Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Necrotizing Fasciitis Caused by ESBL-Producing Raoultella ornithinolytica in an Immunocompromised Patient with VEXAS Syndrome 141 145 EN Moe Sakamoto-Tokunaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Matoba Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomokazu Tamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Natsuki Kubota Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Terajima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Shidahara Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Hirose Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoichi Nawachi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takato Nakadoi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Katayama 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 Yoshia Miyawaki 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 Mariko Takano-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 Ken-Ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuma Tsuji Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University Kazuyoshi Gotoh Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/70456 VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory somatic) syndrome has a poor prognosis, with infections being a major cause of death. Raoultella ornithinolytica is an environmental bacterium found predominantly in soil and water. Although R. ornithinolytica can cause various infections, necrotizing fasciitis due to this bacterium has not been reported. We describe the case of an 84-year-old Japanese male with VEXAS syndrome who developed septic shock and necrotizing fasciitis while he was under immunosuppressive therapy. The pathogen was initially misidentified as R. planticola by mass spectrometry but later confirmed by whole-genome sequencing as extended spectrum β-lactamase (ESBL) produced by R. ornithinolytica. Although a life-saving leg amputation was required, the patient recovered with appropriate antibiotic therapy. R. ornithinolytica is thus able to cause severe skin infections in immunocompromised individuals. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 5 2024 Immunosuppressive Treatment for an anti-U1 Ribonucleoprotein Antibody-positive Patient with Pulmonary Arterial Hypertension 671 676 EN Kazuya Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yoshia Miyawaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takato Nakadoi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenta Shidahara Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kei Hirose Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shoichi Nawachi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Asano Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yu Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Mariko Takano-Narazaki 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 Atsushi Mori Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ei Sada 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 A 34-year-old woman with pulmonary arterial hypertension (PAH) was admitted to the hospital. She had been diagnosed with PAH three years earlier and treated with triple vasodilator therapy. She was positive for anti-U1 ribonucleoprotein antibodies but did not show any other symptoms associated with autoimmune diseases. Corticosteroid and cyclophosphamide therapy was administered, suspecting the involvement of immunological pathophysiology. After 3 weeks, the mean pulmonary artery pressure decreased from 50 to 38 mmHg without any change in the vasodilators. Immunosuppressive therapy was effective in this patient with PAH with an anti-U1 ribonucleoprotein-antibody-positive response and might be an option for patients with these specific features. 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).<br> 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.<br> 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.

BMJ Acta Medica Okayama 2053-8790 9 1 2022 Association of one-point glucocorticoid-free status with chronic damage and disease duration in systemic lupus erythematosus: a cross-sectional study e000772 EN Ken-ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yu Katayama 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 Yoshia Miyawaki 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 Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Mariko Takano-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 Ryusuke Yoshimi Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine Yasuhiro Shimojima Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine Shigeru Ohno Center for Rheumatic Diseases, Yokohama City University Medical Center Hiroshi Kajiyama Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University Kunihiro Ichinose Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Shuzo Sato Department of Rheumatology, Fukushima Medical University School of Medicine Michio Fujiwara Department of Rheumatology, Yokohama Rosai Hospital Nobuyuki Yajima Division of Rheumatology, Department of Medicine, Showa University School of Medicine Objective　It is still unclear how glucocorticoids (GCs) affect the long-term clinical course of patients with SLE. The objective of this study is to explore the factors associated with GC-free treatment status.<br> Methods　Using data from the lupus registry of nationwide institutions, GC dose at registration was compared between short, middle and long disease durations of <5, 5–20 and ≥20 years, respectively. After excluding patients who never used GC, we evaluated the relationship between GC-free status and chronic damage using Systemic Lupus International Collaborating Clinics Damage Index.<br> Results　GC doses at enrolment of the 1019 patients were as follows: GC-free in 101 (10%); 0<prednisolone (PSL) ≤5 mg/day in 411 (40%); 5<PSL ≤7.5 in 169 (17%); 7.5<PSL ≤10 in 194 (19%) and PSL≥10 in 144 (14%) patients. Of the patients who were not currently using GCs, patients who never used GC more frequently had short disease duration (66% with short, 23% with middle and 17% with long disease duration, p=0.00029). Univariate analysis of patients who underwent GC treatment showed that patients without GCs exhibited older age, lower disease activity, less immunosuppressant and hydroxychloroquine use and higher C3 levels. Among patients with a disease duration of ≥20 years, GC-free status was more frequent in patients without chronic damage (11% vs 4%, p=0.023). After adjusting for age, sex and disease activity, no chronic damage accrual was associated with GC-free status (OR 3.6, 95% CI 1.1 to 11.3).<br> Conclusion　Even in the patients with long disease duration, one-point GC-free treatment status might be related to no chronic damage accrual. No potential conflict of interest relevant to this article was reported.

American Society for Clinical Investigation Acta Medica Okayama 1558-8238 132 7 2022 Tankyrase represses autoinflammation through the attenuation of TLR2 signaling e140869 EN Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ioannis D. Dimitriou Princess Margaret Cancer Centre, University Health Network, University of Toronto Jose La Rose Princess Margaret Cancer Centre, University Health Network, University of Toronto Melissa Lim Princess Margaret Cancer Centre, University Health Network, University of Toronto Susan Camilleri Centre for Modeling Human Disease, Toronto Centre for Phenogenomics Napoleon Law Centre for Modeling Human Disease, Toronto Centre for Phenogenomics Hibret A. Adissu Labcorp Early Development Laboratories Inc. Jiefei Tong Program in Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics Michael F. Moran Program in Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics Andrzej Chruscinski Multi-Organ Transplant Program, University Health Network Fang He 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 Takayuki Katsuyama 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 Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Robert Rottapel Princess Margaret Cancer Centre, University Health Network, University of Toronto Dysregulation of Toll-like receptor (TLR) signaling contributes to the pathogenesis of autoimmune diseases. Here, we provide genetic evidence that tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, negatively regulates TLR2 signaling. We show that mice lacking tankyrase in myeloid cells developed severe systemic inflammation with high serum inflammatory cytokine levels. We provide mechanistic evidence that tankyrase deficiency resulted in tyrosine phosphorylation and activation of TLR2 and show that phosphorylation of tyrosine 647 within the TIR domain by SRC and SYK kinases was critical for TLR2 stabilization and signaling. Last, we show that the elevated cytokine production and inflammation observed in mice lacking tankyrase in myeloid cells were dependent on the adaptor protein 3BP2, which is required for SRC and SYK activation. These data demonstrate that tankyrase provides a checkpoint on the TLR-mediated innate immune response. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2045-2322 11 1 2021 Exploratory classification of clinical phenotypes in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis using cluster analysis EN Haruki Watanabe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken-ei Sada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Harigai Department of Rheumatology, Tokyo Women’s Medical University School of Medicine Koichi Amano Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University Hiroaki Dobashi Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University Yoshinari Takasaki Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Shouichi Fujimoto Department of Hemovascular Medicine and Artificial Organs, Faculty of Medicine, University of Miyazaki Tatsuya Atsumi Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Kunihiro Yamagata Department of Nephrology, Faculty of Medicine, University of Tsukuba Sakae Homma Department of Advanced and Integrated Interstitial Lung Diseases Research, School of Medicine, Toho University Yoshihiro Arimura Department of Nephrology and Rheumatology, Kyorin University School of Medicine Hirofumi Makino Okayama University Research Committee of Intractable Vasculitis Syndrome (JPVAS) & Research Committee of Intractable Renal Disease of the Ministry of Health, Labour, and Welfare of Japan A novel patient cluster in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may be identified in Japan. We performed multiple correspondence and cluster analysis regarding 427 clinically diagnosed AAV patients excluding eosinophilic granulomatosis with polyangiitis. Model 1 included the ANCA phenotype, items of the Birmingham Vasculitis Activity Score, and interstitial lung disease; model 2 included serum creatinine (s-Cr) and C-reactive protein (CRP) levels with model 1 components. In seven clusters determined in model 1, the ANCA-negative (n=8) and proteinase 3-ANCA-positive (n=41) groups emerged as two distinct clusters. The other five myeloperoxidase-ANCA-positive clusters were characterized by ear, nose, and throat (ENT) (n=47); cutaneous (n=36); renal (n=256), non-renal (n=33); and both ENT and cutaneous symptoms (n=6). Four clusters in model 2 were characterized by myeloperoxidase-ANCA negativity (n=42), without s-Cr elevation (<1.3 mg/dL) (n=157), s-Cr elevation (<greater than or equal to>1.3 mg/dL) with high CRP (>10 mg/dL) (n=71), or s-Cr elevation (>= 1.3 mg/dL) without high CRP (<= 10 mg/dL) (n=157). Overall, renal, and relapse-free survival rates were significantly different across the four clusters in model 2. ENT, cutaneous, and renal symptoms may be useful in characterization of Japanese AAV patients with myeloperoxidase-ANCA. The combination of s-Cr and CRP levels may be predictive of prognosis. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2466 20 1 2020 Recovery from hypoxemia and Hypercapnia following noninvasive pressure support ventilation in a patient with statin-associated necrotizing myopathy: a case report 156 EN Yuriko Yamamura 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 Koh Tadokoro Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Ohta Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Sato Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Yamamura Center for Rheumatology, Okayama Saiseikai General Hospital Ken-Ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Statin-associated necrotizing myopathy (SANM) is a rare autoimmune disorder caused by administration of statins. SANM is characterized by weakness due to necrosis and regeneration of myofibers. Here we report the first case of SANM with acute respiratory failure treated with noninvasive pressure support ventilation in addition to immunosuppressants. <br/> Case presentation: A 59-year-old woman who had been treated with 2.5 mg/day of rosuvastatin calcium for 5 years stopped taking the drug 4 months before admission to our hospital due to elevation of creatine kinase (CK). Withdrawal of rosuvastatin for 1 month did not decrease the level of CK, and she was admitted to our hospital due to the development of muscle weakness of her neck and bilateral upper extremities. Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies were positive. Magnetic resonance imaging showed myositis, and muscle biopsy from the right biceps brachii muscle showed muscle fiber necrosis and regeneration without inflammatory cell infiltration, suggesting SANM. After the diagnosis, she received methylprednisolone pulse therapy (mPSL, 1 g/day × 3 days, twice) and subsequent oral prednisolone therapy (PSL, 30 mg/day for 1 month, 25 mg/day for 1 month and 22.5 mg/day for 1 month), leading to improvement of her muscle weakness. One month after the PSL tapering to 20 mg/day, her muscle weakness deteriorated with oxygen desaturation (SpO2: 93% at room air) due to hypoventilation caused by weakness of respiratory muscles. BIPAP was used for the management of acute respiratory failure in combination with IVIG (20 g/day × 5 days) followed by mPSL pulse therapy (1 g/day × 3 days), oral PSL (30 mg/day × 3 weeks, then tapered to 25 mg/day) and tacrolimus (3 mg/day). Twenty-seven days after the start of BIPAP, she was weaned from BIPAP with improvement of muscle weakness, hypoxemia and hypercapnia. After she achieved remission with improvement of muscle weakness and reduction of serum CK level to a normal level, the dose of oral prednisolone was gradually tapered to 12.5 mg/day without relapse for 3 months. <br/> Conclusions: Our report provides new insights into the role of immunosuppressants and biphasic positive airway pressure for induction of remission in patients with SANM. No potential conflict of interest relevant to this article was reported.

Lippincott, Williams & Wilkins Acta Medica Okayama 1076-1608 25 4 2019 Cavernous Transformation and Granulomatous Epididymis in Behçet Disease 45 47 EN Yumi Motokura 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 Yuriko Yamamura Department of Nephrology, Rheumatology Endocrinology and Metabolism Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yuzuki Kano 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 Tomoko Kawabata 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 Jun Wada Department of Nephrology, Rheumatology Endocrinology and Metabolism Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 5 2017 Alternative to Rituximab Therapy for a Patient with Ankylosing Spondylitis Who Was Unable to Continue Anti-TNF Therapy 445 448 EN Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Wakabayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama Municipal Hospital, Ken-ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sumie Hiramatsu 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 Keiji Ohashi 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 Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sonia Zeggar 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 Noriko Tatebe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsue S. 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 Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/55444 We herein present a case of a 38-year-old man who had bamboo spine and severe sacroiliitis and who was diagnosed with ankylosing spondylitis (AS). Infliximab (IFX) markedly improved the axial symptom but was discontinued due to the side effect of peripheral neuropathy. Switching from IFX to etanercept worsened the side effect. Rituximab (RTX) administration elicited a good response without side effects. RTX might be a suitable option for AS therapy when TNF inhibitors are difficult to use. No potential conflict of interest relevant to this article was reported.

Taylor & Francis Acta Medica Okayama 1439-7595 26 5 2016 Comparison of severity classification in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study 730 737 EN Ken-ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayoshi Harigai Department of Rheumatology, Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University Koichi Amano Department of Rheumatology and Clinical Immunology , Saitama Medical Center, Saitama Medical University Tatsuya Atsumi Division of Rheumatology, Endocrinology and Nephrology at the Graduate School of Medicine , Hokkaido University Shouichi Fujimoto Department of Hemovascular Medicine and Artificial Organs, Faculty of Medicine , Miyazaki University Yukio Yuzawa Department of Nephrology , Fujita Health University School of Medicine Yoshinari Takasaki Department of Internal Medicine and Rheumatology , Juntendo University School of Medicine Shogo Banno Division of Rheumatology and Nephrology, Department of Internal Medicine , Aichi Medical University School of Medicine Takahiko Sugihara Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Masaki Kobayashi Department of Nephrology , Tokyo Medical University Ibaraki Medical Center Joichi Usui Department of Nephrology, Faculty of Medicine , University of Tsukuba Kunihiro Yamagata Department of Nephrology, Faculty of Medicine , University of Tsukuba Sakae Homma Department of Respiratory Medicine , Toho University Omori Medical Center Hiroaki Dobashi Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine , Kagawa University Naotake Tsuboi Department of Nephrology, Internal Medicine , Nagoya University Graduate School of Medicine Akihiro Ishizu Faculty of Health Sciences , Hokkaido University Hitoshi Sugiyama Department of Chronic Kidney Disease and Peritoneal Dialysis , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasunori Okada Department of Pathology , Keio University School of Medicine Yoshihiro Arimura Nephrology and Rheumatology, First Department of Internal Medicine , Kyorin University School of Medicine Seiichi Matsuo Department of Nephrology, Internal Medicine , Nagoya University Graduate School of Medicine Hirofumi Makino Okayama University Hospital OBJECTIVE: To compare disease severity classification systems for six-month outcome prediction in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Patients with newly diagnosed AAV from 53 tertiary institutions were enrolled. Six-month remission, overall survival, and end-stage renal disease (ESRD)-free survival were evaluated. RESULTS: According to the European Vasculitis Study Group (EUVAS)-defined disease severity, the 321 enrolled patients were classified as follows: 14, localized; 71, early systemic; 170, generalized; and 66, severe disease. According to the rapidly progressive glomerulonephritis (RPGN) clinical grading system, the patients were divided as follows: 60, grade I; 178, grade II; 66, grade III; and 12, grade IV. According to the Five-Factor Score (FFS) 2009, 103, 109, and 109 patients had ≤1, 2, and ≥3 points, respectively. No significant difference in remission rates was found in any severity classification. The overall and ESRD-free survival rates significantly differed between grades I/II, III, and IV, regardless of renal involvement. Severe disease was a good predictor of six-month overall and ESRD-free survival. The FFS 2009 was useful to predict six-month ESRD-free survival but not overall survival. CONCLUSIONS: The RPGN grading system was more useful to predict six-month overall and ESRD-free survival than the EUVAS-defined severity or FFS 2009. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 3 2014 岡山県下のクリニック・診療所におけるリウマチ診療・病診連携の実態に関する研究 209 215 EN Ken-ei Sada Keiichiro Nishida Takao Yamanaka Kenta Misaki Hiroshi Wakabayashi Junko Shinoda Toru Takagi Ryusuke Yano Akihiko Nakamura Yoshifumi Nanba Yoshitaka Morita Yoshinobu Koyama Keiji Yamamoto Kazuhiko Ezawa Yusuke Ota Yoshiki Yoshihara Shinya Miyoshi Masamitsu Natsumeda Masaaki Usui Yasuhiko Yoshinaga Takashi Hayashi Masahiro Yamamura Hiroyuki Hashizume Objective: To survey the current status and problems of cooperation between clinics and hospitals in Okayama Prefecture, Japan for the treatment of rheumatoid arthritis (RA). 　Methods: We distributed a questionnaire to 300 of the 983 Okayama Prefecture clinics that had either an internal medicine or orthopedic surgery department, from December 2013 to February 2014. The questionnaire covered practice pattern for RA treatment in clinics, current status of the hospital and clinic cooperation, and acceptance of the biologic therapy. 　Results: One hundred clinics responded to the questionnaire. Seventy percent of the clinics reported making referrals to rheumatologists before the initiation of RA treatment, and half of the other 30% of the clinics administered methotrexate as the first-line treatment for RA by their own decision. Sixty-six clinics cooperated with flagship hospitals, conducting medical and laboratory examinations, providing prescriptions, and treating common diseases of patients. These clinics expected the cooperating rheumatologists to follow-up patients every 3 to 6 months and to make the diagnosis, make decisions regarding RA treatment changes, and perform surgery. Seventy-one percent of the clinics responded that cooperation with a hospital is possible even for patients who are administered biologics. As reasons for no cooperation with the flagship hospitals, clinics noted the lack of information about rheumatologists in the area and recent trends in the management of RA. 　Conclusion: The current study reported, for the first time, the actual conditions of management of RA in clinics, as well as future problems of hospital and clinic cooperation in Okayama Prefecture. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1342-1751 17 1 2013 Current status of the treatment of microscopic polyangiitis and granulomatosis with polyangiitis in Japan 51 58 EN Koichi Sugiyama Ken-ei Sada Michiko Kurosawa Jun Wada Hirofumi Makino This study aimed to describe the epidemiologic characteristics of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in Japan. We used the database of the Ministry of Health, Labour and Welfare (MHLW) from 2006 to 2008, and analyzed data from 938 patients (MPA = 697, GPA = 241) who fulfilled the MHLW diagnostic criteria and had registered within a year after onset. The mean ages of the MPA and GPA patients were 69.4 +/- A 0.4 and 58.4 +/- A 1.1 years, respectively. Renal (86.9 %), chest (73.7 %), and nervous system (45.2 %) symptoms were common in MPA patients. Ear, nose, and throat (86.7 %), chest (78.0 %), and renal (60.6 %) symptoms were frequently observed in GPA patients. The concomitant use of cyclophosphamide (CY) with corticosteroids was observed in 22.2 % of the MPA patients and 58.5 % of the GPA patients. In multivariate analysis, the concomitant use of CY was associated with a younger age and pulmonary hemorrhage in MPA patients, and the avoidance of CY was associated with nervous system symptoms and rapidly progressive glomerulonephritis in GPA patients. Plasma exchanges were inducted in 5.2 % of the MPA patients and 4.1 % of the GPA patients. The addition of plasma exchange was associated with elevation of the serum creatinine level in patients with both MPA and GPA. A dominance of MPA and a reduced frequency of renal involvement in GPA patients may be significant features of the Japanese population. Clinical practice relating to MPA and GPA in Japan can be characterized as follows: CY is used less commonly, and plasma exchange is employed for patients with deteriorated renal function. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1342-1751 16 5 2012 Mizoribine, tacrolimus, and corticosteroid combination therapy successfully induces remission in patients with lupus nephritis 760 766 EN Hidetoshi Kagawa Tsutomu Hiromasa Takayuki Hara Ayako Takaki Ryutaro Yamanaka Ken-ei Sada Hirofumi Makino Conventional cyclophosphamide-based treatment regimens for lupus nephritis (LN) are still not considered to be optimal. The aim of this study was to evaluate the efficacy and safety of mizoribine, tacrolimus, and corticosteroid combination therapy for LN. We retrospectively evaluated a combination treatment of mizoribine and tacrolimus with corticosteroids as induction therapy in eight newly diagnosed systemic lupus erythematosus (SLE) patients with biopsy-proven LN. All patients were women, and their mean [standard deviation (SD)] age was 48.5 (20) years. All patients (100 %) had positive anti-double-stranded DNA (anti-dsDNA) antibody titers, and four (50.0 %) were nephrotic. Mean (SD) serum creatinine and daily proteinuria levels were 0.72 (0.4) mg/dl (range 0.33-1.55 mg/dl) and 4.56 (2.8) g (range 0.77-8.2 g), respectively. By month 2, significant improvements in the anti-dsDNA antibody titers, levels of proteinuria, serum albumin, and C3, and SLE disease activity index score were observed. By month 6, seven patients (87.5 %) were in complete remission, with normalized levels of both proteinuria and serum creatinine. This pilot study suggests that mizoribine and tacrolimus treatment with corticosteroids is well tolerated and may prove to be an optimal alternative remission-inducing regimen for LN. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0303-7207 348 1 2012 Peroxisome proliferator-activated receptor activity is involved in the osteoblastic differentiation regulated by bone morphogenetic proteins and tumor necrosis factor-α. 224 232 EN Mariko Takano Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci Fumio Otsuka Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci Yoshinori Matsumoto Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci Kenichi Inagaki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci Masaya Takeda Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci Eri Nakamura Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci Naoko Tsukamoto Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci Tomoko Miyoshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci Ken-ei Sada Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci Hirofumi Makino Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci Recent studies have suggested possible adverse effects of thiazolidinediones on bone metabolism. However, the detailed mechanism by which the activity of PPAR affects bone formation has not been elucidated. Impaired osteoblastic function due to cytokines is critical for the progression of inflammatory bone diseases. In the present study, we investigated the cellular mechanism by which PPAR actions interact with osteoblast differentiation regulated by BMP and TNF-alpha using mouse myoblastic C2C12 cells. BMP-2 and -4 potently induced the expression of various bone differentiation markers including Runx2, osteocalcin, type-1 collagen and alkaline phosphatase (ALP) in C2C12 cells. When administered in combination with a PPAR alpha agonist (fenofibric acid) but not with a PPAR gamma agonist (pioglitazone), BMP-4 enhanced osteoblast differentiation through the activity of PPAR alpha. The osteoblastic changes induced by BMP-4 were readily suppressed by treatment with TNF-alpha. Interestingly, the activities of PPAR alpha and PPAR gamma agonists reversed the suppression by TNF-alpha of osteoblast differentiation induced by BMP-4. Furthermore, TNF-alpha-induced phosphorylation of MAPKs, NF kappa B, I kappa B and Stat pathways was inhibited in the presence of PPAR alpha and PPAR gamma agonists with reducing TNF-alpha receptor expression. In view of the finding that inhibition of SAPK/JNK. Stat and NF kappa B pathways reversed the TNF-alpha suppression of osteoblast differentiation, we conclude that these cascades are functionally involved in the actions of PPARs that antagonize TNF-alpha-induced suppression of osteoblast differentiation. It was further discovered that the PPAR alpha agonist enhanced BMP-4-induced Smad1/5/8 signaling through downregulation of inhibitory Smad6/7 expression, whereas the PPAR gamma agonist impaired this activity by suppressing BMPRII expression. On the other hand, BMPs increased the expression levels of PPAR alpha and PPAR gamma in the process of osteoblast differentiation. Thus, PPAR alpha actions promote BMP-induced osteoblast differentiation, while both activities of PPAR alpha and PPAR gamma suppress TNF-alpha actions. Collectively, our present data establishes that PPAR activities are functionally involved in modulating the interaction between the BMP system and TNF-alpha receptor signaling that is crucial for bone metabolism. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 5 2011 Risk Factors for Infection in Patients with Remitted Rheumatic Diseases Treated with Glucocorticoids 329 334 EN Yoshinori Matsumoto Ken-ei Sada Mariko Takano Noriko Toyota Ryutaro Yamanaka Koichi Sugiyama Hiroshi Wakabayashi Tomoko Kawabata Fumio Otsuka Hirofumi Makino Original Article 10.18926/AMO/47015 It is well known that infection is one of the major causes of morbidity and mortality in rheumatic disease patients treated with high-dose glucocorticoids, especially in the early phase after achievement of disease remission. The aim of this study was to identify the risk factors for infection, with a focus on the dose of glucocorticoids administered, following the achievement of disease remission in rheumatic diseases patients. We retrospectively analyzed the medical records of rheumatic disease patients who had been treated with glucocorticoids. The primary endpoint was the incidence rate of infection during a period from 1 to 2 months after the commencement of treatment. From April 2006 to March 2010, 19 of 92 patients suffered from infection during the observation period. Age≧65 yrs, presence of interstitial pneumonia, diagnosis of systemic vasculitis and serum creatinine level≧2.0mg/dl were found to be univariate predictors for infection. However, only the presence of interstitial pneumonia was an independent risk factor for infection (HR＝4.50, 95%CI＝1.65 to 14.44) by the Cox proportional hazard model. Even after achievement of clinical remission, careful observation is needed for patients with interstitial pneumonia, more so than for those receiving high-dose glucocorticoids. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 122 2 2010 岡山県難病医療連絡協議会の活動 139 141 EN Ken-ei Sada No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2006 Altered Levels of Adipocytokines in Association with Insulin Resistance in Patients with Systemic Lupus Erythematosus EN Ken-ei Sada No potential conflict of interest relevant to this article was reported.