Objectives: To study the impact of sex on the clinical presentation of IgG4-related disease (IgG4-RD). Methods: We prospectively enrolled 403 newly diagnosed IgG4-RD patients. We compared the demographic features, clinical manifestations, organ involvement, laboratory tests and treatment outcomes between female and male patients. The organs involved were divided into superficial organs (salivary glands, lacrimal glands, orbit, sinus and skin) and internal organs (all the other organs). The patients treated with glucocorticoids with or without additional immunosuppressants were included in the assessment of treatment outcomes, and potential confounding factors were corrected by propensity score matching or multivariate Cox regression analysis. Results: Female patients showed younger age at both symptom onset and diagnosis, and a longer interval between symptom onset and diagnosis. Allergy history, Mikulicz’s disease and thyroiditis were more common in female patients, while autoimmune pancreatitis, sclerosing cholangitis and retroperitoneal fibrosis were more common in male patients. In accordance, female patients more frequently presented with superficial organ involvement, while male patients more frequently had internal organ involvement, and the discrepancy was more prominent in the patients with older age. Male sex was associated with higher peripheral eosinophils, CRP and IgG4 levels at baseline. In response to glucocorticoid-based therapies, male sex was associated with a higher IgG4-RD responder index during follow-up as well as a greater risk of relapse (hazard ratio 3.14, P = 0.003). Conclusion: Our study revealed the sex disparities in clinical characteristics of IgG4-RD, and indicated that male sex was independently associated with worse prognosis in response to glucocorticoid-based therapies.

Background: The prevalence of hyperuricemia, gout, and heart failure (HF) is on the rise, and these conditions often share similar risk factors. The present study aimed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. Methods: The data on nonpregnant participants aged ≥ 20 years with or without hyperuricemia, gout, and HF from the National Health and Nutrition Examination Survey 2001–2018 and 2007–2018 were included in this study. The binary logistic regression, Kaplan–Meier curve, Cox proportional-hazards model, and restricted cubic spline analysis were employed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. Results: Of 204,179,060 and 223,702,171 weighted eligible participants, 40,044,228 (19.6%) and 9,158,600 (4.1%) had hyperuricemia and gout, respectively. Older age, diabetes, stroke, and coronary artery disease were the risk factors for HF among patients with hyperuricemia and gout. The median survival time was 7.00 years and 6.25 years and the 5-year survival rate was 59.9% and 55.9% for patients with HF and hyperuricemia and those with HF and gout, respectively. Patients with hyperuricemia or gout were 2.46 and 2.35 times more likely to have HF and 1.37 and 1.45 times more likely to experience all-cause mortality compared with those who did not exhibit these conditions. The restricted cubic spline showed a nonlinear correlation between uric acid levels and HF and a J-shaped correlation between uric acid levels and all-cause mortality. Conclusions: Ambulatory patients with hyperuricemia or gout were more likely to have HF compared with those without hyperuricemia or gout. Patients with HF with hyperuricemia or gout were more likely to experience all-cause mortality in the long-term follow-up.

Purpose: Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We aimed to summarize the disease characteristics and to explore factors associated with disease outcome. Methods: A systematic literature review of AIGA associated disease was conducted. Serum-positive cases with detailed clinical presentations, treatment protocols, and outcomes were included. The patients were categorized into controlled and uncontrolled groups based on their documented clinical outcome. Factors associated with disease outcome were analyzed with logistic regression models. Results: A total of 195 AIGA patients were retrospectively analyzed, with 119(61.0%) having controlled disease and 76 (39.0%) having uncontrolled disease. The median time to diagnosis and disease course were 12 months and 28 months, respectively. A total of 358 pathogens have been reported with nontubercular mycobacterium (NTM) and Talaromyces marneffei as the most common pathogens. The recurrence rate was as high as 56.0%. The effective rates of antibiotics alone, antibiotics with rituximab, and antibiotics with cyclophosphamide were 40.5%, 73.5%, and 75%, respectively. In the multivariate logistic analysis, skin involvement, NTM infection, and recurrent infections remained significantly associated with disease control, with ORs of 3.25 (95% CI 1.187 ~ 8.909, P value = 0.022), 4.74 (95% CI 1.300 ~ 17.30, P value = 0.018), and 0.22 (95% CI 0.086 ~ 0.551, P value = 0.001), respectively. The patients with disease control had significant AIGA titer reduction. Conclusions: AIGA could cause severe opportunistic infections with unsatisfactory control, particularly in patients with recurrent infections. Efforts should be made to closely monitor the disease and regulate the immune system.

Background: Cardiac, renal, and metabolic (CRM) conditions are major causes of morbidity and mortality globally. This study aims to explore the relationship between serum uric acid (SUA), hyperuricemia, gout, and CRM conditions in middle‐aged and elderly populations. Methods: Sample 1 included participants from CHARLS (China Health and Retirement Longitudinal Study, n=9341), and Sample 2 from NHANES (National Health and Nutrition Examination Survey, unweighted n=17 913; weighted n=115 646 390). Ordinal logistic regression, Cox regression, and restricted cubic spline analyses were used to assess the relationship between SUA, hyperuricemia, gout, and CRM conditions. A 2‐sample Mendelian randomization analysis was conducted to explore causal associations between SUA and CRM conditions. Results: In both samples, SUA, hyperuricemia, and gout were positively correlated with the risk of CRM conditions. Among participants with 3 or ≥1 CRM condition(s), SUA, asymptomatic hyperuricemia, and gout with poorly controlled hyperuricemia showed significant positive associations with all‐cause mortality, whereas these associations were not observed in patients with gout with normal SUA levels. The restricted cubic spline analysis revealed a positive relationship between SUA levels and the risk of all‐cause mortality in participants with ≥1 CRM condition(s), demonstrating a nonlinear dose–response relationship across both samples ( P for nonlinearity <0.05). Mendelian randomization analysis indicated that SUA was causally associated with cardiovascular disease, chronic kidney disease, and diabetes. Conclusions: Hyperuricemia and gout are strong predictors of increased prevalence and mortality of CRM conditions, emphasizing the importance of managing hyperuricemia and gout in these patients.

Purpose: The results of previous studies on the relationship between serum 25-hydroxyvitamin D [25(OH)D] and hyperuricemia are controversial. We hypothesized that serum 25(OH)D concentrations of U.S. adults would negatively correlate with the risk of hyperuricemia. Method: Data came from the National Health and Nutrition Examination Survey 2007–2014 were used, after excluding those who met at least one of the exclusion criteria, a total of 9096 male individuals and 9500 female individuals aged 18 years or older were included. Binary logistic regression analysis and restricted cubic spline with fully adjusted confounding factors were applied to evaluate the association between serum 25(OH)D and hyperuricemia. We further performed stratified analysis and sensitivity analysis to minimize the influence of gender, metabolic syndrome, obesity and renal dysfunction on the above association. Results: We found a negative correlation between serum 25(OH)D and hyperuricemia. In the binary logistic regression analysis, compared with the highest serum 25(OH)D quartile [Q4: 25(OH)D > 77.10 nmol/L] group, the odds ratios (95% confidence intervals) in the lowest quartile [Q1: 25(OH)D ≤ 43.20 nmol/L] was 1.46 (1.22–1.75) in the fully adjusted model. Restricted cubic spline analysis showed L-shaped and non-linear relationships between 25(OH)D and hyperuricemia. In sensitivity analysis, after restricting to participants without significant renal dysfunction and obesity, the above association remained significant. After restricting to participants who were diagnosed as metabolic syndrome, above association remained significant in the fully adjusted model. In stratified analysis by gender, the association remained significant among males and females. Conclusions: Serum 25(OH)D might be inversely associated with hyperuricemia in general U.S. adults. From our study, for people with unexplained hyperuricemia, screening for serum Vitamin D concentration might be necessary.

Background: Previous studies have suggested that the possible relationship between serum uric acid (SUA) and testosterone. However, the results of previous studies are controversial and there is limited evidence examining the relationship between SUA and testosterone in a general US population of men. The objective of this study is to explore the correlation of SUA and testosterone among adult males from the US. Methods: Data from the National Health and Nutrition Examination Survey 2011–2016 were used, including a total of 7,796 male participants aged 18 years or older and excluding those lacking serum testosterone and uric acid data. Clinical characteristics of the participants among different SUA groups and testosterone groups are compared. Univariate and multivariate linear regression analyses were applied to evaluate the association between SUA and testosterone. Results: We found an inverse association between SUA and testosterone after fully adjusted the potential confounding factors in general US adult males. In the multivariate linear regression analysis, we found that increasing age (estimate testosterone percent difference: −0.20% per year, P<0.01), uric acid (estimate testosterone percent difference: −4.40% per md/dL, P<0.01) and BMI (estimate testosterone percent difference: −2.86% per kg/m2, P<0.01) were associated with declining serum testosterone. This association remained significant in sensitivity analysis, while in the stratified analysis, above association was not significant in men with diabetes or aged 65 and over. Conclusions: SUA levels might be negatively associated with serum testosterone in adult males.