Gram-negative bacteria remain the leading cause of sepsis, a disease that is consistently in the top 10 causes of death internationally. Curing bacteremia alone does not necessarily end the disease process as other factors may cause inflammatory damage. Bacterial outer membrane vesicles (OMVs) are naturally produced blebs from the outer membrane of gram-negative bacteria, which contain various proteins and lipopolysaccharide (LPS). We hypothesize that these vesicles initiate an inflammatory response independent of the parent bacteria. Outer membrane vesicles were isolated from cultures of Escherichia coli, and the concentration of LPS in the OMVs was measured. Adult male Sprague-Dawley rats were separated into five treatment groups: OMV, 2xOMV, LPS, lactated Ringer's, and sham. Our findings show that infused OMVs elicit physiological, histological, and molecular changes in rats that are consistent with sepsis. Hyperdynamic changes in heart rates and mean arterial pressures are observed as well as the elevation of the proinflammatory cytokines tumor necrosis factor α and interleukin 6. Downstream events such as the recruitment of neutrophils into tissues due to the presentation of vascular adhesion molecules also occur in OMV-treated animals. Although soluble LPS elicits stronger responses than did OMVs, responses to the latter consistently exceeded those associated with lactated Ringer's infusion. These results indicate OMVs, independent of the parent bacteria, do initiate an inflammatory response; however, further studies are required to better characterize the temporal biomolecular interactions involved.

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Background The Coronavirus disease 2019 pandemic placed unprecedented strain on healthcare workers and hospital systems. While healthcare institutions across the nation all faced high census numbers, hospitals in rural settings are often burdened with less resources than their urban counterparts. Therefore, we hypothesized that receiving care in rural settings would be associated with poorer clinical outcomes. Objective To compare the characteristics and outcomes of patients with SARS‐CoV‐2 presenting to urban and rural emergency departments in the American southwest. Methods A multisite retrospective chart review of patients admitted to inpatient care due SARS‐CoV‐2 infection from March 1st, 2020 through January 31st, 2021 was conducted at three participating hospitals. Abstracted data included patient demographics, intake laboratory values, and patient outcomes. Analysis was conducted using descriptive statistics, the Pearson chi‐square for categorical data, the Mann‐Whitney U test for continuous data, and Kaplan‐Myer for disease progression. Results A total of 489 patients with confirmed SARS‐CoV‐2 infection via nasopharyngeal sample were included in the analysis with 57.1% (279/489) presenting to an urban emergency department. Patients admitted in the rural and urban setting showed similar demographics in regard to age (p=0.710), sex (p=0.312), and majority/minority status (p=0.062). Upon presentation, patients in rural settings were more likely to have critically low white blood cell counts (p<0.001), abnormally high hematocrit (p=0.001), and abnormally high aspartate aminotransferase levels (p<0.001) than their urban counterparts. Following admission, urban patients were 2.53 times more likely than rural patients to be transferred to critical care (p<0.001) with the transfer contributing to a reduced hospitalization length of 2.7 days in the urban setting (p=0.002). Rural patients unable to transfer to critical care were 4.95 times more likely to expire than urban patients (p=0.014). Conclusion Patients receiving care for SARS‐CoV‐2 infection in the rural setting often present with more severe clinical profiles and are more likely to experience negative outcomes than their urban counterparts. Rural hospitals should attempt to reduce this discrepancy by developing robust prognostic procedures to minimize critical care bed utilization.