Epelbaum, Oleg

AbstractCorticosteroid dosing in the range of 0.5–2 mg/kg/day of methylprednisolone equivalents has become a standard part of the management of intensive care unit (ICU) patients with COVID‐19 pneumonia based on positive results of randomized trials and a meta‐analysis. Alongside such conventional dosing, administration of 1 gm of methylprednisolone daily (pulse dosing) has also been reported in the literature with claims of favorable outcomes. Comparisons between such disparate approaches to corticosteroids for Coronavirus disease 2019 (COVID‐19) pneumonia are lacking. In this retrospective study of patients admitted to the ICU with COVID‐19 pneumonia, we compared patients treated with 0.5–2 mg/kg/day in methylprednisolone equivalents (high‐dose corticosteroids) and patients treated with 1 gm of methylprednisolone (pulse‐dose corticosteroids) to those who did not receive any corticosteroids. The endpoints of interest were hospital mortality, ICU‐free days at Day 28, and complications potentially attributable to corticosteroids. Pulse‐dose corticosteroid therapy was associated with a significant increase in ICU‐free days at Day 28 compared to no receipt: adjusted relative risk (aRR): 1.45 (95% confidence interval [CI]: 1.05–2.02; p = 0.03) and compared with high‐dose corticosteroid administration (p = 0.003). Nonetheless, receipt of high‐dose corticosteroids—but not of pulse‐dose corticosteroids—significantly reduced the odds of hospital mortality compared to no receipt: adjusted Odds ratio (aOR) 0.31 (95% CI: 0.12–0.77; p = 0.01). High‐dose corticosteroids reduced mortality compared to pulse‐dose corticosteroids (p = 0.04). Pulse‐dose corticosteroids—but not high‐dose corticosteroids—significantly increased the odds of acute kidney injury requiring renal replacement therapy compared to no receipt: aOR 3.53 (95% CI: 1.27–9.82; p = 0.02). The odds of this complication were also significantly higher in the pulse‐dose group when compared to the high‐dose group (p = 0.05 for the comparison). In this single‐center study, pulse‐dose corticosteroid therapy for COVID‐19 pneumonia in the ICU was associated with an increase in ICU‐free days but failed to impact hospital mortality, perhaps because of its association with development of severe renal failure. In line with existing trial data, the effect of high‐dose corticosteroids on mortality was favorable.

Abstract Rationale Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings. Objectives To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), β-d-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis). Methods Studies were selected and appraised by pairs of reviewers. Bivariate random effects meta-analysis was used to generate pooled sensitivity, specificity, and diagnostic likelihood ratios. Results Serum GM in patients with impaired immunity suspected of having IA had sensitivity of 0.71 (95% confidence interval [CI], 0.64–0.78) and specificity of 0.89 (95% CI, 0.84–0.92). A cutoff of 1 optical density index yielded optimal sensitivity and specificity. BAL GM in patients with impaired immunity suspected of having IA had sensitivity of 0.84 (95% CI, 0.73–0.91) and specificity of 0.88 (95% CI, 0.81–0.91). Serum or whole-blood PCR in immunocompromised patients with suspected IA had sensitivity of 0.81 (95% CI, 0.73–0.86) and specificity of 0.79 (95% CI, 0.68–0.86). BAL PCR in patients at high risk for IA had high sensitivity of 0.90 (95% CI, 0.77–0.96) and specificity of 0.96 (95% CI, 0.93–0.98) for diagnosing IA. β-d-glucan assay in patients in the intensive care unit at risk for invasive candidiasis or candidemia had sensitivity of 0.81 (95% CI, 0.74–0.86) and specificity of 0.60 (95% CI, 0.49–0.71). Data on diagnostic accuracy of antigen detection and serology testing for endemic mycoses were limited and heterogeneous (varied according to test, patient immunity, and suspected endemic disease). Conclusions The diagnosis of invasive fungal infections remains a challenge. Various serum and BAL markers can aid in diagnosis. This evidence supports the development of clinical practice recommendations by the American Thoracic Society.