A Wrong Fate Decision in Adipose Stem Cells upon Obesity.

Progress has been made in identifying stem cell aging as a pathological manifestation of a variety of diseases, including obesity. Adipose stem cells (ASCs) play a core role in adipocyte turnover, which maintains tissue homeostasis. Given aberrant lineage determination as a feature of stem cell aging, failure in adipogenesis is a culprit of adipose hypertrophy, resulting in adiposopathy and related complications. In this review, we elucidate how ASC fails in entering adipogenic lineage, with a specific focus on extracellular signaling pathways, epigenetic drift, metabolic reprogramming, and mechanical stretch. Nonetheless, such detrimental alternations can be reversed by guiding ASCs towards adipogenesis. Considering the pathological role of ASC aging in obesity, targeting adipogenesis as an anti-obesity treatment will be a key area of future research, and a strategy to rejuvenate tissue stem cell will be capable of alleviating metabolic syndrome.

Cardiovascular Outcomes and Hospitalizations in Asian Patients Receiving Immune Checkpoint Inhibitors: A Population-based Study.

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013 and 2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analyzed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval: 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days' stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations were cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI.