INTRODUCTION: Chest imaging is necessary for diagnosis of COVID-19 pneumonia, but current risk stratification tools do not consider radiographic severity. We quantified radiographic heterogeneity among inpatients with COVID-19 with the Radiographic Assessment of Lung Edema (RALE) score on Chest X-rays (CXRs). METHODS: We performed independent RALE scoring by ≥2 reviewers on baseline CXRs from 425 inpatients with COVID-19 (discovery dataset), we recorded clinical variables and outcomes, and measured plasma host-response biomarkers and SARS-CoV-2 RNA load from subjects with available biospecimens. RESULTS: We found excellent inter-rater agreement for RALE scores (intraclass correlation co-efficient=0.93). The required level of respiratory support at the time of baseline CXRs (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 [interquartile range]: 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, sRAGE and TNFR1 levels (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted hazard ratio 1.04[1.02-1.07], p=0.002). We validated significant associations of RALE scores with baseline severity and mortality in an independent dataset of 415 COVID-19 inpatients. CONCLUSION: Reproducible assessment of radiographic severity revealed significant associations with clinical and physiologic severity, host-response biomarkers and clinical outcome in COVID-19 pneumonia. Incorporation of radiographic severity assessments may provide prognostic and treatment allocation guidance in patients hospitalized with COVID-19.
ObjectivesTo 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.SettingHospitalised patients with COVID-19 in dedicated wards and intensive care units from two different hospital systems.Participants425 patients with COVID-19 in a discovery data set and 415 patients in a validation data set.Primary and secondary outcomesWe 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.ResultsInter-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.ConclusionsWith 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.
e19053 Background: Ruxolitinib, an elective Janus Kinase (JAK) 1/2 inhibitor, has been approved by FDA for the treatment of steroid-refractory chronic graft-versus-host-disease (SR cGVHD) after the failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. However, it remains underutilized despite promising results in the treatment of SR cGVHD. Methods: We did a comprehensive literature search across various data sets, including PubMed, Cochrane, and Embase, and presented data in ASH and ASCO. A review of the most recent data is summarized in this abstract. Results: Two retrospective cohort studies and one pilot prospective study evaluated ruxolitinib in SR cGVHD. In a retrospective cohort study by Yang et al., 36 patients with SR cGVHD treated with ruxolitinib showed complete response (CR) in 27.8% of patients with complete disappearance of cGVHD symptoms and partial response (PR) with symptom relief of 52.7% at a dose of 2.5 to 10 mg two times daily with ruxolitinib tapering one week after symptoms improvement. In the pilot prospective study by Mozo et al., 12 pediatric patients with SR cGVHD received ruxolitinib at a dose of 2.5 to 10 mg two times daily and showed CR in 8.3% of patients and PR in 82.7% of patients. Morozova et al. conducted a prospective pilot study in 20 patients with primary or secondary myelofibrosis who were treated with pre-transplant ruxolitinib 45 mg/day from ruxolitinib (45 mg) starting from seven days before transplant to 2 days before the transplant, and 15 mg from day five after transplant to day 100 after transplant along with cyclophosphamide 50 mg/kg on days three and four after transplant. PR was observed in 47.1% of patients at 6 months with the incidence of cGVHD of 20%. In Phase III trial by Zeiser et al. reported CR of 6.7% and PR of 43% in 165 patients treated with ruxolitinib at a dose of 10 mg daily for 6 cycles (28 days/cycle). The most common all-grade adverse events are listed here. Conclusions: Ruxolitinib was recently approved by FDA for the treatment of SR GVHD and should be utilized more due to its high effectiveness and tolerable safety profile.[Table: see text]
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.