Rationale and design of the Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study.

INTRODUCTION: Disease subtyping and monitoring are essential for the management of nephrotic syndrome (NS). Although various biomarkers for NS have been reported, their clinical efficacy has not been comprehensively validated in adult Japanese patients. METHODS: The Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study is a nationwide, multicenter, and prospective cohort study in Japan, enrolling adult (≥18 years) patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), and lupus nephritis (LN). Baseline clinical information and plasma and urine samples will be collected at the time of immunosuppressive therapy initiation or biopsy. Follow-up data and plasma and urine samples will be collected longitudinally based on the designated protocols. Candidate biomarkers will be measured: CD80, cytotoxic T-lymphocyte antigen 4, and soluble urokinase plasminogen activator receptor for MCD and FSGS; anti-phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A antibodies for MN; fragment Ba, C3a, factor I, and properdin for MPGN/C3G; and CD11b, CD16b, and CD163 for LN. Outcomes include complete and partial remission, relapse of proteinuria, a 30% reduction in estimated glomerular filtration rate (eGFR), eGFR decline, and initiation of renal replacement therapy. The diagnostic accuracy and predictive ability for clinical outcomes will be assessed for each biomarker. RESULTS: From April 2019 to April 2023, 365 patients were enrolled: 145, 21, 138, 10, and 51 cases of MCD, FSGS, MN, MPGN/C3G, and LN, respectively. CONCLUSION: This study will provide valuable insights into biomarkers for NS and serve as a biorepository for future studies.

Progress testing of an objective structured clinical examination during undergraduate clinical clerkship: a mixed-methods pilot study.

BACKGROUND: Progress testing is an assessment method in which an examination reflecting competencies at graduation is regularly administered to students over multiple years, thereby facilitating self-directed learning. However, the significance of the objective structured clinical examination as a progress test in undergraduate education, needs to be determined. This study provides evidence of the role of the objective structured clinical examination for progress testing and optimal scoring methods for assessing students in different academic years. METHODS: We conducted a sequential explanatory mixed-methods pilot study. Participants were assessed using the Item Rating Scale, the year-adjusted Global Rating Scale, and the Training Level Rating Scale. The characteristics of each scale were compared quantitatively. In addition, the influence of the objective structured clinical examination as a progress test on learning attitudes was examined. Qualitative data from a post-examination questionnaire were analyzed, using content analysis to explore influences on self-directed learning. RESULTS: Sixth and fifth year clinical students (n = 235) took the objective structured clinical examination progress test. The total Item Rating Scales were recorded (%) as 59.03 ± 5.27 and 52.64 ± 5.08 (p < 0.01); Training Level Rating Scale was 3.94 ± 0.39 vs 3.22 ± 0.42 (p < 0.01); and the year-adjusted Global Rating Scale was 4.25 ± 0.44 vs 4.32 ± 0.52 (no significant difference), for the sixth and fifth year students, respectively. The correlations across stations and the reliability of each station were satisfactory. Four categories were identified in the qualitative analysis: "motivation to learn during the clinical clerkship was promoted," "dissatisfied with being asked about things they had not experienced," "confusion about being unable to use conventional test-taking strategies," and "insufficient understanding of competencies at graduation." The scores indicated significant differences in performance according to training year. CONCLUSIONS: This study provides evidence that the objective structured clinical examination can be used as a progress testing tool for undergraduate clinical clerkships. Further enhancement of training opportunities and dissemination of performance competency goals in clerkship curricula are required if we intend to promote self-directed learning through progress testing.

Association between magnesium, erythropoietin resistance and mortality: the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS).

Background: Limited data are now available to evaluate the relationship between serum magnesium level, anemia and mortality in the dialysis population. Methods: Using data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phases 5 and 6, we analyzed the association between serum magnesium (s-Mg) levels and the erythropoiesis-stimulating agents resistance index (ERI) as the primary outcome. To estimate the longitudinal relationship, a mixed-effect model was used with ERI at each 4-month period as the dependent variable and quintiles of s-Mg at the previous 4-month period as the independent variable. We also examined incidence of infectious events, and the all-cause and cardiovascular disease (CVD)-related deaths as secondary outcomes by Cox regression with quintiles of s-Mg at baseline. Results: Of the 4776 participants in J-DOPPS, 1650 were included in the analysis. The median of s-Mg at baseline was 2.5 mg/dL. A significant linear association of s-Mg with ERI (P for trend <.001) was revealed. Low and high s-Mg levels were not associated with the clinical outcomes of interest, except for the highest quintile of s-Mg being significantly associated with lower incidence of all-cause mortality and CVD-related deaths compared with the middle (reference) quintile. Conclusions: We observed that lower s-Mg levels subsequently induced higher ERI and that mild higher s-Mg levels were possibly associated with good rather than poor outcomes in Japanese hemodialysis patients. Adjustment of s-Mg levels may be proposed as a new strategy at a low cost and risk to reduce the risk of premature mortality.

Multiple endocrine neoplasia type 2B diagnosed after small intestinal volvulus with progressive megacolon in an adolescent.

Multiple endocrine neoplasia type 2B is a rare autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, Marfan-like fatigue, a peculiar face with thickening of the lips, mucosal neuromas on the lips and tongue, and gastrointestinal phenomena. Most patients harbor pathological variants of the RET gene. Herein, we present the first case of a 14 year-old boy who experienced small intestinal volvulus along with a megacolon, and he was diagnosed with multiple endocrine neoplasia type 2B. The patient complained of constipation since he was 2 years old and slowly progressive abdominal distension at school age. At 14 years of age, he presented with remarkable megacolon mimicking Hirschsprung's disease and complicated with small intestinal volvulus. The volvulus was successfully repaired, and the particularly dilated transverse colon was resected following a rectal biopsy. Histopathological evaluation of the resected transverse colon revealed to be compatible with ganglioneuromatosis. After emergency surgery, the patient was diagnosed with multiple endocrine neoplasia type 2B with medullary thyroid carcinoma, and a de novo variant of RET was confirmed. Gastroenterologists should consider it when treating patients with constipation, especially those with megacolon. Therefore, timely diagnosis may lead to appropriate treatment of medullary thyroid carcinoma and improve mortality.