Elsevier BV Acta Medica Okayama 0012-3692 170 4 2026 Impact of Preexisting Schizophrenia Spectrum Disorders on the Receipt of Surgery and Other Treatments for Non-Small Cell Lung Cancer: A Multicenter Nationwide Cohort Study in Japan EN Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaki Fujiwara Department of Neuropsychiatry, Medical Development Field, Okayama University Taisuke Ishii Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Tomone Watanabe Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Maiko Fujimori Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Naoki Nakaya Tohoku Medical Megabank Organization, Tohoku University Toshihiko Kawamura Department of Medical Informatics, Shimane University Hospital Koji Otsuki Department of Psychiatry, Faculty of Medicine, Shimane University Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Taichi Shimazu Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University Yosuke Uchitomi Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine Masatoshi Inagaki Department of Psychiatry, Faculty of Medicine, Shimane University Background: Patients with schizophrenia spectrum disorders (SSDs) experience higher cancer mortality than the general population. Disparities in treatments for non-small cell lung cancer (NSCLC) among this population remain underexamined. Research Question: Are patients with SSDs less likely to receive surgery, adjuvant chemotherapy for stage II/IIIA, concurrent chemoradiotherapy for stage III, and systemic therapy for stage IV NSCLC compared with those without psychiatric disorders? Study Design and Methods: This retrospective cohort study used national Hospital-Based Cancer Registry data linked to hospital-based administrative data in Japan. It included patients who received initial treatment for NSCLC between 2018 and 2021. Presence of SSDs was defined as a diagnosis using F20 to F29 codes from International Classification of Diseases, 10th Revision. The primary outcome was receipt of surgery for NSCLC. Secondary outcomes were receipt of the following: (1) adjuvant chemotherapy within 180 days in patients with pathologic stage II/IIIA NSCLC; (2) concurrent chemoradiotherapy in clinical stage III NSCLC; and (3) systemic therapy in stage IV NSCLC. Multivariable logistic regression adjusted for age, sex, clinical stage, comorbidities, and functional status was performed. Results: The final cohort comprised 166,663 patients, 1,346 of whom had SSDs. Patients with SSDs were more likely to be diagnosed at stage IV NSCLC (45.0% vs 31.4%) and less likely to undergo surgery (31.5% vs 49.9%; adjusted OR [aOR], 0.70; 95% CI, 0.57-0.85), receive adjuvant chemotherapy (aOR, 0.31; 95% CI, 0.17-0.57), or receive systemic therapy (aOR, 0.54; 95% CI, 0.45-0.65). No significant difference was observed in concurrent chemoradiotherapy for stage III NSCLC (aOR, 0.99; 95% CI, 0.73-1.34). Interpretation: Patients with SSDs were less likely to receive surgery and other stage-appropriate treatments for NSCLC, highlighting the need for targeted interventions to promote equitable cancer care for these individuals. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 2578-5826 48 1 2024 Comparison of different ANCA detection methods in a predominantly MPO-ANCA-associated vasculitis cohort 47 57 EN Yasuhiro Katsumata Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine Ken-ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Kameda Department of Rheumatology, Takamatsu Red Cross Hospital Hiroaki Dobashi Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University Shinya Kaname Department of Nephrology and Rheumatology, Kyorin University School of Medicine Naotake Tsuboi Department of Nephrology, Fujita Health University School of Medicine Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Koichi Amano Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University Naoto Tamura Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Masayoshi Harigai Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine Research Committee of Intractable Vasculitis Syndrome and the Research Committee of Intractable Renal Disease of the Ministry of Health, Labour and Welfare of Japan We compared different antineutrophil cytoplasmic antibody (ANCA) detection methods using a predominantly myeloperoxidase (MPO)-ANCA-associated vasculitis cohort. Stored sera from 147 patients with untreated ANCA-associated vasculitis (AAV), including microscopic polyangiitis and granulomatosis with polyangiitis (n = 115 and 32, respectively), and 124 disease controls were tested for P-ANCA and C-ANCA with immunofluorescence (IIF), and for MPO-ANCA and proteinase 3 (PR3)-ANCA with different antigen-specific immunoassays: direct enzyme-linked immunosorbent assay (ELISA), chemiluminescent enzyme immunoassay (CLEIA), third-generation fluorescent enzyme immunoassay (FEIA), and latex turbidimetrical immunoassay (LTIA). In addition, MPO-ANCA and PR3-ANCA titers were calibrated using certified reference materials (CRMs). The sensitivities and specificities for AAV diagnoses were 95% and 94% (IIF), 86% and 98% (ELISA), 93% and 94% (CLEIA), 92% and 96% (FEIA), and 68% and 88% (LTIA). Dual IIF/antigen-specific immunoassay testing reduced diagnostic accuracies from 94% to 93%. The quantitative agreement between ANCA levels measured using CLEIA and FEIA and calibrated using CRMs was not good. In conclusion, this study demonstrated the high performance of antigen-specific immunoassays for AAV diagnosis in a predominantly MPO-ANCA-associated vasculitis cohort and suggested that the benefit of dual IIF/antigen-specific immunoassay testing is limited. Standardizing ANCA measurements using different immunoassays was difficult, even when using CRMs. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2052-0492 14 1 2026 Sequence and timing of organ donation discussions in brain-dead donors: a subanalysis of the J-RESPECT study 76 EN Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mineji Hayakawa Department of Emergency Medicine, Hokkaido University Hospital Shoji Yokobori Department of Emergency Medicine, Hokkaido University Hospital Kei Nishiyama Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science Takahiro Atsumi Department of Emergency and Disaster Medicine, Hamamatsu University School of Medicine Osamu Tasaki Acute and Critical Care Center, Nagasaki University Hospital Junya Tsurukiri Emergency and Critical Care Medicine, Tokyo Medical University Hachioji Medical Center Mariko Hayamizu Department of Emergency Medicine, Hokkaido University Hospital Shimon Murahashi Acute and Critical Care Center, Nagasaki University Hospital Munehiro Hayashi Department of Emergency and Critical Care Medicine, Japanese Red Cross Medical Center Takeshi Nishimura Department of Emergency and Critical Care Medicine, Hyogo Emergency Medical Center Yukari Goto Department of Emergency Medicine, Nagoya Ekisaikai Hospital Hiromichi Narumiya Department of Emergency and Critical Care Medicine, Japanese Red Cross Kyoto Daini Hospital Atsushi Mizutani Department of Emergency Medicine, Hamamatsu Medical Center Mamoru Miyajima Emergency and Critical Care Center, Nagaoka Red Cross Hospital Junya Shimazaki Department of Emergency and Critical Care Medicine, Kansai Medical University Medical Center Takeshi Miura Department of Emergency and Critical Care Medicine, Institute of Medicine, University of Tsukuba Hospital Nozomu Shima Department of Emergency and Critical Care Medicine, Wakayama Medical University Kazuki Deuchi Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science Hitomi Nakayasu Emergency and Critical Care Medicine, Seirei Hamamatsu General Hospital Hitoshi Kano Department of Emergency Medicine, Hokkaido University Hospital Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University J-RESPECT study group Background The optimal timing of organ donation discussions in patients with catastrophic brain injury remains unclear. In Japan, national guidance recommends providing information after recognition of a state compatible with brain death; however, real-world practice has not been well characterized. This study aimed to evaluate the sequence of organ donation option presentation relative to clinical determination of a brain death-compatible state and to assess option presentation timing. Methods We conducted a multicenter retrospective cohort study using data from the J-RESPECT study, including adult brain-dead donors from 16 institutions in Japan between 2010 and 2023. Donors were classified as brain death-first (option presented after clinical determination of a brain death-compatible state) or option-first (option presented before such determination). Mixed-effects logistic and linear regression models with random intercepts for institution were used to examine factors associated with presentation sequence and timing. Results Among 190 donors, 76 (40%) were classified as brain death-first and 114 (60%) as option-first. In mixed-effects logistic regression, age was the only independent factor associated with presentation sequence (adjusted OR 1.03 per year, 95% CI 1.00–1.07), while substantial between-institution variability was observed (intraclass correlation coefficient = 0.32). Institutional timing policy was not significantly associated with presentation sequence. The median interval from admission to option presentation was 5 days in the brain death-first group and 2 days in the option-first group (p < 0.001). Conclusions Substantial inter-institutional variability exists in the sequence and timing of organ donation discussions in Japan. Further studies are needed to determine optimal approaches to organ donation communication and timing in clinical practice. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-244X 26 1 2026 Timing of emergency department presentation and psychiatric consultation after self-harm or suicide attempts: a registry-based study in Japan 674 EN Shunta Jinno Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromasa Yakushiji Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medical Sciences, Kumamoto University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background Self-harm and suicide attempts are frequent causes of emergency department (ED) visits and are strongly associated with an elevated suicide risk. Early psychiatric evaluation in the ED can help reduce repeated self-harm; however, the relationship between presentation timing and psychiatric consultations remains unclear. This study aimed to explore the association between ED visit timing and the likelihood of psychiatric referrals among patients presenting with self-harm or suicide attempts in Japan. Methods This multicenter, registry-based cohort study analyzed data from the JAPAN Registry of Self-Harm and Suicide Attempt from December 1, 2022, to December 31, 2023. Patients presenting to EDs with intentional self-harm or suicide attempts were included. The primary outcome was psychiatric consultation within one day of presentation, analyzed by day and time of presentation using multiple logistic regression, adjusting for potential confounders. Results Of the 1,721 patients analyzed, the median age was 33 years, and 1,127 (65.5%) were female. A total of 1,199 patients (69.7%) received psychiatric consultations, while 522 (30.3%) did not receive a consultation within the next day after presentation. Hospital presentations on Saturdays (adjusted OR, 0.39; 95% CI, 0.20–0.75) and during 4 p.m. to 8 p.m. (adjusted OR, 0.47; 95% CI, 0.24–0.91) were associated with lower likelihoods of psychiatric consultations, using Monday and the 8 a.m. to 12 p.m. period as the reference, respectively. Conclusions Hospital presentations on Saturdays or evening hours were associated with reduced likelihoods of psychiatric consultations, highlighting disparities in access to care during off-hours. These findings may help inform efforts to improve resource allocation and flexible staffing to ensure timely and consistent psychiatric care in ED settings. Clinical trial number Not applicable. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-4418 16 20 2026 Association Between Urine pH and Kidney Outcomes in Patients with Biopsy-Proven Kidney Disease 3418 EN Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshitaka Inoue Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Lower urine pH has been associated with reduced kidney function and increased risk of kidney disease, but its prognostic and pathological significance in biopsy-proven kidney disease remains unclear. Medullary cast formation has been shown to predict adverse renal outcomes beyond cortical interstitial fibrosis and tubular atrophy (IFTA), although its clinical determinants are not fully understood. We examined the associations of urine pH with kidney outcomes and medullary cast formation in patients undergoing native kidney biopsy. Methods: Among 1167 adults who underwent native kidney biopsy between 2011 and 2024, 503 patients with evaluable medullary tissue were included. Urine pH was analyzed in relation to clinical and histological variables and kidney outcomes. The primary outcome was a ≥40% decline in estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Results: Mean baseline eGFR was 60.7 ± 26.2 mL/min/1.73 m2 and urine pH was 6.15 ± 0.84. During a median follow-up of 2.11 years, 113 patients (22.5%) reached the outcome. Lower urine pH was associated with higher risk of kidney outcomes. In multivariable Cox models, urine pH remained independently associated with outcomes (hazard ratio per 1-unit increase, 0.69; 95% CI, 0.52–0.92). Addition of urine pH modestly improved discrimination (C-index 0.642 to 0.654; likelihood ratio test, p = 0.009). Lower urine pH was associated with greater medullary cast formation in unadjusted analysis. Conclusions: Lower urine pH was independently associated with adverse kidney outcomes and with greater medullary cast formation, suggesting that urine pH may reflect intratubular pathological changes associated with CKD progression. No potential conflict of interest relevant to this article was reported.

Elsevier B.V. Acta Medica Okayama 0300-9572 225 2026 Decline in rescue breathing and its impact on outcomes in pediatric out-of-hospital cardiac arrest due to drowning: a nationwide study, 2012–2023 111049 EN Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Rescue breathing is considered essential in pediatric out-of-hospital cardiac arrest (OHCA) due to drowning, a type of asphyxial arrest where hypoxia precedes circulatory collapse. However, the increasing promotion of compression-only CPR (CO-CPR) may have contributed to changes in bystander CPR practices, including a decline in rescue-breathing CPR (RB-CPR). Whether such temporal changes have influenced outcomes in pediatric drowning OHCA remains unclear. Methods: We analyzed nationwide data from the All-Japan Utstein Registry (2012–2023), including pediatric OHCA patients (≤17 years old) whose arrests were caused by drowning and received bystander CPR from laypersons. Patients were categorized into RB-CPR and CO-CPR groups. The primary outcome was 30-day mortality; secondary outcomes included prehospital absence of return of spontaneous circulation (ROSC) and 30-day unfavorable neurological survival, defined as Cerebral Performance Category score 3–5. We used multivariable Poisson regression to estimate adjusted risk ratio (aRR) and conducted analyses by age and witnessed status. Results: Among 740 eligible patients, 41.6% received RB-CPR and 58.4% received CO-CPR. The proportion of RB-CPR declined over the study period. CO-CPR was associated with higher 30-day mortality (aRR 1.38, 95% CI 1.14–1.67), higher prehospital absence of ROSC, and worse neurological outcomes compared with RB-CPR. The adverse association of CO-CPR was most pronounced in unwitnessed arrests, where ventilation may be particularly important. Conclusions: In pediatric drowning OHCA, CO-CPR was associated with worse survival and neurological outcomes than RB-CPR. These findings underscore the necessity for rescue breathing and the importance of ventilation-focused bystander CPR training in pediatric and drowning-related scenarios. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 33 10 2026 Oncological Outcomes and Safety Profiles of Adjuvant Nivolumab in Muscle‐Invasive Urothelial Carcinoma e70664 EN Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Mori Departmentof Urology, The Jikei University School of Medicine Kosuke Iwatani Departmentof Urology, The Jikei University School of Medicine Shota Inoue Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomofumi Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ichiro Tsuboi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoaki Yamanoi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuma Tsuboi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Wataru Murao Department of Urology, Hiroshima City Hiroshima Citizens Hospital Tetsuya Nakada Department of Urology, National Hospital Organization Iwakuni Clinical Center Kohei Ogawa Department of Urology, Shimane University Hospital Akihiro Matsukawa Departmentof Urology, The Jikei University School of Medicine Takafumi Yanagisawa Departmentof Urology, The Jikei University School of Medicine Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Shimane University Hospital Takahiro Kimura Department of Urology, The Jikei University School of Medicine Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives Perioperative immunotherapy has become the standard of care in patients with high-risk muscle-invasive urothelial carcinoma (MIUC). This study aimed to clarify oncological outcomes and safety profiles of adjuvant nivolumab therapy in MIUC, focusing on upper tract urothelial carcinoma (UTUC). Methods This multicenter study comprised 97 patients undergoing removal of primary tumors, followed by adjuvant nivolumab therapy with a potential follow-up period ≥ 12 months. Patients were divided according to the primary tumor location: bladder cancer (BC), n = 66 (68%); UTUC, n = 31 (32%). Multivariable Cox regression analyses were applied to identify prognostic factors for disease-free survival (DFS). Results Before surgery, 38% of patients had an estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2, but this proportion increased to 57% at nivolumab initiation with 19% of UTUC having eGFR < 30. The overall DFS at 6 months was 61.5%. DFS did not differ significantly between BC and UTUC (p = 0.83). On multivariable analyses, a higher absolute eosinophil count was significantly associated with worse DFS (HR 2.24; 95% CI, 1.24–4.03, p = 0.007), while primary tumor location was not. Immune-related adverse events (irAEs) of adrenal insufficiency and hypophysitis occurred in 8% and 4% of patients, respectively, with grade ≥ 3 occurring at 3.3–18.3 months. Conclusions Adjuvant nivolumab therapy may provide comparable oncological outcomes between BC and UTUC. Baseline eosinophil count was an independent prognosticator for DFS. The incidences of adrenal insufficiency and hypophysitis appeared higher in our real-world data. Clinicians should recognize these irAEs due to nonspecific symptoms and considerable variability in time of onset. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 8 2026 Differential impact of host-related factors on survival outcomes between IO+IO and IO+TKI in metastatic renal cell carcinoma: a multicenter retrospective study 1658 1667 EN Koichi Sugimoto Department of Urology, Kindai University Faculty of Medicine Shingo Toyoda Department of Urology, Kindai University Faculty of Medicine Lan Inoki Department of Urology, Kindai University Faculty of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Keita Tamura Department of Urology, Hamamatsu University School of Medicine Takuhisa Nukaya Department of Urology, Fujita Health University School of Medicine Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Hirofumi Morinaka Department of Urology, Kawasaki Medical School Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumasa Komura Department of Urology, Kawasaki Medical School Kiyoshi Takahara Department of Urology, Fujita Health University School of Medicine Teruo Inamoto Department of Urology, Hamamatsu University School of Medicine Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Kazutoshi Fujita Department of Urology, Kindai University Faculty of Medicine Background Immune checkpoint inhibitor (ICI)-based combination therapies, including immune checkpoint inhibitor plus immune checkpoint inhibitor (IO + IO) and immune checkpoint inhibitor plus tyrosine kinase inhibitor (IO + TKI) regimens, have significantly improved outcomes in metastatic renal cell carcinoma (mRCC). However, the prognostic impact of host-related factors in patients receiving these therapies remains unclear. Methods We retrospectively analyzed 493 patients with mRCC treated with IO+IO (n = 205) or IO+TKI (n = 288) as first-line therapy. Survival outcomes and treatment responses were evaluated according to host-related factors using Cox proportional hazards models. Results In the IO+IO cohort, multiple host-related factors were independently associated with worse overall survival, including BMI < 25 kg/m2 (HR 2.280, p = 0.007), dyslipidemia (HR 2.079, p = 0.019), PPI use (HR 1.605, p = 0.039), and opioid use (HR 2.919, p = 0.008). In contrast, in the IO+TKI cohort, only IMDC poor risk (HR 4.169, p < 0.001) and opioid use (HR 3.328, p < 0.001) were significantly associated with overall survival. Host-related factors showed limited associations with objective response and disease control rates in both cohorts. Conclusion The prognostic impact of host-related factors differs according to treatment regimen in mRCC. These findings suggest that host immune and metabolic conditions play a more prominent role in immune-driven IO+IO therapy, whereas tumor-related factors may predominate in IO+TKI therapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1867-1071 2026 Robots for CT-guided needle insertion: clinical implementation and future perspectives EN Yusuke Matsui Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Tomita Department of Radiology, Medical Development Field, Okayama University Noriyuki Umakoshi Department of Radiology, Medical Development Field, Okayama University Kazuaki Munetomo Department of Radiology, Medical Development Field, Okayama University Yuta Kimura Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiyo Higaki Department of Radiology, Medical Development Field, Okayama University Jun Sakurai Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University So Shimooka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takayuki Matsuno Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tetsushi Kamegawa Faculty of Environmental, Life, Natural Science and Technology, Okayama University Robotic systems for computed tomography (CT)-guided needle insertion have been developed to address the limitations of conventional manual needle insertion. Thus far, various robotic systems have been clinically implemented, and accumulating evidence has suggested their clinical utility. The evidence has evolved beyond initial feasibility and early clinical experience to include larger observational and comparative studies. These studies have demonstrated high success rates of robot-assisted needle insertion in various CT-guided interventions, including thermal ablation, biopsy, and preoperative localization. Furthermore, an increasing number of comparative studies have demonstrated the advantages of robot-assisted procedures over conventional manual procedures. These advantages include improved needle insertion accuracy and reduced radiation doses to patients and/or physicians. Although most currently available robotic systems are needle-guiding robots designed to align a needle guide with a predetermined insertion trajectory, we have developed a CT-guided needle insertion robot capable of robotic needle advancement via remote control. Clinical studies have demonstrated the feasibility of robotic needle insertion using this system, as well as needle placement accuracy comparable to that of manual procedures, while eliminating radiation exposure to physicians. The integration of artificial intelligence and the implementation of telerobotic interventions are expected to contribute significantly to the further advancement of robotic systems for CT-guided needle insertion. This narrative review summarizes the current clinical implementations and available evidence for robotic systems for CT-guided needle insertion, including our system, and discusses future perspectives in this field. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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

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

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

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

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

Elsevier BV Acta Medica Okayama 0959-8049 248 2026 Molecular characteristics and clinical outcomes of ERBB2-activating mutation-positive non-small cell lung cancer: A Japanese nationwide real-world cohort 117443 EN Masahiro Yamashita Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Department of Respiratory Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Eiji Nakata Center for Comprehensive Genomic Medicine, Okayama University Hospital Ayako Morita Department of Respiratory Medicine, Okayama University Hospital Naofumi Hara Department of Respiratory Medicine, Okayama University Hospital Kenji Takada Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Toshio Kubo Department of Respiratory Medicine, Okayama University Hospital Eiki Ichihara Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Department of Respiratory Medicine, Okayama University Hospital Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Background: Erb-b2 receptor tyrosine kinase 2 (ERBB2)-activating mutations are well-documented oncogenic drivers in non-small cell lung cancer (NSCLC), occurring in approximately 1–4% of cases. These alterations include a heterogeneous spectrum of variant subtypes; however, the clinicogenomic characteristics and clinical significance of the individual variants have yet to be elucidated. Methods: We searched the nationwide Center for Cancer Genomics and Advanced Therapeutics database, which integrates comprehensive genome profiling data generated in routine clinical practice across Japan, to investigate the molecular landscape and clinical outcomes of patients with ERBB2-mutated NSCLC. Results: A total of 319 patients with ERBB2-activating mutations were included in this retrospective analysis. Although 74% of the patients harbored canonical tyrosine kinase domain (TKD) in-frame insertions, 26% carried noncanonical variants, including TKD missense (8%), transmembrane/juxtamembrane domain (10%), and extracellular domain (ECD) mutations (8%). Co-occurring oncogenic driver alterations were identified in only 18 cases (5.6%) and were largely restricted to noncanonical variants, whereas no co-occurring driver alterations were detected among patients with TKD in-frame mutations. Noncanonical variants—TKD missense and ECD mutations in particular—were associated with an increased tumor mutational burden. Among 288 patients with available survival data, 78 (27%) received trastuzumab deruxtecan (T-DXd) during their clinical course. After excluding patients who had started treatment with T-DXd before undergoing comprehensive genome profiling testing, time-dependent T-DXd exposure was associated with a reduced risk of death (adjusted hazard ratio, 0.63; 95% confidence interval, 0.39–1.01; P = 0.057). Conclusions: ERBB2-mutated NSCLC exhibited substantial molecular heterogeneity, with canonical TKD in-frame insertions characterized by a low frequency of co-occurring oncogenic driver alterations. Among patients harboring ERBB2-activating mutations, exposure to T-DXd was associated with improved overall survival. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 1718-7729 33 6 2026 Limited Immune-Mediated Efficacy of Anti-PD-L1/VEGF in EGFR-TKI-Naïve Egfr-Mutant Lung Cancer with Non-Inflamed Tumor Microenvironment 315 EN Atsuko Hirabae Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadahiro Kuribayashi Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Sachi Okawa Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Nakasuka Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuya Nishii Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Nishimura Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Hisao Higo Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kammei Rai Center for Innovative Clinical Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masamichi Sugimoto Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Immune checkpoint inhibitors (ICIs) show limited efficacy in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma due to its non-inflamed tumor microenvironment (TME). While quadruple therapy combining chemotherapy, anti-programmed death-ligand 1 (PD-L1), and anti-vascular endothelial growth factor (VEGF) antibodies has shown inconsistent results in EGFR-tyrosine kinase inhibitor (TKI)-pretreated patients, whether anti-VEGF therapy can modulate the intrinsic non-inflamed TME remains unknown. We employed an EGFR-TKI-naïve syngeneic Egfr-mutant mouse model and evaluated effects of anti-VEGF, anti-PD-L1, carboplatin, and paclitaxel as monotherapies and combinations, with TME analysis via immunohistochemistry (IHC), flow cytometry, and RNA sequencing. Anti-PD-L1 showed no antitumor effect, and adding anti-VEGF failed to convert the TME to an inflamed status. Although paclitaxel—but not carboplatin—combined with low-dose anti-VEGF inhibited tumor growth, adding anti-PD-L1 provided no benefit, indicating the anti-VEGF-A antibody evaluated here has a limited role in sensitizing tumors to anti-PD-L1 regardless of chemotherapy. CD8+ T-cell depletion did not attenuate the effect of paclitaxel plus low-dose anti-VEGF, and IHC and RNA sequencing revealed increased natural killer cell infiltration, suggesting a CD8+ T-cell-independent, innate immune mechanism. These findings provide preclinical evidence that the evaluated anti-VEGF has limited immunomodulatory activity in EGFR-TKI-naïve Egfr-mutant tumors with a non-inflamed TME, and suggest immunotherapeutic strategies beyond CD8+ T-cell-mediated immunity warrant investigation. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 1347-9032 2026 Clinical Significance of a Cell-Of-Origin-Based Classification in Pancreatic Ductal Adenocarcinoma EN Tatsuya Kikuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ako Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology, Okayama City Hospital Hideaki Kinugasa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Oda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Hirai Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Kato Bioinformatics Analysis Center, Kagawa University Tomoyuki Honda Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited therapeutic options and poor clinical outcomes. Although PDAC has traditionally been thought to arise from ductal epithelial cells, recent studies using genetically engineered mouse models have demonstrated that acinar cells can also serve as a cell of origin, giving rise to tumors with distinct biological properties. Here, we investigated whether such lineage-specific differences are preserved in human PDAC. RNA sequencing was performed on resected specimens from 40 treatment-naïve patients with PDAC, and tumors were classified into Acinar- and Ductal-subtypes using lineage-specific gene expression signatures derived from mouse models. This classification strategy was further applied to human PDAC cell lines, followed by in vitro drug sensitivity assays. Patients with Acinar-subtype tumors had significantly longer overall survival than those with Ductal-subtype tumors (median, 54.0 vs. 26.5 months; p < 0.01), and multivariate analysis identified the ductal cell-derived tumor signature as an independent predictor of poor prognosis (HR, 3.74 [95% CI, 1.41–9.97]; p = 0.01). Among patients who developed postoperative recurrence, Acinar-subtype tumors were associated with more durable disease control (≥ 10 months) following gemcitabine-based chemotherapy than Ductal-subtype tumors (63.6% vs. 16.7%; p = 0.02). Consistently, pancreatic cancer cell lines classified as Acinar-subtype showed greater sensitivity to gemcitabine (p < 0.01) and paclitaxel (p < 0.05). These findings extend the clinical relevance of cell-of-origin signatures beyond prognostic stratification, highlighting the potential of cell-of-origin-based classification for treatment stratification and precision medicine in PDAC. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 2026 Early progression after immune checkpoint inhibitor therapy in recurrent or metastatic head and neck squamous cell carcinoma: association with disease distribution in a single-center retrospective study hyag167 EN Hiroki Noda Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuma Makino Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuto Naoi Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Immune checkpoint inhibitors (ICIs) are an important treatment option for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, some patients experience rapid disease progression shortly after ICI initiation, potentially resulting in deterioration of general condition and limited opportunities for subsequent treatment. This study investigated clinicopathological factors associated with early progression after ICI initiation in patients with R/M HNSCC. Methods: We retrospectively analyzed 207 patients with R/M HNSCC treated with nivolumab or pembrolizumab at a single institution. Early progression was defined as disease progression within 90 days after ICI initiation. Associations between clinicopathological factors and early progression were evaluated using logistic regression analyses. Results: Early progression was observed in 80 patients (38.6%). In an exploratory survival comparison, patients with early progression had significantly shorter overall survival than those without early progression. Early progression rates increased from distant-only disease to locoregional-only disease and combined locoregional and distant disease. In multivariable analysis, combined locoregional, and distant disease showed the strongest independent association with early progression. Elevated neutrophil-to-lymphocyte ratio and hypoalbuminemia were also independently associated with early progression. In contrast, treatment regimen, treatment line, number of lesions, and bulky disease were not significantly associated with early progression. Conclusion: Disease distribution was associated with early progression after ICI initiation in patients with R/M HNSCC, with combined locoregional and distant disease showing the strongest independent association. These findings suggest that both disease status and host condition may influence failure to achieve adequate disease control shortly after ICI initiation. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1867-1071 43 2 2024 Cranial and spinal computed tomography (CT) angiography with photon-counting detector CT: comparison with angiographic and operative findings 143 151 EN Fumiyo Higaki Department of Radiology, Okayama University Hospital Masafumi Hiramatsu Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takao Yasuhara Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Susumu Sasada Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshihiro Otani Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Jun Haruma Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Division of Radiological Technology, Okayama University Hospital Yusuke Morimitsu Division of Radiological Technology, Okayama University Hospital Noriaki Akagi Division of Radiological Technology, Okayama University Hospital Yusuke Matsui Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University The clinical imaging features of photon-counting detector (PCD) computed tomography (CT) are mainly known as dose reduction, improvement of spatial resolution, and reduction of artifacts compared to energy-integrating detector CT (EID-CT). The utility of cranial and spinal PCD-CT and PCD-CT angiography (CTA) has been previously reported. CTA is a widely used technique for noninvasive evaluation. Cranial CTA is important in brain tumors, especially glioblastoma; it evaluates whether the tumor is highly vascularized prior to an operation and helps in the diagnosis and assessment of bleeding risk. Spinal CTA has an important role in the estimation of feeders and drainers prior to selective angiography in the cases of spinal epidural arteriovenous fistulas and spinal tumors, especially in hemangioblastoma. So far, EID-CTA is commonly performed in an adjunctive role prior to selective angiography; PCD-CTA with high spatial resolution can be an alternative to selective angiography. In the cases of cerebral aneurysms, flow diverters are important tools for the treatment of intracranial aneurysms, and postoperative evaluation with cone beam CT with angiography using diluted contrast media is performed to evaluate stent adhesion and in-stent thrombosis. If CTA can replace selective angiography, it will be less invasive for the patient. In this review, we present representative cases with PCD-CT. We also show how well the cranial and spinal PCD-CTA approaches the accuracy of angiographic and intraoperative findings. No potential conflict of interest relevant to this article was reported.

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

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

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study 1 16 EN Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Takatoshi Fujishita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Akito Hata Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Nobuhisa Ishikawa Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Go Saito Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Department of Respiratory Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Kazuya Nishii Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital Hiroshi Kuraishi Department of Pulmonary Medicine, Nagano Red Cross Hospital Ken Yoshihara Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear. Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy. Design: This was a sub-analysis of the retrospective multicenter NINJA study. Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations. 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). 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.

EpiSmart Science Vector Ltd Acta Medica Okayama 2476-762X 26 1 2025 Preoperative Nutritional Status Influences Enteral Nutrition Weaning 6 Months Post-Surgery in Patients with Esophageal Cancer 263 267 EN Mika Sonoi Department of Foods and Human Nutrition, Faculty of Human Life Sciences, Notre Dame Seishin University Yasuhiro Shirakawa Department of Surgery, Hiroshima City Hiroshima Citizens Hospital Norihiro Sonoi Center for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Tanabe Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoaki Maeda Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective: This study aimed to clarify whether nutritional status at admission affects enteral nutrition weaning 6 months after surgery in patients with esophageal cancer. Methods: This was a retrospective study of 81 patients who underwent subtotal esophageal cancer resection between April 2014 and February 2016. The survey items were as follows: 1) sex, 2) age, 3) presence or absence of family members living together, 4) clinical stage, 5) surgical procedure, 6) reconstructed organs, 7) nutritional status at admission, 8) presence or absence of postoperative complications (anastomotic leakage, chylothorax, and recurrent laryngeal nerve paralysis), and 9) presence or absence of treatment other than surgery (chemo- or radiotherapy). Results: The enteral nutrition withdrawal rate after 6 months was 15.5% in the malnutrition group and 84.5% in the normal nutrition group (p = 0.007). In a comparison between groups with and without enteral nutrition after 6 months, a significant association was observed with surgical procedure, nutritional status at admission, and postoperative complications (p < 0.05). Logistic regression analysis showed that the odds of discontinuing enteral nutrition 6 months later were 5.692 (hazard ratio: 1.545–20.962) for malnutrition on admission and 11.921 (hazard ratio: 3.449–41.207) for complications. Conclusion: Regardless of the presence or absence of treatment other than surgery, preoperative nutritional improvement is beneficial for increasing postoperative oral intake. No potential conflict of interest relevant to this article was reported.

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

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study 1 13 EN Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Ken Yamamoto Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Ken Masuda Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Takuji Suzuki Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Shoichi Kuyama Department of Respiratory medicine, NHO Iwakuni Clinical Center Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital Hiroshi Kuraishi Department of Respiratory Medicine, Nagano Red Cross Hospital Ken Yoshihara Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci + GC) administration. However, the prognostic effect of skin disorders in patients with lung squamous cell carcinoma (LSCC) administered Neci + GC is unclear. Objectives: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration. Design: This was a sub-analysis of the retrospective multicenter NINJA study. 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. 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). 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.

MDPI AG Acta Medica Okayama 2076-2607 14 9 2026 Virotherapy for Spinal and Spinal Cord Tumors: Current Evidence and Future Perspectives 2110 EN Koji Uotani Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Takatori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazutaka Yamashita Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenzaburo Matsumoto Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Oda Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Shinohara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tumors of the spine and spinal cord, including primary and metastatic vertebral tumors, intramedullary gliomas, and refractory intradural lesions, are challenging to treat because curative local therapy is limited by the eloquent, nonregenerating neural tissue surrounding them. Oncolytic virotherapy may offer a rational alternative by combining tumor-selective oncolysis with the induction of systemic antitumor immunity, while sparing normal neural cells. This review summarizes the current field of oncolytic viruses, including adenovirus, herpes simplex virus, reovirus, and others, in the context of spinal and spinal cord tumors. Clinical data in the spine remain scarce; however, the rationale is based on histological evidence from sarcomas and other tumors, extensive glioma experience, including diffuse intrinsic pontine glioma, and preclinical activity in nerve sheath and meningioma models. We discuss the telomerase-specific oncolytic adenovirus OBP-301 and its derivatives, whose hTERT-driven replication provides histology-agnostic tumor selectivity, while sparing the telomerase-silent spinal cord. This telomerase dependence, however, limits activity against tumors that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, such as many osteosarcomas and some spinal cord astrocytomas. We also discuss delivery and safety within the confined spinal canal, combination strategies, and future directions, such as extracellular vesicle-mediated delivery and biomarker-guided patient selection. Although clinical translation to the spine will require dedicated preclinical and early-phase studies, virotherapy represents a promising, mechanistically grounded modality for these therapeutically challenging tumors. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2057-3804 11 1 2025 Incidence and survival outcomes of myocarditis and pericardial diseases associated with immune checkpoint inhibitor therapy 26 EN Aya F. Ozaki School of Pharmacy & Pharmaceutical Sciences, University of California Michael Sayer School of Pharmacy & Pharmaceutical Sciences, University of California Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Misako Nagasaka Division of Hematology and Oncology, University of California Benjamin J. Lee Department of Pharmacy, University of California Jean Doh Department of Pharmacy, University of California Ali Naqvi Division of Cardiology, Department of Medicine, University of California Nareh Nowrouzi School of Pharmacy & Pharmaceutical Sciences, University of California Yoshito Zamami Department of Pharmacy, Okayama University Hospital Pranav M. Patel Division of Cardiology, Department of Medicine, University of California Introduction Immune checkpoint inhibitor(ICI) induced cardiac immune related adverse events are challenging to study; Leveraging large data bases like TriNetX global health network may provide needed insights. Methods We performed a retrospective cohort study including patients diagnosed neoplasm and 18 and older when receiving ICI therapy from 1/1/2011 to 12/31/2022. Queried ICD 9/10 codes identified patients experiencing myocarditis, pericarditis, pericardial effusion, and cardiac tamponade within 1 year of ICI initiation. Survival analyses compared one-year overall survival (OS) of patients experiencing cardiac irAEs against propensity score matched populations not experiencing them. Results In 88,928 identified ICI patients, the incidence of myocarditis(0.48%), pericarditis(0.22%), and cardiac tamponade(0.47%) were less than 1% while pericardial effusion occurred in 4.71% of patients. Hazard ratios (HRs) were significantly higher in all cardiac irAE groups: myocarditis (HR:1.26, 95% CI:1.04–1.54, p = 0.02), pericarditis (HR:1.36, 95% CI:1.02–1.82, p = 0.04), pericardial effusion (HR:1.49, 95% CI:1.39–1.59, p < 0.0001), cardiac tamponade (HR:2.15, 95% CI:1.79–2.57, p < 0.0001), and overall pericardial disease (HR:1.46, 95% CI:1.37–1.56, p < 0.0001). There was no significant difference in OS between myocarditis and pericarditis or overall pericardial diseases. Discussion/conclusion Utilizing a uniquely large cohort of ICI patients, this study further shows the rarity of cardiac inflammatory irAEs and highlights their significant impact on patient survival. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2198-3844 2026 SPRED2 Negatively Regulates CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancer e77909 EN Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kun Zhao Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ziyi Wang Department of Advanced International and Information Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Activation of the RAS/RAF/ERK pathway is crucial for adaptive immunity. Here, we provide evidence that Sprouty-related EVH1 domain containing 2 (SPRED2), an endogenous inhibitor of this pathway, negatively regulates CD8+ T cell-mediated antitumor immunity in breast cancer. In EO771 and 4T1 mouse models, Spred2−/− mice exhibit reduced tumor growth, with lower endpoint lung metastatic burden in the 4T1 model, accompanied by increased T-cell infiltration and activation. Spred2−/− T cells show enhanced cytokine expression, proliferation,survival, in vitro cytotoxicity, and memory-like phenotypes, particularly among CD8+ T cells. Adoptive transfer of Spred2−/− CD8+ T cells into tumor-bearing wild-type hosts similarly reduces endpoint lung metastatic burden. MEK inhibition with U0126 attenuates increased interferon-gamma and granzyme B expression in Spred2−/− CD8+ T cells. Transcriptomic analyses reveal an inverse correlation between SPRED2 expression and antitumor CD8+ T cell states in both humans and mice. In tumor-infiltrating T cells from patients with breast cancer, SPRED2low T cells show enriched effector and cytotoxicity programs and are associated with “immune-hot” tumors, whereas survival associations vary with CD8+ T cell context. Collectively, these findings suggest that SPRED2 functions as a cell-intrinsic negative regulator of CD8+ T-cell activation and highlight its potential as a therapeutic target to enhance T cell–based cancer immunotherapy. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2666-5204 22 2025 Prevalence, characteristics, and outcomes of suicide-related out-of-hospital cardiac arrest among patients committing self-harm and suicide-attempts in Japan: A nationwide registry study 100923 EN Takashi Hongo Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Tetsuya Yumoto Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Shunta Jinno Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Yuka Yamamura Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Epidemiology Takafumi Obara Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Tsuyoshi Nojima Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Kohei Tsukahara Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Hiromichi Naito Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Takashi Yorifuji Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Epidemiology Atsunori Nakao Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Background: Suicide-related out-of-hospital cardiac arrest (OHCA) is characterized by extremely low survival rates and represents a considerable global public health concern. This study aimed to investigate the prevalence, characteristics, and outcomes of suicide-related OHCA. Methods: This multicenter, retrospective cohort study is an analysis of data collected from the JAPAN Registry of Self-harm and Suicide Attempts. Patients were divided into two groups, the OHCA group and the non-OHCA group. The primary outcome was death at 30 days. Results: Among 1,960 self-harm and suicide attempts patients, 213 patients (10.9 %) were assigned to the OHCA group and 1,747 (89.1%) were in the non-OHCA group. Patients in the OHCA group were older (44 vs. 33 years old, p < 0.001), and the OHCA group had a higher proportion of males compared to the non-OHCA group (122 [57.3%] vs. 604 [34.6%], p < 0.001). Despite missing and unknown data, lower proportions of psychiatric consultation history (54 [30.8%] vs. 1177 [70.5%], p < 0.001), psychiatric hospitalization history (9 [5.1%] vs. 386 [23.1%], p < 0.001), and previous suicide attempts (16 [9.2%] vs. 807 [48.4%], p < 0.001) were observed in the OHCA group. Risk of death at 30 days was significantly higher in the OHCA group (200 [93.9%] vs. 31 [1.8%], p < 0.001). Conclusion: Suicide-related OHCA was rare and associated with poorer prognosis compared to patients without OHCA. It was more common in middle-aged men without a history of psychiatric care or prior suicide attempts, although the study was limited by missing data. No potential conflict of interest relevant to this article was reported.

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

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

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

MDPI AG Acta Medica Okayama 2075-4426 16 10 2026 Efficacy and Safety of Switching from Nalfurafine to Difelikefalin in Hemodialysis Patients with Refractory Pruritus 489 EN Yoshimasa Sakurabu Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kumiko Tokunaga Sugimoto Clinic Yuko Ogiso Sugimoto Clinic Miwako Motoie Sugimoto Clinic Megumi Yoshitake Sugimoto Clinic Taro Sugimoto Sugimoto Clinic Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Hemodialysis-associated pruritus is common and can substantially impair quality of life. Given its heterogeneous pathophysiology and variable treatment response, individualized therapeutic strategies are needed. This study investigated the prevalence and severity of pruritus and clinical outcomes after switching from nalfurafine to difelikefalin. Methods: Clinical data from 108 maintenance hemodialysis patients whose pruritus severity was assessed using the Numerical Rating Scale (NRS) were retrospectively reviewed. Ten patients with persistent moderate-to-severe pruritus (NRS ≥ 3) despite treatment with nalfurafine were switched to difelikefalin in routine clinical practice, of whom eight completed the 16-week follow-up and were included in the switch group. Eight patients matched for age, sex, dialysis vintage, and baseline NRS served as controls. Changes in NRS scores at weeks 4 and 16, as well as adverse events, were evaluated. Results: Among 108 patients, 21 (20%) had no pruritus, while 20 (18.5%), 47 (43.5%), and 20 (18.5%) had mild, moderate, and severe pruritus, respectively. Of 14 patients receiving nalfurafine, 13 (92.9%) had persistent moderate-to-severe pruritus. In the switch group, mean NRS decreased from 5.9 ± 1.7 at baseline to 2.3 ± 2.3 at week 4 and 2.0 ± 0.9 at week 16 (p = 0.0156 and p = 0.0078, respectively), with no meaningful change in controls. No serious adverse events strongly related to difelikefalin were identified. Conclusions: Pruritus was highly prevalent in this cohort. Switching to difelikefalin was associated with rapid and sustained improvement in patients inadequately responsive to nalfurafine, with favorable tolerability, supporting its potential role as an individualized treatment option. No potential conflict of interest relevant to this article was reported.

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

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

Oxford University Press (OUP) Acta Medica Okayama 2328-8957 12 3 2025 Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory Mycobacterium avium Complex Pulmonary Disease ofaf118 EN Yu Kurahara Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Shiomi Yoshida Clinical Research Center, NHO Kinki Chuo Chest Medical Center , Osaka , Asami Osugi Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Yuya Tanaka Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Takehiko Kobayashi Clinical Research Center, NHO Kinki Chuo Chest Medical Center Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Yohei Kawasaki Department of Biostatistics, Graduate School of Medicine, Saitama Medical University Satoshi Mitarai Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Kazunari Tsuyuguchi Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Background. Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear. 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. 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. Conclusions. Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD. No potential conflict of interest relevant to this article was reported.

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

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

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

Wiley Acta Medica Okayama 1758-5902 19 1 2026 Transcystostomal Bladder Tumor Resection in a Transgender Man After Phalloplasty e70330 EN Takatoshi Moriwake Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nariaki Ozaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Matsumoto Department of Urology, Miyakekai Good Life Hospital Tomoko Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ichiro Tsuboi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kasumi Yoshinaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoaki Yamanoi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzaburo Namba Gender Center, Okayama University Hospital Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction Phalloplasty in transgender men is frequently complicated by a neourethral stricture, precluding standard transurethral access for bladder tumor resection. We describe the first reported case of a transcystostomal bladder tumor resection in a transgender man after a radial forearm free flap (RFFF) phalloplasty. Materials and Surgical Technique A 65-year-old transgender man, 23 years after an RFFF phalloplasty, presented with gross hematuria and a 15-mm posterior bladder tumor. A 7.95 Fr flexible ureteroscope reached the bladder but with markedly limited maneuverability. A two-stage transcystostomal approach was used: a 14 Fr suprapubic cystostomy (SPC) was placed 1 month before resection for tract maturation, followed by balloon dilation and insertion of a 24 Fr resectoscope. The modified Valdivia position enabled simultaneous transcystostomal and transurethral access with gravity-assisted irrigation drainage. Complete tumor resection was achieved without complications, and pathology confirmed noninvasive papillary urothelial carcinoma (pTa, low-grade) with negative margins. A single immediate intravesical instillation of pirarubicin was administered. Surveillance cystoscopy via the cystostomy tract at 3 and 6 months revealed no recurrence; the patient continues to void while standing with the cystostomy catheter capped. Discussion The two-stage transcystostomal approach, combining prior SPC placement, balloon tract dilation, and the modified Valdivia position, enabled safe oncological control while preserving phallic anatomy and standing voiding function. This technique offers a reproducible option for bladder tumor resection in patients with functionally inadequate transurethral access after phalloplasty. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2577-171X 9 4 2026 Varicocelectomy Restores Spermatogenesis in Fontan‐Associated Varicocele: A Two‐Case Series e70206 EN Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Matsumoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takatoshi Moriwake Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nariaki Ozaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Fontan circulation may cause chronic venous hypertension and predispose patients to varicocele and infertility,but the clinical significance of surgical treatment remains unclear. Case Presentation: We describe two patients with Fontan circulation who developed Fontan-associated varicocele (FAVC). A42-year-old man presented with secondary infertility, bilateral varicocele, and progression to azoospermia after Fontan surgery.A 28-year-old man had asthenozoospermia, bilateral varicocele, and repeated failure of assisted reproductive technology. Bothunderwent bilateral microsurgical varicocelectomy with perioperative heparin bridging. Postoperative semen parameters im-proved in both patients, with sperm reappearing in the first case. Conclusion: Varicocelectomy for FAVC may restore spermatogenesis in selected cases, but the risk of postoperative recurrencemay be increased. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Clinical outcomes of near-infrared photoimmunotherapy according to immune checkpoint inhibitor timing and treatment sequence: a multicenter retrospective study EN Takuma Makino Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shohei Fujimoto Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yorihisa Orita Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Tomoyasu Tachibana Department of Otolaryngology Head and Neck Surgery, Japanese Red Cross Society Himeji Hospital Yuto Naoi Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mizuo Ando Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Near-infrared photoimmunotherapy (NIR-PIT) is a novel local treatment for recurrent or metastatic head and neck cancer. However, the clinical significance of immune checkpoint inhibitor (ICI) timing and treatment sequencing remains unclear. This study investigated their association with clinical outcomes after NIR-PIT. Methods This multicenter retrospective study included 44 patients with 48 lesions who underwent initial NIR-PIT between January 2021 and March 2026. The primary analysis compared outcomes according to prior ICI exposure. An exploratory analysis evaluated outcomes according to treatment sequence and timing of ICI administration. The primary endpoint was local control. Secondary endpoints were objective response rate and disease control rate, while overall survival was assessed exploratorily. Results Median local control duration was 253 days, but was 174 days in the prior ICI exposure group and 342 days in the non-prior ICI exposure group (log-rank P = 0.031). Local progression occurred in 69.2–37.1% of lesions, respectively (P = 0.059). Among 45 evaluable lesions, the objective response rate and disease control rate were 60.0–93.3%, respectively. Median overall survival was 866 days. Exploratory analyses suggested potential differences in clinical outcomes according to treatment sequence and ICI timing. Conclusions Prior ICI exposure was associated with poorer local control after NIR-PIT. Exploratory analyses suggested that ICI timing and treatment sequencing may influence clinical outcomes. Treatment sequencing may represent an important consideration when integrating NIR-PIT and ICIs for recurrent or metastatic head and neck cancer. No potential conflict of interest relevant to this article was reported.

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

Japan Surgical Society Acta Medica Okayama 2198-7793 12 1 2026 Single-Incision Laparoscopic Hartmann’s Reversal Using the Stoma Site in a Patient with Perioperative Anaphylaxis cr.26-0206 EN Tsubasa Yanagihara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences INTRODUCTION: Reversal of Hartmann’s procedure is associated with substantial morbidity, and further reduction of surgical invasiveness may be beneficial in selected patients. Perioperative anaphylaxis caused by anesthetic agents or skin antiseptics poses a significant challenge to surgical management. We report a case of stoma-site single-incision laparoscopic Hartmann’s reversal (HR) performed in a patient with severe perioperative allergies. CASE PRESENTATION: A 73-year-old woman underwent an emergency open Hartmann’s procedure with partial cystectomy for perforated sigmoid colon cancer with bladder invasion. After adjuvant chemotherapy, she developed a progressively enlarging giant parastomal hernia that significantly impaired daily activities. Two attempts at HR were aborted because of perioperative anaphylactic shock. Subsequent allergy evaluations suggested rocuronium and chlorhexidine as causative agents, and povidone-iodine was also avoided based on clinical history. Approximately 14 months after the initial surgery, single-incision laparoscopic HR using the stoma site was successfully performed under general anesthesia without neuromuscular blocking agents. Preoperative skin antisepsis was performed using benzalkonium chloride, avoiding both chlorhexidine and povidone-iodine. No additional abdominal incisions were required. The operative time was 2 h 56 min, with minimal blood loss. The postoperative course was uneventful and she was discharged on POD 9. CONCLUSIONS: Stoma-site single-incision laparoscopic HR may represent a useful surgical option for selected patients with severe perioperative allergies to anesthetic agents and skin antiseptics, in whom minimizing abdominal approach and wound-related risks is particularly important. No potential conflict of interest relevant to this article was reported.

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

Japan Surgical Society Acta Medica Okayama 2198-7793 12 1 2026 Successful Lung Transplantation after Plasma Exchange in a Patient with High Thermal Amplitude Cold Agglutinins: A Case Report cr.26-0502 EN Yuya Miyoshi Department of General Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery, Okayama University Hospital Naomi Asano Division of Transfusion and Cell Therapy, Okayama University Hospital Haruchika Yamamoto Department of General Thoracic Surgery, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery, Okayama University Hospital Shuji Okahara Department of General Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery, Okayama University Hospital, Okayama, Okayama, Japan Seiichiro Sugimoto Department of General Thoracic Surgery, Okayama University Hospital Nobuharu Fujii Division of Transfusion and Cell Therapy, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery, Okayama University Hospital INTRODUCTION: 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. 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. 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.

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

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

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

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

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

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

MDPI AG Acta Medica Okayama 2075-4418 16 17 2026 Granular Swollen Epithelial Cells in Native Kidney Biopsies: Prevalence, Clinicopathological Associations and Kidney Outcomes 2822 EN Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Granular swollen epithelial cells (GSECs) have been described primarily in mitochondrial cytopathies, in which they are regarded as a characteristic pathological finding that may aid in the diagnosis of mitochondrial dysfunction; however, their prevalence and clinical significance in native kidney disease remain unclear. We aimed to evaluate the prevalence, clinicopathological associations, and prognostic significance of GSECs in native kidney biopsy specimens. Methods: Among 1165 adults who underwent native kidney biopsy between 2011 and 2024, 501 patients with evaluable medullary tissue were included in this retrospective cohort study. GSECs were defined as enlarged tubular epithelial cells with conspicuous granular cytoplasm in medullary tubules, and cases were classified as GSEC-positive when at least one unequivocal GSEC was identified. Clinical and histopathological characteristics were compared between groups, and kidney outcomes were evaluated using Cox proportional hazards models. Results: The mean baseline eGFR was 60.8 ± 26.3 mL/min/1.73 m2, and the median urinary protein excretion was 1.1 g/gCr. During a median follow-up of 2.3 years, 112 patients (22.3%) reached the composite kidney outcome. GSECs were identified in 18% of native kidney biopsy specimens containing evaluable medullary tissue, and were observed across a broad spectrum of kidney diseases. GSEC positivity was associated with older age and underlying pathological diagnoses but was not associated with baseline kidney function or proteinuria. Kaplan–Meier and multivariable Cox analyses revealed no significant association between GSECs and kidney prognosis. Conclusions: GSECs are not specific to kidney allografts and are observed in a subset of diverse native kidney diseases. Although associated with certain clinical characteristics, no independent association between GSECs and kidney outcomes was observed in this cohort. These findings suggest that GSECs may reflect disease-dependent biological responses to tubular epithelial stress, potentially related to metabolic or mitochondrial alterations, rather than a marker of progressive kidney injury. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2950-1334 14 2026 Clinical phenotypes and the risk factors of mild pulmonary hypertension 100628 EN Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitake Fukuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Misaki Kanezawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: The definition of pulmonary hypertension (PH) was revised as mean pulmonary arterial pressure (mPAP) >20 mmHg from ≥25 mmHg in the recent PH guidelines; however, the characteristics of PH patients with mPAP 21–24 mmHg have not been well described. Methods: A total of 1080 individuals who underwent right heart catheterization (2018–2022) was categorized into 3 groups by mPAP: no PH with mPAP ≤20 mmHg, mild PH with mPAP 21–24 mmHg, and conventional PH with mPAP ≥25 mmHg. We assessed PH subtypes of hemodynamic and clinical classification and compared survival outcomes (all-cause mortality, heart failure hospitalization, lung transplant) using Cox models. Results: Of them, 391 patients (36.2%) were diagnosed as PH including mild PH (n = 137) and conventional PH (n = 254). Phenotypically, mild PH was predominantly characterized by pre-capillary hemodynamics and Group 2 clinical classification. Mild PH is associated with an intermediate prognosis: outcomes are more favorable than in conventional PH but inferior to no PH (HR 1.74 [95% CI 1.15–2.61]). While the two PH phenotypes appear to share comorbidity-related factors, hemodynamic parameters were associated with survival outcomes not in mild PH but in conventional PH. Conclusions: The observation that mild PH constitutes approximately one-third of overall PH cases carries substantial clinical weight. The newly identified mild PH cohort was characterized mainly by pre-capillary and Group 2 subtypes. While mild PH is associated with an intermediate prognosis, comorbidities appear to be the primary determinant of outcomes in this group, unlike in conventional PH where hemodynamics play a larger role. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 9 2026 Event-free survival and recurrence patterns after curative resection for locally advanced head and neck squamous cell carcinoma: single-institution real-world outcomes prior to the introduction of perioperative immunotherapy 1890 1900 EN Takuma Makino Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuto Naoi Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Go Hasegawa Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuto Yamasaki Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Noda Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junya Matsumoto Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Perioperative immune checkpoint inhibitors have improved outcomes for resectable locally advanced head and neck squamous cell carcinoma (HNSCC). However, real-world surgical outcome data based on contemporary endpoints remain limited. Methods We retrospectively analyzed 233 patients who underwent curative-intent surgery for locally advanced HNSCC. Event-free survival (EFS) and overall survival (OS) were evaluated. Unresectable recurrence-free survival (URFS) was explored as an additional endpoint to capture post-recurrence treatment feasibility. Prognostic factors were assessed using Cox proportional hazards models. Results The median follow-up duration was 18.2 months. The 1-year EFS and OS rates were 67.1% and 89.4%, respectively. pN2 or higher disease, venous invasion, and perineural invasion were identified as independent adverse prognostic factors. Recurrence occurred in 34.8% of patients; among these, disease control at the last follow-up was achieved in 61.7% following curative-intent salvage treatment. Salvage surgery was associated with significantly improved post-recurrence survival (p < 0.001). Conclusions This study provides real-world surgical outcome data for resectable locally advanced HNSCC prior to the introduction of perioperative immunotherapy. Recurrence remains a major clinical challenge, with heterogeneous post-recurrence outcomes influenced by treatment feasibility. These findings may help inform interpretation of treatment outcomes and clinical decision-making in the evolving era of perioperative immunotherapy. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0300-8126 54 4 2026 Rectal syphilis: a great imitator of rectal malignancy 2155 2156 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University A 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.

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

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

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 自然脱落した子宮原発 DLBCL に対して Pola-R-CHP 療法と CNS 再発予防を行った１例 58 61 EN Hikaru Osada Department of Hematology, Japanese Red Cross Okayama Hospital Maiko Kimura Department of Hematology, Japanese Red Cross Okayama Hospital Manaka Muneishi Department of Hematology, Japanese Red Cross Okayama Hospital Kozo Murayama Department of Hematology, Japanese Red Cross Okayama Hospital Daigo Niiya Department of Hematology, Japanese Red Cross Okayama Hospital Makoto Takeuchi Department of Hematology, Japanese Red Cross Okayama Hospital Soichiro Fujii Department of Hematology, Japanese Red Cross Okayama Hospital 　A 55-year-old woman presented to her local physician with the chief complaint of genital bleeding. A 22×19-mm mass was noted on the patient's cervix, and during the internal examination the mass auto-amputated. The pathological examination of the auto-amputated mass revealed diffuse large B-cell lymphoma (DLBCL). An examination by F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) showed FDG uptake at physiological levels in the cervix, with no abnormal uptake in other organs. Cervical tissue was sampled after the spontaneous detachment of the cervical mass, and the biopsy of the cervical mass did not reveal findings suggestive of lymphoma. Six courses of chemotherapy with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone (Pola-R-CHP) plus an intramedually injection of methotrexate, cytarabine, and predonisolone (IT-triple), followed by two courses of high-dose intrathecal methotrexate (HD-MTX) were adiministered, and the patient has remained recurrence-free for the more than 8 months since the completion of this treatment. Primary uterine DLBCL is an extremely rare disease with a high rate of recurrence in the central nervous system and a poor prognosis. Our search of the relevant literature identified very few reports describing the prognoses of cases with spontaneous tumor detachment. No potential conflict of interest relevant to this article was reported.

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

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

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

公益社団法人日本放射線技術学会 Acta Medica Okayama 0369-4305 82 10 2026 ベイズ推定を用いたラジオクロミックフィルムのADC値–線量変換法 26-1707 EN Yuki Tanimoto Department of Radiology, NHO Iwakuni Clinical Center Kohei Sugimoto Department of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Masahide Tamori Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Miho Yatsuki Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Shohei Yoshida Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Kazuma Sugahara Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Masataka Oita Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University 【目的】ラジオクロミックフィルムは高い空間分解能を有することから，患者別IMRT品質保証（IMRT QA）に広く利用されている．一方，ピクセル値を線量へ変換するためのキャリブレーションには，複数の既知線量で照射したフィルムが必要であり，作業負担が大きいことから，施設によってはフィルムロット変更時などに限定して実施される場合がある．本研究では，過去のキャリブレーションデータセットと対象フィルムの未照射時ピクセル値を用いてキャリブレーション曲線を推定するベイズ推定モデルを構築し，キャリブレーション作業の効率化を目的としてその有用性を検証した．【方法】TomoHDを用いて取得した93組のキャリブレーションデータセットを解析対象とした．線量および照射からスキャンまでの経過時間を説明変数とする二次多項式回帰モデルを構築した．モデルはスキャナの読み取り方向（縦方向・横方向）ごとに作成し，対象フィルムの未照射時ピクセル値を切片項として推定した．ベイズ推定にはStanを用い，トレースプロットおよびRhat統計量により収束性を評価した．更にモデル性能の評価には，異なるロットのEBT4フィルム10枚を用いて予測ピクセル値と実測値を比較するとともに，線量誤差を評価した．【結果】すべてのモデルでRhatは1.01未満を示し，良好な収束性が確認された．検証用フィルムでは，ピクセル値の誤差は3.6%未満，決定係数（R2）は0.99以上であった．また，線量誤差は24 cGyで平均2.7 cGy（SD 1.3），868.2 cGyで平均37.5 cGy（SD 12.8）であり，最大線量誤差は710.6 cGyにおいて66.6 cGyであった．【結語】本手法は，過去のキャリブレーションデータセットと対象フィルムの未照射時ピクセル値を用いてキャリブレーション曲線を推定できる可能性を示した．また，ラジオクロミックフィルムのキャリブレーション作業の効率化に寄与する可能性が示唆された．今後は患者別IMRT QAに適用し，線量分布評価への影響を検証する必要がある． No potential conflict of interest relevant to this article was reported.

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

AME Publishing Company Acta Medica Okayama 2304-3865 13 5 2024 Primary angiosarcoma of the breast: a literature review 68 EN Yidan Zhu Department of Breast Surgery, Liaoning Cancer Hospital & Institute Shogo Nakamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Yoko Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Xinfeng Zhang Department of Breast Surgery, Liaoning Cancer Hospital & Institute Maki Tanioka Department of Clinical AI Human Resources Development Program, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background and Objective: Primary angiosarcoma of the breast (PBA) is an extremely rare and heterogeneous disease. PBA is difficult to diagnose and has a poor prognosis. In order to better understand the disease and provide evidence-based treatment for PBA patients, a review of the published literature in the English language was conducted. Methods: A literature review in agreement with the PRISMA protocol was conducted. Medline and Cochrane databases were searched for English articles on PBA patients in September 2023 with a predetermined strategy. The articles were categorized and assessed based on hierarchical levels of scientific evidence. Key Content and Findings: A total of 255 articles were identified, among these 137 publications which included 1,888 patients met the criteria for inclusion in the final analysis. No prospective, randomized trials exclusive to PBA have been recognized. This article provides an overview of the most current and comprehensive evidence concerning the epidemiology, etiology, genomic features, clinical presentations, diagnosis, treatment, and prognosis of PBA. Conclusions: Despite the fact that current evidence is largely derived from retrospective studies, database analyses, and case reports, we utilized this information to tackle important clinical questions concerning optimal patient management practices for PBA. Complete surgical excision continues to be the mainstay treatment for PBA. However, the effectiveness of adjuvant therapies is still unclear. This narrative review highlights the urgent need for more rigorously designed research to enhance the management and treatment strategies for PBA. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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

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

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

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

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

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

Elsevier BV Acta Medica Okayama 1059-1311 141 2026 Transient loss of wakefulness with falls in temporal lobe epilepsy: A retrospective single-centre study 254 261 EN Kohei Izumihara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuya Sasaki Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Okazaki Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shun Tanimoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoya Saijo Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyohei Kin Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: 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. 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. 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. 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.

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

Springer Science and Business Media LLC Acta Medica Okayama 1433-8726 44 1 2026 Preoperative membranous urethral length predicts quality-of-life recovery and urinary incontinence after holmium enucleation of the prostate 552 EN Naoya Nagasaki Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takuya Sadahira Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ichiro Tsuboi Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomofumi Watanabe Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shin Kanemoto Department of Urology, Kochi Health Sciences Center Yusuke Tominaga Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoshi Katayama Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shingo Nishimura Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masami Watanabe Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toyohiko Watanabe Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Motoo Araki Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Purpose Holmium laser enucleation of the prostate (HoLEP) relieves bladder outlet obstruction, but postoperative quality-of-life (QOL) recovery and stress urinary incontinence (SUI) differ among patients. We evaluated whether preoperative membranous urethral length (MUL) on MRI predicts QOL recovery and SUI after HoLEP, independent of clinical and surgical factors. Methods This single-center retrospective study included 135 patients with preoperative MRI. MUL was measured on sagittal T2-weighted images. The primary outcome was 6-month International Prostate Symptom Score (IPSS) -QOL ≤ 1. SUI was defined as the use of ≥1 pad per day at 6 months. IPSS-QOL changes were analyzed with generalized estimating equations. For 6-month QOL recovery and SUI, logistic regression was adjusted for age, enucleated weight, prostate volume, baseline QOL, and surgeon. We evaluated thickness of posterior wall of membranous urethral sphincter (TPWMUS), membranous urethral volume (MUV), and a short-MUL/thin-TPWMUS phenotype. Results The 6-month IPSS-QOL ≤ 1 rate was 40.0%; SUI occurred in 19/135 patients (14.1%). Longer MUL was linked to better QOL recovery at every time point (p ≤ 0.015) and independently predicted both 6-month QOL recovery (adjusted odds ratio [aOR] 1.35, 95% CI 1.14–1.61) and lower SUI risk (odds ratio [OR] 0.76, 0.61–0.93), remaining significant after adjustment. Adding MUL improved prediction (AUC for SUI 0.588→0.704; for QOL 0.716→0.760). Across MUL tertiles, QOL recovery rose from 13.9% to 56.1% ,and SUI fell from 20.0% to 2.2%. Short MUL/thin-TPWMUS showed higher SUI and poorer QOL recovery. Conclusions Preoperative MUL on MRI independently predicted QOL recovery and continence after HoLEP. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2352-5789 66 2026 Pembrolizumab-based systemic therapy associated with opportunities for subsequent local treatment in advanced or recurrent neuroendocrine carcinoma of the cervix: a five-case series 102156 EN Naoyuki Ida Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoji Nagao Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Tanaka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Fujikawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Momoko Tanioka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoko Imatani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Tani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hanako Sugihara Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirofumi Matsuoka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Okamoto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Haraga Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: 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. 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. 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. 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.

Wiley Acta Medica Okayama 2050-0904 14 7 2026 A Biologically Dominant Trophoblastic Component Guiding Neoadjuvant EMA/CO in Endometrial Carcinoma: A Clinical Case Report e72982 EN Shinsuke Shirakawa Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shoji Nagao Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Tanaka Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Fujikawa Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoko Imatani Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Momoko Tanioka Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Tani Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hanako Sugihara Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Okamoto Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoyuki Ida Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirofumi Matsuoka Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junko Haraga Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikako Ogawa Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Nakamura Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Yanai Department of Diagnostic Pathology, Okayama University Hisashi Masuyama Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Endometrial 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 AG Acta Medica Okayama 2072-6694 18 5 2026 The New Era of Intraperitoneal Carboplatin in Ovarian Cancer: From Biological Rationale to Clinical Implementation 764 EN Shoji Nagao Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Fujikawa Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Tanaka Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Momoko Tanioka Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoko Imatani Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Tani Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hanako Sugihara Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Okamoto Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirofumi Matsuoka Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoyuki Ida Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junko Haraga Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikako Ogawa Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hisashi Masuyama Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Epithelial 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 Okayama 1932-6203 21 1 2026 Fertility-sparing surgery with neoadjuvant chemotherapy in early and locally advanced cervical cancer: A clinical protocol e0340963 EN Momoko Tanioka Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shoji Nagao Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoyuki Ida Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Tanaka Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Fujikawa Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoko Imatani Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Tani Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hanako Sugihara Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Okamoto Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirofumi Matsuoka Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junko Haraga Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikako Ogawa Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Nakamura Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hisashi Masuyama Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fertility 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 SA Acta Medica Okayama 2234-943X 16 2026 Case Report: Multidisciplinary approach for complete resection of primary advanced low-grade serous ovarian carcinoma involving the iliac vessels and paraspinal region 1762009 EN Naoyuki Ida Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoji Nagao Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Fujikawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Tanaka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Momoko Tanioka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoko Imatani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Tani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hanako Sugihara Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirofumi Matsuoka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Okamoto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Haraga Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Ogawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: 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. 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. 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. Conclusion: Multidisciplinary collaboration can overcome traditional surgical and oncologic barriers, achieving both radicality and quality-of-life preservation in advanced LGSC. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 2 2025 Short-Term and Long-Term Outcomes of Robotic Gastrectomy for Gastric Cancer: A Single-Center, Single-Arm Prospective Study e79063 EN Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshihiko Kakiutchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masahiko Nishizaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Robotic gastrectomy (RG) has emerged as a promising approach for gastric cancer (GC) treatment, offering advantages such as enhanced dexterity, improved visualization, and increased precision. However, its widespread adoption remains limited due to technical complexity, high costs, limited applications, and insufficient evidence. Methods: We conducted a single-center, prospective study to evaluate the safety and feasibility of RG, including robotic total gastrectomy (RTG), robotic proximal gastrectomy (RPG), and robotic distal gastrectomy (RDG) with D1+ or D2 lymphadenectomy, in clinical stage I/II GC. The primary endpoint was the incidence of intraoperative and postoperative complications, while the secondary endpoints included surgical outcomes and long-term prognosis. Results: Seven patients were enrolled. No intraoperative complications or conversions to open surgery occurred. The primary endpoint was met, with no major postoperative complications. RTG had a longer operative time and more lymph nodes dissected than RDG and RPG. The median postoperative hospital stay was 10 days. Recurrence was observed in two cases, one of which achieved long-term survival without chemotherapy. Conclusion: Our findings demonstrate the safety and feasibility of RG for early and advanced GC. Further multicenter studies with larger cohorts are needed to establish its oncological benefits and cost-effectiveness, facilitating broader clinical adoption. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 3 2025 Cholecystectomy Is Linked to Worse Clinical Outcomes in Primary Sclerosing Cholangitis e80184 EN Nozomi Miyake Department of Gastroenterology and Hepatology, Okayama University Kengo Yasugi Department of Gastroenterology and Hepatology, Okayama University Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Recent findings have suggested that gallbladder-derived retinoic acid signaling plays a crucial role in the regeneration of damaged intrahepatic biliary ducts. This retrospective cohort study analyzed the clinical records of 20 patients with primary sclerosing cholangitis (PSC) treated at our hospital between 2013 and 2024. We investigated the clinical implications of gallbladder removal in patients with PSC, a progressive cholangiopathy with limited therapeutic options. We retrospectively analyzed the data of patients with PSC and compared patients with and without prior cholecystectomy to assess the impact on disease progression using the Mayo risk score, Fibrosis-4 (FIB4) index, and other clinical parameters. Our findings indicated that cholecystectomy was associated with worse Mayo risk scores (p = 0.0004) and an elevated FIB4 index (p = 0.021), suggesting a potential link between gallbladder removal and accelerated disease progression. Furthermore, mortality and transplant-free survival analysis revealed significantly worse outcomes in the cholecystectomy group (odds ratio = 21.0, p = 0.032). However, given the retrospective nature and small sample size of this study, selection bias cannot be excluded, and further research is needed to confirm these findings. These findings support the hypothesis that gallbladder-derived factors, such as retinoic acid, may influence PSC progression and highlight the need for further research into therapeutic interventions targeting this pathway. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 2 2025 A Rare Course of Chiari Malformation With Large Syringomyelia Presenting at 54 Years Old e78399 EN Masato Tanaka Orthopedic Surgery, Okayama University Hospital Sneha Sharma Orthopedics, North Delhi Municipal Corporation (DMC) Medical College Kushal H Gori Orthopedic Surgery, Okayama Rosai Hospital Md Shohidullah Orthopedic Surgery, Okayama Rosai Hospital Koji Uotani Orthopedic Surgery, Okayama University Hospital Chiari malformation type 1 (CM1) is considered a congenital condition. The symptoms include severe headache, hypalgesia, and loss of temperature sensation. It constitutes a significant burden among children and young adults. The onset of symptoms of CM1 is more commonly observed in relatively young children and is very rare in those over 50 years old. This study aims to present a rare surgical case of CM1 associated with a large syringomyelia in a 54-year-old man. 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. 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. Gradually enlarging syringomyelia with slight CM1 is rare, but surgeons should consider this condition's possibility. Foramen magnum decompression achieves good results even in cases with a long history of syringomyelia. This new navigation technique provides an excellent result for a large syringomyelia with CM1. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 16 8 2024 Navigation-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 Technique e66070 EN Koji Uotani Navigation-Guided C-arm-Free Minimally Invasive Transforaminal Masato Tanaka Department of Orthopaedic Surgery, Okayama Rosai Hospital Chetan Kumawat Department of Orthopaedic Surgery, Okayama Rosai Hospital Sharvari Gunjotikar Department of Orthopaedic Surgery, Okayama Rosai Hospital Yoshiaki Oda Navigation-Guided C-arm-Free Minimally Invasive Transforaminal Kensuke Shinohara Navigation-Guided C-arm-Free Minimally Invasive Transforaminal Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama Rosai Hospital Shinya Arataki Department of Orthopaedic Surgery, Okayama Rosai Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: 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. 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. 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. 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 LLC Acta Medica Okayama 2168-8184 16 8 2024 A New Minimally Invasive Technique for Thoracolumbar/Lumbar Focal Kyphosis Due to Osteoporotic Vertebral Fracture: A Case Report e66069 EN Masato Tanaka Department of Orthopedic Surgery, Okayama University Hospital Abd El Kader Al Askar Department of Orthopedic Surgery, Okayama Rosai Hospital Chetan Kumawat Department of Orthopedic Surgery, Okayama Rosai Hospital Shashank J Ekade Department of Orthopedic Surgery, Okayama Rosai Hospital Koji Uotani Department of Orthopedic Surgery, Okayama University Hospital Osteoporotic 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 LLC Acta Medica Okayama 2168-8184 17 3 2025 Effects of Pemafibrate and Eicosapentaenoic Acid Ethyl Ester on Endothelial Function in Patients With Hypertriglyceridemia and Coronary Artery Disease: A Study Protocol for a Multicenter, Open-Label Randomised Controlled Trial e81104 EN Trou Miyoshi Cardiovascular Medicine, Okayama University Yasushi Matsuzawa Cardiovascular Medicine, Kumamoto University Masayuki Doi Cardiology, Kagawa Prefectural Central Hospital Shinsuke Yuasa Cardiovascular Medicine, Okayama University Seigo Sugiyama Cardiovascular Medicine, Jinnouchi Hospital Despite intensive low-density lipoprotein cholesterol-lowering therapies effectively reducing cardiovascular events, residual cardiovascular risks remain significant, with hypertriglyceridemia being an important contributing factor. Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, has shown strong triglyceride-lowering effects and potential vascular benefits. Similarly, eicosapentaenoic acid ethyl ester (EPA) has demonstrated cardiovascular protective effects, particularly in patients with hypertriglyceridemia. However, the comparative impact of these agents on endothelial function, a key marker of atherosclerotic progression, has not been thoroughly evaluated in patients with coronary artery disease (CAD). The PRIME (PRospective comparIson of peMafibrate and Eicosapentaenoic acid ethyl ester on vascular functions for hypertriglyceridemia) trial is a multi-center, open-label, randomised trial designed to compare the effects of pemafibrate and EPA on endothelial function in patients with CAD and hypertriglyceridemia. Patients receiving statin therapy with fasting triglyceride levels ≥150 mg/dL will be randomised into two groups: pemafibrate (0.2 mg/day, with possible dose escalation to 0.4 mg/day) or EPA (1800 mg/day, with possible dose escalation to 2700 mg/day). Endothelial function will be assessed with reactive hyperemia index (RHI). The primary endpoint is the change in RHI at 12 weeks. The secondary endpoints include the changes in RHI at 24 weeks, correlations between changes in RHI and changes in lipid biomarkers, and changes in biochemical parameters at 12 and 24 weeks. This study investigates the comparative effects of pemafibrate and EPA on endothelial function, addressing an unmet need in managing residual cardiovascular risk in patients with CAD. The findings will contribute to the optimisation of treatment strategies in patients with CAD and hypertriglyceridemia. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 5 2025 Influence of Wearing Corsets During Radiation Therapy in Patients With Thoracic or Lumbar Spinal Bone Metastases e84093 EN Yoshite Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Eiji Nakata Department of Orthopedic Surgery, Okayama University Hospital Masato Kikuuchi Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Yoshimi Katayama Department of Rehabilitation Medicine, Okayama University Hospital Haruyoshi Katayama Department of Orthopedic Surgery, Okayama University Hospital Takuto Itano Department of Orthopedic Surgery, Okayama University Hospital Masanori Hamada Department of Rehabilitation Medicine, Okayama University Hospital Shinsuke Sugihara Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Background This study aimed to examine the influence of wearing a corset with radiation therapy (RT) on pain, activities of daily living (ADL), and quality of life (QoL) in patients with thoracic or lumbar spinal bone metastases one month after RT. Methodology Fifty-two patients (24 males and 28 females) with thoracic or lumbar spinal bone metastases whose measurements were recorded at our institute between July 2012 and December 2016 were included in this study. Age, sex, ADL, pain, spinal instability, and QoL were investigated in our analyses. Patients were divided into stable (0-6 points) and unstable (7-18 points) groups based on their spinal instability neoplastic score. Patients in the stable and unstable groups performed early mobilization depending on their condition. The unstable group wore corsets. The corsets were soft and were worn for three months from the start of RT. Results The unstable group showed significant improvements in ADL and QoL and a significant reduction in pain one month after RT (P < 0.05). The stable group showed a significant improvement in QoL one month after RT (P < 0.05). Conclusions Corsets were effective for enabling early movement without lowering QoL in patients with spinal instability of thoracic or lumbar bone metastases. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 16 9 2024 Decreased CD3+CD56+ Natural Killer T Lymphocytes and Increased Human Leukocyte Antigen-DR+ Cells in the Inflamed Area of Pouchitis in Ulcerative Colitis Patients e70066 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: 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. 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. 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. 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.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 8 2025 Efficacy of Ibuprofen Gargle for Oral Lichen Planus: A Single-Center, Placebo-Controlled, Double-Blind, Randomized Crossover Study Trial e91242 EN Yasumasa Kakei Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Yumi Kitahiro Pharmacy, Kobe University Graduate School of Medicine Takeshi Ioroi Pharmacy, Kobe University Graduate School of Medicine Masahiko Kashin Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Masaki Kobayashi Oral and Maxillofacial Surgery, Shin-suma General Hospital Asami Morioka Pharmacy, Kobe University Graduate School of Medicine Kazuhiro Yamamoto Integrated Clinical and Basic Pharmaceutical Sciences, Okayama University Takumi Hasegawa Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Ikuko Yano Pharmacy, Kobe University Graduate School of Medicine Masaya Akashi Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Purpose: Oral lichen planus (OLP) is a chronic, refractory type of stomatitis characterized by abnormal keratinization and often accompanied by pain. The best treatment for OLP, particularly for pain management, remains unclear. This study focuses on the short-term efficacy of ibuprofen gargle for pain relief in patients with OLP. Methods: In this crossover study, 24 patients with painful OLP were enrolled. One group received an ibuprofen gargle (0.6%) on days one and three to five and a placebo on day two. The other group received a placebo on day one and ibuprofen on days two to five. The primary outcome was the change in pain level, measured by a Visual Analogue Scale (VAS) before and after gargling on days one and two. Additionally, changes in each domain of the Patient-Reported Oral Mucositis Symptom (PROMS) scale were evaluated from days one to five. Results: There was no significant difference in the degree of reduction in pain VAS values between the ibuprofen and placebo groups before and five and 15 minutes after use of the gargle. However, the PROMS scale showed a significant reduction in dietary restrictions (p = 0.032) in favor of the ibuprofen gargle compared to baseline. Conclusion: Ibuprofen gargle may help alleviate dietary restrictions associated with oral intake in patients with OLP who experience pain. Trial registration: This study was registered with the Japan Registry of Clinical Trials (jRCT) (jRCTs051220009). No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 16 11 2024 Curve Progression After the Termination of Bracing for Adolescent Idiopathic Scoliosis: Usefulness of Combining the Proximal Femur Maturity Index (PFMI) and Risser Staging e73395 EN Hisakazu Shitozawa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruo Misawa Department of Orthopaedic Surgery, Ryusou Orthopaedic Hospital Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Tomoko Tetsunaga Department of Orthopaedic Surgery, Okayama University Hospital Kensuke Shinohara Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Oda Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masataka Ueda Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Takatori Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazutaka Yamashita Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background The brace therapy for adolescent idiopathic scoliosis (AIS) typically ends upon the end of growth. However, determining the timing of growth cessation can be challenging. The purpose of this study was to evaluate the utility of the proximal femur maturity index (PFMI), which can be assessed simultaneously with Risser staging without requiring additional radiation exposure, in determining the appropriate timing to terminate bracing. To achieve this, we investigated the relationship between skeletal maturity at the end of bracing, post-bracing curve progression, and height growth in patients who had been successfully treated with a brace. Methods Between April 2010 and March 2021, a total of 84 female patients with AIS who started bracing at our hospital with an initial Cobb angle of 20-40 degrees were included. All patients were followed for at least one year after brace termination. Height and radiographic parameters (Risser staging, PFMI, Cobb angle) were retrospectively collected. Results At the end of the bracing period, patients were categorized into Risser stage 4 (85.7%) and 5 (14.3%). By the last follow-up, patients with Risser stage 4 experienced an average main curve progression of 1.8°, whereas those with Risser stage 5 had an average progression of −0.3° (P = 0.03). Patients with Risser stage 4 were further divided into PFMI grade 5 (59.7%) and 6 (40.3%). Significant curve progression was observed in patients with PFMI grade 5 (average: 3.0°) compared to grade 6 (average: -0.6°) (P < 0.0001). The mean height growth was 1.9 cm/year for PFMI grade 5, and 0.3 cm/year for grade 6, with significant differences between these groups (P < 0.001). Conclusions PFMI allowed further categorization within Risser stage 4: PFMI grade 5 indicated remaining growth potential and risk of postbracing curve progression, whereas grade 6 indicated growth cessation. The combined use of Risser staging and PFMI, both evaluable through the same whole-spine radiograph, may provide a more accurate prediction of growth cessation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 16 11 2024 Assessment of All-Inside Sutures to the Posteromedial Capsule in Medial Meniscus Posterior Root Repair: Findings From a Retrospective Three-Dimensional Magnetic Resonance Imaging Study e73778 EN Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yokoyama Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Tamura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koki Kawada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsubasa Hasegawa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose: Medial meniscus (MM) posterior root tears (PRT) cause pathological medial extrusion (MMME) and posterior extrusion (MMPE), particularly during knee flexion, leading to rapidly progressive knee osteoarthritis. We investigated pre- and postoperative MM extrusion using three-dimensional open magnetic resonance imaging (MRI) following two pullout repair techniques: two simple stitches (TSS) and TSS with an additional all-inside suture to the posteromedial capsule (TSS-PM). We hypothesized that TSS-PM would decrease MM extrusion more effectively than TSS. Methods: Thirty patients who underwent MM posterior root repair were retrospectively evaluated. TSS and TSS-PM techniques were used for pullout repair. Open MRI was performed at 10/90° of knee flexion preoperatively and three months postoperatively. MMME, MMPE, and MM extrusion volume (MMEV) were measured and compared between groups. Results: At 90° of knee flexion, postoperative MMPE and MMEV were significantly decreased compared to preoperative values in both the TSS and TSS-PM groups. Furthermore, a significantly decreased ΔMMPE was observed in the TSS group compared to the TSS-PM group, whereas no significant difference was observed in ΔMMEV. Conclusion: TSS and TSS-PM repair techniques helped decrease MMEV at 90° of knee flexion, whereas a significantly decreased ΔMMPE was observed in the TSS group at 90° of knee flexion. An additional all-inside suture at the posteromedial capsule may be insufficient to decrease MMEV and may negatively affect the decrease in ΔMMPE at 90° of knee flexion. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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

Wiley Acta Medica Okayama 2090-6447 2026 1 2026 Carcinoma ex Pleomorphic Adenoma With an Epithelial‐Myoepithelial Carcinoma Component in the Submandibular Gland: A Case Report EN Tomohiro Yasuhara Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Masui Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Takakura Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiji Iwata Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichi Kadoya Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koki Umemori Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norie Yoshioka Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Carcinoma ex pleomorphic adenoma (CXPA) is an uncommon malignant salivary gland tumor arising from pleomorphic adenoma, whereas epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland malignancy. CXPA with an EMC component in the submandibular gland is uncommon. Case Report: A 65-year-old man presented with a painless, firm mass in the left submandibular region and weakness of the left lower lip. Computed tomography and magnetic resonance imaging demonstrated an irregular submandibular mass, and FDG-PET/CT showed increased uptake (maximum standardized uptake value, 9.2). Core biopsy suggested pleomorphic adenoma; however, the clinical and radiological findings strongly indicated malignancy. Incisional biopsy was therefore performed under general anesthesia, with a plan to proceed to definitive treatment if malignancy was confirmed. Intraoperative histopathological examination revealed a malignant salivary gland tumor, and tumor resection with neck dissection was completed during the same procedure. Histopathological examination showed invasive CXPA with an EMC component, accompanied by extracapsular invasion exceeding 6 mm, perineural invasion, and extension into adjacent muscle (pT3N0). Although surgical margins were negative, pulmonary metastases developed 12 months after surgery, followed by suspected pleural dissemination and spinal canal extension. The patient declined further aggressive treatment and died of the disease 48 months after surgery. Conclusion: This case highlights the importance of integrating clinical, radiological, and pathological findings for accurate diagnosis of salivary gland tumors, particularly when biopsy results are inconsistent with clinical suspicion. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 2050-0904 14 7 2026 Custom‐Made Mouthpiece‐Assisted Oral Cryotherapy During Hematopoietic Stem Cell Transplantation in a Patient With Hemimaxillectomy‐Related Oroantral Communication: A Case Report e73156 EN Kumiko Matsuzaki Division of Hospital Dentistry, Okayama University Hospital Fuminobu Miyazaki Dental Laboratory Division, Okayama University Hospital Yasuji Motoyama Dental Laboratory Division, Okayama University Hospital Seiko Takeda Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital Takuo Kuboki Dental Laboratory Division, Okayama University Hospital Yoshihiko Soga Division of Hospital Dentistry, Okayama University Hospital A custom-made mouthpiece enabled safe oral cryotherapy in a patient with extensive oroantral communication after hemimaxillectomy and may also be applicable to other patients with communication between the oral cavity and the maxillary sinus or nasal cavity. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0941-4355 34 8 2026 Incidence and impact of odontogenic infection-related febrile episodes during perioperative doxorubicin-cyclophosphamide or docetaxel-cyclophosphamide chemotherapy for breast cancer 747 EN Yoshihiko Soga Division of Hospital Dentistry, Okayama University Hospital Kumiko Matsuzaki Division of Hospital Dentistry, Okayama University Hospital Hirotaka Kosaki Division of Hospital Dentistry, Okayama University Hospital Tomoko Kishimoto Division of Hospital Dentistry, Okayama University Hospital Aiko Yoshitomi Division of Hospital Dentistry, Okayama University Hospital Makoto Kajizono Department of Pharmacy, Okayama University Hospital Takashi Makita Department of Pharmacy, Okayama University Hospital Yuta Tanaka Department of Pharmacy, Okayama University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Surgery, Kawasaki Medical School General Medical Center Background Doxorubicin-cyclophosphamide (AC) and docetaxel-cyclophosphamide (TC) are standard perioperative chemotherapy regimens for breast cancer. Febrile neutropenia (FN) is a common adverse event, and odontogenic infections may contribute to febrile episodes. This study was performed to investigate the incidence and impact of febrile episodes clinically associated with odontogenic infections during AC and TC chemotherapy. 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. 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%. Conclusions Febrile episodes clinically associated with odontogenic infections occurred in approximately 7%–8% of patients with breast cancer receiving perioperative AC or TC chemotherapy, predominantly during the first cycle. Odontogenic infections should be considered one possible source of febrile episodes during treatment. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1323-8930 75 3 2026 Outcomes following the discontinuation of biologic therapy in patients with severe asthma 400 408 EN Tadao Nagasaki Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital Hisako Matsumoto Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Takashi Iwanaga Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Kazuto Matsunaga Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University Kiyoshi Sekiya Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Tomoya Harada Department of Multidisciplinary Internal Medicine, Division of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University Shogo Sakurai Department of Respiratory Medicine, Shizuoka General Hospital Norihiro Harada Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine Toshiyuki Koya Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Koichi Fukunaga Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine Takeshi Kaneko Department of Pulmonology, Yokohama City University Graduate School of Medicine Kazuhisa Asai Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University Yuko Komase Department of Respiratory Medicine, St.Marianna University School of Medicine, Yokohama Seibu Hospital Yasuhiro Gon Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine Akihiko Tanaka Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine Hironori Sagara Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine Hironobu Sunadome Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University Tatsuya Nagano Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Yoichi Nakamura Medical Center for Allergic and Immune Diseases, Yokohama City Minato Red Cross Hospital Akio Niimi Department of Respiratory Medicine, Allergy, and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences Noboru Hattori Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University Takashi Hajiro Department of Respiratory Medicine, Tenri Hospital Hajime Fujimoto Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine Masayuki Hojo Division of Respiratory Medicine, National Center for Global Health and Medicine Nobuaki Miyahara Department of Medical Technology, Okayama University Graduate School of Health Sciences Masafumi Yamaguchi Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science Kimiko Tsuji Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Akiko Sano Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Ryuta Haraguchi Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Hiroyuki Sano Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Masato Muraki Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital Yuji Tohda Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Background: Biologic therapies are pivotal in managing severe asthma. Despite their efficacy, some patients discontinue biologics, with varying outcomes. Predictors of successful versus unsuccessful discontinuation remain poorly defined. This study aimed to identify clinical factors associated with post-discontinuation outcomes in a real-world practice. 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. 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. 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.

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

Springer Science and Business Media LLC Acta Medica Okayama 1756-0500 19 1 2025 Plasma expression levels of microRNA-101 are downregulated in patients with Parkinson’s disease 19 EN Tomohiro Omura Department of Pharmacy, Kobe University Hospital Hiroki Nishiguchi Department of Pharmacy, Kobe University Hospital Haruka Kaneda Department of Pharmacy, Kobe University Hospital Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Kotaro Itohara Department of Pharmacy, Kobe University Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyasu Sakane Department of Pharmaceutical Technology, Kobe Pharmaceutical University Ikuko Yano Department of Pharmacy, Kobe University Hospital Objective Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Endoplasmic reticulum (ER) stress contributes to PD pathogenesis, with the ER-associated degradation (ERAD) system playing a protective role. HRD1, an ER-resident ubiquitin ligase, and its stabilizer SEL1L are involved in ERAD and neuronal survival. This study investigated alterations in the plasma levels of microRNA-101 (miR-101), which targets SEL1L, in patients with PD, and its potential role as a biomarker. Results Plasma miR-101 levels in patients with PD significantly decreased compared with those in healthy controls. Receiver operating characteristic curve analysis demonstrated that miR-101 could moderately discriminate patients with PD from healthy individuals (area under the curve = 0.781, 95% confidence interval = 0.547–1.00). The optimal cutoff, as determined by the Youden index, was 0.737 (expression ratio relative to that in the healthy control group), yielding a sensitivity of 50% and specificity of 100%. These results suggested that reduced plasma miR-101 expression may reflect the pathophysiological state of PD, and miR-101 has potential as minimally invasive biomarker for PD. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 65 8 2026 Autopsy Case of a Disseminated Cytomegalovirus Infection with a Cutaneous Ulcer Mimicking Rheumatoid Vasculitis 1172 1177 EN Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Yukichika Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoharu Ishida Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Ohki Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences A 60-year-old woman with rheumatoid arthritis and an impaired consciousness was referred to our hospital. Prior to transfer, the patient underwent intensified immunosuppressive therapy under a diagnosis of rheumatoid vasculitis that had developed in her buttocks. Upon hospitalization, she developed severe multiorgan failure and hemophagocytic syndrome. Four days after admission, both blood cytomegalovirus (CMV) antigenemia and the DNA load were markedly elevated. Despite intensive care, the patient died. Later, a histopathological examination revealed that the cutaneous manifestation represented CMV disease, not rheumatoid vasculitis, as was initially suspected. Failure to identify CMV as the underlying cause may result in the inappropriate administration of immunosuppressive therapy, potentially worsening the patient's condition. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-6367 32 4 2026 Spatial Transcriptomics Analysis of Macrophage-to-Myofibroblast Transition in Bronchiolitis Obliterans Following Hematopoietic Stem Cell Transplantation 454 465 EN Akira Yamamoto Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Yusuke Naoi Center for Comprehensive Genomic Medicine, Okayama University Hospital Tomohiro Nagano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Saya Kubota Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Kambara Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine Kanako Fujiwara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiki Terao Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Oyama Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Kunihiro Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Hospital Takumi Kondo Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Bronchiolitis obliterans (BO) is a severe, fibrotic manifestation of chronic graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Macrophage-derived TGF-β is linked to GVHD-related fibrosis; however, its role in BO remains unclear. Given emerging evidence of macrophage-to-myofibroblast transition (MMT) in fibrosis, this study aimed to investigate whether MMT contributes to BO development. We analyzed lung samples from 3 HSCT recipients with BO who underwent lung transplantation, with tissues from 2 patients with lung cancer as controls. Immunofluorescent staining for CD68, CD206, and α-SMA was used to identify cells undergoing MMT. Spatial transcriptomics was performed to profile gene expression in foamy macrophages across anatomical regions and histological stages, compared to control peribronchiolar regions. Immunostaining showed strong co-expression of CD68, CD206, and α-SMA in foamy macrophages within and surrounding bronchioles in BO samples, with minimal expression in controls, suggesting MMT involvement. In BO, spatial transcriptomics revealed upregulation of macrophage- and TGF-β signaling genes, with distinct stage- and region-specific gene expression patterns. Unsupervised clustering revealed a shift from inflammation to fibrosis. These findings indicate that MMT contributes to fibrosis in BO. Gene expression shifts from inflammation to fibrosis as the disease advances, underscoring the importance of early intervention. No potential conflict of interest relevant to this article was reported.

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

American Society of Tropical Medicine and Hygiene Acta Medica Okayama 0002-9637 114 3 2026 A Case of Heavy Paragonimiasis Involving a Multi-Organ Presentation with Hypereosinophilia and Hepatic Migration 486 489 EN Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Yohei Manabe Department of Pharmacy, Okayama University Hospital Mio Kokubo-Tanaka Division of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki Haruhiko Maruyama Division of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki Fumio Otsuka Department of General Medicine, Okayama University Hospital Paragonimiasis 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.

Elsevier BV Acta Medica Okayama 1572-1000 58 2026 Pathological features of residual head and neck cancer after near-infrared photoimmunotherapy: implications of an unfavorable tumor immune microenvironment 105422 EN Takuma Makino Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Department of Hematopathology, Okayama University Graduate School of Health Sciences Asami Nishikori Department of Hematopathology, Okayama University Graduate School of Health Sciences Yuto Naoi Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose: Near-infrared photoimmunotherapy has been approved in Japan for unresectable locally advanced or recurrent head and neck cancer. While this therapy theoretically induces selective necrosis of epidermal growth factor receptor-expressing tumor cells following administration of cetuximab sarotalocan sodium and irradiation with 690-nm light, residual disease is not uncommon in clinical practice. The mechanisms underlying such persistence remain poorly understood. Methods: We examined two patients with head and neck squamous cell carcinoma who underwent salvage resection due to residual disease after four cycles of near-infrared photoimmunotherapy. Resected specimens were subjected to histopathological evaluation, including immunohistochemistry for epidermal growth factor receptor, cluster of differentiation 8, programmed cell death protein 1, and forkhead box P3 proteins. Results: In both cases, residual tumor cells were predominantly localized in the superficial mucosal layers, while deeper layers were replaced by fibrosis. All residual tumors retained expression of epidermal growth factor receptor. Lymphocytic infiltration was sparse, with scattered cluster of differentiation 8-positive cells but few programmed cell death protein 1-positive or forkhead box P3-positive lymphocytes. These findings suggest that the tumor microenvironment surrounding residual tumors may have been unfavorable for the induction of robust antitumor immune responses. Conclusion: Residual tumors after near-infrared photoimmunotherapy can occur despite adequate laser irradiation and epidermal growth factor receptor expression. Our observations imply that insufficient immune activation within the tumor microenvironment may contribute to treatment resistance. Further characterization of the post-photoimmunotherapy tumor microenvironment will be essential to better understand treatment mechanisms and to optimize therapeutic efficacy. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 1472-6831 26 1 2026 Differences in understanding of explanations and risk perception between dental staff and patients: a questionnaire study at a university hospital 1050 EN Shiho Otomo School of Environment and Society, Institute of Science Tokyo Maoko Fujisaki School of Environment and Society, Institute of Science Tokyo Risako Yanagase School of Environment and Society, Institute of Science Tokyo Kanako Noritake Institute of Science Tokyo Hospital, Institute of Science Tokyo Yoshinobu Yanagi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taro Sugihara School of Environment and Society, Institute of Science Tokyo Background and purpose: Proper self-care necessitates behavioral changes, underpinned by correct knowledge. Oral health literacy (OHL) research constitutes a fundamental foundation for fostering effective self-care practices. However, the extent of the awareness gap between patients and dental staff regarding explanations provided during treatment remains unknown. This descriptive study was conducted to serve as an initial step in bridging this gap. Methods: Questionnaires were distributed to 92 dental staff members and 205 patients at university hospitals, with responses from 72 staff members and 157 patients. Results: In the category assessing understanding of explanations (patient vs. dental staff), patients’ self-assessed understanding exceeded the dental staff’s estimates in three aspects: disease name (p = 0.03, r = 0.17), treatment period (p = 0.01, r = 0.21), and pain relief (p = 0.01, r = 0.19). Regarding health self-awareness, the high-scoring group significantly outperformed the low-scoring group in explaining treatment risks (p = 0.03, r = 0.21) and understanding (p = 0.01, r = 0.23). Nevertheless, patients’ risk recognition was higher than that of dental staff in three aspects: root canal treatment (p < 0.01, r = 0.23), holes in the teeth (p < 0.01, r = 0.24), and bleeding during toothbrushing (p = 0.02, r = 0.17). Questions on “crack” (p = 0.02, r = 0.21) by sex, holes in one’s own teeth (p = 0.05, r = 0.03), and feeling one’s own teeth wobble (p < 0.01, r = 0.07) in the intergenerational comparison showed significant differences. Conclusion: Dental staff should not be satisfied merely with having "explained" something to the patient; they must engage in a confirmation process to verify the patient's correct understanding of the information or to identify excessive anxiety. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2090-6447 2026 1 2026 A Rare Case of Hyperplastic Dental Follicle Presenting With an Unusually Large Radiolucent Area 2879891 EN Satoshi Otsuki Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichi Kadoya Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chizuru Kobayashi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kawazu Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hyperplastic dental follicle (HDF) is a rare odontogenic hamartomatous lesion typically associated with unerupted teeth in children and adolescents and is often found incidentally on radiographic imaging. HDF usually presents as a pericoronal radiolucency of 2–3 mm in diameter and is commonly difficult to distinguish from dentigerous cysts on radiographs. We report an unusual case of HDF in an 11-year-old male who was referred for evaluation of delayed eruption of the left maxillary canine. Panoramic radiography and cone-beam computed tomography (CBCT) revealed a remarkably large radiolucent area, with a maximum dimension of 25.3 mm. The initial clinical diagnosis was a dentigerous cyst; however, incisional biopsy revealed solid tissue characteristics, and histopathological examination confirmed HDF, with no evidence of cystic lining, neoplastic transformation, or inflammation. Following the patient′s and parents′ preference for complete removal, resection of the lesion together with extraction of the impacted canine was performed under general anesthesia. At the 6-month follow-up, no recurrence was observed and bone regeneration was confirmed on radiographic examination. This case underscores the diagnostic challenge posed by atypical radiographic findings and highlights the necessity of histopathological confirmation. Given the exceptional size and potential for recurrence, long-term follow-up is warranted. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6643 18 11 2026 GLP-1 Receptor Agonists in the Rehabilitation of Patients with Heart Failure: Mechanisms, Clinical Evidence, and Future Perspectives 1688 EN Luh Oliva Saraswati Suastika Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuko K. Bando Department of Molecular Physiology and Cardiovascular Biology, Mie University Graduate School of Medicine Keiji Hoshino Division of Cardiology, Gunma Prefectural Cardiovascular Center Norimichi Koitabashi Division of Cardiology, Gunma Prefectural Cardiovascular Center Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Heart failure (HF) remains associated with high morbidity and mortality, with heart failure with preserved ejection fraction (HFpEF) becoming increasingly prevalent and therapeutically challenging despite advances in pharmacological and rehabilitative care. Beyond their glucose-lowering effects, glucagon-like peptide-1 receptor agonists (GLP-1RAs) confer cardiometabolic benefits and may serve as effective adjuncts to cardiac rehabilitation (CR), particularly in obese patients with HFpEF. Obesity plays a central role in the pathophysiology of HFpEF, and GLP-1RAs promote weight loss, reduce insulin resistance and leptin signaling, and improve hemodynamic and metabolic abnormalities associated with HFpEF. Accumulating evidence suggests that the benefits of GLP-1RAs are phenotype-specific and more pronounced in patients with HFpEF than in patients with HF with reduced ejection fraction. Current clinical guidelines recommend GLP-1RAs for patients who have type 2 diabetes mellitus and established cardiovascular (CV) disease or are at high CV risk, with recent updates recognizing their potential benefits in patients with HFpEF and obesity. Cardiac rehabilitation, delivered through multidisciplinary programs, remains a cornerstone of HF management. Although caloric restriction and aerobic exercise can be beneficial in patients with HFpEF and obesity, these interventions alone are often insufficient. Sarcopenia is common in older patients with HFpEF and contributes to adverse outcomes, underscoring the importance of incorporating resistance training into CR programs. The most frequent adverse effects of GLP-1RAs are gastrointestinal events, which are generally mild to moderate but may lead to treatment discontinuation in some patients. Future studies should investigate the potential synergistic effects of GLP-1RAs and CR, clarify their long-term safety and efficacy in HF populations, and define their role beyond obese HFpEF phenotypes. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0300-9572 225 2026 Decline in rescue breathing and its impact on outcomes in pediatric out-of-hospital cardiac arrest due to drowning: a nationwide study, 2012–2023 111049 EN Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Rescue breathing is considered essential in pediatric out-of-hospital cardiac arrest (OHCA) due to drowning, a type of asphyxial arrest where hypoxia precedes circulatory collapse. However, the increasing promotion of compression-only CPR (CO-CPR) may have contributed to changes in bystander CPR practices, including a decline in rescue-breathing CPR (RB-CPR). Whether such temporal changes have influenced outcomes in pediatric drowning OHCA remains unclear. Methods: We analyzed nationwide data from the All-Japan Utstein Registry (2012–2023), including pediatric OHCA patients (≤17 years old) whose arrests were caused by drowning and received bystander CPR from laypersons. Patients were categorized into RB-CPR and CO-CPR groups. The primary outcome was 30-day mortality; secondary outcomes included prehospital absence of return of spontaneous circulation (ROSC) and 30-day unfavorable neurological survival, defined as Cerebral Performance Category score 3–5. We used multivariable Poisson regression to estimate adjusted risk ratio (aRR) and conducted analyses by age and witnessed status. Results: Among 740 eligible patients, 41.6% received RB-CPR and 58.4% received CO-CPR. The proportion of RB-CPR declined over the study period. CO-CPR was associated with higher 30-day mortality (aRR 1.38, 95% CI 1.14–1.67), higher prehospital absence of ROSC, and worse neurological outcomes compared with RB-CPR. The adverse association of CO-CPR was most pronounced in unwitnessed arrests, where ventilation may be particularly important. Conclusions: In pediatric drowning OHCA, CO-CPR was associated with worse survival and neurological outcomes than RB-CPR. These findings underscore the necessity for rescue breathing and the importance of ventilation-focused bystander CPR training in pediatric and drowning-related scenarios. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2431 26 1 2026 Sebastidae-specific food allergy causing anaphylaxis: a pediatric case report and fish allergen analysis 628 EN Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Uda Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Ikeda Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Fish allergy affects approximately 0–0.3% of the population. Parvalbumin is the major allergen in fish allergy, and patients with fish allergy sensitized to parvalbumin demonstrate allergic reactions to various fish species. However, a subset of patients exhibits allergic responses to only specific fish species. Fish of the Sebastidae family, widely consumed in Asian, North American, and European countries, has rarely been reported as an allergenic trigger. Case presentation A 14-year-old Japanese boy visited our clinic for evaluation of fish allergy after experiencing allergic reactions to Sebastes alutus (Alaskan rockfish). He developed respiratory symptoms, eyelid edema, and skin erythema after consuming a meal containing Sebastes alutus, suggesting anaphylaxis; however, he was able to consume many other fish species without any issues. Skin prick tests and basophil activation tests using fish species from the Sebastidae family showed positive reactions, whereas other fish species that the patient could tolerate showed negative reactions. Immunoblot analysis performed to identify the causative allergen revealed two IgE-binding bands (17 and 110 kDa) in Sebastidae, distinct from parvalbumin. Mass spectrometry identified these proteins as alpha-actinin-3b, ATPase sarcoplasmic/endoplasmic reticulum Ca2 + transporting 1, and several myosin-related proteins. Conclusions This case highlights the need for clinicians to recognize fish allergy specific to the Sebastidae family. Identifying the causative non-parvalbumin allergens would improve understanding of fish allergy diversity and individualized dietary management for patients. Additional cases and detailed analyses are necessary to identify the specific allergens involved in Sebastidae allergy. No potential conflict of interest relevant to this article was reported.

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

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

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

American Society for Clinical Investigation Acta Medica Okayama 1558-8238 136 10 2026 Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLC e195021 EN Kohsuke Isomoto Department of Medical Oncology, Kindai University Faculty of Medicine Koji Haratani Department of Medical Oncology, Kindai University Faculty of Medicine Takahiro Tsujikawa Department of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Yusuke Makutani Department of Surgery, Kindai University Faculty of Medicine Masayuki Takeda Department of Medical Oncology, Kindai University Faculty of Medicine Kimio Yonesaka Department of Medical Oncology, Kindai University Faculty of Medicine Kaoru Tanaka Department of Medical Oncology, Kindai University Faculty of Medicine Tsutomu Iwasa Department of Medical Oncology, Kindai University Faculty of Medicine Kazuko Sakai Department of Genome Biology, Kindai University Faculty of Medicine Kazuto Nishio Department of Genome Biology, Kindai University Faculty of Medicine Akihiko Ito Department of Pathology, Kindai University Faculty of Medicine Kazuhiko Nakagawa Department of Medical Oncology, Kindai University Faculty of Medicine Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine BACKGROUND. Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 axis have revolutionized metastatic non–small cell lung cancer (mNSCLC) treatment. However, disease progression remains a concern, and the role of the complex tumor microenvironment (TME) in treatment failure is not fully understood. 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. 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. 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.

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

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 47 12 2024 Staphylococcus aureus δ-Toxin Induces Ca2+ Influx-Independent Degranulation of Murine Cultured Mast Cells 2058 2064 EN Kang Liu Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Tomoaki Katayama Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hitomi Sato Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuho Hamaoka-Tamura Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Michiko Saito Bioscience Research Center, Kyoto Pharmaceutical University Kazuyuki Furuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoshi Tanaka Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Cutaneous 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.

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

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

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 0732-183X 43 16 2025 Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin + Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial 1886 1897 EN Hiroaki Hiraga Musculoskeletal Oncology, NHO Hokkaido Cancer Center Ryunosuke Machida Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Akira Kawai Musculoskeletal Oncology, National Cancer Center Hospital Toshiyuki Kunisada Orthopaedic Surgery, Faculty of Medicine, Okayama University Tsukasa Yonemoto Orthopaedic Surgery, Chiba Cancer Center Makoto Endo Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Yoshihiro Nishida Department of Rehabilitation Medicine, Nagoya University Hospital Akihito Nagano Orthopaedic Surgery, Gifu University School of Medicine Keisuke Ae Orthopaedic Surgery, Cancer Institute Hospital Shinichirou Yoshida Orthopaedic Surgery, Tohoku University Graduate School of Medicine Kunihiro Asanuma Orthopaedic Surgery, Mie University Junya Toguchida Department of Tissue Regeneration, Center for Induced Pluripotent Stem Cell Research and Application, Institute for Frontier Medical Sciences, Kyoto University Taisuke Furuta Orthopaedic Surgery, Hiroshima University Robert Nakayama Department of Orthopaedic Surgery, Keio University School of Medicine Toshihiro Akisue Orthopaedic Surgery, Kobe University Toru Hiruma Bone and Soft Tissue Tumour Surgery, Kanagawa Cancer Center Takeshi Morii Orthopaedic Surgery, Kyorin University Hideki Nishimura Orthopaedic Surgery, Kagawa University Hospital Koji Hiraoka Orthopaedic Surgery, Kurume University Hospital Masanobu Takeyama Orthopaedic Surgery, Yokohama City University Hospital Makoto Emori Orthopaedic Surgery, Sapporo Medical University Hospital Satoshi Tsukushi Orthopaedic Surgery, Aichi Cancer Center Hiroshi Hatano Musculoskeletal Oncology, Niigata Cancer Center Hospital Hiroyuki Kawashima Orthopaedic Surgery, Niigata University Medical & Dental Hospital Kazuo Isu Orthopaedic Surgery, Higashi Sapporo Hospital Kazuhiro Tanaka Advanced Medical Sciences, Oita University Faculty of Medicine Tomoko Kataoka Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Haruhiko Fukuda Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Yukihide Iwamoto Orthopaedic Surgery, Kyushu Rosai Hospital Toshifumi Ozaki Orthopaedic Surgery, Faculty of Medicine, Okayama University Purpose Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m2 [4g/m2 once on day 1, then 2g/m2 once on days 2-7] × six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp. 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). 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. Conclusion Evidence from JCOG0905 does not support the addition of IF for patients with PrRsp. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 30 3 2025 Five-year outcomes with gefitinib induction and chemoradiotherapy in EGFR-mutant stage III non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study 497 503 EN Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Sho Saeki Department of Respiratory Medicine, Kumamoto University Hospital Shinya Sakata Department of Respiratory Medicine, Kumamoto University Hospital Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Daijiro Harada Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Kentaro Tanaka Department of Respiratory Medicine, Kyushu University Hospital Koji Inoue Department of Respiratory Medicine, Kitakyushu Municipal Medical Center Koji Inoue Department of Respiratory Medicine, Ehime Prefectural Central Hospital Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Toshio Kubo Department of Respiratory Medicine, Okayama University Hospital Akiko Sato Department of Respiratory Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Hiromi Watanabe Department of Respiratory Medicine, Okayama University Hospital Junji Kishimoto Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University Yoshiyuki Shioyama Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation Kuniaki Katsui Department of Radiology, Kawasaki Medical School Kenji Sugio Division of Radiation Oncology, Department of Thoracic and Breast Surgery, Oita University Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Background We previously showed the 2-year OS rate, the primary endpoint, of 90% in a phase II trial of gefitinib induction followed by chemoradiotherapy (CRT) in unresectable, stage III, EGFR-mutant, non-small-cell lung cancer (NSCLC). However, neither long-term survival data nor late-phase adverse event profiles have been presented. 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. 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. 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. Trial registration numbers UMIN00005086. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000006047&type=summary&language=EjRCTs071180036. https://jrct.niph.go.jp/latest-detail/jRCTs071180036 No potential conflict of interest relevant to this article was reported.

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

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 65 10 2026 Mycobacterium intracellulare Infection in a Japanese Patient with Signal Transducer and Activator of Transcription-3 Gain-of-function Syndrome 1421 1430 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoji Hirai Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Marina Kawaguchi Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Uda Department of Pediatrics, Okayama University Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Kousei Hasegawa Department of Pediatrics, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Signal transducer and activator of transcription-3 (STAT3) gain-of-function (GOF) syndrome predisposes patients to autoimmunity diseases. Yet, nontuberculous mycobacterial (NTM) infections have rarely been described. We herein report a teenage Japanese patient with genetically confirmed STAT3-GOF syndrome who developed Mycobacterium intracellulare disease. Combination antimycobacterial chemotherapy reduced the bacterial burden; however, the refractory NTM infection relapsed after initiation of adjunctive tofacitinib therapy. The present case demonstrates that host-directed therapy must be combined with prolonged antimycobacterial regimens to control drug-resistant NTM in patients with inborn errors of immunity. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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

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

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

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

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Peripheral Blood T-Cell Receptor Repertoire and Host Immune Background in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy 169 178 EN Yuki Nakamura Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Takayuki Iwamoto Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Yukiko Kajiwara Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Akira Hida Department of Pathology, Matsuyama Shimin Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Yuichiro Miyoshi Department of Breast Endocrine Surgery, Kagawa Prefectural Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Masahiko Ikeda Department of Breast and Thyroid Surgery, Fukuyama City Hospital Hiroyoshi Doihara Department of General Surgery, Kawasaki Medical School General Medical Center Ryohei Ogata Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Yoshikazu Koike Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Tsunehisa Nomura Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Katsuhiro Tanaka Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Kazutaka Nakashima Department of General Surgery, Kawasaki Medical School General Medical Center Tomoki Yamatsuji Department of General Surgery, Kawasaki Medical School General Medical Center Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Original Article 10.18926/AMO/70852 The association between peripheral blood T-cell receptor (TCR) repertoire and chemotherapy response remains unclear. We evaluated peripheral blood TCR repertoire and gut microbiota in 21 breast cancer patients receiving neoadjuvant chemotherapy (NAC) who were enrolled in the SBP-14 prospective cohort study between October 2019 and March 2022. We analyzed stool samples obtained pre-NAC and peripheral blood samples obtained pre- and post-NAC. The primary endpoint was the association between baseline peripheral blood TCR repertoire and treatment response. Eleven patients (52%) had hormone receptor-positive breast cancer. All patients received anthracyclines and taxanes, with anti-HER2 therapy for HER2-positive disease. TCR diversity (TCR alpha chain [TRA], p=0.095; TCR beta chain [TRB], p=0.051) and clonality (TRA, p=0.271; TRB, p=0.500) were not significantly associated with treatment response. Gut microbiota diversity was not correlated with TCR diversity (TRA: 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.

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

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

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

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

Wiley Acta Medica Okayama 2197-1153 13 1 2026 Association between discoid lateral meniscus and medial meniscus posterior root tear: A retrospective cohort study e70666 EN Ryosuke Yamashita Department of Orthopaedic Surgery, Okayama University Hospital Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Hospital Keisuke Kintaka Department of Orthopaedic Surgery, Kochi Health Sciences Center Koki Kawada Department of Orthopaedic Surgery, Okayama University Hospital Toshiki Kohara Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Purpose: Medial meniscus (MM) posterior root tear (PRT) has gained increasing attention because of its biomechanical impact and rapid progression to osteoarthritis. Identifying the risk factors for MMPRT is essential for early diagnosis. Although the discoid lateral meniscus (DLM) is a common congenital variant, no studies have reported on the relationship between MMPRT and DLM. This study aimed to examine the relationship between MMPRT and DLM. Methods: This retrospective cohort study included 94 matched knees that underwent arthroscopic surgery between 2015 and 2021 (58 with MMPRT and 36 with other MM injuries). The matching was performed according to age and sex. Morphological analysis of the lateral meniscus (LM) was performed using coronal magnetic resonance imaging (MRI). DLM was defined as an LM ratio (LM width/tibial width) > 0.20. LM width, LM ratio and DLM prevalence were compared between the two groups. In the MMPRT group, subgroup analysis compared the preoperative and 1-year postoperative clinical outcomes between patients with and without DLM. Results: The PRT group showed significantly greater LM width (12.6 ± 3.1 mm vs. 11.1 ± 2.2 mm; p = 0.03) and LM ratio (0.18 ± 0.04 vs. 0.16 ± 0.03; p = 0.01) compared with the other group. The incidence of DLM was also significantly higher in the PRT group (29.3% vs. 8.3%; p = 0.02). No significant differences in clinical scores were observed between the two subgroups either preoperatively or 1 year postoperatively. However, both groups demonstrated significant improvement in all clinical outcomes 1 year postoperatively (p < 0.01). Conclusions: DLM was significantly more prevalent in patients with MMPRT than in those with other MM injuries. Favourable clinical outcomes were achieved following pullout repair in MMPRT knees regardless of the presence of DLM. Level of Evidence: Level III, retrospective cohort study. No potential conflict of interest relevant to this article was reported.

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

Oxford University Press (OUP) Acta Medica Okayama 2753-670X 41 5 2026 Lung Segmental Perfusion Defect Is Associated With Airway Complications After Living-Donor Lobar Lung Transplantation ivag139 EN Kentaro Imanishi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Ryuko Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Tomioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences PURPOSE: 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. 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. 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. 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. 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.

Frontiers Media SA Acta Medica Okayama 1664-2392 17 2026 Behavior of serum thyroglobulin in relation to thyroid function under low-thyrotropin conditions in general practice 1756863 1756863 EN Yosuke Sazumi Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Takase Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Yasuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Furukawa Department of Laboratory Medicine, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Serum thyroglobulin (Tg) and thyroid hormones are essential biomarkers in the diagnosis and management of thyroid diseases. Although Tg is routinely measured as a marker for thyroid neoplasia and an adjunct in the diagnosis of thyrotoxicosis due to destructive thyroiditis, its clinical significance under conditions of abnormal thyroid function remains unclear. Methods: We investigated the association between serum Tg levels and thyroid function in 292 patients who underwent simultaneous evaluation of serum Tg, free thyroxine (FT4), and free triiodothyronine (FT3) levels in routine clinical practice. Based on thyroid-stimulating hormone (TSH) levels, participants were classified into three groups: high-TSH (> 4.23 μIU/mL; n = 38), normal-TSH (0.61–4.23 μIU/mL; n = 191), and low-TSH (< 0.61 μIU/mL; n = 63). Results: The low-TSH group exhibited significantly higher serum Tg levels (118.66 ± 32.13 ng/mL) than the normal-TSH (70.20 ± 23.48 ng/mL) and high-TSH (34.70 ± 13.62 ng/mL) groups. Among patients positive for TSH-receptor antibodies (TRAb) or thyroid-stimulating antibodies (TSAb), elevated Tg levels were observed exclusively in the low-TSH group. Correlation analyses revealed that Tg levels were positively correlated with the FT3/FT4 ratio in the low-TSH group (rho = 0.62, p < 0.01), and this association was more evident in patients positive for both TRAb and TSAb (rho = 0.71, p < 0.01). These associations remained significant after multivariable adjustment and were supported by correlations between Tg and SPINA-GD, a model-based index of thyroid function reflecting deiodinase activity, with similar findings observed in patients with autoimmune hyperthyroidism. Conclusion: These findings suggest that serum Tg levels may reflect biochemical features consistent with T3 predominance in autoimmune hyperthyroidism and have potential clinical utility in characterizing disease pathophysiology. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 33 5 2026 Novel Arterial Reconstruction of the Left Gastric Artery Supplying the Replaced Left Hepatic Artery in Distal Pancreatectomy with Celiac Axis Resection 4118 4121 EN Kosei Takagi Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Atene Ito Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomokazu Fuji Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuya Yasui Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takeyoshi Nishiyama Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuo Nagai Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shohei Yokoyama Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background. Distal pancreatectomy with celiac axis resection (DP-CAR) with reconstruction of the left gastric artery (LGA) is a technically challenging procedure. The middle colic artery is commonly used for LGA reconstruction. This study highlights our novel arterial reconstruction of the LGA using the common hepatic artery (CHA) supplying the replaced left hepatic artery (rLHA) during DP-CAR. Patient and Methods. A 65-year-old man diagnosed with locally advanced unresectable pancreatic body cancer underwent DP-CAR following systemic chemotherapy. As a rLHA arising from the LGA was present, arterial reconstruction was necessary. Results. After confirming resectability, the CHA and LGA were encircled. Following division of the pancreas and radical lymphadenectomy, the origin of the celiac axis (CA) was divided. Subsequently, the CHA and LGA were transected and anastomosed. An indocyanine green fluorescence system was used to confirm adequate arterial blood supply and satisfactory tissue perfusion. Operative time was 215 min, with an estimated blood loss of 35 mL. Conclusions. This study demonstrated a novel arterial reconstruction of the LGA supplying the rLHA during DP-CAR. The CHA may be a candidate for the reconstruction of the LGA in DP-CAR. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 2072-6694 18 4 2026 Outcomes After Robot-Assisted Versus Open Pancreatoduodenectomy: A Propensity Score-Matching Analysis in a High-Volume Center (TAKUMI-7) 602 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Hepatobiliary Pancreatic Surgery, Ehime University Graduate School of Medicine Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atene Ito Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naohiro Okada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shohei Yokoyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Objectives: Although the safety and feasibility of robot-assisted pancreatoduodenectomy (RPD) compared to open pancreatoduodenectomy (OPD) have been reported, studies investigating the advantages of RPD remain limited. Moreover, only a few studies have investigated the effects of robotic surgery on textbook outcomes (TO). Methods: This single-center retrospective study included 400 patients who underwent RPD and OPD at our institution between January 2017 and December 2025. Outcomes were compared between the RPD (n = 162) and OPD (n = 238) groups using propensity score-matching (PSM) analysis. The factors associated with TO were examined. Results: Before PSM, significant differences were observed between the groups. PSM yielded RPD (n = 117) and OPD (n = 117) with equal preoperative factors. The RPD group demonstrated a significantly shorter operative time (402 vs. 444 min, p < 0.001), lesser blood loss (75 vs. 270 mL, p < 0.001), shorter postoperative hospital stays (13 vs. 22 days, p < 0.001), and fewer major complications (17.1 vs. 44.4%, p < 0.001), resulting in a higher TO achievement rate (76.9 vs. 52.1%, p = 0.001). Adjusted multivariate analyses identified robotic surgery (odds ratio 3.04, p < 0.001) as an independent predictor of TO. Conclusions: This study demonstrated that RPD was potentially superior to OPD in terms of short-term outcomes. Robotic surgery was significantly associated with TO after pancreatoduodenectomy at the expert’s hand. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0258-851X 40 1 2026 Modified Subtraction Technique for the Middle Hepatic Vein Tributary and Glissonean Pedicle in Right Lobe Graft Procurement 349 354 EN KOSEI TAKAGI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TOMOKAZU FUJI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KAZUYA YASUI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TAKEYOSHI NISHIYAMA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YASUO NAGAI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences SHOHEI YOKOYAMA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YUZO UMEDA Department of Hepatobiliary Pancreatic Surgery, Ehime University Graduate School of Medicine TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Aim: The procurement of right lobe grafts while preserving the middle hepatic vein (MHV) tributaries (V5 and V8) just before graft retrieval is technically challenging. Moreover, the safe isolation of the hepatic duct from the Glissonean pedicle is essential in living donor hepatectomy. To date, few studies have reported surgical techniques for preserving the MHV tributaries during right lobe graft procurement. Patients and Methods: This report presents our modified subtraction technique for managing the MHV tributaries and Glissonean pedicle during right lobe graft procurement. First, a subtraction technique for the MHV tributaries was initiated by isolating the right Glissonean pedicle. The lower tip of the tape was placed behind the caudate lobe and passed behind the right hepatic vein. Each end of the tape was then passed behind V5 and V8, followed by dissection of the remaining liver parenchyma between them. Subsequently, a subtraction technique for the Glissonean pedicle was applied to safely isolate the right hepatic duct and hilar plate. Results: Between September 2011 and May 2025, seven donors underwent right lobe graft procurement using the subtraction technique for the middle hepatic vein tributaries. The mean operative time was 381 min with an estimated blood loss of 217 ml. Using the subtraction technique, all middle hepatic vein tributaries were preserved just before graft retrieval. Conclusion: This study presents subtraction techniques used during living donor hepatectomy. The technique may facilitate liver parenchyma dissection while preserving MHV tributaries just before graft retrieval and isolating the Glissonean pedicle. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0258-851X 40 3 2026 Impact of Donor Cirrhosis Outcome Risk Estimator (CORE) Score on Recipient Outcomes Following Living-donor Liver Transplantation 1570 1576 EN KOSEI TAKAGI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TOMOKAZU FUJI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KAZUYA YASUI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TAKEYOSHI NISHIYAMA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YASUO NAGAI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences NAOHIRO OKADA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences SHOHEI YOKOYAMA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Aim: Several studies have investigated predictive factors for outcomes of living-donor liver transplantation (LDLT). However, few have examined the clinical significance of the Cirrhosis Outcome Risk Estimator (CORE) score on prognosis following LDLT. This study aimed to investigate the impact of donor CORE scores in predicting the outcomes of patients undergoing LDLT. Patients and Methods: This single-center retrospective study included 362 adult LDLT recipients at our Institution between January 1998 and December 2024. Patient and graft survival rates were compared between the groups with low (≤0.05) and high (>0.05) CORE scores. Subsequently, multivariate analyses were performed to investigate prognostic factors for survival, including the CORE score. Results: Patients in the group with a low CORE score had significantly better survival (p=0.001; 5-year, 85.3% vs. 76.2%) and graft survival (p=0.001; 5-year, 84.1% vs. 74.6%) than those with a high CORE score. Multivariate analyses identified the CORE score (>0.05) as an independent predictor of patient survival (hazard ratio=1.70, 95% confidence interval=1.01-2.62, p=0.018) and graft survival (hazard ratio=1.66, 95% confidence interval=1.07-2.57, p=0.024). Conclusion: This study demonstrated the clinical significance of donor CORE scores in recipient outcomes after LDLT. Assessment of the donor CORE score may be useful for evaluating the quality of liver grafts and estimating recipient outcomes. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 2072-6694 17 18 2025 Outcomes of Robotic Pancreatectomy in the Octogenarian: A Multicenter Retrospective Cohort Study 3038 EN Kosei Takagi Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuichiro Uchida Department of Surgery, Fujita Health University Tomokazu Fuji Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takeshi Takahara Department of Surgery, Fujita Health University Kazuya Yasui Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takeyoshi Nishiyama Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ichiro Uyama Department of Advanced Laparoscopic and Robotic Surgery, Fujita Health University Koichi Suda Department of Surgery, Fujita Health University Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background/Objectives: Due to the increasing incidence of pancreatic and periampullary cancers with advancing age, coupled with the growing evidence supporting minimally invasive pancreatectomy, the demand for such procedures is rising. However, data on the feasibility of robotic pancreatectomy in octogenarian patients remain scant. This study aimed to investigate overall outcomes of robotic pancreatectomy and evaluate its safety and feasibility in octogenarian patients. Methods: A multicenter, retrospective study was conducted, including 380 patients who underwent robotic pancreatectomy at two high-volume centers in Japan from April 2020 to December 2024. Using prospectively collected data, we compared outcomes between younger patients (<80 years) and octogenarian patients (≥80 years). Multivariable logistic regression analyses were performed to assess the impact of age on postoperative outcomes. Results: Among the 380 patients, with a median age of 72 (interquartile range: 61–77) years, 213 underwent robotic pancreatoduodenectomy (RPD), and 167 underwent robotic distal pancreatectomy (RDP). Octogenarian patients were found to have more comorbidities and a higher incidence of malignant diseases. Octogenarians experienced significantly longer hospital stays post-RPD (22 [octogenarian; n = 36] vs. 14 [younger; n = 177] days, p < 0.001) and post-RDP (14 [n = 23] vs. 10.5 [n = 144] days, p = 0.02), yet their perioperative outcomes were comparable. Multivariable analyses indicated that age (≥80 years) was not a significant risk factor for major complications following robotic pancreatectomy (odds ratio, 1.33; 95% confidence interval, 0.59–2.84; p = 0.479). Conclusions: This multicenter study conducted at high-volume centers suggests that robotic pancreatectomy can be safely performed in carefully selected octogenarian patients. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1347-9032 2026 Atezolizumab + Chemotherapy in Older Patients With Lung Cancer in Japan 1 13 EN Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Ichiro Yoshino International University of Health and Welfare Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Kozo Yoshimori Department of Clinical Oncology, Japan Anti‐Tuberculosis Association, Fukujuji Hospital Kazuhiko Shibata Department of Medical Oncology, Kouseiren Takaoka Hospital Takeshi Tsuda Division of Respiratory Medicine, Toyama Prefectural Central Hospital Masahiro Seike Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Takahiro Ota Department of Respiratory Medicine, Kyoto City Hospital Koichi Samata Chugai Pharmaceutical Co., Ltd. Yuki Kobayashi Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School Pivotal phase 3 trials leading to the approvals of atezolizumab─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.

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

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

Elsevier BV Acta Medica Okayama 0196-0709 47 3 2026 Predictors of therapeutic response and pain after near-infrared photoimmunotherapy in head and neck cancer 104848 EN Junya Matsumoto Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuma Makino Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuto Naoi Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: Near-infrared photoimmunotherapy (NIR-PIT) has been approved by the Japanese national health insurance for approximately five years, and clinical experience has steadily accumulated. However, reports analyzing treatment outcomes and pain-related factors remain limited. This study aimed to identify predictors of therapeutic response and pain following NIR-PIT. Methods: This retrospective cohort study included 25 patients who underwent NIR-PIT for head and neck cancer between January 2021 and June 2025. Lesion diameter and thickness were evaluated in relation to complete response (CR), and the frequency and predictors of post-treatment pain were assessed. Results: Among 22 evaluable patients, eight achieved CR. Lesions with a shorter longest diameter and thinner thickness were significantly associated with higher CR rates (p = 0.011 and p = 0.024). Moderate-to-severe pain (Numerical Rating Scale ≥4) occurred in 18 of 48 treatment cycles (37.5%) but was significantly less frequent in patients with a history of reconstructive surgery (p = 0.017). Conclusions: NIR-PIT demonstrated particularly favorable efficacy for short, thin lesions, suggesting that early introduction of treatment may be associated with improved therapeutic outcomes. A history of reconstructive surgery was associated with reduced post-treatment pain, highlighting the importance of individualized treatment and pain management strategies in head and neck cancer patients undergoing NIR-PIT. No potential conflict of interest relevant to this article was reported.

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

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

Elsevier BV Acta Medica Okayama 0753-3322 194 2026 Elucidation of mechanisms underlying the therapeutic effects of cordycepin on pulmonary hypertension, with a focus on cell senescence and gut microbiota 118923 EN Gaopeng Li Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Zhixin Zhao Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University Mitsuhiro Machitani Division of Cancer Stem Cell, National Cancer Center Research Institute Ryou Ishikawa Department of Diagnostic Pathology, Kagawa University Hospital Kaori Ishikawa Department of General Medicine, Kagawa University Hospital Naoya Yokota Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University Reiji Haba Department of Diagnostic Pathology, Kagawa University Hospital Kazufumi Nakamura Center for Advanced Heart Failure, Okayama University Hospital Zhihong Sun Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University Lin-Hai Kurahara Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Katsuya Hirano Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Introduction: Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by excessive pulmonary vascular remodeling and aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs). Emerging evidence suggests that gut microbiota dysbiosis contributes to PH development. Cordycepin, a natural adenosine analogue derived from Cordyceps militaris, has demonstrated antiproliferative and microbiota-modulating properties; however, its mechanism of action in PH remains unclear. Objective: Elucidate the mechanisms underlying the therapeutic effects of cordycepin on PH, focusing on cellular senescence and gut microbiota. Methods: The effects of cordycepin on PH pathology were investigated by transcriptome analysis of PASMCs from patients, and metagenomic analysis of rodent PH models. Cellular senescence was analyzed in lung tissue from p16Ink4a-CreERT2 reporter mice and in rat bone marrow-derived macrophages (BMDMs). Results: RNA sequencing analysis revealed activation of p53 signaling by cordycepin in PASMCs. Cordycepin suppressed CDK1 expression and TERT phosphorylation at threonine 249. It ameliorated vascular and cardiac remodeling in PH rat and mouse models. Cordycepin induced M1-like macrophage senescence in p16 Ink4a reporter mice lungs and rat BMDMs. Cordycepin significantly reshaped the gut microbiota, increasing beneficial genera (e.g. Alistipes and Acetatifactor) and reducing proinflammatory taxa (e.g., Ruminococcus), with modulating key metabolic pathways, including short-chain fatty acid, tryptophan, and vitamin K2 metabolism. Conclusion: Cordycepin exerts multi-target therapeutic effects in PH by inhibiting PASMC proliferation via the p53–CDK1/pTERT axis, modulating gut microbiota-linked immunometabolism and induces proinflammatory macrophage senescence. These findings support cordycepin as a promising candidate for PH therapies targeting the vascular, immune, and gut–lung axes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-7257 19 3 2026 Successful management and 10-year survival of a rectal neuroendocrine tumor with rare systemic metastases via a non-portal venous pathway 491 498 EN Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Kosei Takagi Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takashi Kuise Department of Gastroenterological Surgery, Okayama Red Cross Hospital Takehiro Tanaka Department of Pathology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Metastatic 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.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 33 4 2026 Differences in drug efficacy and prognosis between primary and metastatic sites for de novo stage IV breast cancer: an exploratory analysis of a phase III trial, JCOG1017 829 838 EN Kiyo Tanaka Department of Breast Surgery, Toranomon Hospital Akihiko Shimomura Department of Breast and Medical Oncology, National Center for Global Health and Medicine Makoto Ishitobi Department of Breast Surgery, Osaka Habikino Medical Center Takashi Yamanaka Department of Breast Surgery, Kanagawa Cancer Center Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroji Iwata Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences Fumikata Hara Department of Breast Oncology, Aichi Cancer Center Tomomi Fujisawa Department of Breast Oncology, Gunma Prefectural Cancer Center Keita Sasaki Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Ryo Sadachi Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Riku Kajikawa Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Takehiko Sakai Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Yasuaki Sagara Department of Breast Surgery, Sagara Hospital Hideo Shigematsu Department of Breast Surgery, Hiroshima University Hospital Yukinori Ozaki Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Kazuki Nozawa Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences Kazuki Sudo Department of Medical Oncology, National Cancer Center Hospital Yoichi Naito Department of General Internal Medicine, National Cancer Center Hospital East Kaori Terata Department of Breast and Endocrine Surgery, Akita University Hospital Toshiyuki Ishiba Department of Breast Surgery, Institute of Science Tokyo Hospital Haruhiko Fukuda Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background Breast cancer is a highly heterogeneous disease, with biological factors like estrogen receptor, progesterone receptor, and HER2 receptor differing between primary and metastatic sites, potentially affecting treatment response. This exploratory analysis aims to differentiate drug efficacy and long-term prognosis between these sites in stage IV breast cancer. 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). 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). Conclusions One-fourth of patients exhibited discordant responses between primary and metastatic sites in early treatment phases. These discrepancies were associated with survival differences, emphasizing the importance of evaluating both primary and metastatic lesions when assessing efficacy and determining treatment strategies in de novo stage IV breast cancer. No potential conflict of interest relevant to this article was reported.

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

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

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

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

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 3 2026 Bortezomib Induces Apoptosis via Upregulation of Abhd4 in Peripheral Nerve Cells 496 502 EN Yusuke Konishi Department of Pharmacy, Kobe University Hospital Tomohiro Omura Department of Pharmacy, Kobe University Hospital Takeshi Ijichi Department of Pharmacy, Kobe University Hospital Hiroki Nishiguchi Department of Pharmacy, Kobe University Hospital Ryunosuke Hayakawa Education and Research Center for Clinical Pharmacy, Kobe Pharmaceutical University Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Kotaro Itohara Department of Pharmacy, Kobe University Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ikuko Yano Department of Pharmacy, Kobe University Hospital Bortezomib, a first-in-class proteasome inhibitor, is widely used to treat multiple myeloma and other hematological malignancies. Despite its therapeutic efficacy, bortezomib causes peripheral neuropathy (PN) in approximately 20–30% of patients, often leading to dose reduction or discontinuation. Preventive or therapeutic approaches to bortezomib-induced PN are currently unavailable, as its precise mechanism remains unclear. In this study, we compared the effects of bortezomib and the second-generation proteasome inhibitor carfilzomib on peripheral nerve cells to identify candidate molecules involved in PN development. Transcriptome profiling of differentiated F11 cells, a hybridoma of a rat embryonic dorsal root ganglion and mouse neuroblastoma cell line N18TG2, revealed that bortezomib selectively upregulated α/β-hydrolase containing domain 4 (Abhd4), whereas carfilzomib did not. This finding was confirmed by quantitative RT-PCR and immunoblotting, which demonstrated consistent increases in Abhd4 mRNA and protein levels following bortezomib treatment. Functional analysis further revealed that Abhd4 overexpression promoted early apoptosis, suggesting a mechanistic link between bortezomib-induced Abhd4 elevation and neuronal vulnerability. Therefore, these results suggest that Abhd4 represents a candidate molecular signature associated with bortezomib-induced PN. Although further in vivo validation is needed, these findings warrant further investigation of Abhd4 as a potential contributor to bortezomib-induced PN. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 1 2025 Impact of Polymeric Formula on Outcomes in Robotic Pancreatectomy: A Randomized Controlled Trial 407 414 EN KOSEI TAKAGI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TOMOKAZU FUJI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KAZUYA YASUI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences MOTOHIKO YAMADA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TAKEYOSHI NISHIYAMA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YASUO NAGAI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences MASASHI HASHIMOTO Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TOSHIHARU MITSUHASHI Center for Innovative Clinical Medicine, Okayama University Hospital TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Aim: Evidence regarding the benefits of nutritional therapy after robotic pancreatectomy is limited. This randomized controlled trial aimed to investigate the effects of a polymeric formula (PF) on preventing body weight loss (BWL) following robotic pancreatectomy. Patients and Methods: This single-center, open-label, randomized trial was conducted to assign 46 patients undergoing robotic pancreatectomy in a 1:1 ratio to either the PF (ISOCAL Clear) or control group. The primary endpoint was the percentage of BWL on postoperative days 14 and 28. The secondary endpoints were postoperative outcomes. Results: Of the 52 eligible patients between December 2023 and November 2024, 46 were analyzed using intention-to-treat principles: 23 in the ISOCAL group and 23 in the control group. The %BWL was significantly lower in the ISOCAL group compared with that in the control group on postoperative days 14 (4.8±3.5% vs. 6.6±3.2%, p=0.02) and 28 (6.4±3.0% vs. 8.4±3.5%, p=0.047). Postoperative outcomes, including major complications (p=0.55) and hospital stay (p=0.83), did not differ significantly between the groups. Conclusion: This study demonstrates the safety and feasibility of administering PF to patients undergoing robotic pancreatectomy. The results showed the beneficial effects of PF on mitigating BWL without compromising short-term outcomes. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 9 3 2026 Post Hoc Analysis of Frailty and Tracheostomy Risk in Older Patients Intubated and in an Intensive Care Unit in Japan: An Inverse Association in Older Patients with Advanced Age 643 650 EN Takehide Umeda Takashi Hongo Mototaka Inaba Hiromichi Naito Yoshinori Ariyasu Takashi Yorifuji Introduction: This post hoc analysis of a prospectively collected intensive care unit (ICU) cohort examined the association between frailty and the likelihood of tracheostomy in older Japanese patients (aged ≥65 years). Frailty, a condition of increased vulnerability to stressors, is common among older patients in the ICU and may influence clinical decision-making and outcomes. We aimed to explore whether baseline frailty is associated with the likelihood of receiving tracheostomy in older patients in the ICUs. Methods: We analyzed data from a multicenter prospective study conducted from November 2019 to April 2020 at 17 hospitals in Japan. Patients aged ≥65 years, admitted directly from the emergency department, and requiring mechanical ventilation, were included. After excluding early deaths (≤5 days) or treatment-limit cases, 363 patients with intubation remained. Frailty was assessed using the Clinical Frailty Scale (CFS), with primary cutoff CFS ≥4. The primary outcome was the occurrence of tracheostomy during ICU stay. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using generalized linear models with a Poisson distribution, adjusted for age, sex, Charlson Comorbidity Index, and Acute Physiology and Chronic Health Evaluation II score. Results: Among 363 patients, patients with frailty (CFS ≥4) had a significantly lower adjusted risk of having tracheostomy than did those with less frailty (CFS <4) (adjusted RR: 0.40; 95% CI: 0.27-0.61). In patients aged ≥75 years, the adjusted RR for CFS ≥4 was 0.32 (95% CI: 0.20-0.50), indicating a pronounced reduction in tracheostomy use among patients with frailty. Conclusions: Frailty (CFS ≥4) was independently associated with a lower likelihood of tracheostomy, particularly in patients aged ≥75 years. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 3 2026 Septic Arthritis of the Temporomandibular Joint Complicated by Dislocation e105091 EN Hideka Kanemoto Department of Oral Surgery, Kochi Health Sciences Center Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koki Umemori Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Septic arthritis of the temporomandibular joint (SATMJ) is a rare but potentially serious condition, and standardized diagnostic and therapeutic strategies have not been established. We present the case of a 70-year-old man who developed acute right temporomandibular joint (TMJ) pain, swelling, mandibular deviation, and inability to achieve mouth closure. Computed tomography and magnetic resonance imaging revealed right TMJ dislocation, joint effusion, degenerative changes, and anterior disc displacement with effusion. Aspiration of the joint yielded neutrophil-predominant purulent fluid, although bacterial cultures were negative. The patient was treated empirically with intravenous ceftriaxone followed by oral clindamycin and amoxicillin, resulting in rapid symptom resolution, and the dislocation spontaneously reduced without surgical intervention. No recurrence was observed during three months of follow-up. This case highlights the diagnostic challenges associated with culture-negative SATMJ, supports the role of early empirical antibiotic therapy, and suggests that chronic joint instability due to habitual dislocation may predispose the TMJ to infection. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 4 2026 Immunological effects of amivantamab in EGFR or MET-expressing non-small cell lung cancer 121 EN Ryo Yoshichika Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiaki Mukohara Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kotaro Yamada Department of Respiratory Medicine, Okayama University Hospital Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroko Watanabe Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Epidermal growth factor receptor (EGFR) mutations represent one of the most frequent oncogenic driver in non-small cell lung cancer (NSCLC). Amivantamab, a bispecific antibody targeting EGFR and MET proto-oncogene, receptor tyrosine kinase (MET), has demonstrated clinical benefit in EGFR-mutant NSCLC through dual blockade, but its immunological role in human clinical specimens, especially tumor-infiltrating lymphocytes (TILs), has not been directly evaluated. Methods We analyzed surgically resected tumor samples from 40 patients with NSCLC to investigate immune responses and their associations with EGFR and MET expression. TILs were characterized by flow cytometry (FCM) and immunohistochemistry (IHC). To assess the immunomodulatory potential of amivantamab, fresh tumor digests containing live tumor cells and TILs were cultured ex vivo with CD3 and CD28 stimulation in the absence or presence of amivantamab, followed by FCM. EGFR and MET expression were also evaluated by IHC. Results EGFR mutations and high EGFR protein expression were associated with a trend toward reduced CD8⁺ T-cell and dendritic cell (DC) infiltration. In ex vivo TIL assays, exposure to amivantamab significantly activated CD8⁺ T cells, such as programmed cell death-1 expression and cytokine production, and promoted DC maturation. These effects were most pronounced in tumors with high EGFR or MET protein expression rather than EGFR mutations. Conclusions This study provides the first direct evidence from ex vivo fresh TIL assays using human NSCLC clinical specimens that amivantamab can activate immune responses. EGFR and MET expression may serve as potential biomarkers for amivantamab-induced immune responses. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-3643 7 3 2026 Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study 100926 EN Masayuki Shirasawa Department of Thoracic Oncology, National Cancer Center Hospital Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Ichiro Yoshino International University of Health and Welfare Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Yasushi Yatabe Department of Diagnostic Pathology, National Cancer Center Hospital Tatsuya Yoshida Department of Thoracic Oncology, National Cancer Center Hospital Jumpei Kashima Department of Diagnostic Pathology, National Cancer Center Hospital Masahide Oki Department of Respiratory Medicine, NHO Nagoya Medical Center Hisao Ashimura Chugai Pharmaceutical Co., Ltd. Yuki Kobayashi Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School Introduction: 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. 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. 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. 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.

Springer Science and Business Media LLC Acta Medica Okayama 1865-1380 19 1 2026 Pseudoaneurysm of the thoracoacromial artery associated with habitual shoulder dislocation: a case report 139 EN Honoka Wada Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Aya Hamasaki Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Soichiro Okamoto Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shunki Yamamoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background Shoulder dislocation is one of the most common joint dislocations encountered in emergency departments, but vascular complications are rare and often underrecognized. Pseudoaneurysms of the thoracoacromial artery, a branch of the axillary artery, are extremely uncommon and may present with subtle symptoms, delaying diagnosis. Case presentation An 82-year-old woman with a history of habitual anterior shoulder dislocation presented with a 10-day history of progressive pain and swelling in the left shoulder. She was on edoxaban for atrial fibrillation. Examination revealed localized tenderness and swelling without neurological deficits. Computed tomography angiography showed a 30 × 35 × 35 mm pseudoaneurysm arising from the acromial branch of the thoracoacromial artery. Endovascular embolization was performed using a proximal oxidized regenerated cellulose sheet placement followed by injection of N-butyl cyanoacrylate and Lipiodol due to the risk of coil migration into the joint space. The procedure achieved complete exclusion of the lesion. At three-month follow-up, the patient remained asymptomatic with preserved left upper limb function. Computed tomography angiography demonstrated the pseudoaneurysm remains excluded. Conclusion Although rare, pseudoaneurysms of the thoracoacromial artery can occur after repeated shoulder dislocation and reduction, especially in elderly patients on anticoagulation therapy. Early recognition through imaging and prompt endovascular intervention can prevent serious vascular and neurological complications. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2407 26 1 2026 High-risk soft-tissue sarcomas in elderly patients: does perioperative radiotherapy improve local control and prognosis? 329 EN Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiharu Mitsuhashi Centre for Innovative Clinical Medicine, Medical Development Field, Okayama University Yutaka Nezu Department of Orthopaedic Surgery, Yokohama City University Takashi Tajima Department of Orthopaedic Surgery, Kyorin University Faculty of Medicine Shinji Miwa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Toshio Kojima Department of Orthopaedic Surgery, Nihon University School of Medicine Shuichi Fujiwara Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Akira Kawai Department of Musculoskeletal Oncology, National Cancer Centre Hospital Kazuhiro Tanaka Department of Advanced Medical Sciences, Oita University Faculty of Medicine Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Aims 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. 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. 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. 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.

MDPI AG Acta Medica Okayama 1422-0067 27 2 2026 Possible Involvement of Hypothalamic Dysfunction in Long COVID Patients Characterized by Delayed Response to Gonadotropin-Releasing Hormone 832 EN Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Takase Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yohei Masuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (−0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements. No potential conflict of interest relevant to this article was reported.