Childhood maltreatment and risk of metabolic dysfunction-associated steatotic liver disease - Evidence of sex-specific associations in the general population.

BACKGROUND AND AIMS: Childhood maltreatment (CM) is linked to self-reported liver disease in adulthood. However, specific diagnostic entities, e.g., metabolic dysfunction-associated steatotic liver disease (MASLD) as the most frequent chronic liver disease, and sex-differences have previously not been considered. METHODS: Cross-sectional analyses were conducted in 4188 adults from a population-based cohort in Northeastern Germany after excluding individuals with excessive alcohol consumption, cirrhosis, or chronic viral hepatitis. CM-exposure was assessed using the Childhood Trauma Questionnaire (CTQ). Liver-related outcomes included serologic liver enzymes, fibrosis-4 score (FIB-4) and, in 1863 subjects who underwent magnetic resonance imaging examination, liver fat content. Sex-stratified linear regression and logistic regression models predicting liver-related outcomes and risk for MASLD, respectively, from overall CTQ scores were adjusted for age, school education, alcohol consumption, and waist circumference. Exploratory analyses investigated effects of CTQ-subscales on liver-related outcomes and risk for MASLD. RESULTS: In both sexes, overall CM-exposure was associated with higher levels of serum aspartate aminotransferase and FIB-4 score. In men, effects were mainly driven by physical abuse, and in women by emotional neglect. Only in men, overall CM-exposure (ß = 0.70, 95%-CI 0.26-1.13, p = 0.002) and four CTQ-subscales were associated with greater liver fat content, and physical abuse (aOR = 1.22, 95%-CI 1.02-1.46, p = 0.034) and physical neglect (aOR = 1.25, 95%-CI 1.04-1.49, p = 0.015) were associated with higher risk for MASLD. CONCLUSIONS: These results suggest sex differences in the association between CM and objective serum and imaging markers of MASLD in adulthood. For men especially, a history of CM-exposure may increase risk of developing MASLD in adulthood.

Prednisolone Versus Colchicine for Acute Gout in Primary Care: statistical analysis plan for the pragmatic, multicenter, randomized, and double-blinded COPAGO non-inferiority trial.

BACKGROUND: To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. STUDY DESIGN: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. STATISTICAL ANALYSIS PLAN: N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0-10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients' global assessment of treatment success are secondary outcomes. DISCUSSION: The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).

Sex-specific associations of childhood maltreatment with obesity-related traits - The Study of Health in Pomerania (SHIP).

BACKGROUND: Child maltreatment (CM) is linked to obesity in adulthood. However, sex-differences and direct measurements of body fat have previously been insufficiently considered in this context. OBJECTIVE: To assess sex-specific associations of CM with anthropometric markers of overweight/obesity and direct measures of body fat. PARTICIPANTS AND SETTING: Analyses were conducted in 4006 adults from a population-based cohort in Northeastern Germany (SHIP-TREND-0). METHODS: CM was assessed using the Childhood Trauma Questionnaire (CTQ). Obesity-related traits included anthropometric indicators (i.e., height, weight, body mass index [BMI], waist [WC] and hip circumference [HC], waist-to-hip ratio [WHR], waist-to-height ratio [WHtR]), fat mass (FM) and fat-free mass (FFM) derived from bioelectrical impedance analysis (BIA), and subcutaneous (SAT) and visceral adipose tissue (VAT) ascertained using magnetic resonance imaging (MRI). Sex-stratified linear regression models predicting obesity-related traits from total CTQ scores were adjusted for age and education. Exploratory analyses investigated effects of CTQ subscales on obesity-related traits. RESULTS: In men, CM was positively associated with WHtR (ß = 0.04; p = .030) and VAT (ß = 0.02; p = .031) and inversely with body height (ß = -0.05; p = .010). In women, CM-exposure was positively associated with body weight (ß = 0.07; p = .018), BMI (ß = 0.03; p = .013), WC (ß = 0.07; p = .005), HC (ß = 0.05; p = .046), WHR (ß = 0.03; p = .015), WHtR (ß = 0.04; p = .006), FM (ß = 0.04; p = .006), and SAT (ß = 0.06; p = .041). In both sexes, effects were mainly driven by exposure to emotional and physical abuse. CONCLUSIONS: Results suggest that associations between CM-exposure and obesity-related traits in adulthood are primarily present in women. This may have implications for sex-specific obesity-related cardiometabolic risk after CM.

Complement Activation in Nephrotic Glomerular Diseases.

The nephrotic syndrome holds significant clinical importance and is characterized by a substantial protein loss in the urine. Damage to the glomerular basement membrane or podocytes frequently underlies renal protein loss. There is an increasing belief in the involvement of the complement system, a part of the innate immune system, in these conditions. Understanding the interactions between the complement system and glomerular structures continually evolves, challenging the traditional view of the blood-urine barrier as a passive filter. Clinical studies suggest that a precise inhibition of the complement system at various points may soon become feasible. However, a thorough understanding of current knowledge is imperative for planning future therapies in nephrotic glomerular diseases such as membranous glomerulopathy, membranoproliferative glomerulonephritis, lupus nephritis, focal segmental glomerulosclerosis, and minimal change disease. This review provides an overview of the complement system, its interactions with glomerular structures, and insights into specific glomerular diseases exhibiting a nephrotic course. Additionally, we explore new diagnostic tools and future therapeutic approaches.

Age- and Sex-Specific Reference Values for Renal Volume and Association with Risk Factors for Chronic Kidney Disease in a General Population-An MRI-Based Study.

BACKGROUND: Renal volume (RV) is associated with renal function and with a variety of cardiovascular risk factors (CVRFs). We analysed RV using magnetic resonance imaging (MRI) in a large population-based study (Study of Health in Pomerania; SHIP-TREND) to find sex- and age-specific reference values for RV and to test the influence of several markers on RV. The main objective is to describe reference values for RV in people from the general population without kidney disease. METHODS: 1815 participants without kidney disease (930 women) aged 21-81 years were included in our study. Right and left RV with and without body surface area (BSA) indexation were compared among three age groups (22-39 years, 40-59 years, 60-81 years) by median and interquartile range and tested separately in women and men. RESULTS: The estimated glomerular filtration rate (eGFR), serum uric acid, and right and left RV were higher in men compared to women (all p < 0.001). Left kidneys were larger than right kidneys (both sexes). With age, RV showed a continuously decreasing trend in women and an upside-down U-shaped relation in men. In multivariable linear regression models, current smoking (ß = 14.96, 95% CI 12.12; 17.79), BSA (ß = 97.66, 95% CI 90.4; 104.93), diastolic blood pressure (ß = 0.17, 95% CI 0.01; 0.32), and eGFR (ß = 0.57, 95% CI 0.50; 0.65) were positively associated with both left and right RV, whereas uric acid (ß = -0.03, 95% CI -0.05; -0.01) showed an inverse association with RV. Interestingly, the same eGFR correlated with higher RV in men compared to women. CONCLUSION: Reference values for RV are different for age groups and sex. For any given age, female kidneys are smaller than male kidneys. RV associates positively with eGFR, but for any chosen eGFR, renal volume in females is lower compared to males. RV decreases with age, but in men showed a U-shaped correlation. This may reflect hyperfiltration and glomerular hypertrophy associated with the presence of CVRF in middle-aged males.

Generation of a human induced pluripotent stem cell line (UMGACBi001-A) from urine cells of a chronic kidney disease patient with hypertension, diabetic nephropathy and acute sepsis.

Chronic kidney disease is a major public health burden associated with a drastically reduced quality of living and life span that lacks suitable, individualized therapeutic strategies. Here we present a human induced pluripotent stem cell line (iPSC, UMGACBi001-A) reprogrammed from urine cells of an acute septic dialysis patient suffering from chronic kidney disease using non-integrating administration of RNAs. The generated iPSCs were positively characterized for typical morphology, pluripotency marker expression, directed differentiation potential, non-contamination, chromosomal consistency and donor identity. This iPSC-line can be a useful source for in vitro disease modelling and individualized therapeutic approaches.