Objectives The case fatality rate (CFR) of Coronavirus disease 2019 (COVID-19) varies significantly between countries. We aimed to describe the associations of health indicators with the national CFRs of COVID-19. Methods We identified health indicators for each country potentially associated with the national CFRs of COVID-19. We extracted data for 18 variables from international administrative data sources for 34 member countries of the Organization for Economic Co-operation and Development (OECD). We excluded the collinear variables and examined the 16 variables in multivariable analysis. A dynamic web-based model was developed to analyse and display the associations for the CFRs of COVID-19. We followed the Guideline for Accurate and Transparent Health Estimates Reporting (GATHER). Results In multivariable analysis, the variables significantly associated with the increased CFRs were percent of obesity in ages >18 years ( β = 3.26, 95% CI = [1.20, 5.33], p = 0.003), tuberculosis incidence ( β = 3.15, 95% CI = [1.09, 5.22], p = 0.004), duration (days) since first death due to COVID-19 ( β = 2.89, 95% CI = [0.83, 4.96], p = 0.008), median age ( β = 2.83, 95% CI = [0.76, 4.89], p = 0.009). The COVID-19 test rate ( β = -3.54, 95% CI = [-5.60, -1.47], p = 0.002), hospital bed density ( β = -2.47, 95% CI = [-4.54, -0.41], p = 0.021), and rural population ratio ( β = -2.19, 95% CI = [-4.25, -0.13], p = 0.039) decreased the CFR. Conclusions The pandemic hits the population dense cities. Available hospital beds should be increased. Test capacity should be increased to enable more effective diagnostic tests. Older patients, and patients with obesity, and their caregivers should be warned about a potentially increased risk.
Partial epithelial-to-mesenchymal transition (pEMT) contributes to cellular heterogeneity that is associated with nodal metastases and unfavorable clinical parameters in head and neck squamous cell carcinomas (HNSCCs). We developed a single-cell RNA sequencing signature-based pEMT quantification through cell type-dependent deconvolution of bulk RNA sequencing and microarray data combined with single-sample scoring of molecular phenotypes (Singscoring). Clinical pEMT-Singscores served as molecular classifiers in multivariable Cox proportional hazard models and high scores prognosticated poor overall survival and reduced response to irradiation as independent parameters in large HNSCC cohorts [The Cancer Genome Atlas (TCGA), MD Anderson Cancer Centre (MDACC), Fred Hutchinson Cancer Research Center (FHCRC)]. Differentially expressed genes confirmed enhanced cell motility and reduced oxidative phosphorylation and epithelial differentiation in pEMT high patients. In patients and cell lines, the EMT transcription factor SLUG correlated most strongly with pEMT-Singscores and promoted pEMT, enhanced invasion, and resistance to irradiation in vitro. SLUG protein levels in HNSCC predicted disease-free survival, and its peripheral expression at the interphase to the tumor microenvironment was significantly increased in relapsing patients. Hence, pEMT-Singscores represent a novel risk predictor for HNSCC stratification regarding clinical outcome and therapy response that is partly controlled by SLUG.
Purpose Tocilizumab, a monoclonal IL-6 receptor blocker, is an effective agent for severe-to-critical cases of COVID-19; however, its target patients for the optimum use need to be detailed. We performed a systematic review and meta-analysis to define its effect among severely ill but non-intubated cases with COVID-19. Methods We searched PubMed, Scopus, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Medrxiv, and Biorxiv until February 13, 2022, for non-intubated cases, and included randomized-controlled trials (RCT) based on bias assessment. The primary outcomes were the requirement of invasive mechanical ventilation and mortality. Random effect and fixed-effect models were used. The heterogeneity was measured using the χ 2 and I 2 statistics, with χ 2 p ≤ 0.05 and I 2 ≥ 50% indicating the presence of significant heterogeneity. We registered the study to the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CRD42021232575. Results Among 261 articles, 11 RCTs were included. The pooled analysis of the 11 RCTs demonstrated that the rate of mortality was significantly lower in the tocilizumab group than in the control group (20.0% and 24.2%, OR: 0.84, 95% CI 0.73–0.96, and heterogeneity I 2 = 0%. p = 0.82.). The mechanical ventilation rate was lower in the tocilizumab group than the control group (27% vs 35.2%, OR: 0.76, 95% CI 0.67–0.86, and heterogeneity I 2 = 6%. p = 0.39). Conclusion Among non-intubated severe COVID-19 cases, tocilizumab reduces the risk of invasive mechanical ventilation and mortality compared to standard-of-care treatment.
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