Background The impact of remdesivir (RDV) on COVID-19 mortality is controversial, and the mortality effect in sub-groups of baseline disease severity has been incompletely explored. The purpose of this study was to assess the association of RDV with mortality in patients with COVID-19. Methods In this retrospective cohort study we compared persons receiving RDV to persons receiving best supportive care (BSC). Patients hospitalized between 2/28/20 – 5/28/20 with laboratory confirmed SARS-CoV-2 infection were included when they developed COVID-19 pneumonia on chest radiography, and hypoxia requiring supplemental oxygen or SpO2 ≤ 94% on room air. The primary outcome was overall survival assessed with time-dependent Cox proportional-hazards regression and multivariable adjustment, including calendar time, baseline patient characteristics, corticosteroid use and effects for hospital. Results 1,138 patients were enrolled including 286 who received RDV, and 852 treated with BSC, 400 of whom received hydroxychloroquine. Corticosteroids were used in 20.4% of the cohort (12.6% in RDV and 23% in BSC). In persons receiving RDV compared to those receiving BSC the HR (95%CI) for death was 0.46 (0.31 – 0.69) in the univariate model, p<0.001 and 0.60 (0.40 – 0.90) in the risk-adjusted model, p=0.014. In the sub-group of persons with baseline use of low-flow oxygen, the HR (95%CI) for death in RDV compared to BSC was 0.63 (0.39 – 1.00), p=0.049. Conclusion Treatment with RDV was associated with lower mortality compared to BSC. These findings remain the same in the subgroup with baseline use of low-flow oxygen.
Listeria monocytogenes is a dangerous bacterium that causes the food-borne disease listeriosis and accounts for nearly 20 % of food-borne deaths. This organism can survive the body's natural defences within the digestive tract, including acidic conditions and bile. Although the bile response has been analysed, limited information is available concerning the ability of L. monocytogenes to resist bile under anaerobic conditions, especially at acidic pH, which mimics conditions within the duodenum. Additionally, it is not known how the bile response varies between serotypes. In this study, the survival of strains representing six serotypes was analysed under aerobic and anaerobic conditions following exposure to bile. Exposure to bile salts at acidic pH increased toxicity of bile, resulting in a significant reduction in survival for all strains tested. However, following this initial reduction, no significant reduction was observed for an additional 2 h except for strain 10403S (P = 0.002). Anaerobic cultivation increased bile resistance, but a significant increase was only observed in virulent strains when exposed to bile at pH 5.5. Exposure to pH 3.0 prior to bile decreased viability amongst avirulent strains in bile in acidic conditions; oxygen availability did not influence viability. Together, the data suggested that being able to sense and respond to oxygen availability may influence the expression of stress response mechanisms, and this response may correspond to disease outcome. Further research is needed on additional strains to determine how L. monocytogenes senses and responds to oxygen and how this varies between invasive and non-invasive strains.
Autoimmune diseases such as psoriasis, rheumatoid arthritis, and systemic lupus erythematosus (SLE) have high rates of hypertension and cardiovascular disease. Systemic lupus erythematosus is a prototypic autoimmune disorder that primarily affects women of childbearing age and is associated with a loss of self‐tolerance, autoreactive B and T lymphocytes, and the production of autoantibodies, especially to nuclear components. In this study, we hypothesized that the pristane‐inducible model of SLE would develop hypertension and vascular dysfunction as the disease progressed. To test this hypothesis, female C57BL/6 mice were administered PBS or pristane. Seven months after pristane administration, mice developed various autoantibodies, including anti‐dsDNA IgG, anti‐ssDNA IgG, and anti‐nRNP IgG, as well as hypergammaglobulinemia. Several other immunological changes, including increased circulating neutrophils and increased CD4−CD8− (double negative) thymocytes were also detected. Mean arterial pressure (MAP) was elevated in pristane‐treated mice when compared to PBS‐treated mice. In addition, second‐order mesenteric arteries from pristine‐treated mice had impaired relaxation to the endothelium‐dependent vasodilator acetylcholine compared to PBS‐treated mice. These data suggest that the immune system dysfunction present in the pristane model of lupus contributes to the development of hypertension and vascular dysfunction.
This study uses the Dahl SS/jr rat as a preclinical model of spontaneous superimposed preeclampsia to demonstrate uncoupling of cerebral vascular permeability and blood-brain barrier disruption from cerebral blood flow autoregulatory dysfunction and myogenic tone. Additionally, the data presented in this study lay the foundational framework on which future experiments assessing specific transcellular transport components such as individual transporter protein expression and components of the vesicular transport system (caveolae) can be built to help reveal a potential direct mechanistic insight into the causes of cerebrovascular complications during preeclamptic pregnancies.
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