This study aimed to develop risk scores based on clinical characteristics at presentation to predict intensive care unit (ICU) admission and mortality in COVID-19 patients. 641 hospitalized patients with laboratory-confirmed COVID-19 were selected from 4997 persons under investigation. We performed a retrospective review of medical records of demographics, comorbidities and laboratory tests at the initial presentation. Primary outcomes were ICU admission and death. Logistic regression was used to identify independent clinical variables predicting the two outcomes. The model was validated by splitting the data into 70% for training and 30% for testing. Performance accuracy was evaluated using area under the curve (AUC) of the receiver operating characteristic analysis (ROC). Five significant variables predicting ICU admission were lactate dehydrogenase, procalcitonin, pulse oxygen saturation, smoking history, and lymphocyte count. Seven significant variables predicting mortality were heart failure, procalcitonin, lactate dehydrogenase, chronic obstructive pulmonary disease, pulse oxygen saturation, heart rate, and age. The mortality group uniquely contained cardiopulmonary variables. The risk score model yielded good accuracy with an AUC of 0.74 ([95% CI, 0.63-0.85], p = 0.001) for predicting ICU admission and 0.83 ([95% CI, 0.73-0.92], p<0.001) for predicting mortality for the testing dataset. This study identified key independent clinical variables that predicted ICU admission and mortality associated with COVID-19. This risk score system may prove useful for frontline physicians in clinical decision-making under time-sensitive and resource-constrained environment.
Background There is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. Methods We conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up. Results We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively.The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (8 vs. 5 days, p < 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.41; 95% CI [0.22 – 0.77]). Conclusion An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.
Genome-wide association studies have reported eleven regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10−5). For three cis-eQTL associations (P<1.4×10−3, FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6×10−10 for risk variants (P<10−4) within 10kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
Background The large volume and suboptimal image quality of portable chest X-rays (CXRs) as a result of the COVID-19 pandemic could post significant challenges for radiologists and frontline physicians. Deep-learning artificial intelligent (AI) methods have the potential to help improve diagnostic efficiency and accuracy for reading portable CXRs. Purpose The study aimed at developing an AI imaging analysis tool to classify COVID-19 lung infection based on portable CXRs. Materials and methods Public datasets of COVID-19 (N = 130), bacterial pneumonia (N = 145), non-COVID-19 viral pneumonia (N = 145), and normal (N = 138) CXRs were analyzed. Texture and morphological features were extracted. Five supervised machine-learning AI algorithms were used to classify COVID-19 from other conditions. Two-class and multi-class classification were performed. Statistical analysis was done using unpaired two-tailed t tests with unequal variance between groups. Performance of classification models used the receiver-operating characteristic (ROC) curve analysis. Results For the two-class classification, the accuracy, sensitivity and specificity were, respectively, 100%, 100%, and 100% for COVID-19 vs normal; 96.34%, 95.35% and 97.44% for COVID-19 vs bacterial pneumonia; and 97.56%, 97.44% and 97.67% for COVID-19 vs non-COVID-19 viral pneumonia. For the multi-class classification, the combined accuracy and AUC were 79.52% and 0.87, respectively. Conclusion AI classification of texture and morphological features of portable CXRs accurately distinguishes COVID-19 lung infection in patients in multi-class datasets. Deep-learning methods have the potential to improve diagnostic efficiency and accuracy for portable CXRs.
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