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 Fumio Otsuka Yoshinori Matsumoto Kenichi Inagaki Masaya Takeda Eri Nakamura Naoko Tsukamoto Tomoko Miyoshi Ken-ei Sada Hirofumi Makino 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.