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.

Prognosis of pediatric ulcerative colitis after infliximab failure: A multicenter registry-based cohort study.

BACKGROUND AND AIM: Even with increasing numbers of biologic agents available for management of ulcerative colitis (UC), infliximab (IFX) retains an important place in treatment of pediatric patients with this disease. As few reports have addressed outcomes in pediatric UC patients who had to discontinue IFX, we examined clinical course and prognosis after IFX failure in pediatric UC. METHODS: A prospective cohort study of pertinent cases enrolled in the Japanese Pediatric Inflammatory Bowel Disease Registry between 2012 and 2020 was conducted to determine outcomes for pediatric UC patients who received IFX but required its discontinuation during follow-up (IFX failure). RESULTS: Of the 301 pediatric UC patients in the registry, 75 were treated with IFX; in 36 of these, IFX was discontinued during follow-up. Severity of UC at onset and absence of concomitant immunomodulator therapy were significant risk factors for IFX failure (P = 0.005 and P = 0.02, respectively). The cumulative colectomy rate after IFX failure was 41.3% at 1 year and 47.5% at 2 years. Colectomy was significantly more frequent when IFX was discontinued before June 1, 2018, than when IFX was discontinued later (P = 0.013). This difference likely involves availability of additional biologic agents for treatment of UC beginning in mid-2018 (P = 0.005). CONCLUSION: In pediatric UC patients, approximately 50% underwent colectomy during a 2-year interval following IFX failure. Prognosis after IFX failure appeared to improve with availability of new biologic agents and small-molecule drugs in mid-2018.

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.

Rationale and study design of a randomized controlled trial to investigate the renoprotective effect of canagliflozin assessed by test of renal hemodynamics in diabetic kidney disease (the FAGOTTO study).

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are considered to have the potential to maintain renal function by correcting glomerular hypertension in patients with diabetic kidney disease (DKD). The aim of this study is to demonstrate the renoprotective effect of SGLT2i by measuring renal hemodynamics, including glomerular filtration fraction (FF), in type 2 diabetic patients with moderate renal dysfunction. METHODS: Renoprotective effect of canagliflozin derived from test of renal hemodynamics in diabetic kidney disease (FAGOTTO) study is a 12-week multicenter, open-label, randomized (1:1), parallel-group trial of type 2 diabetic patients with diabetic kidney disease (30 ≤ estimated glomerular filtration rate [eGFR] ≤ 60 mL/min/1.73 m2). A total of 110 patients are to be randomly allocated to receive once-daily canagliflozin 100 mg or control (standard therapy). FF will be calculated by dividing the measured GFR (mGFR) by the effective renal plasma flow (eRPF). mGFR and eRPF will be measured by the clearance of inulin and para-aminohippuric acid (PAH), respectively. The primary endpoint of this trial is the percentage change in FF after 4 weeks of treatment in the canagliflozin and control groups. DISCUSSION: The FAGOTTO study will elucidate the mechanism of the renoprotective action of SGLT2i. The background, rationale, and study design of this trial are presented. To date, > 80 patients have been enrolled in this trial. The study will end in 2025. TRIAL REGISTRATION: jRCT (Japan Registry Of Clinical Trials) jRCTs041200069. Date of registration: November 27, 2020.

Basigin is released in extracellular vesicles derived from the renal tubular epithelium in response to albuminuria.

AIM: Irrespective of the cause, albumin/proteinuria induces tubulointerstitial damage and accelerates the progression of kidney diseases. Our series of studies demonstrated that proteinuria, an independent prognostic factor for chronic kidney disease (CKD), is correlated with urinary basigin/CD147 (Bsg) levels. We examined the morphology and origin of Bsg in the tubular lumen through the effects of filtered glucose and protein solutes on the tubules. METHODS: Diabetic kidney disease (DKD) patients (N = 50) were treated with spironolactone 25 mg for 4 weeks or by conservative treatment. The associations between urinary Bsg values and clinical indicators were examined. Primary-cultured proximal tubular epithelial cells (PTECs) from human adult kidneys were exposed to high glucose or bovine serum albumin (BSA). RESULTS: In patients with early phase DKD, urinary Bsg levels were closely correlated with proteinuria but not HbA1c. Full-length Bsg on extracellular vesicles (EVs) was investigated primarily in urine collected from DKD patients. EVs obtained from the urine of DKD patients included Bsg and SGLT2 proteins. Notably, spironolactone treatment concomitantly suppressed the release of Bsg-bearing EVs in correlation with decreased albuminuria. Exposure of PTECs to BSA (but not high glucose) enhanced the storage of supernatant Bsg in EVs despite the absence of exposure-specific changes in Bsg transcription. CONCLUSION: Proteinuria induces the release of Bsg-bearing EVs derived from PTECs into the tubular lumen.

Relationship between the lower limit of systolic blood pressure target and kidney function decline in advanced chronic kidney disease: an instrumental variable analysis from the REACH-J CKD cohort study.

Intensive antihypertensive treatment decreases cardiovascular disease and mortality risks in chronic kidney disease (CKD), whereas extremely low systolic blood pressure (SBP) is associated with worsening kidney function and poor prognosis. Although the SBP variation is particularly large in patients with CKD, the optimal lower limit of SBP target is unclear. In a nationwide, multicenter cohort study of patients with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2, we evaluated the association between the eGFR slopes and the lower limit of SBP target at ≥110 mmHg using a linear mixed-effects model and an instrumental variable method. The instrumental variable was calculated as the facility-level percentage of nephrologists who answered in the survey that their lower limit of SBP target was 110 mmHg or higher. A total of 1320 patients (mean age 70 years; 66% men) were included. The mean eGFR slope ± standard deviation over the four years to baseline was -2.48 ± 2.15 mL/min/1.73 m2/year. The instrumental variable for the lower limit of SBP target at ≥110 mmHg (vs. ≤100 mmHg) was associated with less eGFR decline (coefficient: +1.05 mL/min/1.73 m2/year; 95% confidence interval: 0.33-1.77), while unassociated with a history of cardiovascular disease. The renoprotective effect was particularly larger in the subgroups of the elderly and those with a history of cardiovascular disease. In conclusion, the lower limit of SBP target at 110 mmHg or higher was associated with improved eGFR slope, suggesting the importance of aiming at avoiding excessively low SBP in patients with advanced CKD.

Evaluating glucose variability through OGTT in early pregnancy and its association with hypertensive disorders of pregnancy in non-diabetic pregnancies: a large-scale multi-center retrospective study.

BACKGROUND: Recent evidence suggests increased glucose variability (GV) causes endothelial dysfunction, a central pathology of hypertensive disorders of pregnancy (HDP). We aimed to investigate the association between GV in early pregnancy and subsequent HDP development among non-diabetes mellitus (DM) pregnancies. METHODS: This multicenter retrospective study used data from singleton pregnancies between 2009 and 2019. Among individuals who had 75 g-OGTT before 20 weeks of gestation, we evaluated GV by 75 g-OGTT parameters and examined its relationship with HDP development, defining an initial-increase from fasting-plasma glucose (PG) to 1-h-PG and subsequent-decrease from 1-h-PG to 2-h-PG. RESULTS: Approximately 3.0% pregnancies (802/26,995) had 75 g-OGTT before 20 weeks of gestation, and they had a higher prevalence of HDP (14.3% vs. 7.5%). The initial-increase was significantly associated with overall HDP (aOR 1.20, 95% CI 1.02-1.42), and the subsequent-decrease was associated with decreased and increased development of early-onset (EoHDP: aOR 0.56, 95% CI 0.38-0.82) and late-onset HDP (LoHDP: aOR 1.38, 95% CI 1.11-1.73), respectively. CONCLUSIONS: A pattern of marked initial-increase and minor subsequent-decrease (i.e., sustained hyperglycemia) was associated with EoHDP. Contrarily, the pattern of marked initial-increase and subsequent-decrease (i.e., increased GV) was associated with LoHDP. This provides a new perspective for future study strategies.

Clinical outcome of ulcerative colitis with severe onset in children: a multicenter prospective cohort study.

BACKGROUND: As best practices for treating children with severe-onset ulcerative colitis remain controversial in the era of biologic agents, we prospectively investigated treatments and outcomes in a multicenter cohort. METHODS: Using a Web-based data registry maintained in Japan between October 2012 and March 2020, we compared management and treatment outcomes in an S1 group defined by a Pediatric Ulcerative Colitis Activity Index of 65 or more points at diagnosis with those in an S0 group defined by an index value below 65. RESULTS: Three hundred one children with ulcerative colitis treated at 21 institutions were included, with follow-up for 3.6 ± 1.9 years. Among them, 75 (25.0%) were in S1; their age at diagnosis was 12.3 ± 2.9 years, and 93% had pancolitis. Colectomy free rates in S1 were 89% after 1 year, 79% after 2, and 74% after 5, significantly lower than for S0 (P = 0.0003). Calcineurin inhibitors and biologic agents, respectively, were given to 53% and 56% of S1 patients, significantly more than for S0 patients (P < 0.0001). Among S1 patients treated with calcineurin inhibitors when steroids failed, 23% required neither biologic agents nor colectomy, similarly to the S0 group (P = 0.46). CONCLUSIONS: Children with severe ulcerative colitis are likely to require powerful agents such as calcineurin inhibitors and biologic agents; sometimes colectomy ultimately proves necessary. Need for biologic agents in steroid-resistant patients might be reduced to an extent by interposing a therapeutic trial of CI rather than turning to biologic agents or colectomy immediately.

Serum positivity of serum anti-tissue transglutaminase immunoglobulin A antibodies in Japanese children with inflammatory bowel disease.

BACKGROUND: Serum anti-tissue transglutaminase immunoglobulin A antibody (tTG-IgA) is a screening test for celiac disease (CeD). In recent years, there have several reports of combined inflammatory bowel disease (IBD) and CeD in children. The purposes of this study are to research the positivity of the tTG-IgA antibody in Japanese children, and whether IBD and CeD co-occur. METHODS: We examined tTG-IgA as a screening test for CeD in symptomatic pediatric patients with IBD (cases) and those without IBD (controls, non-IBD). Those with tTG-IgA levels of 10 U/mL or higher were considered positive. All patients had routine biopsy specimens taken from the second part and bulbus of the duodenum, and were evaluated histologically based on the Marsh classification. RESULTS: Thirty-one patients in the IBD group and 53 patients in the non-IBD group were included. The tTG-IgA was positive in five cases (5.9%) and median titer of positive cases was 12.3 U/mL (10.2-41.7). One patient in the IBD group (3.2%) and four patients in the non-IBD group (7.8%) were positive for tTG-IgA. No cases showed histological features of CeD. There were no statistically significant differences in age, sex, symptoms and laboratory tests between the tTG-IgA positive and negative groups. Patients among the IBD and the non-IBD groups that were tTG-IgA positive demonstrated symptoms after wheat consumption. CONCLUSIONS: We identified a patient who was positive for tTG-IgA antibodies who experienced abdominal symptoms due to wheat ingestion, indicative of subclinical CeD. Further investigation is needed to clarify the co-occurrence of IBD and CeD among Japanese children.

Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia.

INTRODUCTION: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients' quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. METHODS: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6-12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. RESULTS: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (ß coefficient -6.935, 95% confidence interval, 13.313 to-0.556, p = 0.034). CONCLUSION: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

Number and distribution of eosinophils and lymphocytes in the Japanese pediatric gastrointestinal tract: in search of a definition for "abnormally increased eosinophils".

BACKGROUND: Primary eosinophilic gastrointestinal disorders (EGIDs) constitute chronic allergic inflammation. The number of eosinophils is one of the diagnostic criteria; more than 20 eosinophils per high-power field (HPF) in the gastrointestinal (GI) tract are considered abnormal in Japan. However, the quantity of eosinophils considered normal varies according to anatomical location and geographical region; such values have not been reported in Japanese pediatric patients, nor have the numbers of lymphocytes in the normal pediatric stomach. To establish a reference for defining diagnostic criteria for EGIDs, we evaluated the number of eosinophils in the normal Japanese pediatric GI tract. METHODS: We examined 131 biopsy cases without significant clinical history, endoscopic abnormality, or histological abnormality. Immunohistochemical analysis of CD3 and CD20 was performed. RESULTS: The mean eosinophil density was highest in the cecum (49.5 ± 22.4 per HPF). Counts of more than 20 eosinophils per HPF were observed in the duodenum [bulb (20.0 ± 9.6) and second portion (30.0 ± 15.8)], terminal ileum (38.3 ± 22.7), cecum (49.5 ± 22.4), ascending colon (42.3 ± 25.3), transverse colon (29.4 ± 17.0), and descending colon (32.2 ± 17.9). Counts of fewer than 10 eosinophils per HPF were observed in the stomach and rectum; a count of fewer than one eosinophil per HPF was observed in the esophagus. More than 100 CD3-positive T cells per HPF were observed in the stomach. CONCLUSIONS: The mean numbers of eosinophils in the bowel were greater than 20 per HPF. For Japanese pediatrics, the current threshold eosinophil count should be revised.

Impact of etelcalcetide on fibroblast growth factor-23 and calciprotein particles in patients with secondary hyperparathyroidism undergoing haemodialysis.

AIM: Recently, we demonstrated the efficacy of etelcalcetide in the control of secondary hyperparathyroidism (SHPT). This post hoc analysis aimed to evaluate changes in fibroblast growth factor-23 (FGF23) and calciprotein particles (CPPs) after treatment with calcimimetics. METHODS: The DUET trial was a 12-week multicenter, open-label, parallel-group, randomized (1:1:1) study with patients treated with etelcalcetide plus active vitamin D (E + D group; n = 41), etelcalcetide plus oral calcium (E + Ca group; n = 41), or control (C group; n = 42) under maintenance haemodialysis. Serum levels of FGF23 and CPPs were measured at baseline, and 6 and 12 weeks after the start. RESULTS: In the linear mixed model, serum levels of FGF23 in etelcalcetide users were significantly lower than those in non-users at week 6 (p < .001) and week 12 (p < .001). When compared the difference between the E + Ca group and the E + D group, serum levels of FGF23 in the E + Ca group were significantly lower than those in the E + D group at week 12 (p = .017). There were no significant differences in the serum levels of CPPs between etelcalcetide users and non-users at week 6 and week 12, while CPPs in the E + Ca group were significantly lower than those in the E + D group (p < .001) at week 12. CONCLUSION: Etelcalcetide may be useful through suppression of FGF23 levels among haemodialysis patients with SHPT. When correcting hypocalcaemia, loading oral calcium preparations could be more advantageous than active vitamin D for the suppression of both FGF23 and CPPs.

Increased Monocyte/Lymphocyte Ratio as Risk Marker for Cardiovascular Events and Infectious Disease Hospitalization in Dialysis Patients.

INTRODUCTION: In dialysis patients, cardiovascular disease (CVD) and infectious disease contribute to poor clinical outcomes. We investigated if a higher monocyte/lymphocyte ratio (MLR) is associated with an increased risk of CVD events and infectious disease hospitalizations in incident dialysis patients. METHODS: In an ongoing observational prospective cohort study, 132 Japanese dialysis patients (age 58.7 ± 11.7 years; 70% men) starting dialysis therapy were enrolled and followed up for a median of 48.7 months. Laboratory biomarkers, including white blood cell count and its differential count, were determined at baseline. Event-free time and relative risks (RRs) were calculated using the Kaplan-Meier curves and Cox models, respectively. RESULTS: When divided into 2 groups according to median MLR (0.35 [range, 0.27-0.46]), the periods without CVD events were significantly shorter in the high MLR group than in the low MLR group (log-rank test = 5.60, p = 0.018). The RR of CVD events, after adjusting for age, sex, and diabetes, was 2.43 (1.22-4.84) in the high MLR group compared to the low MLR group. The periods without infections requiring hospitalization were also shorter (log-rank test = 4.16, p = 0.041). The RR of infections requiring hospitalization was 1.98 (1.02-3.83) after the same adjustments. The number of CVD events was higher in the high MLR group (18.6 events per 100 person-years at risk [pyr]) than the low MLR group (11.1 events per 100 pyr). The duration of infectious disease hospitalization was longer in the high MLR group (6.3 days per pyr) than in the low MLR group (2.8 days per pyr). CONCLUSION: A higher MLR is associated with increased risks of both CVD events and infectious disease hospitalization in dialysis patients.

Effect of body mass index on the association between alcohol consumption and the development of chronic kidney disease.

The influence of body mass or metabolic capacity on the association between alcohol consumption and lower risks of developing chronic kidney disease (CKD) is not fully elucidated. We examined whether the body mass index (BMI) affects the association between drinking alcohol and CKD. We defined CKD as an estimated glomerular filtration rate decline < 60 mL/min/1.73 m2 and/or positive proteinuria (≥ 1+). Participants were 11,175 Japanese individuals aged 40-74 years without baseline CKD who underwent annual health checkups. Daily alcohol consumption at baseline was estimated using a questionnaire, and the participants were categorized as "infrequent (occasionally, rarely or never)," "light (< 20 g/day)," "moderate (20-39 g/day)," and "heavy (≥ 40 g/day)." Over a median 5-year observation period, 936 participants developed CKD. Compared with infrequent drinkers, light drinkers were associated with low CKD risks; adjusted hazard ratios (95% confidence intervals) were 0.81 (0.69-0.95). Stratified by BMI (kg/m2), moderate drinkers in the low (< 18.5), normal (18.5-24.9), and high (≥ 25.0) BMI groups had adjusted hazard ratios (95% confidence intervals) of 3.44 (1.60-7.42), 0.75 (0.58-0.98), and 0.63 (0.39-1.04), respectively. Taken together, the association between alcohol consumption and CKD incidence was not the same in all the individuals, and individual tolerance must be considered.

Demographic, clinical characteristics and treatment outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulonephritis in Japan: A retrospective analysis of data from the Japan Renal Biopsy Registry.

The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN.

A case of child-to-father transmission of hepatitis B virus in Japan: a rare infection route.

This report describes a rare horizontal transmission of hepatitis B virus (HBV) from an unvaccinated 6-year-old boy to his father. The father had been diagnosed with acute hepatitis B 1 month earlier; therefore, when the child visited the clinic with fever, he was screened for HBV markers and diagnosed as an asymptomatic carrier. Neither the child nor his father was vaccinated against HBV, whereas the child's mother and sister, having received the HBV vaccination as they were medical staff and a nursing student, respectively, tested negative for the hepatitis B surface antigen (HBsAg) and positive for anti-HBs. We performed a phylogenetic analysis of HBV in the child and his father, and identified 100% homologous strains of identical genotype C. At diagnosis, the father tested positive for IgM anti-hepatitis B core with a high titer, whereas the child tested negative for this marker. These data strongly indicated a child-to-father transmission. In this case, the HBV infection route was speculated as close contact including saliva-based transmission between the child and father, mainly attributed to their daily food habits. When clinicians diagnose patients with acute or chronic HBV infection, the household members should have been examined for HBV markers immediately. If some household members are susceptible to HBV infection, all members should be vaccinated against HBV.

Clinicopathological features of nodular gastritis in three classes of age.

BACKGROUND: Nodular gastritis is most often one of the manifestations of Helicobacter pylori (H. pylori) infection, which is a risk factor for gastric cancer. This study aimed to determine if the histological characteristics of nodular gastritis differed across classes of age. METHODS: We conducted a retrospective analysis of consecutive patients who had undergone esophagogastroduodenoscopy with multiple mucosal biopsies of the stomach between 2003 and 2019 for evaluation of updated Sydney System scores. We analyzed and compared the histological characteristics of pediatric (≤15 years old), young (16-29 years old), and older (≥30 years old) patients. RESULTS: Of the 1321 patients enrolled, 1027 patients (78%) had H. pylori infection, with 214 patients (21%) of them displaying nodular gastritis. Among nodular gastritis patients, mononuclear cell infiltration Sydney System scores in the gastric body were significantly higher in the older group than in the pediatric (p < .001) and young (p < .001) groups. Similar results were seen for neutrophil infiltration scores in the gastric body. To clarify the characteristics of older nodular gastritis, we investigated 1056 older patients (66 with nodular gastritis, 754 with atrophic gastritis, and 236 H. pylori-negative). The scores for mononuclear and neutrophil cell infiltration in the gastric body were significantly higher in nodular gastritis patients than in atrophic gastritis patients (both p < .001) and patients negative for H. pylori (both p < .001). CONCLUSIONS: The inflammatory changes in the gastric body in older nodular gastritis patients were more severe as compared with those in pediatric and young nodular gastritis patients in addition to older atrophic gastritis patients.

Nephrotic syndrome with focal segmental glomerular lesions unclassified by Columbia classification; Pathology and clinical implication.

BACKGROUND: The Columbia classification is widely used for diagnosis of focal segmental glomerulosclerosis (FSGS). In practice, we occasionally encounter segmental glomerular lesions unclassified as Columbia classification. We analyzed the clinical implication of unclassified segmental lesions comparing with Columbia-classified FSGS. METHODS: A retrospective cohort study from 13 local hospitals in Japan. From 172 biopsy cases diagnosed with FSGS or minimal change disease (MCD)/FSGS spectrum with unclassified segmental lesions, adult patients with nephrotic syndrome who received immunosuppressive therapies were included. The cases are classified by pathology, i.e., typical FSGS lesions sufficiently classified into subgroups of Columbia classification: collapsing (COL), tip (TIP), cellular (CEL), perihilar (PH), and not otherwise specified (NOS), and unclassified by the Columbia classification into three subgroups: "endothelial damage,"; "simple attachment,"; and "minor cellular lesion,". The response to immunosuppressive treatment and 30% decline of eGFR were compared. RESULTS: Among 48 eligible cases, all were Japanese, 34 were typical FSGS; 13 TIP, 15 CEL, 6 NOS, and no COL or PH cases. Fourteen were unclassified cases: endothelial damage (n = 6), simple attachment (n = 5), and minor cellular lesion (n = 3). The median age of overall patients was 60 years old and the median of eGFR and urinary protein creatinine ratio was 51.5 mL/min/1.73m2 and 7.35, respectively. They received similar therapeutic regimen. Kaplan-Meier analysis revealed no significant difference in treatment response between typical FSGS and unclassified cases. Evaluating among the subgroups, endothelial damage, simple attachment and minor cellular lesion showed similar treatment response to TIP or CEL. No significant difference was also observed in the 30% decline of eGFR. CONCLUSIONS: Japanese adult patients with nephrotic syndrome showing unclassified segmental lesions as Columbia classification may be equivalent clinical impact as Columbia classification of FSGS.

Validity of "One-size-fits-all" Approaches for the National Health Screening and Education Program: A Large-scale Cohort Study of Corporate Insurance Beneficiaries.

Objective Metabolic syndrome represents a unified condition of atherosclerotic diseases caused by abdominal obesity. The aims of this study were to examine the applicability of the prevalent fixed cut-off values of the abdominal circumference (AC) and body mass index (BMI) to age and gender groups and to identify suitable lifestyle modification factors. Methods We defined an outcome as having ≥ 2 risk components that are necessary to diagnose metabolic syndrome and examined the cross-sectional association of the AC and BMI with the outcome. We also assessed the effects of time-updated lifestyle information on metabolic traits using longitudinal data. Patients We enrolled 22,953 beneficiaries of a corporate health insurance scheme who underwent annual health examinations between January 2004 and December 2014. Results The AC [per 5-cm increase, odds ratio (OR) 1.17, 95% confidence interval (CI) 1.12-1.24] and BMI (OR 1.10, 95% CI 1.07-1.13) were significantly associated with the outcome, adjusted for age, gender, current smoking status, drinking habits, and other lifestyle information. The association between the outcome and AC was modified by gender (p for interaction = 0.033), and the association between the outcome and BMI was modified by age group (p for interaction = 0.049). In the longitudinal analysis, current smoking, drinking habits, and unhealthy eating habits were associated with an increased AC and BMI, whereas regular physical activity was associated with a decreased AC and BMI. Conclusion We showed that the association between the AC or BMI and metabolic syndrome was modified by gender or age group. Further studies will be needed to customize the national health screening and education programs.

Clinical impact of urinary CD11b and CD163 on the renal outcomes of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

BACKGROUND: The detection of leukocyte-derived CD11b (α subunit of integrin Mac-1) and CD163 (scavenger receptor) in urine may reflect renal inflammation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). The objective of this study was to evaluate the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) in ANCA-GN. METHODS: U-CD11b and U-CD163 were examined using enzyme-linked immunosorbent assay in ANCA-GN urine samples from our institutional cohort (n = 88) and a nationwide cohort (n = 138), and their association with renal histology was subsequently analyzed. Logistic regression analyses were performed on a nationwide ANCA cohort to determine the associations of the two urinary molecules with renal remission failure at 6 months or with yearly estimated glomerular filtration rate (eGFR) slope over a 24-month observation period. RESULTS: U-CD11b and U-CD163 were significantly associated with cellular crescent formation and leukocyte accumulation in glomerular crescents. With regard to interstitial inflammation, both levels of U-CD11b and U-CD163 at diagnosis remarkably increased in ANCA-GN compared with the levels observed in nonglomerular kidney disorders including nephrosclerosis, immunoglobulin G4-related disease and tubulointerstitial nephritis; however, the presence of U-CD11b alone was significantly correlated with tubulointerstitial leukocyte infiltrates. Although neither U-CD11b nor U-CD163 at diagnosis was associated with remission failure at 6 months, multivariate analysis demonstrated that the baseline U-CD11b levels were significantly associated with the increase in eGFR following immunosuppressive therapy. CONCLUSIONS: Although both U-CD11b and U-CD163 reflect renal leukocyte accumulation, U-CD11b at diagnosis provides additional clinical value by predicting the recovery rate after the treatment of ANCA-GN.