INTRODUCTION: No reports on both blood and fecal bile acids (BAs) in patients with nonalcoholic fatty liver disease (NAFLD) exist. We simultaneously assessed the serum and fecal BA patterns in healthy participants and those with NAFLD. METHODS: We collected stool samples from 287 participants from 5 hospitals in Japan (healthy control [HC]: n = 88; mild fibrosis: n = 104; and advanced fibrosis group: n = 95). Blood samples were collected and analyzed for serum BAs and 7α-hydroxy-4-cholesten-3-one (C4)—a surrogate marker for BA synthesis ability—from 141 patients. Concentrations of BAs, including cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid, ursodeoxycholic acid, and lithocholic acid (LCA), were measured using liquid chromatography-mass spectrometry. RESULTS: The total fecal BA concentration was significantly higher in the NAFLD group with worsening of fibrosis than in the HC group. Most of the fecal BAs were secondary and unconjugated. In the fecal BA fraction, CA, DCA, chenodeoxycholic acid, ursodeoxycholic acid, and LCA were significantly higher in the NAFLD than in the HC group. The total serum BA concentration was higher in the NAFLD group with worsening of fibrosis than in the HC group. In the serum BA fraction, CA, LCA, and C4 concentrations were significantly higher in the NAFLD than in the HC group. DISCUSSION: Fecal and serum BA and C4 concentrations were high in patients with NAFLD with worsening of fibrosis, suggesting involvement of abnormal BA metabolism in NAFLD with fibrosis progression. Abnormalities in BA metabolism may be a therapeutic target in NAFLD with fibrosis.

ObjectivesContinuity of care is a core dimension of primary care, and better continuity is associated with better patient outcomes. Therefore, care fragmentation can be an indicator to assess the quality of primary care, especially in countries without formal gatekeeping system, such as Japan. Thus, this study aimed to describe care fragmentation among older adults in an ageing city in Japan.DesignCross-sectional study.SettingThe most populated basic municipality in Japan.ParticipantsOlder adults aged 75 years and older.InterventionsThis study used a health claims database, including older adults who visited medical facilities at least four times a year in an urban city in Japan. The Fragmentation of Care Index (FCI) was used as an indicator of fragmentation. The FCI was developed from the Continuity of Care Index and is based on the total number of visits, different institutions visited and proportion of visits to each institution. We employed Tobit regression analysis to examine the association between the FCI and age, sex, type of insurance and most frequently visited facility.ResultsThe total number of participants was 413 600. The median age of the study population was 81 years, and 41.6% were men. The study population visited an average of 3.42 clinics/hospitals, and the maximum number of visited institutions was 20. The proportion of patients with FCI >0 was 85.0%, with a mean of 0.583. Multivariable analysis showed that patients receiving public assistance had a lower FCI compared with patients not receiving public assistance, with a coefficient of 0.137.ConclusionsTo our knowledge, this is the first study to demonstrate care fragmentation in Japan. Over 80% of the participants visited two or more medical facilities, and their mean FCI was 0.583. The FCI could be a basic indicator for assessing the quality of primary care.

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Background: Renin suppression in primary aldosteronism indicates mineralocorticoid receptor activation via excessive aldosterone secretion, inducing renal damage. We investigated whether the reversal of renin suppression after the initiation of mineralocorticoid receptor antagonist therapy was associated with long-term renal outcomes in medically treated patients with primary aldosteronism. Methods: This retrospective cohort study included 318 patients with primary aldosteronism treated with mineralocorticoid receptor antagonist between 2008 and 2020 at the Yokohama Rosai Hospital in Japan. The posttreatment renin status was defined as unsuppressed (ie, reversal of renin suppression) when individual plasma renin activity after the initiation of mineralocorticoid receptor antagonist (post-plasma renin activity) was ≥1.0 ng/(mL h); otherwise, it was defined as suppressed. We analyzed the association of posttreatment renin status with subsequent longitudinal estimated glomerular filtration rate changes using linear mixed-effects models for repeated measurements, adjusting for potential confounders. Results: The posttreatment renin status of 119 patients was unsuppressed (median post-plasma renin activity, 1.7 ng/[mL h]) and that of 199 patients was suppressed (median post-PRA, 0.5 ng/[mL h]). Through the median follow-up period of 3.1 years, the decline in estimated glomerular filtration rate was milder among patients with the unsuppressed posttreatment renin (−0.46 [95% CI, −0.63 to −0.28] mL/min per 1.73 m 2 per year) than those with suppressed posttreatment renin (−1.41 [95% CI, −1.56 to −1.27] mL/min per 1.73 m 2 per year; difference, 0.96 [95% CI, 0.72–1.20] mL/min per 1.73 m 2 per year). Conclusions: Our findings may highlight the importance of reversing renin suppression with optimal mineralocorticoid receptor antagonist titration in medically treated primary aldosteronism, which could mitigate adverse renal outcomes.

Background We aimed to investigate the impact of a fourth dose of BNT162b2 vaccine (Comirnaty®, Pfizer-BioNTech) on anti-SARS-CoV-2 (anti-S IgG) antibody titers in patients receiving hemodialysis (HD) and healthcare workers (HCWs). Methods A multi-institutional retrospective study at five dialysis clinics in Japan was conducted using 238 HD patients and 58 HCW controls who received four doses of the BNT162b2 mRNA vaccine. Anti-S IgG titers were measured at 1, 3, and 6 months after the second dose, at 1 and 5/6 months after the third dose, and at 1 month after the fourth dose of vaccine. Results The log anti-S IgG titers of the HD patients after the second vaccination were significantly lower than those of the control group, but equalized 1 month after the third vaccination: 9.94 (95% CI 9.82–10.10) vs. 9.81 (95% CI 9.66–9.96), ( P = 0.32). In both groups, the fold-increase in anti-S IgG titers was significantly lower after the fourth dose than after the third dose of vaccine. In addition, there was a strong negative correlation between antibody titers 1 month after the fourth vaccination and antibody titers immediately before the vaccination. In both groups, the waning rate of anti-S IgG titers from the post-vaccination peak level after the third vaccine dose was significantly slower than that after the second dose. Conclusions These findings suggest that the humoral immune response was blunted after the fourth dose of the conventional BNT162b2 vaccine. However, multiple vaccinations could extend the window of humoral immune protection.