Emergency Medical Services Prehospital Response to the COVID-19 Pandemic in the US: A Brief Literature Review.

This study aimed to analyze prehospital Emergency Medical Services (EMS) response to the COVID-19 pandemic in the US through a brief systematic review of available literature in context with international prehospital counterparts. An exploration of the NCBI repository was performed using a search string of relevant keywords which returned n=5128 results; articles that met the inclusion criteria (n=77) were reviewed and analyzed in accordance with PRISMA and PROSPERO recommendations. Methodical quality was assessed using critical appraisal tools, and the Egger's test was used for risk of bias reduction upon linear regression analysis of a funnel plot. Sources of heterogeneity as defined by P < 0.10 or I^2 > 50% were interrogated. Findings were considered within ten domains: structural/systemic; clinical outcomes; clinical assessment; treatment; special populations; dispatch/activation; education; mental health; perspectives/experiences; and transport. Findings suggest, EMS clinicians have likely made significant and unmeasured contributions to care during the pandemic via nontraditional roles, ie, COVID-19 testing and vaccine deployment. EMS plays a critical role in counteracting the COVID-19 pandemic in addition to the worsening opioid epidemic, both of which disproportionately impact patients of color. As such, being uniquely influential on clinical outcomes, these providers may benefit from standardized education on care and access disparities such as racial identity. Access to distance learning continuing education opportunities may increase rates of provider recertification. Additionally, there is a high prevalence of vaccine hesitancy among surveyed nationally registered EMS providers. Continued rigorous investigation on the impact of COVID-19 on EMS systems and personnel is warranted to ensure informed preparation for future pandemic and infectious disease responses.

SOAT1 promotes mevalonate pathway dependency in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies are needed. Altered metabolism is a cancer vulnerability, and several metabolic pathways have been shown to promote PDAC. However, the changes in cholesterol metabolism and their role during PDAC progression remain largely unknown. Here we used organoid and mouse models to determine the drivers of altered cholesterol metabolism in PDAC and the consequences of its disruption on tumor progression. We identified sterol O-acyltransferase 1 (SOAT1) as a key player in sustaining the mevalonate pathway by converting cholesterol to inert cholesterol esters, thereby preventing the negative feedback elicited by unesterified cholesterol. Genetic targeting of Soat1 impairs cell proliferation in vitro and tumor progression in vivo and reveals a mevalonate pathway dependency in p53 mutant PDAC cells that have undergone p53 loss of heterozygosity (LOH). In contrast, pancreatic organoids lacking p53 mutation and p53 LOH are insensitive to SOAT1 loss, indicating a potential therapeutic window for inhibiting SOAT1 in PDAC.