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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 Sepsis is a major public health burden resulting in 25% to 30% in-hospital mortality and accounting for over 20 billion dollars of US hospital costs. Research Question Does hydrocortisone, ascorbic acid, thiamine (HAT) therapy improve clinical outcomes in sepsis and septic shock? Study Design and Methods This was a randomized, double-blinded, placebo-controlled trial conducted from February 2018 to June 2019, assessing an HAT treatment bundle for the management of septic and septic shock patients admitted to an ICU. The primary outcomes were resolution of shock and change in Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes included 28-day mortality, ICU mortality, hospital mortality, procalcitonin clearance (PCT-c), hospital length of stay (LOS), ICU LOS, and ventilator-free days. Results One hundred thirty-seven patients were randomized to the treatment group (n = 68) and comparator group (n = 69), respectively, with no significant differences in baseline characteristics. A statistically significant difference was found in the time patients required vasopressors, indicating quicker reversal of shock in the HAT group compared with the comparator group (27 ± 22 vs 53 ± 38 hours, P Interpretation Our results suggest that the combination of IV ascorbic acid, thiamine, and hydrocortisone significantly reduced the time to resolution of shock. Additional studies are needed to confirm these findings and assess any potential mortality benefit from this treatment. Trial registration ClinicalTrials.gov; No.: NCT03422159; URL: www.clinicaltrials.gov

Background: Retrospective analysis of the transcriptomic host response in sepsis has demonstrated that sepsis can be separated into three endotypes&mdash, 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&ndash, 101, CE score: HR = 15.5 95% CI 1.15&ndash, 211). Kaplan&ndash, 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.

Purpose To compare rim area rates in patients with and without the visual field (VF) progression endpoint in the Canadian Glaucoma Study and determine whether intraocular pressure (IOP) reduction following the endpoint altered rim area rate. Design Prospective multicenter cohort study. Methods setting: University hospitals. patient population: Two hundred and six patients with open-angle glaucoma were examined at 4-month intervals with standard automated perimetry and confocal scanning laser tomography. intervention: After the endpoint, IOP was reduced by ≥20%. outcome measures: Univariate analysis for change in rim area rate and multivariable analysis to adjust for independent covariates (eg, age, sex, and IOP). Results Patients with an endpoint (n = 59) had a worse rim area rate prior to the endpoint compared to those without (n = 147; median [interquartile range]: −14 [−32, 11] × 10 −3 mm 2 /y and −5 [−14, 5] × 10 −3 mm 2 /y, respectively, P = .02). In univariate analysis, there was no difference in rim area rate before and after the endpoint (median difference [95% CI], 8 (−10, 24) × 10 −3 mm 2 /y), but the muItivariate analysis showed that IOP reduction >2 mm Hg after the endpoint was strongly linked to a reduction in rim area rate decline (8 × 10 −3 mm 2 /y for each additional 1 mm Hg reduction). Conclusions Patients with a VF endpoint had a median rim area rate that was nearly 3 times worse than those without an endpoint. Lower mean follow-up IOP was independently associated with a slower decline in rim area.