Daily Endocrinology Research Analysis

BACKGROUND: Xenotransplantation of porcine cells, tissues or organs offers a promising strategy to address the critical shortage of human donor organs. However, cross-species pathogen transmission, instant blood-mediated inflammatory reaction (IBMIR)-related liver injury, chronic over-immunosuppression, and long-term safety remain major challenges in porcine islet xenotransplantation. In this study, we performed a clinical trial aimed to evaluate the biosafety of neonatal porcine islet xenotransplantation in patients with type 1 diabetes. METHODS: Ten recipients were assigned to two groups receiving non-encapsulated neonatal islet cell clusters via the jugular-hepatic-portal vein at mean doses of 6354 ± 835 IEQ/kg and 11 600 ± 1100 IEQ/kg, respectively. Donor pigs originated from a highly inbred, PERV-C-negative colony reared in designated pathogen-free (DPF) conditions, with rigorous pathogen and PERV screening. Immunosuppression included mycophenolate mofetil, tacrolimus, belatacept, and autologous regulatory T-cell therapy, combined with tocilizumab. Continuous low-dose heparin was infused via a portal vein catheter was used for 7 days as anticoagulation therapy. Recipients and spouses were monitored for over 5 years, with 7 followed for more than 10 years. RESULTS: No PERV transmission or transplant-related infections were detected in any recipient or contact during long-term follow-up. The procedure was safe and well-tolerated, with only transient liver function and coagulation changes and mild adverse events. Both groups showed reduced exogenous insulin requirements and markedly lower hypoglycemia incidence, with better glucose control in the higher-dose group. CONCLUSION: This study demonstrates that DPF PERV-C-free neonatal porcine islet xenotransplantation is biologically safe and partially effective, supporting its value as a reliable donor source and foundational platform for advancing clinical islet xenotransplantation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03162237.

Fundus imaging enables noninvasive, high-resolution visualization of the retinal microvasculature. Advances in artificial intelligence (AI) now allow for extraction of quantitative vascular metrics from retinal images, offering new opportunities for identifying systemic health biomarkers. This study sought to characterize retinal microvascular features in a large healthy population and assess their associations with diverse clinical phenotypes and evaluate their ability to predict incident cardiovascular events. We analyzed fundus photographs from 8,467 healthy individuals aged 40-70 years enrolled in the Human Phenotype Project. For external validation we used fundus images from 16,249 participants from UK Biobank. Using an automated AI-based tool (AutoMorph), we extracted 12 quantitative vascular metrics, such as vessel density, average width, fractal dimension, distance tortuosity, and curvature tortuosity, separately for arteries and veins. We derived age- and sex-stratified reference values and evaluated associations with clinical parameters spanning cardiometabolic, respiratory, and behavioral domains. Retinal vascular features demonstrated strong age- and sex-related patterns. Multiple significant associations were observed between microvascular metrics and systemic traits. Arterial features were particularly associated with cardiometabolic factors including blood pressure, lipid profiles, glycemic indices, and body composition (body mass index, fat mass), as well as sleep apnea parameters. Findings replicated in UK Biobank and demonstrated prognostic value for incident cardiovascular events. This large-scale, AI-driven study provides normative data on retinal vascular traits and supports the utility of fundus imaging for systemic risk stratification and prediction of cardiovascular events. Our findings highlight the potential of retinal biomarkers for early detection and monitoring of cardiometabolic and sleep-related conditions, reinforcing the emerging role of oculomics in predictive and preventive health care.

CONTEXT: Previous studies on mortality outcomes in patients with chronic hypoparathyroidism have reported inconsistent results. OBJECTIVE: To assess all-cause and cause-specific mortality and estimate the prevalence of chronic hypoparathyroidism in Sweden. METHODS: Chronic hypoparathyroidism was defined as the combination of ICD-10 diagnoses and long-term dispensations of active vitamin D. Nationwide diagnostic codes, drug dispensation and mortality data were obtained from the National Patient Register, Prescribed Drugs Register, Cause of Death Register, and the Total Population Register. Mortality was compared between groups using Cox proportional hazards models, adjusting for age and baseline comorbidities. RESULTS: We identified 1,982 individuals with chronic hypoparathyroidism between 1997 and 2018, yielding a minimum prevalence of 19.4 per 100,000 inhabitants. We randomly selected 19,820 controls matched by age, sex and county of residence. After excluding individuals with baseline thyroid cancer and their controls, 1,825 patients and 17,922 controls remained. Patients had higher all-cause mortality than controls (HR 1.55; 95% CI: 1.40-1.72). Mortality was higher in patients with nonsurgical (HR 2.16, 95% CI: 1.76-2.65) than postsurgical hypoparathyroidism (HR 1.39, 95% CI: 1.23-1.58). The strongest associations were observed for endocrine, nutritional and metabolic disorders (HR 6.46, 95% CI: 2.43-17.21), followed by infectious diseases (HR 3.53, 95% CI: 2.07-6.04), genitourinary diseases (HR 2.40, 95% CI: 1.33-4.33), respiratory diseases (HR 1.67, 95% CI: 1.23-2.28), and circulatory diseases (HR 1.47, 95% CI: 1.23-1.77). CONCLUSION: Patients with chronic hypoparathyroidism have an elevated risk of all-cause mortality, particularly those with nonsurgical disease. These findings highlight the clinical burden of the disease.