuni and ST-830 in C. coli and seven novel STs were found in C. jejuni and one in C. coli. Notably, ST-2131, which is rarely seen elsewhere, was positive for a sialylated LOS-related gene (wlaN +neuA + cstIII) associated with Guillain-Barré syndrome. Antibiotic resistance factors predicted from the genome sequence included blaOXA variants (58.9%), tet(O) (54.5%), tet(W) (0.9%), ant(6)-Ia (0.9%), mutation in GyrA (T86I, T86I+D90N, T86I+P104S, T86I+D90N+P104S) (79.5%), and mutation in 23S rRNA (A2075G) (12.5%). In addition to the high drug resistance of Campylobacter in Kolkata, Campylobacter pathogens were circulating that may be associated with Guillain-Barré syndrome. This study indicates the importance of genomic analysis in the surveillance of pathogens, which provides genomic information on genetic diversity, virulence mechanisms, and determinants of antimicrobial resistance. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0019-9567 93 1 2025 A newly developed oral infection mouse model of shigellosis for immunogenicity and protective efficacy studies of a candidate vaccine e00346-2 EN Risha Haldar Division of Clinical Medicine, ICMR-National Institute of Cholera and Enteric Diseases Prolay Halder Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Hemanta Koley Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Shin-ichi Miyoshi Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Santasabuj Das Division of Clinical Medicine, ICMR-National Institute of Cholera and Enteric Diseases Shigella infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl3) plus desferrioxamine intraperitoneally followed by oral infection with virulent Shigella flexneri 2a resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing Shigella invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against Shigella, indicating that the model is suitable for testing of vaccine candidates. To protect both Shigella and Salmonella, a chimeric recombinant vaccine (rIpaB–T2544) was developed by fusing IpaB with Salmonella outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with Shigella (S. flexneri 2a, Shigella dysenteriae, and Shigella sonnei) using our present mouse model and Salmonella (Salmonella Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral Shigella infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against Shigella. No potential conflict of interest relevant to this article was reported.

Japanese Society of Veterinary Science Acta Medica Okayama 0916-7250 87 6 2025 Effects of heat stress on gene expression associated with antioxidant capacity of bovine early antral follicles 680 684 EN Kohei KAWANO Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kenichiro SAKAGUCHI Laboratory of Veterinary Theriogenology, Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University Eri FURUKAWA National Institute of Animal Health, National Agriculture and Food Research Organization Nattapong NINPETCH Department of Animal Science, Faculty of Agriculture at Kamphaeng Saen, Kasetsart University Yojiro YANAGAWA Laboratory of Theriogenology, Department of Clinical Sciences, Division of Veterinary Medicine, Faculty of Veterinary Medicine, Hokkaido University Seiji KATAGIRI Laboratory of Theriogenology, Department of Clinical Sciences, Division of Veterinary Medicine, Faculty of Veterinary Medicine, Hokkaido University Heat exposure at the physiological level of oocyte-cumulus-granulosa cell complexes (OCGCs) during in vitro growth (IVG) culture decreases the reduced glutathione (GSH) level of oocytes, an antioxidant, but its mechanism has been unclear. We subjected OCGCs to IVG for 4, 8, or 12 days and investigated the effects of heat exposure on the gene expression of cumulus-granulosa cells associated with antioxidant capacity. Heat exposure did not alter the expression of genes related to GSH synthesis or reuse. Conversely, heat exposure increased mRNA expression of superoxide dismutase 2 and decreased that of glutathione peroxidase 1, which are antioxidant enzymes. Ultimately, heat exposure alters the gene expression of antioxidant enzymes in growing follicles, which may indirectly decrease the GSH level of oocytes. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0021-9193 206 10 2024 Overexpression of diglucosyldiacylglycerol synthase leads to daptomycin resistance in Bacillus subtilis e00307-24 EN Ryogo Yamamoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuya Ishikawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuyuki Furuta Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-Ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Kaito Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The lipopeptide antibiotic daptomycin exhibits bactericidal activity against Gram-positive bacteria by forming a complex with phosphatidylglycerol (PG) and lipid II in the cell membrane, causing membrane perforation. With the emergence of daptomycin-resistant bacteria, understanding the mechanisms of bacterial resistance to daptomycin has gained great importance. In this study, we aimed to identify the genetic factors contributing to daptomycin resistance in Bacillus subtilis, a model Gram-positive bacterium. Our findings demonstrated that overexpression of ugtP, which encodes diglucosyldiacylglycerol synthase, induces daptomycin resistance in B. subtilis. Specifically, overexpression of ugtP resulted in increased levels of diglucosyldiacylglycerol (Glc2DAG) and decreased levels of acidic phospholipids cardiolipin and PG, as well as the basic phospholipid lysylphosphatidylglycerol. However, ugtP overexpression did not alter the cell surface charge and the susceptibility to the cationic antimicrobial peptide nisin or the cationic surfactant hexadecyltrimethylammonium bromide. Furthermore, by serial passaging in the presence of daptomycin, we obtained daptomycin-resistant mutants carrying ugtP mutations. These mutants showed increased levels of Glc2DAG and a >4-fold increase in the minimum inhibitory concentration of daptomycin. These results suggest that increased Glc2DAG levels, driven by ugtP overexpression, modify the phospholipid composition and confer daptomycin resistance in B. subtilis without altering the cell surface charge of the bacteria. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0304-8608 171 1 2025 Novel Escherichia coli phages representing a distinct genus within the subfamily Stephanstirmvirinae: genome and host range characteristics 18 EN Tomoyoshi Kaneko Department of Life Science and Medical Bioscience, Waseda University Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Osaka Department of Microbiology and Immunology, Tokyo Women�fs Medical University Satoshi Tsuneda Department of Life Science and Medical Bioscience, Waseda University Bacteriophages play crucial roles in microbial ecosystems and have potential for biotechnological applications. However, our understanding of culturable phages remains limited. In this study, we characterized six novel Escherichia coli phages isolated from pig farm wastewater and urban sewage, using comprehensive genomic, morphological, and host-range analysis. Using multiple comparative approaches, including gene-sharing network analysis, average nucleotide identity (ANI), and nucleotide intergenomic similarity (NIS), we demonstrated that five of these phages form a distinct group within the subfamily Stephanstirmvirinae, potentially representing a novel genus, for which we propose the name "Wecvirus�h. We further propose that these phages, each of which exhibits a unique host range pattern, should be classified in two distinct species within the proposed genus. This host specificity is reflected in differences in the amino acid sequences of tail fibers, which are crucial for infection. The remaining phage, which was not classified as a wecvirus, exhibited characteristics that challenged the current classification criteria, highlighting the need for more-flexible taxonomic approaches. These findings expand our understanding of phage diversity within the subfamily Stephanstirmvirinae and contribute to the evolving phage taxonomy framework. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 7 2026 Reappraisal of the Entity of Pediatric Uveitis: Bilateral Iridocyclitis With Retinal Capillaritis (BIRC) in Juveniles in 18 Additional Cases e112232 EN Toshihiko Matsuo Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Objectives: Bilateral iridocyclitis with retinal capillaritis (BIRC) in juveniles is a newly recognized ​​​​​entity of juvenile chronic uveitis with no systemic involvement. In this study, 18 additional consecutive patients with BIRC were reported to show that the entity would be useful in the differential diagnosis.<br> Methods: Clinical features were retrospectively reviewed in 18 consecutive patients diagnosed with BIRC in juveniles at Okayama University Hospital, Okayama, Japan, between 1996 and 2025.<br> Results: The 18 patients comprised 6 males and 12 females, with an age at onset ranging from 9 to 16 years (median, 13 years). All patients presented with aqueous cells and mutton-fat keratic precipitates in both eyes, and fluorescein angiography revealed varying degrees of optic disc leakage and retinal capillary leakage in the midperipheral to peripheral fundus of both eyes. None had systemic symptoms, including skin rashes, joint pain, or fever, and no abnormalities were detected on blood examinations, urinalysis, or plain chest x-rays. Oral prednisolone, tapered from 30 mg daily, together with topical 0.1% betamethasone four times daily, was administered to five patients: two with optic disc edema and three with macular edema in both eyes or the unilateral eye. The remaining 13 patients were treated with topical 0.1% betamethasone eye drops alone. In patients who developed elevated intraocular pressure, often due to a steroid response, the instillation of topical 0.1% betamethasone was reduced to twice daily, or intraocular pressure-lowering eye drops were used in combination. In two patients who showed relapse of unilateral macular edema after oral prednisolone was tapered or discontinued, oral colchicine (1 mg daily) was introduced, resulting in the subsidence of macular edema. Bilateral uveitis in all 18 patients subsided within 6 months to a few years until 19 years of age, and all topical medications were discontinued, with relapse occurring in only one patient.<br> Conclusions: BIRC in juveniles should be included in the differential diagnosis for school-age children and young adolescents. BIRC follows a chronic course of a few years and subsides completely with a good prognosis. In cases of macular edema or optic disc edema that affects vision, oral corticosteroid treatment is recommended, whereas patients with no sight-threatening signs can be treated with topical corticosteroid eye drops alone. The entity of BIRC may be distinct from juvenile chronic iridocyclitis in young girls with onset at preschool age, which shares common features with juvenile idiopathic arthritis-associated uveitis. No potential conflict of interest relevant to this article was reported.

Georg Thieme Verlag KG Acta Medica Okayama 0013-726X 57 04 2024 Efficacy and safety of endoscopic ultrasonography-guided ethanol injections of small pancreatic neuroendocrine neoplasms: a prospective multicenter study 321 329 EN Kazuyuki Matsumoto Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Gastroenterology and Hepatology, Okayama University Hospital Takao Itoi Gastroenterology and Hepatology, Tokyo Medical University Masayuki Kitano Second Department of Internal Medicine, Wakayama Medical University Kazuo Hara Gastroenterology, Aichi Cancer Center Hospital Masaki Kuwatani Gastroenterology and Hepatology, Hokkaido University Hospital Mamoru Takenaka Gastroenterology and Hepatology, Kindai University Faculty of Medicine Graduate School of Medical Sciences Reiko Ashida Second Department of Internal Medicine, Wakayama Medical University Shuntaro Mukai Gastroenterology and Hepatology, Tokyo Medical University Nozomi Okuno Gastroenterology, Aichi Cancer Center Hospital Kazumichi Kawakubo Gastroenterology and Hepatology, Hokkaido University Hospital Tatsuhiro Yamazaki Gastroenterology and Hepatology, Okayama University Hospital Jun Sakurai Center for Innovative Clinical Medicine, Okayama University Hospital Yuki Nakatsuka Center for Innovative Clinical Medicine, Okayama University Hospital Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Motoyuki Otsuka Gastroenterology and Hepatology, Okayama University Hospital Background Endoscopic ultrasonography (EUS)-guided ethanol injection (EI) has recently been introduced as one of the management strategies for pancreatic neuroendocrine neoplasms (PNENs); however, its role as a surgical alternative is unclear. We evaluated the efficacy and safety of EUS-EI in treating small PNENs through a prospective multicenter study.<bR> Methods Patients with grade 1 tumors of ≤15 mm confirmed by pathology were included. The primary end point assessed efficacy and safety, measuring complete ablation using computed tomography at 1 and 6 months, prevention of adverse events (AEs) within 1 month, severe pancreatic fistula at 1 month, and incidence/worsening of diabetes mellitus (DM) at 6 months. The composite end point of EUS-EI was compared with that of historical results of a study based on surgical treatment.<br> Results 25 patients with PNENs, with a median tumor size of 10.1 mm, were treated using EUS-EI. The composite primary end point was achieved by 76.0% of patients (19/25; 95%CI 54.9%–90.6%), a proportion significantly higher than that of surgical treatment (P = 0.008). Regarding efficacy, 88.0% (22/25) of patients achieved complete ablation at 1 and 6 months (95%CI 68.8%–97.5%). Regarding safety, 96.0% (24/25) of patients had no severe AEs within 1 month (95%CI 79.7%–99.9%). No patients had severe pancreatic fistulas at 1 month, and 84.0% (21/25) had no incidence or exacerbation, or both, of DM at 6 months (95%CI 63.9%–95.5%).<br> Conclusion EUS-EI is safe and could be a potent treatment option for patients with small PNENs. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 0732-183X 43 16 2025 Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin + Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial 1886 1897 EN Hiroaki Hiraga Musculoskeletal Oncology, NHO Hokkaido Cancer Center Ryunosuke Machida Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Akira Kawai Musculoskeletal Oncology, National Cancer Center Hospital Toshiyuki Kunisada Orthopaedic Surgery, Faculty of Medicine, Okayama University Tsukasa Yonemoto Orthopaedic Surgery, Chiba Cancer Center Makoto Endo Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Yoshihiro Nishida Department of Rehabilitation Medicine, Nagoya University Hospital Akihito Nagano Orthopaedic Surgery, Gifu University School of Medicine Keisuke Ae Orthopaedic Surgery, Cancer Institute Hospital Shinichirou Yoshida Orthopaedic Surgery, Tohoku University Graduate School of Medicine Kunihiro Asanuma Orthopaedic Surgery, Mie University Junya Toguchida Department of Tissue Regeneration, Center for Induced Pluripotent Stem Cell Research and Application, Institute for Frontier Medical Sciences, Kyoto University Taisuke Furuta Orthopaedic Surgery, Hiroshima University Robert Nakayama Department of Orthopaedic Surgery, Keio University School of Medicine Toshihiro Akisue Orthopaedic Surgery, Kobe University Toru Hiruma Bone and Soft Tissue Tumour Surgery, Kanagawa Cancer Center Takeshi Morii Orthopaedic Surgery, Kyorin University Hideki Nishimura Orthopaedic Surgery, Kagawa University Hospital Koji Hiraoka Orthopaedic Surgery, Kurume University Hospital Masanobu Takeyama Orthopaedic Surgery, Yokohama City University Hospital Makoto Emori Orthopaedic Surgery, Sapporo Medical University Hospital Satoshi Tsukushi Orthopaedic Surgery, Aichi Cancer Center Hiroshi Hatano Musculoskeletal Oncology, Niigata Cancer Center Hospital Hiroyuki Kawashima Orthopaedic Surgery, Niigata University Medical & Dental Hospital Kazuo Isu Orthopaedic Surgery, Higashi Sapporo Hospital Kazuhiro Tanaka Advanced Medical Sciences, Oita University Faculty of Medicine Tomoko Kataoka Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Haruhiko Fukuda Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Yukihide Iwamoto Orthopaedic Surgery, Kyushu Rosai Hospital Toshifumi Ozaki Orthopaedic Surgery, Faculty of Medicine, Okayama University Purpose Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m2 [4g/m2 once on day 1, then 2g/m2 once on days 2-7] �~ six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp.<br> Methods JCOG0905 is a multicenter, open-label, multi-institutional, randomized trial. Eligible patients (50 years and younger) had resectable, high-grade osteosarcoma (stage II or III, Union for International Cancer Control TNM) of the extremities, limb girdles, and thoracic wall. After two MAP cycles and tumor resection, patients with PrRsp were randomly assigned to either the MAP or MAP plus 15 g/m2 (3g/m2 once daily on days 1-5) �~ six IF (MAP + IF [MAPIF]) group. The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The planned sample size was 100 patients with a one-sided ƒ¿ of .1 and a power of 0.7, assuming a 3-year DFS of 50% and 65% for MAP and MAPIF, respectively. This trial is registered with the Japan Registry of Clinical Trials (jRCT; jRCTs031180126).<br> Results Of the 287 patients registered between February 2010 and August 2020, 51 and 52 patients with PrRsp were assigned to the MAP and MAPIF groups, respectively. As of March 2022, DFS did not differ between groups (hazard ratio [HR], 1.05 [95% CI, 0.55 to 1.98]) and OS was numerically inferior in the MAPIF group (HR, 1.48 [95% CI, 0.68 to 3.22]). Nine and zero patients in the MAPIF and MAP groups discontinued treatment because of adverse events, respectively.<br> Conclusion Evidence from JCOG0905 does not support the addition of IF for patients with PrRsp. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-8609 100 1 2024 Different impacts of granulocyte colony�]stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type 66 77 EN Takaaki Konuma Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo Kazuaki Kameda Division of Hematology, Jichi Medical University Saitama Medical Center Kaoru Morita Division of Hematology, Jichi Medical University Tadakazu Kondo Department of Hematology, Kobe City Medical Center General Hospital Fumihiko Kimura Division of Hematology, Department of Internal Medicine, National Defense Medical College Hideki Nakasone Division of Hematology, Jichi Medical University Saitama Medical Center Fumihiko Ouchi Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Naoyuki Uchida Department of Hematology, Toranomon Hospital Masatsugu Tanaka Department of Hematology, Kanagawa Cancer Center Tetsuya Nishida Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Takahiro Fukuda Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Yuta Hasegawa Department of Hematology, Hokkaido University Hospital Mamiko Sakata�]Yanagimoto Department of Hematology, University of Tsukuba Hospital Makoto Onizuka Department of Hematology and Oncology, Tokai University School of Medicine Masashi Sawa Department of Hematology and Oncology, Anjo Kosei Hospital Shuichi Ota Department of Hematology, Sapporo Hokuyu Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Shin�]Ichiro Fujiwara Division of Hematology, Jichi Medical University Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Fumihiko Ishimaru Technical Department, Japanese Red Cross Society Blood Service Headquarters Makoto Yoshimitsu Department of Hematology and Rheumatology, Kagoshima University Hospital Yoshinobu Kanda Division of Hematology, Jichi Medical University Marie Ohbiki Japanese Data Center for Hematopoietic Cell Transplantation Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Masamitsu Yanada Department of Hematology and Oncology, Nagoya City University East Medical Center We retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II–IV acute graft-versus-host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G-CSF administration in BMT and CBT patients, but not in PBSCT patients. G-CSF administration significantly improved overall survival (OS) and leukemia-free survival (LFS) only following CBT. Regarding the timing of G-CSF, in comparison with late initiation of G-CSF (Days 5–10), early initiation (Days 0–4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II–IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G-CSF administration accelerated neutrophil recovery and increased the risk of grades II–IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G-CSF should be considered for CBT in adult patients with AML. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 30 3 2025 Five-year outcomes with gefitinib induction and chemoradiotherapy in EGFR-mutant stage III non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study 497 503 EN Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Sho Saeki Department of Respiratory Medicine, Kumamoto University Hospital Shinya Sakata Department of Respiratory Medicine, Kumamoto University Hospital Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Daijiro Harada Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Kentaro Tanaka Department of Respiratory Medicine, Kyushu University Hospital Koji Inoue Department of Respiratory Medicine, Kitakyushu Municipal Medical Center Koji Inoue Department of Respiratory Medicine, Ehime Prefectural Central Hospital Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Toshio Kubo Department of Respiratory Medicine, Okayama University Hospital Akiko Sato Department of Respiratory Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Hiromi Watanabe Department of Respiratory Medicine, Okayama University Hospital Junji Kishimoto Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University Yoshiyuki Shioyama Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation Kuniaki Katsui Department of Radiology, Kawasaki Medical School Kenji Sugio Division of Radiation Oncology, Department of Thoracic and Breast Surgery, Oita University Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Background We previously showed the 2-year OS rate, the primary endpoint, of 90% in a phase II trial of gefitinib induction followed by chemoradiotherapy (CRT) in unresectable, stage III, EGFR-mutant, non-small-cell lung cancer (NSCLC). However, neither long-term survival data nor late-phase adverse event profiles have been presented.<br> Patients and methods Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy for 8 weeks. After confirming no disease progression during induction therapy, cisplatin and docetaxel on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy were subsequently administered.<br> Results In the enrolled twenty patients, the 5-year OS rate and median survival time were 70.0% [95% confidence interval: 45.1–85.3] and 5.5 years [4.91-NE], respectively, whereas 5-year PFS rate and median PFS time were 15.0% (3.7–33.5) and 1.4 years [0.69–2.29], respectively. Efficacy did not seem influenced even if radiation field was re-planed in response to the effect of gefitinib induction. As for late adverse events, pulmonary fibrosis occurred in 7 patients (35%). The median time from completion of CRT to the occurrence of the event was 245 days. All were grade 1, and there was no evidence of cavitation of the lesions or chronic infections such as Aspergillus infection during the course of the disease. One case of small cell lung cancer occurred during the period.<br> Conclusions With longer follow-up time, we demonstrated favorable efficacy with tolerable toxicity profiles in the EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III, NSCLC.<br> Trial registration numbers UMIN00005086. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000006047&type=summary&language=EjRCTs071180036. https://jrct.niph.go.jp/latest-detail/jRCTs071180036 No potential conflict of interest relevant to this article was reported.

John Wiley & Sons Ltd Acta Medica Okayama 0364-2313 2026 Indicators for Monitoring Recovery From Surgery to Discharge Using Accelerometer in Patients With Esophageal Cancer 1 4 EN Takahiro Yamane Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Yoshikazu Kimura Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Manami Tetsutani Faculty of Health Sciences, Okayama University Medical School Shota Yamamura Faculty of Health Sciences, Okayama University Medical School Airu Ito Faculty of Health Sciences, Okayama University Medical School Moe Tanuma Faculty of Health Sciences, Okayama University Medical School Mina Honjoh Faculty of Health Sciences, Okayama University Medical School Yoshiko Moriwaki Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshikazu Matsuoka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mizuki Morita Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Esophageal cancer is a highly invasive malignancy necessitating esophagectomy, which is associated with considerable postoperative morbidity and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) protocols recommend early mobilization to facilitate recovery; however, objectively assessing physical activity during hospitalization remains challenging. Traditional methods, such as the 6-min walk test or patient-reported questionnaires can be burdensome, or may not accurately reflect recovery. Accelerometer-based measurement provides a low-burden, objective approach, but previous studies focused on the immediate postoperative period or long after discharge, leaving the recovery trajectory from surgery to discharge underexplored. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-8937 5 1 2025 The Early Response After Radiation Therapy on Three-Dimensional Oral Cancer Model Using Patient-Derived Cancer-Associated Fibroblasts 12 EN Izumi Yamamoto Neutron Therapy Research Center, Okayama University Kazuyo Igawa Neutron Therapy Research Center, Okayama University Natsuko Kondo Particle Radiation Oncology Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University Yoshinori Sakurai Particle Radiation Oncology Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University Atsushi Fujimura Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Peng Huang Neutron Therapy Research Center, Okayama University Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenji Izumi Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Background/Objectives: Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been reported to have an adverse effect on conventional radiotherapy. This study aims to elucidate the effects of CAFs in boron neutron capture therapy (BNCT) using a three-dimensional (3D) oral cancer model. Methods: Three-dimensional cancer models were fabricated using patient-derived CAFs or patient-derived normal oral fibroblasts (NOFs) and a human oral squamous cell carcinoma cell line. Each 3D cancer model was performed with either a conventional X-ray treatment or BNCT and additionally analyzed histomorphologically. Results: The 3D oral cancer-CAFs model demonstrated a greater depth of cancer cell invasion than the 3D oral cancer-NOFs model. Radiation therapy for the 3D oral cancer models indicated a trend for decreasing cancer cell invasion and cell number with dose dependence in both X-ray and BNCT. In comparison with X-rays, BNCT showed a consistent increase in the number of NOFs and a significant reduction in the number of CAFs. Conclusions: BNCT for the 3D oral cancer model was shown to be effective against cancer cells and CAFs but not against NOFs, indicating its usefulness as a minimally invasive treatment for advanced cancer. Furthermore, it is indicated that the 3D oral cancer-CAFs model is a valuable tool to evaluate cancer treatment and research, particularly in high-grade malignant tumors with invasion. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2407 25 1 2025 Long-term outcomes of salvage high-dose-rate brachytherapy for localized recurrence of prostate cancer following definitive radiation therapy: a retrospective analysis 524 EN Kenta Watanabe Department of Radiology, Okayama University Hospital Nobuhiko Kamitani Department of Radiology, Kawasaki Medical School Naoki Ikeda Department of Radiology, Kawasaki Medical School Yujiro Kawata Department of Radiology, Kawasaki Medical School Ryoji Tokiya Department of Radiology, Kawasaki Medical School Takafumi Hayashi Department of Radiology, Kawasaki Medical School Yoshiyuki Miyaji Department of Urology, Kawasaki Medical School Tsutomu Tamada Department of Radiology, Kawasaki Medical School Kuniaki Katsui Department of Radiology, Kawasaki Medical School Background Salvage high-dose-rate brachytherapy (HDR-BT) is a potential treatment for localized recurrence of prostate cancer following definitive radiation therapy. This study aimed to evaluate the long-term safety and efficacy of HDR-BT alone, without androgen deprivation therapy (ADT), in this patient population.<br> Methods We conducted a retrospective analysis of patients with prostate cancer who developed pathologically confirmed local recurrence after definitive radiation therapy and were treated with salvage HDR-BT alone at Kawasaki Medical School Hospital between 2007 and 2021. The prescribed HDR-BT dose was 22 Gy in 2 fractions. Biochemical relapse-free survival (bRFS), cause-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan–Meier method. Adverse events were evaluated based on the Common Terminology Criteria for Adverse Events.<br> Results Thirty-five patients were included, with a median follow-up of 66.0 months (range, 8.1–169.1). The 5-year bRFS, CSS, and OS rates were 29.7%, 100%, and 89.3%, respectively. Biochemical recurrence occurred in 21 patients (60.0%). Grade 2 adverse events were reported in eight patients (22.9%), while two (5.7%) experienced grade 3 adverse events. All grade 3 adverse events occurred in patients who had HDR-BT as their initial definitive radiation therapy.<br> Conclusions Salvage HDR-BT without ADT is a safe and effective treatment option for localized prostate cancer recurrence after definitive radiation therapy. It provides excellent CSS rates with acceptable toxicity while potentially reducing the need for ADT. Further prospective studies are warranted to confirm these findings. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1718-7729 32 6 2025 Global Incidence Trend of Early-Onset Obesity-Related and Non-Obesity-Related Cancers 324 EN Miyu Terashima Okayama University Medical School Kota Nakayama Okayama University Medical School Satoko Ugai Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA Hwa-Young Lee Graduate School of Public Health and Healthcare Management, The Catholic University of Korea Yuta Tsukumo Department of Epidemiology, Harvard T.H. Chan School of Public Health Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Mizuno Department of Epidemiology, Harvard T.H. Chan School of Public Health Minkyo Song Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health Naoko Sasamoto Public Health Sciences Division, Fred Hutchinson Cancer Center Ichiro Kawachi Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health Tomotaka Ugai Department of Epidemiology, Harvard T.H. Chan School of Public Health The global rise in obesity prevalence and the incidence of early-onset cancer (diagnosed between 20 and 49 years of age) is a serious public health concern. We, therefore, evaluated the recent global trends in the incidence of early-onset obesity-related cancers and compared them to those of non-obesity-related cancers. We obtained age-standardized incidence rates of early-onset cancers diagnosed between 2000 and 2012 in 44 countries from the Cancer Incidence in Five Continents database. Using joinpoint regression models, we calculated the average annual percentage changes (AAPCs) and their corresponding 95% confidence intervals (95% CIs) for combined and individual categories of obesity-related cancers (11 and 9 cancer types in females and males, respectively) and non-obesity-related cancers (12 cancer types in both females and males). Differences in the AAPC were assessed by comparing 95% CIs, where nonoverlapping 95% CIs were considered statistically significantly different. We observed statistically significant positive AAPCs for early-onset obesity-related cancers in all available countries combined among females (global AAPC, 4.3%; 95% CI, 4.1–4.6%) and males (global AAPC, 1.4%; 95% CI, 1.2–1.7%). When analyzed by countries, we observed statistically significant positive AAPCs in 26 countries among females and 11 countries among males. AAPCs for early-onset obesity-related cancers were statistically significantly higher than those of non-obesity-related cancers in several regions, especially North America and Oceania. In conclusion, this study indicates that the incidence of early-onset obesity-related cancers exhibited a more pronounced increasing trend than non-obesity-related cancers among both sexes in many countries and regions. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 2057-5858 11 4 2025 Whole-genome-based characterization of Escherichia albertii strains isolated from paediatric diarrhoeal cases in Kolkata, India 001363 EN Goutam Chowdhury Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric Diseases Yuki Hoshiko Division of Microbiology, Department of Infectious Medicine, School of Medicine, Kurume University Miki Okuno Division of Microbiology, Department of Infectious Medicine, School of Medicine, Kurume University Kei Kitahara Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric Diseases M John Albert Department of Microbiology, College of Medicine, Kuwait University Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshitoshi Ogura Division of Microbiology, Department of Infectious Medicine, School of Medicine, Kurume University Shanta Dutta Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Thandavarayan Ramamurthy Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Asish K. Mukhopadhyay Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Escherichia albertii is a Gram-negative facultative anaerobic bacterium that causes diarrhoea in humans. This study shows the isolation of E. albertii from hospitalized paediatric diarrhoeal cases and genome-based characteristics with putative virulence factors and antimicrobial resistance. E. albertii isolates were identified by species-specific PCR, targeting the gene encoding cytolethal distending toxin (Ea-cdt). The genome of E. albertii was sequenced to identify (i) genes encoding virulence factors (ii) antibiotic resistance-encoding genes, including the mobile genetic elements and (iii) core gene-based phylogenetic relationships and pan-genome features. A total of 10 (1.2%) E. albertii isolates were isolated from 854 faecal samples, of which 6 (60%) were found as the sole pathogen and the remaining 4 (40%) were identified along with other pathogens, such as enteroaggregative Escherichia coli, rotavirus and adenovirus. Patients from whom E. albertii was isolated presented cholera-like diarrhoea, i.e. with watery stool (60%) with moderate dehydration (100%), fever (20%) and abdominal pain (20%). The antimicrobial susceptibility testing of E. albertii showed that most of the isolates were susceptible or reduced susceptible to most of the antibiotics except resistance to erythromycin (80%), tetracycline (50%), nalidixic acid (40%), ampicillin (40%), doxycycline (30%) and ceftriaxone (20%). In the whole-genome sequence, E. albertii isolates revealed several virulence-encoding genes, namely the intimin (eae, E. coli attaching and effacing), the cytolethal distending toxin type II subunit A (cdt-IIA), adhesion (paa, porcine attaching- and effacing-associated), non-LEE (locus of enterocyte effacement) encoded effector A (nleA) and antimicrobial resistance genes (ARGs) conferring resistance to tetracycline (tetA, tetR), sulphonamides (sul2), fluoroquinolones (qnrS) and beta-lactamases (blaCTX-M, blaTEM). The SNP-based phylogenetic analysis of 647 whole genomes of E. albertii isolates from the National Center for Biotechnology Information databases did not reveal any comparable clustering pattern based on the biological source and place of isolation. The genome of some of the E. albertii was closely related to those of the isolates from China and the United Kingdom. The PFGE patterns revealed that most of the E. albertii isolates were distinct clones. This study reports on the extensive genome analysis of diarrhoea-associated E. albertii harbouring multiple virulence and ARGs. No potential conflict of interest relevant to this article was reported.

Ferrata Storti Foundation (Haematologica) Acta Medica Okayama 1592-8721 111 5 2025 Distinct interleukin-6 production in IPL and TAFRO subtypes of idiopathic multicentric Castleman disease 1705 1715 EN Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Division of Hematology/Oncology, Mayo Clinic Rio Yamada Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tomoka Haratake Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan; Department of Hematology and Oncology, Okayama University Hospital Ryota Chijimatsu Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan; Department of Hematology and Oncology, Okayama University Hospital Toshihiro Ito Department of Immunology, Nara Medical University Tomohiro Koga Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences Sayaka Ochi Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yuri Kawahara Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Himawari Ueta Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yudai Takeda Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Michael V. Gonzalez Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania David C. Fajgenbaum Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Frits Van Rhee University of Arkansas for Medical Sciences Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by systemic inflammation and lymphadenopathy. Two major clinical subtypes, idiopathic plasmacytic lymphadenopathy (iMCD-IPL) and iMCD with thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, and organomegaly (iMCD-TAFRO), have distinct pathophysiological mechanisms. While interleukin-6 (IL-6) is known to be elevated in iMCD, differences in the sources of IL-6 production between subtypes remain unclear. We examined the source of IL-6 production and its transcriptional regulation across iMCD subtypes using immunohistochemistry, in situ hybridization, and gene expression profiling. Immunohistochemistry and in situ hybridization revealed that plasma cells were the predominant IL-6-expressing cells in iMCD-IPL, whereas vascular endothelial cells expressed IL-6 in iMCD-TAFRO. Plasma cells exhibited stronger IL-6 protein expression in iMCD-IPL than in iMCD-TAFRO. Gene expression analysis revealed upregulation of XBP1, MZB1, DERL3, SSR4, FKBP11, FKBP2, PIM2, RABAC1, and SDF2L1 in iMCD-IPL, implicating endoplasmic reticulum stress and plasma cell differentiation in IL-6 dysregulation. Our findings suggest that XBP1-mediated IL-6 production may contribute to the pathogenesis of iMCD-IPL, potentially explaining its favorable responses to IL-6 blockade therapy. In contrast, IL-6 production in iMCD-TAFRO may be predominantly from vascular endothelial cells, suggesting that elevated serum IL-6 is a secondary phenomenon of the cytokine storm in this subtype. Future studies should clarify how proteomics and gene expression profiling could inform subtype-specific therapeutic strategies in iMCD. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-8043 236 2026 An algorithm to calculate physical density of biomedical objects having 3 ≤ Zeff ≤ 20: an application study using clinical photon-counting computed tomography equipment 112768 EN Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Mana Mitani Division of Radiological Technology, Medical Support Department, Okayama University Hospital Noriaki Akagi Division of Radiological Technology, Medical Support Department, Okayama University Hospital Fumiyo Higaki Department of Radiology, Medical Development Field, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Recently, photon-counting computed tomography (PC-CT) devices have become clinically available for X-ray diagnosis, and developments of analysis algorithms to generate various quantitative images have focused attention. This study proposes an algorithm to calculate the effective physical density (ƒÏeff) of biological objects having an effective atomic number (Zeff) of 3–20. In our procedure, ƒÏeff was determined when fitting the interaction cross sections (ƒÐs) to the measured linear attenuation coefficients (ƒÊs), which were determined from virtual monochromatic images (VMIs). In this process, the Zeff was analyzed in advance, and this information was fed back to the ƒÏeff analysis. A key feature of our procedure is that it does not require calibration processes based on specific substances, which allow us to analyze any substance without making assumptions.<br> To validate the availability of the proposed algorithm, we conducted an experiment using a clinical PC-CT scanner. A multi-energy CT phantom, a water phantom, an in-house low-density phantom, food samples, and a chest phantom were scanned. The results showed that our procedure can calculate ƒÏeff of water with an uncertainty of 4.5%. The academic significance of the present research results lies in demonstrating that the factors contributing to contrast, previously obtained from CT values, can be physically interpreted using information from Zeff and ƒÏeff. This analysis cannot be performed with conventional single-energy CT scanners and is possible with PC-CT and dual-energy CT scanners. Our novel procedure is expected to provide useful additional information in X-ray diagnosis. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1931-5244 295 2026 A novel spontaneous rat model of chronic kidney disease with mitochondrial dysfunction driven by thioredoxin insufficiency 51 64 EN Iori K. Ohmori Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University Mamoru Ouchida Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiko Hada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinya Toyokuni Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine Tomoji Mashimo Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo Background: Chronic kidney disease (CKD) is a global health burden with high prevalence and poor prognosis. Although oxidative stress and mitochondrial dysfunction have been implicated in its pathogenesis, in vivo causal evidence remains limited. Thioredoxin (Trx), encoded by Txn1, is a redox-active protein that plays a central role in controlling oxidative stress and maintaining intracellular redox homeostasis.<br> Methods: To address this gap, we investigated the lifelong phenotypes of Txn1-F54L mutant rats harboring approximately one-third of the normal Trx activity. These rats were generated via N-ethyl-N-nitrosourea mutagenesis and validated by clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 genome editing. Comprehensive analyses included biochemical testing, histopathology, immunohistochemistry, transmission electron microscopy, RNA-sequencing, western blotting, and cytokine profiling.<br> Results: Txn1-F54L mutant rats spontaneously developed progressive CKD, with median survival times of 110–119 days for homozygotes and 303–346 days for heterozygotes. Their clinical features�\elevated blood urea nitrogen, hypoalbuminemia, hypercholesterolemia, hypertension, and arterial medial sclerosis�\closely resembled those of human CKD. Histopathological evaluation revealed extensive tubular injury, interstitial fibrosis, and glomerulosclerosis. Transcriptomic profiling identified 3,418 differentially expressed genes significantly enriched in immune activation and fibrosis pathways. Mitochondrial dysfunction was prominent in proximal tubules, accompanied by oxidative stress accumulation and concurrent activation of regulated cell death pathways (apoptosis, necroptosis, and pyroptosis). Elevated serum levels of interleukin-1ƒÀ, interleukin-6, and interferon-ƒÁ indicated systemic inflammation.<br> Conclusions: Our findings demonstrate that lifelong Trx deficiency induces oxidative stress–mediated mitochondrial dysfunction and regulated cell death, leading to inflammation and progressive CKD. This study establishes the Txn1 mutant rat as a valuable spontaneous CKD model, providing translational insights and a platform for developing therapeutic strategies targeting oxidative stress–induced pathways. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Variations in the perceived value of anti-SARS-CoV-2 therapeutics based on physicians�f clinical backgrounds 5705 EN Akihiko Hagiwara Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine Kosaku Komiya Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine Yuichiro Shindo Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Kazufumi Takamatsu Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Naoki Nishimura Department of Respiratory Medicine, National Center for Global Health and Medicine Yukako Takechi Iki-iki Clinic Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Takahiro Takazono Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences Shinyu Izumi Department of Respiratory Medicine, National Center for Global Health and Medicine Shimpei Gotoh Department of Clinical Application, Center for iPS Cell, Research and Application, Kyoto University Seiichiro Sakao Department of Pulmonary Medicine, School of Medicine, International University of Health and Welfare Takehiro Izumo Department of Respiratory Medicine, Japanese Red Cross Medical Center Kazuko Yamamoto Division of Infectious, Respiratory, and Digestive Medicine, First Department of Internal Medicine, University of the Ryukyus Graduate School of Medicine Kazuhiro Yatera Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health Hiroshi Kakeya Department of Infection Control Science, Osaka Metropolitan University Graduate School of Medicine Yoko Shibata Department of Pulmonary Medicine, Fukushima Medical University School of Medicine Keisuke Tomii Department of Respiratory Medicine, Kobe City Medical Center General Hospital Hironori Sagara Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University School of Medicine Yuka Sasaki Center for Pulmonary Disease, National Hospital Organization Tokyo National Hospital Toyohiro Hirai Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University Akihito Yokoyama Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Hiroshi Mukae Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences Takashi Ogura Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center Although the global emergency phase of the coronavirus disease 2019 (COVID-19) pandemic has ended, antiviral therapy remains crucial for patients at high risk of severe illness. In Japan, the out-of-pocket costs for antiviral drugs shifted from full public coverage to partial patient payment in April 2024. However, the impact of physicians�f background characteristics on antiviral cost perceptions and prescribing behavior remains underexplored. This study involved a secondary analysis of a nationwide, web-based interventional survey of 1,500 physicians treating COVID-19. Participants reported whether they avoided prescribing antivirals owing to drug costs and identified what they considered an appropriate cost per treatment course. Associations between physicians�f characteristics and their cost perceptions were analyzed. Among 1,500 physicians surveyed, 1,193 (79.5%) reported avoiding antiviral prescriptions owing to drug costs. The most commonly selected appropriate cost was ≤ 33 USD (65.0%). Generalists, pulmonologists, ear, nose, and throat specialists, and clinic-based physicians were more likely to refrain from prescribing antivirals and favor lower treatment costs compared with physicians in other specialties or hospital settings. A multivariate analysis revealed workplace setting as the only factor independently associated with cost-related prescribing behavior. High antiviral drug costs in Japan may contribute to underprescription, particularly among clinic-based physicians, and this underprescription could hypothetically lead to delays in treatment, which might increase the risk of severe outcomes in high-risk patients. As high-risk patients with mild COVID-19 often first seek care in clinics, promoting appropriate antiviral use in these settings is essential. Strengthening communication and sharing clinical experiences between hospitals and clinics may help reduce prescribing disparities driven by drug costs. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Determination of the Side Responsible for Bilateral Pneumothorax due to Pleural Communication 225 228 EN Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kumi Nakajima Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidejiro Torigoe Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/70859 Simultaneous bilateral spontaneous pneumothorax associated with pleuro-pleural communication is a rare but potentially life-threatening condition, most commonly occurring after major thoracic surgery. We report the case of an 81-year-old man with severe emphysema and a history of esophagectomy who presented with sudden-onset dyspnea. Chest computed tomography revealed bilateral pneumothorax with pleuro-pleural communication. Although bilateral chest tube drainage was performed, the primary side of air leakage could not be identified preoperatively. After induction of general anesthesia, a double-lumen endotracheal tube clamping test identified the right pleural cavity as the source of air leakage, thereby enabling appropriate thoracoscopic surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Common Bile Duct Stone Formed Around an Ingested Fish Bone 219 223 EN Kaitaro Higashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Shuta Tamura Department of Gastroenterological Surgery, Kochi Health Sciences Center Sunao Uemura Department of Gastroenterological Surgery, Kochi Health Sciences Center Teppei Tokumaru Department of Gastroenterological Surgery, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/70858 An 86-year-old man presented with epigastric pain. He had previously undergone distal gastrectomy with Roux-en-Y reconstruction. Computed tomography (CT) revealed a 32�~17 mm common bile duct (CBD) stone with an internal 20 mm linear hyperdense component. Endoscopic removal was unsuccessful due to the size and impaction of the stone. Open choledochotomy retrieved multiple stones and a calcified fish bone, which was confirmed by infrared spectroscopy using the potassium bromide (KBr) wafer method. Although fish bone ingestion is relatively common, this case highlights that such foreign bodies can occasionally serve as a nidus for CBD stone formation, leading to unexpected and clinically significant pathologies. When CT demonstrates a linear high-attenuation intraductal structure, clinicians should suspect a bone fragment and follow a stepwise approach, considering early surgical intervention when endoscopic extraction is unsuccessful or likely to be challenging. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 A Novel Flap Design to Reduce Urethral Complications in Anterolateral Thigh Phalloplasty: The Pipe Flap Technique 213 217 EN Toshiro Imai Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine Toshiyuki Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Shiho Watanabe Department of Plastic and Reconstructive Surgery, National Hospital Organization Tokyo Medical Center Masanobu Hayashi Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine Yusuke Tominaga Department of Urology, Okayama University Hospital Yuzaburo Namba Gender Center, Okayama University Hospital Case Report 10.18926/AMO/70857 Phalloplasty is one of the most challenging procedures in gender-affirming surgery, and urethral complications remain common despite numerous preventive efforts. No definitive solution has been established, and many patients still require subsequent corrective procedures. We designed a novel anterolateral thigh flap that creates a planned external fistula at the penile base to mitigate urethral complications. The fistula was closed in a second-stage procedure one year later, and the postoperative course was uneventful. We report a case of a transgender man treated with this two-stage �gpipe flap�h technique, resulting in satisfactory urinary function. This approach may offer a safe and less invasive option for mitigating urethral complications in phalloplasty. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Evaluation of Bone Mineral Density and Bone Structure in the Cervical and Thoracic Spine 203 212 EN Shingo Aoyama Department of Orthopedic Surgery, Kindai University Hospital Terumasa Ikeda Department of Orthopedic Surgery, Kindai University Hospital Nobuhito Nango Ratoc System Engineering Co., Ltd. Koji Goto Department of Orthopedic Surgery, Kindai University Hospital Original Article 10.18926/AMO/70856 Dropped head syndrome, which has been increasingly reported in recent years, requires correction of cervical kyphosis and may require long-range fixation extending from the cervical to the thoracic spine. Assessing vertebral bone structure may be important for preventing instrumentation failure in the upper thoracic spine, which is a potential complication of surgery. In this study, we evaluated volumetric bone mineral density, trabecular bone porosity, and cortical calcification in the cervical and upper thoracic spine using three-dimensional (3D) trabecular structure measurement software. The study included 79 patients with cervical spine disorders who underwent various surgical procedures and preoperative imaging, including dual-energy X-ray absorptiometry and computed tomography (CT) scans from C3 to Th3. Quantitative analysis using specialized software assessed volumetric bone mineral density and trabecular and cortical bone parameters, and statistical analyses were performed to examine correlations between imaging metrics and indicators of bone fragility. Two-dimensional CT evaluation revealed different trends between cancellous and cortical bone in the cervical and thoracic spine, suggesting that detailed 3D evaluation may also be important. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 HIP COMPASS®: A Mechanical Intraoperative Navigation Guide Associated with Improved Revision-Free Implant Survivorship after Ceramic-on-Ceramic Total Hip Arthroplasty at Minimum 10-Year Follow-up 195 202 EN Yoshiaki Tei Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Norio Imai Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Keishi Kimura Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yuki Hirano Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yoji Horigome Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Ken Suda Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Hiroyuki Kawashima Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Original Article 10.18926/AMO/70855 HIP COMPASS® has demonstrated improved accuracy in intraoperative support for the acetabular component insertion angle. We assessed long-term revision-free implant survivorship following total hip arthroplasty (THA) using HIP COMPASS, with ≥10 years of follow-up. We retrospectively analyzed 210 hips of 186 patients who underwent cementless THA with ceramic-on-ceramic bearing couples, with or without HIP COMPASS. The mean follow-up duration was 10.8 years in the HIp COMPASS group and 12.7 years in the control group. Overall, 86.0% and 78.2% of cups were placed within Lewinnek�fs safe zone with and without HIP COMPASS, respectively. Variability in radiographic inclination and anteversion was greater in the control group than in the HIP COMPASS group. Dislocation rates were 3.2% in the control group and 1.2% in the HIP COMPASS group, with no significant difference between groups. The control group had a significantly higher revision rate than the HIP COMPASS group (7.3% vs. 1.2%). Use of HIP COMPASS was associated with improved long-term revision-free implant survivorship over ≥ 10 years and more consistent acetabular component positioning at an appropriate insertion angle, which may contribute to stable initial fixation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Reducing Hesitation in Resuscitation: Educational Effects of a Female-Appearing Simulator in Basic Life Support Training 185 193 EN Takuya Kubo Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Kosaki Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/70854 Women are less likely than men to receive timely defibrillation during out-of-hospital cardiac arrest. We investigated whether using a simulator that is visually modified to resemble a female affects learners�f attitudes, knowledge, and performance in basic life support (BLS) training. In a BLS simulation training, first-year medical students (n=220) used a standard gender-neutral simulator (control group) or a modified simulator with a female-like appearance (intervention group). Pre- and post-training questionnaires concerning attitudes and knowledge plus a post-training skills evaluation assessed the students�f training outcomes. The intervention group initiated chest compressions significantly faster than the control group (33.1 vs. 39.8 sec, p<0.01) and achieved a significantly higher rate of correct AED pad placement (64.2% vs. 38.5%, p<0.01). While performing the resuscitation on the female-appearing manikin, the intervention group showed significantly greater increases in self-efficacy (p<0.01) and larger decreases in discomfort about removing the patient�fs clothes (p<0.01). They were also significantly more likely to recognize that chest compressions can be performed (p=0.016) and AED pads can be applied (p=0.015) without removing the patient�fs underwear. Using a female-appearing simulator in BLS training was thus associated with faster chest compression initiation, more accurate AED pad placement, and improved gender-sensitive attitudes and knowledge. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Oral Eicosapentaenoic Acid and Paclitaxel-Associated Peripheral Neuropathy: A Retrospective Study at Okayama University Hospital 179 184 EN Ayako Morita Center for Clinical Oncology, Okayama University Hospital Hideki Katayama Center for Clinical Oncology, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Original Article 10.18926/AMO/70853 This retrospective study investigated whether eicosapentaenoic acid (EPA) reduces paclitaxel-associated chemotherapy-induced peripheral neuropathy (CIPN) and acute neuropathic pain in dyslipidemic cancer patients. The medical records of cancer patients treated with paclitaxel or nab-paclitaxel at Okayama University Hospital between January 2018 and December 2022 were reviewed. Patients receiving concomitant therapy for dyslipidemia were categorized as EPA users or non-EPA users. Numbness and pain severity were extracted from medical records. The primary endpoint was the change from baseline in Common Terminology Criteria for Adverse Events (CTCAE) grade for peripheral neuropathy and pain; groups were analyzed using the Mann–Whitney U test. Of 184 eligible patients, 18 received EPA. Bleeding events were more frequent in the EPA group; however, changes in numbness and pain did not differ significantly between groups at any time point. Overall, EPA did not show a preventive effect on paclitaxel-associated CIPN or acute neuropathic pain. Future studies should evaluate EPA in combination with other neuroprotective agents to better define its potential role in CIPN prevention. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Peripheral Blood T-Cell Receptor Repertoire and Host Immune Background in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy 169 178 EN Yuki Nakamura Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Takayuki Iwamoto Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Yukiko Kajiwara Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Akira Hida Department of Pathology, Matsuyama Shimin Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Yuichiro Miyoshi Department of Breast Endocrine Surgery, Kagawa Prefectural Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Masahiko Ikeda Department of Breast and Thyroid Surgery, Fukuyama City Hospital Hiroyoshi Doihara Department of General Surgery, Kawasaki Medical School General Medical Center Ryohei Ogata Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Yoshikazu Koike Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Tsunehisa Nomura Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Katsuhiro Tanaka Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Kazutaka Nakashima Department of General Surgery, Kawasaki Medical School General Medical Center Tomoki Yamatsuji Department of General Surgery, Kawasaki Medical School General Medical Center Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Original Article 10.18926/AMO/70852 The association between peripheral blood T-cell receptor (TCR) repertoire and chemotherapy response remains unclear. We evaluated peripheral blood TCR repertoire and gut microbiota in 21 breast cancer patients receiving neoadjuvant chemotherapy (NAC) who were enrolled in the SBP-14 prospective cohort study between October 2019 and March 2022. We analyzed stool samples obtained pre-NAC and peripheral blood samples obtained pre- and post-NAC. The primary endpoint was the association between baseline peripheral blood TCR repertoire and treatment response. Eleven patients (52%) had hormone receptor-positive breast cancer. All patients received anthracyclines and taxanes, with anti-HER2 therapy for HER2-positive disease. TCR diversity (TCR alpha chain [TRA], p=0.095; TCR beta chain [TRB], p=0.051) and clonality (TRA, p=0.271; TRB, p=0.500) were not significantly associated with treatment response. Gut microbiota diversity was not correlated with TCR diversity (TRA: ƒÏ=0.046, p=0.845; TRB: ƒÏ=0.021, p=0.929); however, three bacterial orders (Erysipelotrichales, Bacillales, and Pasteurellales) were significantly associated with TCR repertoire. Baseline TCR repertoire was not associated with treatment response in this cohort of breast cancer patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Self-Reported Adolescent Menstrual Symptoms and Delayed Gynecologic Consultation among Japanese Women with Endometriosis 159 168 EN Tomoko Ikeda Faculty of Health Sciences, Okayama University Mikiya Nakatsuka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/70851 Endometriosis symptoms often first appear during adolescence, yet delays in seeking gynecologic consultation remain a persistent challenge worldwide. Despite growing international evidence, the specific patterns of symptom recognition and consultation delay among Japanese women �\ particularly in relation to self-monitoring behaviors and cultural barriers �\ remain poorly understood. This study aimed to provide foundational data to guide menstrual education and preconception care strategies by conducting a cross-sectional online survey with retrospective recall among women with endometriosis to assess menstrual characteristics and symptom patterns from adolescence to initial care seeking. The survey was conducted in Japan in January 2024 and enrolled 166 women with endometriosis and 200 controls. Participants reported current and adolescent menstrual characteristics, symptom recognition, analgesic and low-dose estrogen–progestin use, school/work impact, and age at first gynecologic consultation for menstrual problems. Women with endometriosis reported heavier bleeding, stronger pain, and greater school/work absence than controls, both currently and retrospectively. The median age at first recognition of heavy bleeding or school/work absence was 16 years, whereas consultation occurred at approximately 21-23 years, indicating a consultation delay of 5-6 years. Notably, while self-monitoring of symptoms was more frequent among women with endometriosis, it only modestly shortened consultation delays. This study provides evidence from Japan that consultation delay persists despite active self-monitoring of symptoms, highlighting the influence of educational and cultural barriers on health-seeking behavior. These findings underscore the importance of integrating menstrual education with clinical guidance to promote timely gynecologic consultation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0721-832X 2026 Age-related changes in the orbital pulley array of older Japanese adults with acquired exotropia EN Reika Kono Department of Ophthalmology,, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ichiro Hamasaki Lino Eye Clinic Fumiko Kishimoto Division of Ophthalmology, Ibara City Hospital Kiyo Shibata Lino Eye Clinic Shin Morisawa Department of Ophthalmology,, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology,, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose: To evaluate age-related changes in the orbital pulley array using magnetic resonance imaging (MRI) in older Japanese adults with acquired exotropia (XT) compared with young healthy participants (YHP).<br> Methods: In this retrospective cross-sectional case series, MRI images of 30 eyes from fifteen patients (age ≥ 60 years) with distance XT and no high myopia were compared with those of 14 eyes from seven YHP. Rectus muscle (RM) pulley positions relative to the globe center were assessed. The lateral rectus muscle–superior rectus (LR–SR) band was evaluated for rupture.<br> Results: Mean age of patients with XT was 73.7 �} 5.5 years. Compared with YHP, patients with XT showed significant inferior displacement of the lateral rectus (LR) pulley (–3.6 �} 1.2 mm vs. �| 2.0 �} 1.1 mm, p < 0.01) and temporal displacement of the superior rectus (SR) pulley (–0.4 �} 1.2 mm vs. �| 1.6 �} 0.8 mm, p < 0.01). No significant differences were observed in medial rectus or inferior rectus pulley positions. Inferior LR pulley displacement correlated with inferior SR pulley displacement (r = 0.41, p = 0.03), whereas no significant relationship was observed between LR pulley position and MR or IR pulley position. Rupture of the LR–SR band was observed in 24 orbits (80.0%).<br> Conclusion: Older Japanese adults with XT exhibit localized pulley displacement and LR–SR band rupture. These structural changes differ from the global sagging observed in sagging eye syndrome and may contribute to the pathogenesis of acquired exotropia in older adults. No potential conflict of interest relevant to this article was reported.

American Physiological Society Acta Medica Okayama 1040-0605 330 5 2026 The role of S100A8/A9 in the pathogenesis of acute exacerbations of pulmonary fibrosis L593 L609 EN Naoki Nakamura Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hisao Higo Department of Allergy and Respiratory Medicine, Okayama University Hospital Satoru Senoo Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akihiko Taniguchi Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Taichi Ozeki Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryota Sunami Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yumi Inukai Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shusei Yamamoto Department of Medical Laboratory Science, Okayama University Faculty of Health Sciences Junko Itano Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ayaka Tanaka Department of Respiratory Medicine, Kurashiki Central Hospital Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Acute exacerbation of idiopathic pulmonary fibrosis is a life-threatening condition characterized by neutrophilic inflammation. S100A8/A9, an alarmin released by activated neutrophils and monocytes/macrophages, plays a pivotal role in regulating inflammatory responses. However, its specific involvement in acute exacerbations of pulmonary fibrosis remains unclear. This study evaluated the role of S100A8/A9 in the pathogenesis of acute exacerbations of pulmonary fibrosis. S100A8/A9 levels were measured in bronchoalveolar lavage fluid and serum from patients with idiopathic interstitial pneumonia, with and without acute exacerbations. To model acute exacerbations of pulmonary fibrosis, mice were intratracheally administered bleomycin followed by lipopolysaccharide. Subsequently, inflammatory cell infiltration, cytokine levels, morphological changes, and fibrosis marker levels in lung tissue and airways were analyzed. S100A8/A9 levels were significantly higher in the bronchoalveolar lavage fluid and serum of patients with idiopathic interstitial pneumonia experiencing acute exacerbations relative to those without; these levels were correlated with patient prognosis. In an experimental mouse model, intratracheal administration of bleomycin followed by lipopolysaccharide resulted in a significant increase in airway S100A8/A9 levels compared with bleomycin alone and control mice. Anti-S100A8/A9 neutralizing antibody Ab45 mitigated airway inflammation and lung fibrosis in mice with acute exacerbations of pulmonary fibrosis, reducing S100A8/A9 levels and neutrophil extracellular traps. In vitro, recombinant S100A8/A9 or lipopolysaccharide and neutrophils activated and differentiated fibroblasts; these effects were inhibited by anti-S100A8/A9 neutralizing antibody Ab45 and the humanized form of Ab45 (HuAb45). These findings highlight S100A8/A9 as a potential prognostic biomarker and therapeutic target for acute exacerbations of pulmonary fibrosis. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2576-098X 15 4 2026 Draft genome sequence of blaIMP-1-carrying Phytobacter ursingii OUH-01, isolated from the feces of an acute lymphoblastic leukemia patient e0087625 EN Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Iori Urakami Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences We report the 5.7 Mbp draft genome of carbapenem-resistant Phytobacter ursingii strain OUH-01, recovered from the feces of a patient with acute lymphoblastic leukemia. The genome comprises a chromosome (G+C content of 53.5%), three plasmids, and four linear contigs, including the 222 kb plasmid pOUH-phyto-IMP-01 carrying blaIMP-1. Nanopore/Illumina sequencing achieved 235�~ coverage. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0950-9232 45 18 2026 Trisomy 8 alters chromatin conformations and activates Y chromosome genes in stem cells to drive a pre-leukemic state 1675 1687 EN Jie Bai Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University Kimi Araki Institute of Resource Development and Analysis, Kumamoto University Daisuke Kurotaki Laboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto University Eerdunduleng Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University Supannika Sorin Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University Kei Hiramatsu Department of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori University Narumi Uno Laboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences Ai Hamashima Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University Mihoko Iimori Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University Kenta Kikuchi Laboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto University Minoru Terashima Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University Sho Kubota Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensaku Kohrogi Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University Gang Huang Department of Cell Systems & Anatomy, Department of Pathology & Laboratory Medicine, UT Health San Antonio, Joe R. and Teresa Lozano Long School of Medicine, Mays Cancer Center at UT Health San Antonio Minetaro Ogawa Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University Mitsuo Oshimura Chromosome Engineering Research Center, Tottori University Yasuhiro Kazuki Department of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori University Goro Sashida Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University The mechanistic role of trisomy 8 in the development of myelodysplastic syndrome (MDS) remains poorly defined. Here, we generated a trisomy 8 mouse model by transferring a human chromosome 8 into murine embryonic stem cells and prospectively examined the effects on hematopoietic stem cells (HSC) by trisomy 8. The expression of inflammatory genes was enhanced, and hematopoietic programs mediated by transcription factors and polycomb repressive complex 2 (PRC2) were dysregulated in trisomy 8 HSC, which impaired their self-renewal and balanced differentiation. Trisomy 8 HSC altered the chromatin accessibility and conformations and activated Y chromosome genes, such as Uty/Kdm6c epigenetic modifier, which is known to demethylate histone H3K27me3 modification. The Uty gene facilitated the activation of PRC2-target and Runx1-target genes in leukemogenesis and drove the proliferation of human trisomy 8 leukemic cells. Since the RUNX1 gene is frequently mutated in patients with trisomy 8 MDS, its deletion attenuated the enhanced expression of inflammatory genes and mitigated the impaired self-renewal of trisomy 8 HSC in mice. Our findings reveal that trisomy 8 altered the transcriptional programs and chromatin conformations in HSC and drove a pre-malignant state through activating the expression of Uty, suggesting a route for the development of trisomy 8 MDS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 17 1 2026 Structural insights into YheS-mediated release of SecM-arrested ribosome 4963 EN Kaishi Iso Department of Biological Sciences, Graduate School of Science, The University of Tokyo Toma Ikeda School of Life Science and Technology, Institute of Science Tokyo Kohei Yamasaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yushin Ando Department of Biological Sciences, Graduate School of Science, The University of Tokyo Fumiya K. Sano Department of Biological Sciences, Graduate School of Science, The University of Tokyo Tadaomi Furuta School of Life Science and Technology, Institute of Science Tokyo Hideki Taguchi School of Life Science and Technology, Institute of Science Tokyo Osamu Nureki Department of Biological Sciences, Graduate School of Science, The University of Tokyo Yuhei Chadani Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuzuru Itoh Department of Biological Sciences, Graduate School of Science, The University of Tokyo ATP-binding cassette subfamily F (ABCF) proteins interact with the ribosome to resolve translation defects near the peptidyl transferase center (PTC). In Escherichia coli, four ABCF proteins (EttA, Uup, YbiT, and YheS) selectively promote translation of distinct problematic nascent peptide sequences, but their molecular mechanisms remain unclear. Here, we present a 2.8 Å cryo-EM structure of the ribosome in complex with an ATPase-deficient mutant of YheS and investigate how it releases ribosomes arrested by the SecM nascent chain. YheS binds to the ribosomal E-site via the L1 stalk, and its P-site tRNA-interaction motif (PtIM) extends toward the PTC, displacing the CCA end of the P-site tRNA. Notably, the cryo-EM density corresponding to the SecM nascent chain within the exit tunnel is largely lost upon YheS binding. These observations suggest that YheS relieves peptide sequence-dependent stalling by perturbing nascent chain-tunnel interactions through P-site tRNA relocation. Steered molecular dynamics simulations provide qualitative support for this model. Together, our findings provide mechanistic insight into a mode of arrest release distinct from the translocon-mediated release mechanism. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1755-4330 18 6 2026 Two-dimensional metal–organic frameworks offer all-in-one cocatalysts for photocatalytic overall water splitting 1053 1061 EN Jingyan Guan Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University Hajime Suzuki Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University Kazuhide Kamiya Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Takashi Harada Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Rintaro Adachi Graduate School of Natural Science and Technology, Okayama University Osamu Tomita Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University Hirofumi Kurokawa Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Daisuke Unabara Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Koji Yonekura Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Naoya Fukui Research Institute for Science and Technology, Tokyo University of Science Hiroaki Maeda Research Institute for Science and Technology, Tokyo University of Science Kunihisa Sugimoto Department of Chemistry, Kindai University Yuichi Yamaguchi Department of Applied Chemistry, Faculty of Science, Tokyo University of Science Akinori Saeki Innovative Catalysis Science Division, Institute for Open and Transdisciplinary Research Initiatives, The University of Osaka Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Akihiko Kudo Department of Applied Chemistry, Faculty of Science, Tokyo University of Science Ryu Abe Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University Ryota Sakamoto Department of Chemistry, Graduate School of Science, Tohoku University Photocatalytic overall water splitting holds great promise for sustainable hydrogen production. For overall water splitting performed by one-step excitation, both the hydrogen evolution and oxygen evolution reactions are hindered kinetically; hence, it is necessary to employ site-selective modification of photocatalysts with hydrogen-evolving and oxygen-evolving cocatalysts. However, critical challenges remain, including the need for cumbersome, multi-step photodeposition processes and durable blocking layers to inhibit the reverse reactions. Here we find a conductive, two-dimensional metal–organic framework to serve as a simple, multifunctional cocatalyst. We loaded this framework on SrTiO3:Al, an overall water-splitting photocatalyst, using a one-step self-assembly method. The framework cocatalyst promoted steady photocatalysis with an apparent quantum efficiency of 31.5% at 350 nm, free from the reverse reaction even without blocking layers. We proposed the operational principles for the cocatalyst activity using spectroscopic, electrochemical and theoretical analyses. This two-dimensional metal–organic framework offers an all-in-one approach for designing efficient and practical one-step excitation overall water-splitting systems. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2026 Afatinib Overcomes Osimertinib Resistance via Egfr V804F Mutation in a Syngeneic Egfr-Mutant Lung Cancer Mouse Model 1 17 EN Takaaki Tanaka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Fujitani Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research Masataka Taoka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Iwao Shimomura Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research Sachi Okawa Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunta Mori Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadahiro Kuribayashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Nishimura Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Nishimura Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayako Morita Department of Hematology, Oncology and Respiratory Medicine, Okayama University Naofumi Hara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Go Makimoto Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hisao Higo Department of Hematology, Oncology and Respiratory Medicine, Okayama University Kammei Rai Department of Hematology, Oncology and Respiratory Medicine, Okayama University Eiki Ichihara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Yosuke Togashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Hematology, Oncology and Respiratory Medicine, Okayama University Ryohei Katayama Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Osimertinib is the standard first-line treatment for advanced EGFR-mutant non-small cell lung cancer. However, acquired resistance invariably develops, and identifying novel resistance pathways is clinically important as a substantial portion remains undefined. We used an immunocompetent syngeneic lung cancer mouse model harboring an Egfr exon 19 deletion (mDEL tumors) to establish acquired resistance. Osimertinib-resistant tumors were generated in vivo using a drug-holiday/re-challenge protocol. The resistance mechanism was identified using Sanger sequencing, receptor tyrosine kinase arrays, and western blotting. Egfr V804F knock-in cells were generated using CRISPR/Cas9, and their sensitivity to osimertinib and afatinib was assessed in vitro and in vivo. We established two distinct osimertinib-resistant tumor lines in a syngeneic lung cancer mouse model (mDEL OsiR #1/#3). The analysis revealed an on-target secondary Egfr V804F mutation (corresponding to human EGFR V802F) in both tumor lines. Importantly, Egfr V804F knock-in cells demonstrated significant osimertinib resistance, with a 5.7–10.5-fold increase in in vitro IC50 (mean, 8.2-fold), but remained highly sensitive to afatinib. Furthermore, afatinib effectively overcame osimertinib resistance in the V804F knock-in cell-derived mouse model. Consistently, afatinib treatment resulted in marked tumor shrinkage and suppression of EGFR signaling in the established mDEL OsiR #1/#3 in vivo. These findings establish secondary Egfr V804F/EGFR V802F as an on-target osimertinib resistance mechanism, providing a preclinical rationale for evaluating afatinib in biomarker-selected patients harboring this alteration. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1877-959X 17 3 2026 Epidemiological and molecular characteristics of human-biting ticks in areas endemic to Japanese spotted fever: a prospective study 102635 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Sunami Sumiyoshi Fujii Hospital Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Nakamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidemasa Akazawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshimi Hidani Numakuma Hospital Kouji Kida Okayama Prefectural Institute for Environmental Science and Public Health Go Tsurumi Okayama Prefectural Institute for Environmental Science and Public Health Hideharu Hagiya Tick-borne diseases (TBDs) have become a great health concern worldwide. This study aimed to clarify the pathogenic and potentially pathogenic microorganisms carried by ticks that bite humans and to assess the risk of acquiring tick-borne infections in regions endemic for Japanese spotted fever. Tick specimens were prospectively collected from patients who presented with tick bites at 10 medical institutions in the Hiroshima, Okayama, and Kagawa prefectures, Japan between May 2023 and December 2024. The evaluated parameters included the estimated bite location, date of bite, patient age, tick species identification, and presence of TBD-associated pathogens in the collected ticks. Overall, 191 ticks were collected from 181 patients. Among patients with known sex, females were slightly more prevalent than males, and 45.9% of the patients were aged ≥ 70 years. Seasonal distribution demonstrated a peak incidence from April to July, with the highest number of cases observed in June (29.3%). Amblyomma testudinarium was the predominant species, accounting for 152 (79.6%) ticks, followed by Haemaphysalis hystricis (7.3%) and Haemaphysalis longicornis (6.8%). Nymphs represented the majority (83.8%), whereas adults and larvae accounted for 14.6% and 1.0%, respectively. A total of 27 ticks (14.1%) carried Rickettsia species, including two identified species (Rickettsia tamurae and Rickettsia monacensis) and one unclassified Rickettsia species. However, molecular analysis did not detect any known human pathogenic organisms, including Ehrlichia and Anaplasma species, Francisella tularensis, or Rickettsia japonica. Further epidemiological data regarding the abundance of tick-borne pathogens will provide valuable surveillance information with significant clinical utility for disease diagnosis and management. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-1262 41 1 2026 Navigating long-term patient-reported outcomes after colorectal cancer surgery in older adults: ostomy, nutritional status, and living conditions as determinants in a prospective cohort study 97 EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Hospital Shiori Itagaki Perioperative Management Center, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Rie Tamura Perioperative Management Center, Okayama University Hospital Yoshikazu Matsuoka Perioperative Management Center, Okayama University Hospital Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Hospital Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Hospital Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Hospital Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Hospital Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Purpose To elucidate determinants of long-term patient-reported outcomes (PROs) following colorectal cancer (CRC) surgery in older adults, focusing on the impact of ostomy creation, nutritional status, and living conditions on functional independence and quality of life (QoL).<br> Methods This single-center, prospective observational study included patients aged ≥ 75 years who underwent elective CRC resection between July 2020 and December 2023. Comprehensive geriatric assessments were performed preoperatively, and PROs�\including Instrumental Activities of Daily Living (IADL), EQ-5D, and EQ-VAS�\were reassessed more than one year postoperatively. The primary outcomes were postoperative changes in IADL and QoL. Modified Poisson regression identified independent determinants of long-term decline in each PRO domain.<br> Results Sixty patients (median age 79 years; 60% female) completed one-year follow-up. IADL declined in 35.6% of patients, EQ-5D in 26.6%, and EQ-VAS in 43.3%. Multivariate analysis revealed that stoma formation was independently associated with IADL decline (adjusted RR = 3.37, 95% CI 1.50–7.54, p = 0.003), whereas living alone postoperatively correlated with preserved IADL (adjusted RR = 0.14, 95% CI 0.02–0.87, p = 0.035). Low preoperative BMI (< 20 kg/m2) was significantly associated with EQ-5D deterioration (adjusted RR = 5.25, 95% CI 1.20–22.94, p = 0.027). No significant predictors were identified for EQ-VAS decline.<br> Conclusion Among older CRC patients, stoma creation predicts long-term functional decline, while low BMI predicts QoL deterioration. Conversely, independent living appears protective for functional maintenance. Integrating PROs into perioperative assessment and tailoring surgical, nutritional, and social interventions may enhance survivorship outcomes in this aging population. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 18 7 2026 Predictive Nomogram for Recurrence After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2) 1181 EN Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masayoshi Hioki Department of Surgery, Fukuyama City Hospital Takehiro Okabayashi Department of Surgery, Kochi Health Sciences Center Toru Kojima Department of Surgery, Okayama Saiseikai General Hospital Yoshikatsu Endo Department of Surgery, Himeji Red Cross Hospital Daisuke Nobuoka Department of Surgery, Fukuyama City Hospital Kenta Sui Department of Surgery, Kagawa Prefectural Hospital Masaru Inagaki Department of Surgery, National Hospital Organization Fukuyama Medical Center Susumu Shinoura Department of Surgery, Tsuyama Chuo Hospital Masashi Kimura Department of Surgery, Matsuyama Shimin Hospital Tatsuo Matsuda Department of Surgery, Tenwakai Matsuda Hospital Hideki Aoki Department of Surgery, National Hospital Organization Iwakuni Clinical Center Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Objectives: Postoperative recurrence is a critical issue in the treatment of resectable pancreatic ductal adenocarcinoma (rPDAC). Moreover, the prognosis after early recurrence is extremely poor. This study aimed to develop a recurrence prediction model and to define early recurrence after upfront surgery (UFS) for rPDAC. Methods: This multicenter retrospective study included patients who underwent UFS for anatomically rPDAC between January 2013 and December 2017. Multivariate analyses were conducted to identify the risk factors for recurrence-free survival and to construct a recurrence prediction model. Subsequently, a minimum p value approach was used to determine the optimal cutoff values for early and late recurrence. Results: The cohort included 603 patients (325 men and 278 women). During the median follow-up period of 25 months (interquartile range, 15–38 months), 381 patients (63.2%) experienced a recurrence. Multivariate analyses revealed carbohydrate antigen 19-9 ≥37 U/mL (hazard ratio [HR], 1.58; p < 0.001), tumor size ≥ 2.2 cm (HR, 1.59; p < 0.001), lymph node metastasis (HR, 1.86; p < 0.001), R1 resection (HR, 1.56; p = 0.002), and no adjuvant chemotherapy (HR, 1.54; p < 0.001) as independent predictors. The recurrence prediction model demonstrated an area under the curve of 0.72–0.75. The optimal threshold for early and late recurrences was a recurrence-free interval of five months. Carbohydrate antigen 19-9 ≥ 156 U/mL was a significant predictor of early recurrence (OR, 3.28; p < 0.001). Conclusions: This study identified the prognostic risk factors for recurrence and developed a recurrence prediction model for patients undergoing UFS for rPDAC. Moreover, a recurrence-free interval of five months was identified as the optimal threshold for distinguishing between early and late recurrences. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 22 2025 Prognosis Prediction Model After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2) 3694 EN Kosei Takagi Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ryuichi Yoshida Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuya Yasui Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masayoshi Hioki Department of Surgery, Fukuyama City Hospital Takehiro Okabayashi Department of Surgery, Kochi Health Sciences Center Toru Kojima Department of Surgery, Okayama Saiseikai General Hospital Yoshikatsu Endo Department of Surgery, Himeji Red Cross Hospital Daisuke Nobuoka Department of Surgery, Fukuyama City Hospital Kenta Sui Department of Surgery, Kagawa Prefectural Hospital Masaru Inagaki Department of Surgery, National Hospital Organization Fukuyama Medical Center Susumu Shinoura Department of Surgery, Tsuyama Chuo Hospital Masashi Kimura Department of Surgery, Matsuyama Shimin Hospital Tatsuo Matsuda Department of Surgery, Tenwakai Matsuda Hospital Hideki Aoki Department of Surgery, National Hospital Organization Iwakuni Clinical Center Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background/Objectives: Upfront surgery (UFS) remains the standard treatment for patients with resectable pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the prognostic factors for survival after UFS in patients with resectable PDAC and to develop a prognostic prediction model. Methods: This multicenter, retrospective study included 603 patients who underwent UFS for resectable PDAC between January 2013 and December 2017. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival (OS). We constructed a prognostic prediction model for OS after UFS. An internal validation was performed to evaluate the discriminative performance of the model. Results: The 1-, 3-, and 5-year OS rates were 83.7%, 48.2%, and 37.5%, respectively. The Cox proportional hazards model showed that tumor size > 2 cm (hazard ratio [HR] 1.50, p = 0.001); tumor contact with the portal and superior mesenteric veins of ≤180�‹ (HR 1.47, p = 0.003); carbohydrate antigen 19-9 levels of 40 to 500 U/mL (HR 1.59, p = 0.002) and ≥500 U/mL (HR 2.16, p < 0.001); and a modified Glasgow Prognostic Score of two (HR 1.56, p = 0.038) were predictors associated with OS. The prognostic prediction model for 5-year OS demonstrated an area under the curve of 0.68. The calibration plots indicate a concordance index of 0.63. Conclusions: We identified the preoperative prognostic factors for OS and developed a prognostic prediction model to estimate OS in patients undergoing UFS for resectable PDAC. Our model may be useful and internally validated for predicting OS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 33 7 2026 Association of Preoperative Inspiratory Muscle Weakness and Respiratory Sarcopenia with Postoperative Pneumonia Following Esophagectomy: A Multicenter Retrospective Cohort Study 6296 6305 EN Kazuki Okura Department of Rehabilitation Medicine, Akita University Hospital Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Hospital Hiroki Sato Department of Rehabilitation, Kawasaki University of Medical Welfare Sho Katayama Department of Rehabilitation Medicine, Okayama University Hospital Yusuke Takahashi Department of Rehabilitation Medicine, Akita University Hospital Yushi Nagaki Department of Esophageal Surgery, Akita University Hospital Akiyuki Wakita Department of Esophageal Surgery, Akita University Hospital Naoaki Maeda Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Tanabe Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Fujiwara Department of Digestive Surgery, Kawasaki Medical School Kazuhiro Noma Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Sato Department of Esophageal Surgery, Akita University Hospital Yuji Kasukawa Department of Rehabilitation Medicine, Akita University Hospital Naohisa Miyakoshi Department of Rehabilitation Medicine, Akita University Hospital Background Esophagectomy is associated with a high rate of postoperative pneumonia, which significantly impacts patient outcomes, including survival and quality of life. While some modifiable risk factors have been identified, the specific role of preoperative respiratory muscle function remains to be fully elucidated. Therefore, this study was designed to investigate the association of preoperative inspiratory muscle weakness (IMW) and respiratory sarcopenia (RS) with postoperative pneumonia in patients with esophageal cancer who underwent esophagectomy.<br> Methods Patients with esophageal cancer who underwent esophagectomy between July 2021 and June 2023 were enrolled in this multicenter, retrospective, cohort study. The primary outcome was postoperative pneumonia, while preoperative IMW and RS were the main exposures. Respiratory sarcopenia was defined as the presence of both IMW and low skeletal muscle mass, which is assessed by using bioelectrical impedance analysis. Associations were analyzed by using G-computation within a Bayesian framework.<br> Results A total of 213 patients were enrolled in this study. Postoperative pneumonia occurred in 42 patients (19.7%). Preoperative IMW was strongly associated with an increased risk of pneumonia, with a mean risk difference (RD) of 18.1% (95% credible interval [CrI] 5–33.6). The posterior probability that the RD exceeds 5% was > 98%. Respiratory sarcopenia also showed a potential association, although with greater uncertainty (mean RD, 11.2%; 95% CrI �| 3.8 to 27.9). The posterior probability that the RD exceeds 5% was 76.7%.<br> Conclusions Preoperative IMW is a notable risk factor for postoperative pneumonia following esophagectomy. While a potential link with RS was found, its role remains uncertain and requires further investigation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2026 Atezolizumab + Chemotherapy in Older Patients With Lung Cancer in Japan 1 13 EN Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Ichiro Yoshino International University of Health and Welfare Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Kozo Yoshimori Department of Clinical Oncology, Japan Anti�]Tuberculosis Association, Fukujuji Hospital Kazuhiko Shibata Department of Medical Oncology, Kouseiren Takaoka Hospital Takeshi Tsuda Division of Respiratory Medicine, Toyama Prefectural Central Hospital Masahiro Seike Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Takahiro Ota Department of Respiratory Medicine, Kyoto City Hospital Koichi Samata Chugai Pharmaceutical Co., Ltd. Yuki Kobayashi Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School Pivotal phase 3 trials leading to the approvals of atezolizumab„Ÿchemotherapy combinations for non-small cell and extensive-stage small cell lung cancer (NSCLC and ES-SCLC) had strict eligibility criteria. J-TAIL-2 was a prospective, observational study in Japan that evaluated atezolizumab regimens for advanced NSCLC/ES-SCLC, including patients ineligible for global trials. The primary endpoint was 12-month overall survival (OS); safety and efficacy in subgroups defined by age, ECOG PS and/or G8 score, and creatinine clearance were key secondary endpoints. As of February 3, 2023, 1217 patients were treated in clinical practice based on Japanese labeling/treatment guidelines. Patients received atezolizumab with either carboplatin and nab-paclitaxel (atezo + CnP), carboplatin/cisplatin and pemetrexed (atezo + PP), or bevacizumab and carboplatin and paclitaxel (atezo + bev + CP) in the NSCLC cohort (n = 814) or with carboplatin and etoposide (atezo + CE) in the ES-SCLC cohort (n = 403). Overall, 53.5% were ≥ 70 years old, and 11.8% had ECOG PS ≥ 2; median G8 scores were 13 (NSCLC cohort) and 12 (ES-SCLC). Patients < 70 and ≥ 70 years had similar median (m)OS and progression-free survival (mPFS) across treatment regimens. Patients with ECOG PS < 2 and G8 score ≥ median had the highest mOS/PFS vs. patients with ECOG PS ≥ 2 and G8 score<median. Patients ≥ 70 years had higher incidence of Grade ≥ 3 adverse events with atezo + CnP and atezo + PP than patients < 70 years; incidences were similar between groups for other regimens. Older vs. younger patients also had higher incidence of interstitial lung disease. Overall, these results suggest that atezolizumab-containing regimens remain effective in older patients, with no new safety signals. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2026 Plasma Protein Analysis for Biomarker Discovery in Lung Cancer Treated With Atezolizumab Combination Therapy in J-TAIL-2 1 13 EN Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Ichiro Yoshino Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Yasutaka Watanabe Department of Thoracic Oncology, Saitama Cancer Center Nobuyuki Katakami Department of Pulmonary Medicine and Medical Oncology Takarazuka City Hospital Takarazuka Japan Akira Kisohara Department of Respiratory Medicine, Kasukabe Medical Center Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Hirotaka Kuroki Chugai Pharmaceutical Co., Ltd. Masamichi Sugimoto Chugai Pharmaceutical Co., Ltd. Hisao Ashimura Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School J-TAIL-2 evaluated the efficacy and safety of atezolizumab, an anti–programmed death-ligand 1 (PD-L1), plus chemotherapy in patients with non-small cell lung cancer (NSCLC) and extensive-stage small cell lung cancer (ES-SCLC) in Japanese clinical practice, demonstrating comparable outcomes to those in the corresponding Phase 3 trials. Although PD-L1 expression is predictive of atezolizumab efficacy in some settings, additional minimally invasive, blood-based biomarkers are needed. This exploratory biomarker study included 359 J-TAIL-2 patients. The NSCLC cohort received atezolizumab combined with carboplatin and nab-paclitaxel (CnP, n = 42), cisplatin/carboplatin and pemetrexed (n = 72), or bevacizumab plus carboplatin and paclitaxel (bev + CP, n = 135). The ES-SCLC cohort received atezolizumab plus carboplatin and etoposide (n = 100). Approximately 560 cancer- or immune-related proteins were evaluated using the Proximity Extension Assay from blood plasma collected at three timepoints: baseline, before the second atezolizumab dose, and at the onset of immune-related adverse events (irAEs). Protein-wise comparisons were made to evaluate significant changes (P < 0.05 and > 0.5 log2 fold change) and linked to clinical outcomes reported in J-TAIL-2. IL-6, MUC-16, and KRT-19 were associated with shorter progression-free survival across multiple regimens. Granzyme A and B, immune activation markers, were elevated in responders who received atezolizumab + CnP and atezolizumab + bev + CP. High levels of baseline immune stimulation proteins were associated with irAEs across regimens. Protein expression changes were varied and regimen-dependent in subgroup analyses including older patients and those with EGFR-mutant tumors. These data warrant further investigation across different cancer types and atezolizumab-containing regimens to determine their relevance to efficacy and irAE occurrence of atezolizumab combination therapy. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 10 2026 Exploratory Analysis of Serum IGF-I Levels and Symptom Trajectories in Long COVID During the Omicron Period 3702 EN Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Takase Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Although several risk factors have been reported for long COVID (LC), reliable biomarkers for this illness remain lacking. Insulin-like growth factor (IGF)-I, a major mediator of growth hormones, plays an important role in metabolism, neuroprotection, and systemic homeostasis, and therefore may be useful in predicting the severity and prognosis of LC. Methods: This study included patients who visited a specialized clinic for long COVID between 2022 and 2025 during the Omicron period and had serum IGF-I measurements taken. IGF-I levels were expressed as age- and sex-adjusted standard deviation scores (IGF-I SD), and patients were classified into low (SD < �|1.0), normal (�|1.0 ≤ SD < 1.0), and high (SD ≥ 1.0) groups. Clinical characteristics, patient-reported outcomes, laboratory data, and follow-up duration were analyzed. Results: A total of 811 patients were included (median 42 years; 52.5% female). Compared with the normal group, the low-IGF-I group exhibited higher fatigue (FAS: 37.0 vs. 34.0; p < 0.05) and depressive (SDS: 50.0 vs. 49.0; p < 0.05) status. Multivariable linear regression analyses identified lower IGF-I SD as independently associated with higher scores of both FAS and SDS. IGF-I SD values showed negative correlations with ferritin (ƒÏ = �|0.125, p < 0.05) and TSH (ƒÏ = �|0.202, p < 0.01) and positive correlations with albumin (ƒÏ = 0.227, p < 0.01) and FT4 (ƒÏ = 0.165, p < 0.01). Among the 237 patients who completed follow-up, the median duration from the initial visit to recovery tended to be longer in the low-IGF-I group (221 days) compared with the normal (191 days) and high (109 days) groups, although these differences were not statistically significant overall. In patients aged < 50 years, the low-IGF-I group showed a relatively longer follow-up duration (p < 0.05). Furthermore, the low-IGF-I group had a longer time to recovery compared to the high-IGF-I group (p < 0.05), and this difference was more pronounced in patients under 50 years of age, with significant differences observed among the three IGF-I groups. Conclusions: Lower IGF-I levels in LC may be associated with greater fatigue and depressive symptoms and longer recovery time, particularly in younger patients. Further studies are needed to clarify the clinical significance of these findings. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1663-9812 17 2026 Hochuekkito attenuates anxiety-like behavior associated with pulmonary inflammation induced by intratracheal lipopolysaccharides in mice 1774957 EN Yasuhisa Izushi Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University Soichiro Ushio Department of Pharmaceutical Sciences for Health Crisis Management, Faculty of Pharmaceutical Sciences, Fukuoka University Teppei Ueda Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University Yuichi Tasaka Laboratory of Clinical Pharmacy, School of Pharmacy, Shujitsu University Ikuko Miyazaki Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masato Asanuma Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihisa Kitamura Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University Introduction: We have previously demonstrated that intratracheal lipopolysaccharide (LPS) injection induces significant pulmonary inflammation accompanied by hippocampal microglial activation, indicative of neuroinflammation. Hochuekkito (HET) is a traditional Japanese herbal medicine used to treat various conditions, including mental disorders and physical weakness. We have previously reported that HET ameliorates anxiety-like behaviors induced by intraperitoneal LPS injections in mice. However, its anxiolytic effects on anxiety-like behaviors due to pulmonary inflammation remain poorly understood. Therefore, in the present study, we aimed to investigate the effects of HET on anxiety-like behaviors induced by intratracheal LPS injection in mice.<br> Methods: Mice received HET (1.0 g/kg) once daily for 2 weeks through oral gavage prior to LPS treatment. The light-dark box test was conducted 24 h following LPS injection to assess anxiety-like behaviors. Diazepam, a clinically used anxiolytic, served as a positive control. The lung wet-to-dry weight ratio was determined, and the concentrations of interleukin-6 (IL-6) in the lungs and serum were assessed.<br> Results: Repeated administration of HET prevented the development of anxiety-like behaviors and reduced serum IL-6 concentrations and hippocampal Il6 mRNA expression levels in LPS-treated mice. Diazepam failed to exert significant effects in LPS-treated mice, whereas HET remained effective under inflammatory conditions. Moreover, LPS injections significantly increased the number of Iba-1-immunoreactive microglial cells in the CA1 region of the hippocampus, whereas this effect was suppressed by treatment with HET. In the bronchoalveolar lavage fluid (BALF), the LPS-induced increase in white blood cell count was significantly reduced by treatment with HET. Furthermore, HET alleviated LPS-induced pulmonary inflammation, as evidenced by decreased lung wet-to-dry weight ratios.<br> Conclusion: This study suggests that inflammation induced by intratracheal LPS injection contributes to anxiety-like behaviors in mice and that IL-6 may play a key role in linking peripheral inflammation to neuroinflammatory responses. The anxiolytic effects of HET appear to be associated, at least in part, with the suppression of IL-6 elevation in both the periphery and the hippocampus, along with attenuation of microglial activation. Our findings suggest that HET may serve as a potential therapeutic agent for anxiety-like behaviors associated with pulmonary inflammation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 33 5 2026 Comparative Efficacy of First-Line Immune Checkpoint Inhibitor-Based Combination Therapies in Patients With Sarcomatoid Renal Cell Carcinoma: A Japanese Multicenter Cohort Study e70494 EN Keita Tamura Department of Urology, Hamamatsu University School of Medicine Yuto Matsushita Department of Urology, Hamamatsu University School of Medicine Hiromitsu Watanabe Department of Urology, Hamamatsu University School of Medicine Takafumi Yanagisawa Department of Urology, Jikei University School of Medicine Keiichiro Mori Department of Urology, Jikei University School of Medicine Hirofumi Morinaka Department of Urology, Kawasaki Medical School Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shingo Toyoda Department of Urology, Kindai University Faculty of Medicine Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Kazumasa Komura Department of Urology, Kawasaki Medical School Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazutoshi Fujita Department of Urology, Kindai University Faculty of Medicine Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Teruo Inamoto Department of Urology, Hamamatsu University School of Medicine Objectives: Sarcomatoid renal cell carcinoma (sRCC) is an aggressive histological variant associated with a poor prognosis. While immune checkpoint inhibitor (ICI)-based combinations have become the standard of care, the optimal first-line regimen, specifically dual immunotherapy (IO-IO) vs. IO plus tyrosine kinase inhibitor (IO-TKI), remains controversial. We herein examined the real-world clinical outcomes of Japanese patients with sRCC.<br> Methods: We conducted a retrospective multicenter study on 46 patients with advanced or metastatic sRCC receiving first-line ICI-based combination therapy between January 2018 and December 2024 (IO-IO: n = 18; IO-TKI: n = 28). In a comparative survival analysis, three favorable-risk patients in the IO-TKI group were excluded to align risk profiles, focusing on intermediate/poor-risk groups (n = 43). The primary endpoint was overall survival (OS).<br> Results: In the entire cohort (n = 46), the objective response rate was numerically higher in the IO-TKI group (64.3%) than in the IO-IO group (50.0%) (p = 0.37). In the comparative analysis of intermediate/poor-risk patients (n = 43), progression-free survival (PFS) was slightly longer (p = 0.071), and OS was significantly longer (p = 0.016) in the IO-TKI group than in the IO-IO group. A multivariable analysis adjusted for IMDC risk categories showed favorable survival with the IO-TKI regimen (HR 0.37, p = 0.061).<br> Conclusions: The present study indicates that first-line IO-TKI combination therapy represents a promising treatment option with a potential survival advantage over IO-IO therapy for Japanese patients with sRCC. However, due to the retrospective design and small sample size, reliably determining the comparative efficacy of these regimens remains challenging, and further validation is warranted. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0897-3806 2026 What Is the Pterygomandibular Raphe? A Confluence of Fasciae Rather Than a Discrete Structure 1 9 EN Joe Iwanaga Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine Shion Hama Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Keiko Fukino Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University Shogo Kikuta Dental and Oral Medical Center, Kurume University School of Medicine Mi�]Sun Hur Department of Anatomy, Daegu Catholic University School of Medicine Maria Cristina Manzanares Cespedes Human Anatomy and Embryology Unit. Experimental Pathology and Therapeutics Department, Faculty of Medicine and Health Sciences, University of Barcelona Yoshio Ohyama Oral and Maxillofacial Surgery, Shizuoka City Shizuoka Hospital Masaya Akashi Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Noritaka Komune Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Hideaki Kamochi Department of Maxillofacial Surgery, Institute of Science Tokyo Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The pterygomandibular raphe (PMR) has traditionally been described as a fibrous or tendinous band connecting the bucinator (BM) and superior pharyngeal constrictor (SPCM) muscles. However, recent evidence has questioned its existence. This study aimed to reevaluate the anatomy of the pterygomandibular region by preserving fascial continuity and examining the relationships among adjacent muscles and connective tissues. Twenty-five sides from formalin-fixed cadaveric heads were examined. Twenty sides underwent macroscopic dissection under a surgical microscope, and five sides were sectioned axially and analyzed histologically using Masson's trichrome staining to assess muscle–fascia continuity. The buccopharyngeal fascia (BpF) adhered tightly to the posterolateral surface of the BM. A ligament-like bundle observed between the BM and medial pterygoid muscle corresponded to an artificial continuation of the BpF created by dissection. Axial sections revealed that the BpF, masseteric, and temporalis fasciae converged anteriorly on the lateral surface of the BM, while posteriorly, the BpF and temporalis fascia also merged, forming a confluence of fasciae. No discrete tendinous or ligamentous PMR was identified. The so-called PMR represents a dissection artifact rather than a true anatomical structure. These findings emphasize the importance of preserving fascial relationships and using precise terminology in anatomical and clinical contexts. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2090-6749 2026 Arthroscopically Confirmed Complete Healing of Anterior Cruciate Ligament Avulsion Fracture Following Four�]Corner Pullout Repair Using Ultrahigh�]Molecular�]Weight Polyethylene Tapes: A Case Report 5671446 EN Toshiki Kohara Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Yuki Okazaki Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Shinichi Miyazawa Department of Orthopedic Surgery , NHO Fukuyama Medical Center Takayuki Furumatsu Department of Orthopedic Surgery , Japanese Red Cross Okayama Hospital Yusuke Yokoyama Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Masanori Tamura Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Koki Kawada Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Tsubasa Hasegawa Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Tomonori Tetsunaga Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Kazuki Yamada Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences We report a case of tibial insertion avulsion fracture of the anterior cruciate ligament (ACL). A 10-year-old boy who fell from a skateboard was diagnosed with a tibial insertion avulsion fracture of the ACL and was treated arthroscopically. The avulsed fragment was provisionally fixed with guide pins inserted into its four corners, and the lateral view was checked to avoid penetration of the growth plate. Two ultrahigh-molecular-weight polyethylene tapes were passed through the ACL just above its tibial insertion, pulled through the four-corner bone tunnels in an X-shaped configuration, and tightened. The patient was immobilized for 3 weeks, and partial weight bearing was initiated at 4 weeks. Bone union was confirmed at 6 months using plain radiographs, and second-look arthroscopy and implant removal were performed 8 months postoperatively. During arthroscopy, complete union with smooth continuity of the articular cartilage at the fracture site and a stable ACL were observed. The patient had a full knee range of motion and no pain at the final follow-up. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2090-6528 2026 1 2026 Selective ARID1A Loss Restricted to the Undifferentiated Component of a Mismatch Repair�]Deficient Gastric Carcinoma: A Case Report 8863202 EN Rika Omote Department of Diagnostic Pathology, NHO Fukuyama Medical Center Ryosuke Hamano Department of Surgery, NHO Fukuyama Medical Center Shinya Otsuka Department of Surgery, NHO Fukuyama Medical Center Takehiro Tanaka Department of Pathology, Okayama University Hospital Hiroyuki Yanai Department of Pathology, Okayama University Hospital Mismatch repair-deficient (dMMR) gastric carcinomas often harbor ARID1A alteration, but a sharply demarcated undifferentiated/rhabdoid component with selective ARID1A loss is uncommon and may create a diagnostic dilemma. An 80-year-old man underwent esophagogastroduodenoscopy for anemia, which revealed a circumferential Borrmann Type 3 lesion in the gastric body, and distal gastrectomy was performed. Histologically, the tumor was composed predominantly of undifferentiated carcinoma with focal rhabdoid features and a minute well-differentiated adenocarcinoma component, with an abrupt transition between the two. Immunohistochemistry showed loss of nuclear MLH1 and PMS2 in both components, whereas loss of ARID1A expression was confined to the undifferentiated component; SMARCB1 (INI1), SMARCA2 (BRM), and SMARCA4 (BRG1) were retained. EBER in situ hybridization was negative. Because gene-level testing, MSI testing, and MLH1 promoter methylation analysis were not performed, the molecular basis of the dMMR phenotype and ARID1A loss could not be determined. The restricted scope of molecular testing limits the ability to draw broad or generalizable conclusions and to fully establish clinicopathological correlations. The value of this report is, therefore, not mechanistic proof but recognition of a practical morphologic-immunophenotypic observation: When a gastric carcinoma shows a sharply demarcated shift from differentiated to undifferentiated/rhabdoid morphology, dMMR should be considered, and selective ARID1A loss in the undifferentiated component may be associated with dedifferentiation. These findings should be interpreted with caution as preliminary, hypothesis-generating observations that require validation in larger studies with more extensive molecular profiling. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 33 4 2026 Differences in drug efficacy and prognosis between primary and metastatic sites for de novo stage IV breast cancer: an exploratory analysis of a phase III trial, JCOG1017 829 838 EN Kiyo Tanaka Department of Breast Surgery, Toranomon Hospital Akihiko Shimomura Department of Breast and Medical Oncology, National Center for Global Health and Medicine Makoto Ishitobi Department of Breast Surgery, Osaka Habikino Medical Center Takashi Yamanaka Department of Breast Surgery, Kanagawa Cancer Center Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroji Iwata Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences Fumikata Hara Department of Breast Oncology, Aichi Cancer Center Tomomi Fujisawa Department of Breast Oncology, Gunma Prefectural Cancer Center Keita Sasaki Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Ryo Sadachi Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Riku Kajikawa Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Takehiko Sakai Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Yasuaki Sagara Department of Breast Surgery, Sagara Hospital Hideo Shigematsu Department of Breast Surgery, Hiroshima University Hospital Yukinori Ozaki Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Kazuki Nozawa Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences Kazuki Sudo Department of Medical Oncology, National Cancer Center Hospital Yoichi Naito Department of General Internal Medicine, National Cancer Center Hospital East Kaori Terata Department of Breast and Endocrine Surgery, Akita University Hospital Toshiyuki Ishiba Department of Breast Surgery, Institute of Science Tokyo Hospital Haruhiko Fukuda Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background Breast cancer is a highly heterogeneous disease, with biological factors like estrogen receptor, progesterone receptor, and HER2 receptor differing between primary and metastatic sites, potentially affecting treatment response.<br> This exploratory analysis aims to differentiate drug efficacy and long-term prognosis between these sites in stage IV breast cancer.<br> Methods Patients from JCOG1017, a phase III trial evaluating the role of primary tumor resection, who received primary systemic therapy (PST) were evaluated at three months. In this analysis, treatment response was assessed separately in primary and metastatic sites. Patients were categorized into four groups: discordant I (primary non-PD, metastatic PD), concordant I (both PD), discordant II (primary PD, metastatic non-PD), and concordant II (both non-PD).<br> Results Among 271 patients, overall discordance proportion of treatment response between primary and metastatic sites was 25.1%. Group distribution was 24.7% (discordant I), 9.6% (concordant I), 0.4% (discordant II), and 65.3% (concordant II). Discordance was more frequent in luminal (28.9%), triple-negative (25.0%), and luminal-HER2 (22.0%) subtypes than in HER2-enriched (11.1%). Survival analysis showed prognostic differences: concordant II, with both sites non-PD, demonstrated the most favorable outcome compared with discordant I (HR 0.556; 95% confidence interval, 0.396–0.782).<br> Conclusions One-fourth of patients exhibited discordant responses between primary and metastatic sites in early treatment phases. These discrepancies were associated with survival differences, emphasizing the importance of evaluating both primary and metastatic lesions when assessing efficacy and determining treatment strategies in de novo stage IV breast cancer. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 3 2026 Clinical complete response and predictive factors in HER2-positive early breast cancer treated with neoadjuvant chemotherapy aimed at omission of surgery: an exploratory analysis of the JCOG1806 trial 528 536 EN Hideo Shigematsu Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Hospital Tomomi Fujisawa Gunma Prefectural Cancer Center Fumikata Hara Aichi Cancer Center Hiroji Iwata Graduate School of Medical Sciences, Nagoya City University Toshiyuki Ishiba Institute of Science Tokyo Hospital Yukinori Ozaki Cancer Institute Hospital of the Japanese Foundation for Cancer Research Takehiko Sakai Cancer Institute Hospital of the Japanese Foundation for Cancer Research Yasuaki Sagara Hakuaikai Sagara Hospital Akihiko Shimomura National Center for Global Health and Medicine Kazuki Sudo National Cancer Center Hospital Kaori Terata Akita University Hospital Yoichi Naito National Cancer Center Hospital East Kazuki Nozawa Graduate School of Medical Sciences, Nagoya City University Keita Sasaki Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Noriko Mitome Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Ryo Sadachi Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Taro Shibata Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Tadahiko Shien Okayama University Hospital Purpose The JCOG1806 trial (jRCTs031190129) is underway to evaluate the omission of surgery in patients with human epidermal growth factor receptor (HER2)-positive early breast cancer who have a clinical complete response (cCR) after primary systemic therapy (PST). We aimed to assess the cCR rate in this trial and identify predictive factors.<br> Methods HER2-positivity was defined as an immunohistochemistry (IHC) score of 3 + or in situ hybridization-positivity. A cCR was defined as the absence of detectable lesions upon palpation, contrast-enhanced magnetic resonance imaging, and ultrasonography; biopsy-based confirmation was optional in hormone receptor (HR)-negative cases and mandatory in HR-positive cases. Multivariate logistic regression analyses were used to identify predictors of a cCR.<br> Results The cCR rate was 57.6% (196/340 patients; 95% confidence interval [CI]: 52.2–63.0%). Strongly estrogen-receptor (ER)-positive tumors (≥ 10%) were significantly less likely to have a cCR than ER-negative tumors (odds ratio [OR], 0.41; 95% CI: 0.20–0.81). IHC 3 + tumors had higher cCR rates than IHC 1 + or 2 + tumors (OR, 2.19; 95% CI: 1.01–4.74). Compared with histological grade I tumors, cCR odds were higher in grade II (OR: 2.92; 95% CI: 1.07–7.93) and III (OR: 4.90; 95% CI: 1.76–13.7) tumors. Among patients without a cCR patients undergoing surgery, 22.2% were diagnosed with ypT0 tumors upon analysis of surgical specimens.<br> Conclusion ER-negativity, an IHC score of 3 + , and a higher histological grade were independent predictors of a cCR. Identifying these features may improve the feasibility and safety of surgery omission for patients with HER2-positive early breast cancer. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0007-1048 208 6 2026 Decreased renal function predicts severe cytokine release syndrome after CAR-T-cell therapy for large B-cell lymphoma 2124 2133 EN Yasuyuki Arai Department of Hematology, Graduate School of Medicine, Kyoto University Tomoyasu Jo Department of Hematology, Graduate School of Medicine, Kyoto University Takayuki Sato Department of Hematology and Oncology, Kurashiki Central Hospital Masatoshi Sakurai Division of Hematology, Department of Medicine, Keio University School of Medicine Daisuke Kaji Department of Hematology, Toranomon Hospital Toshio Kitawaki Department of Hematology, Graduate School of Medicine, Kyoto University Kazuyuki Shimada Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Tatsu Shimoyama Division of Clinical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Shinichi Makita Department of Hematology, National Cancer Center Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Go Yamamoto Department of Hematology, Toranomon Hospital Keisuke Kataoka Division of Hematology, Department of Medicine, Keio University School of Medicine Emiko Sakaida Department of Hematology, Chiba University Hospital Hideki Goto Department of Hematology, Hokkaido University Hospital Yasuhiro Nakashima Department of Hematology, Osaka Metropolitan University Hospital Akiyo Yoshida Department of Hematology, Kanazawa University Hospital Yoshihiro Umezawa Department of Hematology, Institute of Science Tokyo Hospital Haryoon Kim Division of Hematology, Department of Medicine, Keio University School of Medicine Motohiro Kato Department of Pediatrics, The University of Tokyo Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Koji Kato Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital Cytokine release syndrome (CRS) remains a major toxicity of chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL), and robust pre-infusion predictors are needed for risk-adapted management. We retrospectively analysed LBCL patients in the Japanese nationwide registry who underwent CD19 CAR-T-cell therapy between 2019 and 2024. Among 900 patients (median age 62 years), cumulative incidences of CRS within 30 days after infusion were 75.0% for any grade, 20.8% for grade ≥ 2 and 14.0% for grade ≥ 3. In multivariable analysis, lower estimated glomerular filtration rate (eGFR) (adjusted hazard ratio [aHR] 1.108 per 10 mL/min per 1.73 m2 decrease; 95% confidence interval [CI] 1.015–1.209; p = 0.022), higher ferritin (aHR 1.006 per 100 ng/mL; 95% CI 1.001–1.010; p = 0.016), C-reactive protein (CRP) (aHR 1.142 per mg/dL; 95% CI 1.091–1.195; p < 0.001) and lactate dehydrogenase (LDH) (aHR 1.073 per 100 U/L; 95% CI 1.008–1.142; p = 0.028) independently predicted grade ≥ 2 CRS. We then built a four-factor CRS pre-infusion risk evaluation model, cytokine release syndrome-pre-infusion risk evaluation (CRS-PRE), that stratified grade ≥ 2 CRS risk into low, intermediate and high groups with incidences of 2.8%, 26.0% and 50.0% respectively. Decreased eGFR, a surrogate of host renal reserve, with elevated ferritin, CRP and LDH emerged as predictors of high-grade CRS. The CRS-PRE may facilitate risk-adapted monitoring and intervention in clinical practice. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2667-2421 20 2026 Behavioral effects of a chronic envy-like stress paradigm in mice using an adjacent cage model 148 159 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yoshihiro Tanaka Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Background: Social comparison and envy are significant psychosocial stressors in humans and are known to be involved in the onset and persistence of psychiatric disorders. However, animal models capable of experimentally reproducing the effects of indirect social comparison without physical contact are limited. In this study, we used a newly developed "adjacent-cage paradigm" to investigate whether chronic vicarious exposure to conspecifics in different environments induces envy-like stress in mice.<br> Methods: Male C57BL/6 N mice served as observers, while demonstrator mice were assigned to one of four conditions: (1) an environment enriched with objects, (2) an igloo, (3) a tube, or (4) social isolation. Observers were continuously exposed to these adjacent cages for 21 days. Subsequently, a comprehensive battery of behavioral tests was conducted to assess general health, anxiety-like behavior, spatial memory, social behavior, and depression-like behavior.<br> Results: In the objects condition, a decrease in time spent in the light compartment of the light/dark box indicated an increase in anxiety-like behavior. In the isolation condition, the mean duration per social interaction was shortened, suggesting a qualitative change in social behavior. The igloo condition resulted in reduced immobility time in the forced swim test, suggesting a possible alteration in stress coping behavior. Furthermore, increased nociceptive sensitivity was observed in the hot plate test under both the objects and isolation conditions.<br> Conclusion: Although the envy-like stress paradigm did not affect many behavioral indices, it did cause condition-dependent and limited behavioral changes. This suggests that the paradigm may serve as a novel model for capturing psychological and context-dependent social stress, which differs from conventional physical stress models. Elucidating the neural basis of this paradigm is expected to contribute to the understanding of how social comparison affects mental health in modern society. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Adolescent envy-like social comparison stress induces HPA axis hypoactivity and anxiety in female mice: implications for somatic symptom disorder 15771 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yoshihiro Tanaka Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Adolescence is a critical developmental window marked by heightened neuroplasticity and maturation of the stress response system, conferring vulnerability to psychosocial stress. Chronic stress during this period increases the risk of anxiety and depressive disorders and may contribute to somatic symptom disorder (SSD), which is characterized by medically unexplained physical complaints and shows a striking female predominance. The impact of envy-like stress arising from social comparison, a pervasive psychosocial factor in modern society, remains poorly understood. Male and female C57BL/6N mice were exposed to chronic envy-like stress from postnatal day (P)21 to P52 by housing them adjacent to enriched cages, while control mice were housed without such exposure. From P52 onward, mice underwent behavioral testing of anxiety-like behavior, exploratory activity, social interaction, spatial working memory, motor coordination, nociception, and depression-like behavior. Serum corticosterone and adrenocorticotropic hormone (ACTH) concentrations were measured to assess hypothalamic–pituitary–adrenal (HPA) axis function. Envy-like stress induced sex-specific phenotypes. Male mice exhibited hyperactivity, reduced social interaction, and impaired spatial working memory. In contrast, female mice displayed robust increases in anxiety-like behavior, impaired motor coordination, and significant reductions in basal corticosterone and ACTH levels. Chronic envy-like stress during adolescence elicits distinct, sex-dependent behavioral and endocrine alterations. The phenotype observed in female mice�\characterized by heightened anxiety and lower basal HPA axis hormone levels�\shares some biological features with clinical observations in SSD. This model may serve as a starting point for elucidating the mechanisms linking psychosocial stress and somatic symptoms in a sex-dependent manner. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Post-weaning maternal presence exerts a protective effect against social isolation-induced behavioural alterations in mice 44248 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Parental �gwatchful presence�h is considered an important factor influencing behavioural and emotional development in offspring across mammalian species, including humans. However, the effects of such parental presence remain insufficiently understood, even in human studies. In laboratory mice, offspring are typically weaned at approximately three weeks of age, leaving the impact of post-weaning maternal presence on behavioural development largely unexplored. This study aimed to investigate whether maternal presence in an adjacent cage after weaning can attenuate behavioural effects of social isolation stress in mice. Furthermore, we sought to assess whether this experimental paradigm could serve as a novel animal model for studying the effects of parental watchful presence, with potential relevance to human parent–child relationship research. Mouse pups were weaned at postnatal day 21 and housed either adjacent to their mother (maternal presence group) or without maternal presence (control group). The pups were subsequently housed either in groups with littermates or individually until eight weeks of age. After maturation, behavioural tests were conducted to assess locomotor activity, anxiety-like behaviour, social behaviour, and depression-like behaviour. In group-housed mice, maternal presence did not influence behavioural outcomes. However, in individually housed mice, maternal presence partially attenuated social isolation-induced behavioural alterations, suggesting a subtle protective effect, including hyperlocomotion, reduced anxiety-like behaviour, and abnormal social interactions. Our findings demonstrate that maternal presence during the post-weaning period can offer a protective effect against certain behavioural abnormalities induced by social isolation stress in mice.�@This simple adjacent-cage paradigm provides a novel and practical model for elucidating the impact of parental watchful presence on behavioural and emotional development, offering insights relevant to the understanding of parent–child relationships in humans. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 6 2026 Barriers and facilitators for online genetic care for hereditary cancer in Japan: findings from surveys of both clients and medical professionals 1063 1074 EN Sayaka Ueno Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusaku Urakawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumino Kato Arisa Ueki Division of Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research Keika Kaneko Division of Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research Koji Matsumoto Division of Clinical Genetics, Hyogo Cancer Center Hiromi Sugawara Division of Clinical Genetics, Hyogo Cancer Center Sayoko Takeuchi Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Reiko Yoshida Department of Medical Genetics and Genomics, Saitama Cancer Center Miho Kakuta Center for Genomic Diagnosis, International University of Health and Welfare (IUHW) Narita Hospital Kiwamu Akagi Center for Genomic Diagnosis, International University of Health and Welfare (IUHW) Narita Hospital Kazuo Tamura Center for Genomic Diagnosis, International University of Health and Welfare (IUHW) Narita Hospital Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Online genetic care can offer a promising solution to the shortage of qualified medical professionals in genetic medicine, which leads to regional disparities in access. However, despite global adoption, its use in Japan remains limited.<br> Methods Two questionnaire surveys were conducted to investigate potential needs and barriers regarding online genetic care: one involving 858 medical professionals (738 physicians and 120 genetic counselors or nurses), and the other involving 443 clients who received in-person genetic counseling.<br> Results Only 14.0% of the medical professionals had experience with online genetic care, although 85.9% of the professionals engaged in cancer genetics were willing to consider providing it in the future. Notably, a discrepancy was found regarding hospital selection: clients prioritized access to specialized medical care, whereas professionals assumed clients valued accessibility for family members. Professionals expressed greater concerns about adequacy of online communication, client environments and internet security. Among clients, 89.1% estimated they would sufficiently understand and accept total content of counseling session if were conducted online. Older age and infrequent internet use were associated with lower acceptance and higher anxiety regarding online methods. Concerns about ability to use the necessary technology affected clients�f willingness to encourage online care for their relatives.<br> Conclusion Online genetic care shows high potential for client acceptance and can effectively address regional disparities in Japan. To bridge the gap between client needs and professional perceptions and to overcome the digital divide, it is necessary to develop secure, accessible systems and provide education for both patients and healthcare providers. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1867-1071 2026 A novel robot for CT-guided bone needle insertion with a rotational drilling and force-feedback speed control mechanism: preliminary evaluation in swine EN Yusuke Matsui Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Kimura Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Sasaki Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ryutaro Matsuura Department of Radiological Technology, Faculty of Health Sciences, Okayama University Koji Tomita Department of Radiology, Medical Development Field, Okayama University Noriyuki Umakoshi Department of Radiology, Medical Development Field, Okayama University Soichiro Okamoto Department of Radiology, Medical Development Field, Okayama University Kazuaki Munetomo Department of Radiology, Medical Development Field, Okayama University Fumiyo Higaki Department of Radiology, Medical Development Field, Okayama University Jun Sakurai Center for Innovative Clinical Medicine, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Atsushi Nakazawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kiyoshi Matsumiya Department of Medical Technology, Faculty of Life Science, Okayama University of Science Takayuki Matsuno Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tetsushi Kamegawa Faculty of Environmental, Life, Natural Science and Technology, Okayama University Purpose To evaluate the feasibility and accuracy of computed tomography (CT)-guided needle insertion into swine bones by using a novel robotic system capable of rotational drilling.<br> Materials and methods This was an animal experiment using three swine. A remote-controlled robot equipped with a rotational drilling and force-feedback insertion speed control mechanism was developed for bone needle insertion. Using the robot, CT-guided insertion of a 10-gauge bone access needle was attempted in the lumbar vertebrae, ilia, and femora six times each. Needle insertion accuracy was evaluated using the angle error, which is defined as the difference between the predetermined and post-insertion needle angles on axial and sagittal CT images. The time required for needle insertion was measured. The angle error and time required for needle insertion were compared among the bones using the Kruskal–Wallis test. Adverse events were also evaluated.<br> Results Robotic bone needle insertion was successful in all attempts. The median axial and sagittal angle errors were 0.21 and 0.21�‹ for the lumbar vertebrae, 0.32 and 0.13�‹ for the ilia, and 0.65 and 0.25�‹ for the femora, respectively. Axial angle errors were significantly different among the bone types (p = 0.038). The time required for needle insertion was 23.6, 21.3, and 59.7 s for the lumbar vertebrae, ilia, and femora, respectively. Time was significantly different among bone types (p = 0.017). No adverse events were observed.<br> Conclusion CT-guided bone needle insertion using a robot equipped with a rotational drilling and force-feedback insertion speed control mechanism was feasible and accurate in swine. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 0090-3493 54 6 2026 Institutional Variability in Brain-Dead Organ Donation Processes and Practices: A Multicenter Cohort Study 1319 1328 EN Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mineji Hayakawa Department of Emergency Medicine, Hokkaido University Hospital Shoji Yokobori Department of Emergency and Critical Care Medicine, Nippon Medical School Kei Nishiyama Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science Takahiro Atsumi Department of Emergency and Disaster Medicine, Hamamatsu University School of Medicine Osamu Tasaki Acute and Critical Care Center, Nagasaki University Hospital Junya Tsurukiri Emergency and Critical Care Medicine, Tokyo Medical University Hachioji Medical Center Mariko Hayamizu Department of Emergency Medicine, Hokkaido University Hospital Shimon Murahashi Acute and Critical Care Center, Nagasaki University Hospital Munehiro Hayashi Department of Emergency and Critical Care Medicine, Japanese Red Cross Medical Center Takeshi Nishimura Department of Emergency and Critical Care Medicine, Hyogo Emergency Medical Center Yukari Goto Department of Emergency Medicine, Nagoya Ekisaikai Hospital Hiromichi Narumiya Department of Emergency and Critical Care Medicine, Japanese Red Cross Kyoto Daini Hospital Atsushi Mizutani Department of Emergency Medicine, Hamamatsu Medical Center Mamoru Miyajima Emergency and Critical Care Center, Nagaoka Red Cross Hospital Junya Shimazaki Department of Emergency and Critical Care Medicine, Kansai Medical University Medical Center Takeshi Miura Department of Emergency and Critical Care Medicine, Institute of Medicine, University of Tsukuba Hospital Nozomu Shima Department of Emergency and Critical Care Medicine, Wakayama Medical University Kazuki Deuchi Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science Hitomi Nakayasu Emergency and Critical Care Medicine, Seirei Hamamatsu General Hospital Hitoshi Kano Department of Emergency and Critical Care Medicine, Nippon Medical School Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Japan Comprehensive Process for End-of-Life Care and Organ Donation after Brain Death (J-RESPECT) study group OBJECTIVES: To determine whether key institutional and clinical differences exist between highly and moderately active hospitals in Japan with respect to brain-dead organ donation practices.<br> DESIGN: Retrospective multicenter cohort study.<br> SETTING: Sixteen tertiary emergency and critical care centers across Japan.<br> PATIENTS: All brain-dead organ donors from participating institutions who had at least one organ procured and transplanted between July 17, 2010, and December 31, 2023. Hospitals were categorized as highly active (≥ 14 donations) or moderately active (≤ 13 donations) during the study period.<br> INTERVENTIONS: None.<br> MEASUREMENTS AND MAIN RESULTS: Institutional donation practices were compared, including donor management strategies, use of vasopressors and corticosteroids, time intervals in the donation process, and frequency of multidisciplinary team meetings. A total of 204 donors were included; the median age was 47 years (interquartile range, 37–56), and 92 (45.1%) were female. Donor characteristics were similar between groups. Vasopressin was used in nearly all donors, though dosing protocols varied. Corticosteroid use was significantly higher in highly active hospitals compared with moderately active ones (58.3% vs. 38.0%; p = 0.004). Time from admission to coordinator notification was similar; however, time to family consent (median, 8 vs. 5 d; p < 0.001) and time to organ procurement (median, 12 vs. 9 d; p = 0.006) were longer in highly active hospitals. These hospitals also conducted more multidisciplinary meetings during donor management (median, 2 vs. 0; p < 0.001).<br> CONCLUSIONS: Highly active hospitals demonstrated more intensive donor management practices, longer timeframes for key donation steps, and greater multidisciplinary engagement. Standardization of donation practices may enhance efficiency and support broader dissemination of effective institutional strategies to improve brain-dead organ donation rates in Japan. No potential conflict of interest relevant to this article was reported.