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Background: Retrospective analysis of the transcriptomic host response in sepsis has demonstrated that sepsis can be separated into three endotypes—inflammatory (IE), adaptive (AE), and coagulopathic (CE), which have demonstrated prognostic significance. We undertook a prospective transcriptomic host response analysis in a subgroup of patients enrolled in the Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis (ORANGES) trial. Methods: Blood was obtained from 51 patients and profiled using a pre-established 33-mRNA classifier to determine sepsis endotypes. Endotypes were compared to therapy subgroups and clinical outcomes. Results: We redemonstrated a statistically significant difference in mortality between IE, AE, and CE patients, with CE patients demonstrating the highest mortality (40%), and AE patients the lowest mortality (5%, p = 0.032). A higher CE score was a predictor of mortality; coronary artery disease (CAD) and elevated CE scores were associated with an increase in mortality (CAD: HR = 12.3, 95% CI 1.5–101; CE score: HR = 15.5 95% CI 1.15–211). Kaplan–Meier (KM) analysis of the entire cohort (n = 51) demonstrated a decrease survival in the CE group, p = 0.026. KM survival analysis of hydrocortisone, ascorbic acid, and thiamine (HAT) therapy and control patients not receiving steroids (n = 45) showed CE and IE was associated with a decrease in survival (p = 0.003); of interest, there was no difference in survival in CE patients after stratifying by HAT therapy (p = 0.18). These findings suggest a possible treatment effect of corticosteroids, HAT therapy, endotype, and outcome. Conclusion: This subset of patients from the ORANGES trial confirmed previous retrospective findings that a 33-mRNA classifier can group patients into IE, AE, and CE endotypes having prognostic significance. A novel finding of this study identifying an association between endotype and corticosteroid therapy warrants further study in support of future diagnostic use of the endotyping classifier.

In the early 2000s, there were a significant number of closures in the nursing home industry. This paper analyzes the effect of rural nursing home closure on the quality of care provided by the nursing homes in the market that do not close. We develop a theoretical model that shows that the direction of quality change after a closure is dependent on how quality enters the demand and cost functions. Quality changes for competitor facilities that remained open and are within 15 miles of the closure are compared to quality changes in a comparison group of facilities that are further away. Overall, the quality of care provided by competitor facilities improved after the closure. These improvements are likely because of efficiency gains in the competitor facilities due to economies of scale. From a quality perspective, the potential increase in market power caused by a nursing home closure may not be a concern if the closure occurs in an area that has lower occupancy rates than the national average.

BACKGROUND Our understanding of the severe acute respiratory syndrome coronavirus 2 has evolved since the first reported cases in December 2019, and a greater emphasis has been placed on the hyper-inflammatory response in severely ill patients. The purpose of this study was to determine risk factors for mortality and the impact of anti-inflammatory therapies on survival. AIM To determine the impact of various therapies on outcomes in severe coronavirus disease 2019 patients with a focus on anti-inflammatory and immune-modulating agents. METHODS A retrospective analysis was conducted on 261 patients admitted or transferred to the intensive care unit in two community hospitals between March 12, 2020 and June 17, 2020. Totally 167 patients received glucocorticoid (GC) therapy. Seventy-three patients received GC alone, 94 received GC and tocilizumab, 28 received tocilizumab monotherapy, and 66 received no anti-inflammatory therapy. RESULTS Patient survival was associated with GC use, either alone or with tocilizumab, and decreased vasopressor requirements. Delayed administration of GC was found to decrease the survival benefit of GC therapy. No difference in survival was found with varying anticoagulant doses, convalescent plasma, tocilizumab monotherapy; prone ventilation, hydroxychloroquine, azithromycin, or intravenous ascorbic acid use. CONCLUSION This analysis demonstrated the survival benefit associated with anti-inflammatory therapy of GC, with or without tocilizumab, with the combination providing the most benefit. More studies are needed to assess the optimal timing of anti-inflammatory therapy initiation.

Background: Acute kidney injury (AKI) is a common complication in patients with severe COVID-19. Methods: We retrospectively reviewed 249 patients admitted to an intensive care unit (ICU) during the first wave of the pandemic to determine risk factors for AKI. Demographics, comorbidities, and clinical and outcome variables were obtained from electronic medical records. Results: Univariate analysis revealed older age, higher admission serum creatinine, elevated Sequential Organ Failure Assessment (SOFA) score, elevated admission D-Dimer, elevated CRP on day 2, mechanical ventilation, vasopressor requirement, and azithromycin usage as significant risk factors for AKI. Multivariate analysis demonstrated that higher admission creatinine (p = 0.0001, OR = 2.41, 95% CI = 1.56–3.70), vasopressor requirement (p = 0.0001, OR = 3.20, 95% CI = 1.69–5.98), elevated admission D-Dimer (p = 0.008, OR = 1.0001, 95% CI = 1.000–1.001), and elevated C-reactive protein (CRP) on day 2 (p = 0.033, OR = 1.0001, 95% CI = 1.004–1.009) were independent risk factors. Conversely, the combined use of Tocilizumab and corticosteroids was independently associated with reduced AKI risk (p = 0.0009, OR = 0.437, 95% CI = 0.23–0.81). Conclusion: This study confirms the high rate of AKI and associated mortality among COVID-19 patients admitted to ICUs and suggests a role for inflammation and/or coagulopathy in AKI development. One should consider the possibility that early administration of anti-inflammatory agents, as is now routinely conducted in the management of COVID-19-associated acute respiratory distress syndrome, may improve clinical outcomes in patients with AKI.