Matthew Hutter | PubMed Health

PubMed2025

The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity.

We characterized circulating extracellular vesicles (EVs) in obese and lean humans, identifying transcriptional cargo differentially expressed in obesity (277 unique genes; false discovery rate < 10%). Since circulating EVs may have broad origin, we compared this obesity EV transcriptome with expression from human visceral-adipose-tissue-derived EVs from freshly collected and cultured biopsies from the same obese individuals, observing high concordance. Using a comprehensive set of adipose-specific epigenomic and chromatin conformation assays, we found that the differentially expressed transcripts from the EVs were those regulated in adipose by body mass index-associated SNPs (p < 5 × 10-8) from a large-scale genome-wide association study (GWAS). Using a phenome-wide association study of the regulatory SNPs for the EV-derived transcripts, we identified a substantial enrichment for inflammatory phenotypes, including type 2 diabetes. Collectively, these findings represent the convergence of the GWAS (genetics), epigenomics (transcript regulation), and EV (liquid biopsy) fields, enabling powerful future genomic studies of complex diseases.

Humans↗

PubMedDate not supplied

Residents report on adverse events and their causes.

BACKGROUND: Resident physicians are frontline providers with a unique vantage point from which to comment on patient safety-related events. METHODS: We surveyed trainees at 2 teaching hospitals about experiences with adverse events (AEs), mistakes, and near misses, as well as the potential causes. RESULTS: Responses were obtained from 821 (57%) of 1440 eligible trainees. Analysis was restricted to 689 clinical trainees. More than half (55%) reported ever caring for a patient who had an AE. The most common types of AEs were procedural and medication related. More than two thirds of AEs were considered significant. Of the most recent AEs, 24% were attributed to mistakes. The most common reasons for mistakes, as perceived by residents, were excessive work hours (19%), inadequate supervision (20%), and problems with handoffs (15%). In the last week, 114 respondents (18%) reported having a patient with an AE; of these, 42 (37%) reported AEs involving a mistake for which they considered themselves responsible. In addition, 141 (23%) reported near-miss incidents in the last week for which they considered themselves responsible. In multivariate analyses, significant predictors of AEs in the last week were inpatient rotation, duty hours in the last week, and procedural specialty. Predictors of near-miss errors in the last week were inpatient rotation, days of fatigue in the last month, and postgraduate year 1 status. CONCLUSIONS: These findings support the perception that AEs are commonly encountered by physicians and often associated with errors. Causes of errors in teaching hospitals appear to be multifactorial, and a variety of measures are necessary to improve safety. Eliciting residents' perspectives is important because residents may perceive events, actions, and causal relationships that medical record reviewers or observers cannot.

Fatigue↗