Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease: A Systematic Review, Meta-Analysis and Meta-Regression.

BACKGROUND: Resveratrol is a non-flavonoid polyphenol that shows promise in reducing pro-inflammatory factors and maintaining endothelial function, which hints at its potential role in slowing atherosclerosis and preventing acute coronary events. OBJECTIVE: To study the cardioprotective effects of resveratrol on inflammatory mediators and endothelial function in patients with coronary artery disease (CAD). METHODS: A thorough search was conducted in databases (Cochrane Library, ProQuest, PubMed, LILACS, ScienceDirect, Springer, Taylor&Francis, CNKI, Wanfang, and Weipu) until September 24, 2023. The vasopro-inflammatory mediators, endothelial function and outcomes related to cardiovascular events were observed. Titles and abstracts were assessed, and bias was evaluated with Cochrane RoB 2.0. Heterogeneity of results was explored by meta-regression, certainty of evidence was assessed by the GRADE system, and conclusive evidence was enhanced by trial sequence analysis. RESULTS: Ten randomized controlled trials and 3 animal studies investigated resveratrol's impact on inflammatory mediators and endothelial function. In primary prevention studies, meta-analysis showed a significant reduction (95% CI: -0.73 to -0.20; P=0.0005) in tumor necrosis factor-α (TNF-α) expression with resveratrol, demonstrating a dose-dependent relationship. No significant difference was observed in interleukin-6 (IL-6) expression with P=0.58 for primary prevention and P=0.57 for secondary prevention. Vascular endothelial nitric oxide synthase (eNOS) expression was significantly increased after resveratrol pre-treatment following CAD events. Secondary prevention studies yielded no significant results; however, meta-regression identified associations between age, hypertension, and lower doses with the extent of TNF-α alterations. High certainty of evidence supported TNF-α reduction, while evidence for IL-6 reduction and eNOS elevation was deemed low. CONCLUSION: Resveratrol reduces TNF-α in individuals at risk for CAD, specifically 15 mg per day. However, its usefulness in patients with confirmed CAD is limited due to factors such as age, high blood pressure, and insufficient dosage. Due to the small sample size, the reduction of IL-6 is inconclusive. Animal studies suggest that resveratrol enhances endothelial function by increasing eNOS. (PROSPERO registration No. CRD42023465234).

Outcome in early vs late intubation among COVID-19 patients with acute respiratory distress syndrome: an updated systematic review and meta-analysis.

Timing of endotracheal intubation in COVID-19 patients with acute respiratory distress syndrome (ARDS) remains controversial regarding its risk and benefit in patient outcomes. Our study aims to elucidate early versus late intubation outcomes among COVID-19 patients with ARDS. A protocol of this study is registered at the international prospective register of systematic reviews (PROSPERO) (CRD42021230272). We report our systematic review based on PRISMA and MOOSE guidelines. We searched the Cochrane Library, EBSCOhost, EMBASE, Grey Literature Report, OpenGrey, ProQuest, PubMed, and ScienceDirect from inception until 4 December 2021. Titles and abstracts were reviewed for their relevance. The risk of bias in each study was evaluated using the risk of bias in non-randomised studies-of interventions (ROBINS-I) guideline. Trial sequential analysis is done to elucidate firm evidence. We retrieved 20 observational studies that assessed an intervention (early vs. late intubation). Meta-analysis for in-hospital mortality reduction showed 119 fewer deaths per 1000 patients in early intubation. Early intubation reduces 2.81 days of ICU length of stay (LOS) and 2.12 days of ventilation duration. Benefits for mortality and ICU LOS reduction were based on studies with low to moderate risk of bias while ventilation duration was based on low disease burden setting. According to the contextualized approach, the benefit of mortality reduction showed a trivial effect, while ICU LOS and ventilation duration showed a small effect. GRADE certainty of evidence for mortality reduction in early intubation is moderate. The certainty of evidence for ICU length of stay, ventilation duration, ventilator-free days, and continuous renal replacement therapy are very low. This updated systematic review provided new evidence that early intubation might provide benefits in treating COVID-19 patients with ARDS. The benefits of early intubation appear to have an important but small effect based on contextualized approach for ICU LOS and ventilation duration. In reducing in-hospital mortality, the early intubation effect was present but only trivial based on contextualized approach. TSA showed that more studies are needed to elucidate firmer evidence.

Evaluation of subclinical ventricular systolic dysfunction assessed using global longitudinal strain in liver cirrhosis: A systematic review, meta-analysis, and meta-regression.

Global longitudinal strain (GLS) can identify subclinical myocardial dysfunction in patients with cirrhosis. This systematic review aims to provide evidence of a possible difference in GLS values between patients with cirrhosis and patients without cirrhosis. Studies from inception to August 11, 2021, were screened and included based on the inclusion criteria. The Newcastle Ottawa Scale was used to assess the quality of nonrandomized studies. Meta-analyses were conducted with subsequent sensitivity and subgroup analyses according to age, sex, cirrhosis etiology, and severity. Publication bias was evaluated using Begg's funnel plot, Egger's test, and rank correlation test with subsequent trim-and-fill analysis. The systematic database search yielded 20 eligible studies. Random effect showed a significant reduction of left ventricular (LV) GLS (MD:-1.43;95%; 95%CI,-2.79 to -0.07; p = 0.04; I2 = 95% p<0.00001) and right ventricular (RV) GLS (MD:-1.95; 95%CI,-3.86 to -0.05, p = 0.04; I2 = 90%, p<0.00001) in the group with cirrhosis. A sensitivity test on subgroup analysis based on the study design showed a -1.78% lower LV-GLS in the group with cirrhosis (I2 = 70%, p = 0.0003). Meta-regression analysis showed that the severity of cirrhosis was significantly related to GLS reduction. This research received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors. The study protocol was registered at PROSPERO (CRD42020201630). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guidelines.

Electrocardiographic Manifestation in Thyrotoxic Periodic Paralysis.

Thyrotoxic periodic paralysis (TPP) is an unusual complication of hyperthyroidism that may cause diagnostic difficulties due to its clinical feature that may be similar to other diseases. However, TPP can be detected early based on the weakness presentation, which generally affects the lower extremity with proximal muscle involvement, and, additionally, the ECG findings presenting hypokalemia characteristics. This case illustrates a young Indonesian male presenting in the emergency department with paralysis and typical ECG findings suggesting TPP. Early identification of TPP is necessary for executing proper treatment and reducing complications.

Current evidence for the risk of PR prolongation, QRS widening, QT prolongation, from lopinavir, ritonavir, atazanavir, and saquinavir: A systematic review.

BACKGROUND: Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir. METHODS: In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies. RESULTS: We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment. CONCLUSION: Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.

The Outcome of Ventricular Arrhythmias Associated With Mitral Valve Prolapse After Catheter Ablation: A Systematic Review and Meta-Analysis.

The presence of mitral valve prolapse (MVP) varies from asymptomatic to life-threatening arrhythmias. Catheter ablation (CA) is widely used to treat ventricular arrhythmias (VAs) associated with MVP. Despite having high procedural success, outcome data after CA is limited, especially in a long-term setting. Therefore, this systematic review and meta-analysis were performed. Literature searching was conducted in Pubmed, EuropePMC, Proquest, and Ebsco from inception to December 2020 using keywords: ventricular arrhythmia, premature ventricular complex, ventricular tachycardia, ventricular fibrillation, mitral valve prolapse, and catheter ablation. A total of 407 potential articles were retrieved for further review. The final review resulted in six articles for systematic review and meta-analysis. The study was registered in PROSPERO (CRD42020219144). The most common origin of VAs was papillary muscle. The acute success rate of CA in the MVP group varies between 66% and 94%. Follow-up studies reported a higher percentage of VAs recurrence after CA in the MVP group (22.22%) compared with the non-MVP group (11.38%). However, the difference is not significant (P-value = 0.16). Other studies reported a 12.5%-36% rate and 40% of repeat ablation in the medium term and the long term, respectively. Episodes of sudden cardiac death during exertion could still occur following CA in patients with MVP. Distinct origin of VAs was observed during repeated ablation procedures, which may explain arrhythmic substrate progression. Diffuse left ventricular fibrosis around papillary muscle rather than local fibrosis was observed among older patients. Furthermore, the presence of mitral annular disjunction (MAD) and Filamin C mutation might increase the risk of recurrent VAs. CAn has been done as the treatment of VAs associated with MVP. The acute success rate of CA varies between studies and the number of patients requiring repeat CA varied from 12.5% to 40%. Sudden cardiac death could still occur after CA. Older age during CA, genetic predisposition, deep arrhythmic foci, multifocal VAs origin, diffuse fibrosis, and the presence of MAD may contribute to the recurrence of VAs. Further studies, stratification, and evaluation are needed to prevent fatal outcomes in VA associated with MVP, even after CA.