Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.

AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19.

BACKGROUND: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT). METHODS: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients. RESULTS: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission. CONCLUSIONS: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

d-dimer and Death in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: Hypercoagulability may be a key mechanism for acute organ injury and death in patients with severe coronavirus disease 2019, but the relationship between elevated plasma levels of d-dimer, a biomarker of coagulation activation, and mortality has not been rigorously studied. We examined the independent association between d-dimer and death in critically ill patients with coronavirus disease 2019. DESIGN: Multicenter cohort study. SETTING: ICUs at 68 hospitals across the United States. PATIENTS: Critically ill adults with coronavirus disease 2019 admitted to ICUs between March 4, 2020, and May 25, 2020, with a measured d-dimer concentration on ICU day 1 or 2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was the highest normalized d-dimer level (assessed in four categories: < 2×, 2-3.9×, 4-7.9×, and ≥ 8× the upper limit of normal) on ICU day 1 or 2. The primary endpoint was 28-day mortality. Multivariable logistic regression was used to adjust for confounders. Among 3,418 patients (63.1% male; median age 62 yr [interquartile range, 52-71 yr]), 3,352 (93.6%) had a d-dimer concentration above the upper limit of normal. A total of 1,180 patients (34.5%) died within 28 days. Patients in the highest compared with lowest d-dimer category had a 3.11-fold higher odds of death (95% CI, 2.56-3.77) in univariate analyses, decreasing to a 1.81-fold increased odds of death (95% CI, 1.43-2.28) after multivariable adjustment for demographics, comorbidities, and illness severity. Further adjustment for therapeutic anticoagulation did not meaningfully attenuate this relationship (odds ratio, 1.73; 95% CI, 1.36-2.19). CONCLUSIONS: In a large multicenter cohort study of critically ill patients with coronavirus disease 2019, higher d-dimer levels were independently associated with a greater risk of death.

Early Trends in Bronchoscopic Lung Volume Reduction: A Systematic Review and Meta-analysis of Efficacy Parameters.

INTRODUCTION: The goal of our systematic review and meta-analysis is to examine the therapeutic effectiveness of bronchoscopic lung volume reduction (BLVR), and to compare it with medical management and lung volume reduction surgery. METHODS: Variables of interest were absolute change in FEV1, 6MWT, and SGRQ. Meta-analysis was performed for the BLVR modalities with ≥3 trials. Of the 18 shortlisted publications, only valves (four trials; n = 159) and coils (six trials; n = 194) qualified for meta-analysis. To avoid redundant reporting for valves, only the data for intact fissure subjects were analyzed. Outcome data are presented as the mean difference from baseline with 95% confidence interval at 6-months follow-up. RESULTS: For BLVR using valves, the pooled mean difference (PMD) for FEV1 was 0.146 L (95% CI 0.111-0.181; p < 0.001), 6MWT was 45.225 meters (95% CI 26.954-63.495; p < 0.001), and SGRQ was -8.825 points (95% CI -14.824 to -2.825; p = 0.004). All the PMDs were statistically significant and higher than their respective minimal clinically important difference (MCID). For BLVR using coils, the PMD for FEV1 was 0.080 L (95% CI 0.057-0.104; p < 0.001), 6MWT was 45.320 meters (95% CI 28.040-62.600; p < 0.001), and SGRQ was -10.570 points (95% CI -13.299 to -7.841; p < 0.001). All three variables showed statistically significant PMDs but that for FEV1 was smaller than the MCID. Data from BLVR modalities with <3 major publications are reviewed in the discussion section. CONCLUSIONS: BLVR offers early promise in the palliation of advanced emphysema. Better characterization of patients to identify phenotypes that will derive sustained benefit is needed.

The lung microbiome and exacerbations of COPD.

PURPOSE OF REVIEW: Traditional culture methods have identified airway bacterial pathogens that cause acute exacerbations of chronic obstructive pulmonary disease (COPD), and contribute to airway inflammation and COPD progression. However, conventional microbiology is limited by low sensitivity and bias toward predetermined and predominant pathogens. Highly sensitive, unbiased microbiome techniques overcome these limitations. Here, we present recent lung microbiome data, specifically in the context of smoking, COPD, and exacerbations. RECENT FINDINGS: In contrast to the sterile lung environment found with conventional microbiology, microbiome techniques demonstrate a lower respiratory tract microbiome in health. Alterations in the lung microbiome with smoking and COPD have been clearly demonstrated by culture techniques, however, the findings in microbiome studies are limited and controversial. Increasing COPD disease severity is associated with a reduction in microbial diversity. Though microbial community structure does not change with exacerbation, there are notable changes in its composition. Antibiotic and corticosteroid treatment of acute exacerbations of COPD have significant but opposing effects on microbiome composition. SUMMARY: The composition of the lung microbiome changes with smoking, the severity of COPD, during acute exacerbations and with the use of steroids and/or antibiotics. Understanding the role of the microbiome in disease progression and development of exacerbations will lead to novel therapies.

A Systematic Review and Meta-Analysis of Randomized Controlled Trials on Supine vs. Nonsupine Endotracheal Intubation.

Background: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to compare the safety and efficacy of supine vs. nonsupine positions during intubation. Methods: Based on the literature from inception to October 2020, 13 studies with nonemergent intubation in supine and nonsupine positions were chosen using PRISMA and MOOSE protocols. Pooled estimates were calculated using random-effects models with 95% confidence interval (CI). The primary outcome was a successful intubation, attempt, and duration of intubation. The secondary outcome was adverse events (trauma and hypoxia). Bias was evaluated qualitatively, by visual analysis, and quantitatively through the Egger test. Results: The final analysis included 13 clinical trials with 1,916 patients. The pooled success rates in the supine vs. lateral positions were 99.21% and 98.82%. The supine vs. semierect positions were 99.21% and 98.82%. The 1st attempt success rate in the supine vs. lateral position was 85.35% and 88.56% compared to 91.38% and 90.76% for the supine vs. semierect position. The rate of total adverse events in the supine position was 3.73% vs. 6.74% in the lateral position, and the rate of total adverse events in the supine position was 0.44% vs. 0.93% in semierect position. Low to substantial heterogeneity was noted in our analysis. Discussion. There is no significant difference between total successful intubations and success from 1st intubation attempt between supine and nonsupine positions. However, there are slightly higher rates of adverse events in nonsupine position. Addition of more recent studies on supine vs. nonsupine intubations would improve this study. Given these findings, it is important to develop more studies regarding different intubation positions and techniques with the aim of improving efficacy and decreasing adverse outcomes. Other. This review is not registered in a public database. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Endobronchial lipoma causing progressive dyspnea.

We describe a 63-year-old male who presented with progressive exertional dyspnea, post-obstructive pneumonia and chest CT findings of an endobronchial lesion. Bronchoscopy revealed an endobronchial lipoma, which was resected using snare electrocautery. Complete resolution of the patient's symptoms was noted following bronchoscopic resection.