Safety and efficacy of resmetirom in the treatment of patients with non-alcoholic steatohepatitis and liver fibrosis: a systematic review and meta-analysis.

Introduction: Non-alcoholic fatty liver disease (NAFLD), spanning from non-alcoholic steatohepatitis (NASH) to liver fibrosis, poses a global health challenge amid rising obesity and metabolic syndrome rates. Effective pharmacological treatments for NASH and liver fibrosis are limited. Objective: This study systematically reviews and meta-analyzes the safety and efficacy of resmetirom, a selective thyroid hormone receptor-ß agonist, in NASH and liver fibrosis treatment. By analyzing data from clinical trials, we aim to offer evidence-based recommendations for resmetirom's use in managing these conditions and identify avenues for future research. Methods: Electronic databases (PubMed, Scopus, Science Direct, Google Scholar, ClinicalTrials.gov, and Cochrane CENTRAL) were systematically searched, supplemented by manual screening of relevant sources. Only English-language randomized controlled trials were included. Data extraction, risk of bias assessment, pooled analyses, and meta-regression were performed. Results: Three randomized controlled trials involving 2231 participants were analyzed. Resmetirom demonstrated significant reductions in hepatic fat fraction [standardized mean difference (SMD) -4.61, 95% CI -6.77 to -2.44, P < 0.0001], NASH resolution without worsening fibrosis [risk ratio (RR) 2.51, 95% CI 1.74-3.64, P = 0.00001), and liver fibrosis improvement (RR 2.31, 95% CI 1.20-4.44, P = 0.01). Secondary outcomes showed significant improvements in lipid profiles, liver enzymes, and NASH biomarkers with resmetirom treatment. Meta-regression revealed associations between covariates and primary outcomes. Conclusion: Resmetirom exhibits promising efficacy in reducing hepatic fat, improving NASH resolution, and ameliorating liver fibrosis with a favorable safety profile. Further research is warranted to validate findings and optimize therapeutic strategies for NASH and liver fibrosis management.

Long-term outcomes of titanium-nitride-oxide coated stents and drug-eluting stents in acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: In severe cases of coronary artery disease, percutaneous coronary intervention provide promising results. The stent used could be a drug-eluting stent (DES) or a titanium-nitride-oxide coated stent (TiNOS). AIM: To compare the 5-year effectiveness and safety of the two stent types. METHODS: The following systematic review and meta-analysis was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis guidelines, and PubMed/MEDLINE, Scopus, and Cochrane Central were searched from inception till August 2023. Primary outcomes were major adverse cardiac events (MACE), cardiac death, myocardial infarction (MI), cardiac death or MI, and ischemia-driven total lesion revascularization (ID-TLR). RESULTS: Four randomized controlled trials (RCT), which analyzed a sum total of 3045 patients with acute coronary syndrome (ACS) after a median follow-up time of 5 years were included. Though statistically insignificant, an increase in the ID-TLR was observed in patients receiving TiNOSs vs DESs. In addition, MI, cardiac death and MI, and definite stent thrombosis (DST) were significantly decreased in the TiNOS arm. Baseline analysis revealed no significant results with meta-regression presenting non-ST elevated MI (NSTEMI) as a statistically significant covariate in the outcome of MACE. CONCLUSION: TiNOS was found to be superior to DES in terms of MI, cardiac death or MI, and DST outcomes, however, the effect of the two stent types on ID-TLR and MACE was not significant. A greater number of studies are required to establish an accurate comparison of patient outcomes in TiNOS and DES.

Prognostic value of blood count parameters in patients with acute coronary syndrome.

BACKGROUND: Recent studies have shown that complete blood count (CBC) parameters can effectively predict long-term mortality and re-infarction rates in acute coronary syndrome (ACS). However, the role of these parameters in predicting short term mortality has not been studied extensively. The main objective of this study was to determine whether CBC parameters can predict 30-days mortality and the incidence of major adverse cardiac event (MACE) in ACS patients. METHODOLOGY: A total of 297 patients with ACS were recruited in this prospective study. The relationship of baseline white blood cell (WBC) to mean platelet volume ratio (WMR) with MACE and mortality was assessed during a 30-days follow up. The patients were divided into two groups: Group A [WMR<1000] and Group B [WMR>1000]. Multivariate COX regression was performed to calculate hazard ratios (HR). RESULTS: WMR had the highest area under receiver operating characteristics curve and highest discriminative ability amongst all CBC parameters in predicting mortality. Patients in Group B had a higher mortality rate (p<0.001) than patients in Group A. WBC count (p=0.02), platelet count (p=0.04), WMR (p=0.008), platelet to lymphocyte ratio (p<0.001) and neutrophil to lymphocyte ratio (p=0.03) were significantly higher in the MACE-positive group as compared to MACE-negative. In multivariate cox regression analysis, WMR>1000 (HR=2.9, 95% confidence interval 1.3-6.5, p=0.01) was found to be strongest biochemical marker in predicting mortality. CONCLUSION: WMR is an easily accessible and an inexpensive indicator, which may be used as a prognostic marker in patients with ACS.

Prevalence and Severity of Depression in a Pakistani Population with at least One Major Chronic Disease.

INTRODUCTION: Diabetes, anaemia, hypertension and asthma are major contributors to morbidity in our society. Depression is the commonest psychological malady diagnosed in hospital settings. There tends to be some overlap between certain chronic systemic illnesses and depressive disorders, this point towards the need to determine relationships between them, if any. AIM: To determine the prevalence and compare the severity of depression among individuals diagnosed with four of the most common chronic diseases in our community. MATERIALS AND METHODS: This cross-sectional study was carried out among patients with chronic diseases visiting a tertiary care hospital in Karachi, Pakistan from August 2015 to August 2016. The Beck Depression Inventory-II*, a 21-item self-report instrument was used to assess the severity of depression. Categorical variables were compared using Chi-square test while intergroup comparisons were performed using one way ANOVA test. Logistic regression was employed to estimate the odds of Category B depression (moderate and severe levels of depression) in chronic diseases. RESULTS: The prevalence of anaemia, hypertension, diabetes and asthma was 90%, 47%, 26% and 23% respectively. Predictors of Category B depression were anaemia (OR=4.21, 95% CI: 1.30-13.56) and diabetes (OR=2.03, 95% CI: 1.09-3.77). Asthma predicted Category B depression in males (OR=1.26, 95% CI: 0.29-5.42) but not in females (OR=0.77, 95% CI: 0.39-1.52). Individuals with hypertension were less likely to report Category B depression than non-hypertensive (OR=0.72, 95% CI 0.43-1.21). Female gender had a greater influence to develop Category B depression than males (OR= 2.96, 95% CI: 1.93-4.55). CONCLUSION: Our study points towards a strong correlation between depression and chronic diseases especially anaemia and diabetes. This cautions medical practitioners against treatment of depressive disorders and chronic diseases as separate, independent entities.

Characterization of genetic lesions in apoptosis-regulating and proliferation control genes in diffuse large B-cell non-Hodgkin's lymphoma.

BACKGROUND: This study was conducted to analyze the frequency, expression patterns, and the impact of individual proteins BCL2, BCL6, and p53 on overall survival (OS) in adult, diffuse large B-cell lymphoma (DLBCL) patients. BCL2 gene was further investigated for potential alterations at the DNA level and correlated with OS. MATERIALS AND METHODS: A total of 117 adult well-characterized DLBCL cases were included. The panel of antibodies comprised CD45, CD20, CD79a, CD3, BCL2, BCL6, and p53. PCR was also employed to correlate the events at the DNA level in BCL2. RESULTS: The mean and median ages were 47.74 and 49 with a M:F ratio of 2.07:1. The incidence of BCL2, BCL6, and p53 expression was observed in 64.10%, 37.60%, and 52.13% of cases, respectively. Amplifiable quality DNA was available from 90 cases. BCL2/IGH translocation was found in 35/90 patients (38.88%) with 24 cases showing BCL2 (MBR)/IGH and 11 cases BCL2 (mcr)/IGH translocation. No association between BCL2 overexpression and BCL2 /IGH translocation was seen. Clinical data were available for 52 patients treated by CHOP therapy. It was found that patients with p53 overexpression had decreased overall survival (P = 0.0004) whereas BCL2, BCL6 expression, and BCL2/IGH translocation had no impact on overall survival. CONCLUSION: Our data suggest that simple p53 protein expression by IHC at the time of diagnosis may help to identify high-risk patients, who may benefit with more aggressive and newer treatments in addition to standard CHOP.