Associations between type 2 diabetes mellitus and chronic liver diseases: evidence from a Mendelian ranldomization study in Europeans and East Asians.

Objective: Multiple observational studies have demonstrated an association between type 2 diabetes mellitus (T2DM) and chronic liver diseases (CLDs). However, the causality of T2DM on CLDs remained unknown in various ethnic groups. Methods: We obtained instrumental variables for T2DM and conducted a two-sample mendelian randomization (MR) study to examine the causal effect on nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), viral hepatitis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection risk in Europeans and East Asians. The primary analysis utilized the inverse variance weighting (IVW) technique to evaluate the causal relationship between T2DM and CLDs. In addition, we conducted a series of rigorous analyses to bolster the reliability of our MR results. Results: In Europeans, we found that genetic liability to T2DM has been linked with increased risk of NAFLD (IVW : OR =1.3654, 95% confidence interval [CI], 1.2250-1.5219, p=1.85e-8), viral hepatitis (IVW : OR =1.1173, 95%CI, 1.0271-1.2154, p=0.0098), and a suggestive positive association between T2DM and HCC (IVW : OR=1.2671, 95%CI, 1.0471-1.5333, p=0.0150), HBV (IVW : OR=1.1908, 95% CI, 1.0368-1.3677, p=0.0134). No causal association between T2DM and HCV was discovered. Among East Asians, however, there was a significant inverse association between T2DM and the proxies of NAFLD (ALT: IVW OR=0.9752, 95%CI 0.9597-0.9909, p=0.0021; AST: IVW OR=0.9673, 95%CI, 0.9528-0.9821, p=1.67e-5), and HCV (IVW: OR=0.9289, 95%CI, 0.8852-0.9747, p=0.0027). Notably, no causal association was found between T2DM and HCC, viral hepatitis, or HBV. Conclusion: Our MR analysis revealed varying causal associations between T2DM and CLDs in East Asians and Europeans. Further research is required to investigate the potential mechanisms in various ethnic groups, which could yield new insights into early screening and prevention strategies for CLDs in T2DM patients.

Prevalence and clinical implications of polypharmacy and potentially inappropriate medication in elderly patients with heart failure: results of six months' follow-up.

OBJECTIVES: To investigate the prevalence of polypharmacy and potentially inappropriate medication (PIM) in elderly patients with heart failure (HF) and their impact on readmission and mortality. METHODS: We conducted a study of 274 participants aged 60 years or older with HF. The prevalence of polypharmacy (defined as the use of five or more medications) was calculated, and the 2019 American Geriatrics Society Beers criteria were applied to access PIMs. Medications and PIMs were characterized at admission and discharge, and changes in prescriptions during hospitalization were compared. The impact of polypharmacy and PIM on readmission and mortality were investigated. RESULTS: The median age of this study population was 68 years old. The median number of prescribed drugs was 7 at admission and 10 at discharge. At discharge, 99.27% of all patients were taking five or more drugs. The incidence of composite endpoint and cardiovascular readmission increased with the number of polypharmacy within 6 months. The use of guideline-directed medical therapy reduced the incidence of composite endpoint events and cardiovascular readmission, while the use of non-cardiovascular medications increased the composite endpoint events. The frequency of PIMs was 93.79% at discharge. The incidence of composite endpoint events increased with the number of PIMs. "PIMs in older adults with caution" increased cardiovascular readmission and "PIMs based on kidney function" increased cardiovascular mortality. Several comorbidities were associated with cardiovascular mortality or non-cardiovascular readmission. CONCLUSIONS: Polypharmacy and PIM were highly prevalent in elderly patients with HF, and their use was associated with an increased risk of composite endpoint events, readmission and mortality. Non-cardiovascular medications, "PIMs in older adults with caution", "PIMs based on kidney function" and several comorbidities were important factors associated with hospital readmission and mortality. Our findings highlight the importance of medication optimization in the management of HF in elderly patients.

Comprehensive analysis of the basement membrane in lung adenocarcinoma by bulk and single-cell sequencing analysis.

Background: The basement membrane (BM), as a critical component of the extracellular matrix, plays a role in cancer progression. However, the role of the BM in lung adenocarcinoma (LUAD) remains unclear. Methods: A total of 1383 patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts were enrolled in the study, and BM-related differentially expressed genes (BM-DEGs) were screened using weighted gene coexpression network analysis (WGCNA) and differential expression analysis. We next built a prognostic model using Cox regression analysis and separated patients into two groups based on the median risk score. This signature was validated with in vitro experiments, and its mechanism was investigated by enrichment and tumour microenvironment analyses. We also evaluated whether this signature could predict sensitivity to chemotherapy and immunotherapy. Finally, single-cell RNA sequencing analysis was utilized to analyse the expression of signature genes in different cells. Results: Thirsty-seven BM-DEGs were discovered, and a prognostic signature based on 4 BM-DEGs (HMCN2, FBLN5, ADAMTS15 and LAD1) was obtained in the TCGA cohort and validated in GEO cohorts. Survival curves and ROC curve analysis demonstrated that the risk score was a significant predictor of survival in all cohorts even when considering the effect of other clinical indexes. Low-risk patients had longer survival times, higher immune cell infiltration levels and better immunotherapeutic responses. Single-cell analysis showed that FBLN5 and LAD1 were overexpressed in fibroblasts and cancer cells, respectively, compared to normal cells. Conclusion: This study evaluated the clinical role of the BM in LUAD and primarily explored its mechanism.

Efficacy, safety, and tolerability of combined pirfenidone and N-acetylcysteine therapy: a systematic review and meta-analysis.

BACKGROUND: While antifibrotic drugs significantly decrease lung function decline in idiopathic pulmonary fibrosis (IPF), there is still an unmet need to halt disease progression. Antioxidative therapy with N-acetylcysteine (NAC) is considered a potential additional therapy that can be combined with antifibrotics in some patients in clinical practice. However, data on the efficacy, tolerability, and safety of this combination are scarce. We performed a systematic review and meta-analysis to appraise the safety, tolerability, and efficacy of the combination compared to treatment with pirfenidone alone. METHODS: We systematically reviewed all the published studies with combined pirfenidone (PFD) and NAC (PFD + NAC) treatment in IPF patients. The primary outcomes referred to decline in pulmonary function tests (PFTs) and the rates of IPF patients with side effects. RESULTS: In the meta-analysis, 6 studies with 319 total IPF patients were included. The PFD + NAC group was comparable to the PFD alone group in terms of the predicted forced vital capacity (FVC%) and predicted diffusion capacity for carbon monoxide (DLco%) from treatment start to week 24. Side effects and treatment discontinuation rates were also comparable in both groups. CONCLUSION: This systematic review and meta-analysis suggests that combination with NAC does not alter the efficacy, safety, or tolerability of PFD in comparison to PFD alone in IPF patients.

Blood purification in two patients with clinically amyopathic dermatomyositis associated with interstitial lung disease with anti-melanoma differentiation-associated gene-5 antibody (MDA-5).

Patients of clinically amyopathic dermatomyositis associated with rapidly progressive interstitial pneumonia (CADM-RFIP) with positive anti-MDA5 antibody usually presents rapid deterioration and traditional therapy such as cyclophosphamide combined with high-dose prednisone pulse therapy shows no clear benefit at whiles. However, blood purification combined with traditional therapy works according to the literature. We herein report two CADM-RFIP patients administered with DNA immunoadsorption combined with traditional therapy and then reviewed the literature of blood purification in CADM-RFIP patients at home and abroad to date. We emphasize blood purification such as DNA immunoadsorption could apply in the early stage of CADM-RFIP, which can decrease inflammation and allow us more time to control the condition better.