Tuning the Thromboinflammatory Response to Venous Flow Interruption by the Ectonucleotidase CD39.

Objective- Leukocyte flux contributes to thrombus formation in deep veins under pathological conditions, but mechanisms that inhibit venous thrombosis are incompletely understood. Ectonucleotide di(tri)phosphohydrolase 1 ( ENTPD1 or Cd39), an ectoenzyme that catabolizes extracellular adenine nucleotides, is embedded on the surface of endothelial cells and leukocytes. We hypothesized that under venous stasis conditions, CD39 regulates inflammation at the vein:blood interface in a murine model of deep vein thrombosis. Approach and Results- CD39-null mice developed significantly larger venous thrombi under venous stasis, with more leukocyte recruitment compared with wild-type mice. Gene expression profiling of wild-type and Cd39-null mice revealed 76 differentially expressed inflammatory genes that were significantly upregulated in Cd39-deleted mice after venous thrombosis, and validation experiments confirmed high expression of several key inflammatory mediators. P-selectin, known to have proximal involvement in venous inflammatory and thrombotic events, was upregulated in Cd39-null mice. Inferior vena caval ligation resulted in thrombosis and a corresponding increase in both P-selectin and VWF (von Willebrand Factor) levels which were strikingly higher in mice lacking the Cd39 gene. These mice also manifest an increase in circulating platelet-leukocyte heteroaggregates suggesting heterotypic crosstalk between coagulation and inflammatory systems, which is amplified in the absence of CD39. Conclusions- These data suggest that CD39 mitigates the venous thromboinflammatory response to flow interruption.

Emergency Department Patient Experiences During the COVID-19 Pandemic.

Emergency department (ED) utilization changed notably during the coronavirus disease 2019 (COVID-19) pandemic in the United States. The purpose of the study was to gain a more thorough understanding of ED patient experience during the early stages of the COVID-19 pandemic. This study used the consensual qualitative approach to analyze open-ended responses from post-ED patient experience surveys from February through July 2020. Comments were included in the analysis if they pertained to care during the pandemic (eg, mentioned "the virus," "masks," "PPE"). A total of 242 COVID-specific comments from 192 unique patients were analyzed (median age 49 years; 69% female). Six themes were identified: visually observed changes, experiences of process changes, expressions of understanding or appreciation, sense of security, COVID-19 disease-specific comments, and "classic" satisfaction comments that align with previous literature on patient experience. The COVID-19 pandemic has challenged health care systems across the world in unique and unprecedented ways. This study identified six themes that better elucidate ED patient experience during an unprecedented public health crisis.