Objective: Atherosclerosis is a chronic inflammatory process induced by the influx and entrapment of excess lipoproteins into the intima media of arteries. Previously, our lab demonstrated that systemic PTP1B inhibition protects against atherosclerosis in preclinical LDLR^−/− models. Similarly, it was shown that myeloid-specific PTP1B ablation decreases plaque formation and ameliorates dyslipidaemia in the ApoE^−/− model of atherosclerosis. We hypothesized that the relevant improvements in dyslipidaemia following modification of PTP1B activation may either result from changes in hepatic cholesterol biosynthesis and/or increased uptake and degradation by liver-resident macrophages. We examined this in animal models and patients with coronary artery disease. Methods: In this study, we determined the cholesterol-lowering effect of myeloid-PTP1B deletion in mice fed a high-fat high-cholesterol diet and examined effects on total cholesterol levels and lipoprotein profiles. We also determined the effects of PTP1B inhibition to oxLDL-C challenge on foam cell formation and cholesterol efflux in human monocytes/macrophages. Results: We present evidence that myeloid-PTP1B deficiency significantly increases the affinity of Kupffer cells for ApoB containing lipoproteins, in an IL10-dependent manner. We also demonstrate that PTP1B inhibitor, MSI-1436, treatment decreased foam cell formation in Thp1-derived macrophages and increased macrophage cholesterol efflux to HDL in an AMPK-dependent manner. We present evidence of three novel and distinct mechanisms regulated by PTP1B: an increase in cholesterol efflux from foam cells, decreased uptake of lipoproteins into intra-lesion macrophages in vitro and a decrease of circulating LDL-C and VLDL-C in vivo. Conclusions: Overall, these results suggest that myeloid-PTP1B inhibition has atheroprotective effects through improved cholesterol handling in atherosclerotic lesions, as well as increased reverse cholesterol transport. Trial registration Research registry, researchregistry 3235. Registered 07 November 2017, https://www.researchregistry.com/browse-the-registry#home/registrationdetails/5a01d0fce7e1904e93e0aac5/.

Background/Objectives: Kidney injury is a frequent complication of multiple myeloma (MM) and monoclonal gammopathies. Podocyte stress markers, such as urinary nephrin and podocin, have been studied in other renal diseases but their utility in paraprotein-related kidney disease remains unclear. This pilot study investigated the association of urinary nephrin and podocin levels with albuminuria and biopsy-proven podocytopathy in patients with paraprotein-related diseases. Methods: We retrospectively analyzed 75 patients with plasma cell dyscrasias, including MM and MGRS, along with 11 healthy controls. Urinary podocin and nephrin mRNA levels were measured using qPCR, and urinary podocin protein levels were quantified via ELISA. Associations were assessed between these biomarkers and urinary protein-to-creatinine ratio (uPCR), albumin-to-creatinine ratio (uACR), and histologically confirmed podocytopathia. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Results: Higher urinary podocin protein levels were significantly associated with lower uACR (p = 0.007) and uPCR (p = 0.026). Neither podocin nor nephrin mRNA showed significant associations with proteinuria metrics. ROC analysis indicated that podocin ELISA (AUC = 0.350) and podocin mRNA (AUC = 0.510) lacked diagnostic accuracy for predicting renal involvement. The presence of urinary tract infection (UTI) was a significant confounder, leading to increased levels of podocin and nephrin mRNA. Conclusions: Urinary podocin shows a trend toward elevation in MM/MGRS patients with histological podocyte injury. The study revealed an unexpected inverse association between urinary podocin and albuminuria, suggesting complex release kinetics or stage mismatches in this population. Given the confounding effect of UTIs, and the pilot nature of this study, further research is required to validate these podocyte proteins as biomarkers in paraprotein-related kidney disease.

The relationship between body compartments and lung function including lung volumes as well as the effects of aging on this relationship remains to be explored. The aim of this study is to evaluate the association between appendicular lean mass index (ALMI), lean mass index (LMI), fat mass index (FMI), and visceral adipose tissue index (VATI) on spirometric and body plethysmographic lung function in the adult and elderly population. This observational, cross-sectional study used data from 10.616 adults (≥18-82 years) from the prospective population-based LEAD cohort, conducted between 2011 and 2022 in Vienna, Austria. In total, 1923 participants were elderly (age >65 years). Body compartments were measured by dual-energy X-ray absorptiometry scans and indexed by height squared to account for differences related to body height. Lung function was measured by spirometry (forced expiratory volume in the 1st second; FEV1 and forced vital capacity; FVC) and by body plethysmography (total lung capacity; TLC, fractional residual capacity; FRC, and residual volume; RV). In the overall study population, ALMI was positively associated with FEV1, FVC and TLC and negatively with RV and FRC. In contrast, VATI showed a negative association with all lung function parameters investigated. These effects can also be found in the elderly population. The present study confirms significant associations between body compartments and lung function in adults and in elderly and shows the need to consider body compartments in the assessment and interpretation of lung function results.

Background: The EASO and Lancet Commission (LDEC) recently proposed modern anthropometric frameworks for the diagnosis of obesity. Objective: To evaluate the efficacy of the novel EASO and LDEC anthropometric criteria against standard WHO BMI criteria for identifying individuals with prevalent cardiometabolic impairment, and to establish DEXA-derived reference values for fat mass index (FMI) and visceral adipose tissue index (VATI). Subjects/Methods: We analyzed 10,296 Austrian LEAD study participants. Obesity was classified using WHO (BMI ≥30 kg/m²), EASO, and LDEC criteria. Body composition was assessed via DEXA. Associations with cardiometabolic outcomes were evaluated using logistic regression and ROC analyses. Results: Obesity prevalence was 16.3% (WHO), 44.1% (LDEC), and 50.4% (EASO). EASO and LDEC criteria identified younger individuals and more females than WHO criteria, demonstrating stronger associations with metabolic syndrome (EASO OR: 6.61, 95% CI: 5.81-7.45; LDEC OR: 6.49, 95% CI: 5.78-7.26) compared to WHO (OR: 4.89, 95% CI: 4.31-5.53). FMI showed the highest discriminatory power across all definitions (AUC ≥ 0.92). Conclusion: The anthropometric EASO and LDEC criteria outperform BMI in identifying individuals with prevalent cardiometabolic dysfunction. The established FMI and VATI thresholds provide actionable clinical reference values, supporting a shift toward body composition-focused obesity diagnosis and management.

Background/Objectives: Kidney injury is a frequent complication of multiple myeloma (MM) and monoclonal gammopathies. Podocyte stress markers, such as urinary nephrin and podocin, have been studied in other renal diseases but their utility in paraprotein-related kidney disease remains unclear. This pilot study investigated the association of urinary nephrin and podocin levels with albuminuria and biopsy-proven podocytopathy in patients paraprotein-related diseases. Methods: We retrospectively analyzed 75 patients with plasma cell dyscrasias including MM and MGRS and 11 healthy controls. Urinary podocin and nephrin mRNA levels were measured using qPCR, and urinary podocin protein levels were quantified via ELISA. Associations were assessed between these biomarkers and urinary pro-tein-to-creatinine ratio (uPCR), albumin-to-creatinine ratio (uACR), and histologically confirmed podocytopathia. Diagnostic performance was evaluated using Receiver Op-erating Characteristic (ROC) analysis. Results: Higher urinary podocin protein levels were significantly associated with lower uACR (p=0.007) and uPCR (p=0.026). Neither podocin nor nephrin mRNA showed sig-nificant associations with proteinuria metrics. ROC analysis indicated that podocin ELISA (AUC=0.350) and podocin mRNA (AUC=0.510) lacked diagnostic accuracy for predicting renal involvement. The presence of urinary tract infection (UTI) was a sig-nificant confounder, leading to increased levels of podocin and nephrin mRNA. Conclusions: Urinary podocin shows a trend toward elevation in MM/MGRS patients with histological podocyte injury. The study revealed an unexpected inverse association between urinary podocin and albuminuria, suggesting complex release kinetics or stage mismatches in this population. Given the confounding effect of UTIs and the pilot na-ture of this study, further research is required to validate these podocyte proteins as prognostic biomarkers in paraprotein-related kidney disease.