Inter-rater reliability and prognostic value of baseline Radiographic Assessment of Lung Edema (RALE) scores in observational cohort studies of inpatients with COVID-19.

OBJECTIVES: To reliably quantify the radiographic severity of COVID-19 pneumonia with the Radiographic Assessment of Lung Edema (RALE) score on clinical chest X-rays among inpatients and examine the prognostic value of baseline RALE scores on COVID-19 clinical outcomes. SETTING: Hospitalised patients with COVID-19 in dedicated wards and intensive care units from two different hospital systems. PARTICIPANTS: 425 patients with COVID-19 in a discovery data set and 415 patients in a validation data set. PRIMARY AND SECONDARY OUTCOMES: We measured inter-rater reliability for RALE score annotations by different reviewers and examined for associations of consensus RALE scores with the level of respiratory support, demographics, physiologic variables, applied therapies, plasma host-response biomarkers, SARS-CoV-2 RNA load and clinical outcomes. RESULTS: Inter-rater agreement for RALE scores improved from fair to excellent following reviewer training and feedback (intraclass correlation coefficient of 0.85 vs 0.93, respectively). In the discovery cohort, the required level of respiratory support at the time of CXR acquisition (supplemental oxygen or non-invasive ventilation (n=178); invasive-mechanical ventilation (n=234), extracorporeal membrane oxygenation (n=13)) was significantly associated with RALE scores (median (IQR): 20.0 (14.1-26.7), 26.0 (20.5-34.0) and 44.5 (34.5-48.0), respectively, p<0.0001). Among invasively ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, soluble receptor of advanced glycation end-products and soluble tumour necrosis factor receptor 1 (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted HR 1.04 (1.02-1.07), p=0.002). We replicated the significant associations of RALE scores with baseline disease severity and mortality in the independent validation data set. CONCLUSIONS: With a reproducible method to measure radiographic severity in COVID-19, we found significant associations with clinical and physiologic severity, host inflammation and clinical outcomes. The incorporation of radiographic severity assessments in clinical decision-making may provide important guidance for prognostication and treatment allocation in COVID-19.

Right Heart Thrombi: Patient Outcomes by Treatment Modality and Predictors of Mortality: A Pooled Analysis.

RATIONALE: Right heart thrombi (RiHT) is characterized by the presence of thrombus within the right atrium or right ventricle (RV). Current literature suggests pulmonary embolism (PE) with RiHT carries a high mortality. Guidelines lack recommendations in managing RiHT. We created a pooled analysis on RiHT and report on our institutional experience in managing RiHT. We aimed to evaluate whether patient characteristics and differing treatment modalities predict mortality. METHODS: We created a pooled analysis of case reports and series of patients with RiHT and PE between January 1956 and 2017. We also reviewed a series of consecutive patients with RiHT identified from our institutional PE registry. Age, shock, RV dysfunction, clot mobility, treatment modality, and hospital outcome had to be reported. RESULTS: We identified 316 patients in our pooled analysis. Patients received the following therapies: no treatment 15 (5%), systemic anticoagulation 73 (23%), systemic thrombolysis 108 (34%), surgical embolectomy 101 (32%), catheter-directed therapy 11 (3%), and systemic thrombolysis with surgery 8 (3%). In-hospital mortality was 18.7%. Univariate analysis showed age and shock reduced odds of survival. Multivariate analysis showed shock reduced odds of survival (odds ratios [OR] 0.36, 95% confidence interval [CI]: 0.19-0.72, P ≤ .01) while age, RV dysfunction, and clot-mobility did not affect mortality. In a reduced multivariate analysis adjusting for shock, treatment modality, and clot location alone, systemic thrombolysis increased odds of survival when compared to systemic anticoagulation (OR 2.72, 95% CI: 1.11-6.64, P = .02). Our institutional series identified 18 patients, where in-hospital mortality was 22.2%, 18 (100%) had RV dysfunction, and 5 (28%) had shock. Patients received the following therapies: systemic anticoagulation 8 (44.4%), systemic thrombolysis 4 (22.2%), surgical embolectomy 4 (22.2%), and catheter-directed thrombolysis 2 (11.1%). CONCLUSION: Presence of shock in RiHT is an independent predictor of mortality. Systemic thrombolysis may offer increased odds of survival when compared to systemic anticoagulation. Our findings should be interpreted with caution as they derive from retrospective reports and subject to publication bias.

Association Between CD4+, Viral Load, and Pulmonary Function in HIV.

PURPOSE: The antiretroviral therapy era has shifted the epidemiology of HIV-associated diseases, increasing the recognition of non-infectious pulmonary complications secondary to HIV. We aimed to determine the association between CD4+, viral load, and pulmonary function in individuals with uncontrolled HIV, and determine how changes in these parameters are associated with pulmonary function longitudinally. METHODS: This is a retrospective observational study of individuals with HIV who underwent pulmonary function testing in an urban medical center between August 1997 and November 2015. RESULTS: Of the 146 participants (mean age 52 ± 10 years), 49% were Hispanic, 56% were men, and 44% were current smokers. CD4+ <200 cells/µl was associated with significant diffusion impairment compared to CD4+ ≥200 cells/µl (DLCO 56 vs. 70%, p = <0.01). VL (viral load) ≥75 copies/ml was associated with significant diffusion impairment compared to VL <75 copies/ml (DLCO 60 vs. 71%, p = <0.01). No difference in FEV1, FEV1/FVC, or TLC was noted between groups. In univariate analysis, CD4+ and VL correlated with DLCO (r = +0.33; p = <0.01; r = -0.26; p = <0.01) and no correlation was noted with FEV1, FEV1/FVC, or TLC. Current smoking and history of AIDS correlated with DLCO (r = -0.20; p = 0.03; r = -0.20; p = 0.04). After adjusting for smoking and other confounders, VL ≥75 copies/ml correlated with a 11.2 (CI 95% [3.03-19.4], p = <0.01) decrease in DLCO. In Spearman's Rank correlation, there was a negative correlation between change in VL and change in DLCO over time (ρ = -0.47; p = <0.01). CONCLUSION: The presence of viremia in individuals with HIV is independently associated with impaired DLCO. Suppression of VL may allow for recovery in diffusing capacity over time, though the degree to which this occurs requires further investigation.