MDPI AGActa Medica Okayama1422-00672732026Bioinformatic Prediction of Activation States in Molecular Network Pathways of Eukaryotic Initiation Factor 2 (EIF2) Signaling and Coronavirus Pathogenesis1525ENShihoriTanabeDivision of Risk Assessment, Center for Biological Safety and Research, National Institute of Health SciencesSabinaQuaderInnovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial PromotionRyuichiOnoDivision of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health SciencesHiroyoshi Y.TanakaDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHoracioCabralDepartment of Bioengineering, Graduate School of Engineering, The University of TokyoEukaryotic 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.Elsevier BVActa Medica Okayama0300-28966152025Histological Features and Gene Expression Profiling in Lung Transplantation From Donation After Circulatory Death299302ENMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomohisaSakaueDepartment of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of MedicineShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYujiroKuboDepartment of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-MajadahondaTatsuyaHayashiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesElviraRamilSequencing and Molecular Biology Unit, Hospital Universitario Puerta de Hierro-MajadahondaAntonio J.Sánchez-LópezBiobank, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de AranaMaría JoseCoronadoConfocal Microscopy Unit, Hospital Universitario Puerta de Hierro-MajadahondaLucasHoyosDepartment of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-MajadahondaAlejandraRomeroDepartment of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-MajadahondaShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDavidGomez-de-AntonioDepartment of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-MajadahondaNo potential conflict of interest relevant to this article was reported.SAGE PublicationsActa Medica Okayama1758-8359172025Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study116ENShigeruTanzawaDivision of Medical Oncology, Department of Internal Medicine, Teikyo University School of MedicineHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical University HospitalToshihiroMisumiDepartment of Data Science, National Cancer Center Hospital EastEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalYasunoriMurataDepartment of Respiratory Medicine, Ichinomiya Nishi HospitalMasafumiTakeshitaDepartment of Respiratory Medicine, Ichinomiya Nishi HospitalFumihikoKinoshitaDepartment of Thoracic Oncology, NHO Kyushu Cancer CenterTakatoshiFujishitaDepartment of Thoracic Oncology, NHO Kyushu Cancer CenterShunichiSugawaraDepartment of Pulmonary Medicine, Sendai Kousei HospitalYosukeKawashimaDepartment of Pulmonary Medicine, Sendai Kousei HospitalKazukiHashimotoDepartment of Thoracic Oncology, NHO Osaka Toneyama Medical CenterMasahideMoriDepartment of Thoracic Oncology, NHO Osaka Toneyama Medical CenterAkihikoMiyanagaDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical SchoolAnnaHayashiDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical SchoolHisashiTanakaDepartment of Respiratory Medicine, Hirosaki University Graduate School of MedicineRyoichiHondaDepartment of Respiratory Medicine, Asahi General HospitalMasafumiNojiriDepartment of Respiratory Medicine, Kanazawa Medical UniversityYukiSatoDepartment of Respiratory Medicine, Kobe City Medical Center General HospitalAkitoHataDivision of Thoracic Oncology, Kobe Minimally Invasive Cancer CenterNobuhisaIshikawaDepartment of Respiratory Medicine, Hiroshima Prefectural HospitalToshiyukiKozukiDepartment of Thoracic Oncology and Medicine, NHO Shikoku Cancer CenterTakahisaKawamuraDepartment of Thoracic Oncology, Osaka International Cancer InstituteGoSaitoDepartment of Respirology, Graduate School of Medicine, Chiba UniversityTeppeiYamaguchiDepartment of Thoracic Oncology, Aichi Cancer Center HospitalKazuhiroAsadaDepartment of Respiratory Medicine, Shizuoka General HospitalSatoshiTetsumotoDepartment of Respiratory Medicine and Clinical Immunology, Suita Municipal HospitalHiroshiTanakaDepartment of Internal Medicine, Niigata Cancer Center HospitalSatoshiWatanabeDepartment of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental SciencesYukihiroUmedaDepartment of Respiratory Medicine, Faculty of Medical Sciences, University of FukuiKakuhiroYamaguchiDepartment of Respiratory Medicine, Hiroshima University HospitalKazuyaNishiiDepartment of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Yamaguchi, JapanKosukeTsurunoDepartment of Respiratory Medicine, Iizuka HospitalYukiMisumiDepartment of Respiratory Medicine, Yokohama Municipal Citizen’s HospitalHiroshiKuraishiDepartment of Pulmonary Medicine, Nagano Red Cross HospitalKenYoshiharaDepartment of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of MedicineAkiraNakaoDepartment of Respiratory Medicine, Fukuoka University HospitalAkihitoKuboDepartment of Respiratory Medicine and Allergology, Aichi Medical UniversityToshihikoYokoyamaDepartment of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi HospitalKanaWatanabeDepartment of Respiratory Medicine, Miyagi Cancer CenterNobuhikoSekiDivision of Medical Oncology, Department of Internal Medicine, Teikyo University School of MedicineBackground: 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’s 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.SAGE PublicationsActa Medica Okayama1758-8359172025Skin 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 study113ENFumihikoKinoshitaDepartment of Thoracic Oncology, NHO Kyushu Cancer CenterShigeruTanzawaDivision of Medical Oncology, Department of Internal Medicine, Teikyo University School of MedicineToshihiroMisumiDepartment of Data Science, National Cancer Center Hospital EastHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical UniversityEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalYasunoriMurataDepartment of Respiratory Medicine, Ichinomiya Nishi HospitalMasafumiTakeshitaDepartment of Respiratory Medicine, Ichinomiya Nishi HospitalMasafumiYamaguchiDepartment of Thoracic Oncology, NHO Kyushu Cancer CenterShunichiSugawaraDepartment of Pulmonary Medicine, Sendai Kousei HospitalYosukeKawashimaDepartment of Pulmonary Medicine, Sendai Kousei HospitalKazukiHashimotoDepartment of Thoracic Oncology, NHO Osaka Toneyama Medical CenterMasahideMoriDepartment of Thoracic Oncology, NHO Osaka Toneyama Medical CenterAkihikoMiyanagaDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical SchoolAnnaHayashiDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical SchoolHisashiTanakaDepartment of Respiratory Medicine, Hirosaki University Graduate School of MedicineRyoichiHondaDepartment of Respiratory Medicine, Asahi General HospitalMasafumiNojiriDepartment of Respiratory Medicine, Kanazawa Medical UniversityYukiSatoDepartment of Respiratory Medicine, Kobe City Medical Center General HospitalKenYamamotoDivision of Thoracic Oncology, Kobe Minimally Invasive Cancer CenterKenMasudaDepartment of Respiratory Medicine, Hiroshima Prefectural HospitalToshiyukiKozukiDepartment of Thoracic Oncology and Medicine, NHO Shikoku Cancer CenterTakahisaKawamuraDepartment of Thoracic Oncology, Osaka International Cancer InstituteTakujiSuzukiDepartment of Respirology, Graduate School of Medicine, Chiba UniversityTeppeiYamaguchiDepartment of Thoracic Oncology, Aichi Cancer Center HospitalKazuhiroAsadaDepartment of Respiratory Medicine, Shizuoka General HospitalSatoshiTetsumotoDepartment of Respiratory Medicine and Clinical Immunology, Suita Municipal HospitalHiroshiTanakaDepartment of Internal Medicine, Niigata Cancer Center HospitalSatoshiWatanabeDepartment of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental SciencesYukihiroUmedaThird Department of Internal Medicine, Faculty of Medical Sciences, University of FukuiKakuhiroYamaguchiDepartment of Respiratory Medicine, Hiroshima University HospitalShoichiKuyamaDepartment of Respiratory medicine, NHO Iwakuni Clinical CenterKosukeTsurunoDepartment of Respiratory Medicine, Iizuka HospitalYukiMisumiDepartment of Respiratory Medicine, Yokohama Municipal Citizen’s HospitalHiroshiKuraishiDepartment of Respiratory Medicine, Nagano Red Cross HospitalKenYoshiharaDivision of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of MedicineAkiraNakaoDepartment of Respiratory Medicine, Fukuoka University HospitalAkihitoKuboDepartment of Respiratory Medicine and Allergology, Aichi Medical University School of MedicineToshihikoYokoyamaDepartment of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi HospitalKanaWatanabeDepartment of Respiratory Medicine, Miyagi Cancer CenterNobuhikoSekiDivision of Medical Oncology, Department of Internal Medicine, Teikyo University School of MedicineBackground: 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.Elsevier BVActa Medica Okayama2212-53456332025Practical Guidelines for Asthma Management (PGAM): Digest edition405421ENJunTamaokiDepartment of Respiratory Medicine, Tokyo Women's Medical UniversityHiroyukiNagaseDivision of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of MedicineHiroyukiSanoDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineTakeshiKanekoDepartment of Pulmonology, Yokohama City University Graduate School of MedicineYasuhiroGonDivision of Respiratory Medicine, Department of Internal Medicine, Nihon University School of MedicineNobuakiMiyaharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalHironoriSagaraDepartment of Medicine, Division of Allergology and Respiratory Medicine, School of Medicine, Showa UniversityAkihikoTanakaDepartment of Medicine, Division of Allergology and Respiratory Medicine, School of Medicine, Showa UniversityTakahikoHoriguchiDepartment of Respiratory Medicine, Toyota Regional Medical CenterEtsukoTagayaDepartment of Respiratory Medicine, Tokyo Women's Medical UniversityTomohiroAkabaDepartment of Respiratory Medicine, Tokyo Women's Medical UniversityYujiTohdaKindai University HospitalThe 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 “Basic Roadmap for Asthma Management,” 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.WileyActa Medica Okayama1058-83882026MIT/TFE family transcription factors, Mitf and Tfec, redundantly promote pigment cell differentiation and retinal epithelium pigmentation in teleosts115ENJamesListerDepartment of Human and Molecular Genetics and Massey Cancer Center, Virginia Commonwealth University School of MedicineKeisukeSugiwakaDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityTetsuakiKimuraDepartment of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic BiologyRiekoTanakaWorld Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical GardensMakotoGodaInstitute of Photonics Medicine, Hamamatsu University School of MedicineHikaruKobayashiDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityChikakoInoueR&D Fish Breeding Group, Regional Fish Institute, Ltd.Kawilarang W. A.MasengiFaculty of Fisheries and Marine Science, Sam Ratulangi UniversityKazunoriYamahiraTropical Biosphere Research Center, University of the RyukyusKiyoshiNaruseDepartment of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic BiologySatoshiAnsaiUshimado Marine Institute, Graduate School of Natural Science and Technology, Okayama UniversityRobert N.KelshDepartment of Life Sciences, University of BathMasahikoHibiDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityHisashiHashimotoDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityBackground: Transcription factors of the MIT/TFE family—mitfa, mitfb, and tfec—play essential roles in specifying pigment cells derived from neural crest cells in vertebrates. In teleosts, which possess multiple pigment cell types, these factors exhibit partially redundant but largely distinct functions across different pigment lineages. We previously reported that the combined loss of mitfa and mitfb leads to a complete absence of melanophores, xanthophores, and leucophores in medaka.<br>
Results: Here, we describe newly generated hypomorphic alleles of mitfa and mitfb, which result in delayed melanophore development. Using these hypomorphic mutants in combination with a newly generated null allele of tfec, we show that Tfec can partially compensate for the loss of Mitfa and Mitfb in melanophore, xanthophore, and leucophore differentiation. Consistent with previous findings in zebrafish, loss of tfec alone results in the complete absence of iridophores. Importantly, simultaneous null mutations in all three genes cause a complete loss of all four chromatophore types and lead to defective pigmentation of the retinal pigmented epithelium (RPE), which is not derived from the neural crest in both Oryzias species and in zebrafish. Using an RPE-specific marker, we further show that the RPE is specified and structurally intact but fails to melanize.<br>
Conclusions: These findings indicate that the redundant functions of Mitfa, Mitfb, and Tfec are not only essential for the specification of diverse pigment cell types but also critical for RPE pigmentation.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama2328-89571232025Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory Mycobacterium avium Complex Pulmonary Diseaseofaf118ENYuKuraharaDepartment of Internal Medicine, NHO Kinki Chuo Chest Medical CenterShiomiYoshidaClinical Research Center, NHO Kinki Chuo Chest Medical Center , Osaka ,AsamiOsugiDepartment of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis AssociationYuyaTanakaDepartment of Internal Medicine, NHO Kinki Chuo Chest Medical CenterTakehikoKobayashiClinical Research Center, NHO Kinki Chuo Chest Medical CenterToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalYoheiKawasakiDepartment of Biostatistics, Graduate School of Medicine, Saitama Medical UniversitySatoshiMitaraiDepartment of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis AssociationKazunariTsuyuguchiDepartment of Internal Medicine, NHO Kinki Chuo Chest Medical CenterBackground. 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.Elsevier BVActa Medica Okayama0016-70374302026Pervasive and rapid enrichment of nitrogen in newly erupted oceanic basalt249262ENJuan FelipeBustos-MorenoDepartment of Earth and Environmental Sciences, Lehigh UniversityTobias B.WeisenbergerGeology and Sustainable Mining Institute, University Mohammed VI PolytechnicRyojiTanakaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityHiroshiKitagawaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityGray E.BeboutDepartment of Earth and Environmental Sciences, Lehigh UniversityThe alteration of oceanic crust by seawater is a critical sink in the global nitrogen (N) cycle, yet the mechanisms and timescales of N enrichment remain poorly constrained. We present N concentrations and isotope compositions from a 192-meter drill core (SE-02b) retrieved from the then 50-year-old Surtsey Island in Iceland, a pristine analog for rapid alteration of young oceanic basalt. The altered basaltic tuffs show significant N enrichment (average 11 ± 8 μg/g), relative to unaltered Icelandic basalt glasses (0.028 ± 0.026 μg/g) and MORB (∼1.1 to 1.5 μg/g), matching the global average for altered oceanic crust (11 μg/g; ranging in ages from 5 to 170 Ma). Nitrogen isotope compositions (δ15Nair = −1.7 ± 4.6‰) are primarily consistent with incorporation of seawater- and meteoric-derived ammonium (NH4+), more likely into secondary K-minerals, palagonitized glass and smectites throughout the core. To a lesser extent, N could be incorporated into Na/Ca-minerals such as analcime in the meteoric water altered zone and sulphates such as anhydrite and gypsum when present. Incorporation of NH4+ into secondary phases occurs with little isotope fractionation consistent with equilibrium fractionation between clay and aqueous NH4+. We demonstrate that seawater-rock interaction alone can produce the ubiquitous background N enrichment of the oceanic crust without the addition of remobilized N from sedimentary sources. Such magnitude of enrichment is also observed via meteoric water alteration. Localized high enrichments in N in areas of enhanced fluid flow at core SE-02b with exceptionally low δ15N values (as low as −20.1‰), are attributed to abiotic reduction of dissolved N2 under anoxic conditions and/or microbial activity. We propose that N incorporation into the oceanic crust can occur rapidly in days to decades rather than at a constant rate over geologic time. This has major implications for N transfer in subduction zones, N exchange between the oceanic crust, seawater and the atmosphere and for planetary habitability.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1520-541X2832026Sexual Dimorphism in Vertebral Number: Developmental Implications Inferred From Vertebral and Body Proportionse70062ENKazunoriYamahiraTropical Biosphere Research Center, University of the RyukyusV. K.AnoopTropical Biosphere Research Center, University of the RyukyusRajeevRaghavanDepartment of Fisheries Resource Management, Kerala University of Fisheries and Ocean StudiesYoshitakaTanakaUshimado Marine Institute, Okayama UniversitySatoshiAnsaiUshimado Marine Institute, Okayama UniversitySegmentation is a fundamental feature of vertebrate body plans, and variation in vertebral number contributes substantially to morphological diversity. Although sexual dimorphism in vertebral number has been documented in several vertebrate lineages, its developmental basis remains poorly understood. Here, we report pronounced sexual dimorphism in vertebral number in the western Indian endemic ricefish Oryzias setnai, distributed across ~1800 km. Radiographic analyses of individuals collected throughout its range revealed that vertebral number increased with latitude in both sexes, while males consistently possessed more vertebrae than females irrespective of geographic origin. Size-adjusted analyses showed that this dimorphism is associated with sex differences in head size and position-dependent variation in vertebral length. However, positional allometric analyses demonstrated that both the magnitude and direction of these sex differences vary markedly during growth. In particular, among smaller individuals, posterior vertebrae were relatively shorter in males than in females, suggesting reduced somite length in the posterior body axis of male embryos and potentially reflecting sex-specific differences in the dynamics of somitogenesis. Given that this variation arises between males and females within a single species sharing an essentially identical genetic background, O. setnai provides a rare empirical system not only for linking early developmental processes to intraspecific sexual variation in vertebrate body plans but also as a powerful model to investigate the developmental basis of body plan variation across species.No potential conflict of interest relevant to this article was reported.Japan Surgical SocietyActa Medica Okayama2198-77931212026Successful Lung Transplantation after Plasma Exchange in a Patient with High Thermal Amplitude Cold Agglutinins: A Case Reportcr.26-0502ENYuyaMiyoshiDepartment of General Thoracic Surgery, Okayama University HospitalKentarohMiyoshiDepartment of General Thoracic Surgery, Okayama University HospitalNaomiAsanoDivision of Transfusion and Cell Therapy, Okayama University HospitalHaruchikaYamamotoDepartment of General Thoracic Surgery, Okayama University HospitalShinTanakaDepartment of General Thoracic Surgery, Okayama University HospitalShujiOkaharaDepartment of General Thoracic Surgery, Okayama University HospitalMikioOkazakiDepartment of General Thoracic Surgery, Okayama University Hospital, Okayama, Okayama, JapanSeiichiroSugimotoDepartment of General Thoracic Surgery, Okayama University HospitalNobuharuFujiiDivision of Transfusion and Cell Therapy, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery, Okayama University HospitalINTRODUCTION: Cold agglutinins (CAs) are immunoglobulin M autoantibodies that induce red blood cell agglutination at low temperatures and may cause hemolytic or thrombotic complications during procedures associated with hypothermia. In lung transplantation (LT), blood may be exposed to low temperatures within the reperfused lung graft and the extracorporeal circulation circuit, potentially increasing the risk of CA-mediated complications. However, the perioperative significance of CAs in this setting remains unclear, and optimal management has not been established. We report a case of successful bilateral LT in a patient with high-thermal-amplitude CAs managed with preoperative plasma exchange (PLEX) and strict intraoperative temperature control.<br>
CASE PRESENTATION: A 55-year-old man with diffuse panbronchiolitis and secondary pulmonary hypertension was listed for bilateral LT. Preoperative testing incidentally revealed clinically significant CAs, with a titer of 1:128 at 4°C and a thermal amplitude of 30°C. Because intraoperative blood temperature might approach this threshold despite active warming, a single preoperative session of PLEX using 36 units of fresh frozen plasma was performed to reduce the risk of a CA-mediated complication. Bilateral LT was subsequently completed under meticulous temperature management, including extracorporeal circulation maintained at 37.5°C, continuous systematic warming, avoidance of topical ice application, and rewarming of the donor lungs before reperfusion. After surgery, the CA titer decreased to 1:32. The postoperative course was uneventful, without thromboembolic events, primary graft dysfunction, or bronchial complications.<br>
CONCLUSIONS: LT may be performed safely in selected patients with high-thermal-amplitude CAs when careful perioperative temperature control is combined with preoperative PLEX. PLEX should be considered when the anticipated intraoperative temperature is expected to approach the patient’s thermal amplitude threshold.No potential conflict of interest relevant to this article was reported.American Astronomical SocietyActa Medica Okayama0004-637X99922026Constraining the Effects of Pre- and Post-accretionary Processes on Ryugu Insoluble Organic Matter187ENChristianPotiszilPheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityMasahiroYamanakaPheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityTsutomuOtaPheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityChieSakaguchiPheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityHiroshiKitagawaPheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityRyojiTanakaPheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityTakKunihiroPheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityKatsuraKobayashiPheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityEizoNakamuraPheasant Memorial Laboratory, Institute for Planetary Materials, Okayama UniversityAsteroidal and cometary fragments have been indicated as possible sources of the building blocks of life for the early Earth. Samples returned from the asteroid Ryugu are uncontaminated and contain organic matter. Such samples enable an investigation of the processes that formed and altered extraterrestrial organic matter. Here, the FTIR and Raman responses of insoluble organic matter (IOM) isolated from Ryugu particles and carbonaceous chondrites are reported. Several relationships were observed: (1) a strong positive correlation of CH2/CH3 plotted against aliphatics/C=C; (2) a strong negative correlation of CH2/CH3 plotted against δ15N and δ13C; and (3) strong negative correlations of FTIR band ratios plotted against Raman band parameters and D/G values. The data are not consistent with even moderate heating of the IOM, as indicated by CH2/CH3 ratios that are consistent with unheated carbonaceous chondrites. The C and N isotope data previously collected for each Ryugu particle preclude aqueous alteration based on our understanding of its effects on carbonaceous chondrite IOM. Mixing of several IOM endmembers was considered, but due to the similarities of the particle with the lowest CH2/CH3 ratio to the other particles in terms of its other spectroscopic parameters, this scenario was considered unlikely. Finally, the effects of irradiation were considered, and UV irradiation, in particular, was hypothesised to be the best explanation for the trends observed. Overall, the data highlight the importance of comprehensive data sets for revealing extraterrestrial processes, which could define the nature of organic matter reaching habitable environments, such as those of the Early Earth.No potential conflict of interest relevant to this article was reported.The Society for Free Radical Research JapanActa Medica Okayama0912-00097922026Organ-specific modulation of antioxidant functions by combined voluntary exercise and radon inhalation in mice141149ENReijuTakenakaGraduate School of Health Sciences, Okayama UniversityAyumiTanakaGraduate School of Health Sciences, Okayama UniversityShogoMiyanagaGraduate School of Health Sciences, Okayama UniversityShotaNaoeNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyShunaGotoGraduate School of Health Sciences, Okayama UniversityMitsukiNaganoGraduate School of Health Sciences, Okayama UniversityKotaroTanoGraduate School of Health Sciences, Okayama UniversityNorieKanzakiNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyAkihiroSakodaNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyKiyonoriYamaokaFaculty of Health Sciences, Okayama UniversityTakahiroKataokaFaculty of Health Sciences, Okayama UniversityRadon inhalation as well as voluntary exercise increase antioxidant function in experimental animals. However, the combined effects of radon inhalation and exercise on antioxidant functions have not yet been investigated. In this study, we examined the effects of combined voluntary wheel running (VWR) and radon inhalation on antioxidant functions in various organs of mice. Mice were individually housed in cages equipped with running wheels, and allowed voluntary exercise for 5, 15, or 25 days, followed by radon inhalation at 2,000 Bq/m3 for 24 h. Antioxidant function was enhanced by the combined treatment in the kidneys, pancreas, spleen, and stomach, with responses varying according to exercise duration. In contrast, antioxidant function was reduced in the lungs and heart. No clear interaction effects of the combined treatment were observed in the liver, small intestine, colon, and brain. These findings suggest that the combined effects of voluntary exercise and radon inhalation on antioxidant functions are organ-specific and can be categorized into distinct response patterns across tissues.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0300-81265442026Rectal syphilis: a great imitator of rectal malignancy21552156ENHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityA 48-year-old transgender woman presented with a sudden onset of bloody stool. Colonoscopy revealed an ulcerated, circumscribed mass in the lower rectum, closely resembling a Borrmann type 2 malignancy. The patient lacked classic signs of syphilis, such as anal pain, primary genital chancres, or localized lymphadenopathy. However, serological assays were highly reactive, and immunohistochemical analysis of the biopsy specimen confirmed the presence of Treponema pallidum, establishing the diagnosis of syphilitic proctitis. A four-week oral amoxicillin regimen (1,500 mg/day) led to complete clinical and serological resolution. This elusive condition must be considered when evaluating anorectal mucosal abnormalities.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813822026令和７年度岡山医学会賞 総合研究奨励賞（結城賞）3134ENYuiKambaraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2699-9307662026NUAK2 Inhibition Enhances Macromolecular Drug Delivery in a 3D Fibrotic Model of the Pancreatic Tumor Microenvironmente202500237ENMisakiNakamuraDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyoshi Y.TanakaDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityMayuOhiraDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityHarukoOhta‐OkanoDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityReikaNakamuraDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityYuSenoDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversitySaayaYaraDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversitySakuraFujitaDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityDaichiShibataDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayaYamamotoDepartment of Materials Processing Graduate School of Engineering, Tohoku UniversityShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityKensukeOsadaDepartment of Molecular Imaging and Theranostics Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) HoracioCabralDepartment of Bioengineering Graduate School of Engineering, The University of TokyoAtsushiMasamuneDivision of Gastroenterology Graduate School of Medicine, Tohoku UniversityMitsunobu R.KanoDepartment of Pharmaceutical Biomedicine Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityPancreatic 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-β (TGFβ) 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.Elsevier BVActa Medica Okayama1059-13111412026Transient loss of wakefulness with falls in temporal lobe epilepsy: A retrospective single-centre study254261ENKoheiIzumiharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsuyaSasakiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeOkazakiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunTanimotoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyaSaijoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKyoheiKinDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction: Focal impaired awareness seizures in temporal lobe epilepsy (TLE) typically involve behavioural arrest and automatisms with preserved posture. However, some patients can exhibit a transient loss of wakefulness with fall without any overt motor manifestations, a phenomenon previously described as “temporal lobe syncope.” However, previous reports did not always rigorously exclude FBTCS or ictal asystole. Herein, we aimed to reappraise this semiology by excluding these conditions using simultaneous video-electroencephalogram (VEEG) and electrocardiogram (ECG), clarifying its clinical characteristics.<br>
Methods: We retrospectively analysed 65 patients with drug-resistant TLE who underwent surgery between April 2017 and December 2025. Seizures with transient loss of wakefulness with fall were defined as events without generalized motor manifestations or ECG changes, such as bradycardia or asystole. Outcomes were assessed using the ILAE seizure outcome classification.<br>
Results: Three of 65 patients exhibited seizures characterised by transient loss of wakefulness with fall. All patients were clinically diagnosed with left TLE, and these seizures developed at least 10 years after epilepsy onset. Simultaneous VEEG and ECG excluded ictal asystole and FBTCS as the causes of the falls. One patient achieved seizure freedom after anterior temporal lobectomy, whereas the other two patients did not achieve seizure freedom after surgery.<br>
Conclusion: Our findings suggest that transient loss of wakefulness in TLE patients may represent a distinct seizure semiology that should be differentiated from impaired awareness and from other causes of fall. Although the underlying mechanism remains uncertain, distinguishing wakefulness from awareness may provide a useful conceptual framework for understanding disorders of consciousness during epileptic seizures.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2352-5789662026Pembrolizumab-based systemic therapy associated with opportunities for subsequent local treatment in advanced or recurrent neuroendocrine carcinoma of the cervix: a five-case series102156ENNaoyukiIdaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShojiNagaoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuiTanakaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsushiFujikawaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMomokoTaniokaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyokoImataniDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinoriTaniDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHanakoSugiharaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirofumiMatsuokaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOkamotoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunkoHaragaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisashiMasuyamaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Neuroendocrine carcinoma (NEC) of the cervix is a rare, highly aggressive malignancy with limited evidence supporting immune checkpoint blockade. We evaluated the clinical activity of pembrolizumab-based therapy in patients with advanced or recurrent cervical NEC.<br>
Methods: We retrospectively reviewed five consecutive patients with advanced or recurrent cervical NEC treated with pembrolizumab-based therapy at Okayama University Hospital between November 2022 and April 2025. Clinical characteristics, radiologic responses, molecular profiles, adverse events, local treatments, and survival outcomes were analyzed.<br>
Results: The median age was 52 years. Three patients had newly diagnosed stage IVB disease, and two had recurrent metastatic disease after radical surgery and postoperative irinotecan plus cisplatin chemotherapy. All patients received paclitaxel plus carboplatin with pembrolizumab. An objective response was observed in all patients, including one complete response and four partial responses according to RECIST version 1.1. The median maximum tumor shrinkage was 78.5%, and median progression-free survival was 10.0 months. Comprehensive genomic profiling in four patients showed microsatellite-stable tumors with low tumor mutational burden in all evaluated cases. HPV association was supported by HPV16/18 sequences in three patients and diffuse p16 expression in one additional patient. Immune-related adverse events were grade 2 or lower. In three patients, systemic disease control allowed subsequent local treatment, including radiotherapy, conversion surgery, and stereotactic radiotherapy.<br>
Conclusion: Pembrolizumab-based therapy showed encouraging clinical activity despite microsatellite-stable status and low tumor mutational burden in evaluated cases. Sustained systemic disease control may provide an opportunity for multimodal treatment incorporating subsequent local treatment.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2050-09041472026A Biologically Dominant Trophoblastic Component Guiding Neoadjuvant EMA/CO in Endometrial Carcinoma: A Clinical Case Reporte72982ENShinsukeShirakawaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShojiNagaoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuiTanakaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsushiFujikawaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyokoImataniDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMomokoTaniokaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshinoriTaniDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHanakoSugiharaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOkamotoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaoyukiIdaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirofumiMatsuokaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunkoHaragaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChikakoOgawaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeiichiroNakamuraDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyukiYanaiDepartment of Diagnostic Pathology, Okayama UniversityHisashiMasuyamaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityEndometrial carcinoma with choriocarcinomatous components (ECCC) is a rare and aggressive malignancy for which optimal management remains undefined. We report a case illustrating how preoperative identification of a biologically dominant trophoblastic component can guide treatment sequencing and achieve durable remission. A 61-year-old postmenopausal woman presented with abnormal uterine bleeding. Endometrial biopsy revealed a mixed tumor composed predominantly of choriocarcinomatous elements with a minor grade 1 endometrioid carcinoma component. Despite only superficial myometrial invasion, imaging demonstrated multiple pulmonary nodules, and serum human chorionic gonadotropin (hCG) was markedly elevated (46,538 mIU/mL). This clinicopathological incongruity suggested that the trophoblastic component, rather than the low-grade endometrioid carcinoma, was driving disease progression. Neoadjuvant EMA/CO chemotherapy was therefore prioritized to achieve rapid systemic control. After six cycles, serum hCG normalized and pulmonary lesions completely resolved. The patient subsequently underwent total hysterectomy and bilateral salpingo-oophorectomy, which revealed no residual choriocarcinoma. She remains disease-free more than two years after completion of treatment. This case highlights the importance of recognizing clinicopathological incongruity and identifying the biologically dominant tumor component when determining treatment sequencing in rare mixed malignancies.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-66941852026The New Era of Intraperitoneal Carboplatin in Ovarian Cancer: From Biological Rationale to Clinical Implementation764ENShojiNagaoDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsushiFujikawaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuiTanakaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMomokoTaniokaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyokoImataniDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshinoriTaniDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHanakoSugiharaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOkamotoDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirofumiMatsuokaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaoyukiIdaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunkoHaragaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChikakoOgawaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHisashiMasuyamaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityEpithelial ovarian cancer is predominantly characterized by peritoneal dissemination, providing a strong biological rationale for intraperitoneal (IP) chemotherapy. Although IP cisplatin-based regimens have demonstrated substantial survival benefits in pivotal randomized trials, toxicity and catheter-related complications limit their widespread adoption. IP carboplatin has emerged as a pragmatic alternative with improved tolerability while preserving its pharmacokinetic advantages. This review summarizes the biological and pharmacological rationale for IP carboplatin and critically examines the clinical evidence, with a particular emphasis on the Intraperitoneal Carboplatin for Ovarian Cancer (iPocc) trial and its divergence from Gynecologic Oncology Group (GOG)-252. We further discuss the potential applicability of IP carboplatin beyond the traditional setting of minimal residual disease, including patients undergoing neoadjuvant chemotherapy and interval debulking surgery, as well as its possible use in the contemporary era of maintenance therapy. Collectively, the accumulated evidence supports renewed consideration of IP carboplatin as a versatile component in modern ovarian cancer management.No potential conflict of interest relevant to this article was reported.Public Library of Science (PLoS)Acta Medica Okayama1932-62032112026Fertility-sparing surgery with neoadjuvant chemotherapy in early and locally advanced cervical cancer: A clinical protocole0340963ENMomokoTaniokaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShojiNagaoDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaoyukiIdaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuiTanakaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsushiFujikawaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyokoImataniDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshinoriTaniDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHanakoSugiharaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOkamotoDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirofumiMatsuokaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunkoHaragaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChikakoOgawaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeiichiroNakamuraDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHisashiMasuyamaDepartment of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFertility preservation remains a critical concern in young women with early or locally advanced cervical cancer, as standard radical treatments compromise reproductive potential. This study aims to evaluate the feasibility, oncological safety, and reproductive outcomes of fertility-sparing treatment involving neoadjuvant chemotherapy followed by cervical conization and laparoscopic pelvic lymphadenectomy. This single-center, prospective, open-label, single-arm, Phase II interventional study will assess patients with FIGO stage IB2–IB3 cervical cancer (FIGO stage 2018) desiring fertility preservation. Eligible patients will receive three cycles of dose-dense paclitaxel and carboplatin (dd-TC), followed by conization and laparoscopic lymphadenectomy. The primary endpoint is successful uterine preservation. Patients requiring concurrent chemoradiotherapy due to inadequate treatment response will not be considered successful. Secondary endpoints include 2-year recurrence-free survival (RFS), overall survival (OS), quality of life assessments, menstrual and ovulatory resumption, pregnancy, live birth, miscarriage, and preterm birth. Adverse events will be graded according to CTCAE v5.0.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama2234-943X162026Case Report: Multidisciplinary approach for complete resection of primary advanced low-grade serous ovarian carcinoma involving the iliac vessels and paraspinal region1762009ENNaoyukiIdaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShojiNagaoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsushiFujikawaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuiTanakaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMomokoTaniokaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyokoImataniDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinoriTaniDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHanakoSugiharaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirofumiMatsuokaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOkamotoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunkoHaragaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChikakoOgawaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiroNakamuraDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisashiMasuyamaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Low-grade serous ovarian carcinoma (LGSC) is characterized by indolent progression and relative resistance to cytotoxic chemotherapy, making complete cytoreduction the key prognostic determinant. However, extra-pelvic invasion presents significant surgical and functional challenges requiring coordinated multidisciplinary management.<br>
Case presentation: A 62-year-old woman with FIGO stage IVB LGSC presented with right inguinal swelling infiltrating the femoral vein and abdominal wall. MRI and PET-CT revealed bilateral ovarian tumors and multiple lymph node metastases. A multidisciplinary operation involving gynecologic, orthopedic, plastic, and gastrointestinal surgeons was conducted. The procedures included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymphadenectomy, en bloc resection of the right inguinal lesion, femoral vein repair, and anterolateral thigh flap reconstruction. Complete resection (R0) was achieved. Postoperative recovery was favorable, with transient leg edema resolving within 4 months. The patient remains disease-free at 13 months after surgery.<br>
Discussion: Strategic multidisciplinary collaboration enabled complete resection and functional preservation in this chemotherapy-resistant LGSC case. We propose the “Four Surgical Limits” framework—anatomical, oncological, functional, and interdisciplinary—as a structured concept guiding operative decision-making beyond conventional boundaries.<br>
Conclusion: Multidisciplinary collaboration can overcome traditional surgical and oncologic barriers, achieving both radicality and quality-of-life preservation in advanced LGSC.<br>No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0449-30606742026Enhancement of antioxidant function in various organs in mice using combined thermal and radon inhalation treatment538549ENShogoMiyanagaGraduate School of Health Sciences, Okayama UniversityAyumiTanakaGraduate School of Health Sciences, Okayama UniversityReijuTakenakaGraduate School of Health Sciences, Okayama UniversityShotaNaoeNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyShunaGotoGraduate School of Health Sciences, Okayama UniversityMitsukiNaganoGraduate School of Health Sciences, Okayama UniversityKotaroTanoGraduate School of Health Sciences, Okayama UniversityNorieKanzakiNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyAkihiroSakodaNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyKiyonoriYamaokaFaculty of Health Sciences, Okayama UniversityTakahiroKataokaFaculty of Health Sciences, Okayama UniversityEnhancing antioxidant function is a key strategy for preventing and treating oxidative stress-related diseases. Radon inhalation and thermal treatment (TT) increase the levels of antioxidant enzymes, such as superoxide dismutase (SOD). The positive effects of this combination on pain-related diseases have been reported; however, few studies have elucidated the underlying mechanisms. In this study, we examined the enhancement of antioxidant function in various organs of mice subjected to combined TT and radon inhalation. The mice were placed in an incubator once daily for 40 min at 38.5 ± 0.5°C and treated for 1, 3 and 7 days. The mice then inhaled radon at a concentration of 2000 Bq/m3 for 24 h. The characteristic changes in antioxidant function following combined TT and radon inhalation could be categorized into four groups: (i) increased antioxidant function in the brain and colon; (ii) increased or decreased antioxidant function, as observed in the kidney; (iii) decreased antioxidant function, such as in the lungs and (iv) no changes, such as in the small intestine, spleen, pancreas, heart, liver and stomach. Additionally, SOD may be the antioxidant enzyme most sensitive to combined TT and radon treatment. Collectively, the combined treatment may be the most effective in activating antioxidative functions in the brain and colon. This study provides new insights into the effects of combined TT and radon inhalation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841722025A Rare Course of Chiari Malformation With Large Syringomyelia Presenting at 54 Years Olde78399ENMasatoTanakaOrthopedic Surgery, Okayama University HospitalSnehaSharmaOrthopedics, North Delhi Municipal Corporation (DMC) Medical CollegeKushal HGoriOrthopedic Surgery, Okayama Rosai HospitalMdShohidullahOrthopedic Surgery, Okayama Rosai HospitalKojiUotaniOrthopedic Surgery, Okayama University HospitalChiari 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 LLCActa Medica Okayama2168-81841682024Navigation-Guided C-arm-Free Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Comparative Study of Cage Orientation and Screw Insertion Accuracy Against the Conventional C-arm-Assisted Techniquee66070ENKojiUotaniNavigation-Guided C-arm-Free Minimally Invasive TransforaminalMasatoTanakaDepartment of Orthopaedic Surgery, Okayama Rosai HospitalChetanKumawatDepartment of Orthopaedic Surgery, Okayama Rosai HospitalSharvariGunjotikarDepartment of Orthopaedic Surgery, Okayama Rosai HospitalYoshiakiOdaNavigation-Guided C-arm-Free Minimally Invasive TransforaminalKensukeShinoharaNavigation-Guided C-arm-Free Minimally Invasive TransforaminalTadashiKomatsubaraDepartment of Orthopaedic Surgery, Okayama Rosai HospitalShinyaAratakiDepartment of Orthopaedic Surgery, Okayama Rosai HospitalToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a widely utilized technique in spine surgery. This study compares the efficacy and safety of MIS-TLIF performed with traditional C-arm fluoroscopy and C-arm-free O-arm navigation. To the best of our knowledge, our study is the first to compare cage positioning between C-arm-free and C-arm techniques for MIS- TLIF.<br>
Methods: A retrospective, comparative analysis was conducted on 43 patients undergoing MIS-TLIF. The group was divided based on the utilization of C-arm fluoroscopy or C-arm-free O-arm navigation. Key parameters analyzed included cage orientation, screw insertion accuracy, operative efficiency, and postoperative recovery. Radiographic measurements were used to assess surgical precision and perioperative complications were documented.<br>
Results: The study encompassed 43 patients, with no significant differences in demographic characteristics between the two groups. Surgical time and blood loss were comparable between C-arm-free and C-arm groups. O-arm navigation significantly reduced pedicle screw misplacement (p=0.024). Cage positioning differed between groups (p=0.0063): O-arm cages were mostly mid-center, while C-arm cages were more anterior-center. Such differences in the cage location did not cause any impact on clinical outcome. No significant differences were observed in postoperative complications (screw loosenings, dural tears, surgical site infections) between groups. The Oswestry Disability Index scores at the final follow-up showed no significant difference between the O-arm and C-arm groups, indicating similar levels of postoperative disability.<br>
Conclusion: Despite the clinically insignificant difference in cage placement between C-arm-free and C-arm dependent, C-arm-free MIS-TLIF significantly improves screw placement accuracy and reduces radiation exposure to operating stuff. This suggests its potential as a valuable tool for safer and more precise spinal fusion surgery.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841682024A New Minimally Invasive Technique for Thoracolumbar/Lumbar Focal Kyphosis Due to Osteoporotic Vertebral Fracture: A Case Reporte66069ENMasatoTanakaDepartment of Orthopedic Surgery, Okayama University HospitalAbd El KaderAl AskarDepartment of Orthopedic Surgery, Okayama Rosai HospitalChetanKumawatDepartment of Orthopedic Surgery, Okayama Rosai HospitalShashank JEkadeDepartment of Orthopedic Surgery, Okayama Rosai HospitalKojiUotaniDepartment of Orthopedic Surgery, Okayama University HospitalOsteoporotic vertebral fractures are common fractures in the elderly population and are often associated with low back pain and disruption in daily living activities. Reconstruction surgeries, such as corpectomy, are among the treatment options for these conditions. However, a corpectomy requires a longer surgical procedure and involves a significant amount of blood loss. We present the case of an 80-year-old woman with severe low back pain due to an L2 fracture and focal kyphosis treated with a novel minimally invasive technique. The patient underwent anterior and posterior surgery in the right decubitus position using a C-arm-free technique. Hyperlordotic cages were inserted in the upper and lower disc space via a lateral approach, while percutaneous pedicle screws were inserted from a posterior approach. These procedures were performed simultaneously under navigation guidance only.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818416102024Vonoprazan-Associated Mucosal Redness: A Report of Two Casese71325ENMasayaIwamuroGastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshiyasuKonoGastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaPathology, Okayama University HospitalSeijiKawanoGastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobumasaIkedaInternal Medicine, Clinic IkedaVonoprazan, a potassium-competitive acid blocker, is effective at treating acid-related gastrointestinal disorders but has been linked to gastric mucosal redness, a novel condition. This report describes two cases of vonoprazan-associated mucosal redness. Case 1 involved a 73-year-old woman who developed longitudinal erythema and mild mucosal changes after starting vonoprazan seven years ago. Case 2 involved a 70-year-old man who exhibited significant erythema and atrophic gastritis after seven months of treatment. In both cases, the pathological findings included hemorrhage in the superficial mucosa, highlighting that microhemorrhage may be the corresponding pathological finding for vonoprazan-associated mucosal redness.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841692024Decreased CD3+CD56+ Natural Killer T Lymphocytes and Increased Human Leukocyte Antigen-DR+ Cells in the Inflamed Area of Pouchitis in Ulcerative Colitis Patientse70066ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalMasahiroTakaharaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshihiroInokuchiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSakikoHiraokaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground: Pouchitis is an inflammatory condition that affects the ileal pouch during ileal pouch-anal anastomosis surgery. Despite its clinical significance, precise immunological mechanisms underlying pouchitis remain unclear. This study aimed to investigate the lymphocyte profile in the ileal pouch of patients with pouchitis compared to those with familial adenomatous polyposis (FAP) and ulcerative colitis without pouchitis using flow cytometry and immunohistochemical techniques.<br>
Methods: We prospectively analyzed endoscopic biopsy specimens from the ileal pouches of 15 patients and categorized them into three groups: FAP, ulcerative colitis with an inflammation-free pouch (UC-I), and ulcerative colitis with ulcers and/or erosions in the pouch (UC-UE). Flow cytometry was used to assess various T-lymphocyte markers, including cluster of differentiation (CD) 4, CD8, CD56, and human leukocyte antigen (HLA)-DR. Immunohistochemistry was performed to visualize the spatial distribution of CD3+, CD56+, and HLA-DR+ cells in the pouch mucosa.<br>
Results: We observed significantly reduced CD56+/CD3+ and CD8+/CD3+ ratios in the UC-UE group compared to those in the FAP group, indicating a disruption in natural killer T-cell populations. Immunohistochemical analysis revealed that the spatial distribution of lymphocytes differed among the non-inflamed mucosa, dense lymphocyte infiltration, and lymphoid follicles, with these components frequently intermingling. CD56 + cells were less abundant in areas with dense lymphocyte infiltration, whereas HLA-DR+ cells were more abundant.<br>
Conclusion: Our study revealed a decrease in CD56+ natural killer T cells and an increase in HLA-DR+-activated T cells in areas with dense lymphocyte infiltration, suggesting an association between these cells and pouchitis in ulcerative colitis. The distinct patterns observed in non-inflamed mucosa, areas with dense lymphocyte infiltration, and lymphoid follicles underscore the need for further analyses of these three segments to elucidate the immunological mechanisms underlying pouchitis.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2367-09321072026Photochemical Oxidative Esterification of Aldehydes with Radical-Sensitive Alcohols via CH Brominatione70221ENNova AlfianHariyantoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHaruAndoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAtsuyaMiyamotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroyoshiTakamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityIsaoKadotaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentaTanakaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPhotochemical esterification is an attractive strategy for the synthesis of multifunctionalized esters, and the use of aldehydes as substrates offers an alternative to conventional carboxylic acid–based approaches. In particular, reactions via acyl halide intermediates are useful for accessing functionalized esters; however, examples of such transformations remain limited so far, and their compatibility with radical-sensitive alcohols remains relatively unexplored. Here, we report a photochemical oxidative esterification of aldehydes with radical-sensitive alcohols enabled by CH bromination. This reaction proceeds without stoichiometric additives, such as bases, and enables the incorporation of a broad range of radical-sensitive functional groups into esters. Thus, it represents a promising platform for the synthesis of pharmaceuticals and functional materials.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1639-44882026Triple Oxygen Isotope Compositions of Isotopic Reference Waters: Implications for VSMOW-Scale and VSMOW–SLAP-Scale Δ′17O CalibrationENRyojiTanakaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityAndreasPackGeorg-August-Universität Göttingen, Geowissenschaftliches ZentrumTyler B.CoplenUS Geological SurveyTriple oxygen isotope ratios of waters are commonly reported on the VSMOW–SLAP scale, whereas comparison with theoretical calculations and assessment of instrumental scale distortion require accurate constraints on the measured isotopic compositions of the primary isotopic reference materials (iRMs) themselves. In particular, the measured δ17OVSMOW and Δ′17OVSMOW values for SLAP and its substitute, SLAP2, remain insufficiently constrained and reported values differ among laboratories. Here, we measured triple oxygen isotope ratios for two primary iRMs (VSMOW and SLAP) and twelve secondary iRMs (VSMOW2, SLAP2, GISP, GRESP, USGS45, USGS46, USGS46a, USGS47, USGS48, USGS49, USGS50 and USGS53) using BrF5 fluorination and dual-inlet isotope-ratio mass spectrometry. For SLAP, we obtained δ18OVSMOW = -55.50 ± 0.15‰ and δ17OVSMOW = -29.66 ± 0.08‰, giving Δ′17OVSMOW = 34 ± 6 per meg (all expanded uncertainties, k = 2). The corresponding values for SLAP2 agree within uncertainty. When expressed on the conventional VSMOW–SLAP scale, our Δ′17OVSMOW–SLAP values for all secondary iRMs with available literature values agree with previously published values within uncertainty, confirming interlaboratory comparability on that scale. In contrast, waters with low δ18O values, Δ′17OVSMOW values are systematically higher than the corresponding Δ′17OVSMOW–SLAP values. These results further suggest that accurate determination of the VSMOW-scale isotopic composition of SLAP and/or SLAP2 across laboratories is essential, particularly for low-δ18O samples, for which the difference between VSMOW-scale and VSMOW–SLAP-scale Δ′17O values becomes large, and for meaningful comparison between measured data and theoretical calculations.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2045-89401622026Recurrence of Pulmonary Hypertension After Unilateral Lung Transplantation: Histological Evidence of Vasoconstrictive Mechanisme70289ENSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiIchimuraDepartment of Pathology, Hiroshima City Hiroshima Citizens HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraCenter for Advanced Heart Failure, Okayama University HospitalShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPulmonary hypertension (PH) is widely recognized as a disease driven by both vasoconstriction and vascular remodeling. Vasoconstriction is thought to play a predominant role in the early stages of PH, whereas the contribution of vascular remodeling increases as the disease progresses. However, clinical or histological evidence of this pathological progression has not been reported. We describe a case of recurrent PH after unilateral right lung transplantation, ultimately requiring bilateral transplantation 9 years later, and discuss the pathogenesis of PH based on histological findings in the transplanted normal lungs and changes in pulmonary blood flow observed by lung perfusion scintigraphy. Serial lung perfusion scintigraphy revealed a dynamic shift in pulmonary blood flow, initially favoring the transplanted lung, followed by a gradual decline. Histological examination demonstrated that the right lung of the second transplantation showed minimal vascular remodeling. These findings provide compelling evidence that vasoconstriction was the predominant contributor to PH after the first transplantation, offering unique insight into early PH pathobiology.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0941-43553482026Incidence and impact of odontogenic infection-related febrile episodes during perioperative doxorubicin-cyclophosphamide or docetaxel-cyclophosphamide chemotherapy for breast cancer747ENYoshihikoSogaDivision of Hospital Dentistry, Okayama University HospitalKumikoMatsuzakiDivision of Hospital Dentistry, Okayama University HospitalHirotakaKosakiDivision of Hospital Dentistry, Okayama University HospitalTomokoKishimotoDivision of Hospital Dentistry, Okayama University HospitalAikoYoshitomiDivision of Hospital Dentistry, Okayama University HospitalMakotoKajizonoDepartment of Pharmacy, Okayama University HospitalTakashiMakitaDepartment of Pharmacy, Okayama University HospitalYutaTanakaDepartment of Pharmacy, Okayama University HospitalYoshitoZamamiDepartment of Pharmacy, Okayama University HospitalTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalHiroyoshiDoiharaDepartment of Surgery, Kawasaki Medical School General Medical CenterBackground 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 SocietyActa Medica Okayama1340-34783312026Safe Continuation of Apheresis during Pregnancy using the Double-Filtration Plasmapheresis Thermo Mode in a Pregnant Female with Familial Hypercholesterolemia: A Case Report109115ENYoshimasaSakurabuDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYukaOkuyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesErikoEtoDepartment of Obstetrics and Gynecology, Okayama University HospitalKanakoTakasugiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTomohikoAsakawaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKatsuyoshiKatayamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShugoOkamotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesChihiroFujiharaDepartment of Clinical Engineering Center, Okayama University HospitalKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRyokoUmebayashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesFamilial hypercholesterolemia (FH) is an inherited disorder characterized by elevated LDL cholesterol levels and an increased risk of early-onset atherosclerotic cardiovascular disease. In pregnant female with FH, apheresis is the preferred treatment because standard therapeutic agents such as statins are contraindicated during pregnancy. LDL adsorption therapy is commonly used; however, after 27 weeks of gestation, it is often switched to dual filtration plasma exchange (DFPP) due to the significant drop in blood pressure caused by bradykinin production. However, DFPP has limited ability to adapt to the increase in circulating plasma volume associated with pregnancy. Here we discuss the case of a 32-year-old female with homozygous FH who underwent different apheresis strategies during her pregnancies. In her first pregnancy, she continued LDL adsorption therapy using DFPP but ultimately delivered a small-for-gestational-age infant via cesarean section. For her second pregnancy, double-filtration plasmapheresis thermo mode, DF-thermo, was introduced to mitigate the limitations of DFPP and LDL adsorption therapies, such as hypotension during apheresis and albumin loss. By minimizing these complications, DF-thermo allowed for a successful delivery without compromising fetal growth.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1323-89307532026Outcomes following the discontinuation of biologic therapy in patients with severe asthma400408ENTadaoNagasakiDepartment of Respiratory Medicine and Allergology, Kindai University Nara HospitalHisakoMatsumotoDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineTakashiIwanagaDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineKazutoMatsunagaDepartment of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi UniversityKiyoshiSekiyaClinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National HospitalTomoyaHaradaDepartment of Multidisciplinary Internal Medicine, Division of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori UniversityShogoSakuraiDepartment of Respiratory Medicine, Shizuoka General HospitalNorihiroHaradaDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of MedicineToshiyukiKoyaDepartment of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental SciencesKoichiFukunagaDivision of Pulmonary Medicine, Department of Medicine, Keio University, School of MedicineTakeshiKanekoDepartment of Pulmonology, Yokohama City University Graduate School of MedicineKazuhisaAsaiDepartment of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan UniversityYukoKomaseDepartment of Respiratory Medicine, St.Marianna University School of Medicine, Yokohama Seibu HospitalYasuhiroGonDivision of Respiratory Medicine, Department of Internal Medicine, Nihon University School of MedicineAkihikoTanakaDepartment of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of MedicineHironoriSagaraDepartment of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of MedicineHironobuSunadomeDepartment of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto UniversityTatsuyaNaganoDivision of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineYoichiNakamuraMedical Center for Allergic and Immune Diseases, Yokohama City Minato Red Cross HospitalAkioNiimiDepartment of Respiratory Medicine, Allergy, and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesNoboruHattoriDepartment of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima UniversityTakashiHajiroDepartment of Respiratory Medicine, Tenri HospitalHajimeFujimotoDepartment of Pulmonary and Critical Care Medicine, Mie University Graduate School of MedicineMasayukiHojoDivision of Respiratory Medicine, National Center for Global Health and MedicineNobuakiMiyaharaDepartment of Medical Technology, Okayama University Graduate School of Health SciencesMasafumiYamaguchiDivision of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical ScienceKimikoTsujiDepartment of Respiratory Medicine and Allergology, Kochi Medical School, Kochi UniversityAkikoSanoDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineRyutaHaraguchiDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineHiroyukiSanoDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineMasatoMurakiDepartment of Respiratory Medicine and Allergology, Kindai University Nara HospitalYujiTohdaDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineBackground: 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/μL), 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-4Rα. 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.American Society of Tropical Medicine and HygieneActa Medica Okayama0002-963711432026A Case of Heavy Paragonimiasis Involving a Multi-Organ Presentation with Hypereosinophilia and Hepatic Migration486489ENHidemasaAkazawaDepartment of Infectious Diseases, Okayama University HospitalHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalShinnosukeFukushimaDepartment of Infectious Diseases, Okayama University HospitalKentaNakamotoDepartment of Infectious Diseases, Okayama University HospitalKoheiOguniDepartment of Infectious Diseases, Okayama University HospitalYoheiManabeDepartment of Pharmacy, Okayama University HospitalMioKokubo-TanakaDivision of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of MiyazakiHaruhikoMaruyamaDivision of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of MiyazakiFumioOtsukaDepartment of General Medicine, Okayama University HospitalParagonimiasis is a parasitic disease caused by the genus Paragonimus, typically transmitted through the ingestion of raw or undercooked freshwater crabs. Although pulmonary involvement is typical, ectopic migration to subcutaneous or hepatic sites is rare and poses diagnostic challenges. A case of paragonimiasis in a 29-year-old Cambodian woman residing in Japan who presented with painless subcutaneous nodules on the chest and abdomen is reported in the current study. She had consumed raw crab 4 months before presentation. Laboratory findings revealed marked eosinophilia (21,000/µL) and elevated immunoglobulin E (5,049 IU/mL). Computed tomography scans revealed pleural effusion, club-shaped pulmonary consolidation, funicular hypodense lesions in the liver, and subcutaneous lesions. Stool and sputum test results were negative for parasite eggs; however, a microplate ELISA indicated a Paragonimus westermani infection. The patient responded well to 3 consecutive days of praziquantel (75 mg/kg/day) and was discharged a week later. This case highlights the importance of considering paragonimiasis in patients with unexplained subcutaneous nodules and eosinophilia, especially when supported by dietary risk factors.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Asthma-like bronchodilator responsiveness in patients with neuronal intranuclear inclusion disease16760ENDaisukeTaharaDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityNaoTaharaDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityChisatoTamaiDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityAkioAkagiDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityYuichiRikuDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityHiroakiMiyaharaDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityReiKobayashiDepartment of Neurology, NHO Nagoya Medical CenterHisashiOkadaDepartment of Neurology, NHO Nagoya Medical CenterMichiKawamotoDepartment of Neurology, Kobe City Medical Center General HospitalJunkoIshiiDepartment of Neurology, Kobe City Medical Center General HospitalHirokiYamazakiDepartment of Neurology, Tokushima University Graduate School of Biomedical ScienceTakashiKurashigeDepartment of Neurology, NHO Kure Medical Center and Chugoku Cancer CenterAtsuhikoSugiyamaDepartment of Neurology, Chiba UniversityAkikoNagaishiDepartment of Neurology, NHO Nagasaki Kawatana Medical CenterKatsuyaNishidaDepartment of Neurology, NHO Hyogo Chuo National HospitalKazumaSugieDepartment of Neurology, Nara Medical University HospitalTakayasuFukudomeDepartment of Neurology, NHO Nagasaki Kawatana Medical CenterKazukoHasegawaDepartment of Neurology, NHO Sagamihara National HospitalHiroyukiIshiuraDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHarukiKoikeDepartment of Neurology, Saga UniversityTakashiKasaiDepartment of Neurology, Kyoto Prefectural University of MedicineToshikiMizunoDepartment of Neurology, Kyoto Prefectural University of MedicineMasahiroAndoDepartment of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental SciencesYujiroHiguchiDepartment of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental SciencesFumiakiTanakaDepartment of Neurology and Stroke Medicine, Yokohama City University Graduate School of MedicineYuishinIzumiDepartment of Neurology, Tokushima University Graduate School of Biomedical ScienceGenSobueAichi Medical UniversityYasushiIwasakiDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversitySatoruItoDivision of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical UniversityJunSoneDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityNeuronal 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.American Society for Clinical InvestigationActa Medica Okayama1558-8238136102026Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLCe195021ENKohsukeIsomotoDepartment of Medical Oncology, Kindai University Faculty of MedicineKojiHarataniDepartment of Medical Oncology, Kindai University Faculty of MedicineTakahiroTsujikawaDepartment of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of MedicineShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalYusukeMakutaniDepartment of Surgery, Kindai University Faculty of MedicineMasayukiTakedaDepartment of Medical Oncology, Kindai University Faculty of MedicineKimioYonesakaDepartment of Medical Oncology, Kindai University Faculty of MedicineKaoruTanakaDepartment of Medical Oncology, Kindai University Faculty of MedicineTsutomuIwasaDepartment of Medical Oncology, Kindai University Faculty of MedicineKazukoSakaiDepartment of Genome Biology, Kindai University Faculty of MedicineKazutoNishioDepartment of Genome Biology, Kindai University Faculty of MedicineAkihikoItoDepartment of Pathology, Kindai University Faculty of MedicineKazuhikoNakagawaDepartment of Medical Oncology, Kindai University Faculty of MedicineHidetoshiHayashiDepartment of Medical Oncology, Kindai University Faculty of MedicineBACKGROUND. 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.Pharmaceutical Society of JapanActa Medica Okayama0918-615847122024Staphylococcus aureus δ-Toxin Induces Ca2+ Influx-Independent Degranulation of Murine Cultured Mast Cells20582064ENKangLiuLaboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical UniversityTomoakiKatayamaDivision of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHitomiSatoDivision of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuhoHamaoka-TamuraLaboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical UniversityMichikoSaitoBioscience Research Center, Kyoto Pharmaceutical UniversityKazuyukiFurutaDivision of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoshiTanakaLaboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical UniversityCutaneous colonization with Staphylococcus aureus (SA) is frequently observed in patients with atopic dermatitis. SA produces a wide variety of bacterial toxins, among which δ-toxin was found to induce degranulation of mast cells. Degranulation of mast cells could enhance bacterial clearance and protection from future SA infection but lead to exacerbation of atopic dermatitis. Because it remains to be determined how δ-toxin triggers degranulation, we investigated δ-toxin-induced changes in murine bone marrow-derived cultured mast cells in this study. We found that δ-toxin-induced degranulation could be classified into two phases, an early Ca2+-independent and a late Ca2+-dependent phase. Recent studies suggest that NOD-like receptor family, pyrin domain containing 3 is involved in the degranulation of mast cells, raising a possibility that leakage of K+ induced by δ-toxin is involved in the Ca2+-independent phase. However, Ca2+-independent degranulation remains unchanged although Ca2+-influx and degranulation induced by δ-toxin were significantly suppressed in the presence of high concentrations of K+. Because actin depolymerization was reported to induce degranulation in the absence of Ca2+ in the permeabilized rat peritoneal mast cells, a slow but steady decrease in the amount of filamentous actin observed here may be involved in Ca2+-independent degranulation induced by δ-toxin. Although Mas-related G protein-coupled receptor (MRGPR) X2 in humans and Mrgprb2 in mice are regarded as the receptors responsible for immunoglobulin E-independent degranulation, δ-toxin-induced degranulation remained unchanged in Mrgprb2−/− mast cells. Our findings pave the way for identification of the target receptors of δ-toxin.No potential conflict of interest relevant to this article was reported.American Society of Clinical Oncology (ASCO)Acta Medica Okayama0732-183X43162025Methotrexate, 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 Trial18861897ENHiroakiHiragaMusculoskeletal Oncology, NHO Hokkaido Cancer CenterRyunosukeMachidaJapan Clinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalAkiraKawaiMusculoskeletal Oncology, National Cancer Center HospitalToshiyukiKunisadaOrthopaedic Surgery, Faculty of Medicine, Okayama UniversityTsukasaYonemotoOrthopaedic Surgery, Chiba Cancer CenterMakotoEndoOrthopaedic Surgery, Graduate School of Medical Sciences, Kyushu UniversityYoshihiroNishidaDepartment of Rehabilitation Medicine, Nagoya University HospitalAkihitoNaganoOrthopaedic Surgery, Gifu University School of MedicineKeisukeAeOrthopaedic Surgery, Cancer Institute HospitalShinichirouYoshidaOrthopaedic Surgery, Tohoku University Graduate School of MedicineKunihiroAsanumaOrthopaedic Surgery, Mie UniversityJunyaToguchidaDepartment of Tissue Regeneration, Center for Induced Pluripotent Stem Cell Research and Application, Institute for Frontier Medical Sciences, Kyoto UniversityTaisukeFurutaOrthopaedic Surgery, Hiroshima UniversityRobertNakayamaDepartment of Orthopaedic Surgery, Keio University School of MedicineToshihiroAkisueOrthopaedic Surgery, Kobe UniversityToruHirumaBone and Soft Tissue Tumour Surgery, Kanagawa Cancer CenterTakeshiMoriiOrthopaedic Surgery, Kyorin UniversityHidekiNishimuraOrthopaedic Surgery, Kagawa University HospitalKojiHiraokaOrthopaedic Surgery, Kurume University HospitalMasanobuTakeyamaOrthopaedic Surgery, Yokohama City University HospitalMakotoEmoriOrthopaedic Surgery, Sapporo Medical University HospitalSatoshiTsukushiOrthopaedic Surgery, Aichi Cancer CenterHiroshiHatanoMusculoskeletal Oncology, Niigata Cancer Center HospitalHiroyukiKawashimaOrthopaedic Surgery, Niigata University Medical & Dental HospitalKazuoIsuOrthopaedic Surgery, Higashi Sapporo HospitalKazuhiroTanakaAdvanced Medical Sciences, Oita University Faculty of MedicineTomokoKataokaJapan Clinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalHaruhikoFukudaJapan Clinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalYukihideIwamotoOrthopaedic Surgery, Kyushu Rosai HospitalToshifumiOzakiOrthopaedic Surgery, Faculty of Medicine, Okayama UniversityPurpose 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 α 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.Royal Society of Chemistry (RSC)Acta Medica Okayama1477-052022462024A direct oxidative esterification of aldehydes with alcohols mediated by photochemical C–H bromination90329035ENHaruAndoDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversitySakuraKodakiDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityHiroyoshiTakamuraDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityIsaoKadotaDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityKentaTanakaResearch Institute for Interdisciplinary Science, Okayama UniversityThe photochemical direct esterification of aldehydes with alcohols via in situ-generated acyl-bromides presented in this report is an attractive complementary addition to hitherto reported methods, as these are usually carried out in a two-step, one-pot procedure in order to avoid side reactions such as the oxidation of alcohols by halogen sources.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0361-860910012024Different impacts of granulocyte colony‐stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type6677ENTakaakiKonumaDepartment of Hematology/Oncology, The Institute of Medical Science, The University of TokyoKazuakiKamedaDivision of Hematology, Jichi Medical University Saitama Medical CenterKaoruMoritaDivision of Hematology, Jichi Medical UniversityTadakazuKondoDepartment of Hematology, Kobe City Medical Center General HospitalFumihikoKimuraDivision of Hematology, Department of Internal Medicine, National Defense Medical CollegeHidekiNakasoneDivision of Hematology, Jichi Medical University Saitama Medical CenterFumihikoOuchiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalNaoyukiUchidaDepartment of Hematology, Toranomon HospitalMasatsuguTanakaDepartment of Hematology, Kanagawa Cancer CenterTetsuyaNishidaDepartment of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi HospitalTakahiroFukudaDepartment of Hematopoietic Stem Cell Transplantation, National Cancer Center HospitalYutaHasegawaDepartment of Hematology, Hokkaido University HospitalMamikoSakata‐YanagimotoDepartment of Hematology, University of Tsukuba HospitalMakotoOnizukaDepartment of Hematology and Oncology, Tokai University School of MedicineMasashiSawaDepartment of Hematology and Oncology, Anjo Kosei HospitalShuichiOtaDepartment of Hematology, Sapporo Hokuyu HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalShin‐IchiroFujiwaraDivision of Hematology, Jichi Medical UniversitySatoshiYoshiharaDepartment of Hematology, Hyogo Medical University HospitalFumihikoIshimaruTechnical Department, Japanese Red Cross Society Blood Service HeadquartersMakotoYoshimitsuDepartment of Hematology and Rheumatology, Kagoshima University HospitalYoshinobuKandaDivision of Hematology, Jichi Medical UniversityMarieOhbikiJapanese Data Center for Hematopoietic Cell TransplantationYoshikoAtsutaJapanese Data Center for Hematopoietic Cell TransplantationMasamitsuYanadaDepartment of Hematology and Oncology, Nagoya City University East Medical CenterWe 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 LLCActa Medica Okayama1341-96253032025Five-year outcomes with gefitinib induction and chemoradiotherapy in EGFR-mutant stage III non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study497503ENKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalShoSaekiDepartment of Respiratory Medicine, Kumamoto University HospitalShinyaSakataDepartment of Respiratory Medicine, Kumamoto University HospitalMasafumiYamaguchiDepartment of Thoracic Oncology, NHO Kyushu Cancer CenterDaijiroHaradaDepartment of Thoracic Oncology, National Hospital Organization Shikoku Cancer CenterAkihiroBesshoDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalKentaroTanakaDepartment of Respiratory Medicine, Kyushu University HospitalKojiInoueDepartment of Respiratory Medicine, Kitakyushu Municipal Medical CenterKojiInoueDepartment of Respiratory Medicine, Ehime Prefectural Central HospitalKenichiGembaDepartment of Respiratory Medicine, Chugoku Central HospitalToshioKuboDepartment of Respiratory Medicine, Okayama University HospitalAkikoSatoDepartment of Respiratory Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalHiromiWatanabeDepartment of Respiratory Medicine, Okayama University HospitalJunjiKishimotoDepartment of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu UniversityYoshiyukiShioyamaRadiation Oncology, Ion Beam Therapy Center, SAGA HIMAT FoundationKuniakiKatsuiDepartment of Radiology, Kawasaki Medical SchoolKenjiSugioDivision of Radiation Oncology, Department of Thoracic and Breast Surgery, Oita UniversityKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalBackground 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/jRCTs071180036No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1880-59817812026Electrical conductivity measurements of rhyolitic glass at high pressure and high temperature57ENYusukeHaraguchiGraduate School of Engineering, The University of OsakaKiyoshiFuji-TaGraduate School of Engineering, The University of OsakaTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityMasashiNakamotoGraduate School of Engineering, The University of OsakaMasanoriSuzukiGraduate School of Engineering, The University of OsakaToshihiroTanakaGraduate School of Engineering, The University of OsakaWe performed electrical conductivity measurements of rhyolite glasses across the glass transition temperature at 1 GPa. Our experimental data show that, in the Arrhenius plot, the conductivity of rhyolite with 0.2 wt% H2O has an inflection point between around 760 K, while for rhyolite with 4.9 wt% H2O the gradient changes between 685 and 825 K. These inflection points correlate with the glass transition temperature, and are compared with results of previous experiments. The degree of welding of clastic and hydrous rock can be constrained by estimating glass transition temperatures of volcanic rocks combined with measurements of electrical conductivity structures obtained from electromagnetic soundings beneath volcanic bodies. This, in turn, can be used to aid predictions of volcanic eruption.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0883-29272072026Effects of secondary hydrothermal fluids on gallium distribution and coordination in hot springs silica using Ga K-edge XANES106961ENM.C.RoweSchool of Environment, University of AucklandK.A.CampbellSchool of Environment, University of AucklandD.A.StallardSchool of Environment, University of AucklandB.LyonSchool of Environment, University of AucklandA.LangendamAustralian Synchrotron Facility (Ansto)E.KalininaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityM.YamanakaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityR.TanakaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityT.ChristopherSchool of Chemical Sciences, University of AucklandS.W.RuffArizona State University, School of Earth And Space ExplorationE.NersezovaSchool of Environment, University of AucklandT.OtaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityA.HamiltonSchool of Environment, University of AucklandGallium (Ga), a critical element in the electronics industry, is enriched in hot spring silica deposits (sinter) at concentrations comparable to, and in some cases greater than, bauxite, coal, and sphalerite deposits from which it is currently extracted. Focusing on well characterized Holocene and Pleistocene New Zealand sinters, we utilize synchrotron-X-ray fluorescence (sXRF) and Ga K-edge X-ray absorption near edge structure (XANES) spectroscopy to examine the spatial distribution of Ga as well as its changing coordination number. Ga+3 is the only observed oxidation state in the analyzed sinters. Gallium is predominantly found in tetrahedral coordination in sinter deposited from alkali chloride fluids, with analyses best matching Ga-aluminosilicate standards. However, Ga coordination is octahedral in sinter samples that have undergone alteration by acidic fluids/gases, associated with a change in hydrology from alkali-chloride to acid-sulfate fluid conditions. High Ga concentrations are found associated with both these coordination environments, with a heterogeneous distribution. Octahedral Ga is observed both as particles and in larger regions affected by Fe-rich fluid overprinting. The combined use of sXRF and XANES demonstrates an ability to fingerprint diagenesis and alteration in these complex geothermal settings where tetrahedral and octahedral Ga co-exist. The transition from tetrahedral to octahedral Ga also appears to mimic the inferred natural process forming lateritic bauxite deposits, where remobilized tetrahedral Ga is reconcentrated and adsorbed to oxides. A similar process may occur for sinter Ga enrichment, whereby introduced Ga in acidic conditions is adsorbed to oxide phases as the Fe-rich secondary fluids infiltrate porous sinter material.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama3042-6081222026Interfacial Bond Strength of Resin Cement to Polyetheretherketone (PEEK) Using Experimental Primers Doping Multifunctional Methacrylate and Acrylate Monomers12ENYukinoriMaruoDepartment of Prosthodontics, Okayama UniversityKumikoYoshiharaHealth Research Institute, National Institute of Advanced Industrial Science and TechnologyMasaoIrieOkayama University Dental SchoolNoriyukiNagaokaAdvanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental SchoolNaokiKodamaDepartment of Prosthodontics, Okayama UniversityYukiTanakaDepartment of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMihoKuwaharaDepartment of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroAkiyamaDepartment of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPolyetheretherketone (PEEK) is a high-performance thermoplastic polymer with low surface energy, chemical inertness, and a highly crystalline structure, which limit durable adhesion to resin-based materials and require improved bonding strategies. This in vitro study evaluated the effect of incorporating multifunctional methacrylate (TMPTMA) and acrylate monomers (A-TMPT and A-DPH) into an experimental primer on the 24 h shear bond strength (SBS) of resin cement to PEEK (n = 6 per group). Experimental primers were prepared by adding varying amounts (100–500 µL) of each multifunctional monomer to a UDMA/MMA-based primer, and SBS was measured after cementation with a dual-cure resin cement. TMPTMA-containing primers produced median SBS values of approximately 10–12 MPa, while acrylate-based primers showed slightly higher values, particularly at higher concentrations, reaching up to ~15.8 MPa; however, no statistically significant improvement over the control group was observed (p > 0.05). Failure modes were predominantly mixed across all conditions. These findings indicate that multifunctional monomers, despite their potential to enhance cross-link density and wetting, do not substantially overcome the intrinsic adhesion-resistant nature of polished PEEK. The results underscore that monomer modification alone is insufficient and that effective adhesion to PEEK likely requires integrated strategies combining chemical activation with mechanical surface conditioning.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026Determination of the Side Responsible for Bilateral Pneumothorax due to Pleural Communication225228ENKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruchikaYamamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKumiNakajimaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidejiroTorigoeDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/70859Simultaneous 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 SchoolActa Medica Okayama0386-300X8032026Common Bile Duct Stone Formed Around an Ingested Fish Bone219223ENKaitaroHigashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterMotoyasuTabuchiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShinyaSakamotoDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShutaTamuraDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterSunaoUemuraDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterTeppeiTokumaruDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterTakehiroOkabayashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterCase Report10.18926/AMO/70858An 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 SchoolActa Medica Okayama0386-300X8032026Peripheral Blood T-Cell Receptor Repertoire and Host Immune Background in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy169178ENYukiNakamuraDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalTakayukiIwamotoDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalYukikoKajiwaraDepartment of Breast Surgery, Hiroshima City Hiroshima Citizens HospitalAkiraHidaDepartment of Pathology, Matsuyama Shimin HospitalShogoNakamotoDepartment of Breast and Endocrine Surgery, Okayama University HospitalYuichiroMiyoshiDepartment of Breast Endocrine Surgery, Kagawa Prefectural Center HospitalTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalMasahikoIkedaDepartment of Breast and Thyroid Surgery, Fukuyama City HospitalHiroyoshiDoiharaDepartment of General Surgery, Kawasaki Medical School General Medical CenterRyoheiOgataDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalYoshikazuKoikeDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalTsunehisaNomuraDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalKatsuhiroTanakaDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalKazutakaNakashimaDepartment of General Surgery, Kawasaki Medical School General Medical CenterTomokiYamatsujiDepartment of General Surgery, Kawasaki Medical School General Medical CenterNarutoTairaDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalOriginal Article10.18926/AMO/70852The 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: ρ=0.046, p=0.845; TRB: ρ=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.American Physiological SocietyActa Medica Okayama1040-060533052026The role of S100A8/A9 in the pathogenesis of acute exacerbations of pulmonary fibrosisL593L609ENNaokiNakamuraDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHisaoHigoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalSatoruSenooDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAkihikoTaniguchiDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterTaichiOzekiDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyotaSunamiDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYumiInukaiDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShuseiYamamotoDepartment of Medical Laboratory Science, Okayama University Faculty of Health SciencesJunkoItanoDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAyakaTanakaDepartment of Respiratory Medicine, Kurashiki Central HospitalNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobuakiMiyaharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalAcute 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.WileyActa Medica Okayama1574-78912026Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in <i>Egfr</i> ‐mutated lung cancerENJunNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadahiroKuribayashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJohannesBrägelmannDepartment of Translational Genomics Faculty of Medicine and University Hospital Cologne, University of Cologne GermanySachiOkawaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatakaTaokaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuntaMoriDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokaNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaakiTanakaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesGoMakimotoDepartment of Respiratory Medicine, Okayama University HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalKammeiRaiCenter for Innovative Clinical Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalRyoheiKatayamaDivision of Experimental Chemotherapy, Cancer Chemotherapy Centre, Japanese Foundation for Cancer ResearchKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalMasahiroTabataCenter for Clinical Oncology, Okayama University HospitalYosukeTogashiDepartment of Respiratory Medicine, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMartin L.SosDepartment of Translational Genomics Faculty of Medicine and University Hospital Cologne, University of Cologne GermanyKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalEpidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers (NSCLCs) lack effective immunotherapy due to a noninflamed tumor microenvironment (TME). We previously reported that EGFR tyrosine-kinase-inhibitor (TKI) induced CD8+ T-cell immunity, which was insufficient for tumor eradication. We evaluated the potential of combining EGFR-TKI with stimulator of interferon genes (STING) agonists in activating a systemic antitumor response. Using a syngeneic mouse model of genetically engineered Egfr-mutant NSCLC, we evaluated the antitumor effects of STING agonist ADU-S100, alone and combined with osimertinib. Immunohistochemistry and flow cytometry were used to assess the TME. Osimertinib alone enhanced CD8+ T-cell infiltration but not Natural Killer (NK) cell infiltration. ADU-S100 injection alone modestly suppressed tumor growth with increasing CD8+/NK cell infiltration in the TME, but lacked an abscopal effect. Combining ADU-S100 with osimertinib significantly enhanced the antitumor effects and CD8+/NK cell infiltration. Depletion of either CD8+ or NK cells reduced the combination effect. Crucially, the combination induced an abscopal effect accompanied by PD-1+/CD8+ cell infiltration. Combining osimertinib with a STING agonist augmented innate and adaptive immunity, inducing systemic antitumor responses in EGFR-mutant NSCLC.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322026Afatinib Overcomes Osimertinib Resistance via Egfr V804F Mutation in a Syngeneic Egfr-Mutant Lung Cancer Mouse Model117ENTakaakiTanakaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoFujitaniDivision of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer ResearchMasatakaTaokaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIwaoShimomuraDivision of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer ResearchSachiOkawaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuntaMoriDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadahiroKuribayashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokaNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAyakoMoritaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityNaofumiHaraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalGoMakimotoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityHisaoHigoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityKammeiRaiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityEikiIchiharaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalYosukeTogashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityRyoheiKatayamaDivision of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer ResearchKadoakiOhashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityOsimertinib 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.Oxford University Press (OUP)Acta Medica Okayama2753-670X4152026Lung Segmental Perfusion Defect Is Associated With Airway Complications After Living-Donor Lobar Lung Transplantationivag139ENKentaroImanishiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTsuyoshiRyukoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuakiTomiokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPURPOSE: Airway complications (ACs) are potentially fatal after lung transplantation (LT). Although bronchial blood flow to the graft is supplied mainly from the pulmonary circulation after LT, lung segmental perfusion defects (LSPDs) are occasionally identified on lung perfusion scintigraphy (Q-scinti) after living-donor lobar LT (LDLLT). Lung segmental perfusion defects may impair bronchial healing and contribute to the development of ACs. This study aimed to evaluate the relationship between LSPD and AC after LDLLT.<br>
METHODS: We retrospectively reviewed 86 recipients who underwent LDLLT and 163 living donors at our institution from October 1998 to December 2023. Transplanted lungs that developed AC were classified as the AC group, whereas those without AC were classified as the non-AC group. Blood flow in the transplanted lungs was evaluated using Q-scinti after LDLLT.<br>
RESULTS: AC developed in 8 (4.9%) of 163 transplanted lungs after LDLLT. Although there were no significant differences in recipient-related variables between the 2 groups, LSPD was detected significantly more frequently in the AC group (n = 8) than in the non-AC group (n = 155) (50.0% vs 6.5%, P = .002). Furthermore, transplanted lungs showing LSPD were associated with significantly higher grades of the pulmonary interlobar fissures at the time of living-donor lobectomy (P = .025). Overall survival did not differ between patients with and without AC after LDLLT.<br>
CONCLUSIONS: LSPD on Q-scinti, which may develop in grafts with incomplete interlobar fissures during living-donor lobectomy, is associated with the development of AC after LDLLT.<br>
CLINICAL REGISTRATION NUMBER: This study was approved by the Institutional Review Board of Okayama University Hospital (approval date: August 23, 2024; 2409-027).No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322026Atezolizumab + Chemotherapy in Older Patients With Lung Cancer in Japan113ENJunichiShimizuDepartment of Thoracic Oncology, Aichi Cancer Center HospitalMakotoNishioDepartment of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalAtsushiOsoegawaDepartment of Thoracic and Breast Surgery, Oita University Faculty of MedicineEikiKikuchiDepartment of Respiratory Medicine, Faculty of Medicine, Hokkaido UniversityHideharuKimuraDepartment of Respiratory Medicine, Kanazawa University HospitalYasushiGotoDepartment of Thoracic Oncology, National Cancer Center HospitalEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical UniversityIchiroYoshinoInternational University of Health and Welfare Narita HospitalToshihiroMisumiDepartment of Data Science, National Cancer Center Hospital EastKozoYoshimoriDepartment of Clinical Oncology, Japan Anti‐Tuberculosis Association, Fukujuji HospitalKazuhikoShibataDepartment of Medical Oncology, Kouseiren Takaoka HospitalTakeshiTsudaDivision of Respiratory Medicine, Toyama Prefectural Central HospitalMasahiroSeikeDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical SchoolTakahiroOtaDepartment of Respiratory Medicine, Kyoto City HospitalKoichiSamataChugai Pharmaceutical Co., Ltd. YukiKobayashiChugai Pharmaceutical Co., Ltd.MisaTanakaChugai Pharmaceutical Co., Ltd. AkihikoGemmaNippon Medical SchoolPivotal phase 3 trials leading to the approvals of atezolizumab─chemotherapy 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.WileyActa Medica Okayama1347-90322026Plasma Protein Analysis for Biomarker Discovery in Lung Cancer Treated With Atezolizumab Combination Therapy in J-TAIL-2113ENYasushiGotoDepartment of Thoracic Oncology, National Cancer Center HospitalMakotoNishioDepartment of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalAtsushiOsoegawaDepartment of Thoracic and Breast Surgery, Oita University Faculty of MedicineEikiKikuchiDepartment of Respiratory Medicine, Faculty of Medicine, Hokkaido UniversityHideharuKimuraDepartment of Respiratory Medicine, Kanazawa University HospitalJunichiShimizuDepartment of Thoracic Oncology, Aichi Cancer Center HospitalEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical UniversityIchiroYoshinoDepartment of Thoracic Surgery, International University of Health and Welfare Narita HospitalToshihiroMisumiDepartment of Data Science, National Cancer Center Hospital EastYasutakaWatanabeDepartment of Thoracic Oncology, Saitama Cancer CenterNobuyukiKatakamiDepartment of Pulmonary Medicine and Medical Oncology Takarazuka City Hospital Takarazuka JapanAkiraKisoharaDepartment of Respiratory Medicine, Kasukabe Medical CenterMasafumiYamaguchiDepartment of Thoracic Oncology, NHO Kyushu Cancer CenterHirotakaKurokiChugai Pharmaceutical Co., Ltd.MasamichiSugimotoChugai Pharmaceutical Co., Ltd.HisaoAshimuraChugai Pharmaceutical Co., Ltd.MisaTanakaChugai Pharmaceutical Co., Ltd.AkihikoGemmaNippon Medical SchoolJ-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.Elsevier BVActa Medica Okayama0040-40391832026Photochemical oxidative synthesis of carboxylic acids from aldehydes or alcohols with water via CH bromination156163ENMohamed R.El-kholanyGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAtsuyaMiyamotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMorganeFalconeGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroyoshiTakamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityIsaoKadotaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentaTanakaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe photoinduced oxidation of aldehydes or alcohols with water to give the corresponding carboxylic acids is described. This photochemical carboxylation proceeds via the in-situ generation of acyl-bromide intermediates upon irradiation with purple or UV LED light; these intermediates subsequently react with water to give the desired carboxylic acids. This mild photochemical reaction affords diverse carboxylic acids without peroxide generation or the need to use transition-metal catalysts and a stoichiometric amount of base, highlighting its potential utility for the synthesis of natural products and bioactive compounds.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72571932026Successful management and 10-year survival of a rectal neuroendocrine tumor with rare systemic metastases via a non-portal venous pathway491498ENShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKoseiTakagiDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakashiKuiseDepartment of Gastroenterological Surgery, Okayama Red Cross HospitalTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalMetastatic neuroendocrine tumors (NETs) typically involve the liver and lymph nodes. Metastases in the orbit, heart, and ovary are rare and present unique clinical challenges. We report a woman who was 70 years old at the time of initial presentation with liver metastases from a rectal neuroendocrine tumor. Following a right hepatectomy for liver metastases, she remained free of hepatic recurrence for 10 years. Notably, four years after the right hepatectomy, she developed new metastases in the left orbit, right ventricle, and left ovary, with diplopia as the sole clinical symptom. This clinical course suggests a distinct metastatic pathway associated with the lower rectum that bypasses the portal circulation, consistent with the dual drainage system of the rectal region. Management involved a strategic multimodal approach that includes systemic therapy with everolimus and lanreotide as well as targeted surgical resectioning of the cardiac and ovarian lesions. The orbital lesion achieved a complete response through systemic therapy alone, preserving visual function. Currently, 10 years after the initial treatment, the patient maintains an excellent performance status (ECOG PS 0) while receiving peptide receptor radionuclide therapy (PRRT). This case demonstrates that recognizing atypical metastatic pathways and employing strategic multimodal therapies can achieve long-term survival and functional preservation in rectal NETs.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2090-6528202612026Selective ARID1A Loss Restricted to the Undifferentiated Component of a Mismatch Repair‐Deficient Gastric Carcinoma: A Case Report8863202ENRikaOmoteDepartment of Diagnostic Pathology, NHO Fukuyama Medical CenterRyosukeHamanoDepartment of Surgery, NHO Fukuyama Medical CenterShinyaOtsukaDepartment of Surgery, NHO Fukuyama Medical CenterTakehiroTanakaDepartment of Pathology, Okayama University HospitalHiroyukiYanaiDepartment of Pathology, Okayama University HospitalMismatch 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 LLCActa Medica Okayama1340-68683342026Differences 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, JCOG1017829838ENKiyoTanakaDepartment of Breast Surgery, Toranomon HospitalAkihikoShimomuraDepartment of Breast and Medical Oncology, National Center for Global Health and MedicineMakotoIshitobiDepartment of Breast Surgery, Osaka Habikino Medical CenterTakashiYamanakaDepartment of Breast Surgery, Kanagawa Cancer CenterTakahiroTsukiokiDepartment of Breast and Endocrine Surgery, Okayama University HospitalHirojiIwataDepartment of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical SciencesFumikataHaraDepartment of Breast Oncology, Aichi Cancer CenterTomomiFujisawaDepartment of Breast Oncology, Gunma Prefectural Cancer CenterKeitaSasakiClinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalRyoSadachiClinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalRikuKajikawaClinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalTakehikoSakaiDepartment of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer ResearchYasuakiSagaraDepartment of Breast Surgery, Sagara HospitalHideoShigematsuDepartment of Breast Surgery, Hiroshima University HospitalYukinoriOzakiDepartment of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKazukiNozawaDepartment of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical SciencesKazukiSudoDepartment of Medical Oncology, National Cancer Center HospitalYoichiNaitoDepartment of General Internal Medicine, National Cancer Center Hospital EastKaoriTerataDepartment of Breast and Endocrine Surgery, Akita University HospitalToshiyukiIshibaDepartment of Breast Surgery, Institute of Science Tokyo HospitalHaruhikoFukudaClinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalBackground 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.Elsevier BVActa Medica Okayama2667-2421202026Behavioral effects of a chronic envy-like stress paradigm in mice using an adjacent cage model148159ENHiroshiUenoDepartment of Medical Technology, Kawasaki University of Medical WelfareYoshihiroTanakaDepartment of Psychiatry, Kawasaki Medical SchoolErikoKitanoDepartment of Psychiatry, Kawasaki Medical SchoolYuTakahashiDepartment of Psychiatry, Kawasaki Medical SchoolSachikoMoriDepartment of Psychiatry, Kawasaki Medical SchoolShinjiMurakamiDepartment of Psychiatry, Kawasaki Medical SchoolKentaWaniDepartment of Psychiatry, Kawasaki Medical SchoolYosukeMatsumotoDepartment of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMotoiOkamotoDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityTakeshiIshiharaDepartment of Psychiatry, Kawasaki Medical SchoolBackground: 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 LLCActa Medica Okayama2045-23221612026Adolescent envy-like social comparison stress induces HPA axis hypoactivity and anxiety in female mice: implications for somatic symptom disorder15771ENHiroshiUenoDepartment of Medical Technology, Kawasaki University of Medical WelfareYoshihiroTanakaDepartment of Psychiatry, Kawasaki Medical SchoolErikoKitanoDepartment of Psychiatry, Kawasaki Medical SchoolYuTakahashiDepartment of Psychiatry, Kawasaki Medical SchoolSachikoMoriDepartment of Psychiatry, Kawasaki Medical SchoolShinjiMurakamiDepartment of Psychiatry, Kawasaki Medical SchoolKentaWaniDepartment of Psychiatry, Kawasaki Medical SchoolYosukeMatsumotoDepartment of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMotoiOkamotoDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityTakeshiIshiharaDepartment of Psychiatry, Kawasaki Medical SchoolAdolescence 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.Elsevier BVActa Medica Okayama2666-3643732026Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study100926ENMasayukiShirasawaDepartment of Thoracic Oncology, National Cancer Center HospitalMakotoNishioDepartment of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalAtsushiOsoegawaDepartment of Thoracic and Breast Surgery, Oita University Faculty of MedicineEikiKikuchiDepartment of Respiratory Medicine, Faculty of Medicine, Hokkaido UniversityHideharuKimuraDepartment of Respiratory Medicine, Kanazawa University HospitalYasushiGotoDepartment of Thoracic Oncology, National Cancer Center HospitalJunichiShimizuDepartment of Thoracic Oncology, Aichi Cancer Center HospitalEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical UniversityIchiroYoshinoInternational University of Health and Welfare Narita HospitalToshihiroMisumiDepartment of Data Science, National Cancer Center Hospital EastYasushiYatabeDepartment of Diagnostic Pathology, National Cancer Center HospitalTatsuyaYoshidaDepartment of Thoracic Oncology, National Cancer Center HospitalJumpeiKashimaDepartment of Diagnostic Pathology, National Cancer Center HospitalMasahideOkiDepartment of Respiratory Medicine, NHO Nagoya Medical CenterHisaoAshimuraChugai Pharmaceutical Co., Ltd.YukiKobayashiChugai Pharmaceutical Co., Ltd.MisaTanakaChugai Pharmaceutical Co., Ltd.AkihikoGemmaNippon Medical SchoolIntroduction: Effective predictors of response to atezolizumab plus carboplatin/etoposide (CE) therapy in extensive-stage SCLC (ES-SCLC) remain limited. This exploratory analysis from J-TAIL-2 aimed to identify markers of survival benefit with atezolizumab plus CE therapy in ES-SCLC.<br>
Methods: J-TAIL-2 (ClinicalTrials.gov ID, NCT04501497) was a multicenter observational study that enrolled patients receiving atezolizumab plus CE (ES-SCLC cohort) in clinical practice in Japan per local label and treatment guidelines. In this exploratory analysis, the association of CD8+ tumor-infiltrating lymphocyte (TIL) density and SCLC subtypes (SCLC-A [ASCL1 dominant], SCLC-N [NEUROD1 dominant], SCLC-P [ASCL1/NEUROD1 double-negative with POU2F3 expression], and SCLC-O [ASCL1/NEUROD1 double-negative not otherwise specified]) with overall survival (OS) and progression-free survival (PFS) was evaluated. SCLC subtyping was performed by immunohistochemistry.<br>
Results: SCLC samples (n = 100; data cutoff, February 3, 2023) were categorized as SCLC-A (73%), SCLC-N (16%), SCLC-P (8%), and SCLC-O (3%). Among 96 patients who received first-line atezolizumab plus CE, median age was 72 (range, 39–87) years and 81% were male. Furthermore, 56 patients were classified into the CD8+ TIL-high subgroup and 40 into the TIL-low subgroup. Median (m)PFS with atezolizumab plus CE was 6.1 months (95% confidence interval [CI]: 4.5–7.5) in the TIL-high versus 4.4 months (95% CI: 4.0–5.1) in the TIL-low subgroup (p = 0.01); mOS was 18.4 (95% CI: 11.8–not estimable) versus 10.8 months (95% CI: 7.7–16.2; p = 0.04). mOS and mPFS were not significantly different between SCLC subtypes but were numerically shorter in the SCLC-N group.<br>
Conclusions: CD8+ TIL density is a potential biomarker of clinical benefit in ES-SCLC and may facilitate patient selection for atezolizumab combination therapy.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-903211752026TGF-β Inhibitor Potentiates Osimertinib-Induced Anti-Tumor Immunity in Egfr-Mutant Lung Cancer12601272ENTadahiroKuribayashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSachiOkawaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatakaTaokaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuntaMoriDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaakiTanakaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokaNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAyakoMoritaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaofumiHaraDepartment of Respiratory Medicine, Okayama University HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalGoMakimotoDepartment of Respiratory Medicine, Okayama University HospitalKammeiRaiCenter for Innovative Clinical Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalYosukeTogashiDepartment of Respiratory Medicine, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalImmunotherapy for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) remains challenging. We previously found that EGFR-tyrosine kinase inhibitors induced antitumor immunity but also triggered immunosuppressive cytokines, including transforming growth factor-β (TGF-β), in Egfr-mutant lung cancer. Here, we investigate whether TGF-β inhibition potentiates osimertinib-induced antitumor immunity using a syngeneic mouse model of Egfr-mutated lung cancer, with cancer cells subcutaneously transplanted into wild-type C57BL/6J mice. We evaluated the antitumor effect of the combination therapy with osimertinib and either nintedanib (an indirect TGF-β inhibitor) or vactosertib (a specific TGF-β type I receptor kinase inhibitor). Changes in the tumor microenvironment during treatment were assessed using immunohistochemical staining, western blot analysis, and flow cytometry. We found that TGF-β expression was upregulated in the tumor treated with osimertinib. Nintedanib monotherapy showed no significant antitumor effect, whereas osimertinib combined with nintedanib significantly potentiates the antitumor effect compared with osimertinib monotherapy in vivo. Crucially, no additive effect of nintedanib on osimertinib monotherapy was observed in vitro. Combination therapy with osimertinib and nintedanib significantly increased effector T cells (CD8+CD44+CD62L−) and Granzyme B+ areas and decreased CD206+ cells, while significantly decreasing TGF-β and SMAD2/3 expression. Similar effects were observed with vactosertib but not with a vascular endothelial growth factor receptor 2 inhibitor. In conclusion, combination therapy with osimertinib and TGF-β inhibitors potentiates osimertinib-induced antitumor immunity. These findings highlight a novel therapeutic strategy for EGFR-mutated NSCLC and warrant further clinical investigation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-24072612026High-risk soft-tissue sarcomas in elderly patients: does perioperative radiotherapy improve local control and prognosis?329ENTomohiroFujiwaraDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiharuMitsuhashiCentre for Innovative Clinical Medicine, Medical Development Field, Okayama UniversityYutakaNezuDepartment of Orthopaedic Surgery, Yokohama City UniversityTakashiTajimaDepartment of Orthopaedic Surgery, Kyorin University Faculty of MedicineShinjiMiwaDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa UniversityToshioKojimaDepartment of Orthopaedic Surgery, Nihon University School of MedicineShuichiFujiwaraDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineAkiraKawaiDepartment of Musculoskeletal Oncology, National Cancer Centre HospitalKazuhiroTanakaDepartment of Advanced Medical Sciences, Oita University Faculty of MedicineToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAims Accumulating evidence suggests that advanced age is associated with poor local control and prognosis in patients with soft-tissue sarcomas (STSs), highlighting the need to optimise treatment for this age group. However, real-world data on treatment details and outcomes in elderly patients are limited. This study aimed to clarify the role of perioperative radiotherapy (RT) for treating high-risk STSs in elderly patients.<br>
Methods Patients aged ≥ 70 years who underwent surgery for localised, high-grade, deep-seated non-small round cell STSs measuring ≥ 5 cm were included in the Bone and Soft Tissue Tumour Registry in Japan. Patients with small-round cell STSs or myxoid liposarcomas, or those who received perioperative chemotherapy or intraoperative RT, were excluded.<br>
Results Among the 1,214 patients who met the criteria, 47 (4%), 219 (18%), and 2 (0.2%) received neoadjuvant, adjuvant, and both neoadjuvant and adjuvant RT, respectively. The 5- and 10-year disease-specific survival (DSS) rates were 72.7% and 64.7%, respectively. Tumour size ≥ 10 cm, intralesional margin, and local recurrence were associated with poorer DSS; however, perioperative RT did not affect DSS. The 5- and 10-year cumulative probabilities of local recurrence (LR) were 14.6% and 19.5%, respectively. Trunk wall tumours, dedifferentiated liposarcomas, marginal margins, and intralesional margins were associated with a higher probability of LR. Adjuvant RT was associated with a reduced LR probability in patients with intralesional (p = 0.005) or marginal margins (p = 0.044); however, no such benefit was observed in patients with wide margins, who constituted the majority of the cohort, resulting in no significant association between perioperative RT and LR in overall analyses. In the propensity score-matched cohort, no significant differences in DSS or cumulative probability of LR were observed between patients with and without perioperative RT.<br>
Conclusion Adjuvant RT was associated with reduced LR rates in elderly patients with high-risk STSs who had intralesional or marginal margins. However, because most patients achieved wide margins and no benefit of perioperative RT was observed in this group, RT was not associated with reduced LR or improved survival in the overall or propensity score–matched analyses. Prospective trials are warranted to define the role of perioperative RT in elderly patients with high-risk STSs.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama2673-253X82026Development of a generative AI agent for family support in implementing family-based treatment for children and adolescents with anorexia nervosa1759690ENManaHanzawaDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenJoeHaseiDepartment of Medical Informatics and Clinical Support Technology Development, Faculty of Medicine, Dentistry and Pharmaceutical SciencesAyumiOkadaDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenChieTanakaDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenYoshieShigeyasuDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenChikakoFujiiDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenMakikoHoriuchiClinical Psychology Section, Department of Medical Support, Okayama University HospitalAkikoSugiharaDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenKoichiTakeuchiLife Natural Science and Technology, Graduate School of Environmental, Okayama UniversityRyuichiNakaharaDepartment of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidekiKatayamaDepartment of Palliative and Supportive Care, Okayama University HospitalYasushiTakahashiNEC CorporationToshifumiOzakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokazuTsukaharaDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenIntroduction: Family-based treatment (FBT) is a first-line psychotherapy for children and adolescents with anorexia nervosa (AN). However, families must understand the principles of FBT, provide meal support, and manage their children's pathological behaviors. Difficulties occur outside clinic hours when it is impossible to consult professionals. This “support gap” increases caregivers’ psychological distress and threatens their treatment continuity. To the best of our knowledge, this is the first domain-specific generative artificial intelligence (AI) agent designed to provide situation-specific, FBT-concordant advice and psychological support.<br>
Methods: The system integrates three components: (1) an FBT-specific knowledge base constructed from treatment manuals, family guides, guideline-compliant resources, and a clinical Q&A corpus; (2) a multistage natural language processing pipeline using Retrieval-Augmented Generation (RAG), with intent and sentiment analyses; and (3) safety guardrails that prohibit unsolicited numerical goals or direct hospitalization recommendations and standardized escalation to clinicians. When strong negative emotions are detected, empowerment messages are dynamically incorporated to maintain caregivers’ confidence. Six clinicians with expertise with pediatric mental health authored queries that simulated common FBT-related concerns and evaluated each response for clinical appropriateness and safety, and classified problems as information insufficiency, not FBT concordant, or escalation insufficiency.<br>
Results: Of the 477 queries, 57.0% were FBT-related, 24.5% were general AN, 16.5% were parental psychological distress, and 1.8% were related to other topics. The clinically appropriate response rate was 91.6% (437/477), including 92.3% for FBT-related questions, 88.0% for general knowledge, 93.7% for psychological distress, and 100.0% for other questions. Clinically inappropriate responses (8.4%) were mainly attributable to information insufficiency; not FBT concordant (1.8% of FBT-related responses) and escalation insufficiency (0.6% of all dialogs) rarely occurred.<br>
Discussion: In this expert review, the safety-gated RAG system predominantly generated FBT-concordant responses that provided meal-level guidance and empathic empowerment-oriented support to families. By proceduralizing complex FBT concepts and presenting multiple response options for pathological behaviors, the system translates FBT principles into practical guidance supporting refeeding adherence, preserving family self-efficacy, and suggesting that domain-specific AI may help bridge structural limitations in FBT. Usability studies and randomized controlled trials are warranted to determine their impact on caregiver burden, self-efficacy, treatment adherence, and clinical outcomes.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2666-951X192026Heteroarylation of mono- and dichloroarenes via phenothiazine organophotoredox catalysis100163ENMasatoOishiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroyoshiTakamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityIsaoKadotaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentaTanakaGraduate School of Environmental, Life, Natural Science and Technology, Okayama University2-Arylpyrroles are key structural motifs found in a wide range of pharmaceuticals and functional materials. Although the photocatalytic heteroarylation of pyrroles with aryl iodides and bromides has been extensively developed for the synthesis of 2-arylpyrroles, the corresponding reactions using aryl chlorides remain relatively unexplored owing to the high energy barrier associated with C(sp2)–Cl bond activation. Herein, we report a phenothiazine-based organophotoredox-catalyzed heteroarylation of aryl chlorides with pyrroles for the synthesis of diverse 2-arylpyrroles. Notably, dichloroarenes also efficiently undergo heteroarylation to afford the corresponding products. Therefore, the present reaction represents a versatile approach to heteroarylation and provides a valuable tool for the synthesis of pharmaceuticals and functional materials.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama1463-90762026Phase behaviour of liquid CO2 with an impurity of water: influence of CO2 hydrateENHidekiTanakaResearch Institute for Interdisciplinary Science, Okayama UniversityMasakazuMatsumotoResearch Institute for Interdisciplinary Science, Okayama UniversityTakumaYagasakiDivision of Chemical Engineering, Graduate School of Engineering Science, Osaka UniversityMunetakaTakeuchiEngineering Advancement Association of JapanYoshihitoMoriOchanomizu UniversityTakumiKonoEngineering Advancement Association of JapanThe solubility of water in liquid CO2 coexisting with CO2 hydrate or liquid water is evaluated in order to investigate the thermodynamic conditions to avoid the formation of CO2 hydrate in the transportation processes of liquid CO2. To this end, theoretical calculations have been carried out to obtain the chemical potentials of water and CO2 in all the phases involved in their coexistence. The solubility of water in liquid CO2 coexisting with liquid water decreases with decreasing temperature over a wide range of temperature and pressure, except for in the vicinity of the critical point of CO2. The decrease in the solubility is further enhanced by the formation of hydrate. We estimate the Gibbs energy of hydrate formation, which is an important property for sequestration of CO2, for cases where the temperature or pressure of water-saturated liquid CO2 decreases. We also estimate the amount of water precipitated as hydrate during these processes, which has a direct bearing on flow assurance in CO2 transportation. The present study will contribute to the development of a low-energy, safe CO2 transport network aiming at achieving large-scale carbon neutrality.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841862026Pathway Enrichment Analysis of Whole-Exome Sequencing Data from Formalin-Fixed, Paraffin-Embedded Enucleated Eyes with Retinoblastoma and Choroidal Malignant Melanomae110548ENToshihikoMatsuoOphthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakehiroTanakaPathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityDaisukeEnnishiMedical Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAkiraSaitoGenomic Statistics, Stagen Co. Ltd.MitsuhiroAmemiyaGenomic Statistics, Stagen Co. Ltd.ShigeoKamitsujiGenomic Statistics, Stagen Co. Ltd.Objectives: Intraocular tumors are extremely rare, small in size, and difficult to approach by biopsy. In the era of cancer genome analysis, we designed a pilot study to perform whole-exome sequencing of formalin-fixed paraffin-embedded enucleated eyes of retinoblastoma and choroidal malignant melanoma as two major intraocular malignancies.<br>
Methodology: Genomic DNA was isolated from intraocular tumor areas of 105 paraffin sections with a 5 μm thickness of seven enucleated eyes with retinoblastoma and seven eyes with choroidal malignant melanoma. One of 7 samples of retinoblastoma and another of seven samples of choroidal malignant melanoma were excluded from the study since the sequencing output and depth of reads were lower compared with the other samples. The sequencing data after quality control were aligned to the reference genome sequence (hg38, GRCh38 Assembly, Genome Reference Consortium Human Build 38), and the mapped reads were processed to improve data quality. Somatic mutations (single nucleotide variants, insertions and deletions, and multiple nucleotide variants) in each sample were extracted after excluding variants reported in a Panel of Normals (PON) from the 1000 Genomes Project. Additional selection criteria included a mutation depth of ≥5 reads and either no registration in or an allele frequency of less than 5% in the Tohoku Medical Megabank of Japan (ToMMo 60KJPN-SNV/INDEL Allele Frequency Panel).<br>
Results: Candidate genes with somatic mutations were selected by three criteria: genes with the same mutation shared by two samples or more, recurrently mutated genes three times or over, and genes of driver candidates identified in combining several different driver mutation-detecting programs by Integrative OncoGenomics (IntOGen). Using candidate genes detected by any of the three criteria as input, enrichment analyses identified 28 pathways in Gene Ontology (GO) and 2 pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) for retinoblastoma, while 385 pathways in GO, 12 in KEGG, 2 in the Hallmark gene set of the Molecular Signatures Database (MSigDB), and 47 in Reactome were identified for choroidal malignant melanoma. The enrichment maps showed three major pathways differently in retinoblastoma and choroidal malignant melanoma: one with dynein in retinoblastoma and another with MET in choroidal malignant melanoma.<br>
Conclusions: Although there were limitations related to the small amounts of DNA available from formalin-fixed, paraffin-embedded small-sized tissues and the absence of matched normal control tissue, whole-exome sequencing provided clues to somatic mutations that were enriched in specific pathways and differed between retinoblastoma and choroidal malignant melanoma.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-058410552026Donor selection for patients with HLA-homozygous haplotypes in allogeneic hematopoietic stem cell transplantation244ENNoriyoshiYoshinagaDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityMakotoIwasakiDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityKojiKatoDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical SciencesFumihikoKimuraDivision of Hematology, Department of Internal Medicine, National Defense Medical CollegeMasahiroHirayamaDepartment of Pediatrics, Mie University Graduate School of MedicineMinoruKanayaBlood Disorders Center, Aiiku HospitalSatokoMorishimaCentral Japan Cord Blood BankNaoyukiUchidaDepartment of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon HospitalNorikoDokiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalTakahiroFukudaDepartment of Hematopoietic Stem Cell Transplantation, National Cancer Center HospitalYoshinobuKandaDivision of Hematology, Jichi Medical UniversityTetsuyaNishidaDepartment of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi HospitalYutaHasegawaDepartment of Hematology, Hokkaido University HospitalShinichiKakoDivision of Hematology, Jichi Medical University Saitama Medical CenterMasatsuguTanakaDepartment of Hematology, Kanagawa Cancer CenterMineoKurokawaDepartment of Cell Therapy and Transplantation Medicine, The University of Tokyo HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalToshiroKawakitaDepartment of Hematology, NHO Kumamoto Medical CenterKeisukeKataokaDivision of Hematology, Department of Medicine, Keio University School of MedicineYukioKondoDepartment of Hematology, Toyama Prefectural Central HospitalKazunoriImadaDepartment of Hematology, Japanese Red Cross Osaka HospitalTatsuoIchinoheDepartment of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima UniversityMakotoOnizukaDepartment of Hematology/Oncology, Tokai University School of MedicineYoshikoAtsutaJapanese Data Center for Hematopoietic Cell TransplantationJunyaKandaDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityHLA homozygous haplotypes occur worldwide, but outcomes after allogeneic hematopoietic stem cell transplantation using alternative donor sources remain uncertain. We retrospectively analyzed the Japanese national transplantation registry to compare outcomes after first allogeneic hematopoietic stem cell transplantation in patients with HLA homozygous haplotypes. Donors were classified as homo-to-homo, defined as HLA-matched, or hetero-to-homo, defined as allele-level mismatches at HLA-A, -B, -C, and/or -DRB1 restricted to the host-versus-graft direction. The unrelated donor homo-to-homo group served as the reference. We included 691 patients: related donor homo-to-homo (n = 121), related donor hetero-to-homo (n = 76), unrelated donor homo-to-homo (n = 374), unrelated donor hetero-to-homo (n = 22), cord blood homo-to-homo (n = 40), and cord blood hetero-to-homo (n = 58). Compared with the unrelated donor homo-to-homo group, overall survival was inferior in the cord blood homo-to-homo group (adjusted hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.11–2.64; P = 0.015), whereas the unrelated donor hetero-to-homo group showed a nonsignificant trend toward inferior overall survival (adjusted HR, 1.77; 95% CI, 0.97–3.22; P = 0.061). In this Japanese cohort, cord blood homo-to-homo transplantation was associated with inferior overall survival, whereas related donor hetero-to-homo and cord blood hetero-to-homo transplantation were not. These findings should be interpreted cautiously given the retrospective design and long study period, and require validation in contemporary, ethnically diverse cohorts.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0902-00634062026Risk Factors for Waiting List Mortality in Lung Transplant Candidates With Post‐Hematopoietic Stem Cell Transplantation Non‐Infectious Pulmonary Complicationse70582ENHisaoHigoDepartment of Respiratory Medicine, Okayama University HospitalSatoruSenooDepartment of Respiratory Medicine, Okayama University HospitalSatokoMakimotoDepartment of Radiology, Okayama University HospitalTomohiroNaganoDepartment of Hematology, Okayama University HospitalTakumiKondoDepartment of Hematology, Okayama University HospitalHaruchikaYamamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinobuMaedaDepartment of Respiratory Medicine, Okayama University HospitalYosukeTogashiDepartment of Respiratory Medicine, Okayama University HospitalNobuakiMiyaharaDepartment of Respiratory Medicine, Okayama University HospitalBackground: Late-onset non-infectious pulmonary complications (LONIPCs) following hematopoietic stem cell transplantation (HSCT) are a known indication for need of lung transplantation. This study aimed to clarify the clinical characteristics of patients with LONIPCs after HSCT who were registered for lung transplantation and reveal the risk factors for waiting list mortality.<br>
Methods: We retrospectively reviewed the clinical data of patients with LONIPCs after allogeneic HSCT who were referred to Okayama University Hospital and registered in the Japan Organ Transplant Network for deceased-donor lung transplantation between 2005 and 2023. Pediatric patients aged <18 years at the time of registration were excluded.<br>
Results: Thirty-four patients were included in this study. Notably, two distinct phenotypic groups were identified: One with a bronchiolitis obliterans pattern on high-resolution computed tomography and a mixed ventilatory defect, and the other with a pleuroparenchymal fibroelastosis pattern and a restrictive ventilatory defect. The median waiting duration for a deceased-donor lung transplant was 662 days, and 16 patients died during the waiting period. The cumulative incidence of waiting list mortality was 20.6% (95% confidence interval [CI], 8.9%–35.6%) at 1 year and 46.1% (95% CI, 27.8%–62.7%) at 3 years. A history of pneumothorax, greater dyspnea on exertion, and higher serum Krebs von den Lungen-6 levels were associated with an increased risk of waiting list mortality.<br>
Conclusion: In patients with LONIPCs after HSCT, a history of pneumothorax may be a marker of a poor prognosis and could serve as a criterion for referral of lung transplantation.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Dual molecular therapy targeting tumor cell heterogeneity improves therapeutic efficacy in glioblastomaENShuichiroHIRANOGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Frequency and Characteristics of Gastrointestinal Diseases in Patients With NeurofibromatosisENManamiHONDAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026過分極活性化環状ヌクレオチド依存性チャネル（HCNチャネル）阻害薬が株化ミクログリアの細胞内カルシウムイオン動態に及ぼす影響ENJotaroTANAKAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Japan Surgical SocietyActa Medica Okayama2198-77931212026Tailored Management of Anomalous Systemic Arterial Supply to the Basal Segment of the Lung: A Case Report and Literature Reviewcr.26-0288ENShunsukeMoriDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiTomitaDepartment of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruchikaYamamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKumiNakajimaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidejiroTorigoeDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoHirakiDepartment of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesINTRODUCTION: Parenchyma-preserving strategies for anomalous systemic arterial supply to the basal segment of the lung have gained increasing attention. However, pulmonary infarction of the preserved lung has been reported, and clear criteria for selecting the optimal treatment have yet to be established. We report 2 cases in which detailed preoperative imaging informed tailored management—right posterior basal segmentectomy in 1 patient and endovascular embolization of the aberrant artery in the other—both without postoperative complications. A review of the relevant literature is also provided, with an emphasis on potential selection criteria.<br>
CASE PRESENTATION: Case 1: A 20-year-old asymptomatic woman was referred after an abnormal screening chest radiograph. CT demonstrated an aberrant artery arising from the abdominal aorta supplying the right posterior basal segment (S10) with a large intravascular thrombus. The pulmonary artery showed hypoplasia limited to A10, while the other branches were normal, and no parenchymal congestion was identified. Following resection of the aberrant artery, robot-assisted right S10 segmentectomy was performed. The postoperative course was uneventful, and the patient was discharged on POD 6. Case 2: A 27-year-old woman was incidentally diagnosed on CT for an unrelated indication. An aberrant artery arising from the descending thoracic aorta supplied the left basal segment. Pulmonary arterial branches were preserved, with only minimal congestion in S9-10. Angiography revealed no evidence of an arteriovenous fistula. As surgical lung resection was considered unnecessary, coil embolization of the aberrant artery was performed. No complications occurred, and the patient was discharged on day 3 after the procedure.<br>
CONCLUSIONS: In patients with anomalous systemic arterial supply to the basal segment of the lung, when pulmonary arterial branches are preserved and background parenchymal congestion is minimal, parenchyma-sparing approaches should be considered.No potential conflict of interest relevant to this article was reported.The Japanese Society for Neuroendovascular TherapyActa Medica Okayama1882-40722012026Current Status of Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: An International Perspective Including Japanra.2025-0153ENMasatoKawakamiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiSugiuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasafumiHiramatsuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunHarumaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuKimuraDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutaSoutomeDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJuntaroFujitaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuichiHirataDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFukikoBabaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMiddle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) is gaining global prevalence as a minimally invasive treatment aimed at serving as an adjunct to or method of avoiding surgery; however, its optimal positioning remains unclear. This study outlines the current status of MMAE in Japan, Germany, and the United States based on nationwide survey reports, recently published consensus guidelines, and meta-analyses including randomized controlled trials (RCTs) reported in the New England Journal of Medicine (NEJM; EMBOLISE, STEM, and MAGIC-MT) and examines its efficacy and limitations. Real-world clinical data from Japan, Germany, and the United States indicate that MMAE is primarily used as an adjunctive therapy following surgery for older and high-risk or recurrent cases, or as a stand-alone therapy in selected cases to safely reduce the risk of recurrence and reoperation. While a multidisciplinary consensus statement takes a cautious stance that limits MMAE to recurrent or inoperable cases such as those at high risk associated with interrupting antithrombotic medication, the Society of Vascular and Interventional Neurology guidelines published after the RCTs strongly recommend the concurrent use of MMAE with standard therapy in de novo cases. Meta-analyses integrating the 3 NEJM trials and other RCTs showed that MMAE suppressed recurrence and reoperation versus standard treatment, with particularly pronounced effects in the nonsurgical (conservative treatment) group; however, the additive effect was limited in the surgical adjunct group. No improvement in functional outcomes (modified Rankin Scale score) was observed. Cost-effectiveness analyses suggest that, while MMAE reduces reoperations, routine implementation for all cases is difficult to justify economically because of high procedural costs, indicating the need to narrow the indication to populations at high risk of recurrence. In conclusion, although MMAE is an effective treatment option, the current evidence does not support its uniform introduction in all patients with CSDH. Thus, it is necessary to individualize and adapt the indications for specific patient subgroups, such as those at high risk of recurrence or those for whom surgery is difficult. Finally, we propose a pragmatic treatment strategy for MMAE stratified by disease stage (de novo vs. recurrent) and clinical severity to guide the individualized selection of adjunctive and stand-alone embolization.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2051-33801432026An Atypical Surgical Case of Lung Cancer With Unilateral Absence of the Pulmonary Artery, With Only the Superior Branch Remaininge70554ENKazuhiroOkadaDepartment of Thoracic Surgery, Okayama University HospitalShinTanakaDepartment of Thoracic Surgery, Okayama University HospitalTsuyoshiRyukoDepartment of Thoracic Surgery, Okayama University HospitalYasuakiTomiokaDepartment of Thoracic Surgery, Okayama University HospitalKazuhikoShienDepartment of Thoracic Surgery, Okayama University HospitalKenSuzawaDepartment of Thoracic Surgery, Okayama University HospitalKentarohMiyoshiDepartment of Thoracic Surgery, Okayama University HospitalMikioOkazakiDepartment of Thoracic Surgery, Okayama University HospitalSeiichiroSugimotoDepartment of Thoracic Surgery, Okayama University HospitalShinichiToyookaDepartment of Thoracic Surgery, Okayama University HospitalA 69-year-old woman was referred to our department for an abnormal shadow on chest radiography. Contrast-enhanced computed tomography (CT) revealed a solid nodule in the right lower lobe and defects in the branches of the middle and lower lobes of the pulmonary artery (PA). Furthermore, collateral circulation had developed via the right internal thoracic, bronchial, intercostal, inferior phrenic, and subdiaphragmatic arteries. The solid nodule was diagnosed as adenocarcinoma by CT-guided biopsy. The day before surgery, embolization was performed using interventional radiology (IVR) to mitigate the risk of bleeding during thoracotomy, resulting in minimal intraoperative bleeding during the subsequent right middle and lower lobectomies with lymph node dissection (ND2a-1). UAPA is a rare congenital abnormality characterized by unilateral pulmonary artery agenesis. The presence of recurrent infections, extensive intrathoracic adhesions, and developed collateral circulation may pose challenges during surgical procedures.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2589-00422952026Wnt3-mediated fibrosis and carcinogenesis of lung squamous cell carcinoma in idiopathic pulmonary fibrosis115667ENAtsushiMatsuokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalMasayoshiOhkiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidejiroTorigoeDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaHisamatsuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaFujiwaraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiIshimuraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeMoriDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyunosukeFujiiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAsukaMimataDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOkadaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoYoshichikaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaoYoshikawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumaFukumotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruchikaYamamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKumiNakajimaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirofumiInoueCenter for Comprehensive Genomic Medicine, Okayama University HospitalDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIdiopathic pulmonary fibrosis (IPF) increases the risk of lung squamous cell carcinoma (LUSC), yet its molecular pathogenesis remains unclear. We conducted multi-omics analysis, including single-cell RNA sequencing and digital spatial profiling, on LUSC specimens from seven patients with usual interstitial pneumonia (UIP). In UIP lung tissue, metaplastic basal cells arising from the transdifferentiation of alveolar type 2 (AT2) cells were increased. LUSC tumors arising within UIP exhibited molecular profiles and trajectory dynamics suggesting derivation from these metaplastic basal cells. Both UIP-affected tissue and associated tumors showed activation of Wnt signaling, particularly WNT3 expression. Additionally, enrichment of the nuclear factor erythroid 2-related factor 2 (NRF2)-linked antioxidant response was observed in LUSC within UIP. Targeting Wnt/β-catenin signaling restored the sensitivity of these stress-adapted cancer cell lines to oxidative damage. These findings suggest that LUSC within UIP originates from AT2-derived metaplastic basal cells and involves aberrant Wnt3 activation, linking fibrosis to carcinogenesis and highlighting a potential therapeutic strategy.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0341-81622692026Aeolian dust provenance across the Eurasian Asian steppe from grain-size dependent quartz δ18O in surface soils110109ENGeerTeniGraduate School of Science and Technology, University of TsukubaRyojiTanakaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityMakiAsanoFaculty of Life and Environmental Sciences, University of TsukubaKenjiTamuraFaculty of Life and Environmental Sciences, University of TsukubaAeolian dust from the Eurasian interior significantly impacts climate, ecosystems, and soil formation, but the role of the Eurasian steppe as a dust source remains uncertain. We present grain-size-sorted quartz δ18O values in topsoil at 24 sites across the Eurasian steppe, from Ukraine and Kazakhstan to Xinjiang, Mongolia, and Inner Mongolia. Quartz fractions were separated from four fine soil classes (<2, 2–10, 10–20, 20–50 μm) at all sites, with additional coarse classes (50–200, 200–500, 500–2000 μm) at lithologically distinct locations. Coarse quartz grains in the Mongolian–Inner Mongolian Highlands show a relatively low and narrow δ18O range (7.6–9.0‰) over plutonic bedrocks and more variable higher values (8.9–17.8‰) over sedimentary bedrocks, indicating dependence on local lithology. In contrast, fine quartz grains (2–50 μm) exhibit a δ18O trend independent of bedrock lithology, indicating the values of regionally homogenized dust components. The δ18O values of the finest quartz fractions, exhibiting the highest at each site, decreased from the Western Steppe Plain (19.0 ± 0.8‰) through the Central Upland Steppe (18.0 ± 0.7‰) to the Mongolian–Inner Mongolian Highlands (13.8 ± 1.0‰), reflecting the distal dust input. Comparison with published quartz δ18O values for Mongolian and Northern China deserts and East Asian soils suggests that variable mixtures of these steppe end-members with Gobi and northern Chinese desert sources, along different atmospheric pathways of the East Asian winter monsoon, mid-latitude westerlies, and subtropical jets, can explain the aerosol-sized quartz in Japan and Korea.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8022026Impact of Proteinuria on Postoperative Complications Following Colorectal Cancer Surgery131139ENShunsukeNakataDepartment of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer CenterFumiakiTakatsuDepartment of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer CenterYoshihiroMikuriyaDepartment of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer CenterTomokazuKakishitaDepartment of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer CenterShinjiHatoDepartment of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer CenterKojiOhtaDepartment of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer CenterTakayaKobatakeDepartment of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer CenterOriginal Article10.18926/AMO/70455Colorectal surgery is associated with a high incidence of postoperative complications regardless of the advances in surgical techniques and multidisciplinary treatment. Proteinuria is common in patients with malignancies, but few studies have investigated the association between preoperative proteinuria and patient prognoses, especially postoperative complications. We investigated the impact of proteinuria on patients undergoing colorectal surgery in a single-center, retrospective cohort study of 767 patients who underwent surgical resection for colorectal cancer between January 2016 and December 2022 at the National Hospital Organization Shikoku Cancer Center. Among them, 81 patients with preoperative proteinuria were compared with the control group of 686 patients without proteinuria. Our analyses revealed that the patients with proteinuria had malnutrition with a significantly lower prognostic nutritional index compared to the no-proteinuria control group (p<0.001). The proteinuria group had a significantly advanced tumor stage (p=0.005), experienced more bleeding during the surgery (p=0.002), and required more transfusions (p<0.001). Postoperative complications were significantly more frequent in the proteinuria group (p=0.03), thus demonstrating that proteinuria was independently associated with postoperative complications (p=0.045). Proteinuria in patients undergoing colorectal cancer surgery can therefore be considered a risk factor for postoperative complications.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8022026Mini-open Corpectomy and Posterior Spinal Fixation with Single-Position Surgery in Lateral Decubitus Position for Osteoporotic Thoracolumbar Vertebral Collapse in Elderly Patients119129ENHisanoriIkumaDepartment of Orthopaedic Surgery, Kagawa Prefectural Central HospitalTomohikoHiroseDepartment of Orthopaedic Surgery, Kagawa Prefectural Central HospitalKeisukeKawasakiDepartment of Orthopaedic Surgery, Kagawa Prefectural Central HospitalKazutoshiOtsukaOtsuka Orthopedic ClinicOriginal Article10.18926/AMO/70454We evaluated the clinical outcomes and limitations of anterior and posterior combined surgery with a mini-open corpectomy applying an expandable cage (Xcore®) and percutaneous pedicle screw (PPS) fixation using single-position surgery in the lateral decubitus position in patients aged > 75 years with thoracolumbar vertebral collapse. The cases of 30 consecutive patients who underwent this procedure and had ≥ 1-year follow-up were retrospectively analyzed. The mean operative time was 78.8 min and the estimated blood loss was 115.7 ml per level. The complications included adjacent junctional failure (n=9, 30%), deep venous thrombosis (n=3, 10%), delirium (n=3, 10%), pleural injury (n=2, 6%), screw backout (n=1, 3%) kidney injury (n=1, 3%), chylothorax (n=1, 3%), and wound dehiscence (n=1, 3%). Seven cases (23.3%) required reoperation. Local kyphosis showed significant improvement (p<0.05) that was maintained at the final follow-up. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and a visual analogue scale indicated significant improvement in all categories at the final follow-up (p<0.05). The use of mini-open corpectomy and posterior fixation with SPAPS can thus provide reliable radiological correction and good postoperative clinical outcomes even in patients aged > 75 years. However, a limitation of this procedure is the rate of reoperation (23.3%) for osteoporosis-related adjacent segment fracture and screw backout.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8022026Effects of Nonsurgical Periodontal Treatment on Bacterial and Clinical Parameters in Down Syndrome Patients Based on 16S rRNA Gene Amplicon Sequencing8597ENTakahikoShibaDepartment of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoMitsuhitoTakamoriDepartment of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySayakaKatagiriDepartment of Oral Biology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoRyotaKobayashiDepartment of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoAkiKawauchiDepartment of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoYujinOhsugiDepartment of Oral Biology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoPeiyaLinDepartment of Oral Biology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoDaisukeEkuniDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasahikoEgusaThe center for Special Needs Dentistry, Medical Development Field, Okayama UniversityTakanoriIwataDepartment of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoShigeruMaedaDepartment of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoOriginal Article10.18926/AMO/70451Individuals with Down syndrome (DS) are more susceptible to periodontal disease; however, microbial changes following treatment remain insufficiently understood. This study evaluated the effects of nonsurgical periodontal therapy on clinical outcomes and oral microbiome dynamics in 6 patients with DS using 16S rRNA gene amplicon sequencing. Bacterial diversity, composition, network structure, and predicted functional pathways were analyzed using dental plaque samples. Bleeding on probing decreased significantly (p=0.047) after treatment, with a trend toward reduction in periodontal inflamed surface area (p=0.05). The abundance of Fusobacteria at the class level decreased significantly after treatment. The abundance of Mogibacterium timidum was higher in the pretreatment group than in the posttreatment group. M. timidum was positively correlated with Treponema denticola and associated with multiple bacterial taxa in the network during pretreatment. Predicted functional pathways related to aromatic compound degradation were more abundant in posttreatment samples than in pretreatment samples. An increase in the abundance of Fusobacterium and the positive correlation between T. denticola and M. timidum, together with their associations with other periodontal pathogens before treatment, may contribute to the development of periodontitis in individuals with DS. Nonsurgical periodontal therapy produces measurable clinical improvement and promotes microbial shifts in patients with DS.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2212-53456432026Short- and long-term outcomes of anti-thymocyte globulin-based regimen for acute antibody-mediated rejection after lung transplantation101428ENKentarohMiyoshiDepartment of Thoracic Surgery, Okayama University HospitalShinjiOtaniDepartment of Thoracic Surgery, Okayama University HospitalSeiichiroSugimotoDepartment of Thoracic Surgery, Okayama University HospitalShinTanakaDepartment of Thoracic Surgery, Okayama University HospitalMikioOkazakiDepartment of Thoracic Surgery, Okayama University HospitalShinichiToyookaDepartment of Thoracic Surgery, Okayama University HospitalBackground: Antibody-mediated rejection (AMR) remains a major barrier to successful lung transplantation (LTx). Despite advances in donor-specific alloantibody (DSA) detection, effective treatments are limited, with current management largely empirical. Acute clinical AMR, marked by rapid graft dysfunction, demands urgent intervention. In Japan, where approved therapies for AMR were historically limited, rabbit anti-thymocyte globulin (rATG) has been adopted as a treatment option.<br>
Methods: This retrospective study analyzed 11 patients who developed acute AMR within three months after LTx at Okayama University Hospital between 2013 and 2023. Diagnosis (ISHLT possible AMR) was based on acute graft dysfunction unresponsive to steroids, positive DSA, and exclusion of infection, without histological confirmation due to procedural risk. rATG (1.5 mg/kg/day for 7 days) was administered, along with intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and rituximab when indicated. Outcomes included DSA clearance, clinical response, survival, and adverse events.<br>
Results: Remission was achieved in 64% of patients, with 36% not requiring PLEX and 64% not receiving rituximab. Early rATG treatment correlated with favorable outcomes, whereas delayed therapy resulted in poorer responses. Six patients (55%) survived without chronic lung allograft dysfunction (CLAD) for over one year. Adverse events included cytomegalovirus infection (91%), bacterial pneumonia (36%), fungal infection (18%), and malignancy (18%).<br>
Conclusions: rATG was effective for acute possible AMR management, particularly when initiated early. Some patients achieved remission without adjunct therapy, indicating rATG's potent immunosuppressive activity. However, frequent infectious complications emphasize the need for optimized dosing and further studies to validate its safety and long-term efficacy.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama1359-73452026Synthesis of sulfur- and oxygen-bridged cationic [4]-helicenes mediated by Friedel–Crafts-S <sub>N</sub> Ar tandem reactions for red-light-driven organophotoredox catalysisENRyogaHasebeGraduate School of Environment and Information Sciences, Yokohama National UniversityRumiHanadaGraduate School of Environment and Information Sciences, Yokohama National UniversityYutaTanakaGraduate School of Environment and Information Sciences, Yokohama National UniversityYutaGotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMioTakeuchiGraduate School of Environment and Information Sciences, Yokohama National UniversityHiroyoshiTakamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityIsaoKadotaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentaTanakaResearch Institute for Interdisciplinary Science, Okayama UniversityYujiroHoshinoGraduate School of Environment and Information Sciences, Yokohama National UniversityThe synthesis of sulfur- and oxygen-bridged cationic [4]-helicenes via a tandem Friedel–Crafts–SNAr reaction of a diaryl sulfide or a diaryl ether with a (thio)salicylic acid has been developed. The sulfur-bridged cationic [4]-helicenes are suitable as catalysts for photoredox reactions under low-energy light sources such as red LED light.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama2169-909713142026Investigating the Detectability of Body Wave Phases From Tidal Ice Cracking Events on Titan With the Dragonfly Short-Period Seismometere2025JE009432ENL.DelaroqueUniversité Paris Cité, Institut de Physique du Globe de Paris, CNRST.KawamuraUniversité Paris Cité, Institut de Physique du Globe de Paris, CNRSA.LucasUniversité Paris Cité, Institut de Physique du Globe de Paris, CNRSS.RodriguezUniversité Paris Cité, Institut de Physique du Globe de Paris, CNRSK.OnoderaInstitute for Planetary Materials, Okayama UniversityH.ShiraishiInstitute of Space and Astronautical Science, Japan Aerospace Exploration AgencyR.YamadaThe University of AizuS.TanakaInstitute of Space and Astronautical Science, Japan Aerospace Exploration AgencyM. P.PanningJet Propulsion Laboratory, California Institute of TechnologyR. D.LorenzThe Johns Hopkins University Applied Physics LaboratoryDetecting seismic activity on Saturn's icy moon Titan during the Dragonfly mission could provide crucial information on its internal structure. The geological complexity of the moon's surface suggests significant cyclic tidal deformation, likely leading to the fracturing of the ice shell. Considering realistic source locations and fault geometries, we assess whether a vertical short-period seismometer can detect body waves from a Mw 4.0 icequake. Signal-to-noise ratios are evaluated by comparing the high-frequency content with the expected background noise and instrument capabilities for several ice attenuation scenarios and 1D interior models. Our results indicate that the high-frequency content (≥1Hz) of Mw≤4.0 tidal-induced icequakes is likely undetectable under the most unfavorable attenuation scenarios and atmospheric conditions. However, seismic signals in the 0.5–1 Hz band—where P wave reflections dominate—may still be observable for events occurring in potential seismically active regions at ∼800–1,000 km from the Dragonfly's landing site. These signals could provide constraints on the thickness of Titan's outer ice shell, provided that intrinsic attenuation is low and environmental conditions are favorable.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0040-40391792026Visible-light-induced photocatalytic intermolecular cyclization for synthesis of 2,2-diarylchromanes156034ENSakuraKodakiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMomoKondoLaboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceJuntaMinatoLaboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceShokoItakuraLaboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceHiroyoshiTakamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMakiyaNishikawaLaboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceIsaoKadotaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKosukeKusamoriLaboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceKentaTanakaResearch Institute for Interdisciplinary Science, Okayama UniversityThe photocatalytic cyclization of salicylaldehydes with 1,1-diarylalkenes for the synthesis of 2,2-diarylchromanes has been developed. The catalytic amount of Ir photocatalyst proceeds the cyclization to give the various 2,2-diaryl chromanes under irradiation with blue LEDs. The obtained 2,2-diarylchromanes exhibit noticeable free-radical-scavenging activities, which have been largely unexplored. Notably, the chromane can convert to 2,2-diaryl-2H-naphtho[1,2-b]pyran bearing strong electron withdrawing groups, which are found in various photochromic materials. Thus, the present reaction constitutes a promising tool for the synthesis of functional materials and biologically active compounds.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2192-44491512026A case of tubulointerstitial nephritis with infiltration of neutrophils and interleukin-17-positive cells associated with Behçet’s disease35ENNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesNatsukiKubotaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTakayukiKatsuyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesBehçet’s disease (BD) is a non-infectious inflammatory condition characterized by neutrophilic infiltration. In addition to primary symptoms, including oral and genital ulcers, ocular involvement, and skin lesions, BD can also affect various organs. However, renal involvement, particularly in tubulointerstitial nephritis, has rarely been described. Herein, a rare case of acute tubulointerstitial nephritis in a patient clinically diagnosed with BD is reported. The renal lesion presented with other symptoms of BD and fever, and was considered to be BD-related due to the presence of neutrophilic infiltration and its responsiveness to BD-directed therapy. Alterations in T-helper (Th) 1, Th2, and Th17 cytokine profiles are associated with BD activity. Interleukin (IL)-17 plays a central role in neutrophil activation, and recent studies have demonstrated a strong correlation between IL-17A levels and BD activity. In the present case, elevated serum IL-17A levels and infiltration of IL-17A-positive cells into the renal tissue reflected an active phase of BD and a BD-associated renal lesion.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Tribolium castaneum with longer duration of tonic immobility have more variations corresponding to the human Parkinson’s disease genomic region8840ENKeisukeTanakaNODAI Genome Research Center, Tokyo University of AgricultureKenSasakiGraduate School of Agriculture, Tamagawa UniversityShunsukeYajimaNODAI Genome Research Center, Tokyo University of AgricultureTakahisaMiyatakeFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityParkinson’s disease (PD) is a common neurodegenerative syndrome characterized by the loss of dopaminergic neurons and is also a progressive neurodegenerative disorder that is characterized by dopamine deficiency. We established strains artificially selected for longer and shorter durations of tonic immobility, an antipredator behavior that has received much attention recently, in the red flour beetle, Tribolium castaneum, a model insect species for molecular analyses different from Drosophila melanogaster. Previous studies have shown that the long strains (L-strain) have significantly lower levels of dopamine expression in the brain than the short strains (S-strain) and that they have an abnormal pattern of locomotor activity. Furthermore, previous studies have shown that administering dopamine to L-strain beetles reduces the duration of tonic immobility. Transcriptome analysis of brain and thorax of the L- and S-strains also showed differences in mRNA expression of genes involved in dopamine synthesis and tyrosine metabolism. These results indicate that the phenotype and molecular basis of the L-strain are similar to those of Parkinson’s syndrome symptoms. In order to establish a link between T. castaneum and PD, we compared the DNA sequences of the L- and S-strains to human genes affecting dopaminergic pathways. The DNA comparison revealed many mutated regions in these genes in the L-strain. We discuss the relationship between dopaminergic pathway genes and PD-like phenotypes across humans, Drosophila, and the red flour beetle.No potential conflict of interest relevant to this article was reported.Japan Society of Mechanical EngineersActa Medica Okayama1880-55582012025Numerical analysis validating the standard k-epsilon model for the kinetic energy of turbulence subjected to weak but long-lasting wind tunnel blockage accelerationJFST0004ENAkiraONOGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHirokiSUZUKIGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityToshinoriKOUCHIGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentoTANAKAGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe aim of this study is to investigate the effect of weak but prolonged mean flow accelerations, such as those observed in wind tunnel blockage acceleration, on free-stream turbulence. Specifically, this research aims to validate a model previously developed based on the k-epsilon model. To test this model, the study focuses on scenarios where the turbulence under acceleration is steady and isotropic, since the model suggests that this type of acceleration has no effect on the turbulent kinetic energy. To examine this suggestion, the turbulence within a periodic box was analyzed using large-eddy simulation (LES) based on the conventional Smagorinsky model framework. The numerical analysis is based on a method that conserves velocity fluctuation intensities. The results show that while high rate of acceleration deviates turbulent kinetic energy, low rate acceleration has hardly any effect on turbulent kinetic energy, enstrophy, pressure fluctuation, relative pressure fluctuation intensity, and higher-order statistics of a velocity fluctuation. These results validate the accuracy of the model proposed in the previous studies. These results were obtained by focusing on differences in Reynolds numbers and the spatial scale of the forcing.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0012-15926832026A Simple Method for RNA-Seq of Manually Isolated Chromatophores in Oryzias Fishese70044ENMakotoGodaInstitute of Photonics Medicine, Hamamatsu University School of MedicineAsukaMiyagiInstitute of Photonics Medicine, Hamamatsu University School of MedicineKeisukeSugiwakaDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityMasakatsuWatanabeCellular and Structural Physiology Institute (CeSPI) and Graduate School of Pharmaceutical Sciences, Nagoya UniversityManabuBessho‐UeharaFrontier Research Institute for Interdisciplinary Science, Tohoku UniversityMasahikoHibiDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityAtsushiToyodaComparative Genomics Laboratory, National Institute of GeneticsRiekoTanakaWorld Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical GardensKawilarang W. A.MasengiFaculty of Fisheries and Marine Science, Sam Ratulangi UniversityKazunoriYamahiraTropical Biosphere Research Center, University of the RyukyusSatoshiAnsaiUshimado Marine Institute, Okayama UniversityHisashiHashimotoDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityRNA sequencing (RNA-seq) has become an essential tool for analyzing gene expression and exploring cell type–specific transcriptomes. However, sample preparation and quality control remain challenging, as current approaches typically rely on dissecting tissues containing mixed cell populations or using flow cytometry to isolate fluorescently labeled cells. Here we present a simple and reliable method for RNA-seq of chromatophores (pigment cells) by manually isolating cells based on their natural pigmentation. We analyzed four chromatophore types—melanophores, xanthophores, iridophores, and leucophores—in medaka (Oryzias latipes). Remarkably, as few as 100 cells per type yielded reasonably high-quality transcriptomes sufficient to identify differentially expressed genes (DEGs). Furthermore, this method was successfully applied to a non-model medaka species, O. woworae, which shares the same four chromatophore types. Our approach enables efficient, low-cost, and cross-species transcriptome analysis of chromatophores without requiring transgenic markers or flow cytometry.No potential conflict of interest relevant to this article was reported.岡山大学大学院社会文化科学研究科Acta Medica Okayama1881-1671612026コロナ禍で現地留学中断体験をした日本人学生における心理的変容 ― TEM 図を用いた体験のとらえ直し過程の分析 ―4763ENKoyuriSAKOTomokoTANAKA10.18926/70277No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1613-681021502025Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosise06926ENMayuOhiraDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMoeKitamuraDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyoIwasakiDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHarukoOhta‐OkanoDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiyoriTsujiiDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityReikaNakamuraDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakuyaNakazawaDepartment of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkihiroNishiguchiBiomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials ScienceMasayaYamamotoDepartment of Materials Processing, Graduate School of Engineering, Tohoku UniversityKensukeOsadaDepartment of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST)ShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHoracioCabralDepartment of Bioengineering, Graduate School of Engineering, The University of TokyoAtsushiMasamuneDivision of Gastroenterology, Graduate School of Medicine, Tohoku UniversityMitsunobu R.KanoDepartment of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHiroyoshi Y.TanakaDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFibrosis is a significant barrier to drug delivery in pancreatic ductal adenocarcinoma (PDAC) and contributes to its dismal prognosis. Pancreatic stellate cells (PSCs) drive fibrosis by excessively secreting extracellular matrix proteins such as collagen I. Collagen I is thought to physically obstruct the delivery of macromolecules, such as albumin, antibodies, and nanomedicines. Apart from its structural role, collagen signals through dedicated cell surface receptors, such as the discoidin domain receptors (DDR) 1/2. However, whether and how collagen signaling contributes to fibrotic barrier generation remains uncharacterized. Here, a 3D culture model of PDAC fibrosis constructed from patient PSCs is used to assess the contribution of DDR1/2-mediated collagen signaling. DDR1/2 inhibition diminishes collagen I expression in PSCs to enhance macromolecular delivery. Moreover, MEK inhibitors exacerbate the fibrotic barrier by up-regulating collagen I, an effect reversed by inhibiting DDR1/2. Through isoform-specific targeting, inhibiting DDR1, but not DDR2, is shown to be effective. Downstream of DDR, the involvement of the PI3K/AKT/mTOR pathway is demonstrated, particularly alternative mTOR complexes involving MEAK7 and GIT1. Altogether, the results show in vitro that DDR1-mediated collagen signaling exacerbates the fibrotic barrier and may be targeted to enhance macromolecular drug delivery in PDAC.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0309-01678852025Claudin-18 expression in gastric type adenocarcinoma and HPV-associated adenocarcinoma of the uterine cervix10031015ENNobukoYasutakeDepartment of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu UniversityYukiYokawaDepartment of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama UniversityTakehiroTanakaDepartment of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama UniversityRiriMishimaDepartment of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama UniversityMisatoKomamizuDepartment of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University Fukuoka JapanRyosukeKugaDepartment of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu UniversityRinaJiromaruDepartment of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu UniversityShinichiroKawatokoDepartment of Medicine and Clinical Science, Kyushu University Beppu HospitalKenzoSonodaDepartment of Gynecology, Kyushu University Beppu HospitalHideakiYahataDepartment of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu UniversityKiyokoKatoDepartment of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu UniversityYoshinaoOdaDepartment of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu UniversityHidetakaYamamotoDepartment of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama UniversityAims: Claudin-18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43-14A antibody, or about the gene expression of its isoforms in ECAs.<br>
Methods and results: We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high-risk human papillomavirus (HR-HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV-independent adenocarcinomas (gastric type [GAS], n = 24; non-GAS, n = 11) and 86 HPV-associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non-GASs and 2/86 (2%) HPV-associated ECAs, with positivity defined as staining in ≥75% of tumour cells, as in gastric cancer. When a 5% cut-off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non-GASs and 6/86 (7%) HPV-associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (P < 0.0001). Among the 6 cases of HPV-associated ECAs with CLDN18 expression (ranging from 5% to 80%), the histological patterns included a mix of usual and mucinous features in 4 cases, pure usual type in 1 and villoglandular variant in 1. Otherwise features such as p16 overexpression and the Rb partial loss pattern were consistent with those of HPV-associated ECAs. Six of 22 (27%) CLDN18-positive GASs were also positive for p16, but their other features—such as CLDN18 expression and the Rb preserved pattern—were the same as in p16 negative GASs. Expression of CLDN18.2 mRNA but not CLDN18.1 mRNA was confirmed in both GASs and HPV-associated ECAs.<br>
Conclusions: CLDN18 (43-14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV-associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV-associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841772025The Challenge of Diagnosing Scirrhous Gastric Cancer by Endoscopic Biopsy: A Case Reporte87334ENYukaIkedaDepartment of Internal Medicine, Clinic IkedaDepartment of Internal Medicine, Clinic IkedaMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTadashiYoshinoDepartment of Pathology, Okayama UniversityTakehiroTanakaDepartment of Pathology, Okayama University HospitalNobumasaIkedaDepartment of Internal Medicine, Clinic IkedaMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesScirrhous gastric cancer, also known as linitis plastica, is a rare and aggressive subtype of gastric carcinoma that poses significant diagnostic challenges due to its submucosal infiltration and often normal-appearing mucosa. We report a case involving a 30-year-old Japanese woman who presented with a six-month history of epigastric pain and postprandial vomiting. Initial endoscopic examination revealed erythema and mucosal swelling, with limited antral distensibility and resistance during duodenal intubation. Despite 12 mucosal biopsies, histopathological examination revealed no evidence of malignancy. Given the strong clinical and endoscopic suspicion of scirrhous gastric cancer, additional deep sections and immunohistochemical staining were performed. These revealed scattered signet-ring cell carcinoma and poorly differentiated adenocarcinoma, with positive immunostaining for p53 and Ki67. The patient underwent total gastrectomy, and the diagnosis of scirrhous gastric cancer was confirmed on the resected specimen. This case highlights the importance of a high index of clinical suspicion, close collaboration between endoscopists and pathologists, and the utility of ancillary diagnostic tools, such as immunohistochemistry, in identifying subepithelial gastric malignancies that may be missed on conventional biopsy.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322026Clinical and Genetic Landscape of Glioblastoma, IDH-Wildtype With FGFR Gene Family AlterationsENYasuhitoKegoyaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshihiroOtaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyoMizutaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyosukeIkemachiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMakoKamiuraDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJojiIshidaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinichiToyookaCenter for Comprehensive Genomic Medicine, Okayama University HospitalDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesGlioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH-wt), is a highly aggressive brain tumor with a poor prognosis. Alterations in the fibroblast growth factor receptor (FGFR) gene family—such as FGFR::TACC fusions and FGFR1 mutations—have emerged as potential therapeutic targets; however, their clinical and genetic features in GBM, IDH-wt remain unclear. We analyzed 1076 GBM, IDH-wt cases using comprehensive genomic profiling data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. FGFR alterations were detected in 8.0% of patients, including FGFR::TACC fusions (3.3%) and FGFR1 mutations (2.9%). The FGFR::TACC fusion-positive group was older at diagnosis and showed higher frequencies of TERT promoter mutation and MDM2 amplification, and lower frequencies of EGFR amplification and TP53 mutation, compared with the fusion-negative group. The FGFR1 mutation-positive group was enriched for ATRX, NF1, and PIK3CA mutations and had significantly fewer TERT promoter and PTEN mutations, compared with the mutation-negative group. No significant differences in overall survival were observed, although both groups tended to have longer median overall survival compared with their respective negative groups. This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies.No potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231912026腎機能の理解を促すための教材開発と中学校理科における授業実践111117ENMotonoriANDOFaculty of Education, Okayama UniversityRisaIKEDASeishin Junior High School/Seishin Girls’ High SchoolFukutoTANAKASeishin Junior High School/Seishin Girls’ High School10.18926/bgeou/70200 本研究では腎臓におけるろ過後，ろ液の成分がどのような物質で構成されているのか，その後の腎臓での再吸収過程を含めて，中学生の腎機能の理解を促す教材開発を試みた。まず，市販の果汁を含む飲料水をメンブレンフィルターでろ過し，ろ液が透明になるのは不溶性物質が除去されるためであること，また，ろ液の甘さから水溶性の糖分はろ過されることを確認した。開発した腎臓糸球体モデルは，腎小体に見立てた蓋に孔を開けたプラスチック容器，赤血球や血液中に存在する様々な物質を模した色や大きさの異なるビーズ，から構成される。生徒は，この教材を用いた授業実践を経て，血球以外の水溶性成分は要不要に関わらず一旦腎小体でろ過されてしまうこと，生体に必要なブドウ糖は尿細管において能動的に再吸収されることを理解し，腎臓のろ過と再吸収に関する新しい考え方と関連する概念を獲得することができた，と考えられた。本研究で開発した教材を用いることにより，生徒の腎臓の役割についての理解を深化させること，同時に自身の健康への関心を高めさせること，について有効であることが分かった。No potential conflict of interest relevant to this article was reported.The Japanese Society for Neuroendovascular TherapyActa Medica Okayama1882-40721912025The Qualification Examination for Specialists and Instructors in the Japanese Society of Neuroendovascular Therapy: History and Current Statussr.2024-0099ENShinichiYoshimuraDepartment of Neurosurgery, Hyogo Medical UniversityKenjiSugiuDepartment of Neurological Surgery, Okayama University Graduate School of MedicineMasaruHirohataDepartment of Neurosurgery, Kurume Medical UniversityYukikoEnomotoDepartment of Neurosurgery, Gifu University Graduate School of MedicineHirotoshiImamuraDepartment of Neurosurgery, National Cerebral and Cardiovascular CenterWataroTsurutaDepartment of Endovascular Neurosurgery, Toranomon HospitalToshiyukiFujinakaDepartment of Neurosurgery, National Hospital Organization Osaka National HospitalHitoshiHasegawaDepartment of Neurosurgery, Brain Research Institute, Niigata UniversityToshioHigashiDepartment of Neurosurgery, Fukuoka University Chikushi HospitalTakashiIzumiDepartment of Neurosurgery, Nagoya University of Graduate School of MedicineHiroKiyosueDepartment of Diagnostic Radiology, Kumamoto University Faculty of Life SciencesYasushiMatsumotoDivision of Development and Discovery of Interventional Therapy, Tohoku University HospitalHidenoriOishiOishi Neurosurgery Clinic, and Department of Neurosurgery, The Jikei University School of MedicineTetsuSatowDepartment of Neurosurgery/Stroke Center, Kindai University HospitalMichihiroTanakaDepartment of Neurosurgery and Neuroendovascular Surgery, Kameda Neurocenter, Kameda Medical CenterTomoyukiTsumotoDepartment of Neurosurgery, Showa University Fujigaoka HospitalHiroshiYamagamiDivision of Stroke Prevention and Treatment, Institute of Medicine, University of TsukubaAkiraIshiiDepartment of Neurosurgery, Juntendo University Faculty of MedicineYujiMatsumaruDepartment of Neurosurgery, Institute of Medicine, University of TsukubaShigeruMiyachiDepartment of Neurological Surgery, Aichi Medical UniveristyNeuroendovascular therapy is a key treatment for cerebrovascular disorders, driven by advancements in devices and techniques. The Japanese Society for Neuroendovascular Therapy (JSNET) established a certification system in 1997 to ensure operator competence and minimize complications, with the first examination in 2002. JSNET offers 2 main certifications: specialist and instructor. Specialists perform basic procedures, while instructors lead in practice, education, and research. In 2020, the mechanical thrombectomy practitioner qualification was added to promote mechanical thrombectomy. Applicants must have a JSNET membership, relevant certifications, training, and documented experience. The certification process includes rigorous written and practical examinations that now employ non-fluoroscopic models. Certification renewal every 5 years requires conference participation and a continuing education program. Public awareness and integration into stroke center designations have grown. Over 2200 specialists, including more than 500 instructors, have been certified, significantly advancing neuroendovascular therapy in Japan. JSNET aims to continue improving certification and education to maintain high standards.No potential conflict of interest relevant to this article was reported.Japan Society of Mechanical EngineersActa Medica Okayama2187-97451252025Examining OpenFOAM-based LES analysis in terms of inviscid energy conservation and viscous turbulence decay25-00095ENHirokiSUZUKIGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentoTANAKAGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityToshinoriKOUCHIGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe present study examines an OpenFOAM-based LES analysis from the viewpoints of inviscid energy conservation and viscous turbulence decay. The Smagorinsky model is employed as the sub-grid scale (SGS) model, and a two-dimensional periodic analytical solution and a three-dimensional periodic Taylor-Green vortex (TGV) are employed to represent inviscid flows. The analytical relationship for the kinetic energy K, dK/dt = 0, with t as the dimensionless time, is utilized to validate the OpenFOAM results. For the viscous flow case, the TGV flow in a three-dimensional periodic cubic domain is adopted, and its turbulence kinetic energy distribution is compared with that obtained by a spectral method to examine the analysis. The OpenFOAM-based analysis exhibits energy conservation error in flows that should ideally conserve energy. For the two-dimensional flow, this error decreases with increasing grid resolution N. However, in the three-dimensional flow, the error does not improve even with higher N. In the three-dimensional TGV flow, the turbulence kinetic energy predicted by OpenFOAM exhibits a strong agreement with that from the spectral method when a standard constant value of the Smagorinsky model is employed and the mesh is sufficiently refined. Conversely, for a condition of relatively coarse mesh, the decay characteristics of turbulent kinetic energy deviate from those of the spectral method, and a higher constant value of the Smagorinsky model than the default value becomes necessary to reproduce comparable results. These results suggests that even in LES simulations where highly accurate conservation laws are not satisfied, adjusting the model constants so that the predicted values match experimental or numerical reference data can improve the apparent reliability of the turbulent kinetic energy in the decaying turbulence.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2590-1397282025Flow diverter treatment for internal carotid artery aneurysm following management of distal cerebral aneurysms: Technical note100540ENYuichiHirataDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasafumiHiramatsuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiSugiuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFukikoBabaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJuntaroFujitaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutaSotomeDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoKawakamiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuKimuraDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiEbisudaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunHarumaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohitoHishikawaDepartment of Neurosurgery, Kawasaki Medical SchoolShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: In recent years, the effectiveness of flow diverters (FDs) for the treatment of intracranial aneurysms has been reported. While FDs are effective, their deployment involves advancing a delivery wire distally, which may pose a risk if a distal aneurysm exists within the same artery. In such cases, the delivery wire could potentially perforate the distal aneurysm. Here, we present two cases of tandem aneurysms in which an internal carotid artery (ICA) aneurysm was treated with an FD following the treatment of a distal cerebral aneurysm.<br>
Case description: A 44-year-old woman and a 67-year-old woman underwent magnetic resonance imaging for headache or abducens nerve palsy. In both cases, two aneurysms were revealed: one at the ICA and the other either at the middle cerebral artery or the top of the ICA. Due to the risk of perforation by the delivery wire during FD deployment, the distal aneurysms were treated first—either with surgical neck clipping or stent-assisted coil embolization. One month after the initial treatment, FD placement for the ICA aneurysm was performed as planned without complications in either case.<br>
Discussion: This is the first report where tandem aneurysms were successfully treated with treatment for distal cerebral aneurysms, followed by FDs for proximal ICA aneurysms. We emphasize the potential risk of perforation of the distal aneurysm by the delivery wire during FD placement.<br>
Conclusion: Treatment of distal cerebral aneurysms beforehand can help ensure the safe and effective use of FDs in patients with tandem aneurysms.No potential conflict of interest relevant to this article was reported.Japan Stroke SocietyActa Medica Okayama0912-07264762025頭蓋頚椎移行部動静脈瘻の開頭手術時における上腕動脈穿刺による脳血管撮影の有用性410412ENYuichiHirataDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasafumiHiramatsuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSusumuSasadaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJuntaroFujitaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutaSotomeDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoKawakamiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuKimuraDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiEbisudaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKyoheiKinDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunHarumaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiSugiuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences頭蓋頚椎移行部動静脈瘻の手術では，異常血管の確認のため術中血管撮影が重要であるが，体位変換時のsheathの固定や撮影血管へのカテーテルの誘導が困難である．今回，頭蓋頚椎移行部動静脈瘻の開頭手術において上腕動脈穿刺によりultra-long sheathを鎖骨下動脈に留置して椎骨動脈撮影（vertebral artery angiography: VAG）を行う方法の有用性を報告する．当院で本血管撮影を施行した症例の患者背景や合併症を評価した．企図した4例，5血管でVAGを施行でき，合併症も認めなかった．体位変換も腹臥位における穿刺部の観察も簡便であり，カテーテルの操作性にも優れ，VAGを容易に施行することができた．また，管球を頭側から移動する際の術野との干渉も最小限に抑えられた．本方法は利点が多く，有用な血管撮影方法であり，頭蓋頚椎移行部動静脈瘻の手術における一助となり得ると考える．No potential conflict of interest relevant to this article was reported.Japanese Society for Horticultural ScienceActa Medica Okayama2189-01029442025Effects of Intermittent Low-temperature Storage Duration and Cycle on the Bolting and Flowering of Delphinium elatum in Summer522529ENMikaKawaiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMiwaFukuyasuGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshiyukiTanakaGraduate School of Agriculture, Kyoto UniversityYoshikuniKitamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKen-ichiroYasubaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYuichiYoshidaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTanjuroGotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEarly-bolting in summer is a major problem when growing delphinium seedlings in summer to produce cut flowers that will be shipped in autumn and winter. In this study, an intermittent low-temperature storage (ILTS) treatment that induces flower bud differentiation in strawberry and prevents rosette formation in Eustoma significantly increased the Delphinium elatum cut flower length. Moreover, ILTS was as effective as growing seedlings under cool conditions at preventing early-bolting. We analyzed the effects of six ILTS treatments that differed regarding the treatment temperature (5 and 10°C) and treatment cycle (3 days/3 days, 6 days/6 days, and 12 days/12 days; ambient conditions/cool and dark). Cut flowers were significantly longer with the 6 days/6 days treatment at 10°C than for the control treatment. Furthermore, repeating the ILTS treatment cycle (6 days ambient conditions/6 days at 10°C) a total of four times produced high-quality cut flowers regardless of the cultivar. Therefore, this ILTS treatment may be ideal for preventing early-bolting in D. elatum.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1757-22151912025Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer13ENAnnaRogachevskayaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolYusukeOtaniDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineAkiraOhtsuHarvard Medical SchoolVanessa D.ChinUMass Chan Medical School, UMass Memorial Medical CenterTirsoPeñaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolSeijiAraiDepartment of Urology, Gunma University Graduate School of MedicineShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineAtsushiFujimuraDepartment of Molecular Physiology, Faculty of Medicine, Graduate School of Medicine, Kagawa UniversityAtsushiTanakaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolBackground C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment.<br>
Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2. Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway.<br>
Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2475-0328962025Surgery for Older Cancer Patients: Cross‐Organ Review and Good Practice Statement by the Japanese Geriatric Oncology Guideline Committee11281136ENChieTanakaDepartment of Gastroenterological Surgery, Nagoya University Graduate School of MedicineTakashiOfuchiDepartment of Surgery, Kyushu University Beppu HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalDaisukeInoueDepartment of Obstetrics and Gynecology, University of FukuiKenSugimotoDepartment of General Geriatric Medicine, Kawasaki Medical SchoolKeikoMurofushiDivision of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalToruOkuyamaDepartment of Psychiatry/Palliative Care Center, Nagoya City University West Medical CenterShigeakiWatanukiNational Center for Global Health and Medicine, National College of NursingChiyoImamuraAdvanced Cancer Translational Research Institute, Showa UniversityDaisukeSakaiDepartment of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of MedicineNaomiSakuraiCancer Solutions Co. LtdKiyotakaWatanabeDivision of Medical Oncology, Department of Medicine, School of Medicine, Teikyo UniversityKazuoTamuraNPO Clinical Hematology/Oncology Treatment Study GroupToshiakiSaekiBreast Oncology Service, Saitama Medical University International Medical CenterHiroshiIshiguroBreast Oncology Service, Saitama Medical University International Medical CenterBackground: Although the number of older people is increasing, there is a lack of evidence and insufficient consensus regarding postoperative complications and survival in older cancer patients. In this study, we conducted a literature search and systematic review focusing on the outcomes after surgery for older cancer patients.<br>
Methods: Literature focusing on surgical treatment for older cancer patients was extracted from Japanese clinical practice guidelines for gastric cancer, lung cancer, colorectal cancer, liver cancer, and gynecological cancers (uterine body, uterine cervix, ovary, and external genitalia and vagina). Outcomes were reviewed, and committee members determined the strength of evidence on a four-point scale (A to D), with A being the highest and D being the lowest.<br>
Results: Older cancer patients tend to have a higher incidence of postoperative complications and postoperative syndromes, and their expected survival is generally shorter compared to non-older patients. When extensive surgeries such as para-aortic lymph node dissection and/or resection with other organs are performed for older cancer patients, the postoperative mortality rates tend to increase compared to non-older patients.<br>
Conclusion: Surgical treatments for older cancer patients tend to result in higher morbidity even when the patients are in good health status. Nevertheless, there is still a possibility that a certain fraction of the patients achieve treatment outcomes comparable to those of non-older patients. Therefore, surgical indication and procedure for older cancer patients should be carefully determined based on surgical invasiveness and patient tolerability.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2352-5789592025Evaluation of platinum-free interval and chemotherapeutic effect of subsequent platinum-containing chemotherapy in patients with recurrent ovarian cancer initially treated with bevacizumab: SGSG018/Intergroup study101740ENTamakiTanakaDepartment of Perinatology and Gynecology, Kagawa University Graduate School of MedicineKazuhiroTakeharaDepartment of Gynecologic Oncology, NHO Shikoku Cancer CenterTomokaUsamiDepartment of Obstetrics and Gynecology, Ehime University Graduate School of MedicineMasakoIshikawaDepartment of Obstetrics and Gynecology, Shimane University Faculty of MedicineEijiKondoDepartment of Obstetrics and Gynecology, Mie University Graduate School of MedicineMasahiroKagabuDepartment of Obstetrics and Gynecology, Iwate Medical UniversityKeiHirabayashiDepartment of Obstetrics and Gynecology, JCHO Tokuyama Central HospitalNoriomiMatsumuraDepartment of Obstetrics and Gynecology, Kindai University Faculty of MedicineShinyaSatoDepartment of Obstetrics and Gynecology, Faculty of Medicine Tottori UniversityMasatoNishimuraDepartment of Obstetrics and Gynecology, Tokushima Prefectural Central HospitalAtsushiArakawaDepartment of Obstetrics and Gynecology, Nagoya City University West Medical CenterKeiichiroNakamuraDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeKonnoDepartment of Obstetrics and Gynecology, Hokkaido University HospitalSatoeFujiwaraDepartment of Obstetrics and Gynecology, Osaka Medical and Pharmaceutical UniversityKotaroSueokaDepartment of Obstetrics and Gynecology, Yamaguchi University Graduate School of MedicineHirokoNakamuraDepartment of Obstetrics and Gynecology, NHO Kure Medical Center and Chugoku Cancer CenterIemasaKohDepartment of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Hiroshima UniversityKimihikoItoDepartment of Obstetrics and Gynecology, Kansai Rosai HospitalAtsushiHongoDepartment of Obstetrics and Gynecology, Kansai Rosai HospitalObjective: The effect of bevacizumab on platinum sensitivity in recurrent ovarian cancer remains poorly understood. This study examined the association between platinum-free interval (PFI) and sensitivity to subsequent platinum-containing chemotherapy in patients with first relapsed ovarian cancer after bevacizumab chemotherapy.<br>
Methods: We retrospectively analyzed patients who received platinum-based chemotherapy for platinum-sensitive recurrence between November 2013, and December 2019, and who were initially treated by platinum-based chemotherapy with concurrent and maintenance bevacizumab. The primary endpoint was response rate to subsequent chemotherapy after various periods of PFI. The relevance between response rate and PFI was assessed for each PFI of 6–12, 12–24 and ≧24 months using Cochran-Armitage test. The secondary endpoint was progression-free survival (PFS) defined as time from chemotherapy for first recurrence to subsequent progression and response rate to subsequent chemotherapy for each treatment-free interval since last administration of bevacizumab (Bev-TFI).<br>
Results: A total of 77 patients were eligible. The median PFI until first recurrence was 12 months (range: 6–43). The response rates of subsequent chemotherapy for patients with PFI of 6–12, ≥12-24, and 24 months were 42 %, 65 %, and 80 %, showing a linear trend (p < 0.05). Median PFS among the three groups was 8 (95 %CI: 6.7–9.2), 11 (95 %CI: 8.4–13.5) and 13 months (95 % CI: 5.4–20.5) (p = 0.107, log-rank test), respectively. By contrast, no linear trend was observed between Bev-TFI and response rate (p = 0.225)<br>
Conclusion: In patients with first relapse of primary ovarian cancer and bevacizumab beyond progression, the prolonged PFS effect of bevacizumab does not seem to affect sensitivity to subsequent platinum-based chemotherapy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96253072025How to report and discuss subgroup analyses in clinical practice guidelines? Evaluation procedure of the clinical and statistical relevancy12591267ENKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalSatoruMiuraDepartment of Internal Medicine, Niigata Cancer Center HospitalYukoOyaDepartment of Respiratory Medicine and Allergy, Fujita Health UniversityTomohiroSakamotoDivision of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori UniversityKentaroTanakaGraduate School of Medical Sciences, Research Institute for Diseases of the Chest, Kyushu UniversityShunsukeTeraokaInternal Medicine III, Wakayama Medical UniversityMasahiroMoriseDepartment of Respiratory Medicine, Nagoya University Graduate School of MedicineSatoshiMoritaDepartment of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto UniversityThe results of subgroup analyses of clinical trials are important reference information when considering the generalizability of a study treatment, i.e., providing the best treatment for each individual patient. The results of subgroup analyses are often presented in publications, etc. as forest plots focusing on patient backgrounds. However, it is important to fully understand and grasp some of the issues involved in subgroup analyses and to interpret the results carefully to apply them in clinical practice. Although the literature includes some reports on how subgroup analyses should be evaluated and handled for the purpose of establishing medical practice guidelines, most of the papers have mainly evaluated the reliability of subgroup analyses from a statistical perspective; few of them have incorporated clinical importance in their evaluations. Therefore, in December 2019, we established a Subgroup Analysis Review Committee consisting of oncologists specializing in lung cancer treatment and statistical experts among the members of the Guidelines Review Committee of the Japanese Lung Cancer Association, with the aim of appropriately reflecting subgroup analysis in Japanese lung cancer practice guidelines. We developed a new evaluation strategy to incorporate clinical aspects as well as reliability assessment. Specifically, on the basis of a clinical and statistical review of the problems with subgroup analyses presented as clinical trial results, we developed criteria and procedures to ensure consistency and fairness in the citation of clinical guidelines.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841762025Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Studye86575ENShoSaekiDepartment of Respiratory Medicine, Kumamoto University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalShinyaSakataDepartment of Respiratory Medicine, Kumamoto University HospitalNaohiroOdaDepartment of Respiratory Medicine, Okayama University HospitalKojiInoueDepartment of Respiratory Medicine, Kitakyushu Municipal Medical CenterTomokiTamuraDepartment of Respiratory Medicine, Okayama University HospitalRyoToyozawaDepartment of Thoracic Oncology, National Hospital Organization Kyushu Cancer CenterDaijiroHaradaDepartment of Thoracic Oncology, National Hospital Organization Shikoku Cancer CenterKentaroTanakaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityKojiInoueDepartment of Respiratory Medicine, Ehime Prefectural Central HospitalYoshiyukiShioyamaRadiation Oncology, Ion Beam Therapy Center, SAGA HIMAT FoundationKenichiGembaDepartment of Respiratory Medicine, Chugoku Central HospitalTomonariSasakiDepartment of Radiation Oncology, Iizuka HospitalAkihiroBesshoDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalJunjiKishimotoCenter for Clinical and Translational Research, Kyushu University HospitalKuniakiKatsuiDepartment of Radiology, Division of Radiation Oncology, Kawasaki Medical SchoolKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalKenjiSugioThoracic and Breast Surgery, Oita UniversityBackground and objective: We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression.<br>
Materials and methods: We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients.<br>
Results: Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinib monotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported.<br>
Conclusions: Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291864142025Myeloid Sarcoma in the Small Intestine21552159ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomohiroKamioDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShoichiroHirataDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsunoriMatsuedaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDaisukeKametakaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMyeloid sarcoma is a rare extramedullary tumor of immature myeloid cells that is often associated with acute myeloid leukemia (AML). We herein report an 81-year-old man who presented with intestinal obstruction due to myeloid sarcoma of the small intestine. Diagnostic challenges were overcome using double-balloon enteroscopy and a biopsy, which confirmed the diagnosis of myeloid sarcoma. The patient subsequently developed AML but responded well to chemotherapy. This case underscores the importance of considering myeloid sarcoma in the differential diagnosis of small-bowel tumors. Highlighting the significance of a histological analysis, even in patients presenting with small bowel obstruction, the early diagnosis and treatment are crucial for improving outcomes, particularly in patients without a history of hematologic malignancies.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841752025Pseudoachalasia Due to Malignant Pleural Mesothelioma Involving the Esophaguse84161ENManamiHondaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesWe report a rare case of pseudoachalasia secondary to malignant pleural mesothelioma involving the esophagus. A 66-year-old man presented with progressive dysphagia, weight loss, and postprandial hiccups. Endoscopic examination showed esophageal dilation with luminal narrowing at the esophagogastric junction, but no mucosal abnormalities. Computed tomography revealed an irregular-shaped mass extending from the peri-esophagogastric junction to the retroperitoneum, accompanied by pleural effusion, right-sided hydronephrosis, and multiple hepatic lesions. Endoscopic ultrasound-guided fine-needle aspiration from the mass lesion through the esophageal lumen revealed epithelioid malignant mesothelioma. This case highlights the importance of considering malignant mesothelioma in the differential diagnosis of pseudoachalasia, particularly when imaging reveals extrinsic esophageal compression without mucosal lesions.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841742025Gastrointestinal Stromal Tumors in the Stomach With Tumor Growth and Hemorrhage During Conservative Management: A Report of Two Casese82046ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesGastrointestinal stromal tumors (GISTs) are often detected incidentally during esophagogastroduodenoscopy. Although surgical resection is the standard treatment for GISTs, patients with significant comorbidities may not be eligible for surgery and are managed conservatively. Herein, we report two cases of gastric GISTs that were initially observed during the management of other comorbidities but subsequently became enlarged, resulting in gastrointestinal bleeding. These cases highlight the potential risks of tumor progression and bleeding in patients undergoing conservative management.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72571822025Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab363368ENShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHironariKatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKosakuMorimotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalIntrahepatic cholangiocarcinoma has a poor prognosis. In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed MLH1 pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30 months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the MLH1 pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841722025Gastric Metastasis of Renal Cell Carcinoma Initially Diagnosed by Esophagogastroduodenoscopye79651ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomohiroKamioDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShoichiroHirataDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHere, we report a rare case of renal cell carcinoma (RCC) initially detected as a gastric metastasis. A 58-year-old man with epigastric discomfort underwent esophagogastroduodenoscopy, which revealed a reddish semi-pedunculated lesion with a whitish coating. Biopsy and imaging confirmed clear cell RCC metastasis. Contrast-enhanced computed tomography (CT) revealed a primary renal tumor with pancreatic and lymph node metastases. Despite chemotherapy treatment, the patient died after 10 months. Gastric metastases from RCC, although rare, should be considered in highly vascular gastric lesions with white coatings. Clinicians must be vigilant for metastatic diseases with atypical gastric findings.No potential conflict of interest relevant to this article was reported.IOP PublishingActa Medica Okayama1742-6588302712025LES analysis to investigate a random-phase forcing scheme for steadying anisotropic turbulence fields012009ENKokiMinamiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHirokiSuzukiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityToshinoriKouchiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentoTanakaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe aim of this study is to investigate the effect of phase randomization on forcing mechanisms that stabilize localized turbulence. A trigonometric forcing based on vector potential is combined with uniform random numbers to create a spatially homogeneous forcing field. The analysis is performed using large-eddy simulation (LES) with the Smagorinsky model as the subgrid scale model. The results demonstrate that steady flows are generated regardless of the presence of phase randomization, successfully forming isotropic turbulence. In contrast, for anisotropic turbulent fields, the addition of phase randomization reduces the degree of anisotropy, indicating a smoothing effect on the anisotropy of the flow.No potential conflict of interest relevant to this article was reported.IOP PublishingActa Medica Okayama1742-6588302712025Fundamental examination of coherent structure model prediction using vortex cores in a two-dimensional Taylor’s analytical solution012008ENXuanyouGongGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHirokiSuzukiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityToshinoriKouchiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentoTanakaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThis study focuses on the possibility that flow around vortex tubes in turbulence may resemble laminar flow, and aims to describe the characteristics of turbulent fields using analytical solutions to the governing equations. In the two-dimensional analytical Taylor solution, the velocity and pressure fields are expressed by trigonometric functions, and a structure in which counter-rotating vortices are arranged in a grid pattern is demonstrated. This solution is used to verify the accuracy of numerical analyses and is expected to contribute to a simple yet unambiguous description of turbulent fields based on vortex structures. Predictions of sub-grid scale components and validation of a coherent structure model using invariants of the velocity gradient tensor are also performed.No potential conflict of interest relevant to this article was reported.岡山大学教育推進機構Acta Medica Okayama1881-595232026心理臨床家同士のグループ体験における反省的実践1230ENRyosukeKOBASHIInstitute for Promotion of Education and Campus Life, Okayama UniversityMasashiTANAKATokai UniversityRinMURASEGraduate School of Education and Human Development, Nagoya University10.18926/70109 心理臨床家にとって反省的実践は重要であり，多様な形態のグループに参加をすることによって反省的実践を行っている。本研究では，全般的な心理臨床家同士のグループにおける体験（研究1）および継続的なグループにおける体験（研究2）を探索することを目的として，数名の心理臨床家による話し合いをKJ法を援用して分析した。その結果，心理臨床家同士のグループ体験における反省的実践には，【グループ体験が内省につながるかどうか】などの4つ側面が重要であることが示された。また，継続的なグループにおける体験では，《本来の人としての感覚や欲求》や《自分を不自由にしている要因》などの【会における気づき】が得られることが反省的実践として有意義であることが明らかになった。No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8012026Effective Treatment of Advanced Hepatocellular Carcinoma with Extensive Peritoneal Dissemination Using Lenvatinib6974ENShinyaWakatsukiDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterShinyaSakamotoDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterAkikoUenoDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterTakaomiNambaDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterYoritoYamamotoDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterManabuMatsumotoDepartment of Diagnostic Pathology, Kochi Health Sciences CenterJunIwataDepartment of Diagnostic Pathology, Kochi Health Sciences CenterTakehiroOkabayashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterCase Report10.18926/AMO/70075Patients with hepatocellular carcinoma (HCC) and extensive peritoneal dissemination generally have a poor prognosis and are often resistant to systemic therapy. We report the case of a 47-year-old woman with HCC and massive peritoneal dissemination who presented with malignant ascites requiring repeated cell-free and concentrated ascites reinfusion therapy and peritoneovenous shunt placement, as well as malignant pleural effusion requiring pleurodesis. Combined immunotherapy with durvalumab/tremelimumab was initiated;however, disease progression was observed after three treatment courses, prompting a switch to lenvatinib therapy. Two months after initiation of lenvatinib, CT imaging demonstrated complete disappearance of arterial enhancement in the primary hepatic lesion, along with reduction in the size of peritoneal dissemination nodules. Thirteen months after switching to lenvatinib (16 months after the initial diagnosis), the alpha-fetoprotein level continued to decrease, and the disease remained stable under treatment. Despite the extremely high tumor burden, lenvatinib achieved disease stabilization and symptomatic improvement.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8012026The Preoperative Anterior Pelvic Plane Angle Predicts Cup Anteversion Changes at 1 Year after Total Hip Arthroplasty3137ENKyotaIshibashiDepartment of Orthopedic Surgery, Hachinohe City HospitalHirotakaOishiDepartment of Orthopedic Surgery, Hachinohe City HospitalRyoArakiDepartment of Orthopedic Surgery, Hachinohe City HospitalKosukeKawamuraDepartment of Orthopedic Surgery, Hachinohe City HospitalIsamuSasakiDepartment of Orthopedic Surgery, Hachinohe City HospitalEijiSasakiDepartment of Orthopedic Surgery, Hirosaki University Graduate School of MedicineHikaruKamadaDepartment of Orthopedic Surgery, Hachinohe City HospitalMasakazuKogawaDepartment of Orthopedic Surgery, Hachinohe City HospitalSunaoTanakaDepartment of Orthopedic Surgery, Hachinohe City HospitalTakuyaNumasawaDepartment of Orthopedic Surgery, Hachinohe City HospitalYasuyukiIshibashiDepartment of Orthopedic Surgery, Hirosaki University Graduate School of MedicineOriginal Article10.18926/AMO/70070We investigated global alignment changes following total hip arthroplasty (THA) and predictive alignment parameters for increased cup anteversion (CA) by retrospectively analyzing the primary THA data of 75 patients treated at our hospital (49 women, 26 men; age 65.1±5.7 years, BMI 28.3±3.4 kg/m2). Global alignment parameters, i.e., the anterior pelvic plane angle (APPa) and proximal femoral shaft angle (PFSa) and other alignment parameters were measured. CA was evaluated based on the patients’ standing coronal radiographs. ΔCA was defined as the difference in CA from 2 weeks before to 1 year after each THA. We classified the cases as stable (S) (CA < 10°; n=63) and pelvic retroversion (R) (CA ≥ 10°; n=12) groups. Associations between ΔCA and alignment parameters were evaluated by linear regression and a receiver operating characteristic (ROC) analysis. A significant decrease in the PFSa occurred between the 2-week and 1-year post-THA timepoints (7.8±4.3° vs. 4.2±3.6°, p<0.001), with no notable change in other alignment parameters. At 1-year post-THA, the CA of 12 (16%) patients had increased to 4.5±4.4°. Only the preoperative APPa was positively associated with ΔCA (β=0.165, p=0.020). The ROC analysis revealed that the optimal cut-off value for increased CA in the APPa is 2.1° (area under the curve, 0.700; p=0.020; odds ratio, 4.80). The APPa change predicted increased CA, which emphasizes the importance of the use of preoperative standing radiography for identifying the optimal cup positioning for post-THA changes in CA.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8012026Development of a Stroke Discharge Support Evaluation Scale for Ward Nurses in Acute Care Hospitals1730ENHidekiYanoDepartment of Nursing, Faculty of Human Health Sciences, Niimi UniversityYokoTakahataGraduate School of Health Sciences, Okayama UniversityTakeshiYamaguchiFaculty of Nursing, Shikoku UniversityShinyaSaitoGraduate School of Health Sciences, Okayama UniversityOriginal Article10.18926/AMO/70069This study aimed to develop a scale enabling nurses to objectively evaluate their own stroke discharge support, as a basis for enhancing its overall effectiveness. A draft scale was created based on a literature review, and consisted of a 51-item, 5-point Likert-type questionnaire administered to ward nurses engaged in stroke discharge support at acute care hospitals. Factor analysis was performed to refine the scale. Construct validity was assessed using the known-groups method, and reliability was evaluated through internal consistency analysis. The resulting Stroke Discharge Support Evaluation Scale comprises 29 items across 5 factors, each rated on a 5-point Likert scale. Analysis of the data collected from 237 valid responses demonstrated good internal consistency and supported the scale’s construct validity. The Stroke Discharge Support Evaluation Scale is a reliable and valid tool enabling ward nurses in acute care hospitals to evaluate their own stroke discharge support.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8012026A Novel Nomogram that Predicts Chronic Hemodialysis Patients’ Survival Based on Their Sedentary Behavior916ENKentaroSugaharaDepartment of Hygiene, Faculty of Medicine, Kagawa UniversityTakashiKondoInnoshima General HospitalNobuyukiMiyatakeDepartment of Hygiene, Faculty of Medicine, Kagawa UniversityHiroyukiNishiInnoshima General HospitalKazuhiroUjikeInnoshima General HospitalKiichiKoumotoInnoshima General HospitalKeiichiNamioDepartment of Hygiene, Faculty of Medicine, Kagawa UniversityShuheiHishiiDepartment of Hygiene, Faculty of Medicine, Kagawa UniversityAkihikoKatayamaFaculty of Social Studies, Shikokugakuin UniversityHiromiSuzukiDepartment of Hygiene, Faculty of Medicine, Kagawa UniversityYorimasaYamamotoInnoshima General HospitalOriginal Article10.18926/AMO/70068Appropriate treatments for chronic hemodialysis patients are a public health challenge in Japan. Sedentary behavior appears to be closely associated with these patients’ survival. We thus sought to develop a nomogram that predicts survival based on the duration of chronic hemodialysis patients’ sedentary behavior. One hundred twenty-four patients under chronic hemodialysis (73 men, 51 women, age 71.7±11.1 years) were enrolled in this cohort study. The patients wore a triaxial accelerometer that measured both their sedentary behavior, i.e., total sedentary behavior (minutes) and their maximum sedentary bouts (min) on non-hemodialysis days. We obtained the Kaplan-Meier curve and used the log-rank test and a Cox proportional hazards model to evaluate the relationship between the patients’ sedentary behavior and their survival. We also used a Cox proportional hazards model to develop a nomogram for the patients’ 5-year survival rate. Forty-six patients died during the follow-up period. When we stratified the patients by the medians of total sedentary behavior and maximum sedentary bouts, we observed significant between-group differences. After adjustment for confounding factors in a Cox proportional hazards model, total sedentary behavior and maximum sedentary bouts were identified as critical survival factors, and we generated a nomogram using an index of sedentary behavior. Our analysis results demonstrated that sedentary behavior on non-dialysis days was closely associated with the survival of the chronic hemodialysis patients, suggesting that a decrease in sedentary behavior would prolong their survival. The nomogram developed herein based on sedentary behavior may be useful for predicting the outcomes of chronic hemodialysis patients.No potential conflict of interest relevant to this article was reported.岡山大学文明動態学研究所Acta Medica Okayama2436-832652026Materiality, Making and Movement : A commentary153155ENMasakazuTANAKAFaculty of International Fashion, PROFESSIONAL INSTITUTE OF INTERNATIONAL FASHION特集：Sacred Objects in Religions (Special Issue: Sacred Objects in Religions)10.18926/70060No potential conflict of interest relevant to this article was reported.岡山大学文明動態学研究所Acta Medica Okayama2436-832652026Depicting Buddha : Practice, Prescription and Perception134152ENShijunZHANGDepartment of Sociology & Institute of Sociology and Anthropology, Peking University特集：Sacred Objects in Religions (Special Issue: Sacred Objects in Religions)10.18926/70059Tibetan thangka refers to a genre of pictorial art widely produced across the Tibetan cultural region since the 11th century. Although scroll painting is its most common form, thangkas are also created through embroidery, appliqué, and brocade weaving. The subjects depicted encompass a wide range of themes within Tibetan Buddhism and the Bön religion, including various Buddhas, bodhisattvas, deities, monks, mandalas, as well as astronomical and medical knowledge. Within Tibetan religious beliefs, thangkas are not merely visual representations; they are venerated as supports of Buddha (Tib. sku rten), understood as physical embodiments of divine presence. At the same time, the creation and veneration of thangka constitute a rich aesthetic tradition in which artists repeatedly integrate realist elements into this sacred canvas. <br>
This paper offers a micro anthropological examination (Tanaka 2005; 田中 2006) of the depiction of thangka as a practice oscillating between inscribing the canonical and drawing the real. Through critically engaging with the theory of agency of art (Gell 1998), and the analysis of writing and drawing (Ingold 2017), this study examines the dialectical relationship between rendering sacred images and depicting worldly reality, and how such practices unfold in the tension between prescriptive authority and embodied perception.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841812026Central Serous Chorioretinopathy in Parallel With Onset and Relapses of Minimal Change Nephrotic Syndrome: A 28-Year Case Follow-Upe102426ENToshihikoMatsuoDepartment of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology, and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityCentral serous chorioretinopathy is an idiopathic disease that manifests as one or several localized, small, dome-shaped serous retinal detachments on fundus examination. The pathophysiology involves fluid leakage from the choroidal capillaries, known as the choriocapillaris, into the subretinal space through sites of damage in the retinal pigment epithelium. This case report discusses the underlying causes of central serous chorioretinopathy-like findings in minimal change nephrotic syndrome.<br>
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The patient was a 33-year-old woman who developed nephrotic syndrome that was confirmed to be minimal change disease by renal biopsy. She experienced two major relapses of nephrotic syndrome at the ages of 36 and 41 years. She also had a minor relapse at the age of 37 years, five months after the first major relapse at the age of 36 years, as well as four additional minor relapses at the ages of 44, 46, 50, and 51 years. The onset of central serous chorioretinopathy-like manifestations, which were localized to the left eye, occurred three months after the initial onset of nephrotic syndrome at the age of 33 years. Two subsequent episodes of relapse of central serous chorioretinopathy-like manifestations were observed in both eyes at intervals of five months and one month, respectively, after major relapses of nephrotic syndrome at the ages of 36 and 41 years. Thereafter, she did not develop further central serous chorioretinopathy-like manifestations.<br>
<br>
She discontinued oral prednisolone at the age of 54 years and experienced no further relapses of nephrotic syndrome through her latest visit at the age of 61 years. She maintained normal renal function and good visual acuity in both eyes. The long-term, consistent temporal association between episodes of central serous chorioretinopathy and the onset and relapses of minimal change nephrotic syndrome is strongly supported by longitudinal clinical observations spanning 28 years. This parallel course suggests a possible shared pathophysiological mechanism or common triggering factors underlying both diseases.No potential conflict of interest relevant to this article was reported.Baishideng Publishing Group Inc.Acta Medica Okayama1948-519017122025Endoscopic features of oral and pharyngolaryngeal papillomas and their role in distinguishing squamous cell carcinoma110594ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalKentaHamadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshiyasuKonoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBACKGROUND<br>
Oral and pharyngolaryngeal papillomas are occasionally detected during esophagogastroduodenoscopy. However, their endoscopic features have not been sufficiently investigated.<br>
AIM<br>
To distinguish oral and pharyngolaryngeal papillomas from elevated squamous carcinomas, this study examined their endoscopic features.<br>
METHODS<br>
Forty-seven patients with oral or pharyngeal papilloma participated in this study. The endoscopic characteristics of papillomas were identified by focusing on narrowband and blue laser imaging representations.<br>
RESULTS<br>
Papillomas were classified into three patterns based on their endoscopic features: Salmon roe-like polyps, polyps without capillary transparency, and pinecone-like polyps, with salmon roe-like polyps most prevalent (48.9%). We subsequently analyzed features differentiating papillomas and squamous cell carcinomas in the same region and found that squamous cell carcinomas exhibited at least one of the following three features: Uneven or absent lobulated structure, irregular morphology of capillaries, and coexistence of flat lesions. In contrast, papillomas displayed a uniform lobulated structure, homogeneous or non-visible capillaries, and an absence of flat components. When any of these characteristics were present, two endoscopic specialists evaluated the lesions for the diagnosis of squamous cell carcinoma, with sensitivities of 100% and 97.6% and specificities of 68.9% and 93.3%.<br>
CONCLUSION<br>
Understanding distinct endoscopic patterns of oropharyngeal papillomas and squamous cell carcinomas provides valuable guidance to endoscopists performing esophagogastroduodenoscopy.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama2328-89571312025Impact of Candida Care Bundle Compliance on the Prognosis of Patients With Candidemia: A Multicenter Retrospective Cohort Study With Propensity Score Matching Analysis (2016–2023)ofaf790ENHidemasaAkazawaDepartment of Infectious Diseases, Okayama University HospitalShinnosukeFukushimaDepartment of Infectious Diseases, Okayama University HospitalToshieHiguchiDepartment of General Internal Medicine, Okayama Red Cross HospitalTomokoMiyoshiCenter for Medical Education and Internationalization, Kyoto University Graduate School of MedicineYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalYukinobuAkamatsuDepartment of General Medicine, Tottori Municipal HospitalYutoHarukiDepartment of Pharmacy, Tsuyama Chuo HospitalYoshitakaIwamotoDepartment of General Medicine, NHO Okayama Medical CenterShuichiTanakaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunFujisatoDepartment of Pharmacy, Okayama Rousai HospitalSoichiroAkoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalBackground. Candidemia is a life-threatening infection with high mortality, and appropriate management is essential to improve patient outcomes. The Candida Care Bundle aims to standardize hospital management for patients with candidemia and reduce mortality.<br>
Methods. This retrospective multicenter cohort study included candidemia cases from 9 hospitals in Japan between 2016 and 2023. Compliance to the Candida Care Bundle was evaluated based on 5 elements: central venous catheter removal within 24 hours, appropriate antifungal therapy, ophthalmologic examination, follow-up blood cultures, and antifungal treatment for ≥2 weeks after clearance. Patients were categorized into high (4–5 items) and low (0–3 items) compliance groups. The primary and secondary outcomes were defined as 30-day survival and the development of endophthalmitis, with propensity score matching used to adjust for potential confounders.<br>
Results. Among 230 patients, 160 (69.5%) were classified into the high compliance group, which exhibited significantly lower 30-day mortality than the low compliance group (8.8% vs 57.1%, P < .01). Even after matching, the high compliance group remained independently associated with improved survival (hazard ratio [HR]: 0.15; 95% confidence interval [CI]: .08–.30). C. albicans (HR: 1.95; 95% CI: 1.01–3.52) and central line-associated bloodstream infection (HR: 2.63; 95% CI: 1.35–5.12) were associated with the fatal outcome. Endophthalmitis involved 23.6% of the patients, being associated with C. albicans (odds ratio [OR]: 8.18; 4.46–19.30) and central line-associated bloodstream infection (OR: 2.69; 1.08–6.70).<br>
Conclusions. Strict compliance to the Candida Care Bundle significantly improves survival, underscoring its importance in candidemia management.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322025Atezolizumab + Chemotherapy for Advanced Non-Small Cell Lung Cancer in Japanese Clinical Practice (J-TAIL-2)ENHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical UniversityMakotoNishioDepartment of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalAtsushiOsoegawaDepartment of Thoracic and Breast Surgery, Oita University Faculty of MedicineEikiKikuchiDepartment of Respiratory Medicine, Faculty of Medicine, Hokkaido UniversityHideharuKimuraDepartment of Respiratory Medicine, Kanazawa University HospitalYasushiGotoDepartment of Thoracic Oncology, National Cancer Center HospitalJunichiShimizuDepartment of Thoracic Oncology, Aichi Cancer Center HospitalEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalIchiroYoshinoInternational University of Health and Welfare, Narita HospitalToshihiroMisumiDepartment of Data Science, National Cancer Center Hospital EastYasutakaWatanabeDepartment of Thoracic Oncology, Saitama Cancer CenterAkitoHataDivision of Thoracic Oncology, Kobe Minimally Invasive Cancer CenterAkiraKisoharaDepartment of Respiratory Medicine, Kasukabe Medical CenterShoichiKuyamaDepartment of Respiratory Medicine, NHO Iwakuni Clinical CenterMasafumiYamaguchiDepartment of Thoracic Oncology, NHO Kyushu Cancer CenterAsakoMiwaChugai Pharmaceutical Co., Ltd.ShunichiroIwasawaChugai Pharmaceutical Co., Ltd.MisaTanakaChugai Pharmaceutical Co., Ltd.AkihikoGemmaNippon Medical SchoolFirst-line atezolizumab combination therapies were approved for the treatment of metastatic non-small cell lung cancer (NSCLC) based on results from the global phase 3 trials IMpower130, IMpower132, and IMpower150. These trials reported 12-month overall survival (OS) rates of 60%–67% with atezolizumab combination therapy. J-TAIL-2 (NCT04501497), a prospective, multicenter, observational study, evaluated atezolizumab combination therapy in routine clinical practice in Japan. Patients ≥ 20 years old with NSCLC received atezolizumab plus carboplatin and nab-paclitaxel (atezo + CnP), atezolizumab plus carboplatin or cisplatin plus pemetrexed (atezo + PP), or atezolizumab plus bevacizumab plus carboplatin and paclitaxel (atezo + bev + CP) in clinical practice. The primary endpoint was the 12-month OS rate. Secondary endpoints included OS, progression-free survival, and subgroup analyses, including IMpower-unlike (did not meet the main eligibility criteria of each IMpower trial) and IMpower-like patients. In total, 814 patients were enrolled (atezo + CnP, n = 217; atezo + PP, n = 211; atezo + bev + CP, n = 386). The IMpower-unlike group included patients with Eastern Cooperative Oncology Group performance status ≥ 2, autoimmune disease, or interstitial lung disease. Twelve-month OS rates (95% confidence interval [CI]) were 62.9% (55.8–69.2), 72.1% (65.2–77.9), and 68.3% (63.2–72.9) with atezo + CnP, atezo + PP, and atezo + bev + CP, respectively. OS hazard ratios (95% CI) in the IMpower-unlike vs. -like subgroups were 1.36 (0.91–2.05), 1.08 (0.70–1.68), and 1.49 (1.09–2.06), respectively. No new safety signals were observed. Real-world efficacy and safety for each atezolizumab combination were comparable to those in the relevant IMpower trials.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0301-486X19062025Prognostic Value of Serum (1→3)-β-D-Glucan Levels in Patients with Candidemia Stratified by Compliance with Candida Bundle: A Multicenter Retrospective Cohort Study (2016–2023)90ENHidemasaAkazawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinnosukeFukushimaDepartment of Infectious Diseases, Okayama University HospitalToshieHiguchiDepartment of General Internal Medicine, Okayama Red Cross HospitalTomokoMiyoshiCenter for Medical Education and Internationalization, Kyoto University Graduate School of MedicineYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalYukinobuAkamatsuDepartment of General Medicine, Tottori Municipal HospitalYutoHarukiDepartment of Pharmacy, Tsuyama Chuo HospitalYoshitakaIwamotoDepartment of General Medicine, NHO Okayama Medical CenterShuichiTanakaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunFujisatoDepartment of Pharmacy, Okayama Rousai HospitalSoichiroAkoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalBackground Candidemia is a severe systemic infection with a high mortality risk. While β-D-glucan (BDG) serves as a diagnostic biomarker, its prognostic value in candidemia, particularly in association with Candida bundle compliance, remains unclear.<br>
Methods In this retrospective multicenter cohort study, we evaluated 96 patients with candidemia across nine Japanese hospitals between 2016 and 2023. Candida bundle compliance was assessed using five key components: central venous catheter removal within 24 h of diagnosis, appropriate initial antifungal therapy, ophthalmologic examination, follow-up blood cultures until clearance, and antifungal therapy for at least two weeks post-clearance. Analyses stratified patients by serum BDG status (positive/negative) and compliance with the Candida bundle (high: 4–5 points; low: 0–3 points). The primary outcome was 30-day mortality, and the secondary outcome was defined as endophthalmitis incidence.<br>
Results Of 96 eligible patients with candidemia, 70 (72.9%) were BDG-positive and 26 (27.1%) were BDG-negative. The overall 30-day mortality was 17.7%. Among BDG-positive patients, 15 (21.4%) died, while 2 (7.7%) died in BDG-negative cohorts (p = 0.09). Serum BDG positivity demonstrated a statistically significant association with decreased survival rates in the low bundle adherence group (p = 0.02), whereas this correlation was not observed among patients in the high-compliance cohort (p = 0.66). Endophthalmitis occurred in 25.0% of patients, without significant correlation to serum BDG status. C. albicans was associated with a significantly higher incidence of endophthalmitis compared with non-albicans species (45.7% vs. 8.9%).<br>
Conclusions Serum BDG positivity potentially correlates with worse survival in candidemia, particularly in patients with low bundle compliance. This emphasizes the importance of adherence to standardized Candida management protocols for optimizing patient outcomes.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2772-5723522026Feasibility and Diagnostic Utility of Mucosal T-Cell Flow Cytometry for Intestinal Graft-Versus-Host Disease100820ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakumiKondoDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobuharuFujiiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMaiHiramatsuDivision of Medical Support, Okayama University HospitalArakiHirabataDivision of Medical Support, Okayama University HospitalTakahideTakahashiDivision of Medical Support, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground and Aims: Timely diagnosis of intestinal complications after hematopoietic stem cell transplantation (HSCT), including graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy, and cytomegalovirus infection, is essential for appropriate management. This study evaluated whether mucosal T-cell profiling from endoscopic biopsies could support the diagnosis of these post-transplant conditions.<br>
Methods: We prospectively analyzed 58 intestinal biopsy specimens from 21 post-HSCT patients. Paired samples were obtained from the stomach and duodenum during upper endoscopy and from the ileum and large intestine during colonoscopy. Lymphocytes were isolated from each specimen and analyzed using flow cytometry. These data were integrated with those of a previously collected cohort (35 patients, 51 samples) for comparative immunophenotypic analysis across histologically defined groups.<br>
Results: Duodenal biopsies yielded more lymphocytes than did gastric biopsies (mean ± standard deviation: 532 ± 823 vs 233 ± 392 cells; P = .070), with comparable yields between the ileum and colon. Among 41 evaluable cases, the CD56+:CD3+ ratio was significantly lower in patients with GVHD (5.5 ± 2.2%) than in those with nonspecific or no inflammation (28.4 ± 16.3%; P = .006). A cutoff value of <11% provided 85.7% sensitivity and 83.3% specificity for diagnosing GVHD (area under the curve = 0.91).<br>
Conclusion: Mucosal T-cell profiling using endoscopic biopsies is feasible and may aid in the diagnosis of GVHD after HSCT. A decreased CD56+:CD3+ ratio is a promising marker for distinguishing GVHD from other post-transplant intestinal conditions.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813732025令和６年度岡山医学会賞 胸部・循環研究奨励賞（砂田賞）9597ENShinichiKawanaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.Japanese Society of BreedingActa Medica Okayama1344-76107532025Polyphyletic domestication and inter-lineage hybridization magnified genetic diversity of cultivated melon, Cucumis melo L.168178ENKatsunoriTanakaFaculty of Agriculture and Life Science, Hirosaki UniversityGentaroShigitaGraduate School of Environmental and Life Science, Okayama UniversityTran PhuongDungGraduate School of Environmental and Life Science, Okayama UniversityPhan Thi PhuongNhiUniversity of Agriculture and Forestry, Hue UniversityMamiTakahashiGraduate School of Environmental and Life Science, Okayama UniversityYukiMondenGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidetakaNishidaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRyujiIshikawaFaculty of Agriculture and Life Science, Hirosaki UniversityKenjiKatoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMelon accessions with diverse geographical origins were classified into large and small seed-types by length of seed at the boundary of 9 mm, and into five populations based on polymorphisms in the nuclear genome. They were further divided into three maternal lineages, Ia, Ib, and Ic, by polymorphisms in the chloroplast genome. By combining these three classifications, the Europe/US subsp. melo and the East Asian subsp. agrestis were characterized as [large seed, Ib, PopA1 or A2] and [small seed, Ia, PopB1 or B2], respectively, indicating nearly perfect divergence. In South Asia, in addition to the Europe/US and East Asian types, recombinant types between the two types were detected and accounted for 34.8% of South Asian melon. The finding of such an intermixed structure of genetic variation supported the Indian origin of Ia and Ib types. As to Momordica popular in South Asia, seed length was intermediate between the large and small seed-types, and chloroplast type was a mixture of Ia and Ib, suggesting its origin from the recombinant type. In Africa, three lineages of melon were distributed allopatrically and showed distinct divergence. Subsp. agrestis of the Ic type proved to be endemic to Africa, indicating its African origin.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322025Genomic Profiling of Pediatric Solid Tumors With a Dual DNA/RNA Panel: JCCG-TOP2 StudyENKayokoTaoDepartment of Pediatrics, National Cancer Center HospitalTakakoYoshiokaDepartment of Pathology, National Center for Child Health and DevelopmentMihoKatoDepartment of Childhood Cancer Data Management, National Center for Child Health and DevelopmentKazuyukiKomatsuDepartment of Pediatrics, Hamamatsu University School of MedicineShinichiTsujimotoDepartment of Pediatrics, Yokohama City UniversityKenichiSakamotoDepartment of Pediatrics, Shinshu University School of MedicineKazukiTanimuraDepartment of Pediatrics, National Cancer Center HospitalMinakoSugiyamaDepartment of Pediatrics, National Cancer Center HospitalMasahiroSekiguchiDepartment of Pediatrics, The University of TokyoYoshikoNakanoDepartment of Pediatrics, The University of TokyoYoshihiroOtaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasushiYatabeDepartment of Diagnostic Pathology, National Cancer Center HospitalAkihikoYoshidaDepartment of Diagnostic Pathology, National Cancer Center HospitalHajimeOkitaDepartment of Pathology, Keio University School of MedicineJunkoHiratoDepartment of Pathology, Public Tomioka General HospitalKenichiKohashiDepartment of Pathology, Graduate School of Medicine, Osaka Metropolitan UniversityYukichiTanakaDepartment of Pathology, Kanagawa Children's Medical CenterShinjiKohsakaDivision of Cellular Signaling, National Cancer Center Research InstituteTakashiKuboDepartment of Clinical Genomics, National Cancer Center Research InstituteKunikoSunamiDepartment of Laboratory Medicine, National Cancer Center HospitalMakotoHirataDepartment of Genetic Medicine and Services, National Cancer Center HospitalShuichiTsutsumiGenome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of TokyoHiroyukiAburataniGenome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of TokyoKatsuyoshiKohDepartment of Hematology and Oncology, Saitama Children's Medical CenterMasahiroHirayamaDepartment of Pediatrics, Mie University Graduate School of MedicineShuheiKarakawaDepartment of Pediatrics, Hiroshima University HospitalYukayoTerashitaDepartment of Pediatrics, Hokkaido University HospitalHiroyukiFujisakiDepartment of Pediatric Hematology and Oncology, Osaka City General HospitalTakeshiYagiOkinawa Prefectural Nanbu Medical Center & Children's Medical CenterAkihiroYonedaDepartment of Pediatric Surgery, National Center for Child Health and DevelopmentShinjiMochizukiDepartment of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health SecurityHiroyukiShichinoDepartment of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health SecurityTatsuyaSuzukiDepartment of Hematology, National Cancer Center HospitalTetsuyaTakimotoDepartment of Childhood Cancer Data Management, National Center for Child Health and DevelopmentKoichiIchimuraDepartment of Pathology, Kyorin University Faculty of MedicineChitoseOgawaDepartment of Pediatrics, National Cancer Center HospitalKimikazuMatsumotoChildren's Cancer Center National Center for Child Health and DevelopmentHitoshiIchikawaDepartment of Clinical Genomics, National Cancer Center Research InstituteMotohiroKatoDepartment of Pediatrics, The University of TokyoTo develop an optimized genomic medicine platform for pediatric cancers, a nationwide cancer genome profiling project was conducted from January 2022 to February 2023 in collaboration with the Japan Children's Cancer Group. This prospective observational study analyzed matched blood and FFPE tumor samples from patients aged 0–29 years with solid tumors. Genomic analysis used the TOP2 hybrid capture–enrichment system, targeting 737 and 455 genes in the DNA and RNA panels, along with allele-specific genome copy number alterations. A total of 210 patients from 50 institutions were enrolled across Japan (median age, 8 years; range, 0–25). Of these, 154 (77%) were enrolled at diagnosis or during/after initial treatment and 56 (27%) at disease progression or relapse. The TOP2 findings had great benefits in clarifying the diagnosis of pediatric solid tumors. Among the 204 patients with genomic results, 147 (72%) had potentially actionable findings, including diagnostic, prognostic, and therapeutic findings in 111 (54%), 61 (30%), and 64 (31%), respectively. Oncogenic fusions were noted in 45 (23%) patients. A copy number alteration was identified in at least one genomic region in 170 (83%) patients. Two patients exhibited a high tumor mutation burden. Seventeen (8%) patients harbored a germline pathogenic/likely pathogenic variant in cancer-predisposing genes. This study highlighted the feasibility of implementing a nationwide precision medicine platform and the clinical utility of the TOP2 system for pediatric cancers. The results support the integration of genomic data into the standard clinical care of pediatric patients with cancer, both at diagnosis and at relapse.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2399-3642812025A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS1720ENRyoichiNakamuraDepartment of Neurology, Aichi Medical University School of MedicineGenkiTohnaiDivision of ALS Research, Aichi Medical University School of MedicineNaokiAtsutaDepartment of Neurology, Aichi Medical University School of MedicineYumiMatsudaPublic Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of MedicineSatoruMorimotoKeio University Regenerative Medicine Research Center, KawasakiDaisukeItoDepartment of Neurology, Nagoya University Graduate School of MedicineMasahisaKatsunoDepartment of Neurology, Nagoya University Graduate School of MedicineYuishinIzumiDepartment of Neurology, Tokushima University Graduate School of Biomedical SciencesMitsuyaMoritaDivision of Neurology, Department of Internal Medicine, Jichi Medical UniversityIkukoIwataDepartment of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityIchiroYabeDepartment of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityTomokoNakazatoDepartment of Neurology, Juntendo University School of MedicineNobutakaHattoriDepartment of Neurology, Juntendo University School of MedicineTakehisaHirayamaDepartment of Neurology, Toho University Faculty of MedicineOsamuKanoDepartment of Neurology, Toho University Faculty of MedicineAsakoTamuraDepartment of Neurology, Mie University Graduate School of MedicineNaokiSuzukiDepartment of Neurology, Tohoku University Graduate School of MedicineMasashiAokiDepartment of Neurology, Tohoku University Graduate School of MedicineKazumotoShibuyaDepartment of Neurology, Graduate School of Medicine, Chiba UniversitySatoshiKuwabaraDepartment of Neurology, Graduate School of Medicine, Chiba UniversityMasayaOdaDepartment of Neurology, Vihara Hananosato HospitalRinaHashimotoDepartment of Neurology, NHO Higashinagoya National HospitalIkukoAibaDepartment of Neurology, NHO Higashinagoya National HospitalTomohikoIshiharaDepartment of Neurology, Brain Research Institute, Niigata UniversityOsamuOnoderaDepartment of Neurology, Brain Research Institute, Niigata UniversityToruYamashitaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiIshiuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKotaBokudaDepartment of Neurology, Tokyo Metropolitan Neurological HospitalToshioShimizuDepartment of Neurology, Tokyo Metropolitan Neurological HospitalYoshioIkedaDepartment of Neurology, Gunma University Graduate School of MedicineKazukoHasegawaDivision of Neurology, NHO Sagamihara National HospitalFumiakiTanakaDepartment of Neurology and Stroke Medicine, Yokohama City University Graduate School of MedicineTakanoriYokotaDepartment of Neurology and Neurological Science, NucleoTIDE and PepTIDE Drug Discovery Center (TIDE), Institute of Science TokyoKazuakiKanaiDepartment of Neurology, Fukushima Medical University School of MedicineYu-ichiNotoDepartment of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineRyujiKajiDepartment of Neurology, Tokushima University Graduate School of Biomedical SciencesHirohisaWatanabeDepartment of Neurology, Fujita Health UniversityTomokoKonishiDivision of ALS Research, Aichi Medical University School of MedicineMikikoHasegawaDivision of ALS Research, Aichi Medical University School of MedicineHozukiFukayaDivision of ALS Research, Aichi Medical University School of MedicineJun-ichiNiwaDepartment of Neurology, Aichi Medical University School of MedicineManabuDoyuDepartment of Neurology, Aichi Medical University School of MedicineYoheiOkadaDepartment of Neurology, Aichi Medical University School of MedicineShihoNakamuraKeio University Regenerative Medicine Research Center, KawasakiFumikoOzawaKeio University Regenerative Medicine Research Center, KawasakiHideyukiOkanoKeio University Regenerative Medicine Research Center, KawasakiMasahiroNakatochiPublic Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of MedicineGenSobueDivision of ALS Research, Aichi Medical University School of MedicineAmyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10-8); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10−9). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p = 0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2772-3755112025Robustness of the RGB image-based estimation for rice above-ground biomass by utilizing the dataset collected across multiple locations100998ENKotaNakajimaGraduate School of Agriculture, Kyoto UniversityKazukiSaitoInternational Rice Research Institute (IRRI)YasuhiroTsujimotoJapan International Research Center for Agricultural SciencesToshiyukiTakaiJapan International Research Center for Agricultural SciencesAtsushiMochizukiCHIBA Prefectural Agriculture and Forestry Research CenterTomoakiYamaguchiFaculty of Applied Biological Sciences, Gifu UniversityAliIbrahim Africa Rice Center (AfricaRice), Regional Station for the SahelSalifou GoubeMairouaAfrica Rice Center (AfricaRice)Bruce HajaAndrianaryLaboratoire des Radioisotopes, Université d′AntananarivoKeisukeKatsuraGraduate School of Agriculture, Kyoto UniversityYuTanakaGraduate School of Environment, Life, Natural Science and Technology, Okayama UniversityAbove-ground biomass (AGB) is a critical phenotype representing crop growth. Non-invasive evaluations of AGB, including deep-learning-based red-green-blue (RGB) image analyses, are often specific to the training data. The robustness of the estimation model across untrained conditions is essential to monitor crop productivity globally, but it has yet to be fully assessed. This study aims to assess the robustness of a convolutional neural network (CNN) model for rice AGB estimation across five locations in three countries, and to demonstrate the feasibility of robust model via a practical approach. From transplanting to heading, 1957 RGB images were captured vertically downward over the rice canopy, covering approximately 1 m2. First, a base model was established using data collected from a single location. Then, its robustness was assessed using test datasets taken from the other four locations. The CNN model showed a significant variation in estimation accuracy across the untrained four locations, indicating insufficient robustness of the base model. Subsequently, we quantitatively tested the impact of improving training data diversity on model robustness by adding data from each of the four locations to the base model's training data. Adding at most 48 data points from a location achieved practical accuracy for the added location, with R2Ad above 0.8. Interestingly, adding data from one location sometimes improved the accuracy for other untrained locations as well. These findings suggest that collecting diverse training data for RGB-based estimation, combined with evaluation of robustness paves the way for on-site and instant AGB monitoring of rice.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7962025Ileus Tube-Related Intussusception: A Case Report and Review of 80 Previously Reported Cases469474ENTeruyukiTsujiiDepartment of Surgery, Matsuda HospitalTatsuoMatsudaDepartment of Surgery, Matsuda HospitalYujiKimuraDepartment of Surgery, Matsuda HospitalRyoichiKatsubeDepartment of Surgery, Matsuda HospitalHironoriIwadouDepartment of Surgery, Matsuda HospitalSadamiFunabikiDepartment of Surgery, Matsuda HospitalYasuakiKamikawaDepartment of Surgery, Matsuda HospitalTadakazuMatsudaDepartment of Surgery, Matsuda HospitalCase Report10.18926/AMO/69851We report a rare case of ileus tube-related intussusception in an adult. A 56-year-old man with adhesive bowel obstruction was treated with a nasointestinal ileus tube. Although his condition initially improved, persistent abdominal pain led to the diagnosis of intussusception via CT imaging. Manual repositioning of the tube resolved the intussusception without the need for bowel resection. A review of 80 previously reported cases of ileus tube-associated intussusception (total 81 cases, 95 lesions) highlighted the timing of onset, treatment strategies, and precautions. Early detection and diagnosis are crucial to prevent severe complications and preserve bowel function.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7962025Exacerbation of Proteinuria in a Patient with Behçet’s Disease and IgA Nephropathy Following Colchicine Discontinuation457461ENTomohikoAsakawaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYuKatayamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYoshimasaSakurabuDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKatsuyoshiKatayamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRyokoUmebayashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRikaTakemotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/69849This case involves a 23-year-old male who was diagnosed with Behçet’s disease 5 years ago and managed with colchicine. Two months ago, he underwent renal biopsy due to abnormal urinalysis and kidney dysfunction, leading to a diagnosis of IgA nephropathy. He subsequently underwent tonsillectomy followed by glucocorticoid pulse therapy. However, after the tonsillectomy, discontinuing colchicine led to increased proteinuria, despite the glucocorticoid pulse therapy. Upon reintroducing colchicine, urinary protein excretion decreased, achieving incomplete remission. These findings suggest that colchicine may be effective in decreasing proteinuria in patients with Behçet’s disease complicated by IgA nephropathy.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7962025Effects of Thoron Inhalation and Cyclosporin A Treatment on Dextran Sulfate Sodium-Induced Oxidative Damage in Mice421429ENAyumiTanakaGraduate School of Health Sciences, Okayama UniversityShotaNaoeGraduate School of Health Sciences, Okayama UniversityReijuTakenakaGraduate School of Health Sciences, Okayama UniversityNorieKanzakiNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyAkihiroSakodaNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyKiyonoriYamaokaFaculty of Health Sciences, Okayama UniversityTakahiroKataokaFaculty of Health Sciences, Okayama UniversityOriginal Article10.18926/AMO/69844Radon (222Rn; Rn) and thoron (220Rn; Tn) inhalation have been reported to enhance antioxidant activity in various organs. However, the effects of Tn on the colon have not been investigated. This study aimed to clarify the effects of Tn inhalation, alone and in combination with cyclosporin A (CsA), on dextran sulfate sodium (DSS)-induced colitis, and the accompanying oxidative stress, in mice. Male BALB/c mice were subjected to continuous 8-day Tn inhalation (c-Tn, 533±128 Bq/m3) or alternate-day Tn inhalation over the same period (f-Tn, 577±63Bq/m3), followed by treatment with 3% DSS and either CsA or vehicle for 7 days. Although the disease activity index (DAI) decreased significantly by day 2 in the c-Tn group, scores remained significantly higher than those in the f-Tn group. In the c-Tn group, superoxide dismutase and catalase activity in the colon were significantly elevated compared with those in sham controls. Thus, DSS-induced damage was effectively inhibited in the earlier stages by the c-Tn mode of inhalation than by the f-Tn mode. These findings suggest that continuous Tn inhalation more effectively attenuated early colitis symptoms than alternate-day inhalation, potentially through upregulation of antioxidant defenses. Tn and CsA showed no combined effects.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama2155-543515142025Mesoporous Oxyhalide Aggregates Exhibiting Improved Photocatalytic Activity for Visible-Light H2 Evolution and CO2 Reduction1255112562ENHirotoUekiDepartment of Chemistry, School of Science, Institute of Science TokyoToshiyaTanakaDepartment of Chemistry, School of Science, Institute of Science TokyoShujiAnabukiGraduate School of Natural Science and Technology, Okayama UniversityRyuichiNakadaDepartment of Chemistry, School of Science, Institute of Science TokyoMegumiOkazakiDepartment of Chemistry, School of Science, Institute of Science TokyoKentaAiharaDepartment of Chemistry, School of Science, Institute of Science TokyoMasashiHattoriMaterials and Structures Laboratory, Institute of Integrated Research, Institute of Science TokyoFumitakaIshiwariDepartment of Applied Chemistry, Graduate School of Engineering, Osaka UniversityRieHarukiInstitute of Materials Structure Science, High Energy Accelerator Research OrganizationShunsukeNozawaInstitute of Materials Structure Science, High Energy Accelerator Research OrganizationToshiyukiYokoiNanospace Catalysis Unit, Institute of Integrated Research, Institute of Science TokyoMichikazuHaraMaterials and Structures Laboratory, Institute of Integrated Research, Institute of Science TokyoOsamuIshitaniDepartment of Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima UniversityAkinoriSaekiDepartment of Applied Chemistry, Graduate School of Engineering, Osaka UniversityAkiraYamakataGraduate School of Natural Science and Technology, Okayama UniversityKazuhikoMaedaDepartment of Chemistry, School of Science, Institute of Science TokyoOxyhalides are promising visible-light photocatalysts for water splitting and CO2 conversion; however, those exhibiting high activity for these reactions have rarely been reported. Here, we show that using water-soluble Ti complexes as precursors in the microwave-assisted hydrothermal synthesis of the oxyhalide photocatalyst Pb2Ti2O5.4F1.2 (PTOF) resulted in the production of nanoparticulate PTOF. The primary particle size of the synthesized PTOF ranged from several tens of nanometers to several hundreds of nanometers. Using Ti-citric acid or Ti-tartaric acid complexes as precursors, the PTOF was formed as mesoporous aggregates, compared with a bulky analogue (0.5–1 μm) prepared using a TiCl4 precursor. The PTOF prepared from Ti-citric acid complex had a particle size of 50–100 nm and showed a one-order-of-magnitude greater activity for H2 evolution from an aqueous ethylenediaminetetraacetic acid solution with the aid of a Rh cocatalyst. An apparent quantum yield (AQY) of 15.4 ± 1.0% at 420 nm, which is the highest among the reported oxyhalide photocatalysts, was achieved under optimal conditions. Although excess particle size reduction of PTOF lowered the H2 evolution activity, the PTOF with the smallest possible primary particle size of 15–30 nm, prepared from Ti-tartaric acid complex, showed the highest activity toward the selective reduction of CO2 into formate in a nonaqueous environment when combined with a binuclear Ru(II) complex. The CO2 reduction AQY was 10.4 ± 1.8% at 420 nm, a record-high value among metal-complex/semiconductor binary hybrid photocatalysts. This study highlights the importance of morphological control of oxyhalides for realizing their full potential as photocatalysts for artificial photosynthesis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2399-3642812025Single-cell and spatial transcriptomic characterization of pulmonary pleomorphic carcinoma1773ENAtsushiMatsuokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShutaTomidaMasayoshiOhkiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaHisamatsuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaFujiwaraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiIshimuraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyunosukeFujiiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoakiHigashiharaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaohiroHayashiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOkadaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoYoshichikaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumiakiMukoharaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaoYoshikawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumaFukumotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuakiTomiokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeOtaniDepartment of Pathology, Beth Israel Deaconess Medical CenterAtsushiTanakaDepartment of Pathology, Beth Israel Deaconess Medical CenterHirofumiInoueCenter for Comprehensive Genomic Medicine, Okayama University HospitalYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidetakaYamamotoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPulmonary pleomorphic carcinoma (PPC) is a rare subtype of lung cancer that comprises both epithelial and sarcomatoid components. The molecular basis of PPC, including the cellular dynamics of its components, remains largely unknown. To elucidate potential therapeutic targets for PPC, we perform a multi-omics analysis incorporating digital spatial profiling and single-cell RNA sequencing (scRNA-seq). PPC exhibits diverse driver gene alterations, including MET exon 14 skipping mutation (METex14) and ALK fusion. In spatial transcriptomics, MET gene and protein are overexpressed exclusively within the epithelial component and not in the sarcomatoid component, even in patients harboring METex14. Epithelial-mesenchymal transition (EMT)-related transcriptional changes, along with extracellular matrix (ECM) remodeling between the epithelial and sarcomatoid components, are observed. scRNA-seq identifies cell populations within the epithelial component that contribute to the malignant transformation and differentiation of the sarcomatoid component. They are characterized by an intermediate EMT state with ECM remodeling signature, suggesting their potential as novel therapeutic targets for PPC.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama2771-93162025Photochemical Macrolactonization of Hydroxyaldehydes via C–H BrominationENSakuraKodakiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHaruAndoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroyoshiTakamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityIsaoKadotaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentaTanakaResearch Institute for Interdisciplinary Science, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291864232025Remarkable Efficacy of Capmatinib in a Patient with Cancer of Unknown Primary with MET Amplification34603464ENTakaakiTanakaDepartment of Respiratory Medicine, Okayama University HospitalGoMakimotoDepartment of Respiratory Medicine, Okayama University HospitalRyoheiSumiiDepartment of General Internal Medicine, NHO Fukuyama Medical CenterRikaOmoteDepartment of Pathology, NHO Fukuyama Medical CenterYayoiAndoClinical Research Support Office, National Cancer Center HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasahiroTabataCenter for Clinical Oncology, Okayama University HospitalThis case report describes a 70-year-old female with cancer of unknown primary origin (CUP) who exhibited multiple distant lymph node metastases. Despite conventional chemotherapy (carboplatin and paclitaxel) and immunotherapy (nivolumab), disease progression was noted. Genomic profiling revealed MET amplification, leading to the administration of capmatinib, a selective MET tyrosine kinase inhibitor. The patient experienced substantial tumor reduction with dose adjustments due to adverse effects, indicating the potential efficacy of capmatinib in treating CUP with MET amplification.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Long intervals between repetitive concussions reduce risk of cognitive impairment and limit microglial activation, astrogliosis, and tauopathy in adolescent rats40522ENYuichiHirataDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalKyoheiKinDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalTakayukiNagaseDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalTatsuyaSasakiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalSusumuSasadaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalChiakiSugaharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalTakahiroHirayamaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University HospitalKojiKawaiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalShunTanimotoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalHayatoMiyakeDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalTomoyaSaijoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University HospitalKaoriMasaiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoYasuharaYasuhara ClinicShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalAlthough previous studies have demonstrated the effects of concussions do not accumulate as the time interval between injuries increases, little is known about the relationship between this interval and the effects of repetitive concussions. The objective of this study is to explore the relationship between the time interval and changes in behavior and histology following repetitive concussions. Male adolescent rats received concussions by weight drop and were randomly assigned to one of five experimental groups, receiving concussions three times either daily, every other day, once per week, once every 2 weeks, or receiving sham procedures. Only rats that received daily concussions exhibited cognitive impairment, while the other groups did not. No groups showed motor or anxiety-like impairments. Histological analysis revealed accumulation of microglia, as well as astrogliosis, in the prefrontal cortex, corpus callosum, dentate gyrus, and cornu Ammonis 1 region of the hippocampus in rats subjected to daily concussions. Accumulation of phosphorylated tau was also observed in the prefrontal cortex and cornu Ammonis 1. Longer intervals between concussions may reduce the risk of cognitive impairment and limit microglial activation, astrogliosis, and phosphorylated tau accumulation. These findings may help guide decisions on the appropriate timing for return to play in humans.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1433-73982025A rare case of supratentorial ependymosarcoma harboring ZFTA::RELA fusionENYujiMatsumotoDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasukiSurugaDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKaishiSatomiDepartment of Pathology, Faculty of Medicine, Kyorin UniversityYoheiInoueDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasuhikoHattoriDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineJojiIshidaDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKazuhikoKurozumiDepartment of Neurosurgery, Hamamatsu University HospitalSumihitoNobusawaDepartment of Human Pathology, Gunma University School of MedicineJunkoHiratoDepartment of Pathology, Public Tomioka General HospitalTakehiroTanakaDepartment of Pathology, Okayama University HospitalHiroyukiYanaiDepartment of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKanaWashioDepartment of Pediatrics, Okayama University HospitalKoichiIchimuraDepartment of Pathology, Faculty of Medicine, Kyorin UniversityTomotsuguIchikawaDepartment of Neurosurgery, Kagawa Prefectural Central HospitalYoshihiroOtaniDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShotaTanakaDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineEpendymosarcoma is an exceedingly rare variant of ependymoma characterized by a mixture of ependymomatous and sarcomatous components. We report a case of supratentorial ependymosarcoma harboring a ZFTA::RELA fusion in a 10-year-old girl. Histologically, the tumor comprised an ependymomatous component resembling clear cell ependymoma and a sarcomatous component. ZFTA::RELA fusion was confirmed in both components. Genome-wide methylation profiling classified both components as supratentorial ependymoma, ZFTA fusion–positive by the German Cancer Research Center (DKFZ) CNS tumor classifier v12b8. However, their copy number alteration profiles were distinct. The ependymomatous component exhibited a gain of chromosome 1q and a loss of chromosomes 1p, 9, and 19q, while the sarcomatous component showed a loss of chromosome 14. These findings suggest that both components may have differentiated from a common precursor despite their distinct morphologies. The patient underwent gross total resection followed by adjuvant chemoradiotherapy and remains recurrence-free eight years post-treatment. Further investigation of additional cases is warranted to better understand the pathogenesis of this rare tumor.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025Coherence Generation in Atomic Cesium for Cosmic Dark Matter DetectionENJINGWANGGraduate School of Natural Science and Technology, Okayama universityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025High Prevalence of MYD88 and CD79B Mutations in Primary Sinonasal Diffuse Large B-Cell Lymphoma: Identification of an MCD-like SubtypeENFANGLIPENGGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitisENYukiAOYAMAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025Repeated non-hemorrhagic and non-contusional mild traumatic brain injury in rats elicits behavioral impairment with microglial activation, astrogliosis, and tauopathy: Reproducible and quantitative model of chronic traumatic encephalopathyENChiakiSUGAHARAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025Avoidant/restrictive food intake disorder prognosis and its relation with autism spectrum disorder in Japanese childrenENChieTANAKAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1465-36215542025Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review313326ENYutaKubotaDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityMasanoriKawanoDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityTatsuyaIwasakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityIchiroItonagaDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityNobuhiroKakuDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityToshifumiOzakiDepartment of Orthopaedic Surgery , Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroTanakaDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityIn recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients5762ENYoshiyasuTonguTohoku University School of MedicineTomokoKasaharaDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineYasutoshiAkiyamaLaboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical SciencesTakehiroSuzukiDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineHsin-JungHoDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineYotaroMatsumotoLaboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical SciencesRyotaKujiraiLaboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical SciencesKoichiKikuchiDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineKojiNataDepartment of Medical Biochemistry, School of Pharmacy, Iwate Medical UniversityMakotoKanzakiDepartment of Biomedical Engineering, Tohoku UniversityKenshinSuzukiTohoku University School of MedicineShunWatanabeDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineChiharuKawabeDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineYuiMiyataDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineShunItaiDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineTakafumiToyoharaDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineChitoseSuzukiDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineTetsuhiroTanakaDivision of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of MedicineJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaTomiokaLaboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical SciencesTakaakiAbeDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicinePatients with end-stage renal disease have lower fasting plasma glucose and HbA1c levels, with significantly higher insulin levels. For a long time, it has been believed that this higher insulin level in renal failure is due to decreased insulin clearance caused by reduced renal function. However, here we reported that accumulation of the gut microbiota-derived uremic toxin, phenyl sulfate (PS) in the renal failure, increased insulin secretion from the pancreas by enhanced glucose-stimulated insulin secretion. Other endogenous sulfides compounds which accumulated as in the renal failure also increased glucose-stimulated insulin secretion from β-cell. With RNA-seq analyses and gene knock down, we demonstrated that insulin secretion evoked by PS was mediated by Ddah2. In addition, we also found that PS increased insulin resistance through lncRNA expression and Erk phosphorylation in the adipocytes. To confirm the relationship between PS and glucose metabolism in human, we recruited 2 clinical cohort studies (DKD and CKD) including 462 patients, and found that there was a weak negative correlation between PS and HbA1c. Because these trials did not measure fasting insulin level, we alternatively used the urinary C-peptide/creatinine ratio (UCPCR) as an indicator of insulin resistance. We found that PS may induce insulin resistance in patients with eGFR < 60 mL/min/1.73 m2. These data suggest that the accumulation of uremic toxins modulates glucose metabolism and induced insulin resistance in CKD and DKD patients. Considering HbA1c as a reflection of chronic hyperglycemia and UCPCR as a reflection of chronic hyperinsulinemia, our findings indicate that PS is negatively associated with hyperglycemia independent of CKD, and positively associated with hyperinsulinemia in DKD patients.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0929-19032025p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosisENTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuoNagaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinoriKajiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoyukiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeTakahashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiOharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyoshi Y.TanakaDepartment of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health SystemsMitsunobu R.KanoDepartment of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health SystemsAtsushiMasamuneDivision of Gastroenterology, Tohoku University Graduate School of MedicineYasuoUrataOncolys BioPharma, Inc.ShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPancreatic ductal adenocarcinoma (PDAC)-associated pancreatic stellate cells (PSCs) promote PDAC tumor progression. Notably, PDAC tumors display enhanced macropinocytosis, resulting in enhanced uptake of extracellular particles, including nutrients and viruses. We previously demonstrated the therapeutic potential of telomerase-specific oncolytic adenoviruses OBP-301 and p53-armed OBP-702 against human PDAC cells. However, it remains unclear whether macropinocytosis promotes the virus sensitivity of PDAC-associated PSCs. Here, we show that PSCs activated by human PDAC cells (Panc-1 and BxPC-3) exhibit enhanced sensitivity to wild-type and oncolytic adenoviruses via enhanced macropinocytosis. The virus sensitivity of PSCs was analyzed for the infectivity, replication, and cytopathic activity of wild-type and oncolytic adenoviruses. PDAC-associated PSCs were more sensitive to wild-type and oncolytic adenoviruses than were control PSCs; this sensitivity was mediated by activation of macropinocytosis. In three-dimensional (3D) culture models, p53-armed OBP-702 decreased the viability of PDAC-associated PSCs more strongly than did non-armed OBP-301, reflecting induction of p53-mediated apoptosis. Co-inoculation of PSCs enhanced the growth of PDAC tumors, an effect that was attenuated by OBP-702-mediated p53 activation in the tumor stroma. Our results suggest that p53-armed oncolytic adenovirus OBP-702 eliminates PDAC-associated PSCs via enhancement of macropinocytosis-mediated virus entry and induction of p53-mediated apoptosis.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0007-10482025Impact of methotrexate-dosing regimens for GVHD prophylaxis on clinical outcomes of HLA-matched allogeneic HSCTENTomotakaSuzukiDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical SciencesTomoyasuJoDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityKotaYoshifujiDepartment of Hematology, Institute of Science TokyoTadakazuKondoDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityNorikoDokiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome HospitalYoshinobuKandaDivision of Hematology, Jichi Medical University Saitama Medical CentreTetsuyaNishidaDepartment of Hematology, Japanese Red Cross Aichi Medical Centre Nagoya Daiichi HospitalYasushiOnishiDepartment of Hematology, Tohoku University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalTakahiroFukudaDepartment of Haematopoietic Stem Cell Transplantation, National Cancer Centre HospitalMasashiSawaDepartment of Hematology and Oncology, Anjo Kosei HospitalYutaHasegawaDepartment of Hematology, Hokkaido University HospitalKentaroSerizawaDepartment of Hematology and Rheumatology, Kindai University Faculty of MedicineShuichiOtaDepartment of Hematology, Sapporo Hokuyu HospitalMasatsuguTanakaDepartment of Hematology, Kanagawa Cancer CentreMakotoYoshimitsuDepartment of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences, Kagoshima UniversityYoshikoAtsutaJapanese Data Centre for Haematopoietic Cell TransplantationJunyaKandaDepartment of Hematology, Graduate School of Medicine, Kyoto UniversitySevere graft-versus-host disease (GVHD) remains a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), necessitating optimal immunosuppressive strategies. This retrospective study used data from the Japanese Transplant Registry Unified Management Program to compare three methotrexate (MTX)-dosing regimens for GVHD prophylaxis in patients undergoing human leucocyte antigen (HLA)-matched allo-HSCT: a low-dose 3-day regimen (Ld3:10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6), a low-dose 4-day regimen (Ld4: Ld3 with an additional 7 mg/m2 on day 11) and an original-dose 3-day regimen (Od3: 15 mg/m2 on day 1, 10 mg/m2 on days 3 and 6). Among 2537 analysed patients, Ld3 was the most commonly used regimen. Multivariate analyses showed no significant differences in the cumulative incidence of grade II–IV acute GVHD among regimens. However, Od3 was associated with an increased risk of grade III–IV acute GVHD, and Ld4 was linked to delayed neutrophil engraftment. This study is the first large-scale retrospective analysis of the impact of different MTX-dosing regimens on the outcomes of HLA-matched allo-HSCT, providing valuable insights into optimal MTX-dosing strategies in clinical practice.No potential conflict of interest relevant to this article was reported.American Society of HematologyActa Medica Okayama2473-95299182025Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC46404653ENYuAkahoshiDivision of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount SinaiYoshihiroInamotoDepartment of Blood and Marrow Transplantation and Cellular Therapy, Fujita Health University School of MedicineNikolaosSpyrouDivision of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount SinaiHidekiNakasoneDivision of Hematology, Jichi Medical University Saitama Medical CenterMarcio A.DinizDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount SinaiNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalFrancisAyukDepartment of Stem Cell Transplantation, University Medical Center Hamburg-EppendorfHannah K.ChoeDivision of Hematology, Blood and Marrow Transplantation Program, The Ohio State University Comprehensive Cancer CenterNorikoDokiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalTetsuyaEtoDepartment of Hematology, Hamanomachi HospitalAaron M.EtraDivision of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount SinaiElizabeth O.HexnerDepartment of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of PennsylvaniaNobuhiroHiramotoDepartment of Hematology, Kobe City Medical Center General HospitalWilliam J.HoganDivision of Hematology, Mayo ClinicErnstHollerDepartment of Hematology and Oncology, Internal Medicine III, University of RegensburgKeisukeKataokaDivision of Molecular Oncology, National Cancer Center Research InstituteToshiroKawakitaDepartment of Hematology, National Hospital Organization Kumamoto Medical CenterMasatsuguTanakaDepartment of Hematology, Kanagawa Cancer CenterTakashiTanakaDivision of Hematopoietic Stem Cell Transplantation, National Cancer Center HospitalNaoyukiUchidaDepartment of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon HospitalIngridVasovaDepartment of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital ErlangenSatoshiYoshiharaDepartment of Hematology, Hyogo Medical University HospitalFumihikoIshimaruTechnical Department, Japanese Red Cross Blood Service HeadquartersTakahiroFukudaDivision of Hematopoietic Stem Cell Transplantation, National Cancer Center HospitalYi-BinChenHematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General HospitalJunyaKandaDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityRyotaroNakamuraDepartment of Hematology and Hematopoietic Cell Transplantation, City of HopeYoshikoAtsutaJapanese Data Center for Hematopoietic Cell TransplantationJames L. M.FerraraDivision of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount SinaiYoshinobuKandaDivision of Hematology, Jichi Medical University Saitama Medical CenterJohn E.LevineDivision of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount SinaiTakanoriTeshimaDepartment of Hematology, Hokkaido University Faculty of Medicine and Graduate School of MedicineOverall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96252025Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancerENKohjiTanakayaDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterTatsuroYamaguchiDepartment of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalKeijiHirataDepartment of Surgery 1, University of Occupational and Environmental HealthMasayoshiYamadaEndoscopy Division, National Cancer Center HospitalKensukeKumamotoDepartment of Genome Medical Science and Medical Genetics, Faculty of Medicine, Kagawa UniversityYasukiAkiyamaDepartment of Surgery 1, University of Occupational and Environmental HealthKeiIshimaruDivision of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime UniversityKoichiOkamotoDepartment of Gastroenterology and Oncology, Tokushima University Graduate School of Medical ScienceYukoKawasakiCollege of Nursing, University of HyogoKeigoKomineDepartment of Medical Oncology, Tohoku University HospitalAkiraSakamotoDepartment of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshikoShibataHimawari-No-Kai (Sunflower Association), a Patient Advocacy Group for Individuals and Families Affected By Lynch SyndromeYusakuShimamotoDivision of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of MedicineHidekiShimodairaDivision of Medical Oncology, Faculty of Medicine, Tohoku Medical and Pharmaceutical UniversityShigekiSekineDepartment of Pathology, Keio University School of MedicineAkinariTakaoDepartment of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalMisatoTakaoDepartment of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalYasuyukiTakamizawaDepartment of Colorectal Surgery, National Cancer Center HospitalYojiTakeuchiDepartment of Gastroenterology and Hepatology, Gunma University Graduate School of MedicineNorikoTanabeDepartment of Clinical Genetics, Saitama Medical Center, Saitama Medical UniversityFumitakaTaniguchiDepartment of Surgery, Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens HospitalAkikoChinoDepartment of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchHourinChoEndoscopy Center, Tokyo Medical University HospitalSatoruDoiHarmony Line (Association for Patients and Families With Familial Adenomatous Polyposis)TakeshiNakajimaDivision of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer InstituteSakikoNakamoriDepartment of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalYoshikoNakayamaDepartment of Pediatrics, Shinshu University School of MedicineToshiyaNagasakiDepartment of Gastroenterological Surgery, Saitama Cancer CenterHisashiHasumiDepartment of Urology, Yokohama City UniversityKoujiBannoCenter of Maternal -Fetal/Neonatal Medicine, Hiroshima University HospitalTakaoHinoiDepartment of Clinical and Molecular Genetics, Hiroshima University HospitalKenjiFujiyoshiDepartment of Surgery, Kurume University School of MedicineTakahiroHorimatsuInstitute for Advancement of Clinical and Translational Science, Kyoto University HospitalKentaMasudaDepartment of Obstetrics and Gynecology, Keio University School of MedicineMasashiMiguchiDepartment of Gastroenterological Surgery, Hiroshima Prefectural HospitalYusukeMizuuchiDepartment of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu UniversityYasuyukiMiyakuraDepartment of Colon and Pelvic Surgery, Cancer Prevention and Genetic Counseling, Tochigi Cancer CenterMichihiroMutohDepartment of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of MedicineTakahiroYoshiokaDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShinjiTanakaJA Onomichi General HospitalKazuhiroSakamotoKoshigaya Municipal HospitalKentaroSakamakiFaculty of Health Data Science, Juntendo UniversityMichioItabashiSaiseikai Kazo HospitalHideyukiIshidaDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityNaohiroTomitaDivision of Cancer Treatment , Toyonaka Municipal HospitalKenichiSugiharaInstitute of Science TokyoYoichiAjiokaDivision of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata UniversityApproximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0014-48863862025Therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) with voluntary and forced exercise in a rat model of ischemic stroke115145ENTakayukiNagaseDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoYasuharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKyoheiKinDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSusumuSasadaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKawauchiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruYabunoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChiakiSugaharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuichiHirataDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHayatoMiyakeDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsuyaSasakiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiKawaiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunTanimotoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyaSaijoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIschemic stroke results in significant long-term disability and mortality worldwide. Although existing therapies, such as recombinant tissue plasminogen activator and mechanical thrombectomy, have shown promise, their application is limited by stringent conditions. Mesenchymal stem cell (MSC) transplantation, especially using SB623 cells (modified human bone marrow-derived MSCs), has emerged as a promising alternative, promoting neurogenesis and recovery. This study evaluated the effects of voluntary and forced exercise, alone and in combination with SB623 cell transplantation, on neurological and psychological outcomes in a rat model of ischemic stroke. Male Wistar rats that had undergone middle cerebral artery occlusion (MCAO) were divided into six groups: control, voluntary exercise (V-Ex), forced exercise (F-Ex), SB623 transplantation, SB623 + V-Ex, and SB623 + F-Ex. Voluntary exercise was facilitated using running wheels, while forced exercise was conducted on treadmills. Neurological recovery was assessed using the modified neurological severity score (mNSS). Psychological symptoms were evaluated through the open field test (OFT) and forced swim test (FST), and neurogenesis was assessed via BrdU labeling. Both exercise groups exhibited significant changes in body weight post-MCAO. Both exercises enhanced the treatment effect of SB623 transplantation. The forced exercise showed a stronger treatment effect on ischemic stroke than voluntary exercise alone, and the sole voluntary exercise improved depression-like behavior. The SB623 + F-Ex group demonstrated the greatest improvements in motor function, infarct area reduction, and neurogenesis. The SB623 + V-Ex group was most effective in alleviating depression-like behavior. Future research should optimize these exercise protocols and elucidate the underlying mechanisms to develop tailored rehabilitation strategies for stroke patients.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-22532512025Clinical predictors of extubation failure in postoperative critically ill patients: a post-hoc analysis of a multicenter prospective observational study127ENJunHattoriFaculty of Medicine, Osaka UniversityAikoTanakaDepartment of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of MedicineJunkoKosakaDepartment of Anesthesiology and Resuscitology, Okayama University HospitalOsamuHiraoDepartment of Anesthesiology, Osaka General Medical CenterNanaFurushimaDepartment of Anesthesiology and Intensive Care Medicine, Kobe University HospitalYuichiMakiDepartment of Anesthesiology, Toho University Ohashi Medical CenterDaijiroKabataCenter for Mathematical and Data Science, Kobe UniversityAkinoriUchiyamaDepartment of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of MedicineMoritokiEgiDepartment of Anesthesia, Kyoto University HospitalHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University HospitalSatoshiMizobuchiDepartment of Anesthesiology and Intensive Care Medicine, Kobe University HospitalYoshifumiKotakeDepartment of Anesthesiology, Toho University Ohashi Medical CenterAyumiShintaniDepartment of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan UniversityYukikoKoyamaDepartment of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of MedicineTakeshiYoshidaDepartment of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of MedicineYujiFujinoDepartment of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of MedicineBackground Postoperative patients constitute majority of critically ill patients, although factors predicting extubation failure in this group of patients remain unidentified. Aiming to propose clinical predictors of reintubation in postoperative patients, we conducted a post-hoc analysis of a multicenter prospective observational study.<br>
Methods This study included postoperative critically ill patients who underwent mechanical ventilation for > 24 h and were extubated after a successful 30-min spontaneous breathing trial. The primary outcome was reintubation within 48 h after extubation, and clinical predictors for reintubation were investigated using logistic regression analyses.<br>
Results Among the 355 included patients, 10.7% required reintubation. Multivariable logistic regression identified that the number of endotracheal suctioning episodes during the 24 h before extubation and underlying respiratory disease or pneumonia occurrence were significantly associated with reintubation (adjusted odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05–1.18, p < 0.001; adjusted OR 2.58, 95%CI 1.30–5.13, p = 0.007). The probability of reintubation was increased significantly with the higher frequency of endotracheal suctioning, as indicated by restricted cubic splines. Subgroup analysis showed that these predictors were consistently associated with reintubation regardless of the use of noninvasive respiratory support after extubation.<br>
Conclusions Endotracheal suctioning frequency and respiratory complications were identified as independent predictors of reintubation. These readily obtainable predictors may aid in decision-making regarding the extubation of postoperative patients.No potential conflict of interest relevant to this article was reported.Journal of Neurosurgery Publishing Group (JNSPG)Acta Medica Okayama2694-190210132025Endovascular treatment for a symptomatic dissecting ophthalmic artery aneurysm occurring in the orbit: illustrative caseCASE25483ENKoheiIzumiharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunHarumaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiSugiuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFukikoBabaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJuntaroFujitaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuichiHirataDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutaSotomeDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoKawakamiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuKimuraDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasafumiHiramatsuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBACKGROUND: Peripheral ophthalmic artery aneurysms (POAAs) arising from the main trunk or branches of the ophthalmic artery (OphA) are extremely rare. However, their epidemiology and optimal management remain poorly understood. The authors report a rare case of a symptomatic POAA caused by arterial dissection that was successfully treated using endovascular therapy, leading to favorable visual recovery.<br>
OBSERVATIONS: A 77-year-old woman presented with sudden-onset visual impairment in the right eye. Ophthalmological examination revealed a defect in the right visual field. CT angiography revealed a fusiform aneurysm in the right intraorbital OphA. Digital subtraction angiography revealed a pearl and string sign, consistent with a dissecting aneurysm. A balloon test occlusion (BTO) of the OphA origin confirmed collateral circulation from the external carotid artery. Internal trapping of the OphA was performed under general anesthesia. Postoperatively, the patient’s visual function gradually improved, and complete recovery was achieved within 3 months.<br>
LESSONS: Although POAAs are exceptionally rare, they may lead to significant visual dysfunction owing to optic nerve compression. When visual symptoms are present, prompt intervention may reverse the symptoms. Preoperative assessment of collateral circulation using BTO is essential for treatment planning. Internal trapping may be an effective strategy when sufficient collateral flow is confirmed.No potential conflict of interest relevant to this article was reported.Japan Neurosurgical SocietyActa Medica Okayama2188-4226122025Endovascular Thrombectomy for Large Vessel Occlusion in a Patient on Venoarterial Extracorporeal Membrane Oxygenation: A Case Report445451ENYukiEBISUDANIDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasafumiHIRAMATSUDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiroIWASAKIDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiSUGIUDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunHARUMADepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuKIMURADepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoKAWAKAMIDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutaSOTOMEDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroNISHIHARADepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinsukeYUASADepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTANAKADepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesExtracorporeal membrane oxygenation is utilized in the treatment of severe acute cardiac failure and respiratory failure. While it provides the advantage of oxygenating blood through extracorporeal circulation, it also carries risks of intracranial ischemic and hemorrhagic complications due to the continuous presence of artificial materials within the body. We encountered a case in which venoarterial extracorporeal membrane oxygenation was initiated for fulminant myocarditis, and the patient subsequently developed a large vessel occlusion. The diagnosis was confirmed using perfusion computed tomography. A visible thrombus was observed on the arterial cannula of the extracorporeal membrane oxygenation circuit, and the large vessel occlusion was determined to have been caused by thromboembolism. An immediate extracorporeal membrane oxygenation circuit exchange was performed, followed by endovascular thrombectomy. The patient experienced no perioperative complications and achieved a favorable neurological outcome. Endovascular thrombectomy in extracorporeal membrane oxygenation patients requires careful perioperative management and should be promptly performed in eligible cases of thromboembolic events. Furthermore, because patients on extracorporeal membrane oxygenation are often sedated and under intensive systemic management, regular neurological assessments and intracranial monitoring are essential for the early detection of intracranial pathologies.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2077-038314172025Potential of Kidney Exchange Programs (KEPs) in Japan for Donor-Specific Antibody-Positive Kidney Transplants: A Questionnaire Survey on KEPs and a Multi-Institutional Study Conducting Virtual Cross-Matching Simulations6122ENTaiheiItoDepartment of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health UniversityMikiItoDepartment of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health UniversityNaohiroAidaDepartment of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health UniversityKeiKuriharaDepartment of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health UniversityAkihiroTeraoDepartment of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health UniversityYoshihikoWataraiDepartment of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini HospitalMitsuruSaitoDivision of Blood Purification, Akita University HospitalKeizoKakuDepartment of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu UniversityDaisukeIshiiDepartment of Urology, Kitasato University of MedicineSatoshiSekiguchiTransplantation Surgery, Japan Community Healthcare Organization Sendai HospitalTatsuoYonedaUnit of Dialysis, Department of Urology, Nara Medical UniversityKoheiUnagamiOrgan Transplant Medicine, Tokyo Women’s Medical UniversityMasayukiTasakiDivision of Urology, Department of Regenerative & Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata UniversityHitoshiIwamotoDepartment of Kidney Transplantation Surgery, Tokyo Medical University Hachioji Medical CenterMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroTakahashiDepartment of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of TsukubaKazuakiYamanakaDepartment of Urology, Osaka University Graduate School of MedicineMikioSugimotoDepartment of Urology, Faculty of Medicine, Adrenal Surgery and Renal Transplantation, Kagawa UniversityKouheiNishikawaDepartment of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of MedicineChikashiSetoDepartment of Urology, Toyama Prefectural Central HospitalMasakiMuramatsuDepartment of Nephrology, Toho University Faculty of MedicineToshihiroAsaiDepartment of Kidney Transplant and Dialysis, Osaka City General HospitalDaikiIwamiDivision of Renal Surgery and Transplantation, Department of Urology, Jichi Medical UniversityYasutoshiYamadaDepartment of Blood Purification, Kagoshima University HospitalShigeyoshiYamanagaDepartment of Transplant Surgery, Japanese Red Cross Kumamoto HospitalTomonoriKomatsuDepartment of Urology, Chukyo Hospital, Japan Community Healthcare OrganizationMasayoshiMiuraDepartment of Renal Transplantation Surgery and Urology, Sapporo Hokuyu HospitalTakahiroNoharaDepartment of Urology, Kanazawa University HospitalMichihiroMaruyamaDepartment of Frontier Surgery, Chiba University School of MedicineYukiMiyauchiDepartment of Urology, Ehime UniversityToshiakiTanakaDepartment of Urology, Sapporo Medical UniversityMichioNakamuraDepartment of Transplant Surgery, Tokai University School of MedicineKiyohikoHottaDepartment of Renal and Genitourinary Surgery, Faculty of Medicine, Hokkaido UniversityTakashiKenmochiDepartment of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health UniversityObjectives: To clarify the need for a kidney exchange program (KEP) in Japan by conducting a questionnaire survey on KEPs and simulated KEPs by virtual cross-matching based on past cases of transplantation avoidance. Methods: In addition to the content regarding KEPs, an electronic survey was conducted to investigate the number of cases of kidney transplant abandonment due to “immunological” reasons over the past 10 years (2012–2021). Virtual cross-matching was conducted to simulate the feasibility of avoiding immunological risks and enabling kidney transplantation in patients who were previously unable to undergo the procedure. Results: The survey received responses from 107 facilities (response rate: 81.7%). In response to the question about the necessity of a KEP in Japan, 71 facilities (66.4%) indicated that KEPs are necessary. In addition, 251 living-donor kidney transplants were abandoned for “immunological” reasons over the past decade (2012–2021). Among the 80 pairs for which detailed information was available, virtual cross-matching simulations showed that 37/80 pairs (46.3%) were donor-specific antibody (DSA)-negative for blood type-matched combinations, and 41/80 pairs (51.3%) were DSA-negative for blood type-incompatible transplants. Conclusions: The need for a KEP in Japan and its potential usefulness were demonstrated.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama1359-734561892025The direct photochemical cross-esterification of alcohols via site-selective C–H bromination site-selective C–H bromination1736417367ENAtsuyaMiyamotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroyoshiTakamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityIsaoKadotaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentaTanakaResearch Institute for Interdisciplinary Science, Okayama UniversityWe have developed a direct photochemical cross-esterification of alcohols that proceeds via the in situ generation of acyl bromides. The C–H bond of a benzyl alcohol is selectively activated by a bromo source under light irradiation, enabling the cross-esterification to afford a variety of functionalized esters.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1752-805418102025Effectiveness of Statins for Oxaliplatin‐Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Studye70318ENKenshiTakechiDepartment of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama UniversityTakehiroKawashiriDepartment of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu UniversityKeisukeMineDepartment of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu UniversitySoichiroUshioDepartment of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityHirofumiHamanoDepartment of Pharmacy, Okayama University HospitalNorikoHidaDepartment of Clinical Research and Development, Graduate School of Pharmacy, SHOWA Medical University KenjiMomoDepartment of Hospital Pharmaceutics, Graduate School of Pharmacy, SHOWA Medical UniversityMasanobuUchiyamaDepartment of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityMamiUchidaDepartment of Pharmacy, Fukuoka University HospitalMamoruTanakaDivision of Pharmacy, Ehime University HospitalNoriakiHidakaDivision of Pharmacy, Ehime University HospitalHidekiYasuiCenter for Clinical Research, Hamamatsu University HospitalMasahiroUedaFaculty of Pharmaceutical Sciences, Setsunan UniversityRyoheiFujiiDepartment of Pharmacy, Kansai Medical University HospitalMisakiHashimotoDepartment of Pharmacy, Kansai Medical University HospitalYasutakaSakamotoDepartment of Pharmacy, Yokohama City University HospitalKanaUyamaDepartment of Pharmacy, Yokohama City University HospitalTakahiroNiimuraDepartment of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical SciencesYukiHanaiDepartment of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho UniversityAyakaTsuboyaDepartment of Pharmacy, Kawasaki Municipal Tama HospitalKeisukeSuzukiInnovation Center for Translational Research, National Center for Geriatrics and GerontologyNaoyaKamiyamaAsahikawa Medical University HospitalHiromiHagiwaraNagoya City University HospitalNaotoOkadaPharmacy Department, Yamaguchi University Hospital YoshitoZamamiDepartment of Pharmacy, Okayama University HospitalKeisukeIshizawaDepartment of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical SciencesChemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ≥ 2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (n = 510), statin use was associated with a significantly lower incidence of Grade ≥ 2 OIPN than no statin use (19.8% vs. 28.3%, respectively; p = 0.029). Our findings indicate that statins may protect against OIPN in patients with CRC.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2666-0873762025Risk of Heart Failure Hospitalization in Patients Treated With Osimertinib738748ENYasuhisaTatebeDepartment of Pharmacy, Okayama University HospitalYutaTanakaDepartment of Pharmacy, Okayama University HospitalYoheiManabeDepartment of Pharmacy, Okayama University HospitalShinobuOkanoDepartment of Pharmacy, Okayama University HospitalTsukasaHigashionnaDepartment of Pharmacy, Okayama University HospitalHirofumiHamanoDepartment of Pharmacy, Okayama University HospitalKiminakaMurakawaDepartment of Pharmacy, Okayama University HospitalYoshitoZamamiDepartment of Pharmacy, Okayama University HospitalBackground Osimertinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, is used to treat patients with epidermal growth factor receptor–mutant non–small-cell lung cancer. Although osimertinib has been linked to heart failure (HF), detailed risk estimates remain unclear.<br>
Objectives The aim of this study was to examine the association between osimertinib use and HF hospitalization.<br>
Methods In this retrospective cohort study using a large-scale Japanese claims database, patients diagnosed with lung cancer between April 2008 and December 2021 who received cancer therapy were identified. Patients were categorized into osimertinib and control groups according to treatment received. The incidence of HF hospitalization during the treatment period was compared between the groups. Multivariable analyses were performed before and after propensity score matching.<br>
Results The osimertinib and control groups included 11,391 and 108,144 patients, respectively. Among the entire cohort, the median age was 70 years (Q1-Q3: 64-76 years), and the median follow-up duration was 173 days (Q1-Q3: 73-448 days). The incidence of HF hospitalization was 9.9 and 4.1 cases per 1,000 person-years in the osimertinib and control groups, respectively. In multivariable analysis, osimertinib was associated with a higher risk for HF hospitalization than control therapy (subdistribution HR: 2.56; 95% CI: 2.07-3.18; P < 0.001). This association remained significant after propensity score matching (subdistribution HR: 2.29; 95% CI: 1.62-3.24; P < 0.001).<br>
Conclusions Osimertinib use was associated with an increased risk for HF hospitalization. Cardiac function should be closely monitored in patients receiving osimertinib.No potential conflict of interest relevant to this article was reported.International Institute of Anticancer ResearchActa Medica Okayama1109-65352262025C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma836849ENATSUSHITANAKADepartment of Pathology, Beth Israel Deaconess Medical CenterYUSUKEOTANIDepartment of Pathology, Beth Israel Deaconess Medical CenterMASAKIMAEKAWADepartment of Pathology, Beth Israel Deaconess Medical CenterANNAROGACHEVSKAYADepartment of Pathology, Beth Israel Deaconess Medical CenterTIRSOPEÑADepartment of Pathology, Beth Israel Deaconess Medical CenterVANESSA D.CHINUMass Chan Medical School, UMass Memorial Medical CenterSHINICHITOYOOKADepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMICHAEL H.ROEHRLDepartment of Pathology, Beth Israel Deaconess Medical CenterATSUSHIFUJIMURADepartment of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground/Aim: Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (C1orf50), a gene with a previously uncharacterized function in HCC.<br>
Materials and Methods: We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines.<br>
Results: Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways.<br>
Conclusion: C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0022-510X4782025Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3123708ENKentaOrimoDepartment of Precision Medicine Neurology, Graduate School of Medicine, The University of TokyoTakashiMatsukawaDepartment of Neurology, Graduate School of Medicine, The University of TokyoKazutakaShiomiDivision of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of MiyazakiRyojiGotoDepartment of Neurology, Graduate School of Medicine, The University of TokyoAkihikoMitsutakeDepartment of Neurology, Graduate School of Medicine, The University of TokyoYumikoKuromiDepartment of Neurology, Fukushima Medical UniversityNozomuMatsudaDepartment of Neurology, Fukushima Medical UniversityKazuakiKanaiDepartment of Neurology, Fukushima Medical UniversityRyoKurokawaDepartment of Radiology, Graduate School of Medicine, The University of TokyoHiroyukiIshiuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunMitsuiDepartment of Precision Medicine Neurology, Graduate School of Medicine, The University of TokyoJunkoNomotoInstitute of Medical Genomics, International University of Health and WelfareMasakiTanakaInstitute of Medical Genomics, International University of Health and WelfareYosukeOmaeGenome Medical Science Project, National Institute of Global Health and MedicineYosukeKawaiGenome Medical Science Project, National Institute of Global Health and MedicineKatsushiTokunagaGenome Medical Science Project, National Institute of Global Health and MedicineShojiTsujiDepartment of Neurology, Graduate School of Medicine, The University of TokyoTatsushiTodaDepartment of Neurology, Graduate School of Medicine, The University of TokyoCST3 (NM_000099.4) encodes cystatin C, whose C-terminal truncating variants in this gene have recently been reported to cause adult-onset leukoencephalopathy, characterized by headaches, transient neurological symptoms, and distinct imaging findings. We present four patients from two Japanese families, including one with a novel variant (c.358-2_395del). Three patients from one family developed chronic headaches around the age of 20, whereas the patient from the other family remained asymptomatic until his fifties. mRNA analysis of the patient with c.358-2_395del revealed a splicing alteration leading to an in-frame deletion (p.Lys120_Gln133del), representing the first CST3 variant that does not result in a truncated protein. These findings broaden our understanding of the clinical and genetic spectra of CST3-related leukoencephalopathy (114 words).No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1340-28383242025Reference-based chromosome-scale assembly of Japanese barley (Hordeum vulgare ssp. vulgare) cultivar Hayakiso 2 dsaf016ENTsuyoshiTanakaBioinformatics Unit, Research Center for Advanced Analysis, National Agriculture and Food Research OrganizationYuhiHaraguchiDepartment of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research CenterTakatomoTodorokiDepartment of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research CenterDaisukeSaishoBarley Germplasm Center, Institute of Plant Science and Resources, Okayama UniversityTomomiAbikoLaboratory of Agroecology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu UniversityHiroomiKaiDepartment of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research CenterCurrent advances in next-generation sequencing (NGS) technology and assembling programs permit construct chromosome-level genome assemblies in various plants. In contrast to resequencing, the genome sequences provide comprehensive annotation data useful for plant genetics and breeding. Herein, we constructed a reference-based genome assembly of winter barley (H. vulgare ssp. vulgare) cv. ‘Hayakiso 2’ using long and short read NGS data and barley reference genome sequences from ‘Morex’. We constructed ‘Hayakiso 2’ genome sequences covering 4.3 Gbp with 55,477 genes. Comparative genomics revealed that 14,106 genes had orthologs to two barley data, wheat (A, B, and D homoeologs, respectively), and rice. From the gene ontology analysis, 2,494 orthologs against wheat and rice but not two barley contained agricultural important genes, such as ‘response to biotic and abiotic stress’ and ‘metabolic process’. Phylogenetic analysis using 76 pangenome data indicated that ‘Hayakiso 2’ was clustered into Japanese-type genomes with unique alleles. ‘Hayakiso 2’ genome sequences showed known genes related to flowering and facilitated barley breeding through the development of various markers related to agronomically important alleles such as tolerance to various types of biotic and abiotic stress. Therefore, ‘Hayakiso 2’ genome sequences will be used for the further barley breeding.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417102025Primary Lacrimal Sac Diffuse Large B-cell Lymphoma Treated With Local Radiotherapy Alone: A Case With No Relapse After 21 Years of Follow-Upe95411ENToshihikoMatsuoHealthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakehiroTanakaPathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMitsuhiroTakemotoRadiotherapy, Himeji Red Cross HospitalPrimary lacrimal sac lymphoma is rare and diagnosed as diffuse large B-cell lymphoma in a predominant histopathological type. Systemic chemotherapy would be the standard of care, but local radiotherapy may be a treatment option toward a localized lesion. The present patient is a 54-year-old otherwise healthy woman with a right lacrimal sac mass, which was proven by excisional biopsy to be diffuse large B-cell lymphoma. Since she did not have any other systemic lesions on gallium scintigraphy and neck-to-abdominal computed tomography scans, which were the standard procedure at that time, she underwent local radiotherapy at 40 Gy. Two years later, at the age of 56 years, she developed radiation retinopathy with macular edema in the right eye and had spotty laser photocoagulation in the nasal half of the fundus. At the age of 57 years, she developed radiation cataract and underwent cataract surgery with intraocular lens implantation in the right eye. At the age of 58 years, the macular edema in the right eye became worse and remained active, resulting in poor visual acuity of 0.1. She thus underwent 25-gauge vitrectomy in the right eye to peel off the adhering posterior vitreous surface, together with the internal limiting membrane, as the standard procedure at that time. The visual acuity in the right eye was elevated to 0.6. She maintained the visual acuity afterward and had no relapse of lymphoma in 21 years from the diagnosis of primary right lacrimal sac diffuse large B-cell lymphoma. Local radiotherapy would still be a treatment option for localized lymphoma lesions such as primary lacrimal sac lymphoma.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0962-88193412025Highly efficient transgenesis mediated by Tip100 transposon system in medaka46ENYoshitakaTanakaUshimado Marine Institute (UMI), Okayama UniversityTakahideSekiDepartment of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityAtsushiHoshinoNational Institute for Basic BiologySatoshiAnsaiUshimado Marine Institute (UMI), Okayama UniversityTransgenesis mediated by transposon is an effective approach for introducing exogenous DNA into the nuclear genome and establishing stable transgenic strains that efficiently express genetic tools. Although the DNA transposon Tol2 is widely used for transgenesis in zebrafish, its endogenous transpositional activity can lead to unintended transgene mobilization, making it unsuitable for transgenesis in medaka (Oryzias latipes). Here, we demonstrated that the DNA transposon Tip100, originally identified in the common morning glory (Ipomoea purpurea), an ornamental plant, can serve as a useful tool for transgenesis in Japanese medaka. The GFP transgene cassette, when co-injected with Tip100 transposase mRNA, was expressed in significantly higher number of somatic cells in the injected fish. Furthermore, a transgene flanked by truncated recognition sequences (100 bp each) exhibited expression levels comparable to those of the original vector containing the full 2.2 kb recognition sequence. Injection of a transgene driven by a germline-specific promoter revealed that fish injected with Tip100 mRNA exhibited a significantly higher germline transmission rate (42/68; 62.7%) compared to those injected without the mRNA (13/62; 21.0%). We successfully established transgenic strains by outcrossing injected founders with GFP-positive germ cells (7/7; 100%) and demonstrated that the transgenes were randomly integrated into the medaka genome, generating 8-bp duplications at the insertional sites–an insertional signature of the hAT superfamily of transposons. Our findings indicate that the Tip100 system is a promising tool for generating stable transgenic strains that express various genetic tools in medaka and potentially other fish species.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7952025Gastroduodenal Artery-Preserving Pancreatoduodenectomy after Esophagectomy with Gastric Conduit Reconstruction393398ENAkariMasunagaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuoNagaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMotohikoYamadaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNoriyukiKanehiraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumiSotaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/69441Pancreatoduodenectomy (PD) after esophagectomy with gastric conduit reconstruction is technically challenging. Preserving the blood supply of the gastric conduit is crucial in performing PD after esophagectomy. We report the case of a 66-year-old man who underwent gastroduodenal artery-preserving PD after esophagectomy with gastric conduit reconstruction for intraductal papillary mucinous neoplasm. The patient developed pseudoaneurysm rupture postoperatively, but was successfully treated with interventional radiology. Precise assessment is important in developing a surgical strategy depending on the patient’s specific anatomy and tumor characteristics. Moreover, special attention should be paid to avoid accidental injuries of the gastric conduit and gastric vessels during surgery.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7952025The Utility of a Preoperative 3D Imaging Analysis System for Trigonal Meningioma387392ENYusukeMoriDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihiroOtaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoOmaeDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuichiroHiranoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJojiIshidaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroFujiiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunHarumaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasafumiHiramatsuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiMatsushitaDivision of Radiological Technology, Okayama University HospitalFumiyoHigakiDepartment of Radiology, Medical Development Field, Okayama UniversityKenjiSugiuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/69440Trigonal meningiomas are rare and pose surgical challenges due to their deep location and proximity to critical neuroanatomical structures. We present the case of a 67-year-old woman with a growing trigonal meningioma successfully resected with guidance by a preoperative 3D imaging analysis system. Integration of CT and MRI including diffusion tensor imaging (DTI) enabled precise mapping of the optic radiation, guiding a middle temporal gyrus approach. Preoperative embolization reduced tumor vascularity, facilitating gross total resection with minimal blood loss. This case highlights the effectiveness of preoperative 3D imaging systems in optimizing surgical planning and improving outcomes in complex neurosurgical cases.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7952025Advantages of Single-Position Surgery over Posterior Fusion for Single-Level Degenerative Lumbar Diseases359368ENTomohikoHiroseDepartment of Orthopedic Surgery, Kagawa Prefectural Central HospitalHisanoriIkumaDepartment of Orthopedic Surgery, Kagawa Prefectural Central HospitalKazutoshiOtsukaOtsuka Orthopedic ClinicKeisukeKawasakiDepartment of Orthopedic Surgery, Kagawa Prefectural Central HospitalOriginal Article10.18926/AMO/69437Single-position surgery with lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screws (PPSs) is gaining attention for its reduced invasiveness. We developed SPAPS, a technique allowing two surgeons to perform anterior LLIF and posterior PPS insertion simultaneously in a single lateral decubitus position. This retrospective study compared SPAPS (SPAPS-LLIF, Group SL) and minimally invasive posterior/transforaminal lumbar interbody fusion (MIS-PLIF/TLIF, Group PT) in patients treated between 2016 and 2019 with a two-year follow-up. Operative time, estimated blood loss (EBL), length of hospital stay (LOS), JOABPEQ and VAS scores, segmental lordotic angle, lumbar lordotic angle, segmental Cobb’s angle, PPS misplacement, PPS loosening, fusion status, and muscle cross-sectional areas were compared. Fifty-two patients were analyzed (Group SL: 25; Group PT: 27). SPAPS significantly reduced operative time (118.0 vs. 165.3 min, p <0.01) and estimated blood loss (8.6 vs. 164.1 mL, p<0.01). While clinical outcomes and hospital stay were comparable, Group SL had significantly lower PPS loosening (0% vs. 13%, p<0.01) and non-union rates (0% vs. 22.2%, p=0.02). Multifidus muscle atrophy was also less in Group SL (−14.3 vs. −121.5 mm2, p<0.01). SPAPS demonstrated advantages in reducing surgical invasiveness without compromising clinical efficacy, offering a promising alternative to conventional posterior fusion surgery.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7952025Current Status of Extracorporeal Membrane Oxygenation as a Treatment Strategy for Primary Graft Dysfunction after Lung Transplantation329337ENKeiMatsubaraDepartment of Thoracic Surgery, Hiroshima City Hiroshima Citizens HospitalKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesReview10.18926/AMO/69433Primary graft dysfunction (PGD) is one of the major risk factors affecting patients’ short- and long-term survival after lung transplantation. No particular management strategy has been established for PGD; supportive care is the mainstay of PGD treatment. When a supportive strategy fails, the patient may require the introduction of extracorporeal membrane oxygenation (ECMO) as the last-resort measure for severe PGD. A variety of study of ECMO as a PGD treatment was reported and the management of PGD patients developed so far. Early recognition of a patient’s need for ECMO and its prompt initiation are critical to improved outcomes. The use of venovenous-ECMO became the preferred procedure for PGD rather than venoarterial-ECMO. However, the current ECMO strategy has limitations, and using ECMO to manage patients with PGD is not sufficiently effective. Further studies are required to develop this promising technology.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7952025A Review of the Endoscopic Treatment for Bile Leak Following Cholecystectomy and Hepatic Surgery321328ENTaisukeObataDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalReview10.18926/AMO/69432Bile leak occurs in 2-25% of liver transplant, 3-27% of hepatic resection, and 0.1-4% of cholecystectomy cases. The clinical course of bile leak varies depending on the type of surgery that caused the fistula, as well as the type, severity, and timing of bile duct injury. Although infections resulting from bile leak can be life-threatening, the introduction of endoscopic treatment has enabled some patients to avoid reoperation and has reduced the negative impact on quality of life associated with external fistulas for percutaneous drainage. Endoscopic interventions, such as sphincterotomy and stent placement, reduce the pressure gradient between the bile duct and duodenum, facilitating bile drainage through the papilla and promoting the closure of the leak. We reviewed the literature from 2004 to 2024 regarding bile leak following cholecystectomy and liver surgery, examining recommended techniques, timing, and treatment outcomes. In cases of bile leak following cholecystectomy, clinical success was achieved in 72-96% of cases, while success rates for bile leak following liver surgery ranged from 50% to 100%. Although endoscopic treatment is effective, it is not universally applicable, and its limitations must be carefully considered.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0305-736413572025Molecular polymorphisms of the nuclear and chloroplast genomes among African melon germplasms reveal abundant and unique genetic diversity, especially in Sudan13291343ENOdirichi NnennayaImohGraduate School of Environmental and Life Science, Okayama UniversityGentaroShigitaGraduate School of Environmental and Life Science, Okayama UniversityMitsuhiroSugiyamaInstitute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization (NARO)Tran PhuongDungGraduate School of Environmental and Life Science, Okayama UniversityKatsunoriTanakaFaculty of Agriculture and Life Science, Hirosaki UniversityMamiTakahashiGraduate School of Environmental and Life Science, Okayama UniversityKazusaNishimuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYukiMondenGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidetakaNishidaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMashaerGodaPlant Genetic Resources Conservation and Research Center, Agricultural Research CorporationMichelPitratINRAE, UR1052, Génétique et amélioration des fruits et légumesKenjiKatoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityBackground and Aims Africa is rich in wild species of Cucumis and is considered one of the places of origin of melon. However, our knowledge of African melon is limited, and genetic studies using melon germplasms with wide geographical coverage are required. Here, we analysed the genetic structure of African melons, with emphasis on Sudan.<br>
Methods Ninety-seven accessions of African melon were examined along with 77 reference accessions representing Asian melon and major horticultural groups. Molecular polymorphisms in the nuclear and chloroplast genomes were investigated using 12 RAPD, 7 SSR and 3 SNP markers. Horticultural traits, including seed size, were measured for 46 accessions, mainly from Sudan.<br>
Key Results African melons were divided into large and small seed-types based on seed length: large seed-type from Northern Africa and small seed-type from Western and Southern Africa. Both seed types are common in Sudan. Molecular genetic diversity in these geographical populations was as high as in India, the Asian centre of melon domestication. Large seed-types from Northern Africa were assigned to Pop4 by structure analysis and had Ib cytoplasm in common with Cantalupensis, Inodorus and Flexuosus. Small seed-types were highly diversified and geographically differentiated; specifically, Pop1 with Ia cytoplasm in Southern Africa and South Asia, Pop2 with Ia in East Asia, including Conomon and Makuwa, and Pop3 with Ia or Ic in Africa. Sudanese small seed-types were grouped in Pop3, while their cytoplasm type was a mixture of Ia and Ic. Sudanese Tibish had Ic cytoplasm, which was unique in Africa, common in Western Africa and Sudan, and also found in wild or feral types.<br>
Conclusions Melon of Ic lineage, including Tibish, originated from wild melon in the ‘western Sudan region’, and independently of melon with Ia or Ib cytoplasm, which originated in Asia. This clearly indicates the polyphyletic origin of melon.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0960-741212352025RNA processing/modifying enzymes play key roles in the response to thermospermine in Arabidopsis thalianae70476ENMitsuruSaraumiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTakahiroTanakaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityDaikiKoyamaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshitakaNishiGraduate School of Engineering, Kyushu Sangyo UniversityYoshihiroTakahashiDepartment of Life Science, Faculty of Life Science, Kyushu Sangyo UniversityHiroyasuMotoseGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTakuTakahashiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThermospermine is involved in negative regulation of xylem differentiation by enhancing the translation of mRNAs of the SAC51 gene family in Arabidopsis (Arabidopsis thaliana). These mRNAs contain conserved upstream open reading frames (uORFs) that interfere with the translation of the main ORF. To investigate the mechanism by which thermospermine acts in this process, we isolated mutants insensitive to thermospermine, named ‘its’. We show that the four genes responsible for these mutants, its1 to its4, encode: (i) a homolog of SPOUT RNA methyltransferase, (ii) an rRNA pseudouridine synthase CBF5/NAP57, (iii) a putative spliceosome disassembly factor STIPL1/NTR1, and (iv) a plant-specific RNA-binding protein PHIP1. These four mutants were found to have much higher levels of thermospermine than the wild-type. While all these mutants except its1 appear almost normal, they enhance the dwarf phenotype of a mutant of ACL5, which encodes thermospermine synthase, resulting in tiny plants resembling a double knockout of ACL5 and SACL3, a member of the SAC51 family. Reporter assays revealed that GUS activity from the CaMV 35S promoter-SAC51 5′-GUS fusion construct was significantly reduced in its1 and its4 or not affected in its2 and its3, while it was slightly increased in its1, its3, and its4, or not changed in its2 by thermospermine. These findings underscore the critical role of RNA processing and modification in the thermospermine-dependent translational regulation of uORF-containing transcripts.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1367-22232812024Can online interactions reduce loneliness in young adults during university closures in Japan? The directed acyclic graphs approache12658ENKoheiKambaraDoshisha UniversityAkihiroToyaHiroshima UniversitySuminLeeHiroshima UniversityHarukaShimizuNishikyushu Univ. Junior CollegeKazuakiAbeHiroshima UniversityJunShigematsuToyama UniversityQingyuanZhangHiroshima UniversityNatsukiAbeHiroshima Bunkyo UniversityRyoHayaseChubu UniversityNobuhitoAbeKyoto UniversityRyusukeNakaiKyoto UniversityShuntaroAokiFukushima Medical UniversityKoheiAsanoKyoto UniversityRyosukeAsanoKurume UniversityMakotoFujimuraFukuoka Jo Gakuin UniversityKen’ichiroFukuiKwassui Women's UniversityYoshihiroFukumotoKansai Medical UniversityKaichiroFurutaniKansai UniversityKojiHasegawaKomazawa UniversityHirofumiHashimotoOsaka Metropolitan UniversityMikotoHashimotoChukyo Gakuin UniversityHirokiHosogoshiKansai UniversityHiroshiIkedaKyushu UniversityToshiyukiIshiokaKobe UniversityChiharuItoUniversity of Human EnvironmentsSuguruIwanoFukushima Medical UniversityMasafumiKamadaShujitsu Junior CollegeYoshihiroKanaiTohoku Gakuin UniversityTomonoriKaritaEhime UniversityYuKasagiRissho UniversityEmiko S.KashimaLa Trobe UniversityJuriKatoKanazawa Institute of TechnologyYousukeKawachiTohoku UniversityJun‐ichiroKawaharaHokkaido UniversityMasanoriKimuraGraduate School of Business Administration, Kobe UniversityYugoKiraKurume UniversityYukoKiyonaga (Sakoda)Kyushu Kyoritsu UniversityHiroshiKohguchiRyutsu Keizai UniversityAsukaKomiyaHiroshima UniversityKeitaMasuiOtemon Gakuin UniversityAkiraMidorikawaChuo UniversityNobuhiroMifuneKochi University of TechnologyAkimineMizukoshiAsahi UniversityKengoNawataFukuoka UniversityTakashiNishimuraHiroshima International UniversityDaisukeNogiwaSeikei UniversityKenjiOgawaHokkaido UniversityJunkoOkadaPrefectural University of HiroshimaAkiOkamotoOkayama UniversityReikoOkamotoOsaka UniversityKyokoSasakiKanagawa University of Human ServicesKosukeSatoKurume UniversityHiroshiShimizuKwansei Gakuin UniversityAtsushiSugimuraTokai UniversityYokoSugitaniSophia UniversityHitomiSugiuraKindai UniversityKyokoSumiokaOkayama UniversityBumpeiSunaguchiGraduate School of Business Administration, Kobe UniversityMasatakaTakebeOtsuma Women's UniversityHiroki C.TanabeNagoya UniversityAyumiTanakaDoshisha UniversityMasanoriTanakaHokkai‐Gakuen UniversityJunichiTaniguchiTezukayama UniversityNamijiTokunagaEhime Prefectural University of Health SciencesRyozoTomitaMusashino UniversityYumikoUedaAsahi UniversityTomomiYamashitaJumonji UniversityKazuhoYamauraRitsumeikan UniversityMasaoYogoDoshisha UniversityKenjiYokotaniTokushima UniversityAyanoYoshidaTohoku Fukushi UniversityHiroakiYoshidaShinshu UniversityKatsueYoshiharaFukuoka Institute of Technology Junior CollegeAyumiYoshikawaOsaka Dental University Faculty of NursingKuniakiYanagisawaKobe UniversityKen'ichiroNakashimaHiroshima UniversityAs a countermeasure to the increased loneliness induced by the COVID-19 pandemic-related university closures, universities provided students with online interaction opportunities. However, whether these opportunities contributed to reducing loneliness during the university closures remains unclear, as previous studies have produced contradictory findings. We conducted a nationwide cross-sectional survey. Data were collected on demographics, social environment, social support, interactions, health and loneliness from 4949 students from 60 universities across Japan. We used psychological network and Directed Acyclic Graphs (DAGs) to examine the effect of online interactions on loneliness during university closures during COVID-19. The results showed that the frequency of online interactions with friends did not exert a significant influence on loneliness during university closures. A comparative examination of the DAGs further illuminated that the social environment exhibited fewer pathways for interpersonal interactions and social support during these closure periods. The psychosocial pathways influencing young adults' loneliness show variations contingent on the university's closure status. Notably, the impact of heightened online interactions with friends on loneliness appears to be less pronounced among young adults in the context of university closure.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0016-70374002025Lithium- and oxygen-isotope compositions of a Si-rich nebular reservoir determined from chondrule constituents in the Sahara 97103 EH3 chondrite5171ENToriiDouglas-SongThe Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama UniversityTsutomuOtaThe Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama UniversityMasahiroYamanakaThe Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama UniversityHiroshiKitagawaThe Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama UniversityRyojiTanakaThe Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama UniversityChristianPotiszilThe Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama UniversityTakKunihiroThe Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama UniversityHere we report the in situ ion-microprobe analyses of the Li- and O-isotope compositions of enstatite, FeO-rich pyroxene, olivine, glass, and cristobalite grains from six chondrule-related objects from the Sahara 97103 EH3 chondrite. The O-isotope composition of the enstatite grains scattered around the intersection between the terrestrial fractionation and primitive chondrule minerals lines. Whereas, that of olivine varied along the primitive chondrule minerals line. Based on the mineralogy, we found cristobalite formed as a result of Si saturation, instead of the reduction of FeO-rich silicates, consistent with Si-enrichment of whole rock enstatite chondrites. Based on the mineralogy and O-isotope compositions, we infer that olivines in some chondrules are relict grains. In chondrules that contained olivine, no abundant niningerite [(Mg,Fe,Mn)S] was observed. Thus, enstatite formation can be explained by the interaction of an olivine precursor with additional SiO2 (Mg2SiO4 + SiO2 → Mg2Si2O6), instead of sulfidation (Mg2SiO4 + S → 1/2 Mg2Si2O6 + MgS + 1/2 O2). Using the equation Mg2SiO4 + SiO2 → Mg2Si2O6 and the O-isotope compositions of enstatite and olivine, the O-isotope composition of the additional SiO2 was estimated. Based on the O-isotope composition, we infer that there could be a Si-rich gas with an elevated Δ17O value similar to, or greater than the second trend line (Δ17O = 0.9 ‰) suggested by Weisberg et al. (2021), during chondrule formation. The variation in the Li-isotope compositions of enstatite and olivine grains from EH3 chondrules is smaller than that for the same phases from CV3 chondrules. The variation in the Li-isotope compositions of the enstatite and olivine grains from EH3 chondrules is also smaller than that of their O-isotope compositions. During the recycling of enstatite-chondrite chondrules, both Li- and O-isotope compositions were homogenized. Although enstatite is the major carrier of Li in EH3 chondrules, the Li-isotope composition (δ7Li) of enstatite is lower than that of whole rock EH3 chondrites, suggesting the existence of a phase with higher δ7Li. Meanwhile, the Li-isotope composition and concentration (δ7Li, [Li]) of enstatite is higher than that of olivine. The Li-isotope composition of the Si-rich gas was estimated to be δ7Li = 1 ‰, using a similar mass-balance calculation as applied for the O-isotope composition. The Li-isotope composition of the Si-rich gas from the enstatite-chondrite-chondrule forming-region, is consistent with that of whole rock EH3 chondrites, and differs significantly from that of the Si-rich gas from the carbonaceous-chondrite-chondrule forming-region (δ7Li = −11 ‰) determined by a previous study. We speculate that the Si-rich gas in the carbonaceous-chondrite-chondrule forming-region maintained the Li-isotope heterogeneity inherited from light lithium synthesized by galactic cosmic-ray spallation in the interstellar medium.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama1359-73452025Generation of alkyl radicals via C(sp3)–C(sp3) bond cleavage of xanthene-based precursors for photocatalytic Giese-type reactionENShutaHoriuchiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMasatoOishiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAsukaMizutaniGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroyoshiTakamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityIsaoKadotaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentaTanakaResearch Institute for Interdisciplinary Science, Okayama UniversityNovel xanthene-based alkyl radical precursors were developed and subjected to photocatalytic C(sp3)–C(sp3) bond cleavage for the efficient generation of alkyl radicals, which were subsequently reacted with various alkenes to afford the corresponding Giese-type products. After the reaction, the produced xanthones can be recovered in high yield.No potential conflict of interest relevant to this article was reported.Japan Neurosurgical SocietyActa Medica Okayama0470-81056592025Real-world Experience of Embolization for Intracranial Tumors in Japan: Analysis of 2,756 Cases from Japanese Registry of NeuroEndovascular Therapy 4396406ENJunHARUMADepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiSUGIUDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohitoHISHIKAWADepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutaSOUTOMEDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiEBISUDANIDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuKIMURADepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisanoriEDAKIDepartment of Neurosurgery, Kawasaki Medical SchoolMasatoKAWAKAMIDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiMURAIDepartment of Neurosurgery, Kawasaki Medical SchoolMasafumiHIRAMATSUDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTANAKADepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTetsuSATOWDepartment of Neurosurgery, Kindai UniversityKojiIIHARADepartment of Neurosurgery, National Cerebral and Cardiovascular CenterHirotoshiIMAMURADepartment of Neurosurgery, National Cerebral and Cardiovascular CenterAkiraISHIIDepartment of Neurosurgery, Juntendo University Graduate School of MedicineYujiMATSUMARUDepartment of Neurosurgery, Institute of Medicine, University of TsukubaChiakiSAKAIDepartment of Neurosurgery, Kyoto UniversityShinichiYOSHIMURADepartment of Neurosurgery, Hyogo Medical UniversityNobuyukiSAKAIDepartment of Neurological Surgery, Shimizu HospitalJapanese Registry of Neuroendovascular Therapy (JR-NET) InvestigatorsEmbolization of intracranial tumors is predominantly performed in Japan, primarily before neurosurgical resection. The Japanese Registry of NeuroEndovascular Therapy (JR-NET) Study Group, established in 2005, aims to clarify the factors influencing the outcomes of neuroendovascular treatment. Japanese Registry of NeuroEndovascular Therapy 4 is a nationwide, multicenter retrospective observational study that evaluates real-world data on intracranial tumor embolization in Japan. Japanese Registry of NeuroEndovascular Therapy 4 is based on data collected from 166 neurosurgical centers in Japan between January 2015 and December 2019. Of 63,230 patients, 2,664 (4.2%) with intracranial tumors underwent embolization. The primary endpoint was the proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 30 days post-procedure. Secondary endpoints included procedure-related complications. Among the 2,664 patients, 61 records lacked sufficient data, leaving 2,603 patients (1,612 females, median age: 61 years [interquartile range 51-71]). The proportion of patients with mRS scores ≤2 at 30 days after the procedure was 86.9%. The overall incidence of procedure-related complications was 4.8%, with 1.8% hemorrhagic, 2.0% ischemic, and 1.0% classified as other complications. In the multivariate analysis, general anesthesia and embolization of vessels other than the external carotid artery were identified as risk factors for the development of complications. Meningioma cases had a complication rate of 4.3%, with major complications occurring in 3.5%. Hemangioblastoma cases had a 14.9% complication rate, with major complications at 9.9%. Japanese Registry of NeuroEndovascular Therapy 4 provides comprehensive real-world data on intracranial tumor embolization in Japan, identifying risk factors to inform and improve the safe practice of intracranial tumor embolization in neuroendovascular therapy.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-669417162025Prognostic Impact of Gastrointestinal Immune-Related Adverse Events Depends on Nutritional Status in Cancer Patients Treated with Immune Checkpoint Inhibitors2634ENShoichiroHirataDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshiyasuKonoDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityEmiTanakaDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasahikoSueDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasutoTakeuchiDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokiYoshikawaDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshieMakiDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohiroKamioDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDaisukeKametakaDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKatsunoriMatsuedaDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChihiroSakaguchiDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKentaHamadaDepartment of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayaIwamuroDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeijiKawanoDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: Gastrointestinal immune-related adverse events (GI-irAEs) are recognized complications of immune checkpoint inhibitors (ICIs), but their prognostic relevance and associated risk factors remain unclear. This study aimed to assess whether baseline nutritional status, measured using the prognostic nutritional index (PNI), modifies the prognostic impact of GI-irAEs, and to identify clinical factors associated with their occurrence. Methods: We retrospectively analyzed 1104 cancer patients treated with ICIs at a single institution. GI-irAEs were defined as gastrointestinal symptoms requiring clinical intervention. Patients were stratified by irAE type and PNI (≥40 vs. <40), and differences in survival and treatment response were evaluated. Potential risk factors for developing GI-irAEs were also examined. Results: GI-irAEs occurred in 2.7% of patients and were associated with prolonged overall survival (median: 28.7 vs. 14.0 months) among those with PNI ≥ 40. This survival advantage was not observed in patients with PNI < 40. The PNI-dependent prognostic pattern was specific to GI-irAEs and not observed for non-GI irAEs. Similar trends were confirmed in 4- and 8-week landmark analyses. Differences in objective response rate and disease control rate by PNI status were most pronounced in patients with GI-irAEs. The use of anti-CTLA-4 antibodies was significantly associated with GI-irAE development (odds ratio 4.24; 95% confidence interval 1.73–10.39). Conclusions: GI-irAEs appear to confer a survival benefit primarily in patients with preserved nutritional status. PNI may serve as a useful tool to contextualize the clinical relevance of GI-irAEs and help identify patients most likely to benefit from immune activation during ICI therapy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841782025Craniofacial Fibrous Dysplasia to Affect or Not the Optic Nerve in Long-Term Follow-Up of Three Casese91072ENToshihikoMatsuoDepartment of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKiyoshiYamadaDepartment of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMitsuhiroOkanoDepartment of Otorhinolaryngology, School of Medicine, International University of Health and WelfareFibrous dysplasia of the bone is characterized by immature fibrous bones of trabeculae and fibrovascular proliferation in the medulla. In this study, we report three consecutive patients with craniofacial fibrous dysplasia with or without optic nerve involvement. In Case 1, a 43-year-old man with blurred vision in the right eye at the first visit was well until the age of 54 years, when he came back with symptoms suggestive of paranasal sinusitis. Computed tomography scans disclosed a mucocele in the right sphenoid sinus and thickened bilateral ethmoid, sphenoid, and frontal bones. He underwent an emergency nasal endoscopic surgery to make a drainage opening to the sphenoid and ethmoid sinuses on the right side with incomplete success. The pathology of the resected tissue confirmed fibrous dysplasia. With intravenous antibiotics, he recovered from blepharoptosis, complete ophthalmoplegia, and visual acuity decrease on the right side. He was well until the age of 71 years when he had a self-limiting episode of visual field cloudiness caused by the right sphenoid sinus mucocele. At the age of 75 years, he developed abrupt vision loss to no light perception in the right eye. He underwent an open skull surgery to extirpate the sphenoid mucocele on the right side and died of an unknown cause two years later. In Case 2, a 29-year-old man had a two-week-long headache, and computed tomography scans revealed fibrous dysplasia in the bilateral sphenoid bones. Nasal biopsy at the spheno-ethmoid recess proved a pathological diagnosis of fibrous dysplasia. Goldmann perimetry showed normal visual fields in both eyes. He was followed every year by magnetic resonance imaging to maintain normal visual fields until the latest visit at the age of 41 years. In Case 3, a 12-year-old girl was referred to an ophthalmologist to check her vision. She had been diagnosed with fibrous dysplasia of the left maxillary bone at the age of six years by a dentist. She had a gingival resection on the left maxilla at the age of 15 years and had a left maxillary bone resection at 18 years at another hospital. One month after the resection, Goldmann perimetry showed superior peripheral field depression in the left eye, in contrast with the normal visual field in the right eye. She maintained the visual acuity of 1.5 in both eyes until the last visit at the age of 21 years. In fibrous dysplasia as a rare disease, functional and cosmetic problems, including vision problems, should be considered in a case-based approach.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2227-905912102024Development and Characterization of a Three-Dimensional Organotypic In Vitro Oral Cancer Model with Four Co-Cultured Cell Types, Including Patient-Derived Cancer-Associated Fibroblasts2373ENYukaAizawaDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityKentaHagaDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityNagakoYoshibaDepartment of Oral Health and Welfare, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityWitsanuYortchanDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityShoTakadaDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityRintaroTanakaDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityErikoNaitoDivision of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityTatsuyaAbéDivision of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversitySatoshiMaruyamaDivision of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityManabuYamazakiDivision of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityJun-ichiTanumaDivision of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityKazuyoIgawaNeutron Therapy Research Center, Okayama UniversityKeiTomiharaDivision of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityShinsakuTogoDepartment of Respiratory Medicine, Graduate School of Medicine, Juntendo UniversityKenjiIzumiDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityBackground/Objectives: Cancer organoids have emerged as a valuable tool of three-dimensional (3D) cell cultures to investigate tumor heterogeneity and predict tumor behavior and treatment response. We developed a 3D organotypic culture model of oral squamous cell carcinoma (OSCC) to recapitulate the tumor–stromal interface by co-culturing four cell types, including patient-derived cancer-associated fibroblasts (PD-CAFs). Methods: A stainless-steel ring was used twice to create the horizontal positioning of the cancer stroma (adjoining normal oral mucosa connective tissue) and the OSCC layer (surrounding normal oral mucosa epithelial layer). Combined with a structured bi-layered model of the epithelial component and the underlying stroma, this protocol enabled us to construct four distinct portions mimicking the oral cancer tissue arising in the oral mucosa. Results: In this model, α-smooth muscle actin-positive PD-CAFs were localized in close proximity to the OSCC layer, suggesting a crosstalk between them. Furthermore, a linear laminin-γ2 expression was lacking at the interface between the OSCC layer and the underlying stromal layer, indicating the loss of the basement membrane-like structure. Conclusions: Since the specific 3D architecture and polarity mimicking oral cancer in vivo provides a more accurate milieu of the tumor microenvironment (TME), it could be crucial in elucidating oral cancer TME.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1439-75952025Recommendations for the treatment of juvenile idiopathic arthritis with oligoarthritis or polyarthritis from the 2024 update of the Japan College of Rheumatology Clinical Practice Guidelines for the management of rheumatoid arthritis including juvenile idiopathic arthritis with oligoarthritis or polyarthritis – secondary publicationroaf042ENTakakoMiyamaeDepartment of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University HospitalNamiOkamotoDepartment of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and SafetyYuzaburoInoueDepartment of General Medical Science, Graduate School of Medicine, Chiba UniversityTomohiroKubotaDepartment of Pediatrics, Kagoshima Prefectural Satsunan HospitalTakasukeEbatoDepartment of Pediatrics, Kitasato UniversityHitoshiIrabuDepartment of Pediatrics and Development Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental UniversityHidetoKamedaDivision of Rheumatology, Department of Internal Medicine, Toho UniversityYukoKanekoDivision of Rheumatology, Department of Internal Medicine, Keio University School of MedicineHiroshiKuboDepartment of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of MedicineKanakoMitsunagaDepartment of Allergy and Rheumatology, Chiba Children's HospitalMasaakiMoriDepartment of Lifetime Clinical Immunology, Tokyo Medical and Dental UniversityAyakoNakajimaCenter for Rheumatic Diseases, Mie University HospitalKenichiNishimuraDepartment of Pediatrics, Yokohama City University Graduate School of MedicineNaoakiOhkuboIizuka HospitalTomomiSatoClinical Education Center For Physicians, Shiga University of Medical ScienceYukoSugitaDepartment of Pediatrics, School of Medicine, Osaka Medical and Pharmaceutical UniversitySatoshiTakanashiDivision of Rheumatology, Department of Internal Medicine, Keio University School of MedicineTakayukiTanakaDepartment of Pediatrics, Japanese Red Cross Otsu HospitalHiroakiUmebayashiDepartment of Rheumatology and Infectious Diseases, Miyagi Children’s HospitalMasatoYashiroDepartment of Pediatrics, Okayama University HospitalShingoYamanishiDepartment of Pediatrics, Nippon Medical SchoolMieFusamaHealth Sciences Department of Nursing, Kansai University of International StudiesShintaroHirataDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalMitsumasaKishimotoDepartment of Nephrology and Rheumatology, Kyorin University School of MedicineMasatakaKohnoInflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineMasayoKojimaGraduate School of Medical Sciences, Nagoya City UniversityToshihisaKojimaDepartment of Orthopedic Surgery, National Hospital Organization Nagoya Medical CenterAkioMorinobuDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityTakahikoSugiharaDivision of Rheumatology, Department of Internal Medicine, Toho University School of MedicineEiichiTanakaDivision of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical UniversityNobuyukiYajimaDivision of Rheumatology, Department of Medicine, Showa University School of MedicineRyoYanaiDivision of Rheumatology, Department of Medicine, Showa University School of MedicineYutakaKawahitoInflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineMasayoshiHarigaiDivision of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical UniversityObjectives: To conduct systematic reviews (SRs) and develop clinical practice guidelines (CPGs) for managing juvenile idiopathic arthritis (JIA) with oligoarthritis or polyarthritis.<br>
Methods: The Grading of Recommendations, Assessment, Development, and Evaluation methodology was employed to carry out SRs and formulate the CPGs. An expert panel, including patients, paediatric and nonpaediatric rheumatologists, guideline specialists, and patient representatives, used the Delphi method to discuss and agree on the recommendations.<br>
Results: Six clinical questions (CQs) on the efficacy and safety of medical treatments were evaluated. These included CQ1 on methotrexate (MTX), CQ2 on non-MTX conventional synthetic disease-modifying antirheumatic drugs, CQ3 on glucocorticoids, CQ4 on tumour necrosis factor inhibitors, CQ5 on interleukin-6 inhibitors, and CQ6 on Janus kinase inhibitors. Two randomized controlled trials were identified for CQ1, three for CQ2, two for CQ3, eight for CQ4, two for CQ5, and two for CQ6. Based on these evaluations, three strong and three conditional recommendations were established. The CPGs have been endorsed by the Japan College of Rheumatology and the Pediatric Rheumatology Association of Japan.<br>
Conclusions: The SRs provided the necessary evidence to develop the CPGs, which are intended to guide not only paediatric but also nonpaediatric rheumatologists, caregivers, patients, and their families in treatment decision-making.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0009-26739862025Redox-potential-controlled intermolecular [2 + 2] cycloaddition of styrenes for the regio- and diastereoselective synthesis of multisubstituted halogenocyclobutanesuoaf044ENAsukaMizutaniGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMomoKondoLaboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceShokoItakuraLaboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceHiroyoshiTakamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYujiroHoshinoGraduate School of Environment and Information Sciences, Yokohama National UniversityMakiyaNishikawaLaboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceIsaoKadotaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKosukeKusamoriLaboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceKentaTanakaResearch Institute for Interdisciplinary Science, Okayama UniversityThe redox potential is an important factor for controlling the outcome of photoredox catalysis. Particularly, the selective oxidation of substrates and the control over the reactions are challenging when using photoredox catalysts that have high excited-state reduction potentials. In this study, a redox-potential-controlled intermolecular [2 + 2] cycloaddition of styrenes using a thioxanthylium organophotoredox (TXT) catalyst has been developed. This TXT catalyst selectively oxidizes β-halogenostyrenes and smoothly promotes the subsequent intermolecular [2 + 2] cycloadditions to give multisubstituted halogenocyclobutanes with excellent regio- and diastereoselectivity, which has not been effectively achieved by the hitherto reported representative photoredox catalysts. The synthesized halogenocyclobutanes exhibit interesting free radical scavenging activity. The present reaction contributes to the field of redox-potential-controlled electron transfer chemistry.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291863232024Successful Treatment for Life Threatening Recurrent Non-traumatic Rectus Sheath Hematoma in a Case with Microscopic Polyangiitis with Rapidly Progressive Glomerulonephritis32433248ENHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShihoMorimotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYuyaTerajimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShugoOkamotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTakayukiKatsuyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYoshinoriMatsumotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMorinagaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesMayuUkaDepartment of Radiology, Okayama University HospitalKojiTomitaDepartment of Radiology, Okayama University HospitalHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTakaoHirakiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesA 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2090-47625612025Evaluating a discretized data acquisition method for couch modeling to streamline the commissioning process of radiological instruments64ENSyoutaTomimotoDepartment of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama UniversityYusukeSaekiDepartment of Radiological Technology, Kawasaki Medical School HospitalOkihiroMotodaDepartment of Radiological Technology, Kawasaki Medical School HospitalMasatoTanakaDepartment of Radiological Technology, Kawasaki Medical School HospitalSyoukiTsumotoDepartment of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama UniversityHanaNishikawaDepartment of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama UniversityYukiMiyashimaDepartment of Radiological Technology, Kawasaki Medical School HospitalMakikoHiguchiDepartment of Radiological Technology, Kawasaki Medical School HospitalTadashiTaniDepartment of Radiological Technology, Kawasaki Medical School HospitalKuniakiKatsuiDepartment of Radiology, Kawasaki Medical SchoolYoshinoriTanabeDepartment of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama UniversityBackground The commissioning of radiotherapy treatment planning system (RTPS) involves many time-consuming tests to maintain consistency between actual and planned dose. As the number of new technologies and peripheral devices increases year by year, there is a need for time-efficient and accurate commissioning of radiation therapy equipment. Couch modeling is one type of commissioning, and there are no recommended values for CT due to differences in equipment calibration between facilities. This study evaluated the optimal electron density (ED) for the couch using discretized gantry angles.<br>
Results All discrete-angle groups showed a high correlation between the surface ED and dose difference between the actual and planned doses (|r|> 0.9). AcurosXB did not demonstrate a significant correlation between dose differences and each energy. For a small number of discretized gantry groups, the optimal couch modeling results revealed several combinations of surface and interior ED with the same score. Upon adding all couch thickness scores, all energy scores, and both algorithm scores, the optimal surface and interior EDs with the highest score across all couch thicknesses were 0.4 and 0.07, respectively.<br>
Conclusions The optimal couch surface ED dose difference trend was identified, and the effectiveness indicated using the dose difference score from discrete-angle couch modeling. Using this method, couch modeling can be evaluated in a highly precise and quick manner, which helps in the commissioning of complicated linear accelerator and radiological treatment plans.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2950-133482025Downward hyperinflation of the native lung after right single lung transplantation for COPD: A case report highlighting diaphragmatic mobility100268ENShinTanakaDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTsuyoshiRyukoDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuakiTomiokaDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesA 60-year-old male with COPD underwent right single lung transplantation. Despite progressive hyperinflation of the native left lung, the transplanted lung maintained function, as downward expansion of the left lung displaced the diaphragm without compressing the mediastinum. This suggests diaphragm mobility, aided by the absence of the liver beneath the left diaphragm, contributes to favorable outcomes in right single lung transplantation by preventing mechanical compression of the transplanted lung.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291863122024Gastric Mucosa-associated Lymphoid Tissue Lymphoma That Relapsed after 11 Years Subsequent to Achieving Complete Remission16971702ENShokoInooDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Okayama University HospitalMotoyukiOotukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesA 38-year-old Japanese man was diagnosed with extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue in the stomach (gastric MALT lymphoma). Fluorescence in situ hybridization analysis revealed the absence of t (11;18) (q21;q21) translocation but the presence of extra copies of MALT1, indicating tetrasomy 18. Helicobacter pylori eradication led to complete remission (CR). However, the gastric MALT lymphoma relapsed after 11 years old. This case underscores the need for long-term observation (>10 years) of patients with gastric MALT lymphoma. Further investigation is warranted to elucidate the correlation between trisomy/tetrasomy 18 and the recurrence propensity.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291863102025Idiopathic Gastric Antral Ulcers13671371ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesA Japanese woman presented with gastric antral ulcers accompanied by erosion and edema, demonstrating a chronic pattern of improvement and recurrence for more than six years. The patient had no relevant treatment history, and Helicobacter pylori infection was ruled out. Other potential etiologies contributing to gastric ulcers were eliminated on the basis of endoscopic biopsy and blood laboratory findings. Consequently, the patient was diagnosed with idiopathic gastric antral ulcer. This disease is often overlooked, and the chronological endoscopic images provided in this report can be used as a reference.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama2753-670X3822024Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantationivae021ENToshioShiotaniDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalSeiichiroSugimotoDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalYasuakiTomiokaDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalShinTanakaDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalKenSuzawaDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalKazuhikoShienDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalKentarohMiyoshiDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalHiromasaYamamotoDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalMikioOkazakiDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalOBJECTIVES: Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction.<br>
METHODS: According to the primary graft dysfunction grade at post-transplant 72 h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0–1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation.<br>
RESULTS: A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 h was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups [non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040]. Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/ml at post-transplant 72 h had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/ml.<br>
CONCLUSIONS: Plasma histidine-rich glycoprotein concentrations at post-transplant 72 h might be associated with the risk of development of primary graft dysfunction.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1342-17512972025The association of fasting triglyceride variability with renal dysfunction and proteinuria in medical checkup participants920927ENNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohikoAsakawaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshimasaSakurabuDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKatsuyoshiKatayamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShugoOkamotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRikaTakemotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyokoUmebayashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground The association between the variability of triglyceride (TG) and chronic kidney disease (CKD) progression remains unclear. We examined whether intraindividual variability in fasting TG was associated with the exacerbation of CKD.<br>
Methods We conducted a retrospective and observational study. 18,339 participants, who went through medical checkups and had checked their estimated glomerular filtration rate (eGFR) and semi-quantitative proteinuria by urine dipstick every year since 2017 for 4 years were registered. Variability in fasting TG was determined using the standard deviation (SD), and maximum minus minimum difference (MMD) between 2017 and 2021. The primary end point for the analysis of eGFR decline was eGFR < 60 mL/min/1.73 m2. The secondary end point for the analysis of proteinuria was the incidence of proteinuria ≥ ( ±) by urine dipstick.<br>
Results The renal survival was lower in the higher-SD, and higher-MMD groups than in the lower-SD, and lower-MMD groups, respectively (log-rank test p < 0.001, and < 0.001, respectively). Lower SD and lower MMD were significantly associated with renal survival in the adjusted model (hazard ratio (HR), 1.12; 95% confidence intervals (CI), 1.04–1.21, and HR, 1.13; 95% CI 1.05–1.23, respectively). The non-incidence of proteinuria was lower in the higher-SD, and higher-MMD groups than in the lower-SD, and lower-MMD groups, respectively (log-rank test p < 0.001 and < 0.001, respectively).<br>
Conclusion Fasting TG variability was associated with CKD progression in participants who went through medical checkups.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7942025A Rare Presentation of Pneumonic-Type Adenocarcinoma Hidden behind Empyema305309ENSatoruSenooDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterEitoNimanDepartment of General Thoracic Surgery, National Hospital Organization Fukuyama Medical CenterRyokoTsujiDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterKoheiTakataDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterShunsukeMatsumoriDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterFumikaMuranoDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterYukaSugisakiDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterHirokiOmoriDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterAkihikoTaniguchiDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterRikaOmoteDepartment of Diagnostic Pathology, National Hospital Organization Fukuyama Medical CenterEikiIchiharaDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterKenjiTakahashiDepartment of General Thoracic Surgery, National Hospital Organization Fukuyama Medical CenterToshiakiOkadaDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterCase Report10.18926/AMO/69158Pneumonic-type adenocarcinoma (P-ADC) can closely mimic pneumonia. We report a P-ADC initially diagnosed as pneumonia which developed into a pulmonary abscess and empyema. A 50-year-old Japanese male diagnosed with pneumonia, pulmonary abscess, and empyema was administered antibiotics and a chest tube for drainage, which improved his symptoms and blood test results. However, chest computed tomography showed an enlarged infiltrative shadow. The patient underwent bronchoscopy and was diagnosed with an adenocarcinoma. This case highlights the importance of considering P-ADC in differential diagnoses when a pneumonia-like shadow enlarges post-empyema treatment. Diagnostic and clinical tests, e.g., bronchoscopy, should be performed in such cases.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7942025Effectiveness of Pallidal Stimulation for Dystonic Storm and Subsequent Ssevere Posterior Reversible Encephalopathy Syndrome in a Patient with GNAO1 Variant293297ENKojiKawaiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsuyaSasakiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunTanimotoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyaSaijoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSusumuSasadaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyukiAkiyamaDepartment of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaHiraideDepartment of Biochemistry, Hamamatsu University School of MedicineHirotomoSaitsuDepartment of Biochemistry, Hamamatsu University School of MedicineShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/69156GNAO1 variant affects primarily the brain and neurodevelopment, leading to a range of motor disorders including seizures beginning in infancy and involuntary movements such as dyskinesia and dystonia. Our patient, a 15-year-old Japanese female, began exhibiting involuntary movements at age 4. A de novo missense mutation (NM_020988.3: c.228C>G, NP_066268.1: p.(Asn76Lys)) in the GNAO1 gene was identified when the patient was 15, and during the same year she developed influenza pneumonia, accompanied by dystonic storm. She required intensive care with mechanical ventilation and underwent a tracheostomy. She also developed posterior reversible encephalopathy syndrome. Globus pallidal stimulation was administered, leading to an improvement in the dystonic storm. Early consideration of globus pallidal stimulation is recommended when treating difficult-to-manage dystonic storms.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7942025Parieto-Occipital Disconnection for Drug-Resistant Parieto-Occipital Lobe Epilepsy: A Case Report and Surgical Technique287292ENShunTanimotoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsuyaSasakiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiKawaiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyaSaijoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKyoheiKinDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSusumuSasadaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/69155We report a case of drug-resistant parieto-occipital lobe epilepsy successfully treated with parieto-occipital disconnection (POD). An 18-year-old left-handed female, who had undergone surgery for an acute subdural hematoma at 10 months of age, developed drug-resistant epilepsy at age 15. Despite antiepileptic drug treatment, her seizures remained uncontrolled, and at age 18 she was referred to our hospital for evaluation. Magnetic resonance imaging (MRI) revealed atrophy in the left occipital and parietal lobes. Ictal electroencephalography (EEG) confirmed occipital onset of seizures without temporal lobe involvement. She had pre-existing homonymous hemianopsia. POD surgery was performed, carefully preserving the temporal lobe structures. Postoperatively, she experienced transient right-sided paresis, which fully resolved, and achieved complete seizure control at 3 years without memory loss. This case demonstrates that POD, a rare surgical approach, is a viable option for parieto-occipital lobe epilepsy, effectively controlling seizures while minimizing functional impairment in the absence of temporal lobe involvement.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7942025Outcome of Decompression Surgery Following Rapid Neurological Deterioration in Patients with Spinal Cord Injury Without Radiographic Evidence of Trauma (SCIWORET)261267ENYuichiHirataDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChiakiSugaharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSusumuSasadaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHayatoMiyakeDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayukiNagaseDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoYasuharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/69151Cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) increase the likelihood of spinal cord injury without radiographic evidence of trauma (SCIWORET). Opinions regarding the optimal timing for surgery in such cases vary, however. We retrospectively investigated the demographics and outcomes of patients with SCIWORET who underwent surgery shortly after experiencing rapid neurological deterioration, and we matched patients who underwent standby surgery for CSM or OPLL. Although the optimal timing of surgery for SCIWORET remains unclear, our findings suggest that early stage surgery for SCIWORET may yield favorable neurological improvements.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7942025The Work Productivity of Cancer-survivor and Non-cancer-survivor Workers243251ENMikaKamanoDepartment of Public Health, Faculty of Medicine, Kagawa UniversityKanaeKandaDepartment of Public Health, Faculty of Medicine, Kagawa UniversityNlandu RogerNgatuDepartment of Public Health, Faculty of Medicine, Kagawa UniversityAkitsuMurakamiCancer Center, Kagawa University HospitalYusukeYamadoriDepartment of Anesthesiology, Faculty of Medicine, Kagawa UniversityTomohiroHiraoDepartment of Public Health, Faculty of Medicine, Kagawa UniversityOriginal Article10.18926/AMO/69149We investigated the work productivity levels of employed cancer survivors and non-cancer-survivor workers by conducting a cross-sectional study in Japan between February and March 2019, using an online survey. A total of 561 employed individuals aged 20-64 years were analyzed. Work productivity was assessed using the Work Productivity and Activity Impairment-General Health questionnaire which evaluates absenteeism, presenteeism, and overall work productivity loss. The questionnaire responses demonstrated that the cancer survivors within 1 year of diagnosis had significantly higher absenteeism compared to the non-cancer workers (p=0.048). Although presenteeism and overall work productivity loss were also higher in the non-cancer-survivor group, the differences were not significant. Cancer survivors within 1 year of diagnosis exhibited higher absenteeism, but their work productivity appeared to recover to levels comparable to those of the non-cancer workers over time. These findings may contribute to workplace policies supporting cancer survivors’ return to work.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1434-516169122024Association study of GBA1 variants with MSA based on comprehensive sequence analysis -Pitfalls in short-read sequence analysis depending on the human reference genome-613621ENKentaOrimoDepartment of Neurology, Graduate School of Medicine, The University of TokyoJunMitsuiDepartment of Precision Medicine Neurology, Graduate School of Medicine, The University of TokyoTakashiMatsukawaDepartment of Neurology, Graduate School of Medicine, The University of TokyoMasakiTanakaInstitute of Medical Genomics, International University of Health and WelfareJunkoNomotoInstitute of Medical Genomics, International University of Health and WelfareHiroyukiIshiuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeOmaeGenome Medical Science Project, National Center for Global Health and MedicineYosukeKawaiGenome Medical Science Project, National Center for Global Health and MedicineKatsushiTokunagaGenome Medical Science Project, National Center for Global Health and MedicineNCBN Controls WGS ConsortiumTatsushiTodaDepartment of Neurology, Graduate School of Medicine, The University of TokyoShojiTsujiDepartment of Neurology, Graduate School of Medicine, The University of TokyoMultiple system atrophy (MSA) is a neurodegenerative disorder characterized by various combinations of autonomic failure, parkinsonism, and cerebellar ataxia. To elucidate variants associated with MSA, we have been conducting short-read-based whole-genome sequence analysis. In the process of the association studies, we initially focused on GBA1, a previously proposed susceptibility gene for MSA, to evaluate whether GBA1 variants can be efficiently identified despite its extraordinarily high homology with its pseudogene, GBA1LP. To accomplish this, we conducted a short-read whole-genome sequence analysis with alignment to GRCh38 as well as Sanger sequence analysis and compared the results. We identified five variants with inconsistencies between the two pipelines, of which three variants (p.L483P, p.A495P–p.V499V, p.L483_M489delinsW) were the results of misalignment due to minor alleles in GBA1P1 registered in GRCh38. The miscalling events in these variants were resolved by alignment to GRCh37 as the reference genome, where the major alleles are registered. In addition, a structural variant was not properly identified either by short-read or by Sanger sequence analyses. Having accomplished correct variant calling, we identified three variants pathogenic for Gaucher disease (p.S310G, p.L483P, and p.L483_M489delinsW). Of these variants, the allele frequency of p.L483P (0.003) in the MSA cases was higher than that (0.0011) in controls. The meta-analysis incorporating a previous report demonstrated a significant association of p.L483P with MSA with an odds ratio of 2.85 (95% CI; 1.05 – 7.76, p = 0.0400).No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2662-4435612025Biogeochemical impact of nickel and urea in the great oxidation event654ENDilan M.RatnayakeThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityRyojiTanakaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityEizoNakamuraThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityThe Great Oxidation Event marks the first substantial increase in atmospheric oxygen on Earth. Despite the oxygenic photosynthesis that emerged hundreds of million years before this event, the specific biogeochemical mechanisms responsible for maintaining low oxygen levels for an extended period remain elusive. Here, we show the critical role of urea as a nitrogen source for cyanobacteria, the cascading impact of nickel on abiotic urea production, and their combined effects on the proliferation of cyanobacteria leading to the great oxidation event. Urea formation was experimentally evaluated under simulated Archean conditions and cyanobacterial growth was monitored providing urea as the nitrogen source. Our findings demonstrate that urea can be produced in the Archean cyanobacterial habitats with UV-C irradiation, shedding light on the controversy regarding the evolution of nitrogen-fixing enzymes in primitive cyanobacteria. We propose that environmental conditions in the early Archean, characterized by elevated urea and nickel concentration, may have hindered cyanobacterial expansion, contributing to the delay between the evolution of oxygenic photosynthesis and the onset of the great oxidation event.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1201-97121562025Recurrent diffuse panbronchiolitis after lung transplantation: Off-label use of inhaled tobramycin for Pseudomonas aeruginosa control in a transplant recipient107913ENShinTanakaDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTuyoshiRyukoDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuakiTomiokaDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalMikioOkazakiDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjectives: This report highlights a clinical case of recurrent diffuse panbronchiolitis (DPB) after bilateral lung transplantation (LTx), with a focus on the therapeutic impact of off-label inhaled tobramycin solution for inhalation (TSI) in managing Pseudomonas aeruginosa colonization.<br>
Methods: A Japanese woman with a history of DPB experienced disease recurrence following bilateral LTx. Persistent colonization by P. aeruginosa and recurrent respiratory symptoms were observed. Off-label TSI therapy, commonly used in cystic fibrosis, was introduced. Clinical response was assessed through radiologic imaging, bronchoscopy, and microbiological cultures.<br>
Results: TSI administration led to significant clinical and radiological improvement. P. aeruginosa was eradicated from sputum cultures within one month and remained absent throughout six months of follow-up. No hospitalizations or adverse events were reported during therapy.<br>
Conclusion: This case suggests the potential of TSI as a therapeutic approach for managing recurrent DPB and indicates its role in stabilizing post-transplant outcomes. Further studies may clarify its efficacy and expand its application in broader DPB management strategies.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1201-97121542025Secondary pneumothorax due to Aspergillus welwitschiae in a lung transplant recipient107863ENShinnosukeFukushimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalSayakaBanMedical Mycology Research Center, Chiba UniversityTakashiYaguchiMedical Mycology Research Center, Chiba UniversityAkiraWatanabeMedical Mycology Research Center, Chiba UniversityShinTanakaDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalSeiichiroSugimotoDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.Life Science Alliance, LLCActa Medica Okayama2575-10777122024Chromosome-specific barcode system with centromeric repeat in cultivated soybean and wild progenitore202402802ENAhmet LTekDepartment of Agricultural Genetic Engineering, Ayhan Şahenk Faculty of Agricultural Sciences and Technologies, Niğde Ömer Halisdemir UniversityKiyotakaNagakiInstitute of Plant Science and Resources, Okayama UniversityHümeyraYıldız AkkamışDepartment of Agricultural Genetic Engineering, Ayhan Şahenk Faculty of Agricultural Sciences and Technologies, Niğde Ömer Halisdemir UniversityKeisukeTanakaNODAI Genome Research Center, Tokyo University of AgricultureHisatoKobayashiNODAI Genome Research Center, Tokyo University of AgricultureWild soybean Glycine soja is the progenitor of cultivated soybean Glycine max. Information on soybean functional centromeres is limited despite extensive genome analysis. These species are an ideal model for studying centromere dynamics for domestication and breeding. We performed a detailed chromatin immunoprecipitation analysis using centromere-specific histone H3 protein to delineate two distinct centromeric DNA sequences with unusual repeating units with monomer sizes of 90–92 bp (CentGm-1) and 413-bp (CentGm-4) shorter and longer than standard nucleosomes. These two unrelated DNA sequences with no sequence similarity are part of functional centromeres in both species. Our results provide a comparison of centromere properties between a cultivated and a wild species under the effect of the same kinetochore protein. Possible sequence homogenization specific to each chromosome could highlight the mechanism for evolutionary conservation of centromeric properties independent of domestication and breeding. Moreover, a unique barcode system to track each chromosome is developed using CentGm-4 units. Our results with a unifying centromere composition model using CentGm-1 and CentGm-4 superfamilies could have far-reaching implications for comparative and evolutionary genome research.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1439-75953542025Telemedicine as an alternative to in-person care in the field of rheumatic diseases: A systematic scoping review715721ENKen-eiSadaDepartment of Clinical Epidemiology, Kochi Medical SchoolShigeruIwataDepartment of Rheumatology and Clinical Immunology, Wakayama Medical UniversityYuzaburoInoueDepartment of General Medical Science, Graduate School of Medicine, Chiba UniversityEiichiTanakaDepartment of Rheumatology, Tokyo Women’s Medical University School of MedicineKeiichiroNishidaLocomotive Pain Center, Okayama University HospitalYutakaKawahitoInflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineAsamiAbeDepartment of Rheumatology, Niigata Rheumatic CenterAtsushiKawakamiDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesTakakoMiyamaeDepartment of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical UniversityObjective: The COVID-19 pandemic prompted the widespread adoption of telemedicine as an alternative to in-person care. This systematic scoping review evaluated the effectiveness, cost-efficiency, and challenges of telemedicine for patients with rheumatic diseases.<br>
Methods: A comprehensive search of the MEDLINE database was conducted using specific terms related to rheumatoid or juvenile arthritis, and telemedicine. The literature search included studies published up to March, 2024. In this review, we only considered studies assessing telemedicine as an alternative to in-person care.<br>
Results: The search, conducted on 15 March 2024, generated 258 references. Eight reports from three randomized controlled trials and three observational studies were included. Randomized controlled trials have shown that the outcomes of telemedicine intervention are comparable to those of in-person care in terms of disease activity, functional status, and quality of life, while enabling fewer outpatient visits and cost-effectiveness. However, the high dropout rates highlight the importance of patient preferences and comprehensive education. Observational studies revealed similar findings but were limited by a high confounding bias.<br>
Conclusion: Telemedicine offers economic advantages and maintains clinical outcomes comparable to those of in-person care. Its success depends on structured patient education and alignment with patient preferences. Further research is required, particularly in the context of healthcare in Japan.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291863242024A Preliminary Survey of Rheumatologists on the Management of Late-onset Rheumatoid Arthritis in Japan32993306ENSatoshiTakanashiDivision of Rheumatology, Department of Internal Medicine, Keio University School of MedicineYukoKanekoDivision of Rheumatology, Department of Internal Medicine, Keio University School of MedicineYutakaKawahitoInflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineTakashiKidaInflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineTakahikoSugiharaDivision of Rheumatology, Department of Internal Medicine, Toho University School of MedicineToshihisaKojimaNational Hospital Organization Nagoya Medical Center, Orthopaedic Surgery and RheumatologyRyozoHaradaDepartment of Orthopaedic Surgery, Kurashiki Sweet HospitalMichinoriIshitokuDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalShintaroHirataDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalMotomuHashimotoDepartment of Clinical Immunology, Osaka Metropolitan University Graduate School of MedicineToshihikoHidakaMiyazaki-Zenjinkai HospitalAsamiAbeDepartment of Rheumatology, Niigata Rheumatic CenterHajimeIshikawaDepartment of Rheumatology, Niigata Rheumatic CenterHiromuItoKurashiki Central HospitalMitsumasaKishimotoDepartment of Nephrology and Rheumatology, Kyorin University School of MedicineKazuoMatsuiDepartment of Rheumatology, Teine Keijinkai HospitalToshihiroMatsuiDepartment of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National HospitalIsaoMatsushitaDepartment of Rehabilitation Medicine, Kanazawa Medical UniversityAkiraOnishiDepartment of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto UniversityAkioMorinobuDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityKeiichiroNishidaDepartment of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShujiAsaiDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Graduate School of MedicineEiichiTanakaDivision of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of MedicineMasayoshiHarigaiDivision of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of MedicineMasayoKojimaDepartment of Public Health, Nagoya City University Graduate School of Medical SciencesObjective We investigated the current perspectives regarding the management of late-onset rheumatoid arthritis (LORA) among rheumatologists in clinical practice.<br>
Methods This study was performed in October 2021, and included 65 rheumatologists certified by the Japan College of Rheumatology, who were administered questionnaires (including multiple choice and descriptive formulae) regarding the management of LORA. We aggregated and analyzed the responses.<br>
Results All 65 rheumatologists responded to the survey; 47 (72%) answered that >50% of newly diagnosed patients were aged ≥65 years, 42 (65%) answered that achievement of remission or low disease activity was the treatment goal, and 40 (62%) considered patient safety to be the highest priority. Most rheumatologists are concerned about the management of conditions other than RA, such as comorbidities, financial constraints, and life circumstances that interfere with standard or recommended treatment implementation.<br>
Conclusion This preliminary survey highlighted various rheumatologists' perspectives regarding the management of LORA.No potential conflict of interest relevant to this article was reported.JMIR Publications Inc.Acta Medica Okayama2561-326X92025Usefulness of Interventions Using a Smartphone Cognitive Behavior Therapy Application for Children With Mental Health Disorders: Prospective, Single-Arm, Uncontrolled Clinical Triale60943ENShinichiroNagamitsuDepartment of Pediatrics, Faculty of Medicine, Fukuoka UniversityAyumiOkadaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoichiSakutaChild Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical CenterRyutaIshiiDepartment of Pediatrics & Child Health, Kurume University, School of MedicineKenshiKoyanagiNagasaki Prefectural Center of Medicine and Welfare for ChildrenChizuHabukawaDepartment of Pediatric Allergy, Minami Wakayama Medical CenterTakashiKatayamaL2B IncMasayaItoNational Center for Cognitive Behavior Therapy and Research, National Center of Neurology and PsychiatryAyakoKanieNational Center for Cognitive Behavior Therapy and Research, National Center of Neurology and PsychiatryRyokoOtaniChild Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical CenterTakeshiInoueChild Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical CenterTasukuKitajimaChild Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical CenterNaokiMatsubaraChild Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical CenterChieTanakaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChikakoFujiiDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshieShigeyasuDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMichikoMatsuokaDepartment of Neuropsychiatry, Kurume University School of MedicineTatsuyukiKakumaBiostatistics Center, Kurume UniversityMasaruHorikoshiNational Center for Cognitive Behavior Therapy and Research, National Center of Neurology and PsychiatryBackground: The prevalence of mental health disorders among children in Japan has increased rapidly, and these children often show depressive symptoms and reduced quality of life (QOL). We previously developed a smartphone-based self-monitoring app to deliver cognitive behavioral therapy (CBT), implemented it in healthy children, and reported its effectiveness for health promotion.<br>
Objective: This study aims to examine the usefulness of the CBT app for improvement in depressive symptoms and QOL in children with mental health disorders.<br>
Methods: The participants were 115 children with mental health disorders (eg, school refusal, orthostatic hypotension, eating disorders, developmental disorders, among others) and aged 12‐18 years. The CBT app–based program comprised 1 week of psychoeducation followed by 1 week of self-monitoring. After reading story-like scenarios, participants created a self-monitoring sheet with 5 panels: events, thoughts, feelings, body responses, and actions. All participants received regular mental health care from physicians in addition to the app-based program. To evaluate the participants’ depressive symptoms and QOL, Patient Health Questionnaire for Adolescents (PHQ-9A), Depression Self-Rating Scale for Children (DSRS-C), and Pediatric Quality of Life Inventory (PedsQL) were measured at the beginning of the intervention, and at 2 and 6 months thereafter. Questionnaire for Triage and Assessment with 30 items (QTA30), and Rosenberg Self-Esteem Scale (RSES) were also used to measure their health and self-esteem. Participants were divided into 4 groups on the basis of the PHQ-9A score (above or below the cutoff; PHQ-9A≥5 or PHQ-9A<5) and completion or noncompletion of the CBT app–based program (app [+] or app [-]). The primary outcome was improvement in the DSRS-C score, and secondary outcomes were improvement in other psychometric scales including PedsQL, QTA30, and RSE. A paired-samples t test was used for statistical analysis. The Medical Ethics Committee of Fukuoka University Faculty of Medicine (approval U22-05-002) approved the study design.<br>
Results: There were 48, 18, 18, and 7 participants in the PHQ-9A≥5 app (+), PHQ-9A≥5 app (-), PHQ-9A<5 app (+), and PHQ-9A<5 app (-) groups, respectively. A total of 24 participants dropped out. No improvement in the DSRS-C score was observed in all groups. However, PedsQL scores improved significantly at 2 and 6 months in the PHQ-9A<5 app (+) group (t17=6.62; P<.001 and t17=6.11; P<.001, respectively). There was a significant positive correlation between the PHQ-9A scores and the number of self-monitoring sheets completed.<br>
Conclusions: The CBT app was useful for improving PedsQL scores of children with mental health disorders. However, a higher-intensity CBT program is necessary for more severely depressed children.<br>
Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000046775; center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053360No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2692-4609612025A Case of Gastric Atypical Lipomatous Tumor/Well‐Differentiated Liposarcoma With Endoscopic Morphological Changese70146ENRikaOmoteDepartment of Diagnostic Pathology, NHO Fukuyama Medical CenterShizumaOmoteDepartment of Internal Medicine, Fukuyama Minami HospitalHiroshiSonobeDepartment of Diagnostic Pathology, NHO Fukuyama Medical CenterRyosukeHamanoDepartment of Surgery, NHO Fukuyama Medical CenterTatsuyaToyokawaDepartment of Gastroenterology, NHO Fukuyama Medical CenterShinyaOtsukaDepartment of Surgery, NHO Fukuyama Medical CenterTakehiroTanakaDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiYanaiDepartment of Pathology, Okayama University HospitalMasaruInagakiDepartment of Surgery, NHO Fukuyama Medical CenterHidetakaYamamotoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtypical lipomatous tumor/well-differentiated liposarcoma is a locally aggressive mesenchymal neoplasm composed of adipocytes and stromal cells. Gastric cases are exceedingly rare, and their malignant potential remains unclear. We report a case of a woman in her 60s who was found to have multiple submucosal tumor-like lesions of the stomach. Over time, the tumors increased in size, requiring a laparoscopic partial gastrectomy. Histological examination revealed a tumor composed of both fatty tissue and fibrous stroma with nuclear atypia. Immunohistochemistry showed positivity for CDK4 and MDM2, and fluorescence in situ hybridization confirmed MDM2 amplification, leading to a diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma. This case presented an unusual gastric manifestation, with multiple submucosal tumor-like lesions on endoscopy and exhibiting progressive morphological changes over several years.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2075-44181552025Review Article: Diagnostic Paradigm Shift in Spine Surgery594ENAras EfeLeventDepartment of Orthopedic Surgery, Okayama Rosai HospitalMasatoTanakaDepartment of Orthopedic Surgery, Okayama Rosai HospitalChetanKumawatDepartment of Orthopedic Surgery, Okayama Rosai HospitalChristianHengDepartment of Orthopedic Surgery, Okayama Rosai HospitalSalamalikisNikolaosDepartment of Orthopedic Surgery, Okayama Rosai HospitalKajetanLatkaDepartment of Orthopedic Surgery, Okayama Rosai HospitalAkiyoshiMiyamotoDepartment of Orthopedic Surgery, Okayama Rosai HospitalTadashiKomatsubaraDepartment of Orthopedic Surgery, Okayama Rosai HospitalShinyaAratakiDepartment of Orthopedic Surgery, Okayama Rosai HospitalYoshiakiOdaDepartment of Orthopedic Surgery, Okayama University HospitalKensukeShinoharaDepartment of Orthopedic Surgery, Okayama University HospitalKojiUotaniDepartment of Orthopedic Surgery, Okayama University HospitalMeticulous clinical examination is essential for spinal disorders to utilize the diagnostic methods and technologies that strongly support physicians and enhance clinical practice. A significant change in the approach to diagnosing spinal disorders has occurred in the last three decades, which has enhanced a more nuanced understanding of spine pathology. Traditional radiographic methods such as conventional and functional X-rays and CT scans are still the first line in the diagnosis of spinal disorders due to their low cost and accessibility. As more advanced imaging technologies become increasingly available worldwide, there is a constantly increasing trend in MRI scans for detecting spinal pathologies and making treatment decisions. Not only do MRI scans have superior diagnostic capabilities, but they also assist surgeons in performing meticulous preoperative planning, making them currently the most widely used diagnostic tool for spinal disorders. Positron Emission Tomography (PET) can help detect inflammatory lesions, infections, and tumors. Other advanced diagnostic tools such as CT/MRI fusion image, Functional Magnetic Resonance Imaging (fMRI), Upright and Kinetic MRI, magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) could play an important role when it comes to detecting more special pathologies. However, some technical difficulties in the daily praxis and their high costs act as obstacles to their further spread. Integrating artificial intelligence and advancements in data analytics and virtual reality promises to enhance spinal procedures’ precision, safety, and efficacy. As these technologies continue to develop, they will play a critical role in transforming spinal surgery. This paradigm shift emphasizes the importance of continuous innovation and adaptability in improving the diagnosis and treatment of spinal disorders.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1648-91446042024A Novel Technique for Basilar Invagination Treatment in a Patient with Klippel–Feil Syndrome: A Clinical Example and Brief Literature Review616ENMasatoTanakaDepartment of Orthopaedic Surgery, Okayama Rosai HospitalAbd El Kader AlAskarDepartment of Orthopaedic Surgery, Okayama Rosai HospitalChetanKumawatDepartment of Orthopaedic Surgery, Okayama Rosai HospitalShinyaAratakiDepartment of Orthopaedic Surgery, Okayama Rosai HospitalTadashiKomatsubaraDepartment of Orthopaedic Surgery, Okayama Rosai HospitalTakuyaTaokaDepartment of Orthopaedic Surgery, Okayama Rosai HospitalKojiUotaniDepartment of Orthopaedic Surgery, Okayama University HospitalYoshiakiOdaDepartment of Orthopaedic Surgery, Okayama University HospitalObjectives and Background: To present a novel technique of treatment for a patient with basilar invagination. Basilar invagination (BI) is a congenital condition that can compress the cervicomedullary junction, leading to neurological deficits. Severe cases require surgical intervention, but there is debate over the choice of approach. The anterior approach allows direct decompression but carries high complication rates, while the posterior approach provides indirect decompression and offers good stability with fewer complications. Materials and Methods: A 15-year-old boy with severe myelopathy presented to our hospital with neck pain, bilateral upper limb muscle weakness, and hand numbness persisting for 4 years. Additionally, he experienced increased numbness and gait disturbance three months before his visit. On examination, he exhibited hyperreflexia in both upper and lower limbs, muscle weakness in the bilateral upper limbs (MMT 4), bilateral hypoesthesia below the elbow and in both legs, mild urinary and bowel incontinence, and a spastic gait. Radiographs revealed severe basilar invagination (BI). Preoperative images showed severe BI and that the spinal cord was severely compressed with odontoid process. Results: The patient underwent posterior surgery with the C-arm free technique. All screws including occipital screws were inserted into the adequate position under navigation guidance. Reduction was achieved with skull rotation and distraction. A follow-up at one year showed the following results: Manual muscle testing results and sensory function tests showed almost full recovery, with bilateral arm recovery (MMT 5) and smooth walking. The cervical Japanese Orthopedic Association score of the patient improved from 9/17 to 16/17. Postoperative images showed excellent spinal cord decompression, and no major or severe complications had occurred. Conclusions: Basilar invagination alongside Klippel–Feil syndrome represents a relatively uncommon condition. Utilizing a posterior approach for treating reducible BI with a C-arm-free technique proved to be a safe method in addressing severe myelopathy. This novel navigation technique yields excellent outcomes for patients with BI.No potential conflict of interest relevant to this article was reported.