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AIM The global burden of chronic liver disease is substantial. Limited studies have reported the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis among middle-aged and older people. Therefore, we aimed to determine the nationwide prevalence of and associated factors for MAFLD and fibrosis in adults aged 45-79 years from the United States. METHODS This cross-sectional study utilized data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey conducted with a nationally representative sample of the civilian, noninstitutionalized US population. Hepatic steatosis and fibrosis were assessed by transient elastography with controlled attenuation parameter and liver stiffness measurement, respectively. RESULTS A total of 1186 eligible participants aged 45-79 years were finally included in the analyses. The estimated prevalence of MAFLD, significant fibrosis (F ≥ F2), and advanced fibrosis (F ≥ F3) was 48.6% (95% confidence interval [CI], 43.1%-54.0%), 9.5% (95% CI, 6.8%-12.7%), and 6.7% (95% CI, 4.1%-10.1%), respectively. Multivariable logistic regression revealed an increased MAFLD predisposition in subjects with metabolic disorders including overweight/obesity, abdominal obesity, hypertension, and diabetes mellitus. Moreover, the presence of depression was an independent and strong predictor of MAFLD risk (odds ratio = 3.23; 95% CI, 1.37-7.11). Elevated liver enzymes, hypertension, diabetes mellitus, hepatitis virus infection, and steatosis were associated with a high risk of significant fibrosis. CONCLUSIONS Newly defined MAFLD is highly prevalent in the US middle-aged and older population. Approximately 1 in 10 people has significant liver fibrosis. In addition to metabolic disorders, the presence of depression potentially increases the risk of MAFLD.

Type 2 diabetes (T2D) increases the risk of coronavirus disease (COVID-19). This study investigates the association between glucose control of COVID-19 patients with T2D in first 7 days after hospital admission and prognosis. A total of 252 infected inpatients with T2D in China were included. Well-controlled blood glucose was defined as stable fasting blood glucose (FBG) levels in the range of 3.9–7.8 mmol/L during first 7 days using indicators of average (FBGA), maximum (FBGM) or first-time (FBG1) FBG levels. The primary endpoint was admission to intensive care unit or death. Hazard ratio (HR) of poorly controlled glucose level group compared with well-controlled group were 4.96 (P = 0.021) for FBGM and 5.55 (P = 0.014) for FBGA. Well-controlled blood glucose levels in first 7 days could improve the prognosis of COVID-19 inpatients with diabetes.

Background: Cytokine storms are a common complication in severely ill patients with COVID-19, for which corticosteroid therapy (CsT) is used as adjuvant treatment. Therefore, we evaluated the efficacy and safety of CsT in patients with COVID-19.Methods: A single-center, retrospective cohort study was conducted in 1,392 severely ill patients with COVID-19 from Wuhan Huoshenshan Hospital. Patients received at least one dose (1–2 mg·kg-1·day-1 for 3–5 days) of methylprednisolone were divided into CsT group, whereas the rest were assigned into the non-CsT group. Results: Of 1,392 patients, 116 were assigned to the CsT group and 1,226 to the non-CsT group. Patients in the CsT group showed comparable mortality rate (1.8% vs. 1.2%, P > 0.99) and viral clearance time (44.5 days vs. 46.0 days, P = 0.48), but longer hospitalization time (21 days vs. 12 days, P < 0.001) than those in non-CsT group. During CsT, the proportion of lymphocytes was lower (14.7 % vs. 18.5 %, P = 0.01), while neutrophils was higher (77.1 % vs. 69.8 %, P < 0.001), than before treatment. The C-reactive protein (CRP) level was significantly lower after CsT (3.1 mg/L vs. 9.5 mg/L, P < 0.001). Furthermore, indicators of liver function (gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT], and aspartate aminotransferase [AST]) and cardiac function (brain natriuretic peptide [BNP], α-hydroxybutyrate dehydrogenase [α-HBDH], and lactate dehydrogenase [LDH]) increased significantly during CsT but returned to normal after CsT. Patients who developed liver damage showed higher GGT, ALT, AST, LDH, Cre, and CRP; patients who developed heart injury had higher AST, LPH, CRP, lymphocyte (LYM), glucose, BNP, and α-HBDH; and patients who developed kidney failure had higher α-HBDH, LDH, CRP, and LYM values than before CsT. Additionally, patients who received CsT with cardiovascular disease showed a continuous elevation in D-dimer levels.Conclusions: CsT effectively attenuates the inflammatory response in severely ill patients with COVID-19 at a relatively low dose in a short duration; however, CsT increases the risk of hepatic and cardiac abnormalities.

We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single-cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Longitudinal transcriptome analysis showed that expression subtype is retained in 55% of cases. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence associated with CD8+ Tcell enrichment. Frequency of M2 macrophages detection associated with short-term relapse after radiation therapy.