RESUMO
Skeletal muscle health and function is a critical determinant of clinical outcomes in patients with peripheral arterial disease (PAD). Herein, we identify fatty infiltration, the ectopic deposition of adipocytes in skeletal muscle, as a histological hallmark of end-stage PAD, also known as chronic limb threatening ischemia (CLTI). Leveraging single cell transcriptome mapping in mouse models of PAD, we identify a pro-adipogenic mesenchymal stromal cell population marked by expression of Vcam1 (termed Vcam1+ FAPs) that expands in the ischemic limb. Mechanistically, we identify Sfrp1 and Nr3c1 as regulators of Vcam1+ FAP adipogenic differentiation. Loss of Sfrp1 and Nr3c1 impair Vcam1+ FAP differentiation into adipocytes in vitro . Finally, we show that Vcam1+ FAPs are enriched in human CLTI patients. Collectively, our results identify a pro-adipogenic FAP subpopulation in CLTI patients and provide a potential therapeutic target for muscle regeneration in PAD.
RESUMO
BACKGROUND: Short-Stay Emergency Department Observation Units (OU) are an alternative to hospitalization, but data on OU care of pediatric poisoning exposures is limited. We report the experience of a pediatric OU with this population. METHODS: We retrospectively reviewed the charts of children with poison exposure admitted to a pediatric OU during a 30-month period. Data was collected pertaining to demographics, type of exposure, clinical presentation, and rate of hospitalization, and was compared to nonpoisoned OU patients. RESULTS: Of the 91 pediatric patients with poison exposure, 86 complete charts were available for review (94.5%). Of these patients, 49.5% were female, and 82.4% were <6 years of age (range 1.5 months to 16.6 years). There were a total of 98 toxicants implicated, the most common of which were psychoactive drugs (25%) and cardiovascular agents (19%). At OU admission, 33 of 88 patients (38%) had altered mental status or abnormal vital signs. Only 2 of the 53 remaining patients developed abnormal vital signs within the OU. Two patients were hospitalized unexpectedly with respiratory distress due to hydrocarbon and charcoal aspiration pneumonitis, respectively; the unexpected hospitalization rate was 2.2%. Three more planned hospitalizations for endoscopy or psychiatric evaluation led to a total hospitalization rate of 5.4%. This hospitalization rate is significantly lower (RR=0.26, 95% CI=0.11-0.62) than the hospitalization rate from the OU for nonpoisoned patients (20.3%) during that time. Mean OU length of stay for nonadmitted poisoned patients was 14.35 hours. There were no adverse events noted as a result of OU placement. CONCLUSION: Select poisoned pediatric patients appear suitable for OU management and had less frequent unexpected hospitalization from the OU than other diagnoses.
