Springer Science and Business Media LLC Acta Medica Okayama 1478-6362 28 1 2026 Real-world comparative effectiveness of sarilumab versus Janus kinase inhibitors as monotherapy in rheumatoid arthritis 32 EN Yuji Nozaki Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Kazuya Kishimoto Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Tetsu Itami Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Daisuke Tomita Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Yumiko Wada Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University Takuya Kotani Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University Tohru Takeuchi Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University Toshihiko Hidaka Rheumatology Center, Miyazaki Zenjinkai Hospital Shoichi Hino Department of Rheumatology and Clinical Immunology, Izumi City General Medical Center Toshiaki Miyamoto Miyamoto Internal Medicine and Rheumatology Clinic Hirofumi Miyake Department of General Internal Medicine, Tenri Hospital Kazunari Hatta Department of General Internal Medicine, Tenri Hospital Kenji Mamoto Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka Metropolitan University Yutaro Yamada Center for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of Medicine Tadashi Okano Center for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of Medicine Takaichi Okano Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Jun Saegusa Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Masahiro Horita Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Koji Kinoshita Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Shinya Rai Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Background: Sarilumab (SAR), an interleukin-6 receptor inhibitor (IL-6Ri), and Janus kinase inhibitors (JAKi) are approved options for rheumatoid arthritis (RA) when methotrexate (MTX) cannot be used. Real-world evidence for MTX-free monotherapy remains limited. Methods: We conducted a multicenter retrospective cohort study of RA patients receiving SAR or JAKi as MTX-free monotherapy. To reduce confounding, 1:1 propensity score matching was performed in the overall cohort (n = 252, 126 per group) and separately within treatment-line strata: Phase 2 first-line biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs: 45 per group), Phase 3 second-line b/tsDMARDs (53 per group), and Phase 3 ≥ third-line b/tsDMARDs (47 per group). Outcomes over 12 months included drug retention, change in Clinical Disease Activity Index (CDAI), glucocorticoid (GC) tapering and discontinuation, low disease activity (LDA, CDAI ≤ 10), and safety profiles. Predictors of LDA were evaluated with logistic regression. This multicenter real-world. Results: Across matched strata by prior b/tsDMARDs, retention and CDAI change did not differ significantly between SAR and JAKi through 12 months. When classified by cause, adverse events (AEs)-related discontinuation was higher with JAKi, yielding lower AE-specific retention. Both groups demonstrated GC sparing overtime, with a greater increase in GC discontinuation for SAR than for JAKi in Phase 2. Baseline predictors of achieving LDA at 12 months included higher C-reactive protein (CRP) and platelet count (Plt) in both groups, with additional associations of younger age and lower hemoglobin (Hb) in the SAR. In safety analyses, overall AEs were less frequent with SAR than with JAKi, driven by lower risks of infection including herpes zoster, while other categories were similarly infrequent. Conclusion: SAR and JAKi showed no statistically significant differences in 12-month retention or disease control in MTX-free monotherapy settings. Higher CRP and Plt with lower Hb, particularly in younger patients, identified better response to SAR and support biomarker guided selection between IL-6Ri and JAKi. In Phase 2, GC discontinuation with SAR suggests a practical strategy to reduce AEs while maintaining efficacy. Prospective studies should validate these findings and define actionable thresholds. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2261 25 1 2025 Prognostic value of right atrial strain in patients with chronic heart failure 908 EN Rie Nakayama Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yoichi Takaya Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Mitsutaka Nakashima Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Takahiro Nishihara Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Miyoshi Toru Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Kazufumi Nakamura Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Aims Right ventricular dysfunction is a well-established prognostic marker in patients with heart failure (HF). However, the prognostic significance of right atrial (RA) function remains unclear. Given its sensitivity to systemic congestion, RA function may provide additional insights into HF disease progression and management. This study aimed to investigate whether RA reservoir function serves as an independent prognostic indicator in patients with chronic HF. Methods A total of 613 patients with chronic HF and a left ventricular (LV) ejection fraction of less than 50% who underwent echocardiographic assessment at Okayama University Hospital between January 2018 and March 2023 were included (median age: 68 (58–76) years; 69% male). RA reservoir function was quantified using two-dimensional speckle-tracking echocardiography. The primary endpoint was cardiovascular death or HF-related hospitalization. Kaplan–Meier survival analysis was performed to examine the association between RA reservoir function and clinical outcomes. Results During a median follow-up period of 41 months (range: 12–91 months), 119 patients experienced cardiac events. Compared with event-free patients, those with cardiac events exhibited a significantly larger RA maximum volume index (38 mL/m2 vs. 31 mL/m2, P < 0.001) and a significantly lower RA reservoir longitudinal strain (RASr) (17% vs. 22%, P < 0.001). Kaplan–Meier analysis demonstrated that patients with RASr ≤ 20% had significantly poorer event-free survival than those with RASr > 20%, even without RA volume enlargement (log-rank test, P < 0.001). Multivariate Cox regression analysis identified RASr as an independent predictor of cardiac events (hazard ratio: 0.95, 95% confidence interval: 0.93 to 0.97, P < 0.001). Conclusions In patients who experienced adverse cardiac events, a reduced RASr and an increased RA maximum volume were observed. Furthermore, a reduced RASr was independently associated with an increased risk of cardiovascular death and HF-related hospitalization in patients with chronic HF and LV dysfunction. These findings indicate that RASr may serve as a valuable prognostic marker for the risk stratification and management of chronic HF. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1546-0096 23 1 2025 Comparison of clinical practices during the transitional and young adult phases between patients with oligoarticular/polyarticular juvenile idiopathic arthritis and those with rheumatoid arthritis in Japan 120 EN Sho Mori Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine Kosuke Shabana Department of Pediatrics, Osaka Medical and Pharmaceutical University Toshihiro Matsui Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Tomo Nozawa Department of Pediatrics, Graduate School of Medicine, Yokohama City University Yuko Sugita Department of Pediatrics, Osaka Medical and Pharmaceutical University Minako Tomiita Department of Allergy and Rheumatology, Chiba Children’s Hospital Yasuo Nakagishi Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children’s Hospital Yuichi Yamasaki Department of Pediatrics, Kagoshima University Hospital Hiroaki Umebayashi Department of General Pediatrics, Miyagi Children’s Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Naomi Iwata Department of Infection and Immunology, Allergy and Immunology Center, Aichi Children’s Health and Medical Center Junko Yasumura Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences Hiroyuki Wakiguchi Department of Pediatrics, Yamaguchi University Graduate School of Medicine Takeshi Yamamoto Department of Pediatrics, Chiba University Graduate School of Medicine Shunichiro Takezaki Department of Pediatrics, Faculty of Medicinea and Graduate School of Medicine, Hokkaido University Yuka Okura Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center Tadafumi Yokoyama Department of Pediatrics, Kanazawa University Masaki Shimizu Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Masahiro Hirayama Department of Pediatrics, Mie University Graduate School of Medicine Shigeto Tohma Department of Rheumatology, National Hospital Organization Tokyo National Hospital Nami Okamoto Department of Pediatrics, Osaka Medical and Pharmaceutical University Masaaki Mori Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine Background Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition that frequently persists into adulthood, posing long-term challenges in disease control and quality of life. However, clinical management during the transitional and young adult phases remains insufficiently characterized, especially in comparison with adult-onset rheumatoid arthritis (RA). This study aimed to compare disease activity, medication use, and treatment practices between patients with oligoarticular/polyarticular JIA and those with RA, focusing on individuals aged 16–30 years. Methods Data were derived from two nationwide multicenter databases in Japan—NinJa (National Database of Rheumatic Diseases in Japan) for RA and CoNinJa (a pediatric counterpart of NinJa) for JIA. A total of 176 JIA and 152 RA patients, all aged 16–30 years, were analyzed. Clinical parameters, disease activity indices, and medication profiles were compared using the Mann–Whitney U test and Fisher’s exact test. Results Compared to RA patients, JIA patients demonstrated significantly lower disease activity (median SDAI 0.6 vs. 2.4) and higher remission rates, particularly Boolean remission (70% vs. 44%) (p < 0.001). MTX usage was less frequent in JIA (49% vs. 68%, p < 0.001), whereas biologic use was notably more common (69% vs. 38%, p < 0.001), with 31% involving off-label prescriptions. Among patients in CDAI remission, biologic monotherapy was observed more frequently in JIA (29% vs. 7%, p < 0.001). Discontinuation of MTX was most commonly attributed to disease improvement (58%) or gastrointestinal intolerance (nausea, 29%). Subcutaneous tocilizumab, though unapproved for JIA in Japan, had the lowest discontinuation rate (4%), suggesting favorable tolerability. Conclusions Despite an overlap in age, patients with JIA and RA exhibit distinct disease characteristics and therapeutic patterns. These differences underscore the need to expand approved treatment options for JIA, promote equitable access to biologics, and strengthen transitional care frameworks. Further research is warranted to explore long-term outcomes, reproductive health considerations, and socioeconomic barriers that influence treatment continuity in young adults with childhood-onset arthritis. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 5 2026 Effect of Surgical Procedures for Rheumatoid Forefoot Deformities on Radiographic Foot Length and Width Variations 1877 EN Masahiro Horita Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University Yohei Kiso Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama City Hospital Ryuichi Nakahara Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenta Saiga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Background: The number of patients with rheumatoid arthritis (RA) undergoing forefoot arthroplasty has increased to better control the disease. Despite patients frequently expressing concerns regarding postoperative foot appearance and footwear-related expectations, no study has investigated postoperative changes in foot length and width in patients with RA. The aim of this study was to evaluate the effect of surgical procedures for rheumatoid forefoot deformities on variations in radiologically determined foot length and width. Methods: In total, 72 feet of 50 women and 3 men (average age: 66.7 years) underwent joint-preserving arthroplasty (n = 33) and arthrodesis of the first metatarsophalangeal joint with shortening osteotomy of the lesser metatarsals or resection arthroplasty of the lesser metatarsal heads (n = 39); procedures were carried out in our institute from August 2013 to February 2020. The mean disease duration was 23.5 years, and the average follow-up period was 17.5 months. Pre- and postoperative hallux valgus angle (HVA), intermetatarsal angle (IMA) of the first and second metatarsals (M1M2A), and IMA of the first and fifth metatarsals (M1M5A) were measured on weightbearing radiographs as well as foot length and width. We also evaluated the correlation between changes in radiographic parameters and variations in radiologically determined foot length and width. Results: Radiologically determined foot width changed significantly from 10.1 cm to 9.7 cm (p < 0.01), while no significant difference was found between pre- and postoperative radiologically determined foot length. HVA, M1M2A, and M1M5A were significantly improved after the surgery (p < 0.01, p < 0.01, and p < 0.01, respectively). A significant negative correlation was found between the variation in radiologically determined foot length and changes in HVA (r = −0.29, p = 0.02) and M1M5A (r = −0.23, p < 0.05), while a significant positive correlation was found between the variation in the foot width and changes in HVA (r = 0.34, p < 0.01), M1M2A (r = 0.55, p < 0.01), and M1M5A (r = 0.45, p < 0.01). There were no significant differences between operative procedures regarding variation in radiologically determined foot length and width. Conclusions: Surgical procedure for rheumatoid forefoot deformity improved radiographic parameters and reduced radiographic foot width while maintaining foot length. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 4 2026 Perioperative Ozoralizumab Management for Patients with Rheumatoid Arthritis Who Underwent Orthopaedic Surgery: A Retrospective Case Series 1422 EN Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama City Hospital Ryozo Harada Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Ryuichi Nakahara Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Masahiro Horita Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Masamitsu Natsumeda Rheumatic Disease Center, Mabi Memorial Hospital Shuichi Naniwa Department of Orthopaedic Surgery, 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/Objectives: Launched in Japan in 2022, ozoralizumab (OZR) is a novel, anti-tumour necrosis factor (TNF)-α inhibitor for treating rheumatoid arthritis (RA) that is refractory to conventional therapies. However, there is a lack of evidence regarding its perioperative management. Methods: This retrospective case series included nine patients with RA who underwent a total of 12 either RA-related (n = 9) or unrelated (n = 3) orthopaedic procedures. We reviewed patient demographics, surgical procedures, perioperative OZR discontinuation periods, and postoperative complications. Results: The mean preoperative OZR discontinuation period was 15.8 days (range, 2–25 days). Sutures were removed at a mean of 12.8 days postoperatively (range, 11–14 days) after adequate wound healing had been confirmed. The mean total discontinuation period was 34.9 days (range, 27–43 days). No cases of surgical site infection (SSI) or delayed wound healing (DWH) were observed during a minimum follow-up period of three months. One patient experienced a disease flare before OZR was restarted. Conclusions: Preoperative OZR discontinuation for up to four weeks appeared to be safe in this cohort. These findings may assist orthopaedic surgeons in determining an appropriate perioperative discontinuation strategy for OZR that minimises SSI and DWH risk while reducing the likelihood of RA flare. No potential conflict of interest relevant to this article was reported.

China Anti-cancer Association Acta Medica Okayama 2095-3941 2026 SPRED2 suppresses the stemness of hepatocellular carcinoma through the p53/miR-506-3p/KLF4 pathway EN Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sachio Ito Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aye Moh-Moh-Aung Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tianyi Wang Department of Pathology and Experimental Medicine, Graduate School 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 Teizo Yoshimura 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 Objective: We previously reported that endogenous Sprouty-related, EVH1 domain-containing protein 2 (SPRED2), an inhibitor of the Ras/Raf/ERK-MAPK pathway, controls hepatocellular carcinoma (HCC) cell stemness by downregulating the expression of pluripotency factors, such as Nanog, c-Myc, and KLF4, in an ERK-dependent fashion. However, the exact mechanisms by which SPRED2 regulates HCC cell stemness have not been established. Methods: Three human HCC cell lines [HepG2 (parental and SPRED2-deficient), HLE, and Hep3B] were used. Cells were transfected to downregulate or overexpress proteins. Western blot and RT-qPCR were used to evaluate the level of protein and mRNA expression. Co-immunoprecipitation and ChIP-qPCR were used to examine protein-protein interactions and the activation of gene transcription. Clinical HCC tissues were also used to validate in vitro data. Results: KLF4 was identified as the major pluripotency factor responsible for SPRED2-mediated downregulation of HCC cell stemness and KLF4 expression was regulated by miR-506-3p. SPRED2 formed a protein complex with the tumor suppressor (p53) and upregulated miR-506 gene transcription by binding to the promoter region, resulting in subsequent downregulation of KLF4 mRNA expression. There was a negative correlation between KLF4 expression and miR-506-3p and a positive correlation between miR-506-3p expression and SPRED2 in human HCC samples, highlighting the relevance of the study findings. Conclusions: The current study revealed a novel SPRED2/p53/miR-506-3p/KLF4 axis through which SPRED2 contributes to the suppression of HCC cell stemness and provides a potential new target to prevent HCC progression. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Frailty at 1 Month before ICU Admission Poses a Hospital Mortality Risk in Cancer Survivors whose Condition Has Deteriorated due to Medical Factors 437 444 EN Junya Matsumi Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital Tetsufumi Sato Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital Original Article 10.18926/AMO/69846 The optimal indications for intensive care unit (ICU) treatment for critically ill cancer survivors whose condition has deteriorated due to medical factors are unclear. To test our hypothesis that frailty before deterioration was associated with hospital mortality in this patient population, we retrospective analyzed the cases of the patients admitted to the ICU at the National Cancer Center Hospital, Japan (April 2014-March 2022). We excluded patients who underwent surgery within 28 days or were denied critical care within 24 h or admitted after cardiopulmonary arrest. Their Clinical Frailty Scale (CFS) scores at 1 month before ICU admission (Pre-ICU) were obtained. Frailty was defined as CFS scores ≥4 points. We analyzed 298 admissions and observed that the mortality rate at hospital discharge was significantly higher in the frailty group (n=119). A multivariate analysis demonstrated that the following factors were significantly associated with hospital mortality: Pre-ICU frailty (OR 2.00, 95%CI: 1.19-3.36, p=0.009), cancer type (hematological: OR 2.93, 95%CI: 1.42-6.05, p=0.004), and Sequential Organ Failure Assessment score at ICU admission (OR 0.88, 95%CI: 0.82-0.95, p=0.0008). Frailty retrospectively assessed using the CFS at 1 month pre-ICU admission is a risk factor for hospital mortality in these cancer survivors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration in Patients Aged 85 or Older 405 412 EN Chihiro Ouchi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Morizane Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita 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 Original Article 10.18926/AMO/69842 We investigated the treatment outcomes of patients aged ≥85 years with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy using either treat-and-extend (TAE) or pro re nata (PRN) regimens for 1 year in real-world clinical practice. Eighty-five eyes from 85 patients were included. Among them, types 1, 2, and 3 macular neovascularization and polypoidal choroidal vasculopathy were present in 27.1%, 17.6%, 18.8%, and 36.5%, respectively. TAE and PRN regimens were used in 43.5% and 56.5% of patients, respectively. At baseline, the PRN group was older and had worse best-corrected visual acuity (BCVA), greater central retinal thickness, and more intraretinal fluid than the TAE group. In the TAE group, the mean number of injections was 7.6, BCVA improved significantly, and all retinal fluid rates decreased. In the PRN group, the mean number of injections was 3.9, BCVA remained unchanged, and the rates of macular fibrosis and atrophy increased. No serious adverse events were observed in either group. Anti-VEGF therapy was safe for patients aged ≥ 85 years with nAMD, and the TAE regimen effectively improved BCVA in this population. BCVA remained unchanged in the PRN-treated patients, with baseline disease severity and/or undertreatment potentially influencing the outcomes. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 27 35 2025 Synthesis of a Pseudocytidine Nucleoside to Form a Stable and Selective Base Pair with Iso-guanosine in RNA 9749 9752 EN Ryo Miyahara Graduate School of Pharmaceutical Sciences, Kyushu University Yosuke Taniguchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Non-natural base pair formation provides insight into new functions of nucleic acids. Therefore, various artificial base pairs have been developed in both DNA and RNA. In this work, we successfully synthesized pseudocytidine from commercially available pseudouridine to form base pairs with isoguanine, also known as 2-OH-adenine, in RNA. Measurement of the melting temperature with the base pair incorporated at the center of a 13-mer RNA showed the highest value for the ψ-rC and iso-rG (2-OH-rA) base pair. This base pair formation exhibited a high melting temperature regardless of whether it was incorporated into the pyrimidine or purine strand, indicating that it can form a stable and selective duplex RNA. 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 Does perioperative discontinuation of anti-rheumatic drugs increase postoperative complications in orthopedic surgery for rheumatoid arthritis? 219 EN Hiromu Ito Department of Orthopaedic Surgery, Kurashiki Central Hospital Hajime Ishikawa Department of Rheumatology, Niigata Rheumatic Center Shigeyoshi Tsuji Department of Orthopaedic Surgery, Osaka Minami Medical Center Masanori Nakayama Department of Orthopaedic Surgery, International University of Health and Welfare Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Takeshi Mochizuki Department of Orthopaedic Surgery, Kamagaya General Hospital Kosuke Ebina Department of Orthopaedic Surgery, Osaka University Faculty of Medicine Graduate School of Medicine Toshihisa Kojima Department of Orthopaedic Surgery, Nagoya University Hospital Takumi Matsumoto Department of Orthopaedic Surgery, University of Tokyo Ayako Kubota Department of Orthopaedic Surgery, Toho University Omori Medical Center Arata Nakajima Department of Orthopaedic Surgery and Rehabilitation, Toho University Sakura Medical Center Atsushi Kaneko Department of Orthopaedic Surgery, Nagoya Medical Center Isao Matsushita Department of Rehabilitation Medicine, Kanazawa Medical University Ryota Hara The Center for Rheumatic Diseases, Nara Medical University Koji Sakuraba Department of Orthopaedic Surgery, Kyushu Medical Center Yukio Akasaki Department of Orthopaedic Surgery, Kyushu University Tsukasa Matsubara Department of Orthopaedic Surgery, Matsubara Mayflower Hospital Yuichi Mochida Department of Orthopaedic Surgery, Yokohama City University Medical Center Katsuaki Kanbe Department of Orthopaedic Surgery, Nippori Orthopaedics and Rheumatic Clinic Natsuko Nakagawa Department of Orthopaedic Surgery, Kakogawa Medical Center Koichi Murata Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine Shigeki Momohara Endowed Course for Advanced Therapy for Musculoskeletal Disorders, Keio University School of Medicine Objective This study aimed to investigate whether discontinuation of biological or targeted synthetic antirheumatic disease-modifying drugs (bDMARDs or tsDMARDs) influences the incidence of postoperative complications in patients with rheumatoid arthritis (RA) undergoing orthopedic surgery. Methods A retrospective multicenter cohort study including patients receiving bDMARDs or tsDMARDs who underwent orthopedic surgery was conducted. Data collected encompassed the duration of drug discontinuation and postoperative adverse events, such as delayed wound healing, surgical site infection (SSI), disease flare-ups, and mortality. The association between drug discontinuation and these outcomes was analyzed. Multivariate analyses were conducted to identify potential risk factors for these events. Results A total of 2,060 cases were initially enrolled. After applying inclusion and exclusion criteria, data from 1,953 patients were analyzed. No significant differences were observed between the groups regarding delayed wound healing, SSI, or mortality. However, the incidence of disease flare-ups was substantially higher in the drug discontinuation group and in the interleukin (IL)-6 inhibitor group. Multivariate analysis identified that tumor necrosis factor α and IL-6 inhibitor use was associated with a higher risk of delayed wound healing relative to T-cell function modifiers. Conclusion In orthopedic surgery for patients with RA, maintaining the standard or the half of administration interval of bDMARD appears safe in the preoperative period. However, the drug discontinuation may increase the risk of postoperative flare-ups, particularly with IL-6 inhibitors. In addition, T-cell function modifiers may be associated with a lower risk of delayed wound healing, suggesting their safety profile in this context. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0167-4889 1873 2 2026 SPRED2 controls the severity of cisplatin-induced acute kidney injury by inhibiting ERK activation and TNFα production in mice 120091 EN Xu Yang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jiali He 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 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 Steven L. Kunkel Department of Pathology, University of Michigan Medical School Teizo Yoshimura 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 Cisplatin is an effective chemotherapeutic agent used to treat solid tumors, but its clinical use is limited by acute kidney injury (AKI), in which ERK signaling plays a crucial role. Here, we investigated whether Sprouty-related EVH1 domain-containing protein 2 (SPRED2), an endogenous inhibitor of the Ras/Raf/ERK pathway, protects against cisplatin-induced AKI. Spred2−/− mice showed more severe renal injury and stronger ERK activation than wild-type (WT) mice, whereas pretreatment with the MEK inhibitor U0126 markedly attenuated the injury. In HK-2 cells (proximal tubular cells), SPRED2 knockdown enhanced cisplatin-induced apoptosis and caspase-3 activation, accompanied by decreased Bcl-2 expression. Spred2−/− kidneys displayed increased macrophage infiltration and elevated Tnfα, Il1b, and Ccl2 expression. Neutralization of TNFα with anti-TNFα antibody ameliorated renal injury and reduced the levels of Il1b and Ccl2 mRNA in Spred2−/− mice. In vitro, TNFα slightly decreased the viability of control and SPRED2 knockdown HK-2 cells without cisplatin treatment, but the decreased viability was augmented in SPRED2 knockdown cells by cisplatin. Immunohistochemistry revealed that macrophages were the predominant TNFα-positive cell population. Bone marrow–derived macrophages from Spred2−/− mice produced higher levels of TNFα in response to cisplatin compared with control cells, and this increase was markedly suppressed by U0126. These findings indicate that endogenous SPRED2 protects kidneys from cisplatin-induced AKI by limiting ERK activation, tubular apoptosis, and TNFα-mediated inflammation. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 20 2025 Neurofibromin Encoded by the Neurofibromatosis Type 1 (NF1) Gene Promotes the Membrane Translocation of SPRED2, Thereby Inhibiting the ERK Pathway in Breast Cancer Cells 10072 EN Nang Thee Su Pwint Department of Pathology and Experimental 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 Yuze Wang Department of Pathology and Experimental Medicine, Graduate School 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 Masakiyo Sakaguchi Department of Cell Biology, 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 Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Neurofibromin (NF) inhibits the RAS/RAF/ERK pathway through its interaction with SPRED1 (Sprouty-related EVH1 domain-containing protein 1). Here, we investigated the functional relationship between NF and SPRED2 in breast cancer (BC). Human BC cell lines were transfected to downregulate or overexpress NF and SPRED2 and subsequently subjected to functional assays. Protein and mRNA levels were analyzed by Western blotting and RT-qPCR, respectively. Protein–protein interactions were examined by immunoprecipitation. Database analyses and immunohistochemistry (IHC) of BC tissues were performed to validate the in vitro findings. Downregulating NF or SPRED2 expression in BC cells enhanced cell proliferation, migration and invasion accompanied by RAF/ERK activation, whereas overexpression produced opposite effects. NF formed a protein complex with SPRED2 and facilitated its translocation to the plasma membrane. By IHC, SPRED2 membrane localization was absent in NF-negative luminal A and triple-negative BC (TNBC) but present in a subset of luminal A BC. By database analyses, both NF1 and SPRED2 mRNA levels were reduced in BC tissues, and luminal A BC patients with high expression of both NF1 and SPRED2 mRNA exhibited improved relapse-free survival. These results suggest a critical role for the NF–SPRED2 axis in BC progression and highlight it as a potential therapeutic target. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Blood Pressure and Heart Rate Patterns Identified by Unsupervised Machine Learning and Their Associations with Subclinical Cerebral and Renal Damage in a Japanese Community: The Masuda Study 369 379 EN Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sosuke Munetomo Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Fukuda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhide Kojima Department of Radiology, Okayama University Hospital Kaori Taniguchi Department of Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine Noriko Nakahata Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69438 We applied unsupervised machine learning to analyze blood pressure (BP) and resting heart rate (HR) patterns measured during a 1-year period to assess their cross-sectional relationships with subclinical cerebral and renal target damage. Dimension reduction via uniform manifold approximation and projection, followed by K-means++ clustering, was used to categorize 362 community-dwelling participants (mean age, 56.2 years; 54.9% women) into three groups: Low BP and Low HR (Lo-BP/Lo-HR), High BP and High HR (Hi-BP/Hi-HR), and Low BP and High HR (Lo-BP/Hi-HR). Cerebral vessel lesions were defined as the presence of at least one of the following magnetic resonance imaging findings: lacunar infarcts, white matter hyperintensities, cerebral microbleeds, or intracranial artery stenosis. A high urinary albumin-to-creatinine ratio (UACR) was defined as the top 10% (≥ 12 mg/g) of the mean value from ≥2 measurements. Poisson regression with robust error variance, adjusted for demographics, lifestyle, and medical history, showed that the Hi-BP/Hi-HR group had relative risks of 3.62 (95% confidence interval, 1.75-7.46) for cerebral vessel lesions and 3.58 (1.33-9.67) for high UACR, and the Lo-BP/Hi-HR group had a relative risk of 3.09 (1.12-8.57) for high UACR, compared with the Lo-BP/Lo-HR group. These findings demonstrate the utility of an unsupervised, data-driven approach for identifying physiological patterns associated with subclinical target organ damage. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Advantages of Single-Position Surgery over Posterior Fusion for Single-Level Degenerative Lumbar Diseases 359 368 EN Tomohiko Hirose Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Hisanori Ikuma Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Kazutoshi Otsuka Otsuka Orthopedic Clinic Keisuke Kawasaki Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Original Article 10.18926/AMO/69437 Single-position surgery with lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screws (PPSs) is gaining attention for its reduced invasiveness. We developed SPAPS, a technique allowing two surgeons to perform anterior LLIF and posterior PPS insertion simultaneously in a single lateral decubitus position. This retrospective study compared SPAPS (SPAPS-LLIF, Group SL) and minimally invasive posterior/transforaminal lumbar interbody fusion (MIS-PLIF/TLIF, Group PT) in patients treated between 2016 and 2019 with a two-year follow-up. Operative time, estimated blood loss (EBL), length of hospital stay (LOS), JOABPEQ and VAS scores, segmental lordotic angle, lumbar lordotic angle, segmental Cobb’s angle, PPS misplacement, PPS loosening, fusion status, and muscle cross-sectional areas were compared. Fifty-two patients were analyzed (Group SL: 25; Group PT: 27). SPAPS significantly reduced operative time (118.0 vs. 165.3 min, p <0.01) and estimated blood loss (8.6 vs. 164.1 mL, p<0.01). While clinical outcomes and hospital stay were comparable, Group SL had significantly lower PPS loosening (0% vs. 13%, p<0.01) and non-union rates (0% vs. 22.2%, p=0.02). Multifidus muscle atrophy was also less in Group SL (−14.3 vs. −121.5 mm2, p<0.01). SPAPS demonstrated advantages in reducing surgical invasiveness without compromising clinical efficacy, offering a promising alternative to conventional posterior fusion surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 A Review of the Endoscopic Treatment for Bile Leak Following Cholecystectomy and Hepatic Surgery 321 328 EN Taisuke Obata 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/69432 Bile leak occurs in 2-25% of liver transplant, 3-27% of hepatic resection, and 0.1-4% of cholecystectomy cases. The clinical course of bile leak varies depending on the type of surgery that caused the fistula, as well as the type, severity, and timing of bile duct injury. Although infections resulting from bile leak can be life-threatening, the introduction of endoscopic treatment has enabled some patients to avoid reoperation and has reduced the negative impact on quality of life associated with external fistulas for percutaneous drainage. Endoscopic interventions, such as sphincterotomy and stent placement, reduce the pressure gradient between the bile duct and duodenum, facilitating bile drainage through the papilla and promoting the closure of the leak. We reviewed the literature from 2004 to 2024 regarding bile leak following cholecystectomy and liver surgery, examining recommended techniques, timing, and treatment outcomes. In cases of bile leak following cholecystectomy, clinical success was achieved in 72-96% of cases, while success rates for bile leak following liver surgery ranged from 50% to 100%. Although endoscopic treatment is effective, it is not universally applicable, and its limitations must be carefully considered. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 A Case of Surgical Treatment for a Large Pulmonary Artery Aneurysm with a Quadricuspid Pulmonary Valve 317 320 EN Kei Morioka Department of Cardiovascular Surgery, Okayama University Hospital Yosuke Kuroko Department of Cardiovascular Surgery, Okayama University Hospital Sachiko Kadowaki Department of Cardiovascular Surgery, Okayama University Hospital Junko Kobayashi Department of Cardiovascular Surgery, Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery, Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Hospital Case Report 10.18926/AMO/69160 A 65-year-old man was referred to our hospital for the annual assessment of the diameter and dilation of a pulmonary artery (PA) aneurysm. He had a small ventricular septal defect (VSD) that had closed naturally. Echocardiography revealed a dilated main PA, mild pulmonary regurgitation and no VSD. Computed tomography confirmed the dilation of the main PA (66.7×47.8 mm), right PA (37.1×32.9 mm), and left PA (36.7×34.0 mm). The patient underwent pulmonary artery replacement using a prosthetic vascular graft. A quadricuspid pulmonary valve was identified intraoperatively. Early surgical intervention could help to prevent rupture and dissection of PA aneurysms. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 A Study of Periprosthetic Femoral Stem Fractures in Hip Arthroplasty for Femoral Neck Fracture 253 259 EN Yoshiaki Miyake Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Toru Takagi Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Taizo Konishiike Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Original Article 10.18926/AMO/69150 This study investigated the risk factors for bone fragility and perioperative periprosthetic femoral stem fractures in patients undergoing hip arthroplasty for femoral neck fractures. The records of 215 patients (42 male, 173 female; mean age, 84.4 years) were analyzed to assess correlations among periprosthetic fracture rates and sex, age, body mass index (BMI), Dorr classification, femoral stem fixation type (cemented/cementless), and bone mineral density (BMD) of the contralateral proximal femur. The overall prevalence of perioperative periprosthetic fractures was 4.7%. All patients with periprosthetic fractures were female, and all but one were ≥ 80 years of age. Fracture rates were higher in patients with lower BMI, although this difference was not significant. The fracture rates were 0%, 4.7%, and 7.9% for Dorr types A, B, and C, respectively, and 0% and 5.3% for patients who received cemented and cementless stems, respectively. The findings indicated that female patients, those of advanced age, those with lower BMI, and those with Dorr type C had lower BMDs. Although BMD was significantly lower in patients who received cemented stems compared to those who received cementless stems, no fractures were observed in the former group, suggesting that the use of cemented stems is safe for this high-risk population. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 The Work Productivity of Cancer-survivor and Non-cancer-survivor Workers 243 251 EN Mika Kamano Department of Public Health, Faculty of Medicine, Kagawa University Kanae Kanda Department of Public Health, Faculty of Medicine, Kagawa University Nlandu Roger Ngatu Department of Public Health, Faculty of Medicine, Kagawa University Akitsu Murakami Cancer Center, Kagawa University Hospital Yusuke Yamadori Department of Anesthesiology, Faculty of Medicine, Kagawa University Tomohiro Hirao Department of Public Health, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/69149 We investigated the work productivity levels of employed cancer survivors and non-cancer-survivor workers by conducting a cross-sectional study in Japan between February and March 2019, using an online survey. A total of 561 employed individuals aged 20-64 years were analyzed. Work productivity was assessed using the Work Productivity and Activity Impairment-General Health questionnaire which evaluates absenteeism, presenteeism, and overall work productivity loss. The questionnaire responses demonstrated that the cancer survivors within 1 year of diagnosis had significantly higher absenteeism compared to the non-cancer workers (p=0.048). Although presenteeism and overall work productivity loss were also higher in the non-cancer-survivor group, the differences were not significant. Cancer survivors within 1 year of diagnosis exhibited higher absenteeism, but their work productivity appeared to recover to levels comparable to those of the non-cancer workers over time. These findings may contribute to workplace policies supporting cancer survivors’ return to work. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Organ Donation after Extracorporeal Cardiopulmonary Resuscitation: Clinical and Ethical Perspectives 221 229 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 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 Kohei Ageta 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 Kohei Tsukahara 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 Review 10.18926/AMO/69147 Extracorporeal cardiopulmonary resuscitation (ECPR) has evolved into a life-saving therapy for select cardiac arrest patients, yet a growing body of evidence suggests it also holds promise as a bridge to organ donation in non-survivors. This review explores the clinical outcomes, ethical complexities, and evolving policies surrounding organ donation after ECPR. We summarize recent international and Japanese data demonstrating favorable graft function from ECPR donors, with the exception of lung transplantation. The ethical challenges — particularly those involving brain death determination on extracorporeal membrane oxygenation and adherence to the dead donor rule — are discussed in the context of Japan’s recent regulatory reforms. Additionally, we highlight the importance of structured end-of-life communication through multidisciplinary team meetings in facilitating ethically sound transitions from rescue efforts to donation pathways. Moving forward, improvements in donor management, standardized legal frameworks, and public and professional education are essential to optimizing the life-saving and life-giving potential of ECPR. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 10 2025 Experience of High Tibial Osteotomy for Patients with Rheumatoid Arthritis Treated with Recent Medication: A Case Series 3332 EN Yasuhiro Takahara Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Hirotaka Nakashima Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Keiichiro Nishida Department of Orthopedic Surgery, Okayama University Hospital Yoichiro Uchida Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Hisayoshi Kato Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Satoru Itani Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Yuichi Iwasaki Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Background: High tibial osteotomy (HTO) was generally not indicated in patients with rheumatoid arthritis (RA) because synovial inflammation may exacerbate joint damage postoperatively. Recently, joint destruction in RA has dramatically changed with the introduction of methotrexate (MTX) and biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the clinical outcomes of HTO for patients with RA treated with recent medication. Methods: In this study, patients with RA who underwent HTO between 2016 and 2020 were retrospectively reviewed. Patients whose follow-up period was <2 years and those whose onset of RA occurred after HTO were excluded. Clinical outcomes were investigated using the Japanese orthopedic Association (JOA) and visual analog scale (VAS) scores. Results: Seven patients (two males and five females, mean age 72.0 ± 6.2 years, mean body mass index 24.0 ± 2.9 kg/m2) were included in this study. The mean follow-up period was 62.1 ± 21.4 months. Open-wedge and hybrid closed-wedge HTO were performed in two and five cases, respectively. MTX was used for all cases. The bDMARDs were used in six cases (golimumab and tocilizumab in four and two cases, respectively). JOA scores significantly improved from 63.6 ± 10.7 preoperatively to 90.7 ± 5.3 postoperatively (p = 0.0167 Wilcoxon rank test). VAS scores significantly decreased from 48.6 ± 12.2 preoperatively to 11.4 ± 6.9 postoperatively (p = 0.017 Wilcoxon rank test). None of the patients underwent total knee arthroplasty. Conclusions: This study showed seven RA patients who underwent HTO treated with recent medication. The prognosis of RA, including joint destruction, has dramatically improved with induction of MTX and bDMARDs. HTO may be one of effective joint preservation surgeries even for patients with RA. To achieve the favorable outcomes, surgeons should pay attention to timing and indication of surgery. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 24 2024 A Preliminary Survey of Rheumatologists on the Management of Late-onset Rheumatoid Arthritis in Japan 3299 3306 EN Satoshi Takanashi Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine Yuko Kaneko Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine Yutaka Kawahito Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Takashi Kida Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Takahiko Sugihara Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine Toshihisa Kojima National Hospital Organization Nagoya Medical Center, Orthopaedic Surgery and Rheumatology Ryozo Harada Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Michinori Ishitoku Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital Shintaro Hirata Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital Motomu Hashimoto Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine Toshihiko Hidaka Miyazaki-Zenjinkai Hospital Asami Abe Department of Rheumatology, Niigata Rheumatic Center Hajime Ishikawa Department of Rheumatology, Niigata Rheumatic Center Hiromu Ito Kurashiki Central Hospital Mitsumasa Kishimoto Department of Nephrology and Rheumatology, Kyorin University School of Medicine Kazuo Matsui Department of Rheumatology, Teine Keijinkai Hospital Toshihiro Matsui Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Isao Matsushita Department of Rehabilitation Medicine, Kanazawa Medical University Akira Onishi Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University Akio Morinobu Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University Keiichiro Nishida Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuji Asai Department of Orthopaedic Surgery and Rheumatology, Nagoya University Graduate School of Medicine Eiichi Tanaka Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine Masayoshi Harigai Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine Masayo Kojima Department of Public Health, Nagoya City University Graduate School of Medical Sciences Objective We investigated the current perspectives regarding the management of late-onset rheumatoid arthritis (LORA) among rheumatologists in clinical practice. Methods This study was performed in October 2021, and included 65 rheumatologists certified by the Japan College of Rheumatology, who were administered questionnaires (including multiple choice and descriptive formulae) regarding the management of LORA. We aggregated and analyzed the responses. Results All 65 rheumatologists responded to the survey; 47 (72%) answered that >50% of newly diagnosed patients were aged ≥65 years, 42 (65%) answered that achievement of remission or low disease activity was the treatment goal, and 40 (62%) considered patient safety to be the highest priority. Most rheumatologists are concerned about the management of conditions other than RA, such as comorbidities, financial constraints, and life circumstances that interfere with standard or recommended treatment implementation. Conclusion This preliminary survey highlighted various rheumatologists' perspectives regarding the management of LORA. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Continuous Stimulation with Glycolaldehyde-derived Advanced Glycation End Product Reduces Aggrecan and COL2A1 Production via RAGE in Human OUMS-27 Chondrosarcoma Cells 157 166 EN Omer Faruk Hatipoglu Department of Pharmacology, Faculty of Medicine, Kindai University Takashi Nishinaka Department of Pharmacology, Faculty of Medicine, Kindai University Kursat Oguz Yaykasli Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen Shuji Mori Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Watanabe Department of Pharmacology, School of Pharmacy, Shujitsu University Takao Toyomura Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Nishibori Department of Translational Research & Dug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Hideo Takahashi Department of Pharmacology, Faculty of Medicine, Kindai University Hidenori Wake Department of Pharmacology, Faculty of Medicine, Kindai University Original Article 10.18926/AMO/68723 Chondrocytes are responsible for the production of extracellular matrix (ECM) components such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With age, advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, causing and accelerating pathological changes associated with chronic diseases such as OA. Glycolaldehyde-derived AGE (AGE3), which is toxic to a variety of cell types, have a stronger effect on cartilage compared with other AGEs. To understand the long-term effects of AGE3 on cartilage, we stimulated a human chondrosarcoma cell line (OUMS-27), which exhibits a chondrocytic phenotype, with 10 μg/ml AGE3 for 4 weeks. As a result, the expressions of COL2A1 and aggrecan were significantly downregulated in the OUMS-27 cells without inducing cell death, but the expressions of proteases that play an important role in cartilage destruction were not affected. Inhibition of the receptor for advanced glycation end products (RAGE) suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Immunometabolic Regulation of Innate Immunity in Systemic Lupus Erythematosus 147 155 EN Haruki Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/68722 Pathogens or their components can induce long-lasting changes in the behavior of innate immune cells, a process analogous to “training” for future threats or environmental adaptation. However, such training can sometimes have unintended consequences, such as the development of autoimmunity. Systemic lupus erythematosus (SLE) is a chronic and heterogeneous autoimmune disease characterized by the production of autoantibodies and progressive organ damage. Innate immunity plays a central role in its pathogenesis, contributing through impaired clearance of apoptotic cells, excessive type I interferon production, and dysregulated formation of neutrophil extracellular traps. Recent studies have revealed that metabolites and nucleic acids derived from mitochondria, a crucial energy production site, directly regulate type I interferon and anti-inflammatory cytokine production. These insights have fueled interest in targeting metabolic pathways as a novel therapeutic approach for SLE, offering promise for improving long-term patient outcomes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1572-9613 192 5 2025 The Intertwining Property for Laguerre Processes with a Fixed Parameter 58 EN Alexander I. Bufetov Steklov Mathematical Institute of RAS Yosuke Kawamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University We investigate the intertwining of Laguerre processes of parameter α in different dimensions. We introduce a Feller kernel that depends on α and intertwines the α-Laguerre process in N + 1 dimensions and that in N dimensions. When α is a non-negative integer, the new kernel is interpreted in terms of the conditional distribution of the squared singular values: if the singular values of a unitarily invariant random matrix of order (N+α+1)×(N+1) are fixed, then the those of its (N+α) × N truncation matrix are given by the new kernel. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 A Case of Retinitis Pigmentosa Diagnosed with Severe Anterior Capsule Contraction after Cataract Surgery 129 134 EN Akihiro Tsuji Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosuke Takahashi Fukuyama City Hospital, Fukuyama City Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/68652 A 66-year-old woman presented with significant anterior capsule contraction and intraocular lens dislocation in both eyes 4 months after cataract surgery. Postoperative examinations such as fluorescein angiography, Goldmann perimetry, and electroretinography revealed retinitis pigmentosa (RP). Patients with significant anterior capsule contraction after cataract surgery should be closely examined because RP may be a contributing factor. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Macular Hole Formation Six Months after Hemorrhage Displacement for Submacular and Henle Fiber Layer Hemorrhage due to Retinal Arterial Macroaneurysm Rupture 123 127 EN Riku Akatsuka Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Morizane Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichiro Doi 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 Case Report 10.18926/AMO/68651 A 78-year-old woman presented with sudden vision loss and central scotoma. Visual acuity in the right eye was 20/222, with submacular hemorrhage (SMH) and Henle fiber layer hemorrhage (HFLh) due to retinal arterial macroaneurysm (RAM) rupture. She underwent SMH displacement, including cataract surgery, vitrectomy, intravitreal injection of tissue-plasminogen activator, and air tamponade. Three months postoperatively the SMH and HFLh had disappeared and visual acuity had improved to 20/200. Six months postoperatively, a macular hole had developed. We performed an inverted internal limiting membrane flap and gas tamponade. Ten months later, the hole had closed and visual acuity had improved to 20/100. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Effectiveness of Postoperative Irradiation in Patients with cN0 Early Breast Cancer Treated with Sentinel Lymph Node Surgery 101 107 EN Hiroshi Isozaki Department of Surgery, Oomoto Hospital Sasau Matsumoto Department of Surgery, Oomoto Hospital Takehiro Takama Department of Surgery, Oomoto Hospital Yuka Isozaki Department of Surgery, Oomoto Hospital Original Article 10.18926/AMO/68648 To evaluate the effectiveness of postoperative irradiation (POI) for patients with cN0 early breast cancer, we retrospectively analyzed the cases of 650 consecutive breast cancer patients who underwent sentinel lymph node (SLN)-guided surgery (2005-2022) at our hospital. In this cohort, 53% (278/521) of the patients who underwent breast conservative surgery (BCS) and 96% (124/129) of those treated with mastectomy did not receive POI. The patients who underwent BCS were treated with POI using opposing tangential field irradiation. A false negative (FN) SLN was retrospectively defined as a negative metastasis in SLN plus positive recurrence in the axillary lymph nodes. Recurrence was detected in 83 patients. A logistic regression analysis revealed that the nuclear grade (odds ratio [OR] 1.69), POI (OR 0.41), and postoperative hormone therapy (OR 0.40) were each significantly related to recurrence. The 26.1% (12/46) FN rate of the non-POI patients decreased to 5.8% (1/17) compared to those treated with POI. The rate of axillary recurrence was significantly lower in the POI group (0.4%) versus the non-POI group (2.7%) (p=0.0355). The rate of locoregional recurrence was also significantly lower in the POI group (2.0%) versus the non-POI group (13.4%) (p<0.0001). No significant difference was observed in the rate of distant recurrence between the POI (4.0%) and non-POI (3.3%) (p=0.831) groups. These results indicated that the postoperative opposing tangential field irradiation of conserved breast tissue inhibited recurrence in the axillary lymph nodes. No potential conflict of interest relevant to this article was reported.

The Japanese Society for Neuroendovascular Therapy Acta Medica Okayama 1882-4072 19 1 2025 Non-Sinus-Type Dural Arteriovenous Fistula at the Foramen Magnum: A Review of the Literature ra.2023-0019 EN Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Tomohiko Ozaki Department of Neurosurgery, National Hospital Organization Osaka National Hospital Rie Aoki Department of Neurosurgery, Tokai University Hachioji Hospital Shinri Oda Department of Neurosurgery, Tokai University Hachioji Hospital Jun Haruma Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Tomohito Hishikawa Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Sugiu Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Dural arteriovenous fistula (dAVF) of the foramen magnum (FM) region is rare. Moreover, the terminology of dAVF is very confusing in this region. In the narrow sense, the FM dAVF is the non-sinus-type dAVF with direct venous reflux to the medulla oblongata or spinal cord via the bridging veins (BVs) of the FM. Previous literature was systematically reviewed to investigate the clinical characteristics, angioarchitecture, and effective treatment of the FM dAVF. From the literature review, almost all the feeders of FM dAVF were dural branches. Spinal pial arteries were rarely involved as the feeder. All lesions had venous reflux to the medulla oblongata via medullary BVs. The FM dAVF is characterized by a significant male predominance and a high incidence of aggressive symptoms. The most common symptom is congestive myelopathy, followed by hemorrhage. The FM dAVF differs from the craniocervical junction (CCJ) arteriovenous fistula (AVF) and is similar to the thoracolumbar spinal dAVF. Direct surgery for the FM dAVF is effective and safe. Endovascular treatment for the FM dAVF may be more effective and has lower complication rates than that for the CCJ AVF. No potential conflict of interest relevant to this article was reported.

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 64 2 2024 Atypical lymphoplasmacytic and immunoblastic proliferation: A Systematic Review 97 106 EN Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Toshiaki Takahashi Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Kensuke Takaoka Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Sharina Macapagal Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Chalothorn Wannaphut Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Hiroko Toda Department of Pathology, Chugoku Central Hospital Yoshito Nishimura Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including “atypical lymphoplasmacytic and immunoblastic lymphadenopathy” from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Endothelial Cell Polarity in Health and Disease 1 7 EN Moe Thiha Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Hikita Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Nakayama Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/68353 Endothelial cell polarity is fundamental to the organization and function of blood vessels, influencing processes such as angiogenesis, vascular stability, and response to shear stress. This review elaborates on the molecular mechanisms that regulate endothelial cell polarity, focusing on key players like the PAR polarity complex and Rho family GTPases. These pathways coordinate the front–rear, apical–basal and planar polarity of endothelial cells, which are essential for the proper formation and maintenance of vascular structures. In health, endothelial polarity ensures not only the orderly development of blood vessels, with tip cells adopting distinct polarities during angiogenesis, but also ensures proper vascular integrity and function. In disease states, however, disruptions in polarity contribute to pathologies such as coronary artery disease, where altered planar polarity exacerbates atherosclerosis, and cancer, where disrupted polarity in tumor vasculature leads to abnormal vessel growth and function. Understanding cell polarity and its disruption is fundamental not only to comprehending how cells interact with their microenvironment and organize themselves into complex, organ-specific tissues but also to developing novel, targeted, and therapeutic strategies for a range of diseases, from cardiovascular disorders to malignancies, ultimately improving patient outcomes. No potential conflict of interest relevant to this article was reported.

Japan Society of Plastic and Reconstructive Surgery Acta Medica Okayama 2436-259X 2 3 2023 A Case of a Transwoman with Colorectal Cancer after Flap Vaginoplasty 98 101 EN Shiho Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Fuminori Teraishi Department of Minimally Invasive Therapy Center, Okayama University Hospital Sari Fujimoto Department of Plastic and Reconstructive Surgery, Okayama University Hospital Toshiyuki Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Sho Takeda Department of Gastroenterological Surgery, Okayama University Hospital Shuhei Narita Department of Gastroenterological Surgery, Okayama University Hospital Koya Yamashita Department of Gastroenterological Surgery, Okayama University Hospital Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Hospital Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Hospital Yuzaburo Namba Department of Gender Center, Okayama University Hospital Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Hospital Vaginoplasty is a gender-affirming surgery (GAS) for transwomen that laid its foundation in the 1950s and continues to be widely practiced worldwide. We present here a case of a 70-year-old transwoman who underwent lower anterior resection for rectal cancer 12 years after vaginoplasty. The preoperative diagnosis was rectal cancer (Rb-Ra, type 2, cT2N0M0, stage 1). All imaging studies showed a cord-like structure between the prostate and the anterior wall of the rectum, which was thought to be the neovagina. Careful dissection of the anterior rectal wall was required because the distance between the neovagina and the rectum was only 1.5 mm. The role of hormonal therapy and GAS in cancer development in transwomen is unclear. It is important to have regular check-ups for malignancies in patients who have undergone GAS, and if surgical procedures are needed, they should be treated by physicians who are familiar with the procedure. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Focal Cerebral Hypoperfusion Detected by Arterial Spin-Labeled Magnetic Resonance Imaging in Patients with Migraine Presenting with Neurological Symptoms Concomitant with or without Headache 413 421 EN Kenichi Kashihara Okayama Neurology Clinic Minoru Irisawa Department of Radiology, Okayama Kyokuto Hospital Wataru Takao Division of Radiology, Okayama Kyokuto Hospital Case Report 10.18926/AMO/67666 We investigated patients with migraine or migraine variants who exhibited focal cerebral hypoperfusion on arterial spin-labeled (ASL) magnetic resonance (MR) imaging along with neurological symptoms. Fourteen patients with migraine demonstrated focal cerebral hypoperfusion. Three other patients did not have a history of recurrent headaches but exhibited comparable cerebral hypoperfusion to migraine patients on ASL-MRI in addition to neurological symptoms. Patients with migraine may present with neurological symptoms associated with cortical spreading depression during, after, or even without a headache phase. Additionally, the isolated neurological symptoms may be caused by a pathophysiology identical to that of migraine but without presenting with recurrent headaches. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Phenotypic and Genetic Characteristics of Carbapenemase-Producing Enterobacterales Isolates at Okayama University Hospital 371 376 EN Kazuyoshi Gotoh Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makoto Miyoshi Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University I Putu Bayu Mayura Department of Clinical Microbiology, Faculty of Medicine, Udayana University Shuma Tsuji Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Original Article 10.18926/AMO/67657 Spread of carbapenemase-producing Enterobacterales (CPE) is an ongoing public health issue worldwide, including in Japan. In this study, we investigated the phenotypic and genetic characteristics of CPE isolates at Okayama University Hospital over the 5 years (2013-2018) prior to the outbreak of the 2019 coronavirus pandemic. Of 24 carbapenem-resistant Enterobacterales isolated during the study period, we identified 8 CPE isolates harboring blaIMP-1 (5 isolates) and blaIMP-6 genes (3 isolates). Bacterial species and carbapenem susceptibility patterns exhibited diversity. Minimum inhibitory concentrations (MICs) of meropenem were generally higher than those of imipenem and biapenem. Results of pulsed-field gel electrophoresis demonstrated that neither clonal nor plasmid-mediated outbreaks of blaIMP-harboring CPE isolates have developed at our hospital. One Klebsiella oxytoca isolate showed a high MIC (128 μg/mL) of meropenem, which could be explained by the high plasmid copy number. Subsequent analysis of this isolate may elucidate the intricacies of carbapenem resistance profiles among CPE isolates. Collectively, our findings underscore the necessity for ongoing genetic surveillance of CPE, complemented by tailored approaches for infection prevention and control. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6643 16 17 2024 Cyclic Oligosaccharide-Induced Modulation of Immunoglobulin A Reactivity to Gut Bacteria Contributes to Alterations in the Bacterial Community Structure 2824 EN Taisei Miyamoto Graduate School of Environmental and Life Science, Okayama University Takeshi Tsuruta Graduate School of Environmental and Life Science, Okayama University Mao Teraoka Graduate School of Environmental and Life Science, Okayama University Tianyang Wang Graduate School of Environmental and Life Science, Okayama University Naoki Nishino Graduate School of Environmental and Life Science, Okayama University Immunoglobulin A (IgA) is a major gut antibody that coats commensal gut bacteria and contributes to shaping a stable gut bacterial composition. Although previous studies have shown that cyclic oligosaccharides, including cyclic nigerosyl-1,6-nigerose (CNN) and cyclodextrins (CDs, including alpha CD, beta CD, and gamma CD), alter the gut bacterial composition, it remains unclear whether cyclic oligosaccharides modify the IgA coating of gut bacteria, which relates to cyclic oligosaccharide-induced alteration of the gut bacterial composition. To address this issue, mice were maintained for 12 weeks on diets containing CNN, alpha CD, beta CD, or gamma CD; the animals' feces were evaluated for their bacterial composition and the IgA coating index (ICI), a measure of the degree of IgA coating of bacteria. We observed that the intake of each cyclic oligosaccharide altered the gut bacterial composition, with changes in the ICI found at both the phylum and genus levels. The ICI for Bacillota, Lachnospiraceae NK4A136 group, UC Lachnospiraceae, and Tuzzerella were significantly and positively correlated with the relative abundance (RA) in total bacteria for these bacteria; in contrast, significant correlations were not seen for other phyla and genera. Our observations suggest that cyclic oligosaccharide-induced modulation of the IgA coating of gut bacteria may partly relate to changes in the community structure of the gut bacteria. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 4 2024 Middle-Ear Salivary Gland Choristoma with Congenital, Single-Sided Hearing Loss 349 355 EN Yuichiro Tominaga Department of Otolaryngology, Head and Neck Surgery, Hiroshima City, Hiroshima Citizens Hospital Akiko Sugaya Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology, Head and Neck Surgery, Kawasaki Medical School Hospital Aiko Shimizu Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Kataoka 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 Case Report 10.18926/AMO/67554 Middle-ear salivary gland choristoma (SGCh) is a rare, benign tumor that causes conductive hearing loss owing to middle-ear morphological abnormalities. Early diagnosis is challenging, and surgical resection is indispensable for a definitive diagnosis. We report the case of a 3-year-old boy diagnosed with middle-ear SGCh during the follow-up period for left-sided hearing loss discovered at newborn hearing screening (NHS). Long-term follow-up after the NHS result, subsequent computed tomography/magnetic resonance imaging, and surgical resection led to its relatively early diagnosis and treatment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 4 2024 Effect of Recipient Age on Perioperative Complications after Pediatric Liver Transplantation: A Single-Center Retrospective Study 323 330 EN Akira Katayama Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kimura Department of Anesthesia, Kyoto University Hospital Takashi Matsusaki Department of Anesthesiology, Mie University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/67548 It has not been clear how recipient age affects the incidence of serious complications after pediatric living donor liver transplantation (LDLT). We investigated the records of 42 pediatric patients receiving LDLT, dividing our sample into two groups: the infant group (aged < 1 year) and the non-infant group (aged ≥ 1 year and ≤15 years). The primary outcome was postoperative complications assessed using the Clavien-Dindo classification. Multivariate analysis using the Cox regression model was applied to adjust for confounding factors in assessing the incidence of Clavien-Dindo grade ≥ III (C-D ≥ III) complications. The incidence of C-D ≥ III complications was higher in the non-infant group (46.2%) than in the infant group (12.5%) (odds ratio 6.00, 95% confidence interval [CI] 1.13-31.88, p=0.03). In multivariate analysis using the Cox regression model, the Graft-to-Recipient Weight Ratio (GRWR) was independently associated with the incidence of C-D ≥ III complications (hazard ratio [HR] 0.62, 95%CI 0.40-0.95, p=0.03), but being an infant was not (HR 0.84, 95%CI 0.35-1.98, p=0.68). In conclusion, the incidence of C-D ≥ III complications was higher in the non-infant group than in the infant group, but this was largely a function of GRWR: multivariate analysis revealed that GRWR was independently associated with complications. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2055-5822 11 6 2024 Prognostic value of right atrial function in patients with significant tricuspid regurgitation 4019 4027 EN Takahiro Nishihara 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 Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihisa Toh 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 Aims　Although right ventricular (RV) dysfunction is associated with adverse outcomes in tricuspid regurgitation (TR), the potential role of right atrial (RA) function is unknown. We aimed to investigate the relationship between RA function and clinical outcomes in patients with significant TR. Methods　This retrospective study included 169 outpatients with moderate or severe TR due to left-sided heart diseases who underwent transthoracic echocardiography between June 2020 and April 2023 (average age, 75 ± 10 years; male, 40%). Patients with atrial fibrillation were excluded from this study due to the inaccuracy of the evaluation using 2D speckle-tracking echocardiography. RA function was compared between patients with and without events, which were defined as all-cause mortality or hospitalization due to heart failure. RA function was calculated as RA global longitudinal strain (RAGLS) with the 2D speckle-tracking echocardiography. Results　During a median follow-up of 13 months, 19 patients had events (all-cause mortality: 14 cases, hospitalization due to heart failure: 5 cases). RAGLS was lower in patients with events than in those without events (13% ± 10% vs. 18% ± 9%, P = 0.02). When the patients were categorized into two groups [low RAGLS ≤ 16.2% vs. high RAGLS > 16.2%, high RA volume index (RAVI) ≥ 50 mL/m2 vs. low RAVI < 50 mL/m2], Kaplan–Meier curves showed that patients with low RAGLS had higher event rates than those with high RAGLS (log-rank test, P = 0.003). Patients with high RAVI had higher event rates than those with low RAVI (log-rank test, P < 0.001). In the multivariate Cox regression analysis, low RAGLS (≤16.2%) was significantly associated with events in a model that included RV dysfunction (RV fractional area change ≤ 35%) or high RAVI (≥50 mL/m2) (hazard ratio: 4.55, 95% confidence interval: 1.51–13.71, P < 0.01; hazard ratio: 4.57, 95% confidence interval: 1.52–13.79, P < 0.01, respectively). Conclusions　RAGLS is associated with all-cause mortality and hospitalization due to heart failure in patients with significant TR. Our results suggest that RA function is a sensitive marker for identifying the risk stratification of significant TR. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis 259 270 EN Gonul Vural Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University Esra Demir Department of Neurology, Ankara City Hospital Sadiye Gumusyayla Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University Funda Eren Department of Clinical Biochemistry, Ankara City Hospital Serdar Barakli Department of Neurology, Ankara City Hospital Salim Neselioglu Department of Clinical Biochemistry, Ankara City Hospital Ozcan Erel Department of Clinical Biochemistry, Ankara City Hospital Original Article 10.18926/AMO/67201 The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol–disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients’ sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol–disulfide homeostasis and ischaemia-modified albumin were measured. We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol–disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol–disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol–disulfide homeostasis in multiple sclerosis patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 Comparative Analysis of Thoracic Rotation Exercises: Range of Motion Improvement in Standing and Quadruped Variants 251 258 EN Koji Murofushi Sports Science Center, Tokyo Medical and Dental University (TMDU) Sho Mitomo Japan Sports Agency Kenji Hirohata Clinical Center for Sports Medicine and Sports Dentistry, Tokyo Medical and Dental University (TMDU) Hidetaka Furuya Department of Rehabilitation, Sonoda Third Hospital/Tokyo Medical Institute Tokyo Spine Center Hiroki Katagiri Department of Orthopedics, Dokkyo Medical University Saitama Medical Center Koji Kaneoka Faculty of Sport Science, Waseda University Kazuyoshi Yagishita Clinical Center for Sports Medicine and Sports Dentistry, Tokyo Medical and Dental University (TMDU) Original Article 10.18926/AMO/67200 There have been few investigations into the effectiveness of thoracic spine exercises for improving thoracic range of motion (ROM) in any plane. This study assessed the effectiveness of two thoracic spine exercises: one in the quadruped position and one in the thoracic standing position. We determined how these exercises affect thoracic spine mobility ROM over a 2-week intervention period. Thirty-nine healthy participants were enrolled and assigned to a Quadruped Thoracic Rotation group (n=17 participants: 9 females and 8 males) or Flamenco Thoracic Spine Rotation group (n=22: 14 females and 8 males). All participants were administered a KOJI AWARENESSTM screening test, and the initial thoracic spine ROM before intervention exercise was measured in a laboratory setting. Quadruped Thoracic Rotation was performed as the quadruped exercise and Flamenco Thoracic Spine Rotation as the standing exercise. The KOJI AWARENESSTM thoracic spine test and ROM were evaluated on the day after the first exercise session and again after the program. Despite their different approaches to thoracic mobility, the quadruped exercise and standing exercise achieved equivalent improvement in thoracic ROM after 2 weeks. Practitioners have a range of exercise options for enhancing thoracic mobility based on their environmental or task-specific needs. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 The Impact of Reduced Skeletal Muscle Mass on Patients with Knee Osteoarthritis 245 250 EN Manabu Akagawa Department of Orthopedic Surgery, Omagari Kousei Medical Center Hidetomo Saito Department of Orthopedic Surgery, Akita University Graduate School of Medicine Yasuhiro Takahashi Department of Orthopedic Surgery, Omagari Kousei Medical Center Yosuke Iwamoto Department of Orthopedic Surgery, Omagari Kousei Medical Center Junpei Iida Department of Orthopedic Surgery, Omagari Kousei Medical Center Takayuki Yoshikawa Department of Orthopedic Surgery, Omagari Kousei Medical Center Toshiki Abe Department of Orthopedic Surgery, Omagari Kousei Medical Center Kimio Saito Department of Orthopedic Surgery, Akita University Graduate School of Medicine Hiroaki Kijima Department of Orthopedic Surgery, Akita University Graduate School of Medicine Yuji Kasukawa Department of Orthopedic Surgery, Akita University Graduate School of Medicine Michio Hongo Department of Orthopedic Surgery, Akita University Graduate School of Medicine Naohisa Miyakoshi Department of Orthopedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/67199 Although several studies have suggested a possible association between sarcopenia and knee osteoarthritis (OA) in the elderly, there remains no definitive evidence. Recently, however, the serum creatinine/cystatin C ratio (sarcopenia index: SI) was reported to correlate with skeletal muscle mass. The present retrospective study therefore investigated the impact of reduced skeletal muscle mass on advanced knee OA using SI. In 55 individuals scheduled for knee osteotomy or knee arthroplasty, correlations between SI and patient-reported outcomes such as the Knee Society Score (KSS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Oxford Knee Score (OKS) were explored. Significant associations were found between SI and the KSS functional activity score (β=0.37; p=0.022), KOOS subscale for activities of daily living (β=0.42; p=0.0096), and OKS (β=0.42; p=0.0095). This study underscores the role of reduced muscle mass in functional outcomes and introduces SI as a valuable marker for assessing muscle loss in knee OA patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD 123 134 EN Kyosuke Saeki Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Taiga Kuroi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuharu Fujii Division of Transfusion, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66915 Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response 95 106 EN Junko Itano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Review 10.18926/AMO/66912 The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2474 25 1 2024 The first presentation of a case of nail-patella syndrome newly diagnosed at the onset of rheumatoid arthritis: a case report 139 EN Kazuya Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shoichi Nawachi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Asano Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yu Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshia Miyawaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihisa Nasu Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken-Ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Nail-patella syndrome (NPS) is a rare autosomal dominant disorder that is characterized by dysplasia of the nails, hypoplasia and/or dislocation of the patella and the presence of iliac horns. Using the CARE guidelines, we present the first reported case of NPS that was newly diagnosed at the onset of rheumatoid arthritis (RA). Case presentation A 74-year-old man was admitted to our hospital due to an 8-month history of arthralgia in bilateral wrists, elbows and fingers. He had a past history of glaucoma and left patella dislocation that had been operatively recentered at the age of 15 years. Laboratory data showed elevated levels of serum C-reactive protein and rheumatoid factor and an elevated titer of anti-SS-A antibodies, while estimated glomerular filtration rate (eGFR), titers of other antibodies and the results of a urinary test were normal. An X-ray showed deformity of bilateral radial heads and the right elbow, and magnetic resonance imaging (MRI) of his hands showed synovitis and erosion in the multiple swollen joints of the wrists and fingers. In addition to these typical features of RA, he had bilateral thumb nail dysplasia with mild hypoplasia of bilateral patellae and iliac horns as shown by the X-ray. He was diagnosed as having autosomal dominant disorder NPS co-existing with RA and he was treated with methotrexate in combination with an oral Janus kinase (JAK) inhibitor, leading to induction of remission. Conclusions We have presented a rare case of NPS that was newly diagnosed at the onset of RA. Clinical and radiographic findings of NPS are highlighted in this case report for diagnosing NPS on the basis of typical manifestations. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Ectopic Breast Cancer Arising within an Axillary Lymph Node 89 93 EN Kei Toshima Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Midori Filiz Nishimura Department of Molecular Hematopathology, Graduate School of Health Sciences, Okayama University Yoko Suzuki Department of Breast and Endocrine Surgery, Okayama University Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Maya Uno Department of Breast and Endocrine Surgery, Okayama University Hospital Ryo Yoshioka Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyuki Yanai Department of Diagnostic Pathology, Okayama University Hospital Case Report 10.18926/AMO/66676 We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 High Fracture Rate of AVANTA Silicone Implant Following Arthroplasty of the Thumb MCP Joint of Rheumatoid Arthritis Patients with Boutonniere Deformities 71 78 EN Daisuke Kaneda Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama University Hospital Ryuichi Nakahara Department of Orthopaedic Surgery, Okayama University Hospital Ryozo Harada Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Yoshifumi Hotta Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuichi Naniwa 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 Original Article 10.18926/AMO/66673 We retrospectively investigated the mid-term outcomes of arthroplasty using the AVANTA silicone implant for thumb metacarpophalangeal (MCP) joints with boutonniere deformity in patients with rheumatoid arthritis (RA). This study involved 36 thumbs of 33 RA patients with a mean follow-up period of 5.1 years (range, 2.0-13.3). Postoperatively, the mean extension was significantly increased and the mean flexion was significantly decreased (p<0.001, p<0.001, respectively), resulting in the mean arc of range of motion (ROM) shifting in the direction of extension after surgery. Implant fracture was observed in 10 thumbs (28%), and 4 of these (11%) underwent revision surgery. The survivorship with implant fracture and revision surgery as endpoints were 73.4% and 91.8% at 5 years, respectively. The preoperative arc of ROM and the postoperative flexion range of the implant-fracture group were significantly greater than those in the no-implant-fracture group (p=0.039, 0.034, respectively). These results suggest the importance of patient education and careful rehabilitation to prevent excessive flexion. Overall, the AVANTA silicone implant showed a relatively high rate of implant fracture at our institute. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Long-Term Follow-up Data of a Multi-Institutional Phase-2 Study of S-1/oxaliplatin and Bevacizumab Therapy in Patients with Advanced Colorectal Cancer: The HiSCO-02 Study 47 52 EN Manabu Shimomura Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Katsunori Shinozaki Division of Clinical Oncology, Hiroshima Prefectural Hospital Takuya Yano Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Shintaro Akabane Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Hideki Ohdan Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Hiroshima Surgical study group of Clinical Oncology (HiSCO) Original Article 10.18926/AMO/66670 Oral fluoropyrimidines (FUs) have certain advantages over intravenous FUs, such as longer intervals between outpatient visits, no requirement for central venous port (CVP) implantation, and lower incidence of neutropenia. We previously reported the efficacy of S-1/oxaliplatin (SOX) with bevacizumab therapy as a first-line treatment for advanced colorectal cancer (CRC) in a prospective phase-II multi-institutional clinical trial (HiSCO-02 study). However, our prognostic data at the time lacked a sufficient observation period. Herein, we analyze the longer-term follow-up data, focusing on the status of eventual CVP implantation via an open-label, non-randomized, multicenter study. This study enrolled 55 patients (mean age, 64 years), of whom 43 died (41 of primary cancer). The median overall survival was 22.7 months (95% CI: 20.1-34.7 months). Post-treatment regimens after failure of first-line treatment were initiated in 43 patients; CPT11-based regimens were selected in most cases, and other oral FU combinations in nine. CVP was implanted in 35 patients prior to first-line treatment; eleven of the remaining 20 patients did not require CVP implantation. In conclusion, we report here the final prognostic update of the Phase II clinical trial examining the efficacy of SOX plus bevacizumab therapy, the results of which confirm the clinical efficacy of this regimen. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Is Proximal Triangular Fixation Better than the Conventional Method in Adult Spinal Deformity Surgery? 37 46 EN Masato Tanaka Department of Orthopaedic Surgery, Okayama Rosai Hospital Umesh Meena Department of Orthopaedic Surgery, Okayama Rosai Hospital Takuya Taoka Department of Orthopaedic Surgery, Okayama Rosai Hospital Yoshihiro Fujiwara Department of Orthopaedic Surgery, Okayama Rosai Hospital Daiichiro Yokomizo Department of Orthopaedic Surgery, Okayama Rosai Hospital Santosh Kumar Bashyal Department of Orthopaedic Surgery, Okayama Rosai Hospital Naveen Sake Department of Orthopaedic Surgery, Okayama Rosai Hospital Shinya Arataki Department of Orthopaedic Surgery, Okayama Rosai Hospital Original Article 10.18926/AMO/66669 In adult spinal deformity (ASD) surgery, one of the key factors working to prevent proximal junctional kyphosis is the proximal anchor. The aim of this study was to compare clinical and radiographic outcomes of triangular fixation with conventional fixation as proximal anchoring techniques in ASD surgery. We retrospectively evaluated 54 patients who underwent corrective spinal fusion for ASD. Fourteen patients underwent proximal triangular fixation (Group T; average 74.6 years), and 40 patients underwent the conventional method (Group C; average 70.5 years). Clinical and radiographic outcomes were assessed using visual analogue scale (VAS) values for back pain and the Oswestry disability index (ODI). Radiographic evaluation was also collected preoperatively and postoperatively. Surgical times and intraoperative blood loss of the two groups were not significantly different (493 vs 490 min, 1,260 vs 1,173 mL). Clinical outcomes such as VAS and ODI were comparable in the two groups. Proximal junctional kyphosis in group T was slightly lower than that of group C (28.5% vs 47.5%, p=0.491). However, based on radiology, proximal screw pullout occurred significantly less frequently in the triangular fixation group than the conventional group (0.0% vs 22.5%, p=0.049). Clinical outcomes in the two groups were not significantly different. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Assessing the Frequency and Effectiveness of Various Arthroscopic Treatments in the Management of Symptomatic Isolated Medial Meniscus Injuries Including Medial Meniscus Posterior Root Tear: A Retrospective Observational Cohort Study 21 27 EN Masanori Tamura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Furumatsu 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 Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naohiro Higashihara 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 Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66667 The use of various strategies for arthroscopic meniscal repairs to save the meniscus and prevent the progression of knee osteoarthritis has gradually increased. We investigated the frequency of various arthroscopic treatments and the short-term clinical outcomes of symptomatic isolated medial meniscus (MM) injuries. This retrospective observational study included 193 patients (197 knees) who underwent arthroscopic meniscal treatment for isolated MM injuries between January 2016 and April 2019. Arthroscopic meniscal repairs were divided into two groups: transtibial pullout repairs of MM posterior root tears (MMPRTs) and arthroscopic meniscal repairs for other types of MM injuries. MMPRT pullout repair, other meniscal repairs, and partial meniscectomy were performed in 71.0%, 16.8%, and 12.2% of the knees, respectively. The ratio of women to men and the patient age were higher in the pullout-repair group than the meniscal-repair group. The Preoperative Knee Injury and Osteoarthritis Outcome Score subscale (as an index of daily living activities) was significantly lower in the pullout-repair group than the meniscus-repair group. However, no significant differences were observed in these scores among the two groups postoperatively. Our results suggest that familiarity with the diagnosis and treatment of MMPRTs is necessary for orthopedic surgeons to manage isolated MM injuries. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Lung Oligometastasis of Breast Cancer: Prospective Cohort Study of Treatment Strategies (SBP-06) 15 20 EN Reina Maeda Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Mina Takahashi Department of Breast Oncology, NHO Shikoku Cancer Center Kengo Kawada Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital Yukiko Kajiwara Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Shinichiro Kubo Department of Breast and Thyroid Surgery, Fukuyama City Hospital Daisuke Takabatake Department of Breast Surgery, Kochi Health Sciences Center Shoichiro Ohtani Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Kinya Matsuoka Department of Breast and Thyroid Surgery, Ehime Prefectural Central Hospital Hajime Hikino Department of Breast Surgery, Matsue Red Cross Hospital Yutaka Ogasawara Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Shozo Osumi Department of Breast Oncology, NHO Shikoku Cancer Center Masahiko Ikeda Department of Breast and Thyroid Surgery, Fukuyama City Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Original Article 10.18926/AMO/66666 While local treatment of metastases is considered to be unrelated to prognosis, previous studies have suggested that local treatment of isolated lung metastases may have positive prognostic impact. We designed this prospective cohort study to investigate the clinical situation and its outcomes. We enrolled patients with fewer than 3 lung nodules suspected of being oligometastases after curative breast cancer surgery. Treatments, including local and systemic therapy, were selected by the physician and patient in consultation. The primary outcome was overall survival (OS); secondary outcomes were the efficacy and the safety of the surgery for lung oligometastases. Between May 2015 and May 2019, 14 patients were enrolled. Resection of lung nodules (metastasectomy) was performed in 11 (78.6%) of 14 patients, and one of these cases was diagnosed as primary lung cancer. Metastasectomies were all performed employing video-assisted thoracic surgery (VATS) without perioperative complications. Systemic therapies were administered to all patients except one. The respective 3-year and 5-year OS rates of patients with lung oligometastases were 91.6% and 81.5%, respectively. Progression occurred in 6 patients: 3 of the 10 with metastasectomy and all 3 without this surgical procedure. Lung metastasectomy was worthwhile as a diagnostic evaluation and may provide long-term benefit in some patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Role of Macrophages in Liver Fibrosis 1 8 EN Cuiming Sun Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/66664 Liver fibrosis, which ultimately leads to liver cirrhosis and hepatocellular carcinoma, is a major health burden worldwide. The progression of liver fibrosis is the result of the wound-healing response of liver to repeated injury. Hepatic macrophages are cells with high heterogeneity and plasticity and include tissue-resident macrophages termed Kupffer cells, and recruited macrophages derived from circulating monocytes, spleen and peritoneal cavity. Studies have shown that hepatic macrophages play roles in the initiation and progression of liver fibrosis by releasing inflammatory cytokines/chemokines and pro-fibrogenic factors. Furthermore, the development of liver fibrosis has been shown to be reversible. Hepatic macrophages have been shown to alternately regulate both the regression and turnover of liver fibrosis by changing their phenotypes during the dynamic progression of liver fibrosis. In this review, we summarize the role of hepatic macrophages in the progression and regression of liver fibrosis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Omental Abscess after Laparoscopic Proximal Gastrectomy Successfully Treated with Percutaneous Drainage 665 669 EN Atsunobu Sakurai Department of Radiology, Okayama University Hospital Mayu Uka Department of Radiology, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Koji Tomita Department of Radiology, Okayama University Hospital Yusuke Matsui Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Case Report 10.18926/AMO/66160 We report the case details of a 65-year-old Japanese man with an omental abscess that was discovered 43 days after he underwent a laparoscopic proximal gastrectomy for gastric cancer. His chief complaint was mild abdominal pain that had persisted for several days. The abscess was diagnosed as a rare postoperative complication. We hesitated to perform a reoperation given the invasiveness of general anesthesia and surgery, plus the possibility of postoperative adhesions and because the patient’s general condition was stable and he had only mild abdominal pain. Percutaneous drainage using a 10.2-F catheter was performed with the patient under conscious sedation and computed tomography–fluoroscopy guidance, with no complications. After the procedure, the size of the abscess cavity was remarkably reduced, and 23 days later the catheter was withdrawn. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 A Case of Migration of a Hydrogel Spacer for Radiotherapy into the Pulmonary Artery 647 650 EN Katsuhide Kojima Department of Radiology, Okayama University Hospital Yuka Takahashi Department of Radiology, Okayama University Hospital Soichi Sugiyama Department of Proton Beam Therapy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yudai Asano Department of Radiology, Okayama University Hospital Nanako Okawa Department of Radiology, Okayama University Hospital Satoko Makimoto Department of Radiology, Okayama University Hospital Fumiyo Higaki Department of Radiology, 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 Case Report 10.18926/AMO/66157 A 67-year-old man was referred to our hospital for the diagnosis and treatment of prostate cancer. Multidisciplinary discussion led to intensity-modulated radiotherapy preceded by hormone therapy. Before radiotherapy, a biodegradable hydrogel spacer (HS) was placed between the prostate and rectum to reduce radiation injury risk. Three weeks postplacement, pelvic magnetic resonance imaging revealed HS migration into the pelvic vein. Subsequent whole-body contrast-enhanced computed tomography (CECT) revealed HS migration into the pulmonary artery. The patient showed no symptoms or clinical signs. Radiotherapy was completed uneventfully. Complete absorption of the migrated HS was confirmed using CECT images 5 months postplacement. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Effects of Nutritional Support Combined with Neuromuscular Electrical Stimulation on Muscle Strength and Thickness: A Randomized Controlled Trial in Healthy Young Adult Males 635 645 EN Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Hospital Kazunori Okamura Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Masaki Hasegawa Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Satoshi Tanaka Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Shusaku Kanai Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Original Article 10.18926/AMO/66156 In the management of post-injury patients with activity limitations, methods to prevent musculoskeletal disorders and hasten recovery are important. This randomized controlled, single-blinded study was a preliminary investigation of the combined effect of nutritional support with neuromuscular electrical stimulation (NMES) on muscle strength and thickness. Healthy young adult males (median age, 21 years) were enrolled; each of their hands was randomly assigned to one of the following four groups: Placebo, Nutrition, NMES, and Nutrition + NMES. All participants received whey protein or placebo (3x/week for 6 weeks) and NMES training (3x/week for 6 weeks) on the abductor digiti minimi (ADM) muscle of either the left or right hand. ADM muscle strength and thickness were analyzed at baseline and at week 7. We analyzed 38 hands (9 Placebo, 10 Nutrition, 9 NMES, 10 Nutrition + NMES). There was significantly greater muscle strengthening in the Nutrition + NMES group compared to the Placebo group or the NMES group, but no significant difference in gain of muscle thickness. The combined intervention may be effective in improving muscle strength. Future clinical trials targeting various muscles after sports-related injuries are warranted. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Abnormal Vaginal Cytology after Total Laparoscopic Hysterectomy in Patients with Cervical Intraepithelial Neoplasia 627 634 EN Yumi Hibino Department of Gynecologic Oncology, NHO Shikoku Cancer Center Mika Okazawa-Sakai Department of Gynecologic Oncology, NHO Shikoku Cancer Center Takanori Yokoyama Department of Gynecologic Oncology, NHO Shikoku Cancer Center Etsuko Fujimoto Department of Gynecologic Oncology, NHO Shikoku Cancer Center Shinichi Okame Department of Gynecologic Oncology, NHO Shikoku Cancer Center Norihiro Teramoto Department of Pathology, NHO Shikoku Cancer Center Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Original Article 10.18926/AMO/66155 To explore the incidence of abnormal vaginal cytology after total laparoscopic hysterectomy for the treatment of cervical intraepithelial neoplasia 3, we retrospectively analyzed the medical records of patients treated at NHO Shikoku Cancer Center (Japan) in 2014-2019. The cases of 99 patients who underwent a laparoscopic (n=36) or open (n=63) hysterectomy and postoperative follow-up were examined. Abnormal vaginal cytology was detected in 13.9% (5/36) of the laparoscopic-surgery (LS) group and 14.3% (9/63) of the open-surgery (OS) group. A vaginal biopsy was performed at the physicians’ discretion; one LS patient and six OS patients were diagnosed with vaginal intraepithelial neoplasia. The cumulative incidence of abnormal vaginal cytology at 3 years post-hysterectomy was 21.4% (LS group) and 20.5% (OS group), a nonsignificant difference. A multivariate analysis showed that age > 50 years was the only independent risk factor for abnormal vaginal cytology among the covariates examined including age; body mass index; histories of vaginal delivery, abdominal surgery, and smoking; and surgical approach (hazard ratio 8.11; 95% confidence interval 1.73-37.98; p=0.01). These results suggest that the occurrence of abnormal vaginal cytology after a hysterectomy may not be influenced by the laparoscopic procedure but is associated with older age. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Fine Particulate Matter and Diabetes Prevalence in Okayama, Japan 607 612 EN Yasunari Tani Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Saori Kashima Environmental Health Sciences Laboratory, Graduate School of Advanced Science and Engineering, Center for the Planetary Health and Innovation Science, The IDEC Institute, Hiroshima University Toshiharu Mitsuhashi Center for Innovate Clinical Medicine, Okayama University Hospital Etsuji Suzuki Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66152 Many studies have shown an association between long-term exposure to particulate matter having an aerodynamic diameter of 2.5 μm or less (PM2.5) and diabetes mellitus (DM), but few studies have focused on Asian subjects. We thus examined the association between long-term exposure to PM2.5 and DM prevalence in Okayama City, Japan. We included 76,591 participants who had received basic health checkups in 2006 and 2007. We assigned the census-level modeled PM2.5 data from 2006 and 2007 to each participant and defined DM using treatment status and the blood testing. PM2.5 was associated with DM prevalence, and the prevalence ratio (95% confidence interval) was 1.10 (1.00-1.20) following each interquartile range increase (2.1 μg/m3) in PM2.5. This finding is consistent with previous results and suggests that long-term exposure to PM2.5 is associated with an increased prevalence of DM in Okayama City, Japan, where the PM2.5 level is lower than in other cities in Asian countries. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Concomitant Use of Multiple Nephrotoxins including Renal Hypoperfusion Medications Causes Vancomycin-Associated Nephrotoxicity: Combined Retrospective Analyses of Two Real-World Databases 595 605 EN Takashi Bando Department of Pharmacy, Tokushima University Hospital Masayuki Chuma Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Hirofumi Hamano Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Takahiro Niimura Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Naoto Okada Department of Pharmacy, Tokushima University Hospital Masateru Kondo Department of Pharmacy, Tokushima University Hospital Yuki Izumi Department of Pharmacy, Tokushima University Hospital Shunsuke Ishida Department of Pharmacy, Tokushima University Hospital Toshihiko Yoshioka Department of Pharmacy, Tokushima University Hospital Mizuho Asada Department of Medical Molecular Informatics, Meiji Pharmaceutical University Yoshito Zamami Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Kenshi Takechi Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University Mitsuhiro Goda Department of Pharmacy, Tokushima University Hospital Koji Miyata Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Kenta Yagi Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Yuki Izawa-Ishizawa Department of Pharmacology, Tokushima University Graduate School of Biomedical Sciences Momoyo Azuma Department of Infection Control and Prevention, Tokushima University Hospital Hiroaki Yanagawa Department of Nursing, Faculty of Health and Welfare, Tokushima Bunri University Yoshikazu Tasaki Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University Keisuke Ishizawa Department of Pharmacy, Tokushima University Hospital Original Article 10.18926/AMO/66151 There is a growing concern about the relationship between vancomycin-associated nephrotoxicity (VAN) and concomitant use of nephrotoxins. We examined this relationship by combined retrospective analyses of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was analyzed for the effects of concomitant use of one or more nephrotoxins on VAN and the types of combinations of nephrotoxins that exacerbate VAN. Next, electronic medical records (EMRs) of patients who received vancomycin (VCM) at Tokushima University Hospital between January 2006 and March 2019 were examined to confirm the FAERS analysis. An elevated reporting odds ratio (ROR) was observed with increases in the number of nephrotoxins administered (VCM + one nephrotoxin, adjusted ROR (95% confidence interval [CI]) 1.67 [1.51-1.85]; VCM + ≥2 nephrotoxins, adjusted ROR [95% CI] 1.54 [1.37-1.73]) in FAERS. EMRs analysis showed that the number of nephrotoxins was associated with higher incidences of VAN [odds ratio: 1.99; 95% CI: 1.42-2.78]. Overall, concomitant use of nephrotoxins was associated with an increased incidence of VAN, especially when at least one of those nephrotoxins was a renal hypoperfusion medication (furosemide, non-steroidal anti-inflammatory drugs, and vasopressors). The concomitant use of multiple nephrotoxins, especially including renal hypoperfusion medication, should be avoided to prevent VAN. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Cochlear Implantation in the Poorer-Hearing Ear Is a Reasonable Choice 589 593 EN Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medial University Yukihide Maeda Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunihiro Fukushima Hayashima Clinic of Otolaryngology and Dermatology Yuko Kataoka Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazunori Nishizaki 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 Original Article 10.18926/AMO/66150 Choosing the optimal side for cochlear implantation (CI) remains a major challenge because of the lack of evidence. We investigated the choice of the surgery side for CI (i.e., the better- or poorer-hearing ear) in patients with asymmetric hearing. Audiological records of 74 adults with a unilateral hearing aid who had undergone surgery at Okayama University Hospital were reviewed. The definition of ‘better-hearing ear’ was the aided ear, and the unaided ear was considered the poorer-hearing ear. We performed a multiple regression analysis to identify potential predictors of speech recognition performance after unilateral CI in the patients. Fifty-two patients underwent CI in the poorer-hearing ear. The post-Ci bimodal hearing rate was far higher in the poorer-ear group (77.8% vs. 22.2%). A multivariate analysis revealed that prelingual hearing loss and the patient’s age at CI significantly affected the speech recognition outcome (beta coefficients: 24.6 and −0.33, 95% confidence intervals [11.75-37.45] and [−0.58 to −0.09], respectively), but the CI surgery side did not (−6.76, [−14.92-1.39]). Unilateral CI in the poorer-hearing ear may therefore be a reasonable choice for adult patients with postlingual severe hearing loss, providing a greater opportunity for postoperative bimodal hearing. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer 517 525 EN Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kosaku Morimoto 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 Tatsuhiro Yamazaki Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Original Article 10.18926/AMO/65974 We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Relationship between the Hip Abductor Muscles and Abduction Strength in Patients with Hip Osteoarthritis 461 469 EN Daisuke Homma Division of Orthopaedic Surgery, Niigata University Graduate School of Medical and Dental Sciences Izumi Minato Division of Orthopaedic Surgery, Niigata Rinko Hospital Norio Imai Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Dai Miyasaka Division of Orthopaedic Surgery, Niigata Bandai Hospital Yoshinori Sakai Division of Orthopaedic Surgery, Niigata City General Hospital Yoji Horigome Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Hayato Suzuki Division of Orthopaedic Surgery, Niigata University Graduate School of Medical and Dental Sciences Yoichiro Dohmae Division of Orthopaedic Surgery, Niigata Bandai Hospital Naoto Endo Division of Orthopaedic Surgery, Niigata Prefectural Tsubame Rosai Hospital Original Article 10.18926/AMO/65968 This study aimed to determine which muscle the gluteus maximus, gluteus medius, gluteus minimus (Gmin), or tensor fasciae latae (TFL) contributes most to hip abduction strength and to identify effective sites for cross-sectional area (CSA) Gmin and TFL measurement in hip osteoarthritis (OAhip) patients. Twenty-eight patients with OAhip were included. The muscle CSA and volume were determined using magnetic resonance imaging. Peak isometric strength was determined using hand-held dynamometry. Muscle volumes were normalized to the total muscle volume of hip abductors. Multiple regression analysis was performed. The difference between the CSA of Gmin and TFL was calculated, and correlations with volume and muscle strength were determined. Gmin volume was related to abductor muscle strength (p=0.042). The peak CSA of the Gmin correlated with muscle volume and strength. The CSA of the TFL correlated with volume, with no difference between the CSA of the most protruding part of the lesser trochanter and peak CSA. Gmin volume was strongly related to abductor muscle strength. Peak CSA is a useful parameter for assessing the CSA of the Gmin among patients with OAhip. The CSA of the TFL should be measured at the most protruding part of the lesser trochanter. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2005 Involvement of Ras/extracellular signal-regulated kinase, but not Akt pathway in risedronate-induced apoptosis of U937 cells and its suppression by cytochalasin B EN Hirofumi Fujita No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Usefulness of Force-Controlled Pelvic Stress Radiograph in the Evaluation and Treatment of Fragility Fractures of the Pelvis in Geriatric Patients: A Pilot Study 407 414 EN Kensuke Hotta Department of Orthopaedic Surgery, Amagi Chuo Hospital Takaomi Kobayashi Department of Orthopaedic Surgery, Karatsu Red Cross Hospital Original Article 10.18926/AMO/65751 This study aimed to investigate the usefulness of force-controlled pelvic stress radiographs in the evaluation and treatment of fragility fractures of the pelvis (FFP) using a functional treatment strategy. We conducted a retrospective study of 55 geriatric patients with FFP who underwent pelvic stress radiographs on admission. The differences in the sacral width, pelvic ring width, and medial femoral head width between the radiographs with and without the Sam Sling II M size were defined as Δ sacral width, Δ pelvic ring width, and Δ medial femoral head width, respectively. We used Pearson’s correlation test to assess the relationship between the degree of radiographic instability and the Johns Hopkins highest level of mobility scale (JH-HLM) at 10-days postadmission. Conventional receiver-operating-characteristic curve analysis was used to identify cases requiring surgery using the best cutoff value for radiographic instability. The JH-HLM was significantly correlated with Δ sacral width (r=−0.401, p=0.017), but not with Δ pelvic ring width (r=−0.298, p=0.080) nor with Δ medial femoral head width (r= −0.261, p=0.128). The best cutoff value of Δ sacral width in identifying surgical cases was 10.7 mm (sensitivity 75.0%, specificity 98.0%). Force-controlled pelvic stress radiographs could be helpful in assessing the need for surgery on admission. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Association between Radon Hot Spring Bathing and Health Conditions: A Cross-Sectional Study in Misasa, Japan 387 394 EN Takahiro Kataoka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Hiroshi Habu Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Tanaka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Shota Naoe Department of Radiological Technology, Okayama University Graduate School of Health Sciences Kaito Murakami Department of Radiological Technology, Okayama University Graduate School of Health Sciences Yuki Fujimoto Department of Radiological Technology, Okayama University Graduate School of Health Sciences Ryohei Yukimine Department of Radiological Technology, Okayama University Graduate School of Health Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumihiro Mitsunobu Department of Longevity and Social Medicine (Geriatrics), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyonori Yamaoka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Original Article 10.18926/AMO/65749 No epidemiological studies have examined the health effects of daily bathing in radon hot springs. In this cross-sectional study, we investigated the associations between radon hot spring bathing and health conditions. The target population was 5,250 adults ≥ 20 years old in the town of Misasa, Japan. We collected information about the participants’ bathing habits and alleviation of a variety of disease symptoms, and their self-rated health (SRH). Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated. In both the adjusted and unadjusted models of hypertension, significant associations between the > 1×/week hot spring bathing and the alleviation of hypertension symptoms were observed compared to the group whose hot spring bathing was <1×/week: adjusted model, OR 5.40 (95%CI: 1.98-14.74); unadjusted model, 3.67 (1.50-8.99) and for gastroenteritis: adjusted model, 9.18 (1.15-72.96); unadjusted model, 7.62 (1.59-36.49). Compared to the no-bathing group, higher SRH was significantly associated with both bathing < 1×/week: unadjusted model, 2.27 (1.53-3.37) and > 1×/week: adjusted model, 1.91 (1.15-3.19). These findings suggest that bathing in radon hot springs is associated with higher SRH and the alleviation of hypertension and gastroenteritis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Relationship between the Arthroscopic Findings and Pathology of Greater Trochanteric Pain Syndrome 371 375 EN Yosuke Iwamoto Department of Orthopedic Surgery, Akita University Graduate School of Medicine Mitsunori Kaya Kaya Orthopedic Surgery Sports Clinic Hiroaki Kijima Department of Orthopedic Surgery, Akita University Graduate School of Medicine Masashi Fujii Akita Hip Research Group Itsuki Nagahata Akita Hip Research Group Naohisa Miyakoshi Department of Orthopedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/65746 In recent publications on greater trochanteric pain syndrome (GTPS), the pathology receiving the most attention has been gluteus medius muscle tendinous injury, and surgical techniques such as gluteus medius tendon repair and their outcomes for GTPS have been reported. In our department-related facilities, arthroscopic surgeries are routinely performed for the patients with recalcitrant GTPS. A total of 51 patients were diagnosed with GTPS. Surgical treatment was carried out 22 patients (24 joints; 4 males and 18 females; mean age at surgery of 52.0 years). Arthroscopic findings confirmed bursitis in all 24 joints. In all cases, debridement of the greater trochanter bursa provided rapid relief of greater trochanter pain. The Numerical Rating Scale showed significant improvement, from the preoperative mean of 7.8 (range, 6-10) to the postoperative day 7 mean of 1.6 (range, 0-3). The modified Harris Hip Score was significantly improved from the preoperative mean of 65.5 (range, 52.5-78.3) to the final follow-up (average 2.9 months) mean of 96.0 (range, 85.2-100). Fascial damage of the gluteus medius muscle was observed in 21 joints while only 2 patients had a gluteus medius tendinous injury. Greater trochanteric bursitis and fascia or muscle-fiber injury of the gluteus medius muscle are the most common pathologies in patients with lateral hip pain. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Feasibility of Flow Cytometry Analysis of Gastrointestinal Tract-Residing Lymphocytes in Hematopoietic Stem Cell Transplant Recipients 347 357 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takumi Kondo Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahide Takahashi Division of Medical Support, Okayama University Hospital Araki Hirabata Division of Medical Support, Okayama University Hospital Takehiro Tanaka 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 Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65740 The feasibility of lymphocyte isolation and flow cytometry using a single endoscopic biopsy specimen from the gastrointestinal tract of patients who have undergone hematopoietic stem cell transplantation has not been investigated. We acquired 51 endoscopic biopsy specimens from the gastrointestinal tract of 35 patients. We divided the flow cytometry samples into two groups: group A, successful lymphocyte isolation (n=24), and group B, incomplete isolation (n=27). We compared the backgrounds of the samples between the groups to reveal crucial elements in the successful isolation of lymphocytes residing in the gastrointestinal tract. Comparison between the groups revealed lymphocyte isolation success rates differed between biopsy sites. Isolation was most successful in samples from the duodenum (8/9, 88.9%), followed by the ileum (4/8, 50.0%), large intestine (4/11, 36.4%), and stomach (8/23, 34.8%). Tacrolimus was used more frequently in group B (92.6%) than in group A (62.5%) (p=0.015). Logistic regression analysis revealed that isolation from the duodenum or ileum was a significant factor for successful isolation, while tacrolimus use was not statistically significant. In conclusion, the duodenum and ileum are more suitable sites than the stomach and colorectum for acquiring samples for flow cytometry. No potential conflict of interest relevant to this article was reported.

British Editorial Society of Bone & Joint Surgery Acta Medica Okayama 2633-1462 4 1 2023 Outcome of unlinked total elbow arthroplasty for rheumatoid arthritis in patients younger than 50 years old 19 26 EN Keiichiro Nishida Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama University Hospital Kenzo Hashizume Department of Orthopaedic Surgery, Chugoku Central Hospital Shunji Okita Department of Orthopaedic Surgery, Okayama Saiseikai General Hospital Ryuichi Nakahara Department of Orthopaedic Surgery, Okayama University Hospital Taichi Saito Department of Intelligent Orthopaedic System, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hajime Inoue Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aims There are concerns regarding complications and longevity of total elbow arthroplasty (TEA) in young patients, and the few previous publications are mainly limited to reports on linked elbow devices. We investigated the clinical outcome of unlinked TEA for patients aged less than 50 years with rheumatoid arthritis (RA). Methods We retrospectively reviewed the records of 26 elbows of 21 patients with RA who were aged less than 50 years who underwent primary TEA with an unlinked elbow prosthesis. The mean patient age was 46 years (35 to 49), and the mean follow-up period was 13.6 years (6 to 27). Outcome measures included pain, range of motion, Mayo Elbow Performance Score (MEPS), radiological evaluation for radiolucent line and loosening, complications, and revision surgery with or without implant removal. Results The mean MEPS significantly improved from 47 (15 to 70) points preoperatively to 95 (70 to 100) points at final follow-up (p < 0.001). Complications were noted in six elbows (23%) in six patients, and of these, four with an ulnar neuropathy and one elbow with postoperative traumatic fracture required additional surgeries. There was no revision with implant removal, and there was no radiological evidence of loosening around the components. With any revision surgery as the endpoint, the survival rates up to 25 years were 78.1% (95% confidence interval 52.8 to 90.6) as determined by Kaplan-Meier analysis. Conclusion The clinical outcome of primary unlinked TEA for young patients with RA was satisfactory and comparable with that for elderly patients. A favourable survival rate without implant removal might support the use of unlinked devices for young patients with this disease entity, with a caution of a relatively high complication rate regarding ulnar neuropathy. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 13 1 2023 ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer 2078 EN Nanako Hata 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 Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuya Yano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sho Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Yoshida 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 Ryuichi Yoshida 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 Hibiki Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki Takahashi 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 Hiroyuki Kishimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiko Mori Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Keiichiro Nakamura Department of Obstetrics and Gynecology, 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 Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 A Case of High-Grade Glioma in an Eloquent Area Treated with Awake Craniotomy in an 85-year-old Patient 335 340 EN Kentaro Fujii Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shuichiro Hirano Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Kurozumi Department of Neurological Surgery, Hamamatsu University School of Medicine, University Hospital Isao Date Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/65504 An 85-year-old woman presented with aphasia due to an occupying lesion in the left frontal lobe near the language area. Complete resection of the contrast-enhancing lesion was performed under awake conditions. The pathological diagnosis was anaplastic astrocytoma, and postoperative radiochemotherapy was administered. Awake surgery is a useful technique to reduce postoperative neurological sequelae and to maximize surgical resection. Although the patient was elderly, which is generally considered high risk, she did not have any severe neurological deficits and had a good outcome. Even in the extreme elderly, awake surgery can be useful for gliomas in language cortices. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Cerebral Hypoperfusion Detected by Arterial Spine-Labelled MR Imaging in a Patient Presenting with Migraine and Panic Attacks 319 321 EN Kenichi Kashihara Department of Neurology, Okayama Kyokuto Hospital Case Report 10.18926/AMO/65497 I report a case of arterial spine-labelled MR imaging (ASL)-detected cerebral hypoperfusion during migraine and panic attacks. A 20-year-old woman with a history of headache for 6 years and independent panic attacks for 3 years was transferred to Okayama Kyokuto Hospital for panic attacks. On that day, she had had severe headache that was improved by taking non-steroidal anti-inflammatory drug, but panic attacks initiated. On arrival, she also complained of a mild headache. ASL revealed cerebral hypoperfusion in the right temporo-occipital region. The threshold to induce panic attacks in migraine patients could be lowered by the physiopathology underlying migraine attacks. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Current Femoral Stem Fixation Selection in Hip-Fracture Bipolar Hemiarthroplasties, and Factors Affecting Surgeons’ Confidence in Their Ability to Teach about Cemented Stems: A Questionnaire in a Region of Japan with Super-Aged Patients 311 318 EN Takanori Miura Department of Orthopedic Surgery, Tazawako Hospital Hiroaki Kijima Akita Hip Research Group, Akita University Graduate School of Medicine Hiroshi Tazawa Akita Hip Research Group, Akita University Graduate School of Medicine Naohisa Miyakoshi Akita Hip Research Group, Akita University Graduate School of Medicine Original Article 10.18926/AMO/65496 Japan’s hip fracture management guidelines now recommend the use of cemented stems in cases of bone fragility. However, the current stem selection practices in bipolar hemiarthroplasty (BHA) in a super-aging area in Japan remain unclear. This study aimed to examine the stem selection policies, the surgeons’ concerns about cemented stems, and factors affecting their confidence in their ability to coach others on cemented stem procedures. Ninety-four orthopedic surgeons (27 facilities) responded to our web-based questionnaire conducted in January/February 2022. Cementless stem was the first choice of 97.8% of the surgeons; <15% of the respondents expected to increase their use of cemented stems in the future. The cement technique was the greatest concern; almost half of the surgeons described having insufficient experience with cemented stems. The factor that most affected the surgeons’ expertise in using cemented stems is the number of surgeries they had conducted with a cemented stem (multivariable analysis odds ratio 8.42, p=0.001). Greater experience was associated with increased expertise of the surgeons in using cemented stems, with a threshold of 11 cases showing sensitivity of 41.7% and specificity of 98.3% for their confidence to instruct cemented stems. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Brown Adipose Tissue PPARγ Is Required for the Insulin-Sensitizing Action of Thiazolidinediones 243 254 EN Yusuke Shibata Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi 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 Original Article 10.18926/AMO/65489 Brown adipose tissue (BAT) plays a critical role in metabolic homeostasis. BAT dysfunction is associated with the development of obesity through an imbalance between energy expenditure and energy intake. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis. However, the roles of PPARγ and thiazolidinediones (TZDs) in the regulation of BAT metabolism remain unclear. TZDs, which are selective PPARγ activators, improve systemic insulin resistance in animals and humans. In the present study, we generated brown adipocyte-specific PPARγ-deficient mice (BATγKO) to examine the in vivo roles of PPARγ and TZDs in BAT metabolism. In electron microscopic examinations, brown adipocyte-specific PPARγ deletion promoted severe whitening of brown fat and morphological alteration of mitochondria. Brown adipocyte-specific PPARγ deletion also reduced mRNA expression of BAT-selective genes. Although there was no difference in energy expenditure between control and BATγKO mice in calorimetry, norepinephrine-induced thermogenesis was impaired in BATγKO mice. Moreover, pioglitazone treatment improved diet-induced insulin resistance in the control mice but not in the BATγKO mice. These findings suggest that BAT PPARγ is necessary for the maintenance of brown adipocyte function and for the insulin-sensitizing action of TZDs. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Withdrawal from Hemodialysis in a Patient with IgD Type Multiple Myeloma: A Case-based Review 221 225 EN Hiroki Iriyoshi Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Ken-ei Sada Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Atsushi Miyauchi Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Hirotaka Yamamoto Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Daisuke Hashimoto Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Shigeru Nojima Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Shingo Yamanaka Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Masafumi Kawamura Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Satoshi Oka Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Case Report 10.18926/AMO/65154 Several previous case reports have shown that patients with immunoglobulin D (IgD) multiple myeloma (MM) can be withdrawn from hemodialysis, however, the characteristics that can predict withdrawal in these patients have not yet been elucidated. A 57-year-old Japanese woman required hemodialysis because of renal dysfunction due to IgD-λ and Bence Jones protein-λ MM. Bortezomib-based chemotherapy nine days after admission led to her withdrawal from hemodialysis on Day 50. In our case-based review, younger age and early initiation of bortezomib-based chemotherapy emerged as possible predictors of successful hemodialysis withdrawal. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Case Series of Granulicatella Bacteremia: A Single-centered, Five-year Retrospective Study 203 207 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hiroyuki Honda 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 Hirokazu Nagaoka Department of General Medicine, 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 Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/65151 Granulicatella species are rare, nutritionally variant streptococci that cause infective endocarditis. Their clinical and microbiological characteristics remain unknown. We reviewed five years of Granulicatella cases in our hospital database (Jan 2017-Jun 2022), finding 6 Granulicatella adiacens cases and 1 Granulicatella elegans case. Clinical backgrounds and bacteremia sources were diverse; 3 cases developed polymicrobial bacteremia. Antimicrobial testing showed non-susceptibility to penicillin G in 4 of 7 cases (57.1%), and high susceptibility to carbapenems and vancomycin in all cases. Determining optimal antibiotic therapy for Granulicatella infections is vital in this era of antimicrobial resistance. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Organ Donation after Extracorporeal Cardiopulmonary Resuscitation and Brain Death 117 120 EN Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Aoshima Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/64372 A 38-year-old primipara Japanese woman suffered cardiac arrest due to a pulmonary thromboembolism 1 day after undergoing a cesarean section. Extracorporeal cardiopulmonary resuscitation was initiated and extracorporeal membrane oxygenation support was needed for 24 h. Despite intensive care, the patient was diagnosed with brain death on day 6. With the family’s consent, comprehensive end-of-life care including organ donation was discussed based on our hospital’s policy. The family decided to donate her organs. Specific training and education are required for emergency physicians to optimize the process of incorporating organ donation into end-of-life care while respecting the patient’s and family’s wishes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Osteonecrosis of the Jaw in Two Rheumatoid Arthritis Patients Not Treated with a Bisphosphonate 111 116 EN Katsuhiko Amano Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akinari Sugauchi The first department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry Chiaki Yamada Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikihiko Kogo The first department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/64371 Medication-related osteonecrosis of the jaw (MRONJ) is a side effect in patients taking bone-modifying agents (BMAs), which are highly beneficial for treating osteoporosis and cancer. Bisphosphonates are prescribed to treat secondary osteoporosis in patients with rheumatoid arthritis (RA). We recently encountered two unusual cases of intraoral ONJ in RA patients who had not been treated with a BMA and did not have features of methotrexate- associated lymphoproliferative disorder. Their ONJ stage II bone exposures were treated by conservative therapy, providing good prognoses. These cases indicate that ONJ can occur in RA patients not treated with bisphosphonates. Several risk factors are discussed. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Initial Two Doses of COVID-19 Vaccine mRNA-1273 for an Individual Previously Vaccinated with Two Doses of an Inactivated Vaccine CoronaVac That Has Not Been Approved in Japan 105 109 EN Yoshiaki Iwasaki Health Service Center, Okayama University Chigusa Higuchi Health Service Center, Okayama University Case Report 10.18926/AMO/64370 The inactivated coronavirus disease 2019 vaccine CoronaVac has not been approved in Japan. Little information is available on cases in Japan in which an approved mRNA vaccine was administered as the initial (first or second) dose after two doses of CoronaVac. Furthermore, the safety and efficacy of this combination are not established. We here evaluated the safety and efficacy in a patient who showed an antibody response to an approved vaccine, mRNA-1273, after a previous vaccination with CoronaVac. The adverse events consisted of only mild local and systemic common reactions and were transient. In addition, a strong and persistent antibody response was observed. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 A Case of Radiation-Induced Osteosarcoma with RB1 Gene Alteration Treated by Skull Base Surgery and Craniofacial Reconstruction 85 90 EN Yuki Matsuda Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Yasuhara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaya Higaki Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuma Makino Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Oyama Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/64367 A 35-year-old female presented with headache, photophobia and developed sudden loss of vision after having undergone right-side ophthalmectomy and radiochemotherapy for retinoblastoma in infancy. A neoplastic lesion was found in the left middle cranial fossa and was surgically removed. The diagnosis was radiation-induced osteosarcoma with RB1 gene alteration. Although she received chemotherapy for the residual tumor, it progressed 17 months later. Maximal surgical resection with craniofacial reconstruction was required. We utilized two three-dimensional models for surgical planning. She was discharged without neurological deficits other than loss of light perception subsequent to left ophthalmectomy. In cases where retinoblastoma is treated with radiotherapy, long-term follow-up is necessary to monitor for radiation-induced tumor development. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Ipsilateral Periprosthetic Fractures above and below the Knee Associated with Navigation Tracker Pin and Bone Fragility 71 74 EN Yasuaki Yamakawa Department of Orthopedic Surgery, Kochi Health Sciences Center Yusuke Kamatsuki Department of Orthopedic Surgery, Kochi Health Sciences Center Tomoyuki Noda Department of Orthopaedic Surgery, Okayama University Hospital Miho Kure Department of Orthopaedic Surgery, Okayama University Hospital Shinichi Miyazawa Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Case Report 10.18926/AMO/64364 We report a case of ipsilateral periprosthetic fractures above and below the knee that occurred at different times due to navigation tracker pin and bone fragility. A 66-year-old Japanese woman with rheumatoid arthritis (RA) underwent a total knee arthroplasty. Four months post-surgery, a periprosthetic fracture above the knee at the navigation pin hole was detected. She underwent osteosynthesis and could walk independently, but she developed an ipsilateral tibial component fracture. Conservative treatment with a splint was followed by bone union. Patients with RA treated with oral steroids tend to develop ipsilateral periprosthetic fractures around the knee due to bone fragility. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Effect of a Cyclooxygenase-2 Inhibitor in Combination with (−)-Epigallocatechin Gallate or Polyphenon E on Cisplatin-Induced Lung Tumorigenesis in A/J Mice 65 70 EN Ken Sato Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nagio Takigawa Department of General Internal Medicine 4, Kawasaki Medical School Toshio Kubo Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Katayama Department of Medicine, Yamaguchi-Ube Medical Center Daizo Kishino Department of Medicine, Yamaguchi-Ube Medical Center Toshiaki Okada Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Hisamoto Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Mimoto Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Ochi Department of General Internal Medicine 4, Kawasaki Medical School Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ueoka Department of Medicine, Yamaguchi-Ube Medical Center Mitsune Tanimoto Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshionobu 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 Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/64363 We investigated the effects of celecoxib combined with (−)-epigallocatechin-3-gallate (EGCG) or polyphenon E in a cisplatin-induced lung tumorigenesis model. Four-week-old female A/J mice were divided into seven groups: (i) Control, (ii) 150 mg/kg celecoxib (150Cel), (iii) 1,500 mg/kg celecoxib (1500Cel), (iv) EGCG+150 mg/kg celecoxib (EGCG+150Cel), (v) EGCG+1,500 mg/kg celecoxib (EGCG+1500Cel), (vi) polyphenon E+150 mg/kg celecoxib (PolyE+150Cel), and (vii) polyphenon E+1,500 mg/kg celecoxib (PolyE+1500Cel). All mice were administered cisplatin (1.62 mg/kg of body weight, i.p.) 1×/week for 10 weeks and sacrificed at week 30; the numbers of tumors on the lung surface were then determined. The tumor incidence and multiplicity (no. of tumors/mouse, mean±SD) were respectively 95% and 2.15±1.50 in Control, 95% and 2.10±1.29 in 150Cel, 86% and 1.67±1.20 in 1500Cel, 71% and 1.38±1.24 in EGCG+150Cel, 67% and 1.29±1.38 in EGCG+1500Cel, 80% and 1.95±1.36 in PolyE+150Cel, and 65% and 1.05±0.10 in PolyE+1500Cel. The combination of high-dose celecoxib with EGCG or polyphenon E significantly reduced multiplicity in cisplatin-induced lung tumors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Development, Disappearance, and Clinical Course of Melanosis Coli: Sex Differences in the Progression of Severity 57 64 EN Ryo Katsumata Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Noriaki Manabe Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center Yasumasa Monobe Pathology, Kawasaki Medical School General Medical Center Maki Ayaki Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center Mitsuhiko Suehiro Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Minoru Fujita Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center Tomoari Kamada Health Care Medicine, Kawasaki Medical School General Medical Center Hirofumi Kawamoto Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Ken Haruma Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Original Article 10.18926/AMO/64362 Melanosis coli (MC) is an acquired colorectal disorder visualized as colonic mucosa pigmentation. Disease severity is confirmed based on MC depth, shape, and coloration, although the clinical course is not fully understood. This study sought to clarify characteristics of MC development and disappearance and to investigate its clinical course and severity. Contributors to MC grade progression were explored. This study reviewed MC cases discovered via colonoscopy at a single institution over a 10-year period. Of all 216 MC cases, 17 developing and 10 disappearing cases were detected. Anthranoid laxative use was a key factor: 29.4% of the developing cases had used such agents before the initial MC diagnosis, whereas 40% of disappearing cases had discontinued anthranoids prior to detection of MC disappearance. Among 70 grade I cases, progression to grade II occurred in 16 cases during a mean follow-up of 3.67±2.1 years (rate of progression=22.8%). Males more commonly showed progressive than stable grade I cases, and the probability of progression was higher for male than for female cases. An association between anthranoid administration and MC presence was presumed, and grade I MC was found to progress in severity over 5 years. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Image Quality Assessment of Deep Learning Image Reconstruction in Torso Computed Tomography Using Tube Current Modulation 45 55 EN Kazuhiro Takeuchi Department of Radiology, Kagawa University Hospital Yasuhiro Ide Department of Radiology, Kagawa University Hospital Yuichiro Mori Department of Radiology, Kagawa University Hospital Yusuke Uehara Department of Radiology, Kagawa University Hospital Hiroshi Sukeishi Department of Radiology, Kagawa University Hospital Sachiko Goto Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/64361 Novel deep learning image reconstruction (DLIR) reportedly changes the image quality characteristics based on object contrast and image noise. In clinical practice, computed tomography image noise is usually controlled by tube current modulation (TCM) to accommodate changes in object size. This study aimed to evaluate the image quality characteristics of DLIR for different object sizes when the in-plane noise was controlled by TCM. Images acquisition was performed on a GE Revolution CT system to investigate the impact of the DLIR algorithm compared to the standard reconstructions of filtered-back projection (FBP) and hybrid iterative reconstruction (hybrid-IR). The image quality assessment was performed using phantom images, and an observer study was conducted using clinical cases. The image quality assessment confirmed the excellent noise- reduction performance of DLIR, despite variations due to phantom size. Similarly, in the observer study, DLIR received high evaluations regardless of the body parts imaged. We evaluated a novel DLIR algorithm by replicating clinical behaviors. Consequently, DLIR exhibited higher image quality than those of FBP and hybrid-IR in both phantom and observer studies, albeit the value depended on the reconstruction strength, and proved itself capable of providing stable image quality in clinical use. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 The Efficacy of Inflammatory and Immune Markers for Predicting the Prognosis of Patients with Stage IV Breast Cancer 37 43 EN Kosho Yamanouchi Department of Surgery, National Hospital Organization, Nagasaki Medical Center Shigeto Maeda Department of Surgery, National Hospital Organization, Nagasaki Medical Center Original Article 10.18926/AMO/64360 Systemic therapy for stage IV breast cancer is usually an initial treatment and is based on findings regarding biomarkers (e.g., hormone receptors and human epidermal growth factor receptor-2 [HER2]). However, the response to therapy and outcomes sometime differ among patients with similar prognostic factors including grade, hormone receptor, HER2, and more. We conducted retrospective analyses to evaluate the correlations between the overall survival (OS) of 46 stage IV breast cancer patients and (i) the peripheral absolute lymphocyte count (ALC) and (ii) composite blood cell markers. The peripheral blood cell markers included the neutrophil- to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the systemic immune-inflammation index (SII), the systemic inflammation response index (SIRI), and the most recently introduced indicator, the pan-immune-inflammatory value (PIV). The SIRI and PIV showed prognostic impacts on the patients: those with a low SIRI or a low PIV showed significantly better OS than those with a high SIRI (5-year, 66.0% vs. 35.0%, p<0.05) or high PIV (5-year, 68.1% vs. 38.5%, p<0.05), respectively. This is the first report indicating the possible prognostic value of the PIV for OS in patients with stage IV breast cancer. Further studies with larger numbers of patients are necessary for further clarification. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Safety and Efficacy of a Well-Fitting Brassiere after Breast Reconstruction: A Qualitative Study 11 19 EN Satoko Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Miho Saiga Department of Plastic and Reconstructive Surgery, Okayama University Hospital Takayuki Motoki Department of General Surgery, Okayama Saiseikai General Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Naruto Taira Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Hospital Original Article 10.18926/AMO/64356 The importance of a well-fitted, comfortable brassiere to overall quality of life after breast reconstruction has not been evaluated. Our aim was to determine the impact of a semi-customized brassiere on patients’ health-related quality of life after breast reconstruction. The subjects were prospective patients with mastectomy who were to undergo immediate or delayed breast reconstruction at our hospital. After surgery, a professional bra fitter sized each patient for a semi-customized brassiere and provided follow-up consultations. A self-reported questionnaire on breast aesthetics, postoperative pain, and satisfaction was used to assess the primary outcomes. Data were prospectively collected at baseline (before surgery) and at 1, 3, 6, and 12 months after surgery and analyzed. Forty-six patients (50 breasts) were included in the analysis. Consistent wearing of the brassiere reduced pain (p<0.05), with good overall satisfaction (p<0.001). Aesthetic scores on breast shape and size were higher with than without the custom brassiere at 3 months (p=0.02) and 6 months (p=0.03) after surgery. Wearing the brassiere reduced anxiety at all time points of measurement. A well-fitting brassiere ensured safety and provided a high degree of satisfaction without anxiety for patients after breast reconstruction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Serum miR-377 Can Be Used as a Diagnostic Marker for Acute Coronary Syndrome and Can Regulate Proinflammatory Factors and Endothelial Injury Markers 723 730 EN Quan Zhang Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College Lixia Yang Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College Guozhen Wan Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College Xiaoqiang Zhang Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College Ying Wang Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College Guannan Zhao Department of Dermatological, Pingliang Traditional Chinese Medicine Hospital Original Article 10.18926/AMO/64123 The diagnostic value of microRNA-377 (miR-377) in patients with acute coronary syndrome (ACS) and explored miR-377’s potential mechanisms. We performed an qRT-PCR to assess serum miR-377 levels in ACS patients and coronary artery ligation rat models. The diagnostic value of miR-377 was evaluated by determining the ROC curve. An ELISA assay was conducted to detect the model rat endothelial damage markers von Willebrand factor (vWF) and heart-type fatty acid binding protein (H-FABP), and proinflammatory cytokines TNF-α, IL-6, and IL-1β. The serum miR-377 level was elevated in the ACS patients and significantly increased in the ACS rats. MiR-377 has a high diagnostic value in ACS patients, with a 0.844 ROC, 76.47% specificity, and 87.10% sensitivity. MiR-377 was positively correlated with the expressions of vWF, H-FABP, cTnI, TNF-α, IL-6, and IL-1β. In ACS rats, reducing the expression of miR-377 significantly inhibited the increases in vWF, H-FABP, TNF-α, IL-6, and IL-1β. An elevated miR-377 level can be used as a diagnostic marker in patients with ACS. A reduction of miR-377 may alleviate ACS by improving myocardial damage such as endothelial injury and the inflammatory response. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus 705 713 EN Toshihiro Higashikawa Kanazawa Medical University Himi Municipal Hospital Tomohiko Ito Kanazawa Medical University Himi Municipal Hospital Takurou Mizuno Kanazawa Medical University Himi Municipal Hospital Keiichiro Ishigami Kanazawa Medical University Himi Municipal Hospital Kengo Kuroki Kanazawa Medical University Himi Municipal Hospital Naoto Maekawa Kanazawa Medical University Himi Municipal Hospital Daisuke Usuda Kanazawa Medical University Himi Municipal Hospital Toshihide Izumida Kanazawa Medical University Himi Municipal Hospital Shinya Yamada Kanazawa Medical University Himi Municipal Hospital Ryusho Sangen Kanazawa Medical University Himi Municipal Hospital Kazu Hamada Kanazawa Medical University Himi Municipal Hospital Jun Kiyosawa Kanazawa Medical University Himi Municipal Hospital Atsushi Saito Kanazawa Medical University Himi Municipal Hospital Masaharu Iguchi Kanazawa Medical University Himi Municipal Hospital Yuji Kasamaki Kanazawa Medical University Himi Municipal Hospital Takeshi Nakahashi Kanazawa Medical University Himi Municipal Hospital Akihiro Fukuda Kanazawa Medical University Himi Municipal Hospital Hitoshi Saito Kanazawa Medical University Himi Municipal Hospital Tsugiyasu Kanda Kanazawa Medical University Himi Municipal Hospital Masashi Okuro Department of Geriatric Medicine, Kanazawa Medical University Original Article 10.18926/AMO/64121 The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin’s osmotic diuresis mechanism, patients’ serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (β1=−0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e’ tended to decrease (β1=−0.382, p=0.13, LRA). Compared to the baseline, E/e’ was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e’ group (E/e’≥10, n=34), E/e’ decreased significantly (β1=−0.63, p<0.05, LRA). ΔE/e’ was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e’ in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Intraoperative Hypothermia Is Not Associated with Surgical Site Infections after Total Hip or Knee Arthroplasty 651 660 EN Bright Osman Abugri Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Matsusaki Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Wanxu Ren Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/64115 Maintaining perioperative normothermia decreases the post-surgery surgical site infection (SSI) rate. We investigated whether SSI is associated with intraoperative hypothermia in total hip (THA) and total knee (TKA) arthroplasties by retrospectively analyzing 297 THA and TKA cases. The patients’ intraoperative core body temperature (BT) was measured by bladder catheter or forehead sensor. We evaluated the associations between SSI and intraoperative BT and other variables and patient characteristics. Fifty-six patients (18.8%) had hypothermia (BT <36°C); 43 developed SSI (14.5%); only five had hypothermia (11.6%). Intraoperative hypothermia and SSI were not significantly associated. The SSI group had more men (34.9% vs. 18.1%) and THA patients (77.4%), a longer mean surgical duration (174.3 vs. 143.5 mins), and a higher average BT (36.4°C vs. 36.2°C) than the no-SSI group. The SSI patients had a higher intraoperative BT. A multivariable analysis revealed that SSI was associated with male sex (OR 2.3, 95%CI: 1.031-4.921, p=0.042), longer surgery (OR, 1.01, 95%CI: 1.003-1.017, p=0.004), THA (OR 3.6, 95%CI: 1.258-10.085, p=0.017), and intraoperative BT >36.0°C (OR 3.6, 95%CI: 1.367-9.475, p=0.009). Intraoperative hypothermia was not associated with SSI in adults who underwent THA or TKA. These results suggest that hypothermia might not be the problem for SSI. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Idiopathic Pneumonia Syndrome Refractory to Ruxolitinib after Post-Transplant Cyclophosphamide-based Haploidentical Hematopoietic Stem Cell Transplantation: Lung Pathological Findings from an Autopsy Case 609 615 EN Ken Matsumoto Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Keigo Fujishita Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Masayuki Matsuda Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Satoshi Oka Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Yuka Fujisawa Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Takuya Machida Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Case Report 10.18926/AMO/64044 A 69-year-old Japanese man with acute leukemia received post-transplant cyclophosphamide-based haploidentical stem cell transplantation (PTCY-haplo-SCT) but was readmitted with dyspnea and ground-glass-opacities of the lungs. Bronchoscopy showed inflammatory changes with no signs of infection. He received steroids but required intubation as his condition deteriorated. In addition to antithymocyte globulin and cyclophosphamide, we administered ruxolitinib but failed to save him. Autopsy findings revealed fibrotic nonspecific interstitial pneumonia (NSIP) without evidence of organizing pneumonia or infection. Thus, we diagnosed idiopathic pneumonia syndrome (IPS). As far as our knowledge, this is the first case of IPS with NSIP histology after PTCY-haplo-SCT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Surgical Resection for Local and Lateral Lymph Node Recurrence of MSI-high Cecal Cancer with the BRAF V600E Mutation 605 608 EN Fuminori Teraishi Department of Surgery, Fukuyama Daiichi Hospital Atsushi Jikuhara Department of Surgery, Fukuyama Daiichi Hospital Ryunosuke Ogawa Department of Surgery, Fukuyama Daiichi Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/64043 An 84-year-old female underwent open right hemicolectomy with D3 lymph node dissection for cecal cancer, pathologically identified as pT4aN2M0 Stage IIIc and BRAF mutation-positive. Due to early recurrence of abdominal wall and right lateral lymph nodes, the patient was treated with FOLFOXIRI+Bevacizumab. Imaging after 5 courses of chemotherapy found tumor shrinkage and no new metastases. The patient did not tolerate chemotherapy well, and tumor resection was performed. Microsatellite instability (MSI) testing using multiplex polymerase chain reaction (PCR) fragment analysis revealed MSI-high status. The patient is currently recurrence-free without chemotherapy at 1 year postoperatively. BRAF-mutated colorectal cancer has a poor prognosis, and may require resection of the metastatic or recurrent tumor after comprehensive evaluation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Surgery Outcomes for Pulmonary Metastases from Renal Cell Carcinoma 585 591 EN Haruki Choshi Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Mototsugu Watanabe Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Shinichi Furukawa Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Hiroyuki Ujike Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Kazuhiko Kataoka Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Original Article 10.18926/AMO/64040 Pulmonary metastatic resection is a standard therapy for renal cell carcinoma (RCC). Although patients with pulmonary metastases who do not undergo any treatment have poor prognoses, it has been reported that resection for pulmonary metastases yields good clinical outcomes. We investigated the prognoses of the 10 Japanese patients (eight males, two females) who underwent a surgical resection of pulmonary metastasectomy from RCC at our institution between April 1, 2012 and March 31, 2020 and analyzed the prognostic factors. We determined the prognoses and calculated the 5-year overall survival (OS) and disease-free survival (DFS) rates. To identify prognostic factors, we compared the median DFS duration for each factor. Elderly patients (median age, 75.5 years) were more predominant compared to previous studies, and all 10 patients underwent a complete resection. The 5-year DFS rate was 30.5% (95%CI: 0.045-0.63) and the 5-year OS rate was 80% (95%CI: 0.20-0.97). The following factors were associated with better prognosis: female, disease-free interval≥36 months, and metastases size<12 mm. These results indicate that complete resection for pulmonary metastases from RCC resulted in good clinical outcomes, particularly for patients with better prognostic factors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Correlation between Mean Arterial Pressure and Regional Cerebral Oxygen Saturation on Cardiopulmonary Bypass in Pediatric Cardiac Surgery 557 564 EN Yu Pan Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Qingqing Song Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Kanazawa Department of Anesthesiology and Resuscitology, 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 Original Article 10.18926/AMO/64037 Some pediatric cardiac patients might experience low regional cerebral oxygen saturation (rSO2) during surgery. We investigated whether a pediatric patient’s mean arterial pressure (MAP) can affect the rSO2 value during cardiopulmonary bypass (CPB). We retrospectively analyzed the cases of the pediatric patients who underwentcardiac surgery at our hospital (Jan. –Dec. 2019; n=141). At each MAP stage, we constructed line charts through the mean of the rSO2 values corresponding to each MAP and then calculated the correlation coefficients. We next divided the patients into age subgroups (neonates, infants, children) and into cyanotic congenital heart disease (CHD) and acyanotic CHD groups and analyzed these groups in the same way. The analyses of all 141 patients revealed that during CPB the rSO2 value increased with an increase in MAP (r=0.1626). There was a correlation between rSO2 and MAP in the children (r=0.2720) but not in the neonates (r=0.06626) or infants (r=0.05260). Cyanotic CHD or acyanotic CHD did not have a significant effect on the rSO2/MAP correlation. Our analysis demonstrated different patterns of a correlation between MAP and rSO2 in pediatric cardiac surgery patients, depending on age. MAP was positively correlated with rSO2 typically in children but not in neonate or infant patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 First-line Combination Strategy Provides Favorable 5-year Outcomes for Patients with Lupus Nephritis: A Single-center Observational Study 547 555 EN Hidetoshi Kagawa Department of Nephrology and Rheumatology, Japanese Red Cross Society Himeji Hospital Ryutaro Yamanaka Department of Nephrology and Rheumatology, Japanese Red Cross Society Himeji Hospital Tsutomu Hiromasa Department of Nephrology and Rheumatology, Japanese Red Cross Society Himeji Hospital Original Article 10.18926/AMO/64036 This observational study aimed to clarify the long-term results of the combination of mizoribine (MZB), tacrolimus (TAC) and prednisolone as first-line therapy for lupus nephritis (LN). This was our institution’s standard therapy between 2009 and 2015, when we saw 36 patients with LN. When a patient thus treated achieved SLEDAI remission (= 0) and/or the prednisolone dose could be tapered to 5 mg/day, either MZB or TAC was stopped, and the other was continued for maintenance therapy. If treatment failure or relapse occurred, second-line therapy was introduced. At years 1 and 5, overall complete renal response and SLEDAI remission were 94% and 88%, and 50% and 62%, respectively. Excluding 2 cases lost to follow-up, medications after 5 years were as follows: 20 (59%) were stable on 1 drug (MZB or TAC), 11 (32%) required continuation of both drugs (MZB + TAC), and 3 (9%) required second-line therapy. The 5-year retention rate was 91% (non-secondline), with 0% of relapse in this group. Our first-line combination strategy showed high remission rates in the induction phase, and subsequent maintenance therapy demonstrated good outcomes for up to 5 years. Research that fine-tunes the order of therapeutic agents and institutes appropriate treatment goals may further improve long-term outcomes for patients with LN. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Relationship between Wearing a Lead Apron and Work-related Musculoskeletal Disorders: A Questionnaire Survey of Japanese Radiological Technologists 541 545 EN Toru Akebi Department of Physical Therapy, Faculty of Health Sciences, Okayama Healthcare Professional University Ryutaro Matsugaki Department of Preventive Medicine and Community Health, School of Medicine, University of Occupational and Environmental Health Toshiro Ono Department of Physical Therapy, Faculty of Health Sciences, Okayama Healthcare Professional University Original Article 10.18926/AMO/64035 The purpose of this study was to conduct a self-reported questionnaire survey of work-related musculoskeletal disorders (WMSDs) among Japanese radiological technologists (RTs) and to report on the relationship between wearing a lead apron and WMSDs. Between February and April of 2021, RTs in Okayama Prefecture, Japan, were surveyed by mail and through a website. Information on individual characteristics, physical factors at work, and the presence of WMSDs were collected. All participants were also asked whether they frequently wore lead aprons. A multiple logistic regression analysis was used to assess the relationship between wearing a lead apron and WMSDs. The model was adjusted for age, sex, body mass index (BMI), and working hours. Of the 123 participants, 67 (54.5%) had WMSDs. Multiple logistic regression analysis revealed that WMSDs were significantly associated with wearing a lead apron. Compared to the “Never wear” group, the odds ratios for the “Always/Frequently wear” and “Sometimes/Rarely wear” groups were 7.87 (95% confidence interval [CI]=1.28-48.46; p=0.026) and 7.80 (95% CI=1.43-42.44; p=0.017), respectively. Our analysis suggests that wearing a lead apron is associated with WMSDs, and thus design modifications in lead aprons may improve the occupational health management of RTs. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Gestational Outcomes and Birth Weight in Japanese Women at the Upper and Lower limits of the Normal BMI range 519 526 EN Yoko Ishioka Graduate School of Health Sciences, Okayama University Hiroyuki Yamashita Yamaguchi Rosai Hospital Kinya Hamaguchi Hamaguchi Women's Clinic Yoshitaka Kuwahara Kuwahara Obstetrics and Gynecology Clinic Kaoru Nakamura Okinawa Kyoudou Hospital Mikiya Nakatsuka Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/64032 To examine the outcome of gestational blood pressure and birth weight in women with normal pre-pregnancy BMI (18.5-25 kg/m2) who are at the lower and upper limits of this range, i.e., slightly underweight or slightly overweight. Overall, 2,038 Japanese women with low -risk who had delivered during January 2014–December 2016 were classified according to their pre-pregnancy BMI: underweight (< 18.5 kg/m2), slightly underweight (18.5≤BMI<21 kg/m2), normal (21≤BMI<23 kg/m2), slightly overweight (23≤BMI<25 kg/m2) and overweight (≤ 25 kg/m2). Their blood pressure during each trimester and birth weight was evaluated. The slightly overweight group showed a significantly higher blood pressure than the underweight and slightly underweight groups. Birth weight was lower in the slightly underweight than in the slightly overweight group (p<0.01). The incidence rate of “heavy for dates” (HFD) infants was significantly higher in the slightly overweight and overweight groups than in the other groups (p<0.05 and p<0.01, respectively). Weight gain of < 7 kg significantly increased the rate of “light for dates” (LFD) infants, while a weight gain of ≥13 kg significantly increased the rate of HFD infants (p<0.05 and p<0.01, respectively). Blood pressure during pregnancy was ssociated with pre-pregnancy BMI. The birth weight of infants of low-risk pregnant women is affected by both pre-pregnancy BMI and gestational weight gain. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Viral Sequences Are Repurposed for Controlling Antiviral Responses as Non-Retroviral Endogenous Viral Elements 503 510 EN Hirohito Ogawa Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyuki Honda Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Review 10.18926/AMO/64025 Eukaryotic genomes contain numerous copies of endogenous viral elements (EVEs), most of which are considered endogenous retrovirus (ERV) sequences. Over the past decade, non-retroviral endogenous viral elements (nrEVEs) derived from ancient RNA viruses have been discovered. Several functions have been proposed for these elements, including antiviral defense. This review summarizes the current understanding of nrEVEs derived from RNA viruses, particularly endogenous bornavirus-like elements (EBLs) and endogenous filovirus-like elements (EFLs). EBLs are one of the most extensively studied nrEVEs. The EBL derived from bornavirus nucleoprotein (EBLN) is thought to function as a non-coding RNA or protein that regulates host gene expression or inhibits virus propagation. Ebolavirus and marburgvirus, which are filoviruses, induce severe hemorrhagic fever in humans and nonhuman primates. Although the ecology of filoviruses remains unclear, bats are believed to be potential reservoirs. Based on the knowledge from EBLs, it is postulated that EFLs in the bat genome help to maintain the balance between filovirus infection and the bat’s defense system, which may partially explain why bats act as potential reservoirs. Further research into the functions of nrEVEs could reveal novel antiviral systems and inspire novel antiviral approaches. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Current Insights into Mesenchymal Signatures in Glioblastoma 489 502 EN Yuji Matsumoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomotsugu Ichikawa Department of Neurological Surgery, Kagawa Prefectural Central Hospital Kazuhiko Kurozumi Department of Neurosurgery, Hamamatsu University Hospital Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Review 10.18926/AMO/64024 Glioblastoma (GBM) is a fatal primary malignant brain tumor in adults. Despite decades of research, the prognosis for GBM patients is still disappointing. One major reason for the intense therapeutic resistance of GBM is inter- and intra-tumor heterogeneity. GBM-intrinsic transcriptional profiling has suggested the presence of at least three subtypes of GBM: the proneural, classic, and mesenchymal subtypes. The mesenchymal subtype is the most aggressive, and patients with the mesenchymal subtype of primary and recurrent tumors tend to have a worse prognosis compared with patients with the other subtypes. Furthermore, GBM can shift from other subtypes to the mesenchymal subtype over the course of disease progression or recurrence. This phenotypic transition is driven by diverse tumor-intrinsic molecular mechanisms or microenvironmental factors. Thus, better understanding of the plastic nature of mesenchymal transition in GBM is pivotal to developing new therapeutic strategies. In this review, we provide a comprehensive overview of the current understanding of the elements involved in the mesenchymal transition of GBM and discuss future perspectives. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1660-4601 19 17 2022 Immunomodulatory Effects of Radon Inhalation on Lipopolysaccharide-Induced Inflammation in Mice 10632 EN Takahiro Kataoka Faculty of Health Sciences, Okayama University Shota Naoe Graduate School of Health Sciences, Okayama University Kaito Murakami Graduate School of Health Sciences, Okayama University Yuki Fujimoto Graduate School of Health Sciences, Okayama University Ryohei Yukimine Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Typical indications for radon therapy include autoimmune diseases such as rheumatoid arthritis (RA). We had previously reported that radon inhalation inhibits Th17 immune responses in RA mice by activating Th1 and Th2 immune responses. However, there are no reports on how radon inhalation affects the activated Th1 and Th17 immune responses, and these findings may be useful for identifying new indications for radon therapy. Therefore, in this study, we investigated the effect of radon inhalation on the lipopolysaccharide (LPS)-induced inflammatory response, focusing on the expression of related cytokines and antioxidant function. Male BALB/c mice were exposed to 2000 Bq/m(3) radon for one day. Immediately after radon inhalation, LPS was administered intraperitoneally at 1.0 mg/kg body weight for 4 h. LPS administration increased the levels of Th1- and Th17-prone cytokines, such as interleukin-2, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor, compared to no treatment control (sham). However, these effects were suppressed by radon inhalation. IL-10 levels were significantly increased by LPS administration, with or without radon inhalation, compared to sham. However, radon inhalation did not inhibit oxidative stress induced by LPS administration. These findings suggest that radon inhalation has immunomodulatory but not antioxidative functions in LPS-induced injury. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Liquid Biopsy Revealed HBOC Pedigree and Led to Medical Management Among the Relatives 479 483 EN Chikako Ogawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Reimi Sogawa Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital Kayoko Hasuoka Department of Nursing, Okayama University Hospital Shuta Tomida Department of Center for Comprehensive Genomic Medicine, Okayama University Hospital Biobank, Okayama University Hospital Mashu Futagawa Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital Yusaku Urakawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Kochi Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital Hideki Yamamoto Department of Clinical Genomic Medicine, 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 Case Report 10.18926/AMO/63908 A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient’s daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Efficacy of 0.01% Atropine Eye Drops in Controlling Myopia Progression and Axial Elongation in Children: A Meta-analysis Based on Randomized Controlled Trials 457 463 EN Weiying Sun Department of Ophthalmology 2, Kawasaki Medical School Satoshi Hasebe Department of Ophthalmology 2, Kawasaki Medical School Original Article 10.18926/AMO/63905 To clarify the preventive effects of 0.01% atropine eye drops against myopia progression and axial elongation in children, a meta-analysis was carried out based on data obtained from PubMed and Web of Science as of August 1, 2021. Randomized controlled trials (RCTs) that enrolled myopic children who had received atropine for at least one year were included in this study, Key search terms included myopia, children, and 0.01% or low-dose atropine. Heterogeneity was quantified by I2 statistics, and meta-analyses were performed using the fixed-effect model. Five RCTs involving 809 unique children were analyzed. One trial was excluded because of a poor Jadad score and markedly rapid myopia progression in controls. The mean effect sizes for 12 months in myopia progression and axial elongation synthesized from the remaining 4 RCTs were 0.20 (95% CI: 0.13 to 0.27) D and −0.08 (−0.11 to −0.04) mm, respectively (p<0.0001). The corresponding inhibition ratios were 28% and 19%. I2 statistics were 6% or less. Sensitivity analysis and funnel plots demonstrated the robustness of the estimation. The 0.01% atropine-induced inhibition ratio for myopia progression in Asian children was roughly half of that originally reported and did not reach the minimum requirement for clinical treatment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Effects of Exercise Therapy and Nutrition Therapy on Patients with Possible Malnutrition and Sarcopenia in a Recovery Rehabilitation Ward 423 428 EN Satoshi Takahashi Department of Rehabilitation Medicine, Saiseikai Imabari Daini Hospital Takuya Kushibe Department of Rehabilitation Medicine, Saiseikai Imabari Daini Hospital Yoshiteru Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Norio Horiike Department of Internal Medicine, Saiseikai Imabari Daini Hospital Original Article 10.18926/AMO/63901 We compared the effects of an exercise intervention with that of exercise combined with nutrition therapy in patients with possible malnutrition and sarcopenia admitted to a recovery rehabilitation ward, and we examined the differences in the patients’ physical function and activities of daily living (ADLs). There were 16 patients in the Exercise group with exercise therapy and ADL exercises, and 14 patients in the Combined intervention group with exercise therapy, ADL exercises, and nutrition therapy. The survey items were body weight, body mass index, grip strength, lower-leg circumference, gait speed, and ADLs, each of which was measured at the baseline and at 2 weeks, 4 weeks, and at discharge. Significant improvements in grip strength were observed in the Combined intervention group as follows: at 4 weeks>at 2 weeks (p<0.05), and at discharge>baseline and 2 weeks (p<0.05). There were no significant changes in the Exercise group, and an interaction was recognized in both groups. Comprehensive rehabilitation including nutrition therapy is necessary for patients with possible malnutrition and/or sarcopenia, as our results indicate that nutrition therapy in addition to exercise therapy has the effect of promoting improvements of physical function in such patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 5-Nitro-2-(3-phenylpropylamino) Benzoic Acid Inhibits the Proliferation and Migration of Lens Epithelial Cells by Blocking CaMKII Signaling 415 421 EN Haijun Kang Department of Ophthalmology, Suining Central Hospital Dongmei Huang Department of Cardiovascular, Suining Central Hospital Gangjin Kang Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University Xu Yang Department of Ophthalmology, Suining Central Hospital Heng Li Department of Ophthalmology, Suining Central Hospital Siyuan Liu Department of Ophthalmology, Suining Central Hospital Wenjun Gou Department of Ophthalmology, Suining Central Hospital Linglin Liu Department of Ophthalmology, Suining Central Hospital Yuyan Qiu Department of Ophthalmology, Suining Central Hospital Original Article 10.18926/AMO/63896 Posterior capsule opacification (PCO) is a post-surgery complication of cataract surgery, and lens epithelial cells (LECs) are involved in its development. A suppressive effect on LECs is exerted by the non specific chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) exerts. Herein, the growth and migration inhibitory effects of NPPB on LECs were assessed, and the mechanism underlying the effects were investigated by focusing on Ca2+/CaMKII signaling. LECs were treated with different concentrations of NPPB, and the changes in cell viability, cell-cycle distribution, anchorage-dependent growth, migration, Ca2+ level, and CaMKII expression were evaluated. NPPB inhibited LECs’ proliferation and induced G1 cell-cycle arrest in the cells. Regarding LECs’ mobility, NPPB suppressed the cells’ anchorage-dependent growth ability and inhibited their migration. Changes in cell phenotypes were associated with an increased intracellular Ca2+ level and down-regulation of CaMKII. Together these results confirmed the inhibitory effect of NPPB on the proliferation and migration of LECs, and the effect was shown to be associated with the induced level of Ca2+ and the inhibition of CaMKII signaling transduction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Gene Expression Profiling between Patient Groups with High and Low Ki67 Levels after Short-term Preoperative Aromatase Inhibitor Treatment for Breast Cancer 399 408 EN Yukiko Kajiwara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Iwamoto Departments of Breast and Endocrine Surgery, Okayama University Hospital Yidan Zhu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Kochi Departments of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Departments of Breast and Endocrine Surgery, Okayama University Hospital Naruto Taira Departments of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Departments of Breast and Endocrine Surgery, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63894 According to a recent report, a low Ki67 level after short-term preoperative hormone therapy (post-Ki67) might suggest a more favorable prognosis compared with a high post-Ki67 level in patients with hormone receptorpositive/human epidermal growth factor 2-negative (HR+/HER2−) breast cancer with high levels of Ki67. This study aimed to evaluate the pre-treatment genetic differences between these two patient groups. Forty-five luminal B-like patients were stratified into two groups, namely, a group with high (H→H) and one with low (H→L) Ki67 levels after short-term preoperative aromatase inhibitor (AI) treatment. We compared pre-treatmentgene expression profiles between the two groups. In gene level analysis, there was no significant difference between the two groups by the class comparison test. In pathway analysis, five metabolism-related gene sets were significantly upregulated in the H→L group (p≤0.05). In the search for novel targets, five genes (PARP, BRCA2, FLT4, CDK6, and PDCD1LG2) showed significantly higher expression in the H→H group (p≤0.05). Several metabolism-related pathways were associated with sensitivity to AI. In the future, it will be necessary to seek out new therapeutic strategies for the poor prognostic group with high post-Ki67. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Central and Enteric Neuroprotective Effects by Eucommia ulmoides Extracts on Neurodegeneration in Rotenone-induced Parkinsonian Mouse 373 383 EN Fuminori Imafuku Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jin Sun Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sunao Kamimai Department of Medical Neurobiology, Okayama University Medical School Takashi Shimizu Department of Medical Neurobiology, Okayama University Medical School Toshiaki Toyota Department of Medical Neurobiology, Okayama University Medical School Yusei Okamoto Department of Medical Neurobiology, Okayama University Medical School Nami Isooka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kikuoka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Pharmacy, Okayama University Hospital Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63889 Parkinson’s disease (PD) is a progressive neurodegenerative disease of both the central and peripheral / enteric nervous systems. Oxidative stress and neuroinflammation are associated with the pathogenesis of PD, suggesting that anti-oxidative and anti-inflammatory compounds could be neuroprotective agents for PD. Eucommia ulmoides (EU) is a traditional herbal medicine which exerts neuroprotective effects by anti-inflammatory and anti-oxidative properties. Our previous study showed that treatment with chlorogenic acid, a component of EU, protected against neurodegeneration in the central and enteric nervous systems in a PD model. In this study, we examined the effects of EU extract (EUE) administration on dopaminergic neurodegeneration, glial response and α-synuclein expression in the substantia nigra pars compacta (SNpc), and intestinal enteric neurodegeneration in low-dose rotenone-induced PD model mice. Daily oral administration of EUE ameliorated dopaminergic neurodegeneration and α-synuclein accumulation in the SNpc. EUE treatment inhibited rotenone- induced decreases in the number of total astrocytes and in those expressing the antioxidant molecule metallothionein. EUE also prevented rotenone-induced microglial activation. Furthermore, EUE treatment exerted protective effects against intestinal neuronal loss in the PD model. These results suggest that EU exerts neuroprotective effects in the central and enteric nervous systems of rotenone-induced parkinsonism mice, in part by glial modification. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Therapeutic Approaches Targeting miRNA in Systemic Lupus Erythematosus 359 371 EN Sumie Hiramatsu-Asano 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 Review 10.18926/AMO/63887 Systemic lupus erythematosus (SLE) is a potentially fatal systemic autoimmune disease, and its etiology involves both genetic and environmental factors such as sex hormone imbalance, genetic predisposition, epigenetic regulation, and immunological factors. Dysregulation of microRNA (miRNA) is suggested to be one of the epigenetic factors in SLE. miRNA is a 22-nucleotide single-stranded noncoding RNA that contributes to post-transcriptional modulation of gene expression. miRNA targeting therapy has been suggested to be useful for the treatment of cancers and other diseases. Gene knockout and miRNA targeting therapy have been demonstrated to improve SLE disease activity in mice. However, these approaches have not yet reached the level of clinical application. miRNA targeting therapy is limited by the fact that each miRNA has multiple targets. In addition, the expression of certain miRNAs may differ among cell tissues within a single SLE patient. This limitation can be overcome by targeted delivery and chemical modifications. In the future, further research into miRNA chemical modifications and delivery systems will help us develop novel therapeutic agents for SLE. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 12 1 2022 Treatment resistance of rheumatoid arthritis relates to infection of periodontal pathogenic bacteria: a case-control cross-sectional study 12353 EN Kazu Takeuchi-Hatanaka Department of Periodontics and Endodontics, Okayama University Hospital Yoshinobu Koyama Center for Autoimmune Diseases, Division of Rheumatology, Japan Red Cross Okayama Hospital Kentaro Okamoto Department of Periodontics and Endodontics, Okayama University Hospital Kyosuke Sakaida Department of Periodontics and Endodontics, Okayama University Hospital Tadashi Yamamoto Department of Pathophysiology‑Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shogo Takashiba Department of Pathophysiology‑Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Recent studies have shown that periodontitis is associated with rheumatoid arthritis (RA) and periodontal bacteria, such as Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are involved in the pathogenesis of RA via citrullinated proteins. Smoking has also been shown to be involved in the pathogenesis of RA; however, the extent of this involvement is still poorly understood. In addition, RA and polymyalgia rheumatica (PMR) are sometimes difficult to differentiate; however, the relationship between PMR and the factors from smoking and periodontal bacteria is unclear. The aim of this study was to clarify the relationship between periodontal pathogenic bacterial infections and smoking in patients with RA or PMR. This case-control study included 142 patients with untreated RA or PMR. This study evaluated the serum antibody titers against periodontal pathogenic bacterial antigens and an anti-citrullinated peptide antibody (ACPA). In patients with RA, the relationship between antibody titers and disease activity of RA and response after 3 months of treatment was also investigated. Additionally, the effects of smoking were evaluated. Although there was no significant difference in serum antibody titer against periodontal pathogenic bacteria between the ACPA-positive RA group and the ACPA-negative PMR group, we found an association between the elevated antibody titer against Pg and the degree of ACPA value, especially between negative group and high-value positive group (>= 100 U/mL). The antibody titers against Aa and Pg did not differ depending on disease activity score 28 (DAS28) at baseline; however, patients with high antibody titers had poor RA therapeutic response as judged by DAS28 after 3 months. We could not find any association between smoking and any of these parameters. Periodontal pathogenic bacteria, especially Pg, are associated with elevated ACPA levels. Our findings suggest that Pg and Aa infections interfere with the therapeutic response of RA. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Bilateral Blunt Ocular Trauma Caused by an Exercise Resistance Band during Muscle Building Exercise for Swimming 349 354 EN Kanazu Ariyasu Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Morizane Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichiro Doi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kanzaki 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 Case Report 10.18926/AMO/63747 An 18-year-old male high school student presented to our clinic with bilateral blunt ocular trauma caused by an exercise resistance band (ERB) during a muscle-building exercise. Best-corrected decimal visual acuities (BCVAs) for right and left eyes were light perception and 0.15, respectively. The right eye was operated 10 days after injury for persistent vitreous hemorrhage, and the left eye 5 months later because of macular hole onset. After 36 months, the right eye showed extensive retinal degeneration (BCVA 0.04), and the left eye macular hole closure (BCVA 1.2). ERBs should be used cautiously as they can cause serious ocular trauma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Successful Treatment of Atypical Femoral Fracture with Bowed Femur Using Contralateral Intramedullary Nail Combined with Early Daily Teriparatide 333 338 EN Manabu Akagawa Department of Orthopedic Surgery, Omagari Kosei Medical Center Naohisa Miyakoshi Department of Orthopedic Surgery, Akita University Graduate School of Medicine Hiroyuki Tsuchie Department of Orthopedic Surgery, Akita University Graduate School of Medicine Yuji Kasukawa Department of Orthopedic Surgery, Akita University Graduate School of Medicine Takashi Kawaragi Department of Orthopedic Surgery, Omagari Kosei Medical Center Itsuki Nagahata Department of Orthopedic Surgery, Omagari Kosei Medical Center Masazumi Suzuki Department of Orthopedic Surgery, Omagari Kosei Medical Center Takayuki Yoshikawa Department of Orthopedic Surgery, Omagari Kosei Medical Center Toshiki Abe Department of Orthopedic Surgery, Omagari Kosei Medical Center Yoichi Shimada Department of Orthopedic Surgery, Akita University Graduate School of Medicine Case Report 10.18926/AMO/63744 We report a case of atypical femoral fracture achieving early fracture union with combination therapy comprising contralateral nail and immediate teriparatide injection. Fracture union of atypical fractures is often delayed due to bowing deformity and bone metabolic disorders. Combination treatment that takes both problems into consideration represents a useful treatment option for atypical femoral fracture. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 A Case of a Solitary Cortical Tuber with No Other Manifestations of Tuberous Sclerosis Complex Mimicking Focal Cortical Dysplasia Type II with Calcification 323 328 EN Kakeru Hosomoto 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 Koji Kawai 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 Yuki Hyodo Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Shibata Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Yasuhara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhiro Kobayashi Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Yanai Department of Diagnostic Pathology,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/63742 Cortical tubers are one of the typical intracranial manifestations of tuberous sclerosis complex (TSC). Multiple cortical tubers are easy to diagnose as TSC; however, a solitary cortical tuber without any other cutaneous or visceral organ manifestations can be confused with other conditions, particularly focal cortical dysplasia. We report a surgical case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Hip Fractures after Intramedullary Nailing Fixation for Atypical Femoral Fractures: Three Cases 317 321 EN Norio Yamamoto Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Tomoo Inoue Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Mochizuki Yusuke Department of Orthopaedic Surgery, Kaneda Hospital Noda Tomoyuki Department of Orthopaedic Surgery and Traumatology, Kawasaki Medical School, General Medical Center Kawasaki Keisuke Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Ozaki Toshifumi Department of Orthopaedic Surgery, Okayama University Hospital Case Report 10.18926/AMO/63741 Secondary hip fractures (SHFs) rarely occur after intramedullary nailing (IMN) fixation without femoral neck fixation for atypical femoral fractures (AFFs). We report three cases of older Japanese women who sustained SHFs presumably caused by osteoporosis and peri-implant stress concentration around the femoral neck after undergoing IMN without femoral neck fixation for AFF. All cases were fixed with malalignment. In AFF patients, postoperative changes due to postoperative femoral bone malalignment may affect the peri-implant mechanical environment around the femoral neck, which can result in insufficiency fractures. At the first AFF surgery, we recommend femoral neck fixation after adequate reduction is achieved. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Factors Associated with Work Efficiency in Home Health Care by Pharmacists 307 315 EN Satoshi Sugiura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhisa Izushi Department of Pharmacotherapy, School of Pharmacy, Shujitsu University Soichiro Ushio Department of Pharmacy, Okayama University Hospital Toshiaki Sendo Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63740 In recent years, medical staff including physicians and nurses have been participating in home health care, reflecting the needs of an aging society in Japan. Pharmacists are also asked to work on home health care teams to ensure the medical safety of patients. It currently remains unclear whether direct communication, i.e. a meeting, between home-visiting physicians and pharmacists contributes to the proper use of medications and continuous medical care. We retrospectively analyzed the medication management guidance records of home-visited patients who received their first home visit between April 2014 and March 2017. We collected data on pharmacist inquiries, the duration of visits, and details from a meeting between home-visiting physicians and pharmacists. Thirty-five patients were included. At the first visit, the inquiry rate by pharmacists was 65.7%. The prescription question rate was significantly lower in patients with a meeting than in those without (p=0.033). The average duration of visits was significantly shorter for home-visited patients whose health care providers had a meeting (p=0.007). These results suggest that pharmacists who held a meeting with the home-visiting physician before the first patient visit were able to resolve drug-related issues earlier, which increased the work efficiency of home-visiting pharmacists. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 A Case of Primary Osteosarcoma of the Mandible That Responded to Preoperative Chemotherapy: p16 as a Potential Prognostic Factor 229 233 EN Takashi Kono Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Nobuya Monden Division of Head and Neck Surgery, National Hospital Organization Shikoku Cancer Center Nobuyuki Chikuie Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Takayuki Taruya Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Takao Hamamoto Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Ishino Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Tsutomu Ueda Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Sachio Takeno Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Case Report 10.18926/AMO/63428 We report a case of mandibular osteosarcoma in a Japanese woman in her 70s who was p16-positive. Despite the rapid growth of the tumor, the patient responded well to chemotherapy and was then able to undergo surgery. Head and neck osteosarcoma (HNOS) is a very rare cancer, and although the importance of surgery has been pointed out, the effectiveness of chemotherapy is unclear. Resection margin negativity and response to chemotherapy have been reported as prognostic factors; another report assessed the effectiveness of the immunohistochemical expression of p16 protein as a predictor of response to chemotherapy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 Mediastinal and Hilar Lymph Node Metastases from Renal Cell Carcinoma with Concomitant Lung Carcinoma: A Rare Case with Unique Diagnostic Challenges 225 228 EN Yu Mori Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Yoshifumi Sano Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Ryujiro Sugimoto Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Nobuhiko Sakao Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Tsuyoshi Ryuko Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Masashi Takeda Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Riko Kitazawa Department of Molecular Pathology, Ehime University Graduate School of Medicine Shungo Yukumi Department of Surgery, National Hospital Organization Ehime Medical Center Hironori Izutani Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Case Report 10.18926/AMO/63427 A 75-year-old man presented to our hospital 1 year after partial renal resection for clear cell carcinoma. A right lower lobe lung nodule noted at the time of surgery had increased to 3.0 cm in diameter and was confirmed as squamous cell lung carcinoma by bronchoscopic cytology. Computed tomography had also revealed paratracheal lymph node swelling. He underwent right lower lobectomy with lymph node dissection by video-assisted thoracic surgery. Pathological examination confirmed squamous cell carcinoma of the lung but diagnosed the right hilar and mediastinal lymph node metastases as clear cell carcinoma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 A Pediatric Case of Cauda Equina Dermoid Cyst Resected by Minimally Invasive Unilateral Hemilaminectomy 217 223 EN Satoru Yabuno Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michiari Umakoshi Department of Neurosurgery, Kagawa Rosai Hospital Takayuki Nagase Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Sugahara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kawauchi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Yasuhara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/63426 A 3-year-old boy had difficulty sitting up and walking for several months. Magnetic resonance imaging (MRI) revealed an intradural tumor at the L3-4 level. The tumor was successfully resected by unilateral hemilaminectomy and diagnosed as dermoid cyst. The patient had an uneventful postoperative course without pain, and MRI found no recurrence after surgery. A small bone defect remained that might be favorably reconstructed with autologous and artificial bone. Hemilaminectomy allowed us to resect the cauda equina dermoid cyst with minimal invasiveness. Pediatric patients require follow-up as they are more likely to experience spinal deformity or instability after surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells 203 215 EN Tomoya Masuda Department of Gastroenterological 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 Yuuri Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Ieda 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 Shinji Kuroda Department of Gastroenterological Surgery, 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 Yasuo Urata Oncolys BioPharma Inc. 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 Original Article 10.18926/AMO/63425 The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 Retrospective Cohort Study of Clinical Efficacy and Safety of Cefozopran for Treating Febrile Neutropenia during Chemotherapy in Patients with Lung Cancer 167 172 EN Tsukasa Higashionna Department of Pharmacy, Okayama University Hospital Soichiro Ushio Department of Pharmacy, Okayama University Hospital Satoru Esumi Department of Pharmacy, Okayama University Hospital Kiminaka Murakawa Department of Pharmacy, Okayama University Hospital Yoshihisa Kitamura Department of Pharmacy, Okayama University Hospital Toshiaki Sendo Department of Pharmacy, Okayama University Hospital Original Article 10.18926/AMO/63410 Febrile neutropenia (FN) is a serious side effect in patients undergoing cancer chemotherapy and frequently proves fatal. Since infection control is crucial in the management of FN, the antimicrobial agent cefozopran (CZOP) has been recommended but not approved for routine use in clinical care of FN in Japan. However, few studies of CZOP in the management of FN have used a thrice daily dose schedule. The aim of this study was to retrospectively compare the efficacy and safety of CZOP at a dose of 1 g three times daily to those of cefepime (CFPM) in the treatment of FN in our lung cancer patients. The response rates of the CZOP and CFPM groups were 89.5% (17/19 cases) and 83.0% (39/47 cases), respectively, with no significant difference between the two groups. The median duration of antimicrobial treatment was 6 days (4-10 days) in the CZOP group and 7 days (3-13 days) in the CFPM group, with no significant difference between groups. The incidence rates of adverse events were 21.1% (4/19 cases) in the CZOP group and 19.1% (9/47 cases) in the CFPM group. No adverse events of Grade 3 or higher were observed in either group. The findings of the present study suggest that CZOP administration at a dose of 1 g three times per day as an antimicrobial treatment alternative against FN. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 Clinicopathological Features and Surgical Outcomes of Small Bowel Metastasis from Renal Cell Carcinoma 155 165 EN Jiro Kimura Department of Gastroenterological Surgery, National Center for Global Health and Medicine Takehiro Okabayashi Department of Gastroenterological Surgery, National Center for Global Health and Medicine Kenta Sui Department of Gastroenterological Surgery, National Center for Global Health and Medicine Motoyasu Tabuchi Department of Gastroenterological Surgery, National Center for Global Health and Medicine Jun Iwata Department of Diagnostic Pathology, National Center for Global Health and Medicine Yasuhiro Hata Department of Radiology, National Center for Global Health and Medicine Tatsuo Iiyama Department of Biostatistics, National Center for Global Health and Medicine Noriaki Ono Department of Urology, Kochi Health Sciences Center Original Article 10.18926/AMO/63409 Small bowel metastasis from renal cell carcinoma (RCC) is rare, and its clinicopathological characteristics are unclear; thus, we revisited the concept of this tumor and reviewed its diagnostic and treatment modalities. We filtered MEDLINE searches of articles published in English between 1950 and 2019, and identified 100 patients who had undergone treatment, including 1 patient from our clinic. We extracted patient characteristics, treatment, and prognostic data, resulting in clinicopathological data on 100 patients (83 men, 17 women). Mean age was 63 years (range, 16-86 years). Tumor sites were duodenum, jejunum, ileum, and multiple sites in 30, 37, 25, and 7 patients, respectively. The 1-, 3-, and 5-year overall survival rates after diagnosis were 53.0%, 36.0%, and 36.0%. Curative resection patients showed 62.1% 5-year survival after surgery, vs. 27.5% in noncurative surgical management cases. Good prognoses can be expected if these tumors are identified early for complete removal. Surgery is the only curative option. To determine the best management strategy and improve prognostic accuracy, we continue to collect and analyze epidemiological and pathological data. Although this condition is rare, surgery should be considered if curative resection is expected. Prognosis after curative resection is not poor, but recurrence is not unlikely. No potential conflict of interest relevant to this article was reported.

ELSEVIER Acta Medica Okayama 0022-2275 48 4 2007 The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis 768 781 EN Masako Tabuchi Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsumi Inoue Department of Pathology, Kokura Memorial Hospital Hitomi Usui-Kataoka Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuko Kobayashi Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Misako Teramoto Department of Pathology, Kokura Memorial Hospital Koji Takasugi Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenichi Shikata Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masahiro Yamamura Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Ando Department of Cardiology, Kokura Memorial Hospital Keiichiro Nishida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Junko Kasahara Department of Internal Medicine, Okayama Central Hospital Noriaki Kume Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Luis R. Lopez Corgenix, Inc. Kazuaki Mitsudo Department of Cardiovascular Medicine, Kurashiki Central Hospital Masakiyo Nobuyoshi Department of Cardiology, Kokura Memorial Hospital Tatsuji Yasuda Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toru Kita Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Hirofumi Makino Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiji Matsuura Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta 2-glycoprotein I (beta 2GPI), implicating oxLDL/P2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta 2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/R2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta 2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of adierosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta 2GPI complexes correlated with total cholesterol and hemoglobin Al c. Thus, the generation of CRP/oxLDL/beta 2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/R2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis. No potential conflict of interest relevant to this article was reported.

Oxford Univ Press Acta Medica Okayama 2514-2119 6 1 2022 Pacemaker implantation via femoral vein and successful arrhythmia management in an elderly patient with Fontan circulation: a case report ytac003 EN Tomofumi Mizuno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background The frequency of arrhythmias increases after the Fontan operation over time; atrial tachycardia (AT) and sinus node dysfunction (SND) are frequently observed. Case summary Our patient was 63-year-old woman who underwent a lateral tunnel Fontan operation for double outlet right ventricle at age 36. She experienced paroxysmal AT for 1 year, and antiarrhythmic medication was not feasible due to symptomatic SND. Computed tomography revealed a 45 mm-sized thrombus in the high right atrium (RA). The patient had three coexisting conditions: paroxysmal AT, symptomatic SND, and the right atrial thrombus, for which total cavopulmonary connection conversion and epicardial pacemaker implantation (PMI) would have been effective; however, given her age and comorbidities, surgical treatment was considered high risk. Catheter ablation was avoided because of the right atrial thrombus. Finally, a transvenous pacemaker was implanted via the right femoral vein to avoid the right atrial thrombus and severe venous tortuosity from the left subclavian vein to the RA. After PMI, the patient was prescribed amiodarone and bisoprolol for AT suppression. Atrial tachycardia occurred once in the third month after discharge. We increased the dose of amiodarone, and she has been tachycardia-free. Discussion Transvenous PMI must be considered in cases where open thoracic surgery or catheter ablation cannot be performed. This is the first report of transvenous PMI via the right femoral vein and successful AT and SND management in an elderly Fontan patient. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Rapidly Progressive Stenosis of the Left Main Trunk Ostium Starting 21 Months After Stent Implantation 99 104 EN Yoichiro Naito Department of Cardiovascular Medicine, Fukuyama City Hospital Masaki Yoshikawa Department of Cardiovascular Medicine, Fukuyama City Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoki Kubo Department of Cardiovascular Medicine, Fukuyama City Hospital Hiroyasu Sugiyama Department of Cardiovascular Medicine, Fukuyama City Hospital Hideyuki Suzuki Department of Cardiovascular Medicine, Fukuyama City Hospital Shinpei Fujita Department of Cardiovascular Medicine, Fukuyama City Hospital Yasunori Arai Department of Cardiovascular Medicine, Fukuyama City Hospital Sho Takahashi Department of Cardiovascular Medicine, Fukuyama City Hospital Yuichi Kato Department of Cardiovascular Medicine, Fukuyama City Hospital Yu Yoshida Department of Cardiovascular Medicine, Fukuyama City Hospital Hiroaki Akai Department of Cardiovascular Medicine, Fukuyama City Hospital Shuhei Murakami Department of Cardiovascular Medicine, Fukuyama City Hospital Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/63219 Rapidly progressive in-stent restenosis (ISR) after stent deployment from the left main trunk (LMT) to the left anterior descending artery (LAD) without plaque at the LMT ostium has not been reported. A 60-year-old Japanese man with a history of scleroderma, pulmonary fibrosis, and type 2 diabetes developed acute myocardial infarction of the right coronary artery (RCA) and was treated by emergency percutaneous coronary intervention (PCI) for RCA. Nine days later he underwent PCI from the LMT to the LAD. Follow-up coronary angiography (CAG) at 9 and 21 months post-PCI did not reveal ISR in any lesion, but the patient experienced cardiac arrest at 25 months post-PCI. Emergency CAG after resuscitation revealed ISR of the LMT ostium; emergency PCI was conducted. The development of ISR at the ostium of the LMT although the patient was free of plaque 4 months before is extremely unusual. This rare ISR of the LMT ostium progressed rapidly after follow-up CAG revealed no ISR at 21 months post-stent implantation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Cystic Intracranial Recurrence of Olfactory Neuroblastoma without Accumulation on Fluorine-18-fluorodeoxyglucose Positron Emission Tomography 93 98 EN Yukitomo Ishi Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Shigeru Yamaguchi Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Kanako C. Hatanaka Department of Surgical Pathology, Hokkaido University Hospital Emi Takakuwa Department of Surgical Pathology, Hokkaido University Hospital Hiroaki Motegi Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Taishi Honda Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Hiroyuki Kobayashi Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Shunsuke Terasaka Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Akihiro Homma Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Miki Fujimura Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Kiyohiro Houkin Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Case Report 10.18926/AMO/63218 A 66-year-old man underwent multimodal treatment for olfactory neuroblastoma (ONB). When he was 72 years old, a cystic intracranial lesion without accumulation on fluorine-18-fluorodeoxyglucose positron emission tomography was detected. Surgical resection was performed when the patient was 73 years old. The pathological examination revealed recurrence of ONB, and the patient underwent focal irradiation. At age 81, he presented with a second recurrence in the right occipital lobe with radiological and pathological findings similar to the prior recurrence. This case suggests that pathological confirmation should be considered in cases with atypical radiological findings following the treatment of ONB. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Completely Video-assisted Thoracoscopic Lobectomy for Congenital Lobar Emphysema in a Young Adult 89 92 EN Tsuyoshi Ryuko Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Ken Suzawa Department of Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of Thoracic Surgery, Okayama University Hospital Shinji Otani Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Masaomi Yamane Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Case Report 10.18926/AMO/63217 Congenital lobar emphysema (CLE) is defined as the hyperinflation of pulmonary lobes due to obstruction of the flow of air via a known or unknown etiology, which causes pressure symptoms in the adjacent organs. CLE is mainly diagnosed in the neonatal period, and very few adult cases have been reported. Here we report a 34-year-old male with muscular dystrophy who was diagnosed with CLE on examination. He underwent a right lower lobectomy via 3-portal completely video-assisted thoracoscopic surgery, and his symptoms improved. Thoracoscopic surgery helped preserve the respiratory muscles and led to the improvement of respiratory function in this patient. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Chidamide and Decitabine in Combination with a HAG Priming Regimen for Acute Myeloid Leukemia with TP53 Mutation 63 70 EN Bei Zhang Department of Hematology, Jiaozuo People’s Hospital Zhixin Pei Department of Hematology, Jiaozuo People’s Hospital Hongxia Wang Department of Hematology, Jiaozuo People’s Hospital Huimin Wu Department of Hematology, Jiaozuo People’s Hospital Junjie Wang Department of Hematology, Jiaozuo People’s Hospital Junjun Bai Department of Hematology, Jiaozuo People’s Hospital Qinglin Song Department of Hematology, Jiaozuo People’s Hospital Original Article 10.18926/AMO/63213 We analyzed the treatment effects of chidamide and decitabine in combination with a HAG (homoharringtonine, cytarabine, G-CSF) priming regimen (CDHAG) in acute myeloid leukemia (AML) patients with TP53 mutation. Seven TP53 mutated AML patients were treated with CDHAG. The treatment effects were assessed using hemogram detection and bone marrow aspirate. The possible side effects were evaluated based on both hematological and non-hematological toxicity. Four of the seven patients were classified as having achieved complete remission after CDHAG treatment; one patient was considered to have achieved partial remission, and the remaining two patients were considered in non-remission. The overall response rate (ORR) to CDHAG was 71.4%. Regarding the side effects, the hematological toxicity level of the seven patients ranged from level III to level IV, and infections that occurred at lung, blood, and skin were recorded. Nausea, vomiting, liver injury, and kidney injury were also detected. However, all side effects were attenuated by proper management. The CDHAG regimen clearly improved the ORR (71.4%) of TP53-mutated AML patients, with no severe side effects. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Urinary Protein-to-creatinine Ratios Predict Recurrence in Pediatric and Young Adult Cases of Minimal Change Nephrotic Syndrome 41 49 EN Hiroyuki Miyahara Department of Pediatrics, Okayama University Hospital Takayuki Miyai Department of Pediatrics, Okayama University Hospital Kunihiko Aya Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63207 High-dose steroids are required for the treatment of minimal change nephrotic syndrome (MCNS), especially for episodes of recurrence. Predicting and avoiding recurrence can help reduce the steroid dose, but prediction is currently difficult. We herein examined whether changes in laboratory data, especially the urinary protein- to-creatinine ratio (UTP/UCr), can predict clinical recurrence. We also assessed differences in clinical features between children and young adults. We included 36 patients with MCNS; for each case, we retrospectively studied laboratory data during stable remission and pre-recurrence, with the “stable” period defined as all but the 6 weeks before recurrence, and pre-recurrence defined as the 4±2 weeks before recurrence. UTP/UCr, serum albumin, etc. were measured every 5 years during stable periods. We divided patients into cohorts by age at recurrence, < 15 years and ≥ 15 years, and compared stable and pre-recurrence values for the two groups. UTP/UCr values during stable periods tended to be higher in younger patients. UTP/UCr and serum albumin showed statistically significant changes during pre-recurrence periods, but only in those aged ≥ 15 years. Thus, clinical features of recurrence differed depending on age. Signs of recurrence can be confirmed via UTP/UCr or serum albumin several weeks before recurrence in patients ≥ 15 years. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Plasma Concentrations of Trace Elements Selenium and Cobalt During and After Coronary Artery Bypass Grafting Surgery 33 39 EN Jia-Yi Zhou The Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital Hai-Tao Hou Unit of Perfusion, Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospita Shi-Fu Wang Unit of Perfusion, Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital Qin Yang The Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital Guo-Wei He The Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital Original Article 10.18926/AMO/63206 Trace elements selenium (Se) and cobalt (Co) are essential in the human body, and a correlation between Se and cardiac surgery has been suggested. We investigated the plasma concentrations of Se and Co during and after coronary artery bypass grafting (CABG) surgery under cardiopulmonary bypass (CPB). From December 2019 to January 2020, preoperative plasma samples from isolated first-time CABG patients (n=20; 10 males, 10 females) were prospectively collected post-anesthesia and before CPB (T1), 45 min after CPB started (T2), 90 min after CPB started (T3), and postoperative days 1 (T4), and day 4 (T5). The plasma concentrations of Se and Co were measured. The Se concentration was significantly decreased at T2 (105.24±4.08 vs. 68.56±2.42 μg/L, p<0.001) and T3 (105.24±4.08 vs. 80.41±3.40 μg/L, p<0.001). The Co concentration was significantly decreased at T4 (0.35±0.19 vs. 0.26±0.13 μg/L, p<0.01) and T5 (0.35±0.19 vs. 0.23±0.11 μg/L, p<0.001). Five patients developed atrial fibrillation (AF); there was no other operative mortality or major morbidity. This is the first report of alterations of plasma Se and Co concentrations during and after CABG surgery. Our results may indicate that Se supplementation before or during CABG and Co supplementation after CABG may become necessary for patients undergoing CABG. No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 1932-6203 16 11 2021 Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder e0254289 EN Shinsuke Oda Department of Pathology and Experimental Medicine, Graduate School 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 Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihiro Ito Department of Immunology, Nara Medical University Takahiro Yamaguchi 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 Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aberrant activation of the Ras/Raf/ERK (extracellular-signal-regulated kinase)-MAPK (mitogen-activated protein kinase) pathway is involved in the progression of cancer, including urothelial carcinoma; but the negative regulation remains unclear. In the present study, we investigated pathological expression of Spred2 (Sprouty-related EVH1 domain-containing protein 2), a negative regulator of the Ras/Raf/ERK-MAPK pathway, and the relation to ERK activation and Ki67 index in various categories of 275 urothelial tumors obtained from clinical patients. In situ hybridization demonstrated that Spred2 mRNA was highly expressed in high-grade non-invasive papillary urothelial carcinoma (HGPUC), and the expression was decreased in carcinoma in situ (CIS) and infiltrating urothelial carcinoma (IUC). Immunohistochemically, membranous Spred2 expression, important to interact with Ras/Raf, was preferentially found in HGPUC. Interestingly, membranous Spred2 expression was decreased in CIS and IUC relative to HGPUC, while ERK activation and the expression of the cell proliferation marker Ki67 index were increased. HGPUC with membranous Spred2 expression correlated significantly with lower levels of ERK activation and Ki67 index as compared to those with negative Spred2 expression. Thus, our pathological findings suggest that Spred2 counters cancer progression in non-invasive papillary carcinoma possibly through inhibiting the Ras/Raf/ERK-MAPK pathway, but this regulatory mechanism is lost in cancers with high malignancy. Spred2 appears to be a key regulator in the progression of non-invasive bladder carcinoma. No potential conflict of interest relevant to this article was reported.

Future Science Ltd. Acta Medica Okayama 2056-5623 Concordance of acquired mutations between metastatic lesions and liquid biopsy in metastatic colorectal cancer FSO757 EN Fumitaka Taniguchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences Akihiro Nyuya Department of Clinical Oncology, Kawasaki Medical School Toshiaki Toshima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences Yoshiko Mori Department of Clinical Genetics & Digestive Tract & General Surgery, Saitama Medical Center, Saitama Medical University, Makoto Okawaki Department of Clinical Oncology, Kawasaki Medical School Hiroyuki Kishimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences Hiroaki Tanioka Department of Clinical Oncology, Kawasaki Medical School Yoshiyuki Yamaguchi Department of Clinical Oncology, Kawasaki Medical School Ajay Goel Department of Molecular Diagnostics & Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center Takeshi Nagasaka Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences Aim: To evaluate whether PCR-reverse sequence-specific oligonucleotide can examine the concordance between liquid biopsy and metastatic lesions with acquired resistance. Materials & methods: We examined acquired mutations in chemoresistant lesions and blood obtained from four patients with RAS wildtype metastatic colorectal cancer who underwent treatment with anti-epidermal growth factor receptor antibodies. Results: In one patient, metastatic lesions harbored diverse acquired mutations in KRAS in all seven metastases; the two acquired mutations were detectable in blood collected after the patient acquired resistance. None of the other patients exhibited liquid biopsy mutations, except one, with a BRAF mutation confirmed in primary tumor and peritoneal dissemination. Conclusion: Liquid biopsy based on PCR-reverse sequence-specific oligonucleotide is a successful procedure for capturing acquired mutations with precise information on the RAS mutational spectrum. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Non-Invasive Prenatal Genetic Testing (NIPT) Leading to Prenatal Diagnosis of Trisomy 21 Mosaicism and 18q Deletion Syndrome: Two Cases 745 750 EN Kei Hayata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Akiko Ohira Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazumasa Tani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Chikako Ogawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Case Report 10.18926/AMO/62816 NIPT is non-definitive testing to estimate the possibility that fetuses have trisomy 21, trisomy 18, or trisomy 13. However, in NIPT-positive and indeterminate cases, rare chromosomal disease may become apparent, requiring advanced genetic considerations and counseling skills. We experienced two such cases, a trisomy 21 mosaicism case triggered by NIPT-positive status and 18q deletion syndrome triggered by NIPT-indeterminate status. These cases have two clinical implications for NIPT. First, it was revealed that trisomy mosaicism might be found in NIPT-positive cases that have lower Z-Scores than those inferred from the fraction of fetal cfDNA in the case of standard trisomy. Second, it is possible that microdeletion syndrome could be the reason for an indeterminate NIPT result. Today’s genetic counseling requires more expertise in ethics and communication as well as genetic science because NIPT can lead to totally unexpected results. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Sublingual Gland Carcinoma Revealed by Choroidal Metastasis 741 744 EN Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichiro Doi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosuke Takahashi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/62815 A 65-year-old man presented with a 1-week history of left eye distortion. An elevated choroidal lesion covering 6 disc diameters was found in the posterior retina of the left eye. Systemic examination revealed sublingual gland carcinoma and multiple lung metastases, and the diagnosis was choroidal metastasis from sublingual gland carcinoma. Following chemotherapy and radiation therapy, the choroidal lesion shrunk and the patient’s visual acuity improved. The patient died 23 months after his first visit. To the best of our knowledge, this is the first reported case of choroidal metastasis from sublingual gland carcinoma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Guideline-based Treatment of Glucocorticoid-induced Osteoporosis in Patients with Rheumatoid Arthritis: A Retrospective Study with the AORA Registry 699 704 EN Tetsuya Kawano Department of Orthopedic Surgery, Akita University Graduate School of Medicine Naohisa Miyakoshi Department of Orthopedic Surgery, Akita University Graduate School of Medicine Hiroyuki Tsuchie Department of Orthopedic Surgery, Akita University Graduate School of Medicine Takeshi Kashiwagura Department of Orthopedic Surgery, Akita City Hospital Moto Kobayashi Department of Orthopedic Surgery, Hiraka General Hospital Yokote City Hiroshi Aonuma Department of Orthopedic Surgery, Ogachi Central Hospital Yuzawa City Yusuke Sugimura Department of Orthopedic Surgery, Nakadori General Hospital Akita City Yoichi Shimada Department of Orthopedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/62809 Glucocorticoid-induced osteoporosis (GIOP) is one of the side effects associated with glucocorticoid (GC) therapy. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) provided new guidelines for the management and treatment of GIOP. The aim of the present study was to clarify the prevalence of patients with rheumatoid arthritis (RA) requiring treatment according to the new guidelines and to identify risk factors associated with lack of treatment in these patients. Patients in the 2018 Akita Orthopedic group on Rheumatoid Arthritis (AORA) database were enrolled. Of 2,234 patients with RA in the database, 683 (30.6%) met the 2014 JSBMR guideline treatment criteria, and 480 (70.3%) had been treated. The untreated group included a larger number of males, younger patients, and patients treated in clinics rather than hospital (p<0.001, p=0.015, and p<0.001, respectively). Multivariate analyses found that male sex, younger age, and clinic-based RA care were significant risk factors associated with lack of treatment (p<0.001, p=0.013, and p<0.001, respectively). Thus, male sex, younger age, and clinic-based care were identified as risk factors No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 EG-VEGF Induces Invasion of a Human Trophoblast Cell Line via PROKR2 677 684 EN Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Mitsui Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Ohira Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jota Maki 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 Kei Hayata 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 Original Article 10.18926/AMO/62806 Extravillous trophoblast (EVT) invasion is important for embryo implantation, placental development, and successful remodeling of the uterine spiral artery. Endocrine gland derived-vascular endothelial growth factor (EG-VEGF) and matrix metalloproteinases (MMPs) are implicated in EVT invasion; however, the high con-centrations found in pregnancy pathologies have not been investigated in non-tumor trophoblasts. The roles of EG-VEGF, prokineticin receptors (PROKR1/2), MMP-2, and MMP-9 in EVT invasion during spiral artery remodeling were evaluated using human EVT from HTR-8/SVneo cell lines. The expression of MMP-2, MMP-9, and mitogen-activated protein kinase (MAPK), and Akt pathways in HTR-8/SVneo cells treated with recom-binant EG-VEGF alongside anti-PROKR1 and/or anti-PROKR2 antibodies was evaluated using quantitative reverse transcription-PCR and western blotting. Wound-healing and cell invasion assays were performed to assess the migration and invasion of these treated cells. Interestingly, 20 nM EG-VEGF activated ERK1/2 sig-naling and upregulated MMP-2 and MMP-9. This effect was suppressed by anti-PROKR2 antibody via ERK1/2 downregulation. Anti-PROKR2 antibody inhibited the migration and invasion of EG-VEGF-stimulated HTR-8/SVneo cells. Elevated concentrations of EG-VEGF enhance EVT invasion in a human trophoblast cell line by upregulating MMP-2 and MMP-9 via PROKR2. These new insights into the regulation of epithelial cell invasion may help in developing therapeutic interventions for placental-related diseases during pregnancy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 O-arm Navigation-Guided Surgical Resection and Posterior Fixation for a Large Sacral Schwannoma 647 652 EN Koji Uotani Department of Orthopaedic Surgery, Okayama Rosai Hospital Taro Yamauchi Department of Orthopaedic Surgery, Okayama Rosai Hospital Keisuke Sano Department of Orthopaedic Surgery, Ehime Rehabilitation Center for children Hiroshi Sonobe Department of Pathology, Okayama Rosai Hospital Yoshihiro Fujiwara Department of Orthopaedic Surgery, Okayama Rosai Hospital Praful Suresh Maste Department of Orthopaedic Surgery, Okayama Rosai Hospital Sumeet Sonawane Department of Orthopaedic Surgery, Okayama Rosai Hospital Masato Tanaka Department of Orthopaedic Surgery, Okayama Rosai Hospital Case Report 10.18926/AMO/62779 Sacral schwannoma is a rare tumor with relatively few symptoms; it thus tends to be large at diagnosis and is challenging to treat surgically. We present the case of a 12-year-old girl with a large sacral schwannoma that was successfully surgically resected using O-arm navigation in a two-stage operation. First, we performed tumor resection from the posterior aspect with assisted O-arm navigation. One week later, resection from the anterior aspect was conducted with posterior spinopelvic fixation and fibula graft. We performed partial resection of the tumor from the anterior and posterior aspects as much as possible. O-arm navigation contributed to precise and safe tumor resection and implant insertion. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Factors for Acute Kidney Injury Following Total Arch Replacement and Association with Temperature Management During Cardiopulmonary Bypass: A Single-center Retrospective Observational Study 585 593 EN Hiroki Omiya Department of Anesthesiology and Critical Care Medicine, Hiroshima Citizens Hospital Makoto Takatori Department of Anesthesiology and Critical Care Medicine, Hiroshima Citizens Hospital Keiji Yunoki Department of Cardiovascular Surgery, Hiroshima Citizens Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitation, Okayama University Hospital Original Article 10.18926/AMO/62771 Many patients develop acute kidney injury (AKI) after vascular surgery. In this retrospective observational study, we investigated the risk factors for AKI defined using the Kidney Disease Improving Global Outcomes criteria after total arch replacement (TAR). Additionally, we investigated the influence of temperature manage-ment during cardiopulmonary bypass (CPB) on postoperative renal function by propensity score-matched anal-ysis. We retrospectively analyzed 161 consecutive patients who underwent TAR between 2016 and 2019. Postoperative AKI occurred in 48.7% of the patients. In the multivariate analysis, male sex (odds ratio [OR] 3.95, 95% confidence interval [95%CI] 1.56-8.27, p = 0.002), ACE inhibitors/ARB medication (OR 3.19, 95%CI 1.49-6.82, p = 0.003), preoperative chronic kidney disease (OR 2.47, 95%CI 1.17-5.23, p = 0.02), pro-longed CPB time (OR 2.36, 95%CI 1.05-5.34, p = 0.04), and lower body ischemic time during CPB (OR 2.20, 95%CI 1.05-4.46, p = 0.04) were identified as independent risk factors for AKI. Propensity score-matched anal-ysis showed no significant difference in the risk of AKI following TAR between mild hypothermia or normo-thermia and moderate hypothermia (37.2% vs. 41.9%, p = 0.83). In conclusion, modifiable risk factors for AKI included prolonged CPB time and lower body ischemic time. Temperature management during CPB had no clear effect on outcomes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Relationship between Pressure Ulcers in Elderly People and Physiological Indices of the Skin 557 565 EN Hiroko Takeshima Kohara Department of Nursing, University of Kochi Mitsunori Ikeda Department of Nursing, University of Kochi Masami Okawa Shiragikuen Hospital Original Article 10.18926/AMO/62768 This study examined the relationship between skin physiological indices and pressure ulcers in elderly people. The subjects were 55 bedridden elderly Japanese patients with a median age of 85 years. The following parame-ters were measured using non-invasive devices: skin surface temperature, moisture content in the stratum corneum, moisture content in the dermis, transepidermal water loss as an index of skin barrier function, skin erythema and skin elasticity. The sacral and 2 heel areas were observed as sites predisposed to pressure ulcers. Within one month after measuring the skin physiological indices, we confirmed pressure ulcers of National Pressure Ulcer Advisory Panel classification Stage II or worse based on medical records. Among the 55 patients, 4 (7.3%) prospectively developed a total of 5 pressure ulcers within 16 days. Only the skin erythema score was significantly higher with than without pressure ulcers (p < 0.001). We performed a binary logistic regression analysis and confirmed a significant relationship between pressure-ulcer development and the level of erythema (odds ratio = 1.026; 95% confidence interval: 1.011-1.042). Skin erythema increased before the development of pressure ulcers. Taken together, our results show that the high skin erythema score can be a predictive indicator of pressure ulcers. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Glial Cells as Possible Targets of Neuroprotection through Neurotrophic and Antioxidative Molecules in the Central and Enteric Nervous Systems in Parkinson’s Disease 549 556 EN Nami Isooka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/62767 Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. The loss of nigrostriatal dopaminergic neurons produces its characteristic motor symptoms, but PD patients also have non-motor symptoms such as constipation and orthostatic hypotension. The pathological hallmark of PD is the presence of α-synuclein-containing Lewy bodies and neurites in the brain. However, the PD pathology is observed in not only the central nervous system (CNS) but also in parts of the peripheral nervous system such as the enteric nervous system (ENS). Since constipation is a typical prodromal non-motor symptom in PD, often preceding motor symptoms by 10-20 years, it has been hypothesized that PD pathology propagates from the ENS to the CNS via the vagal nerve. Discovery of pharmacological and other methods to halt this progression of neurodegeneration in PD has the potential to improve millions of lives. Astrocytes protect neurons in the CNS by secretion of neurotrophic and antioxidative factors. Similarly, astrocyte-like enteric glial cells (EGCs) are known to secrete neuroprotective factors in the ENS. In this article, we summarize the neuroprotective function of astrocytes and EGCs and discuss therapeutic strategies for the prevention of neurodegeneration in PD targeting neurotrophic and antioxidative molecules in glial cells. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 22 17 2021 Effect of Angiotensin II on Chondrocyte Degeneration and Protection via Differential Usage of Angiotensin II Receptors 9204 EN Takashi Nishida Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sho Akashi Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The renin-angiotensin system (RAS) controls not only systemic functions, such as blood pressure, but also local tissue-specific events. Previous studies have shown that angiotensin II receptor type 1 (AT(1)R) and type 2 (AT(2)R), two RAS components, are expressed in chondrocytes. However, the angiotensin II (ANG II) effects exerted through these receptors on chondrocyte metabolism are not fully understood. In this study, we investigated the effects of ANG II and AT(1)R blockade on chondrocyte proliferation and differentiation. Firstly, we observed that ANG II significantly suppressed cell proliferation and glycosaminoglycan content in rat chondrocytic RCS cells. Additionally, ANG II decreased CCN2, which is an anabolic factor for chondrocytes, via increased MMP9. In Agtr1a-deficient RCS cells generated by the CRISPR-Cas9 system, Ccn2 and Aggrecan (Acan) expression increased. Losartan, an AT(1)R antagonist, blocked the ANG II-induced decrease in CCN2 production and Acan expression in RCS cells. These findings suggest that AT(1)R blockade reduces ANG II-induced chondrocyte degeneration. Interestingly, AT(1)R-positive cells, which were localized on the surface of the articular cartilage of 7-month-old mice expanded throughout the articular cartilage with aging. These findings suggest that ANG II regulates age-related cartilage degeneration through the ANG II-AT(1)R axis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Usefulness of Middle Colic Artery Transposition Technique for Hepatic Arterial Reconstruction in Conversion Surgery for an Initially Unresectable, Locally Advanced Pancreatic Cancer 543 548 EN Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahito Yagi 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 Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Yoshida 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 Kenjiro Kumano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshimoto 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 Case Report 10.18926/AMO/62410 The outcomes of pancreatectomy with resection and reconstruction of the involved arteries for locally advanced pancreatic cancer following chemotherapy have improved in recent years. In pancreatic head cancers in which there is contact with the common and proper hepatic arteries, margin-negative resection requires pancreati-coduodenectomy, with the resection of these arteries and the restoration of hepatic arterial flow. Here, we describe a middle colic artery transposition technique in hepatic arterial reconstruction during pancreatoduo-denectomy for an initially unresectable locally advanced pancreatic cancer. This technique was effective and may provide a new option for hepatic artery reconstruction in such cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Tumor Lysis Syndrome due to Eribulin Administration for Metastatic Undifferentiated Pleomorphic Sarcoma of the Buttock 533 538 EN Hiroyuki Tsuchie Department of Orthopedic Surgery, Akita University Graduate School of Medicine Naohisa Miyakoshi Department of Orthopedic Surgery, Akita University Graduate School of Medicine Hiroyuki Nagasawa Department of Orthopedic Surgery, Akita University Graduate School of Medicine Yoichi Shimada Department of Orthopedic Surgery, Akita University Graduate School of Medicine Case Report 10.18926/AMO/62408 Tumor lysis syndrome (TLS) is a complication of cancer treatment that requires urgent intervention. It is extremely rare in the treatment of soft tissue sarcoma (STS) of the limbs or trunk, and there are currently no reports of TLS occurrence from eribulin therapy. We report the case of a 78-year-old woman with an undiffer-entiated pleomorphic sarcoma on the right buttock. We initiated chemotherapy with intravenous eribulin mesylate. Deterioration of renal function, mild hyperkalemia, hyperuricemia, hypocalcemia, and hyperphos-phatemia were confirmed on examination, suggesting the presence of TLS. We present an extremely rare case of TLS from eribulin for STS. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Effects of Tablet Size and Head Posture on Drug Swallowing: A Preliminary Examination Using Endoscopy in Healthy Subjects 495 503 EN Shuntaro Sugiyama Division of Medically Compromised Geriatric Dentistry, Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Hospital Graduate School of Dentistry Takatoshi Iida Division of Medically Compromised Geriatric Dentistry, Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Hospital Graduate School of Dentistry Yoshinari Morimoto Division of Medically Compromised Geriatric Dentistry, Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Hospital Graduate School of Dentistry Yuki Yamazaki Division of Medically Compromised Geriatric Dentistry, Department of Pharmacy, Kanagawa Dental University Hospital Lou Mikuzuki Division of Medically Compromised Geriatric Dentistry, Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Hospital Graduate School of Dentistry Megumi Hayashi Division of Medically Compromised Geriatric Dentistry, Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Hospital Graduate School of Dentistry Original Article 10.18926/AMO/62402 Tablet size and head posture have been reported to affect swallowing of medications, but no previous studies have evaluated their effects in detail. Our aim was to investigate for the first time the effect of tablet size and head posture on drug swallowing by endoscopic evaluation in healthy subjects. Round tablets (7 , 10 , 12, and 14 mm in diameter) were swallowed by 15 healthy adults with an endoscope inserted in the neutral, head flex-ion, and head extension positions. Evaluation of swallowing difficulty using a numeric rating scale (NRS), presence or absence of pharyngeal residue and its location, and tablet oral transit time (TOTT) were recorded. In the neutral position, the NRS score was higher with the 14 mm tablets than with the 7 mm tablets. The TOTT with the 7 mm tablets was significantly shorter in the head extension than in the neutral position. Swallowing difficulty increased when the tablet diameter was more than 7 mm. Residues were found in the epi-glottis, pyriform sinus, and tongue base. These findings suggest that head extension shortens the TOTT and assists oral-pharyngeal transport. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Assessment of the Concordance Rate between Intraoperative Pathological Diagnosis and the Final Pathological Diagnosis of Spinal Cord Tumors 455 460 EN Sosuke Muraoka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Yamane Department of Intelligent Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruo Misawa Department of Orthopaedic Surgery, Okayama University Hospital Tomoyuki Takigawa Department of Orthopaedic Surgery, Okayama University Hospital Tomoko Tetsunaga Yoshiaki Oda Department of Orthopaedic Surgery, Okayama University Hospital Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62397 The intraoperative pathological diagnosis (IPD) plays an important role in determining the optimal surgical treatment for spinal cord tumors. The final pathological diagnosis (FPD) is sometimes different from the IPD. Here, we sought to identify the accuracy of the IPD of spinal cord tumors compared to the FPD. We retrospec-tively analyzed the cases of 108 patients with spinal cord tumors treated surgically in our institute; the IPD, FPD, mismatched cases, and concordance rate between the IPD and FPD were investigated. Five cases involved a mismatch between the IPD and FPD. The overall concordance rate was 95.4%, with 90.9% for extra-dural lesions, 98.5% for intradural extramedullary lesions, 84.2% for intramedullary lesions, and 100% for dumbbell-type tumors. The concordance rate of intramedullary lesions tended to be lower than that of other lesions (p = 0.096). A lower concordance rate was revealed for intramedullary lesions compared to the other lesions. Despite the IPD clearly remaining a valuable tool during operative procedures, surgeons should recog-nize the limitations of IPDs and make comprehensive decisions about surgical treatments. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Differences in Attitudes and Practices of Cancer Pain Management between Medical Oncologists and Palliative Care Physicians 431 437 EN Toshiki Kunitomi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichirou Nasu Department of Internal Medicine, Okayama Saiseikai General Hospital Daisuke Minami Palliative Care Team, Okayama University Hospital Takayuki Iwamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nishie Palliative Care Team, Okayama University Hospital Shinya Saito Palliative Care Team, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junji Matsuoka Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62394 This study aimed to evaluate whether there are differences in the attitudes and practices of cancer pain manage-ment between medical oncologists and palliative care physicians. An online nationwide survey was used to collect responses from board-certified medical oncologists and palliative care physicians in Japan. The survey questionnaire comprised 30 questions. The differences in responses between medical oncologists and palliative care physicians were examined. Out of the 1,227 questionnaires sent, 522 (42.5%) were returned. After apply-ing the exclusion criteria, 445 questionnaires (medical oncologists: n = 283; palliative care physicians: n = 162) were retained for analysis. Among the questions about potential barriers to optimal cancer pain man-agement, both medical oncologists and palliative care physicians considered the reluctance of patients to take opioids due to fear of adverse effects as the greatest barrier. Significantly different ratings between medical oncologists and palliative care physicians were observed on 5 of the 8 questions in this area. Significantly differ-ent ratings were observed for all questions concerning pain specialists and their knowledge. For effective cancer pain management, it is important to account for differences in attitudes and practice between medical oncolo-gists and palliative care physicians. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Medial Meniscus Posterior Root Repair Using a Modified Mason-Allen Suture Can Prevent the Progression of Cartilage Degeneration on the Loading Surface of the Medial Compartment: A Second-Look Arthroscopic Evaluation 423 430 EN Shota Takihira Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Kodama Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Miyazawa 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 Original Article 10.18926/AMO/62380 The treatment of medial meniscus posterior root tears (MMPRTs) has evolved to include a variety of repair strategies. This study investigated the location of the articular cartilage degeneration during second-look arthroscopy after transtibial pullout repair with a modified Mason-Allen suture using FasT-Fix (F-MMA) in 22 patients with MMPRTs. Second-look arthroscopy was performed approximately 1 year postoperatively to eval-uate the healing status of the medial meniscus (MM). Articular cartilage degeneration was assessed using the International Cartilage Repair Society grade at primary surgery and again at second-look arthroscopy. Articular surfaces of the medial/lateral femoral condyles, the medial/lateral tibial plateaus, the patella and the trochlea were divided into several subcompartments (MF 1-9, LF 1-9, MT 1-5, LT 1-5, P 1-9, T 1-3). Clinical evaluations used the Japanese Knee Injury and Osteoarthritis Outcome, Lysholm, and International Knee Documentation Committee scores. Second-look arthroscopic findings showed complete healing of the MM posterior root in all patients. Significant differences between pullout repair and second-look arthroscopy were observed for MF 2 and 4, LF 7, and P 7. All clinical outcomes were improved. Our results indicate that this technique improves clinical outcomes postoperatively and may prevent the progression of cartilage degenera-tion on the loading surface of the medial knee compartment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Surgical Treatment of Epiretinal Membrane 403 413 EN Ryo Matoba 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 Review 10.18926/AMO/62378 Epiretinal membrane (ERM) is a common retinal disease characterized by cellular proliferation and metaplasia that lead to the formation of a pathological fibrocellular membrane immediately superjacent to the inner retinal surface. The vast majority of ERMs are considered idiopathic. However, ERM formation can result from various primary intraocular diseases, including retinal breaks and detachment, retinal vascular diseases, and vitreoretinal inflammatory conditions. Although ERMs are generally asymptomatic or cause mild metamorphopsia and/or a modest decrease in visual acuity, some can cause severe macular distortion and macular edema, resulting in significantly impaired function. Surgical removal of ERM is the only treatment, and improvements in vitrectomy systems have enabled less invasive treatment. However, there are currently no standardized criteria for ERM surgery, and the indications for surgery are determined from the patient’s subjective symptoms. Another problem with ERM surgery is that not all patients show satisfactory postoperative recovery of visual function. Thus, further research is needed to determine the criteria for ERM surgery and methods to improve the postoperative prognosis. No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 1932-6203 16 7 2021 RANKL expression in chondrocytes and its promotion by lymphotoxin-alpha in the course of cartilage destruction during rheumatoid arthritis e0254268 EN Ayumu Takeshita Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nishida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Nakahara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Kaneda Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Ohashi 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 We investigated the expression and localization of the receptor activator nuclear factor kappa B ligand (RANKL) in cartilage from patients with rheumatoid arthritis (RA) of relevance to cartilage degeneration. We also examined the role of exogenous lymphotoxin (LT)-alpha on RANKL expression in human chondrocytes and its effect on in vitro osteoclast differentiation. Cartilage and synovial fluid samples were obtained from 45 patients undergoing total joint replacement surgery or joint puncture, including 24 patients with osteoarthritis (OA) and 21 patients with RA. RANKL expression in articular cartilage was examined by immunohistochemistry. LT-alpha concentrations in synovial fluid were measured using an enzyme-linked immunosorbent assay (ELISA). Normal human chondrocytes were stimulated with LT-alpha, and the relative mRNA levels of RANKL, osteoprotegerin (OPG), matrix metalloproteinase-9, and vascular endothelial growth factor were examined by real-time polymerase chain reaction. Soluble RANKL protein in culture media was measured using ELISA, and membrane-bound RANKL protein in cells was examined by western blotting. Co-cultures of human chondrocytes with peripheral blood mononuclear cells (PBMCs) were stimulated with macrophage-colony stimulating factor and LT-alpha, and osteoclast differentiation was evaluated by staining for tartrate-resistant acid phosphatase. LT-alpha concentrations were higher in RA synovial fluid than in OA samples. The population of RANKL-positive chondrocytes of RA cartilage was higher than that of OA cartilage, and correlated with cartilage degeneration. Stimulation of cultured human chondrocytes by LT-alpha increased RANKL expression, the RANKL/OPG ratio, and angiogenic factors. Membrane-bound RANKL in chondrocytes was up-regulated after stimulation of LT-alpha, whereas soluble RANKL in culture medium did not increase. Co-cultures of human chondrocytes and PBMCs demonstrated that LT-alpha stimulated human chondrocytes to produce RANKL and induced osteoclastic differentiation of PBMCs. RANKL produced by chondrocytes may contribute to cartilage destruction during RA and LT-alpha could promote the expression of RANKL in human chondrocytes. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1660-4601 18 14 2021 A Novel Radiographic Measurement Method for the Evaluation of Metatarsophalangeal Joint Dislocation of the Lesser Toe in Patients with Rheumatoid Arthritis 7520 EN Hideki Ohashi Department of Orthopaedic Surgery, Takahashi Central Hospital Keiichiro Nishida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama University Hospital Kenta Saiga Department of Orthopaedic Surgery, Okayama University Hospital Ryuichi Nakahara Department of Orthopaedic Surgery, Okayama University Hospital Masahiro Horita Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunji Okita Department of Orthopaedic Surgery, Okayama City Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Dorsal dislocation of metatarsophalangeal (MTP) joints of the lesser toe frequently occurs in patients with rheumatoid arthritis (RA), and may cause painful and uncomfortable plantar callosities and ulceration. The current study examined the reliability and clinical relevance of a novel radiographic parameter (the MTP overlap distance [MOD]) in evaluating the severity of MTP joint dislocation. The subjects of the current study were 147 RA patients (276 feet; 1104 toes). MOD, defined as the overlap distance of the metatarsal head and the proximal end of the phalanx, was measured on plain radiographs. The relationship between the MOD and clinical complaints (forefoot pain and/or callosity formation) was analyzed to create a severity grading system. As a result, toes with callosities had a significantly larger MOD. ROC analysis revealed that the MOD had a high AUC for predicting an asymptomatic foot (-0.70) and callosities (0.89). MOD grades were defined as follows: grade 1, 0 <= MOD < 5 mm; grade 2, 5 <= MOD < 10 mm; and grade 3, MOD >= 10 mm. The intra- and inter-observer reliability of the MOD grade had high reproducibility. Furthermore, the MOD and MOD grade improved significantly after joint-preserving surgeries for lesser toe deformities. Our results suggest that MOD and MOD grade might be useful tools for the evaluation of deformities of the lesser toe and the effect of surgical intervention for MTP joints in patients with RA. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Successful Surgical Management of Acute Appendicitis in a Centenarian 385 389 EN Atsushi Okita Endoscopic Surgery Center, Daiichi Towakai Hospital Masaki Fujimura Endoscopic Surgery Center, Daiichi Towakai Hospital Isao Sato Endoscopic Surgery Center, Daiichi Towakai Hospital Yoshihide Chino Endoscopic Surgery Center, Daiichi Towakai Hospital Takafumi Yuba Endoscopic Surgery Center, Daiichi Towakai Hospital Makoto Mizutani Endoscopic Surgery Center, Daiichi Towakai Hospital Tomotake Tabata Endoscopic Surgery Center, Daiichi Towakai Hospital Minoru Iida Endoscopic Surgery Center, Daiichi Towakai Hospital Kimitsuka Kumano Endoscopic Surgery Center, Daiichi Towakai Hospital Case Report 10.18926/AMO/62235 No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Predictors of Hypotension after Adrenalectomy for Pheochromocytoma 345 349 EN Kanae Koyama Department of Urology, Graduate School of Medicine, Ehime University Noriyoshi Miura Department of Urology, Graduate School of Medicine, Ehime University Ryuta Watanabe Department of Urology, Graduate School of Medicine, Ehime University Yuichiro Sawada Department of Urology, Graduate School of Medicine, Ehime University Terutaka Noda Department of Urology, Graduate School of Medicine, Ehime University Kenichi Nishimura Department of Urology, Graduate School of Medicine, Ehime University Seiji Asai Department of Urology, Graduate School of Medicine, Ehime University Tetsuya Fukumoto Department of Urology, Graduate School of Medicine, Ehime University Yutaka Yanagihara Department of Urology, Graduate School of Medicine, Ehime University Yuki Miyauchi Department of Urology, Graduate School of Medicine, Ehime University Tadahiko Kikugawa Department of Urology, Graduate School of Medicine, Ehime University Takashi Saika Department of Urology, Graduate School of Medicine, Ehime University Original Article 10.18926/AMO/62229 The management of blood pressure is a significant concern for surgeons and anesthesiologists performing adrenalectomy for pheochromocytoma. We evaluated clinical factors in pheochromocytoma patients to identify the predictors of postoperative hypotension. The medical records of patients who underwent adrenalectomy for pheochromocytoma between 2001 and 2017 were retrospectively reviewed and clinical and biochemical data were evaluated. Of 29 patients, 13 patients needed catecholamine support in the perisurgical period while 16 patients did not. There were significant differences in median age, tumor size, and blood pressure drop (maxmin) between the 2 groups (68 vs 53 years old, p=0.045; 50 vs 32 mm diameter, p=0.022; 110 vs 71 mmHg, p=0.015 respectively). In univariate logistic analysis, age > 65.5 years, tumor size > 34.5 mm, urine metanephrine > 0.205 mg/day and urine normetanephrine > 0.665 mg/day were significant predictors of prolonged hypotension requiring postoperative catecholamine support. Tumor size and urine metanephrine and urine normetanephrine levels were correlated with postoperative hypotension. These predictors may help in the safe perioperative management of pheochromocytoma patients treated with adrenalectomy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Efficacy and Safety of Early Intravenous Landiolol on Myocardial Salvage in Patients with ST-segment Elevation Myocardial Infarction before Primary Percutaneous Coronary Intervention: A Randomized Study 289 297 EN Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa 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 Atsushi Mori Department of Cardiology, Tsuyama Central Hospital Masaki Yoshikawa Department of Cardiology, Fukuyama City Hospital Takefumi Oka Department of Cardiology, Tsuyama Central Hospital Keishi Ichikawa 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 Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62220 Early treatment with an oral β-blocker is recommended in patients with a ST-segment–elevation myocardial infarction (STEMI). In this multicenter study, we evaluated the effects of a continuous administration of landiolol, an ultrashort-acting β-blocker, before primary percutaneous coronary intervention (PCI) on myocardial salvage and its safety in STEMI patients. A total of 47 Japanese patients with anterior or lateral STEMI undergoing a primary PCI within 12 h of symptom onset were randomized to receive intravenous landiolol (started at 3 μg/min/kg dose and continued to a total of 50 mg; n=23) or not (control; n=24). Patients with Killip class III or more were excluded. The primary outcome was the myocardial salvage index on cardiac magnetic resonance imaging (MRI) performed 5-7 days after the PCI. Cardiac MRI was performed in 35 patients (74%). The myocardial salvage index in the landiolol group was significantly greater than that in the control group (44.4±14.6% vs. 31.7±18.9%, respectively; p=0.04). There were no significant differences in adverse events at 24 h between the landiolol and control groups. A continuous administration of landiolol before a primary PCI may increase the degree of myocardial salvage without additional hemodynamic adverse effects within the first 24 h after STEMI. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Effects of Gram-negative Rod Blood Stream Infection on Acute GVHD in Allogeneic Hematopoietic Stem Cell Transplantation: A Single-institute Analysis 279 287 EN Masa-aki Nishinohara Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noboru Asada Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62219 A bloodstream infection (BSI) is the most common serious infectious complication of hematopoietic stem cell transplantation (HSCT). BSI promotes an inflammatory state, which exacerbates acute graft-versus-host disease (GVHD). We investigated whether a Gram-negative rod bloodstream infection (GNR-BSI), which develops early after allo-HSCT, affected the onset or exacerbated acute GVHD in 465 patients who underwent allo-HSCT from 1995 through 2015 at a single institution. Eighty-eight patients (19%) developed BSI during the study period. Among the cultures, 50 (57%) were Gram-positive cocci (GPC) and 31 (35%) were GNR. Of the 465 patients, 187 (40%) developed acute GVHD of grade II or higher within the first 100 days post-allogeneic HSCT: 124 (27%) had acute GVHD grade II, 47 (10%) had grade III, and 16 (3%) had grade IV. Multivariate analysis revealed that GNR-BSI was a significant risk factor for grade II-IV acute GVHD (grade II-IV: hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.03-2.97; grade III-IV: HR 2.37, 95% CI 1.03-5.43). These results suggest that GNR-BSI may predict the onset and exacerbation of acute GVHD. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Dental Treatment for Special Needs Patients Under General Anaesthesia: A 14-year Experience from South Bosnia and Herzegovina 261 268 EN Lidija Lasic Arapovic Health Care Center Mostar, University of Mostar Zoran Karlovic School of Medicine, University of Mostar Valentina Rajic Brzovic School of Medicine, University of Mostar Amer Bukvic Primary Health Care Center Novi Travnik Anka Coric Health Care Center Mostar, University of Mostar Katarina Vukojevic School of Medicine, University of Mostar Zeljko Verzak School of Medicine, University of Mostar Original Article 10.18926/AMO/62217 We conducted a retrospective analysis of records of special needs patients (SNPs) who received dental treatment under orotracheal-intubation general anaesthesia (OIGA) at Caritas Centre St. Family in Mostar, Bosnia and Herzegovina during the 14-year period from January 2005 to December 2018. Of the 7,085 SNPs who received dental treatment, 1,220 (17.2%) received dental treatment under OIGA: 829 (67.9%) males and 391 (32.1%) females. The patients’ mean age was 18.3±10.9 years (747 paediatric and 473 adult patients). Mental retardation and psychiatric problems were the most common medical conditions (81.22%). The most common indication for dental treatment under OIGA was behaviour management (87.21%), and 81% of the patients had an urgent need for treatment. Many of the patients had restorative treatment (3,833) and tooth extractions (3,681). From 2011 onwards, the number of tooth extractions decreased significantly. Annual trends revealed a rapid increase of patients every year. The mean dental treatment duration was 95.3±12.1 min; the mean time under OIGA was 98±8.5 min. No serious adverse effects occurred. There was increase of annual trend of SNP in OIGA. The number of extractions decreased while the number of preventive and restorative dental treatments increased. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Histological Analysis of Repaired Tissue after Pullout Repair of a Medial Meniscus Posterior Root Tear 225 230 EN Haowei Xue Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ximing Zhang Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida 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 Case Report 10.18926/AMO/61905 A 65-year-old man presented with a left medial meniscus (MM) posterior root tear (PRT). Unicompartmental knee arthroplasty was performed 12 months after transtibial pullout repair of the MMPRT. Repaired MM posterior root tissue was subjected to histological analysis. Immunostaining and picrosirius red staining showed sufficient deposition of type I collagen, and hematoxylin-eosin staining using a polarized microscope showed well-aligned fiber orientation in the repaired tissue. The repaired posterior root (post-transtibial pullout repair) showed mature and well-aligned ligament-like tissue. Preserving the MM posterior root remnant to mimic the original posterior root tissue might be useful when performing pullout repair. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 A Case of Dual-pathology Hepatocellular Carcinoma (HCC) and Cholangiolocellular Carcinoma (CoCC) after Eradication of Hepatitis C Virus (HCV) Infection 213 218 EN Manabi Miyashita Department of Hepatology, National Hospital Organaization of Iwakuni Clinical Center Yousuke Saragai Department of Gastroenterology, National Hospital Organaization of Iwakuni Clinical Center Tsuyoshi Fujimoto Department of Gastroenterology, National Hospital Organaization of Iwakuni Clinical Center Shouichi Tanaka Department of Gastroenterology, National Hospital Organaization of Iwakuni Clinical Center Hideki Aoki Department of Surgery, National Hospital Organaization of Iwakuni Clinical Center Yumiko Sato Department of Pathology, National Hospital Organaization of Iwakuni Clinical Center Case Report 10.18926/AMO/61903 A 75-year-old Japanese man visited our hospital for further examination of liver tumors. He had a history of successful hepatitis C virus (HCV) eradication and therapy for hepatocellular carcinoma (HCC) at another hospital. Magnetic resonance imaging (MRI) revealed two tumors in the liver. He underwent anterior inferior (S5) and posterior inferior (S6) subsegmentectomy of the liver. Microscopic examination found that one tumor was HCC while the other was cholangiolocellular carcinoma (CoCC). We experienced a rare case of liver cancer with two synchronous pathologies, HCC and CoCC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Osteosynthesis for Geriatric Acetabular Fractures: An Epidemiological and Clinico-Radiological Study Related to Marginal or Roof Impaction 177 185 EN Madoka Inoue Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Noda Department of Emergency Healthcare and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takenori Uehara Department of Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomonori Tetsunaga Department of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Yamada Department of Musculoskeletal Sports Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taichi Saito Department of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasunori Shimamura Department of Orthopedic Surgery, Kochi Health Sciences Center Yasuaki Yamakawa Department of Orthopedic Surgery, Kochi Health Sciences Center Toshifumi Ozaki Department of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/61895 This retrospective study sought to elucidate the incidence rates of roof impaction (RI) and marginal impaction (MI) and radiological and clinical outcomes of open reduction and internal fixation (ORIF) for RI and MI in geriatric acetabular fractures. The cases of 68 patients aged ≥ 65 years (mean 71 years) treated with ORIF were analyzed. MI was present in 12 fractures (67%) and an RI of the weight-bearing surface was present in 24 (46%) of the potential fracture types. Regarding the reduction quality, 54% of the reductions were graded as anatomical, 37% as imperfect, and 9% as poor. In the clinical evaluations of the 45 patients who had > 1-year follow-up (follow-up rate: 66.2%), 18% were graded as excellent, 53% as good, 16% as fair, and 13% as poor. An anatomic reduction was strongly associated with good or excellent clinical and radiological outcomes. CT was superior to radiographs for detecting the residual displacement postoperatively. Postoperative deep infection occurred in four patients. Three patients (6.7%) underwent a total hip arthroplasty conversion due to secondary osteoarthritis of the hip. We recommend ORIF as the preferred surgical treatment option for displaced acetabular fractures in elderly patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Knee Flexion-induced Translation of Pullout Sutures Used in the Repair of Medial Meniscus Posterior Root Tears 147 152 EN Haowei Xue Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masataka Fujii Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ximing Zhang 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 Original Article 10.18926/AMO/61881 Medial meniscus posterior root tears (MMPRTs) have recently attracted considerable interest in orthopedics. To date, no in vivo human study has investigated suture translation changes in repaired MMPRTs with different degrees of knee flexion. This study examined suture translation at various degrees of knee flexion in 30 patients undergoing medial meniscus posterior root repair using the modified Mason-Allen suture technique between August 2016 and September 2017. Intraoperatively, sutures were provisionally fixed to an isometric positioner at the tibial site of the desired meniscal attachment, and the suture translation was measured at 0°, 30°, 60°, and 90° of knee flexion. The results showed significant increases in mean suture translation at the knee flexion positions from 0° to 30°, 30° to 60°, and 60° to 90° (p<0.01 for all). Our findings indicate that surgeons should carefully assess the degree of knee flexion at the moment when the meniscus is refixed by surgical sutures. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Bone Histomorphometry of Femoral Head Cancellous Bone in Patients Who Underwent Total Hip Arthroplasties due to Destructive Hip in Rheumatoid Arthritis 125 131 EN Yasufumi Kijima Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Naoki Kondo Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Go Okumura Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Naoto Endo Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Original Article 10.18926/AMO/61878 Rheumatoid arthritis (RA) affects the hip joints. The microarchitecture of the cancellous bone in RA-affected hip joints has been unclear. Here we investigated the bone metabolism changes in the subcapital cancellous bone of destructive hips of RA patients (n=26 patients; 28 hip joints) which were classified by Larsen grade on X-ray into the groups: destructive hip (Des) (Larsen grade IV, n=18) and neck fracture (Fx) (Larsen grade 0 or 1, n=10). The femoral heads of the Des-group showed significantly higher trabecular thickness versus those of the Fx-group (179±30.8 vs. 151±23.5 μm, p=0.02). The Des-group had significantly higher osteoid volume/tissue volume (OV/TV) and osteoid volume/bone volume (OV/BV) ratios than the Fx-group (OV/TV: 0.72±0.70% vs. 0.27±0.32%, p=0.028; OV/BV: 2.96±2.85% vs. 1.24±1.31%, p=0.039). The osteoblast and osteoclast surface areas of the Des-group were remarkably higher than those of the Fx-group (9.80±10.9 vs. 0.15±0.15%, p=0.0005; 0.34±0.48 vs. 0.06±0.06%, p=0.0285, respectively). The T-scores of hip (femoral neck) bone mineral density (BMD) of the Fx-group were significantly lower versus those of the Des-group (−3.1±0.76 vs. −1.6±1.17, p<0.01). Increased osteoid and resorption parameters and higher femoral neck BMD demonstrate a high bone-turnover state in response to destructive changes in the hips of RA patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Minimally Invasive Spinal Stabilization with Denosumab before Total Spondylectomy for a Collapsing Lower Lumbar Spinal Giant Cell Tumor 95 101 EN Keitaro Minato Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Toru Hirano 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 Tetsuro Yamagishi Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Keigo Watanabe Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Masayuki Ohashi Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Akira Ogose Department of Orthopedic Surgery, Uonuma Kikan Hospital Naoto Endo Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Case Report 10.18926/AMO/61442 A 21-year-old man consulted our hospital for treatment of a spinal giant cell tumor (GCT) of Enneking stage III. Lower lumbar-spine tumors and severe spinal canal stenosis are associated with high risk for surgical mor-bidity. Stability was temporarily secured with a percutaneous pedicle screw fixation in combination with deno-sumab, which shrank the tumor. Total en bloc spondylectomy was then performed 6 months after initiation of denosumab, and the patient was followed for 3 years. There was no local recurrence, and bony fusion was obtained. Minimally invasive surgery and denosumab allowed safer and easier treatment of a collapsing lower lumbar extra-compartmental GCT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Long-term Follow-up of Living-Donor Kidney Transplantation after Cadaveric Lung Transplantation 87 89 EN Toshio Shiotani Department of Organ Transplant Center, Okayama University Hospital Seiichiro Sugimoto Department of Organ Transplant Center, Okayama University Hospital Kota Araki Department of General Thoracic Surgery, Okayama University Hospital Yasuaki Tomioka Department of Organ Transplant Center, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery, Okayama University Hospital Shinji Otani Department of General Thoracic Surgery, Okayama University Hospital Masaomi Yamane Department of General Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery, Okayama University Hospital Case Report 10.18926/AMO/61439 Although chronic kidney disease (CKD) commonly develops after lung transplantation (LT), living-donor kid-ney transplantation (LDKT) for CKD after LT is known to provide favorable outcomes. We describe the long-term follow-up findings of a patient who underwent LDKT after bilateral cadaveric LT. A 37-year-old male underwent LDKT for CKD 18 years after receiving bilateral cadaveric LT. He developed chronic lung allograft dysfunction (CLAD) 20 years after the LT; however, at 26 years after the initial LT, he is still alive with no pro-gression of CLAD or CKD. KT could be a viable option for CKD even after LT in Japan. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 The Optimal Prepregnancy Body Mass Index for Lactation in Japanese Women with Neonatal Separation as Analyzed by a Differential Equation 63 69 EN Katsuhiko Tada Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Yasunari Miyagi Miyake Ofuku Clinic Kazue Nakamura Department of Neonatology, National Hospital Organization, Okayama Medical Center Moe Yorozu Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Emi Fukushima Department of Nursing, National Hospital Organization, Okayama Medical Center Kazumasa Kumazawa Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Makoto Nakamura Department of Neonatology, National Hospital Organization, Okayama Medical Center Misao Kageyama Department of Neonatology, National Hospital Organization, Okayama Medical Center Original Article 10.18926/ATM/61436 We used a differential equation to identify the biological relationship between the maternal prepregnancy body mass index (BMI) and lactation on postpartum day 4 in Japanese women with neonatal separation. This retro-spective observational study included 252 mothers (135 primiparas, 117 multiparas) whose singleton neonates were admitted to a neonatal ICU. We formulated hypotheses based on breast anatomy to analyze the relation-ship between the expressed milk obtained on postpartum day 4 and the maternal prepregnancy BMI with the following differential equation: y’(x) = k y(x)/x, where k is the constant, x is the prepregnancy BMI, and y is the expressed milk volume. The formula was then obtained as y(x) = axk, where a is the constant. The Akaike information criterion (AIC) was used to estimate the regression equation with the maximum likelihood for primiparas and multiparas. The best criteria for BMI determined by the AIC were 20.89 kg/m2 in primiparas and 20.19 kg/m2 in multiparas. These were the optimal BMI values for lactation, coinciding with the median prepregnancy BMI in the study population (20.78 kg/m2 in primiparas and 20.06 kg/m2 in multiparas). The formula based on biomathematics might help establish the biological relationship between prepregnancy BMI and breastmilk volume. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Clinical Characteristics of Low Androgen Status in Males with Type 2 Diabetes Mellitus 1 8 EN Jun Hamahara 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 Koichiro Yamamoto 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 Yoshihisa Hanayama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikako Obika 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 Masayuki Kishida 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 Original Article 10.18926/AMO/61424 To determine the clinical characteristics of low androgen status in adult males with diabetes, we retrospectively analyzed the medical records of patients with type 2 diabetes mellitus in whom serum free testosterone (FT) levels were examined for 1 year. Among the 46 patients (56 ± 1.5 years old), decreases in serum FT levels to < 8.5 pg/ml (indicating the occurrence of late-onset hypogonadism [LOH]) were detected in 18 (39%). The per-centages of patients with low FT levels were high in the ≥ 50 years age group (83%), the HbA1c < 7% group (67%), and the 25 ≤ BMI < 30 kg/m2 group (56%). The serum FT levels tended to decrease age-dependently. The level of HbA1c was significantly correlated with the Heinemann Aging Male Symptoms (AMS) score (R = 0.47). The low-FT group had decreased levels of hemoglobin. Of note, the serum FSH level (R = −0.32) was negatively correlated with the serum FT level, whereas the serum TSH level (R = 0.36) was positively correlated with the serum FT level. Collectively, these results revealed that many diabetic males may have low FT levels and that the AMS score is related to the HbA1c level. A slightly anemic condition, thyroid dysfunction, and obesity (class 1) might be involved in LOH in middle-aged diabetic males. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 2049-9434 13 5 2020 Panel‑based next‑generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings 46 EN Hisashi Ishida Department of Pediatrics/Pediatric Hematology and Oncology, Okayama University Hospital Akihiro Iguchi Department of Pediatrics, Hokkaido University Hospital Michinori Aoe Division of Medical Support, Okayama University Hospital Ritsuo Nishiuchi Department of Pediatrics, Kochi Health Sciences Center Takehiro Matsubara Division of Biobank, Center for Comprehensive Genomic Medicine, Okayama University Hospital Dai Keino Department of Pediatrics, St. Marianna University School of Medicine Hospital Masashi Sanada Clinical Research Center, National Hospital Organization Nagoya Medical Center Akira Shimada Department of Pediatrics/Pediatric Hematology and Oncology, Okayama University Hospital Acute myeloid leukemia (AML) accounts for ~20% of pediatric leukemia cases. The prognosis of pediatric AML has been improved in recent decades, but it trails that of most other types of pediatric cancer, with mortality rates of 30‑40%. Consequently, newer more targeted drugs are required for incorporation into treatment plans. These newer drugs selectively target AML cells with specific gene alterations. However, there are significant differences in genetic alterations between adult and pediatric patients with AML. In the present study, inexpensive and rapid next‑generation sequencing (NGS) of >150 cancer‑related genes was performed for matched diagnostic, remission and relapse (if any) samples from 27 pediatric patients with AML. In this analysis, seven genes were recurrently mutated. KRAS was mutated in seven patients, NRAS was mutated in three patients, and KIT, GATA1, WT1, PTPN11, JAK3 and FLT3 were each mutated in two patients. Among patients with relapsed AML, six harbored KRAS mutations at diagnosis; however, four of these patients lost these mutations at relapse. Additionally, two genetic alterations (FLT3‑ITD and TP53 alterations) were detected among patients who eventually relapsed, and these mutations are reported to be adverse prognostic factors for adult patients with AML. This panel‑based, targeted sequencing approach may be useful in determining the genetic background of pediatric AML and improving the prediction of treatment response and detection of potentially targetable gene alterations. RAS pathway mutations were highly unstable at relapse; therefore, these mutations should be chosen as a target with caution. Incorporating this panel‑based NGS approach into the clinical setting may allow for a patient‑oriented strategy of precision treatment for childhood AML. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 2050-3911 2020 9 2020 Improved method for measuring low-concentration radium and its application to the Super-Kamiokande Gadolinium project 093H02 EN S. Ito Okayama University, Faculty of Science K. Ichimura Kamioka Observatory, Institute for Cosmic Ray Research, University of Tokyo Y. Takaku Institute for Environmental Sciences, Department of Radioecology K. Abe Kamioka Observatory, Institute for Cosmic Ray Research, University of Tokyo M. Harada Okayama University, Faculty of Science M. Ikeda Kamioka Observatory, Institute for Cosmic Ray Research, University of Tokyo H. Ito Kamioka Observatory, Institute for Cosmic Ray Research, University of Tokyo Y. Kishimoto Kamioka Observatory, Institute for Cosmic Ray Research, University of Tokyo Y. Nakajima Kamioka Observatory, Institute for Cosmic Ray Research, University of Tokyo T. Okada Kamioka Observatory, Institute for Cosmic Ray Research, University of Tokyo H. Sekiya Kamioka Observatory, Institute for Cosmic Ray Research, University of Tokyo Chemical extraction using a molecular recognition resin named "Empore Radium Rad Disk" was developed to improve sensitivity for the low concentration of radium (Ra). Compared with the previous method, the extraction process speed was improved by a factor of three and the recovery rate for Ra-226 was also improved from 81 +/- 4% to > 99.9%. The sensitivity on the 10(-1) mBq level was achieved using a high-purity germanium detector. This improved method was applied to determine Ra-226 in Gd-2(SO4)(3)center dot 8H(2)O which will be used in the Super-Kamiokande Gadolinium project. The improvement and measurement results are reported in this paper. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 A Japanese Patient with Gastric Cancer and Dihydropyrimidine Dehydrogenase Deficiency Presenting with DPYD Variants 557 562 EN Mikako Ishiguro Department of Internal Medicine, Tsuyama Chuo Hospital Ryuta Takenaka Department of Internal Medicine, Tsuyama Chuo Hospital Kenichiro Ogura Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences Akira Hiratsuka Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences Hiromasa Takeda Department of Internal Medicine, Tsuyama Chuo Hospital Daisuke Kawai Department of Internal Medicine, Tsuyama Chuo Hospital Hirofumi Tsugeno Department of Internal Medicine, Tsuyama Chuo Hospital Shigeatsu Fujiki Department of Internal Medicine, Tsuyama Chuo Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/61217 A 63-year-old Japanese male with stomach adenocarcinoma received oral 5-fluorouracil derivative, cisplatin and trastuzumab chemotherapy. On day 8, severe diarrhea and mucositis developed; chemotherapy was stopped. On day 14, the patient developed renal dysfunction and febrile neutropenia. He also suffered from pneumonia due to Candida albicans. Systemic symptoms improved after intensive conservative treatment. Best supportive care was continued until the patient died from gastric cancer. The dihydropyrimidine dehydroge-nase protein level was low at 3.18 U/mg protein. The result of DPYD genotyping revealed three variants at posi-tions 1615 (G > A), 1627 (A > G), and 1896 (T > C) in exons 13, 13, and 14, respectively. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 Four Cases with Rare Complications of Intramedullary Screw Fixation for Jones Fracture 537 544 EN Yusuke Morimoto Department of Orthopaedic Surgery, Nihon University School of Medicine Taichi Komatsu Department of Orthopaedic Surgery, Nihon University School of Medicine Yasuaki Tokuhashi Department of Orthopaedic Surgery, Nihon University School of Medicine Case Report 10.18926/AMO/61214 Active treatment with intramedullary screw fixation is now common for athletes with Jones fracture. Outcomes are generally good, but complications can occur. We report 4 rare complications of intramedullary screw fixa-tion. Two cases developed osteomyelitis and pseudarthrosis caused by thermal necrosis. In the other two cases, screw-related complications occurred during the insertion of the tapered headless screw. Although thermal necrosis and screw insertion failures are considered rare complications and not widely reported in the litera-ture, they do occur occasionally. Knowing the mechanisms underlying these complications could help prevent them, and knowing their course could lead caregivers to appropriate interventions when they do occur. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 9 11 2020 Rab11A Functions as a Negative Regulator of Osteoclastogenesis through Dictating Lysosome-Induced Proteolysis of c-fms and RANK Surface Receptors 2384 EN Yuka Okusha Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manh Tien Tran Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Itagaki Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chiharu Sogawa Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Eguchi Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuo Okui Department of Oral and Maxillofacial Surgery and Biopathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Kadowaki Department of Frontier Life Science, Graduate School of Biomedical Sciences, Nagasaki University Eiko Sakai Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University Takayuki Tsukuba Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University Kuniaki Okamoto Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Osteoclast differentiation and activity are controlled by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-kappa B ligand (RANKL). Rab11A GTPase, belonging to Rab11 subfamily representing the largest branch of Ras superfamily of small GTPases, has been identified as one of the crucial regulators of cell surface receptor recycling. Nevertheless, the regulatory role of Rab11A in osteoclast differentiation has been completely unknown. In this study, we found that Rab11A was strongly upregulated at a late stage of osteoclast differentiation derived from bone marrow-derived macrophages (BMMs) or RAW-D murine osteoclast precursor cells. Rab11A silencing promoted osteoclast formation and significantly increased the surface levels of c-fms and receptor activator of nuclear factor-kappa B (RANK) while its overexpression attenuated osteoclast formation and the surface levels of c-fms and RANK. Using immunocytochemical staining for tracking Rab11A vesicular localization, we observed that Rab11A was localized in early and late endosomes, but not lysosomes. Intriguingly, Rab11A overexpression caused the enhancement of fluorescent intensity and size-based enlargement of early endosomes. Besides, Rab11A overexpression promoted lysosomal activity via elevating the endogenous levels of a specific lysosomal protein, LAMP1, and two key lysosomal enzymes, cathepsins B and D in osteoclasts. More importantly, inhibition of the lysosomal activity by chloroquine, we found that the endogenous levels of c-fms and RANK proteins were enhanced in osteoclasts. From these observations, we suggest a novel function of Rab11A as a negative regulator of osteoclastogenesis mainly through (i) abolishing the surface abundance of c-fms and RANK receptors, and (ii) upregulating lysosomal activity, subsequently augmenting the degradation of c-fms and RANK receptors, probably via the axis of early endosomes-late endosomes-lysosomes in osteoclasts. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2045-2322 10 1 2020 Risk of higher dose methotrexate for renal impairment in patients with rheumatoid arthritis 18715 EN Keigo Hayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Asano Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sumie Hiramatsu Asano Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuriko Yamamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiji Ohashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michiko Morishita Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruki Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Narazaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto 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 Renal impairment is a major concern in patients taking high-dose methotrexate (MTX) for malignancy, but it has not been fully explored in rheumatoid arthritis (RA) patients taking low-dose MTX. This study aimed to elucidate the dose-dependent effects of MTX on the renal function of patients with RA. We retrospectively reviewed 502 consecutive RA patients who were prescribed MTX for >= 1 year at Okayama University Hospital between 2006 and 2018. The primary outcome was the change in estimated glomerular filtration rate (eGFR) over 1 year. The association between MTX dosage (<8, 8-12, and >= 12 mg/week) and the change in eGFR was evaluated using multiple linear regression analysis with adjustment for possible confounding factors including age, sex, disease duration, body weight, comorbidity, baseline eGFR, concomitant treatment, and disease activity. Mean patient age was 63 years; 394 (78%) were female. Median disease duration was 77 months, while mean MTX dosage was 8.6 mg/week. The last 1-year change of eGFR (mean +/- SD) in patients treated with MTX<8 (n=186), 8-12 (n=219),>= 12 mg/week (n=97) decreased by 0.2 +/- 7.3, 0.6 +/- 8.6, and 4.5 +/- 7.9 mL/min/1.73 m(2)/year, respectively (p<0.0001). After adjustment for the confounding factors, MTX >= 12 mg/week was still correlated with a decrease in 1-year eGFR (beta-coefficient:-2.5; 95% confidence interval,-4.3 to-0.6; p=0.0089) in contrast to MTX 8-12 mg/week. Careful monitoring of renal function is required in patients with MTX >= 12 mg/week over the course of RA treatment regardless of disease duration. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 A Disseminated Fusarium fujikuroi Species Complex Infection Prior to Allogeneic Hematopoietic Stem Cell Transplantation 435 441 EN Keigo Fujishita Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Satoshi Oka Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Katsuhiko Kamei Medical Mycology Research Center, Chiba University Katsuma Tani Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Yuka Fujisawa Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Wataru Kitamura Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Takuya Machida Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Case Report 10.18926/AMO/60805 A 53-year-old man was diagnosed with acute myeloid leukemia, which was refractory to chemotherapies. Systemic papules appeared afterward. The skin biopsies revealed filamentous fungal infection including fusariosis. Despite antifungal therapy, the infection did not resolve, because neutropenia persisted with the leukemia. He underwent hematopoietic stem cell transplantation (HSCT) to overcome the leukemia and restore normal hematopoiesis but died from fusariosis just before engraftment. Fusarium fujikuroi species complex was detected in blood cultures with poor antifungal susceptibility. Because restoring normal hematopoiesis is important in the treatment of fusariosis, HSCT might be considered for patients with persistent pancytopenia. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Evaluation of Prognosis of Juvenile Differentiated Thyroid Carcinoma 401 406 EN Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Yusuke Ohtani Department of Breast and Endocrine Surgery, Okayama University Hospital Miwa Fujihara Department of Breast and Endocrine Surgery, Okayama University Hospital Yoko Suzuki Department of Breast and Endocrine Surgery, Okayama University Hospital Yukiko Kajihara Department of Breast and Endocrine Surgery, Okayama University Hospital Minami Hatono Department of Breast and Endocrine Surgery, Okayama University Hospital Kengo Kawada Department of Breast and Endocrine Surgery, Okayama University Hospital Mariko Kochi Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Hirokuni Ikeda Department of Breast and Endocrine Surgery, Okayama University Hospital Naruto Taira Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Original Article 10.18926/AMO/60799 Differentiated thyroid carcinoma (DTC) in juvenile patients is often an extensive and aggressive disease with a high frequency of recurrence. However, the prognosis is excellent, with a low mortality rate even when advanced disease is present, although prognostic factors and treatment strategy remain uncertain. Between April 2004 and March 2017, 33 juvenile patients (< 30 years old) were diagnosed with DTC and treated at our institution. We retrospectively investigated prognosis and factors including sex, reason for discovery, treatment, pathological factors and treatment progress to clarify the risk factors. All patients underwent curative surgical treatment. Pathologically, lymph node metastasis was identified in 25 patients (75%). Thirteen patients (39%) had bilateral cervical metastasis. In addition, 9 (27%) had more than 10 metastatic lymph nodes. The 2 patients with more than 20 metastatic lymph nodes were treated with radioactive iodine (RAI). Five patients (15%) had local recurrences and received surgery. There have been no further recurrences or deaths. However, no factors were determined to significantly predict the recurrence of juvenile DTC. Local recurrent disease was treated with surgery and/or RAI until remission, and survival was excellent in juvenile DTC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Anaplastic Lymphoma Kinase Fusion: A Review of Therapeutic Drugs and Treatment Strategies 371 379 EN Go Makimoto Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Review 10.18926/AMO/60796 The prognosis of advanced non-small cell lung cancer (NSCLC) patients has improved in recent decades, especially for patients with an oncogenic driver mutation. Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are effective for patients with the echinoderm microtubule-associated protein-like 4-ALK fusion gene. Several ALK-TKIs have been established: the first-generation ALK-TKI, crizotinib; second-generation ALK-TKIs, alectinib and ceritinib; and third-generation ALK-TKI, lorlatinib. Some ALK-TKIs are effective for tumors that are resistant to other ALK-TKIs; however, as is known in epidermal growth factor receptormutant lung cancer, tumor resistance is inevitable. ALK-positive NSCLCs acquire resistance via various mechanisms, making it a heterogeneous disease. Therefore, it is necessary to develop next-generation treatment strategies, such as the use of next-generation ALK-TKIs for secondary mutations, or combination therapies with ALK-TKIs and other TKIs. In this review, we summarize the development and use of ALK-TKIs, prior pivotal clinical trials, and resistance mechanisms. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Successful Vancomycin Dose Adjustment in a Sepsis patient with Bacterial Meningitis Using Cystatin C 365 370 EN Masayuki Chuma Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Masateru Kondo Department of Pharmacy, Tokushima University Hospital Yoshito Zamami Department of Pharmacy, Tokushima University Hospital Kenshi Takechi Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Mitsuhiro Goda Department of Pharmacy, Tokushima University Hospital Naoto Okada Department of Pharmacy, Tokushima University Hospital Akitomo Shibata Department of Pharmacy, Saiseikai Kumamoto Hospital Mizuho Asada Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University Jun Oto Department of Emergency and Critical Care Medicine, Tokushima University Graduate School of Biomedical Sciences Hiroaki Yanagawa Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Keisuke Ishizawa Department of Pharmacy, Tokushima University Hospital Case Report 10.18926/AMO/60376 Cystatin C-guided vancomycin (VCM) dosing is useful in critically ill patients. Its usefulness in septic patients with bacterial meningitis remains unknown, as there are no published reports. In this study, we sought to clarify its benefit. Cystatin C was used to guide VCM dosing in a septic bacterial meningitis patient with normal kidney function, according to therapeutic drug monitoring (TDM). Using cystatin C, the Bayesian method-based TDM made optimal VCM dosing possible, and decreased the predicted error (4.85 mg/L) compared to serum creatinine (16.83 mg/L). We concluded TDM of VCM using cystatin C can be considered in sepsis patients with bacterial meningitis with normal kidney function. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Recurrence of Solitary Fibrous Tumor/Hemangiopericytoma Could Be Predicted by Ki-67 Regardless of Its Origin 335 343 EN Yumiko Yamamoto Department of Diagnostic Pathology, Kochi University Yoshihiro Hayashi Department of Equipment of Support Planning Office, Kochi University Ichiro Murakami Department of Diagnostic Pathology, Kochi University Original Article 10.18926/AMO/60372 Since the discovery of the NAB2-STAT6 gene fusion in 2013, solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) have been considered the same disease. STAT6 nuclear stain is approved as a highly sensitive and specific marker to diagnose SFT/HPC from other tumors with similar histology. As the next step, detection of fusion variants that may predict clinical malignancy of SFT/HPC has been attempted. However, no fusion variants with a clear relation to malignancy have been identified. In this study, the clinical and histological backgrounds of 23 Japanese patients diagnosed with SFT/HPC from 2000 to 2019 at Kochi University Hospital were examined to identify factors potentially related to recurrence. A significant relationship to recurrence was detected for mitosis ≥ 1/10 HPF (400×), necrosis, and Ki-67>5%. These findings indicate that a deliberate investigation of histological features such as mitosis and necrosis is crucial for the clinical observation of SFT/ HPC patients. In addition, Ki-67 was revealed to be a useful parameter to predict recurrence in SFT/HPC patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Comparison of Two Different Intensive Care Unit Systems for Severely Ill Children in Japan: Data from the JaRPAC Registry 285 291 EN Kohei Tsukahara Department of Emergency, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromichi Naitou Department of Emergency, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuyuki Nosaka Department of Pediatrics, Cedars-Sinai Medical Center Hirotsugu Yamamoto Department of Emergency, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaaki Osako Department of Emergency, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences the JaRPAC Study Group Original Article 10.18926/AMO/60365 The importance of centralizing treatment services for severely ill children has been well established, but such entralization remains difficult in Japan. We aimed to compare the trauma and illness severity and mortality of children admitted to two common types of ICUs for children. According to the type of management and disposition of the medical provider, we classified ICUs as pediatric ICUs [PICUs] or general ICUs, and analyzed differences in endogenous and exogenous illness settings between them. Overall, 1,333 pediatric patients were included, with 1,143 patients admitted to PICUs and 190 patients to general ICUs. The Pediatric Cerebral Performance Category score (PCPC) at discharge was significantly lower in the PICU group (adjusted OR: 0.45; 95%CI: 0.23-0.88). Death and unfavorable neurological outcomes occurred less often in the PICU group (adjusted OR: 0.29; 95%CI: 0.14-0.60). However, when limited to exogenous illness, PCPC scores (adjusted OR: 0.38; 95%CI: 0.07-1.99) or death/unfavorable outcomes (adjusted OR: 0.72; 95%CI: 0.08-6.34) did not differ between the groups. PCPC deterioration and overall sequelae/death rates were lower in PICUs for children with endogenous illnesses, although the outcomes of exogenous illness were similar between the 2 unit types. Further studies on the necessity of centralization are warranted. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Decreased Serum Antioxidant Marker is Predictive of Early Recurrence in the Same Segment after Radical Ablation for Hepatocellular Carcinoma 275 283 EN Taiko Muro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichiro Nakamura Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Onishi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomu Wada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yasunaka 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 Atsushi Oyama Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Adachi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidenori Shiraha Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/60364 Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a promising method for controlling tumors, although it does not entirely eliminate recurrence. Oxidative stress is associated with the progression of hepatocarcinogenesis, while also acting as an anticancer response. The objective of the present study was to investigate the factors influencing post-RFA outcomes. We recruited 235 newly diagnosed HCC patients who received RFA for single tumors. The patients with recurrence were sub-grouped into early and segmental recurrence groups. The characteristics of the sub-grouped patients were evaluated, including by measuring oxidative stress marker reactive oxygen metabolites and antioxidant marker OXY-adsorbent tests. The factors associated with poor survival were a high Child-Pugh score and early recurrence within 2 years in the same segment. The patients who experienced recurrence within 2 years in the same segment showed a larger tumor diameter than did others. According to a multivariate analysis, the OXY values were also significantly low in these patients. In conclusion, maintaining the antioxidant reservoir function with a high OXY value might be necessary to prevent early recurrence within the RFA-treated segment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 A Randomized Phase 2 Trial of Antibiotic Prophylaxis Versus No Intervention for Muscle Biopsy in A Neurology Department 261 264 EN Keiichi Nakahara Department of Neurology, Graduate School of Medical Sciences, Kumamoto University Tokunori Ikeda Department of Clinical Investigation, Kumamoto University Hospital Koutaro Takamatsu Department of Neurology, Graduate School of Medical Sciences, Kumamoto University Nozomu Tawara Department of Neurology, Graduate School of Medical Sciences, Kumamoto University Kentaro Hara Department of Neurology, Graduate School of Medical Sciences, Kumamoto University Yuki Enokida Department of Pharmacy, Kumamoto University Hospital Naomi Tanoue Department of Pharmacy, Kumamoto University Hospital Sawana Narita Department of Clinical Investigation, Kumamoto University Hospital Akiko Fujii Department of Clinical Investigation, Kumamoto University Hospital Yoshinori Yamanouchi Department of Clinical Investigation, Kumamoto University Hospital Jun Morinaga Department of Clinical Investigation, Kumamoto University Hospital Satoshi Yamashita Department of Neurology, Graduate School of Medical Sciences, Kumamoto University Clinical Study Protocol 10.18926/AMO/59961 Muscle biopsy can be used to confirm the diagnosis of neuromuscular diseases. However, it is unclear whether antibiotic prophylaxis prior to muscle biopsy is needed to prevent surgical site infection (SSI). We are conducting a phase 2, single-center, open-labeled, prospective randomized trial to clarify the need for antibiotic prophylaxis in patients at low risk for SSI undergoing muscle biopsy. Patients will be randomized to an antibiotic prophylaxis group or a control group, and the incidence of SSI will be compared between the groups. Our findings will clarify the need for antibiotic prophylaxis in this patient population. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 Serum REIC/Dickkopf-3 Protein Level Predicts Disease-Free Survival in Patients with Hepatocellular Carcinoma 237 243 EN Atsushi Oyama 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 Hidenori Shiraha Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroaki Sawahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kato Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro 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 Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/59957 The physiological role of the reduced expression of immortalized cells (REIC)/Dickkopf-3 (Dkk-3) protein in patients with hepatocellular carcinoma (HCC) remains unclear. In this study, we evaluated the effect of the REIC/Dkk-3 protein on HCC cell proliferation and assessed the relationship between the serum REIC/Dkk-3 protein level and the prognosis in patients with HCC. We evaluated the REIC/Dkk-3 protein-induced anticancer effects on Huh7 and Hep3B cells (HCC cell lines) in the presence of peripheral blood mononuclear cells (PBMCs), and found that combination treatment with REIC/Dkk-3 protein and PBMCs reduced the proliferation of HCC cells (Hep3B: 82.0%±16.3%; Huh7: 72.6%±9.1%). We also studied 194 HCC patients who underwent primary liver resection or primary radiofrequency ablation from 2008 to 2017. Serum REIC/Dkk-3 protein levels were measured by an enzyme-linked immunosorbent assay and compared to the prognostic data. The 3-year disease-free survival of the REIC/Dkk-3 high group was significantly higher than that in the REIC/Dkk-3 low group. In conclusion, this is the first study investigating the relationship between HCC patient survival and serum REIC/Dkk-3 protein levels in a large population. Based on the results, the serum REIC/Dkk-3 protein level should be considered a new prognostic marker for patients with HCC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 A Possible Protective Effect of the 'Cam Deformity' on Femoral Neck Fracture: The Relationship between Hip Morphology and the Types of Hip Fracture 221 227 EN Takuma Yagura Department of Orthopaedic Surgery, Kansai Medical University Kenichi Oe Department of Orthopaedic Surgery, Kansai Medical University Masaaki Paku Department of Orthopaedic Surgery, Osaka Saiseikai Izuo Hospital Takeshi Tajima Department of Orthopaedic Surgery, Meisei Hospital Masaya Nakamura Department of Orthopaedic Surgery, McSYL Tatsumi Hospital Hirokazu Iida Department of Orthopaedic Surgery, Kansai Medical University Takanori Saito Department of Orthopaedic Surgery, Kansai Medical University Original Article 10.18926/AMO/59954 We retrospectively evaluated the cases of 169 hip fracture patients, their previous fractures, and the contralateral hip joint’s morphology. A history of contralateral hip fracture was present in 23 patients (Contra group). The other patients had a unilateral hip fracture: a trochanteric fracture (Troch group, n=73) or a femoral neck fracture (Neck group, n=73). In the Troch and Neck groups, we used anteroposterior and cross-table axialview radiographs of the contralateral hip to evaluate the proximal femur’s anatomy. In the Contra group, the concordance rate between the first and second types of hip fracture was 65.2%, and the second hip fracture’s morphology indicated that the trochanteric fracture had a cam deformity in terms of the femoral head-neck ratio. The average alpha angle and femoral head-neck offset in the Troch group were significantly larger than those in the Neck group. In the Neck group, pistol-grip deformities of Arbeitsgemeinschaft für Osteosynthesefragen types B1 (subcapital), B2 (transcervical), and B3 (displaced) were observed in 42.1%, 75%, and 6% of cases, respectively. There was a smaller alpha angle and a larger femoral head-neck offset in the contralateral hip of femoral neck fractures; thus, the “cam deformity” may protect against femoral neck fractures. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 Risk Factors for Chronic Damage Accumulation Across Different Onset Eras in Systemic Lupus Erythematosus: A Cross-sectional Analysis of a Lupus Registry of Nationwide Institutions (LUNA) 191 198 EN Keiji Ohashi Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ei Sada Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Asano Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Hayashi Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuriko Yamamura Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sumie Hiramatsu Asano Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshia Miyawaki Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michiko Morishita Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruki Watanabe Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriko Tatebe Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Narazaki Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsue Sunahori-Watanabe Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kawabata Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuyuki Yajima Division of Rheumatology, Department of Medicine, Showa University School of Medicine Jun Wada Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/59949 Chronic damage accumulation affects not only mortality but also quality of life in patients with systemic lupus erythematosus (SLE). Risk factors for chronic damage were explored in SLE through different onset eras. Two hundred forty-five patients at Okayama University Hospital and Showa University Hospital were divided into three groups based on the onset era: a past-onset group (onset before 1995; n=83), middle-onset group (1996-2009; n=88), and recent-onset group (after 2010; n=74). The mean Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score as an index of chronic damage was 1.93, 1.24, and 0.53 in the past-, middle-, and recent-onset groups, respectively. In the pastonset group, the total SDI score was significantly associated with glucocorticoid monotherapy by linear regression analysis (β-coefficient [β]=0.63; 95% confidence interval [CI], 0.21-1.05) and C-reactive protein levels (β=0.67; 95% CI, 0.27-1.07). In the middle-onset group, the total SDI score was significantly associated with the SLE Disease Activity Index at registration (β=0.09; 95% CI, 0.03-0.12). Reducing the accumulation of chronic damage in SLE patients might be possible with the concomitant use of immunosuppressants and tight control of disease activity. No potential conflict of interest relevant to this article was reported.

Hindawi Acta Medica Okayama 1687-9627 2020 2020 Methotrexate-Associated Lymphoproliferative Disorder Developed Ectopically in the Maxillary Gingiva and Bilateral Lungs 4814519 EN Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Tatsuo Okui Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Koji Kishimoto Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences A 58-year-old Japanese woman complained of a painful right maxillary premolar gingiva and ulcer. The patient had RA and had been treated with several immunosuppressive drugs such as methotrexate. Head and neck CT indicated no obvious bone destruction with maxillary. However, chest CT indicated the presence of nodular mass of the bilateral lungs. FDG-PET/CT indicated the presence of increased uptake in both lesions. On immunohistochemistry, atypical large-sized lymphocytes were positive for CD20 and EBER-ISH and negative for CD3, CD5, and CD10; the Ki-67 labeling index was high, the histopathological diagnosis was EBV-positive DLBCL, and the clinical diagnosis was MTX-LPD. The patient's treatment with MTX was then discontinued; we removed the alveolar bone which necrosed after 5 weeks. The lesion and the nodular mass at the bilateral lungs had completely disappeared after 7 weeks. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 9 3 2020 HMGB1 Translocation in Neurons after Ischemic Insult: Subcellular Localization in Mitochondria and Peroxisomes 643 EN Dengli Wang Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keyue Liu Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yusuke Fukuyasu Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kiyoshi Teshigawara Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Li Fu Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hidenori Wake Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Aiji Ohtsuka Department of Human Morphology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masahiro Nishibori Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University High mobility group box-1 (HMGB1), a nonhistone chromatin DNA-binding protein, is released from neurons into the extracellular space under ischemic, hemorrhagic, and traumatic insults. However, the details of the time-dependent translocation of HMGB1 and the subcellular localization of HMGB1 through the release process in neurons remain unclear. In the present study, we examined the subcellular localization of HMGB1 during translocation of HMGB1 in the cytosolic compartment using a middle cerebral artery occlusion and reperfusion model in rats. Double immunofluorescence microscopy revealed that HMGB1 immunoreactivities were colocalized with MTCO1(mitochondrially encoded cytochrome c oxidase I), a marker of mitochondria, and catalase, a marker of peroxisomes, but not with Rab5/Rab7 (RAS-related GTP-binding protein), LC3A/B (microtubule-associated protein 1 light chain 3), KDEL (KDEL amino acid sequence), and LAMP1 (Lysosomal Associated Membrane Protein 1), which are endosome, phagosome, endoplasmic reticulum, and lysosome markers, respectively. Immunoelectron microscopy confirmed that immune-gold particles for HMGB1 were present inside the mitochondria and peroxisomes. Moreover, HMGB1 was found to be colocalized with Drp1 (Dynamin-related protein 1), which is involved in mitochondrial fission. These results revealed the specific subcellular localization of HMGB1 during its release process under ischemic conditions. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 Non-traumatic Atypical Peri-implant Femoral Fracture at the Distal Screw after Short Femoral Nail Fixation for a Pertrochanteric Fracture 151 157 EN Norio Yamamoto Department of Orthopedic Surgery, Unnan City Hospital Tomoyuki Dan’ura Department of Orthopedic Surgery, Unnan City Hospital Tomoyuki Noda Department of Musculoskeletal Traumatology, 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 Case Report 10.18926/AMO/58274 This is the second report of an atypical peri-implant femoral fracture occurring at the distal screw after intramedullary nail fixation of a pertrochanteric fracture. A 94-year-old Japanese female with a 5-year history of alendronate intake presented with prodromal pain in her right thigh after intramedullary nail fixation. Plain radiographs showed an incomplete noncomminuted transverse fracture at the distal screw, suggesting an atypical peri-implant femoral fracture. The pathogenesis of an atypical peri-implant femoral fracture could be a combined systemic bone metabolism disorder and repetitive overloading at the screw, similar to the pathogenesis of an atypical periprosthetic femoral fracture around stem implantation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 Association between Histological Types and Enhancement of Dynamic CT for Primary Lung Cancer 129 135 EN Shogo Fukuma Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayoshi Shinya Department of Radiology, Okayama University Hospital Junichi Soh Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichiro Fukuhara Department of Pediatric Radiology, Okayama University Hospital Nanako Ogawa Department of Radiology, Okayama University Hospital Fumiyo Higaki Department of Radiology, Okayama City General Medical Center Takehiro Tanaka Department of Pathology, Okayama University Hospital Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Takao Hiraki Department of Radiology, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Kanazawa Department of Radiology, Okayama University Hospital Original Article 10.18926/AMO/58271 The aim of this study was to explore enhancement patterns of different types of primary lung cancers on 2-phase dynamic computed tomography (CT). This study included 217 primary lung cancer patients (141 adenocarcinomas [ADs], 48 squamous cell carcinomas [SCCs], 20 small cell lung carcinomas [SCLCs], and 8 others) who were examined using a 2-phase dynamic scan. Regions of interest were identified and mean enhancement values were calculated. After excluding the 20 SCLCs because these lesions had different clinical stages from the other cancer types, the mean attenuation values and subtractions between phases were compared between types of non-small cell lung carcinomas (NSCLCs) using the Kruskal–Wallis test. Late phase attenuation and attenuation of the late minus unenhanced phase (LMU) of SCCs were significantly higher than those of ADs (p<0.05). To differentiate SCC and AD in the late phase, a threshold of 80.21 Hounsfield units (HU) gave 52.9% accuracy. In LMU, a threshold of 52.16 HU gave 59.3% accuracy. Dynamic lung CT has the potential to aid in differentiating among NSCLC types. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 Effects of Switching from Treatment with Amlodipine and Atorvastatin Using Two Pills to an Equal Dose of Single-Pill Therapy in Japanese Outpatients 103 108 EN Yasumasa Kawada Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Toru Kubo Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Yuichi Baba Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Takayoshi Hirota Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Katsutoshi Tanioka Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Naohito Yamasaki Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Hiroaki Kitaoka Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Original Article 10.18926/AMO/58267 This study examined whether switching from amlodipine and atorvastatin treatment using two pills to an equal dose of single-pill therapy is useful in Japanese outpatients. We retrospectively reviewed data obtained from 94 outpatients for whom treatment with two pills, namely amlodipine and atorvastatin, was switched to an equal dose of single-pill therapy in 11 hospitals. The criterion for enrollment in this study was that patients had switched their medication without changing other anti-hypertensive or anti-cholesterol drugs. Neither systolic nor diastolic blood pressure changed significantly after switching to an equal dose of single-pill therapy, whereas low-density lipoprotein (LDL) cholesterol levels significantly decreased after the medication was switched from 94±24 mg/dl to 89±17 mg/dl (p=0.015). A switch from medication with two separate pills of amlodipine and atorvastatin to an equal dose of single-pill therapy resulted in an overall decrease in LDL cholesterol. The results indicated that the switch to single-pill therapy might be a useful treatment. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2041-1723 11 1 2020 Structural basis for the adaptation and function of chlorophyll f in photosystem I 238 EN Koji Kato Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Toshiyuki Shinoda Faculty of Science, Tokyo University of Science Ryo Nagao Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Seiji Akimoto Graduate School of Science, Kobe University Takehiro Suzuki Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science Naoshi Dohmae Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science Min Chen School of Life and Environmental Sciences, University of Sydney Suleyman I. Allakhverdiev K.A. Timiryazev Institute of Plant Physiology RAS Jian-Ren Shen Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Fusamichi Akita Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Naoyuki Miyazaki Institute for Protein Research, Laboratory of Protein Synthesis and Expression, Osaka University Tatsuya Tomo Faculty of Science, Tokyo University of Science Chlorophylls (Chl) play pivotal roles in energy capture, transfer and charge separation in photosynthesis. Among Chls functioning in oxygenic photosynthesis, Chl f is the most red-shifted type first found in a cyanobacterium Halomicronema hongdechloris. The location and function of Chl f in photosystems are not clear. Here we analyzed the high-resolution structures of photosystem I (PSI) core from H. hongdechloris grown under white or far-red light by cryo-electron microscopy. The structure showed that, far-red PSI binds 83 Chl a and 7 Chl f, and Chl f are associated at the periphery of PSI but not in the electron transfer chain. The appearance of Chl f is well correlated with the expression of PSI genes induced under far-red light. These results indicate that Chl f functions to harvest the far-red light and enhance uphill energy transfer, and changes in the gene sequences are essential for the binding of Chl f. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 1 2020 A Multicenter, Open-label, Clinical Trial to Assess the Effectiveness and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced-intensity Conditioning in Relapsed/refractory Anaplastic Large-cell Lymphoma in Children 89 94 EN Akiko Kada Clinical Research Center, NHO Nagoya Medical Center Reiji Fukano Department of Pediatrics, Yamaguchi University Graduate School of Medicine Tetsuya Mori Department of Pediatrics, St. Marianna University School of Medicine Hospital Michi Kamei Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences Fumiko Tanaka Department of Pediatrics, Saiseikai Yokohamashi Nanbu Hospital Junichi Ueyama Department of Pediatrics, Tottori University Hospital, Masahiro Sekimizu Department of Pediatrics, NHO Nagoya Medical Center Tomoo Osumi Children’s Cancer Center, National Center for Child Health and Development Takeshi Mori Department of Hematology and Oncology, Children’s Cancer Center, Kobe Children’s Hospital Yuhki Koga Department of Pediatrics, Graduate School of Medical Sciences Kyushu University Kentaro Ohki Department of Pediatric Hematology and Oncology Research, National Center for Child Health and Development Naoto Fujita Department of Pediatrics, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Tetsuo Mitsui Department of Pediatrics, Yamagata University Hospital Akiko M. Saito Clinical Research Center, NHO Nagoya Medical Center Hiroya Hashimoto Clinical Research Center, NHO Nagoya Medical Center Ryoji Kobayashi Department of Pediatrics and Adolescence, Sapporo Hokuyu Hospital Clinical Study Protocol 10.18926/AMO/57959 No standard treatment for relapsed or refractory anaplastic large-cell lymphoma (ALCL) has been established. This study is a multicenter, open-label trial to examine the effectiveness and safety of transplantation with reduced-intensity conditioning (RIC) for patients under 20 years old with relapsed or refractory ALCL. We defined RIC as the administration of fludarabine (30 mg/m2/day) for five days plus melphalan (70 mg/m2/day) for two days and total body irradiation at 4 Gy, followed by allogeneic hematopoietic stem cell transplantation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 1 2020 Clinical Relevance of Blood Glucose and Gastroesophageal Reflux Symptoms to Depressive Status in Patients with Type 2 Diabetes Mellitus 33 40 EN Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Hanayama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikako Obika Department of General Medicine, 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 Jun Hamahara Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayuki Kishida Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitomi Kataoka 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 Original Article 10.18926/AMO/57950 A relationship between diabetes and depression is apparent. To clarify the clinical relevance of diabetic patients’ gastroesophageal symptoms to their psychological status, we retrospectively analyzed the data from a Selfrating Depression Scale (SDS) and a Frequency Scale for Symptoms of Gastroesophageal reflux disease (FSSG) among 143 type 2 diabetic patients who visited a general medicine department. Among the 45 Japanese patients enrolled, the group with relatively high SDS scores (≥ 36) showed higher (FSSG) dysmotility symptom scores versus the low-SDS (< 36) group, although the 2 groups’ characteristics and laboratory data were not significantly different. Positive correlations of postprandial plasma glucose (PPG) levels with FSSG scores (R=0.321, p<0.05), particularly with reflux scores (R=0.455, p<0.01) were revealed. PPG and HbA1c levels were not correlated with SDS scores. The patients’ SDS scores were significantly correlated with their FSSG scores (R=0.41, p<0.01), suggesting that depressive status is linked to GERD-related manifestations. Considering that the patients’ PPG levels were correlated with GERD-related symptoms, diabetic patients’ blood glucose levels are associated with depressive status. Collectively, key symptoms related to GERD and glucose level values would be helpful No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 1 2020 A Promising New Anti-Cancer Strategy: Iron Chelators Targeting CSCs 1 6 EN Yuehua Chen Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Boyi Xing Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jiping Qi Department of Pathology, the First Affiliated Hospital of Harbin Medical University Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/57946 Iron is a trace but vital element in the human body and is necessary for a multitude of crucial processes in life. However, iron overload is known to induce carcinogenesis via oxidative stress. Cancer cells require large amounts of iron for their rapid division and cell growth. Iron was recently found to play a role in cancer stem cells (CSCs); it maintains stemness during development. Iron also plays an important role in stemness by moderating reactive oxygen species. Thus, iron metabolism in CSCs is a promising therapeutic target. In this review, we summarize the roles of iron in cancer cells and CSCs. We also summarize anti-cancer therapeutic studies with iron chelators and describe our expectation of a new therapeutic strategy for CSCs on the basis of our findings. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0941-1291 49 8 2019 Impact of chronic lung allograft dysfunction, especially restrictive allograft syndrome, on the survival after living-donor lobar lung transplantation compared with cadaveric lung transplantation in adults: a single-center experience 686 693 EN Seiichiro Sugimoto Department of General Thoracic Surgery, Okayama University Hospital Haruchika Yamamoto Department of General Thoracic Surgery, Okayama University Hospital Takeshi Kurosaki Department of Organ Transplant Center, Okayama University Hospital Shinji Otani Department of Organ Transplant Center, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery, Okayama University Hospital Masaomi Yamane Department of General Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery, Okayama University Hospital Takahiro Oto Department of Organ Transplant Center, Okayama University Hospital PURPOSE: The differences in chronic lung allograft dysfunction (CLAD) between living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT) remain unclear. We conducted this study to compare the impact of CLAD on the outcomes after LDLLT vs. CLT. METHODS: We conducted a retrospective review of the data of 97 recipients of bilateral lung transplantation, including 51 recipients of LDLLT and 46 recipients of CLT. RESULTS: The CLAD-free survival and overall survival after LDLLT were similar to those after CLT. CLAD and restrictive allograft syndrome (RAS), but not bronchiolitis obliterans syndrome (BOS), developed significantly later after LDLLT than after CLT (p = 0.015 and p = 0.035). Consequently, patients with CLAD and RAS, but not those with BOS, after LDLLT had a significantly better overall survival than those after CLT (p = 0.037 and p = 0.0006). Furthermore, after the diagnosis of CLAD, the survival of patients with RAS after LDLLT tended to be better than that after CLT (p = 0.083). CONCLUSION: CLAD, especially RAS, appears to develop later after LDLLT than after CLT and seems to have a lower impact on the overall survival after LDLLT than that after CLT. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 7 3 2019 Very rare solitary primary peripheral nerve onset cytotoxic molecule-positive peripheral T-cell lymphoma (PTCL) 146 149 EN Namiko Matsumoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuko Kawahara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Maiko Sakamoto Department of Hematology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eisei Kondou Department of Hematology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rei Shibata Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yoshino Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Here we present the first report of solitary primary peripheral nerve onset cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (PTCL) diagnosed after nerve biopsy. An 84-year-old female with rheumatoid arthritis (RA) complained of asymmetric severe tenderness in her upper limbs. The biopsy pathology revealed a direct invasion of CM-positive PTCL. When RA patients complain of numbness, tenderness, or weakness, lymphomatic peripheral nerve invasion should be considered. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 6 2019 Two Cases of High Tibial Osteotomy in Patients with Rheumatoid Arthritis Treated with Biologic Disease-modifying Anti-rheumatic Drugs 537 542 EN Yasuhiro Takahara Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Keiichiro Nishida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirotaka Nakashima Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Nobuaki Ochi Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Yoichiro Uchida Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Hisayoshi Kato Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Satoru Itani Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Makoto Nakamura Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Yuichi Iwasaki Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Yoshitaka Tsujimura Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital Case Report 10.18926/AMO/57720 High tibial osteotomy (HTO) procedure is generally contraindicated in rheumatoid arthritis (RA) patients because synovial inflammation may exacerbate joint damage post-surgery. The natural course of joint destruction in RA changed dramatically with new treatment strategies and the introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDs). We report the cases of two RA patients who underwent HTO and whose disease activities were well controlled by bDMARDs. Despite their short follow-up periods, they showed acceptable objective and subjective clinical results. We believe that the combination of bDMARDs and HTO can be indicated for selected RA patients before total knee arthroplasty. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 6 2019 The Early Arthroscopic Pullout Repair of Medial Meniscus Posterior Root Tear Is More Effective for Reducing Medial Meniscus Extrusion 503 510 EN Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Miyazawa Department of Intelligent Orthopaedic System, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Kodama Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohito Hino Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Masuda Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Noda Department of Musculoskeletal traumatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Yamakawa Department of Emergency Healthcare and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Tetsunaga 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 Original Article 10.18926/AMO/57714 Clinical studies have demonstrated that transtibial pullout repair led to favorable midterm outcomes in patients with medial meniscus posterior root tears (MMPRTs) although medial meniscal extrusion (MME) continued to be present. It has been unclear whether these residual postoperative MMEs existed after the pullout repair or had progressed at the very short-term evaluation after surgery. We sought to determine which characteristics of patients with MMPRTs influence the incidence of postoperative MME. The cases of 23 patients whose date of injury was known were analyzed. All patients underwent MMPRT pullout fixation. Preoperative and 3-month postoperative magnetic resonance imaging (MRI) examinations were performed. MME was retrospectively assessed on the mid-coronal plane of MRI scans. The preoperative and postoperative MME values were 4.2±1.2 mm and 4.3±1.5 mm, respectively (p=0.559). Pullout repair surgery was performed significantly earlier after the MMPRT-specific injury in patients whose postoperative MME improved compared to the patients whose MME did not improve (p<0.001). Our findings demonstrated that an early transtibial pullout repair of an MMPRT was more effective in reducing MME than a late repair. Surgeons should not miss the optimal timing for the pullout repair of an MMPRT, considering the period from the injury and the preoperative MME. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 6 2019 Transtibial Pullout Repair Reduces Posterior Extrusion of the Medial Meniscus 495 501 EN Shin Masuda Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Kodama Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiji Nakata 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 Original Article 10.18926/AMO/57713 Medial meniscus posterior root tear causes rapid knee cartilage degradation by inducing posteromedial displacement of the medial meniscus. We evaluated medial meniscus posterior extrusion before and after pullout repair for medial meniscus posterior root tear using magnetic resonance images. Twenty-eight patients with symptomatic medial meniscus posterior root tear were included. The inclusion criteria were: acute (< 3 months) or chronic (≥3 months) medial meniscus posterior root tear after painful popping events. The exclusion criteria were: other meniscus and anterior cruciate ligament injuries. We measured medial meniscus posterior extrusion and medial meniscus anteroposterior interval at knee flexion angles of 10° and 90° preoperatively and at 3 months postoperatively. The posterior extrusion at 90° knee flexion decreased from 4.42±1.38 mm preoperatively to 3.09±1.06 mm (p<0.001) postoperatively, while at 10° knee flexion it was −4.17±1.63 mm preoperatively and −3.77±1.72mm postoperatively, showing no significant change. The anteroposterior interval at 10° knee flexion increased from 19.74±4.27 mm preoperatively to 22.15±5.10 mm postoperatively (p<0.001); at 90° knee flexion, it increased from 16.81±4.51 mm preoperatively to 19.20±4.30 mm postoperatively (p<0.001). Medial meniscus posterior extrusion and movement decreased after pullout repair. Pullout repair for medial meniscus posterior root tear improves medial meniscus posterior extrusion, especially at 90° knee flexion. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 6 2019 Foveal Structural Analysis of Amblyopic Eyes with Two Types of Fixation Behavior by Spectral-Domain Optical Coherence Tomography 487 494 EN Fumiko Kishimoto Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Phamaceutical Sciences Chiaki Fujii Division of Ophthalmology, Ibara Municipal Hospital Toshio Okanouchi Division of Ophthalmology, Kurashiki Medical Center Hiroshi Ohtsuki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Phamaceutical Sciences Original Article 10.18926/AMO/57712 We used spectral-domain optical coherence tomography (SD-OCT) to compare the foveal and parafoveal structures of 19 subjects aged 16-58 years (8 men, 11 women): 6 amblyopic patients with eccentric fixation, 5 amblyopic patients with central fixation, and 8 visually normal controls. We obtained foveal horizontal line scans using SD-OCT on all of the patients and controls. The total and layer thicknesses at foveal areas were analyzed. The mean (SD) ages of individuals in the eccentric fixation, central fixation, and control groups were 43.0 (13.9), 42.2 (16.3), and 38.5 (15.5) years, respectively. We observed no significant differences in the foveal or parafoveal retinal thicknesses at 500 and 1,500 μm from the foveal center among the 3 groups or between the amblyopic and fellow eyes. No significant differences were observed in the thickness of the ganglion cell complex layer or outer retinal layer at 500 and 1,500 μm from the foveal center among the three groups or between the two eyes. Overall, our SD-OCT analyses revealed no characteristic structural change in foveal regions in amblyopic eyes irrespective of the fixation behavior. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 6 2019 The Aging Population and Research into Treatments for Abdominal Aortic Aneurysms 475 477 EN Ryoko Umebayashi 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 Junzo Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/57710 Abdominal aortic aneurysms (AAAs) usually expand asymptomatically until the occurrence of a life-threatening event such as aortic rupture, which is closely associated with high mortality. AAA and aortic dissection are ranked among the top 10 causes of death in Japan. The major risk factors for AAA are age over 65 years, male gender, family history, and smoking. Thus, for prevention, smoking cessation is the most important lifestyle-intervention. For treatment, since AAA generally affects elderly people, less invasive treatment is preferable. However, the only established treatment for AAA is open repair and endovascular repair. This review describes potential medical treatments to slow aneurysm growth or prevent AAA rupture. No potential conflict of interest relevant to this article was reported.

Frontiers Media S.A Acta Medica Okayama 1664-3224 10 2019 Spred2 Regulates High Fat Diet-Induced Adipose Tissue Inflammation, and Metabolic Abnormalities in Mice 17 EN Takahiro Ohkura Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teizo Yoshimura Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Marutani Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaya Usami Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chronic low-grade inflammation in visceral adipose tissues triggers the development of obesity-related insulin resistance, leading to the metabolic syndrome, a serious health condition with higher risk of cardiovascular disease, diabetes, and stroke. In the present study, we investigated whether Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, plays a role in the development of high fat diet (HFD)-induced obesity, adipose tissue inflammation, metabolic abnormalities, and insulin resistance. Spred2 knockout (KO) mice, fed with HFD, exhibited an augmented body weight gain, which was associated with enhanced adipocyte hypertrophy in mesenteric white adipose tissue (mWAT) and deteriorated dyslipidemia, compared with wild-type (WT) controls. The number of infiltrating macrophages with a M1 phenotype, and the crown-like structures, composed of macrophages surrounding dead or dying adipocytes, were more abundant in Spred2 KO-mWAT compared to in WT-mWAT. Exacerbated adipose tissue inflammation in Spred2 KO mice led to aggravated insulin resistance and fatty liver disease. To analyze the mechanism(s) that caused adipose tissue inflammation, cytokine response in mWAT was investigated. Stromal vascular fraction that contained macrophages from Spred2 KO-mWAT showed elevated levels of tumor necrosis factor α (TNFα) and monocyte chemoattractant protein-1 (MCP-1/CCL2) compared with those from WT-mWAT. Upon stimulation with palmitate acid (PA), bone marrow-derived macrophages (BMDMs) derived from Spred2 KO mice secreted higher levels of TNFα and MCP-1 than those from WT mice with enhanced ERK activation. U0126, a MEK inhibitor, reduced the PA-induced cytokine response. Taken together, these results suggested that Spred2, in macrophages, negatively regulates high fat diet-induced obesity, adipose tissue inflammation, metabolic abnormalities, and insulin resistance by inhibiting the ERK/MAPK pathway. Thus, Spred2 represents a potential therapeutic tool for the prevention of insulin resistance and resultant metabolic syndrome. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 5 2019 Relationship between Sedentary Behavior and All-cause Mortality in Japanese Chronic Hemodialysis Patients: A Prospective Cohort Study 419 425 EN Shuhei Hishii Department of Hygiene, Faculty of Medicine, Kagawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiroyuki Nishi Innoshima General Hospital Akihiko Katayama Faculty of Social Studies, Shikokugakuin University Kazuhiro Ujike Innoshima General Hospital Kiichi Koumoto Innoshima General Hospital Hiromi Suzuki Department of Hygiene, Faculty of Medicine, Kagawa University Hiroo Hashimoto Innoshima General Hospital Original Article 10.18926/AMO/57372 We investigated the relationship between sedentary behavior and all-cause mortality in patients undergoing hemodialysis. A total of 71 patients (39 men, 32 women, aged 72.1±11.7 years) were enrolled in this longitudinal study. Their sedentary behavior was measured using a tri-accelerometer that provides relative values per daily wearing time. We classified the sedentary behavior time into 2 groups (under the median: short-sedentary behavior (SB) group; over the median: long-SB group) and compared the groups’ clinical parameters. We compared the groups’ survival rates by using Kaplan-Meier curves and the log-rank test, and we performed multivariate analyses by a Cox-proportional hazard model to evaluate the relationship between the sedentary behavior and the survival rate. Twenty patients (28.2%) died during the observation period. The survival rate of the short-SB group was significantly higher than that of the long-SB group. Sedentary behavior was thus an important factor for all-cause mortality even after adjusting for confounding factors by a Cox-proportional hazard model. Sedentary behavior is closely linked to all-cause mortality, especially total days and non-hemodialysis days, and reducing sedentary behavior may be beneficial to reduce the all-cause mortality of patients on chronic hemodialysis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 A Case of Primary Colonic Signet Ring Cell Carcinoma in a Young Man which Preoperatively Mimicked Phlebosclerotic Colitis 361 365 EN Ayako Watanabe Department of Surgery, Japanese Red Cross Kobe Hospital Yoshihiko Kadowaki Department of Surgery, Japanese Red Cross Kobe Hospital Kenji Hattori Department of Surgery, Japanese Red Cross Kobe Hospital Mika Ohmori Department of Radiology, Japanese Red Cross Kobe Hospital Hiroyuki Tsukayama Department of Surgery, Japanese Red Cross Kobe Hospital Nobuhito Kubota Department of Surgery, Japanese Red Cross Kobe Hospital Tatsuo Okumoto Department of Surgery, Japanese Red Cross Kobe Hospital Nobuhiro Ishido Department of Surgery, Japanese Red Cross Kobe Hospital Takeshi Okino Department of Pathology, Japanese Red Cross Kobe Hospital Case Report 10.18926/AMO/56939 A 35-year-old man was referred to our hospital for chronic abdominal pain and diarrhea. Computed tomography showed wall thickening, poor contrast enhancement and calcification of the ascending colon, which were consistent with phlebosclerotic colitis. Malignant character was not detected from a biopsy specimen. Operatively, we observed a scirrhous mass of the ascending colon invading surrounding tissue, which was diagnosed as signet ring cell carcinoma based on analysis of an intraoperative frozen section. Right hemicolectomy with regional lymph node dissection was performed. This case was extremely similar to phlebosclerotic colitis in clinical findings; surgical resection was required for correct diagnosis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 Significance of Microcalcifications on Mammography in the Surgical Treatment of Breast Cancer Patients with a Preoperative Diagnosis of Ductal Carcinoma in Situ by Core Needle Biopsy 349 356 EN Hiroshi Isozaki Department of Surgery, Oomoto Hospital Yasuhisa Yamamoto Department of Surgery, Oomoto Hospital Shigeki Murakami Department of Surgery, Oomoto Hospital Sasau Matsumoto Department of Surgery, Oomoto Hospital Takehiro Takama Department of Surgery, Oomoto Hospital Original Article 10.18926/AMO/56937 To clarify the surgical outcomes of breast cancer patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) (abbreviated as CNBDCIS), we retrospectively analyzed the cases of 131 patients with CNBDCIS who underwent surgery at Oomoto Hospital (32 total mastectomies, 99 conservative mastectomies). Our analysis of underestimation and predictors of invasive breast cancer of CNBDCIS revealed that the underestimation rate of CNBDCIS was 40.5% (53/131). A logistic regression analysis revealed that palpable tumors (yes to no, odds ratio [OR] 3.25), mammography (MMG) category group (category 4 or 5 to categories 1 , 2, or 3, OR 4.69) and MMG microcalcifications (no to yes, OR 0.24) were significant predictive factors for CNBDCIS invasion. In our analysis of the predictors of positive margins during CNBDCIS surgery, 36 (27.5%) of the 131 patients had positive margins after postoperative pathological examination. A logistic regression analysis revealed that the operative procedure (conservative surgery to total mastectomy, OR 21.4) and MMG microcalcifications (yes to no, OR 3.35) were significant factors related to positive margins during CNBDCIS surgery. Thus, MMG microcalcifications are a negative predictor of upgrading of CNBDCIS and a positive predictor of positive surgical margins for CNBDCIS. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 Construction and Characterization of a PGN_0297 Mutant of Porphyromonas gingivalis: Evidence of the Contribution of PGN_0297 to Gingipain Activity 315 323 EN Shintaro Ono Department of Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaaki Nakayama Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Tachibana Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Abu Saleh Muhammad Shahriar Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Wang Heling Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shogo Takashiba Department of Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoya Ohara Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56933 The periodontal pathogen Porphyromonas gingivalis shows colonial pigmentation on blood agar and produces gingipains (Kgp, RgpA, and RgpB), cysteine proteases involved in an organism’s virulence and pigmentation. We showed previously that deletion of the PGN_0300 gene abolished the pigmentation activity and reduced the proteolytic activity of gingipains. The role of the PGN_0297 gene, which consists of an operon with the PGN_0300 gene, is unclear. Herein we examined the effect of PGN_0297 gene deletion on the pigmentation and proteolytic activities and transcriptional levels of gingipains. A PGN_0297 gene deletion mutant (ΔPGN_0297) did not exhibit the pigmentation. The proteolytic activity of the gingipains was decreased in the culture supernatant and on the cell surface of ΔPGN_0297. The mutant ΔPGN_0297 failed to attenuate Akt phosphorylation at Thr308 and Ser473, but both phosphorylations were attenuated in the wild-type and its complementation strain. The deletion of PGN_0297 gene did not substantially affect the transcriptional levels of the gingipain genes kgp, rgpA, and rgpB. Taken together, these results indicate that PGN_0297 is closely involved in the secretion and maturation of gingipains. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 Dynamic Reorganization of Microtubule and Glioma Invasion 285 297 EN Yoshihiro Otani Department of Neurosurgery, The University of Texas Health Science Center at Houston Tomotsugu Ichikawa Department of Neurosurgery, Kagawa Prefectural Central Hospital Kazuhiko Kurozumi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/56930 Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 A Case of Nager Syndrome Diagnosed Before Birth 273 277 EN Kei Hayata 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 Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Mitsui Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoko Tamada Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Eguchi Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumasa Tani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Ohira Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Washio Department Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Yoshimoto Department Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Hasegawa Department Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/56872 Nager syndrome is a rare disease involving severe micrognathia and upper limb shortening. In this report, we describe a case in which micrognathia of the fetus was suspected based on the observation of upper limb shortening during detailed B mode and 3D/4D ultrasonographic observation, and combined fetal MRI and 3D-CT led to a prenatal diagnosis of Nager syndrome. Upon birth, because severe micrognathia caused airway obstruction and made it difficult to spread the larynx for intubation, effective ventilation could not be carried out and a tracheostomy was necessary. Since a differential diagnosis of Nager syndrome can be made based on the fact that micrognathia typically co-occurs with upper limb shortening, it is possible to diagnose the disease before birth and prepare for life-saving measures accordingly. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Prevalence of and Risk Factors for the Progression of Upper Cervical Lesions in Patients with Rheumatoid Arthritis 235 240 EN Masahiro Horita Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nishida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenzo Hashizume Department of Rehabilitation, Japan Labour Health and Walfare Organization, Okayama Rosai Hospital Yoshihisa Sugimoto Department of Orthopaedic Surgery, Okayama City Hospital Yoshihisa Nasu Department of Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Nakahara Department of Intelligent Orthopaedic ystem, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryozo Harada 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 Original Article 10.18926/AMO/56866 We investigated the prevalence of and risk factors for the progression of upper cervical lesions (UCLs) in patients with rheumatoid arthritis (RA). A retrospective analysis of 49 patients with RA (4 males, 45 females) was conducted. The UCLs included atlanto-axial subluxation and vertical subluxation. We investigated the clinical factors including the Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) and the modified Health Assessment Questionnaire-Disability Index as well as radiographic changes between the baseline (at May 2010 to April 2013) and final follow-up. Forty patients (81.6%) were classified as the non-progressive group, and the other 9 patients (18.4%) comprised the progressive group. The progressive group’s final CRP values, baseline or final MMP-3 levels, DAS28-CRP, and rate of pre-existing lesions at baseline were all significantly higher than those of the non-progressive group (p=0.017, p=0.043, p=0.002, p=0.008, p<0.001, and p=0.008 respectively). A multivariate logistic regression analysis demonstrated that DAS28-CRP at baseline was a risk factor for radiographic progression (p=0.018, odds ratio: 2.54, 95% confidence interval: 1.17-5.51). Our findings indicate that higher disease activity might influence the progression of UCLs in patients with RA. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Spiral Trajectory Modulation of Rheotaxic Motile Human Sperm in Cylindrical Microfluidic Channels of Different Inner Diameters 213 221 EN Saori Nishina Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Matsuura Department of Biomedical Engineering, Faculty of Engineering, Okayama University of Science Keiji Naruse Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56863 We investigated the relationship between human sperm rheotaxis and motile sperm trajectories by using poly-(dimethylsiloxane) (PDMS)-based cylindrical microfluidic channels with inner diameters of 100 μm, 50 μm, and 70 μm, which corresponded to the inner diameter of the human isthmus, the length of a sperm and a diameter intermediate between the two, respectively. We counted the number of rheotaxic sperm and sperm with spiral motion. We also analyzed motile sperm trajectories. As the cylindrical channel diameter was decreased, the percentage of sperm cells exhibiting rheotaxis, the percentage of sperm cells exhibiting spiral motion, the frequency-to-diameter ratio of the sperm cells’ spiral trajectories, and the surface area of the microfluidic channel increased, while the flagellar motion at the channel wall decreased. The percentage of sperm exhibiting a spiral trajectory and the frequency-to-diameter ratio of the sperm cells’ spiral trajectories were thus affected by the channel diameter. Our findings suggest that the oviduct structure affects the swimming properties of sperm cells, guiding them from the uterus to the ampulla for egg fertilization. These results could contribute to the development of motile sperm-sorting microfluidic devices for assisted reproductive technologies. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 2 2019 Salvage Haploidentical Transplantation Using Low-dose ATG for Early Disease Relapse after First Allogeneic Transplantation: A Retrospective Single-center Review 161 171 EN Sachiyo Okamoto Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Maiko Sakamoto Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Yoshiaki Usui Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Yuki Fujiwara Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Takumi Kondo Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Katsuma Tani Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Kyosuke Saeki Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Yusuke Meguri Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Noboru Asada Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Keiko Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Original Article 10.18926/AMO/56652 Second allogeneic stem cell transplantation (allo-SCT) is a potentially curative therapy for patients who relapse after first allo-SCT. Human leukocyte antigen (HLA)-haploidentical related donors provide the broad opportunity to conduct second SCT at the appropriate time, but the efficacy of second SCT from haploidentical donors after relapse has not been established. We retrospectively analyzed the records of 33 patients who underwent second SCT. Twenty patients underwent haplo-SCT with low-dose antithymocyte globulin (ATG), and the other 13 patients underwent conventional- SCTs, including HLA-matched related peripheral blood, unrelated bone marrow or cord blood. Three years after the second SCT, the overall survival (OS) and progression-free survival (PFS) of all patients were 32.5% and 23.9%. Multivariate analyses indicated that non-complete response at second SCT, less than 1-year interval to relapse after first- SCT, and total score ≥ 3 on the hematopoietic cell transplantation-specific comorbidity index were significantly associated with a lower PFS rate. The haplo- and conventional- SCT groups showed equivalent results regarding OS, PFS, cumulative incidences of relapse, non-relapse mortality and graft-versus-host disease. The neutropenic period after transplantation was significantly shorter in haplo- SCT than conventional- SCT (10.5 days vs. 16 days, p=0.001). Our analysis revealed that haplo-SCT could be an alternative therapeutic option for relapsed patients after first SCT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 2 2019 Thyroid Function Decline and Diet in Female High School Long-distance Runners 127 133 EN Yukari Iwasaki Graduate School of Health Sciences, Okayama University Kimiko Miyahara Faculty of Health Care, Department of Nutrition, Kiryu University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Mikiya Nakatsuka Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/56648 We aimed to clarify the state of thyroid function in female high school long-distance runners. We evaluated the associations between thyroid function and menstrual condition, bone mineral density (BMD), nutritious status, and body composition. The subjects’ height and weight were measured, along with fat percentage, fat mass, muscle mass, and BMD with dual-energy X-ray absorptiometry. A nutrition and dietary survey measured the subjects’ intake of energy and nutrients based on meals provided at the subjects’ dorm for 3 days in July of 2016 and 2017. Blood parameters including thyroid hormone and estradiol were measured. Most of the subjects (81.3%) were underweight (body mass index <18.5). The thyroid hormone free T3 value was decreased, but TSH was not increased and was similar to that observed in individuals with anorexia nervosa. In our subjects, thyroid hormone was associated with BMD and nutritional intake. To improve the menstruation abnormality of female athletes and to increase their bone density, the athletes’ weight should be managed by proper nutrient intake and the maintenance of their thyroid function. No potential conflict of interest relevant to this article was reported.