start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=e1088 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=2023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Decreased expression of hyaluronan synthase and loss of hyaluronan-rich cells in the anterior tibial fascia of the rat model of chemotherapy-induced peripheral neuropathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Previous studies on chemotherapy-induced peripheral neuropathy (CIPN) have focused on neuronal damage. Although some studies have revealed that the fascia is an important sensory organ, currently, we do not know about chemotherapy drug-induced fascial dysfunction.
Objectives: This study aimed to explore the fascia as a nonneural cause of mechanical hypersensitivity in CIPN by investigating the expression of hyaluronic acid synthase (HAS) and histology of the fascia in an animal model of CIPN.
Methods: Rats were intraperitoneally administered with vincristine (VCR). Mechanical hypersensitivities of the hind paw and the anterior tibial muscle were assessed. The expression of HAS mRNA in the fascia of the anterior tibial muscles was quantitated using reverse transcription polymerase chain reaction. Immunohistochemistry was also performed for HAS2, hyaluronic acid-binding protein, and S100A4 in the fascia.
Results: Vincristine administration significantly decreased mechanical withdrawal thresholds in the hind paw and the anterior tibial muscle after day 3. Quantitative polymerase chain reaction showed significant downregulation of HAS mRNAs in the fascia of VCR-treated rats. Immunohistochemical analysis showed that the number of cells with strong HAS2 immunoreactivity, classified as fasciacytes by morphology and colocalized marker S100A4, decreased significantly in the VCR group.
Conclusion:Hyaluronic acid plays a critical role in somatic pain sensation. Damaged fascia could be a possible cause of musculoskeletal pain in patients with CIPN. This study suggests that fascia is a nonneural cause and novel therapeutic target for chemotherapy-induced "peripheral neuropathy." en-copyright= kn-copyright= en-aut-name=WangRuilin en-aut-sei=Wang en-aut-mei=Ruilin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaYoshikazu en-aut-sei=Matsuoka en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SueNobutaka en-aut-sei=Sue en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakatsukaKosuke en-aut-sei=Nakatsuka en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuboiChika en-aut-sei=Tsuboi en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Chemotherapy-induced peripheral neuropathy kn-keyword=Chemotherapy-induced peripheral neuropathy en-keyword=Fascia kn-keyword=Fascia en-keyword=Fasciacyte kn-keyword=Fasciacyte en-keyword=Hyaluronic acid kn-keyword=Hyaluronic acid en-keyword=Musculoskeletal pain kn-keyword=Musculoskeletal pain en-keyword=Neuropathic pain kn-keyword=Neuropathic pain END start-ver=1.4 cd-journal=joma no-vol=101 cd-vols= no-issue=50 article-no= start-page=e32424 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Safety and efficacy of capsule endoscopy for patients with newly diagnosed Crohn's disease: A multicenter retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Crohn's disease (CD) is a chronic inflammatory disease that develops at a young age and frequently leads to intestinal resection. Capsule endoscopy (CE) can directly and non-invasively inspect the entire small bowel mucosa. We suspected that CE could be a good diagnostic tool for detecting CD in young patients. The aim of this study was to investigate the safety and efficacy of CE in patients with newly diagnosed CD and to evaluate the CE findings, especially in the upper small bowel of young patients. We retrospectively investigated 32 patients with newly diagnosed CD from 5 institutions. Patient characteristics, clinical course, and characteristics of CE findings were analyzed. The total small intestine observation rate was 93%, and the retention rate was 3% (1/32). No abnormality was identified by ileocolonoscopy in 46% (15/32), and transition of small bowel lesions (TSL) was found in 35% (12/34) of the patients. The frequency of longitudinal ulcers and cobblestones in the upper small intestine was significantly higher in younger patients (<= 20 years). Moreover, positive findings in the upper small intestine were predominantly observed in younger patients (<= 20 years). CE for patients with newly diagnosed CD was safe and useful, especially for the detection of upper small bowel lesions in young patients. en-copyright= kn-copyright= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkaShiro en-aut-sei=Oka en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiotaniAkiko en-aut-sei=Shiotani en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoShinichi en-aut-sei=Hashimoto en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiSakuma en-aut-sei=Takahashi en-aut-mei=Sakuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HandaOsamu en-aut-sei=Handa en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakamiTaro en-aut-sei=Takami en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InabaTomoki en-aut-sei=Inaba en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaShinji en-aut-sei=Tanaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Metabolism, Hiroshima University Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Metabolism, Hiroshima University Hospital kn-affil= en-keyword=capsule endoscopy kn-keyword=capsule endoscopy en-keyword=Crohn's disease kn-keyword=Crohn's disease en-keyword=upper small intestine kn-keyword=upper small intestine en-keyword=young patients kn-keyword=young patients END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=4 article-no= start-page=704 end-page=711 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Objective and quantitative estimation of the optimal timing for epiretinal membrane surgery on the basis of metamorphopsia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To establish an objective and quantitative biomarker of metamorphopsia in epiretinal membranes (ERMs) and determine the optimal timing for ERM surgery.
Methods: Retrospectively, 172 eyes with ERM were reviewed. Retinal folds due to tangential traction by ERM were visualized by en face optical coherence tomography (OCT). The maximum depth of retinal folds (MDRF) within the parafovea was quantified. Metamorphopsia was quantified by M-CHARTS. The change in the distance between the retinal vessels after ERM surgery and the preoperative total depth of retinal folds between the vessels were quantified using en face OCT and OCT angiography.
Results: Significant correlations were observed between preoperative MDRF and M-CHARTS scores before and at 6 months after surgery (r=0.617 and 0.460, respectively; P<0.001) and change in the distance between the retinal vessels after ERM surgery and preoperative total depth of retinal folds between the vessels (r=0.471, P=0.013). The preoperative MDRF values at which M-CHARTS scores were 0.5 before and 6 months after surgery were 69 μm and 118 μm, respectively.
Conclusion: MDRF is an objective and quantitative biomarker of metamorphopsia in ERM. To maintain patients’ quality of vision, ERM surgery may be performed when the preoperative MDRF ranges between 69 and 118 μm. en-copyright= kn-copyright= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DoiShinichiro en-aut-sei=Doi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanzakiSayumi en-aut-sei=Kanzaki en-aut-mei=Sayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HosokawaMio M. en-aut-sei=Hosokawa en-aut-mei=Mio M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakasuIppei en-aut-sei=Takasu en-aut-mei=Ippei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Takasu Eye Clinic kn-affil= affil-num=9 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=en-face optical coherence tomography kn-keyword=en-face optical coherence tomography en-keyword=epiretinal membrane kn-keyword=epiretinal membrane en-keyword=maximum depth of the retinal folds kn-keyword=maximum depth of the retinal folds en-keyword=M-CHARTS kn-keyword=M-CHARTS en-keyword=metamorphopsia kn-keyword=metamorphopsia END start-ver=1.4 cd-journal=joma no-vol=100 cd-vols= no-issue=3 article-no= start-page=e24028 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Granulomatosis with polyangiitis with obstructive pneumonia progressing to hypertrophic pachymeningitis A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rationale:
Bronchial involvement alone is a rare initial manifestation of granulomatosis with polyangiitis (GPA). Herein, we report a case of refractory GPA with obstructive pneumonia caused by bronchial involvement.
Patient concerns:
A 65-year-old man complained of a 2-week cough and fever.
Diagnoses:
Considering the presence of opacities and multiple consolidations in both lungs due to obstruction or stenosis on the bronchus, which did not respond to antibiotics, and proteinase-3-antineutrophil cytoplasmic autoantibody positivity, he was diagnosed with GPA. Positron emission tomography- computed tomography scan revealed no abnormal findings in the upper respiratory tract.
Interventions:
He was treated with prednisolone (PSL, 50 mg/d) and intravenous cyclophosphamide.
Outcomes:
His general and respiratory symptoms improved. However, 8 weeks after PSL treatment at 20 mg/d, he developed a relapse of vasculitis along with sinusitis and hypertrophic pachymeningitis. Hence, PSL treatment was resumed to 50 mg/d, and weekly administration of rituximab was initiated. Consequently, the symptoms gradually mitigated.
Lessons:
GPA with bronchial involvement is often intractable and requires careful follow-up, which should include upper respiratory tract and hypertrophic pachymeningitis assessment. en-copyright= kn-copyright= en-aut-name=HayashiKeigo en-aut-sei=Hayashi en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamuraYuriko en-aut-sei=Yamamura en-aut-mei=Yuriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsanoYosuke en-aut-sei=Asano en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaYukitoshi en-aut-sei=Katayama en-aut-mei=Yukitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Hiramatsu-AsanoSumie en-aut-sei=Hiramatsu-Asano en-aut-mei=Sumie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhashiKeiji en-aut-sei=Ohashi en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorishitaMichiko en-aut-sei=Morishita en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NarazakiMariko en-aut-sei=Narazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bronchial stenosis kn-keyword=bronchial stenosis en-keyword=granulomatosis with polyangiitis kn-keyword=granulomatosis with polyangiitis en-keyword=hypertrophic pachymeningitis kn-keyword=hypertrophic pachymeningitis en-keyword=rituximab kn-keyword=rituximab END start-ver=1.4 cd-journal=joma no-vol=99 cd-vols= no-issue=38 article-no= start-page=e22297 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200918 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pediatric growing teratoma syndrome of the ovary A case report and review of the literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rationale:
Growing teratoma syndrome is defined as an increase in tumor size during or after systemic chemotherapy for germ cell tumors. These cases involve normal tumor maker levels and histological features of only mature teratoma. We report a rare case of an ovarian immature teratoma in a Japanese child that was diagnosed as growing teratoma syndrome.
Patient concerns:
A 12-year-old girl presented a painful abdominal mass. She underwent left salpingo-oophorectomy for grade 1 immature teratoma in the left ovary. She did not undergo additional chemotherapy or radiotherapy. Four months later, she presented with grade 3 immature teratoma disseminated into the abdomen and pelvis. Chemotherapy resulted in the tumor maker levels returning to their normal ranges, although the tumors had grown slightly.
Diagnosis:
The specimens resected by laparotomy after the chemotherapy consisted of mature tissue predominantly, although primitive neuroepithelium was observed in a small part of the specimen. The pathological diagnosis was grade 1 immature teratoma, notwithstanding the clinical diagnosis was growing teratoma syndrome based on the clinical features and pathogenesis.
Interventions:
Laparotomy was performed at 7 months after the first operation, with resection of various tumors as well as the rectum, sigmoid colon, residual left fallopian duct, and a small part of the ileum and omentum. Some small tumors at the parietal peritoneum were ablated, although many tiny tumors around the uterus were left untreated.
Outcomes:
The patient has been free from recurrence for 5 years.
Lessons:
Growing teratoma syndrome can develop in children, and their tumor size is comparable to that in adolescents and adults. Furthermore, development of growing teratoma syndrome from a primary germ cell tumor is presumably faster in children than in adolescents and adults. Complete resection of all growing teratoma tissue is recommended, although fertility-sparing surgery should be considered when possible. en-copyright= kn-copyright= en-aut-name=OyamaTakanori en-aut-sei=Oyama en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NodaTakuo en-aut-sei=Noda en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimadaAkira en-aut-sei=Shimada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Pediatric Surgery,Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatric Surgery,Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= en-keyword=growing teratoma syndrome kn-keyword=growing teratoma syndrome en-keyword=immature teratoma kn-keyword=immature teratoma en-keyword=ovarian tumor kn-keyword=ovarian tumor en-keyword=pediatric kn-keyword=pediatric END start-ver=1.4 cd-journal=joma no-vol=99 cd-vols= no-issue=21 article-no= start-page=e20464 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nivolumab-induced IgA nephropathy in a patient with advanced gastric cancer A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Immune checkpoint inhibitors including nivolumab, an antibody against programmed death-1, have been increasingly introduced in various cancer treatment regimens, and are reported to be associated with immune-related adverse events. Nivolumab-induced renal injury is generally caused by acute interstitial nephritis and is managed by drug discontinuation and steroid therapy. Although this agent can infrequently induce glomerulonephritis, the pathogenesis and therapeutic strategy remain undetermined. Patient concerns: A 78-year-old man was diagnosed with advanced gastric cancer with portal thrombosis. First- and second-line chemotherapies were ineffective; thus, nivolumab monotherapy was initiated. Although it effectively prevented tumor growth, proteinuria and microhematuria appeared 2 months later. Despite drug discontinuation, serum creatinine progressively increased from 0.72 to 1.45 mg/dL. Renal biopsy revealed mesangial IgA and C3 deposition in immunofluorescence analysis and mesangial proliferation with crescent formation in light microscopy. Diagnosis: The patient was diagnosed with IgA nephropathy. Based on the temporal relationship between the nivolumab therapy and abnormal urinalysis, IgA nephropathy was considered to have been induced by nivolumab. Interventions: A moderate dose (0.6 mg/kg/day) of prednisolone was orally administrated, with tapering biweekly. Outcomes: Steroid therapy stabilized his serum creatinine levels and markedly reduced proteinuria. However, bacterial pneumonia substantially impaired his performance status; thus, nivolumab could not be restarted despite tumor regrowth. Lessons: IgA nephropathy should be recognized as an uncommon renal adverse event during nivolumab therapy. After drug discontinuation, nivolumab-induced IgA nephropathy is likely to respond to moderate doses of steroid therapy with early tapering. However, more evidence is needed to determine whether nivolumab can be safely restarted during or after steroid therapy. en-copyright= kn-copyright= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaTakahira en-aut-sei=Wada en-aut-mei=Takahira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakashimaYuri en-aut-sei=Nakashima en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism kn-affil= affil-num=5 en-affil=Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism kn-affil= en-keyword=case report kn-keyword=case report en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=IgA nephropathy kn-keyword=IgA nephropathy en-keyword=nivolumab kn-keyword=nivolumab en-keyword=steroid kn-keyword=steroid END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=e2797 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202004 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utilization of a Simple Surgical Guide for Multidirectional Cranial Distraction Osteogenesis in Craniosynostosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Multidirectional cranial distraction osteogenesis (MCDO) can achieve a desired shape for deformities of the cranium. In the past, visual estimation was used to reflect on the actual skull, but it was time-consuming and inaccurate. Here we demonstrate an effective osteotomy navigation method using surgical guides made from a dental impression silicone.
Methods: Seven patients who underwent MCDO between August 2013 and September 2016 were included in the study. Five cases involved utilization of the surgical guide for osteotomy. Three-dimensional (3D) printed cranium models were made using 3D computed tomography (3DCT) imaging data and dental impression silicone sheets were molded using the printed cranium models. These surgical guides were sterilized and used for intraoperative osteotomy design. Vertical distance between nasion/porion and osteotomy lines were calculated using 3D printed cranial models and postoperative 3DCT images to assess reproducibility.
Results: The average surgical time/design time was 535/37.0 minutes for the nonsurgical guide group and 486.8/11.8 minutes for the surgical guide group (SG). Treatment using the surgical guide was significantly shorter in terms of operative time and time required for design. For the vertical distance comparison, the average distance was 5.7mm (SD = 0.3) in the non-SG and 2.5mm (SD = 0.44) in the SG, and SG was more accurate.
Conclusions: Shorter operative times and higher reproducibility rates could be achieved by using the proposed surgical guide, which is accurate, low-cost, and easily accessible. en-copyright= kn-copyright= en-aut-name=MatsuiChihiro en-aut-sei=Matsui en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TokuyamaEijiro en-aut-sei=Tokuyama en-aut-mei=Eijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SenooTakaya en-aut-sei=Senoo en-aut-mei=Takaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaKiyoshi en-aut-sei=Yamada en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamedaMasahiro en-aut-sei=Kameda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakeuchiTetsuo en-aut-sei=Takeuchi en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery,Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Plastic and Reconstructive Surgery,Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Plastic and Reconstructive Surgery,Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery,Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Plastic and Reconstructive Surgery,Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=3 article-no= start-page=364 end-page=370 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202003 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypothesis: Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1β and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in lipopolysaccharide-induced otitis media. Background: NLRP3 inflammasome and macrophage migration inhibitory factor are critical molecules mediating inflammation. However, the interaction between the NLRP3 inflammasome and macrophage migration inhibitory factor has not been fully examined. Methods: Wild-type mice and macrophage migration inhibitory factor gene-deficient (MIF−/−) mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 hours after the injection. Concentrations of IL-1β, NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry. Results: In the immunohistochemical study using the wild-type mice, positive staining of macrophage migration inhibitory factor, NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear. The number of inflammatory cells caused by lipopolysaccharide administration decreased remarkably in the MIF−/− mice as compared with the wild-type mice. The concentrations of IL-1β, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF−/− mice with lipopolysaccharide had decreased levels of IL-1β, NLRP3, ASC, and caspase-1 as compared with the wild-type mice. Conclusion: Macrophage migration inhibitory factor has an important role in the production of IL-1β and the NLRP3 inflammasome. Controlling the inflammation by modulating macrophage migration inhibitory factor and the NLRP3 inflammasome may be a novel therapeutic strategy for otitis media. en-copyright= kn-copyright= en-aut-name=KariyaShin en-aut-sei=Kariya en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkanoMitsuhiro en-aut-sei=Okano en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhaoPengfei en-aut-sei=Zhao en-aut-mei=Pengfei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaYukihide en-aut-sei=Maeda en-aut-mei=Yukihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KataokaYuko en-aut-sei=Kataoka en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigakiTakaya en-aut-sei=Higaki en-aut-mei=Takaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishihiraJun en-aut-sei=Nishihira en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TachibanaTomoyasu en-aut-sei=Tachibana en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishizakiKazunori en-aut-sei=Nishizaki en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Otolaryngology—Head and Neck Surgery, Kagawa Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Medical Bioinformatics, Hokkaido Information University kn-affil= affil-num=9 en-affil=Departments of Otolaryngology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=10 en-affil=Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cytokine kn-keyword=Cytokine en-keyword=Infection kn-keyword=Infection en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Interleukin kn-keyword=Interleukin en-keyword=NOD-like receptor kn-keyword=NOD-like receptor en-keyword=Toll-like receptor kn-keyword=Toll-like receptor END start-ver=1.4 cd-journal=joma no-vol=477 cd-vols= no-issue=8 article-no= start-page=1892 end-page=1901 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Temporary External External Fixation Can Stabilize Hip Transposition Arthroplasty After Resection of Malignant Periacetabular Bone Tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The choice of reconstructive procedure to restore limb function is challenging after internal hemipelvectomy. Hip transposition arthroplasty, also known as resection arthroplasty, removes a malignant or aggressive tumor of the pelvis and acetabulum after which the remaining femoral head is moved proximally to the lateral surface side of the sacrum or the underside of the resected ilium after internal hemipelvectomy. It may provide reasonable functional results and have some advantages such as lowering the risk of an infected implant compared with other reconstructions because no foreign implants are used. Hip transposition is generally managed with prolonged bed rest or immobilization postoperatively to stabilize the soft tissue surrounding the remaining femur. Because enabling patients to be mobile while the soft tissues heal might be advantageous, we reviewed our experience with an external fixation for this procedure.
Questions/purposes: (1) Does temporary external fixation facilitate postoperative physiotherapy in patients who undergo hip transposition arthroplasty? (2) What functional Musculoskeletal Tumor Society (MSTS) scores were achieved at short term in a small series of patients treated with hip transposition and temporary external fixation? (3) What were the complications of using external fixation in a small series of patients who received it for malignant tumors?
Methods: Between 2008 and 2012, we treated seven patients (three men and four women; median age, 37 years; age range, 18-53 years) with acetabular resection for malignant bone tumors; all were managed with a hip transposition, initially stabilized using external fixation. No other types of procedures were used for this indication in this period. Minimum followup in this retrospective study was 45 months, except for one patient who died at 18 months (range of followup duration, 18-90 months; median followup, 57 months), and no patients were lost to followup. The pins for external fixation were inserted into the affected side of the femur and the healthy contralateral ilium. External fixation was removed 6 weeks postoperatively and weightbearing was started at that time. Preoperative chemotherapy was administrated in four patients, but postoperative chemotherapy was delayed since it was given after external fixation removal in three patients. The postoperative rehabilitation course and functional results were assessed by chart review, functional results were determined using MSTS scores, tallied by physiotherapists who were not part of the surgical team, and complications were ascertained through chart review. Major complications were defined as complications that were treated with additional operations, such as deep infection, or ones that could cause severe postoperative dysfunction, such as nerve injury.
Results: With temporary external fixation, standing next to a bed was achieved in median 7 days (range, 6-9 days) postoperatively, transferring to a wheel chair in median 8 days (range, 6-28 days), and gait training using parallel bars in median 15 days (range, 7-48 days). At most recent followup, three patients could walk without a crutch or cane, three could walk with a cane, and one could walk with a crutch. The median MSTS score at most recent followup (median, 57 months) was 63%. Two patients had complications that resulted in reoperations; one had a wound dehiscence, and one had an abdominal herniation that gradually developed, and which was reconstructed using polypropylene mesh 2 years after pelvic resection. Two patients had nerve palsies that recovered by the end of the first year. All patients had pin tract infections that resolved with nonsurgical approaches.
Conclusions: Hip transposition with temporary external fixation can stabilize the bone soft tissue after pelvic resection. Although we did not have a comparison group of patients, we believe that external fixation facilitates early postoperative physiotherapy and rehabilitation and provides good functional results without major surgical complications. Because it delays the resumption of chemotherapy, more patients with longer followup are needed to determine whether this will be associated with poorer oncologic results. en-copyright= kn-copyright= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SendaMasuo en-aut-sei=Senda en-aut-mei=Masuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Rehabilitation, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=4 article-no= start-page=45 end-page=47 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cavernous Transformation and Granulomatous Epididymis in Behçet Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MotokuraYumi en-aut-sei=Motokura en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamuraYuriko en-aut-sei=Yamamura en-aut-mei=Yuriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanoYuzuki en-aut-sei=Kano en-aut-mei=Yuzuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawabataTomoko en-aut-sei=Kawabata en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SadaKen-ei en-aut-sei=Sada en-aut-mei=Ken-ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology Endocrinology and Metabolism Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology Endocrinology and Metabolism Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology Endocrinology and Metabolism Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology Endocrinology and Metabolism Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology Endocrinology and Metabolism Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology Endocrinology and Metabolism Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology Endocrinology and Metabolism Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology Endocrinology and Metabolism Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= END