IntroductionWith intense deficiency of medical resources during COVID-19 pandemic, risk stratification is of strategic importance. Blood glucose level is an important risk factor for the prognosis of infection and critically ill patients. We aimed to investigate the prognostic value of blood glucose level in patients with COVID-19.Research design and methodsWe collected clinical and survival information of 2041 consecutive hospitalized patients with COVID-19 from two medical centers in Wuhan. Patients without available blood glucose level were excluded. We performed multivariable Cox regression to calculate HRs of blood glucose-associated indexes for the risk of progression to critical cases/mortality among non-critical cases, as well as in-hospital mortality in critical cases. Sensitivity analysis were conducted in patient without diabetes.ResultsElevation of admission blood glucose level was an independent risk factor for progression to critical cases/death among non-critical cases (HR=1.30, 95% CI 1.03 to 1.63, p=0.026). Elevation of initial blood glucose level of critical diagnosis was an independent risk factor for in-hospital mortality in critical cases (HR=1.84, 95% CI 1.14 to 2.98, p=0.013). Higher median glucose level during hospital stay or after critical diagnosis (≥6.1 mmol/L) was independently associated with increased risks of progression to critical cases/death among non-critical cases, as well as in-hospital mortality in critical cases. Above results were consistent in the sensitivity analysis in patients without diabetes.ConclusionsElevation of blood glucose level predicted worse outcomes in hospitalized patients with COVID-19. Our findings may provide a simple and practical way to risk stratify COVID-19 inpatients for hierarchical management, particularly where medical resources are in severe shortage during the pandemic.

Highlights d High-fat diet induces colonic lysine homocysteinylation (K-Hcy) catalyzed by MARS d Increased MARS copy number is a risk factor for human colorectal cancer (CRC) d K-Hcy impedes DNA damage repair in CRC d K-Hcy inhibition decreases high-fat-induced oncogenic effects

The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)-GATA-binding protein 3 (GATA3)enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK-GATA3-ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic. Significance: These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK-GATA3-ECHS1 pathway as a potential therapeutic target and prognostic biomarker.

Background Systemic corticosteroids are now recommended in many treatment guidelines, though supporting evidence is limited to one randomised controlled clinical trial (RECOVERY). Objective To identify whether corticosteroids were beneficial to COVID-19 patients. Methods 1514 severe and 249 critical hospitalized COVID-19 patients from two medical centers in Wuhan, China. Multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (inverse-probability-of-treatment-weighting (IPTW) and propensity score matching (PSM)) were used to estimate the association of corticosteroid use with risk of in-hospital mortality in severe and critical cases. Results Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to non-corticosteroid group, systemic corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality in both severe cases (HR=1.77, 95% CI: 1.08-2.89, p=0.023), and critical cases (HR=2.07, 95% CI: 1.08-3.98, p=0.028). Findings were similar in time-varying Cox analysis. For severe COVID-19 patients at admission, corticosteroid use was not associated with improved or harmful outcome in either PSM or IPTW analysis. For critical COVID-19 patients at admission, results were consistent with multivariable Cox model analysis. Conclusion Corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality for severe or critical cases in Wuhan. Absence of the beneficial effect in our study in contrast to that was observed in the RECOVERY clinical trial may be due to biases in observational data, in particular prescription by indication bias, differences in clinical characteristics of patients, choice of corticosteroid used, timing of initiation of treatment and duration of treatment.