A mini-review of Vutrisiran and Eplontersen in hereditary transthyretin-mediated amyloidosis with polyneuropathy.

Hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis), known as Corino de Andrade disease, is a rare neurodegenerative disorder with a significant global impact characterized by the misfolding of transthyretin (TTR) protein leading to amyloid aggregation, ATTRv amyloidosis, especially with polyneuropathy, poses a considerable challenge in managing its rapid progression and debilitating effects. This mini-review focuses on the recent advancements in the treatment landscape for ATTRv amyloidosis with polyneuropathy, specifically the RNA interference therapeutic Vutrisiran and the ligand-conjugated antisense oligonucleotide Eplontersen. We aim to provide a comprehensive overview of the mechanisms, current evidence from clinical trials, and future directions for these novel therapeutic agents. Vutrisiran and Eplontersen have demonstrated significant clinical efficacy in improving neuropathic impairment, quality of life, and serum TTR levels in various trials. The distinct mechanistic approaches of these therapies, coupled with their acceptable safety profiles, offer promising avenues for addressing the complexities of ATTRv amyloidosis with polyneuropathy. The introduction of Vutrisiran and Eplontersen marks a pivotal moment in the quest for effective therapies against ATTRv amyloidosis with polyneuropathy. While clinical evidence is promising, ongoing research is crucial to deepen mechanistic understanding and address research gaps. Future perspectives include the potential expansion of therapeutic options and a more inclusive approach to cater to the diverse needs of individuals globally. This mini-review provides valuable insights into the evolving landscape of ATTRv amyloidosis management and sets the stage for further exploration in this challenging domain.

Can Semaglutide offer hope for patients with obesity-related heart failure?

Heart failure with preserved ejection fraction (HFpEF) is a growing clinical challenge with limited treatment options. This review explores the potential of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, for HFpEF treatment. Studies suggest promising benefits, including symptom improvement, weight management, and the potential for enhanced exercise capacity. However, the evidence for semaglutide's impact on exercise capacity and heart function remains inconclusive, and its anti-inflammatory effects require further investigation. The safety profile appears favorable, with gastrointestinal side effects being the most common adverse events. It is crucial to emphasize that additional research with longer follow-up, head-to-head comparisons, and exploration of optimal dosage and mechanisms of action are necessary to solidify semaglutide's role in HFpEF treatment. Semaglutide is promising to improve symptoms, promote weight loss, and potentially influence underlying HFpEF mechanisms. Future research can refine treatment strategies and unlock the full potential of semaglutide for this patient population.

Can CSL-112 revolutionize atherosclerosis treatment? A critical look at the evidence.

CSL-112, a recombinant human apolipoprotein A-I, holds promise for treating atherosclerotic disease by promoting reverse cholesterol transport. This review evaluates the current evidence on CSL-112's impact on atherosclerotic disease. A search identified studies investigating the effect of CSL-112 on apolipoprotein A-I levels, cholesterol efflux capacity, clinical outcomes, safety profile, pharmacokinetics, pharmacodynamics, and subgroup analysis in patients with atherosclerotic disease. All nine studies consistently demonstrated a dose-dependent increase in apolipoprotein A-I levels following CSL-112 administration. Most studies also reported a corresponding rise in cholesterol efflux capacity. However, the AEGIS-II trial, the largest study to date, did not show a statistically significant reduction in major adverse cardiovascular events in patients with acute myocardial infarction treated with CSL-112 compared to placebo. While some smaller studies suggested potential benefits, particularly in stable atherosclerotic disease, their limitations in size and duration necessitate further investigation. CSL-112 appeared to be generally well-tolerated, with mostly mild or moderate adverse events reported. However, the AEGIS-II trial identified a higher incidence of hypersensitivity reactions in the CSL-112 group, requiring further exploration. CSL-112 demonstrates promise in raising apolipoprotein A-I levels and enhancing cholesterol efflux capacity, potentially promoting reverse cholesterol transport. However, its clinical efficacy for atherosclerotic disease remains unclear. Larger, well-designed trials with longer follow-up periods are necessary to definitively establish its clinical benefit and safety profile before widespread clinical use can be considered. Future research should also explore deeper into the pharmacokinetic and pharmacodynamic profile of CSL-112 and explore its efficacy and safety in different patient subgroups.

Correction: Impact of School-Based Interventions on Pediatric Obesity: A Systematic Review.

[This corrects the article DOI: 10.7759/cureus.43153.].

The Impact of Contemporary Antiretroviral Drugs on Atherosclerosis and Its Complications in People Living With HIV: A Systematic Review.

With the advent of modern antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been modified into a chronic manageable condition, prolonging the lifespan of people living with HIV (PLHIV). This has resulted in an increased non-AIDS-related morbidity in the HIV-infected population. Our aim is to study the role of contemporary ART in tackling the risk of atherosclerosis and cardiovascular disease (CVD) in PLHIV. We searched through the databases of PubMed, PubMed Central, and Cochrane Library for pertinent articles using the medical subject headings (MeSH) "HIV infection", "Atherosclerosis", and "Antiretroviral agents". The articles published in the past five years were retrieved, screened for relevance, and assessed for quality before being included in the review. This review was performed following the PRISMA 2020 guidelines. The results indicate that the incidence of dyslipidemia with integrase strand transfer inhibitors (INSTIs) is greater than with non-nucleoside reverse transcriptase inhibitors (NNRTIs) and lesser than with protease inhibitors (PIs). INSTIs are indispensably associated with weight gain and obesity. High triglyceride (TG) and oxidized low-density lipoproteins to low-density lipoproteins (oxLDL/LDL) ratio levels and low high-density lipoprotein (HDL) levels are seen in patients taking PIs. A higher incidence of hypertension and metabolic syndrome (MetS) was noticed with INSTIs compared to NNRTIs. PI intake for >5 years increases the risk of subclinical atherosclerosis. Increased risk of myocardial infarction with INSTIs was observed in a study, while another study reported decreased risk. HIV infection independently increases the risk for atherosclerosis and CVD. Although contemporary ART decreases this enhanced risk, it inherently increases the risk for abnormal lipid profile, MetS, weight gain, and obesity. Further research into the risk of atherosclerosis and CVD with newer ART drugs is essential for decoding the underlying mechanisms and preventing adverse cardiac outcomes in PLHIV.

Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Cardiovascular Risk Management in Patients With Type 2 Diabetes Mellitus: A Systematic Review.

People with type 2 diabetes mellitus have a greater risk of developing cardiovascular problems. Since cardiovascular diseases are a major cause of mortality all over the world, we need to find more efficient measures to control this risk in the diabetes population in addition to conventional glycemic control. In this systematic review, we aim to explore the latest findings on the cardiovascular effects of glucagon-like peptide-1 (GLP-1) agonists and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) agonists in patients with type 2 diabetes mellitus. We conducted a comprehensive literature search using PubMed and Google Scholar as the main sources for data collection. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations for conducting this review. The outcomes of interest included mortality due to cardiovascular causes, non-fatal myocardial infarction, stroke, effects on cardiovascular risk factors, heart failure, and development of arrhythmias. After thorough literature screening and quality analysis, 14 articles were finally included for qualitative synthesis. GLP-1 receptor agonists appeared to be effective in reducing the risk of cardiovascular mortality, myocardial infarction, and stroke. They were found to reduce the risk of composite major adverse cardiovascular event (MACE) outcomes by 12-14% when compared to placebo. Their role in preventing heart failure and arrhythmias is uncertain, and further trials are needed to confirm the same. The cardiovascular outcomes of GLP-1/GIP dual agonists are currently under investigation. Studies completed to date show that they do not increase the risk of cardiovascular disease when compared to placebo.

On the Menu: Analyzing the Macronutrients, Micronutrients, Beverages, Dietary Patterns, and Pancreatic Cancer Risk.

This narrative review summarizes the principal findings of observational studies, systematic reviews, and meta-analyses on diet and dietary patterns' role in the risk of pancreatic cancer. Etiologically pancreatic cancer is multifactorial. Evidence exists of an association between nutrients, dietary patterns, and pancreatic cancer. An extensive literature search was conducted on PubMed, Cochrane, and Google Scholar. A thorough search of articles published in English till May 2023 and related to the review was performed. The relationship between all macronutrients, micronutrients, and various dietary patterns with the risk of pancreatic cancer was assessed. It is concluded that a diet high in nutrients like red and processed meat, refined sugars, saturated and monounsaturated fats, alcohol, copper, and a Western dietary pattern can increase the likelihood of pancreatic cancer. Contrary to this, a diet consisting of fruits, vegetables, appropriate quantities of vitamins and minerals, and a Mediterranean dietary pattern is associated with a decreased risk of pancreatic cancer.

Crohn's Disease is a Greater Risk Factor for Nonalcoholic Fatty Liver Disease Compared to Ulcerative Colitis: A Systematic Review.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases that have been associated with nonalcoholic fatty liver disease (NAFLD). This systematic review aimed to examine whether Crohn's disease confers a greater risk for nonalcoholic fatty liver disease compared to ulcerative colitis. A comprehensive search of electronic databases from January 2000 to May 2023 was conducted to identify observational studies investigating the association between Crohn's disease or ulcerative colitis and nonalcoholic fatty liver disease. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 checklist ensured transparent reporting, and the Newcastle-Ottawa Scale was used to assess study quality. Data synthesis revealed higher nonalcoholic fatty liver disease prevalence among Crohn's disease patients compared to ulcerative colitis patients across regions. Ten studies published between 2016 and 2022, encompassing a total of 4164 participants from three continents, were included in the review. The median proportion of Crohn's disease patients with nonalcoholic fatty liver disease was 37.22% (range: 10.95-53.80%), while it was 27.55% (range: 8.60-46.20%) for ulcerative colitis patients. Subgroup analysis by region confirmed CD's higher NAFLD risk. Median proportions for CD patients who developed NAFLD from North America, Europe, and Asia were 25.97% (range: 14.6-37.33%), 47.01% (range: 14.2-53.8%), and 20.78% (range: 10.95-30.6%), respectively, and the median proportion of persons with UC who developed NAFLD in studies from North America, Europe, and Asia were 17.28% (range: 8.6-25.96%), 37.70% (range: 25.64-46.20%), and 19.52% (range: 10.14-28.90%), respectively. Variations suggest differing mechanisms, disease features, and therapeutics. Transmural inflammation in Crohn's disease may increase metabolic abnormalities, including nonalcoholic fatty liver disease. Geographic differences in lifestyle, genetics, and environmental variables may also contribute. This review demonstrates that Crohn's disease patients face a higher nonalcoholic fatty liver disease risk than ulcerative colitis patients, emphasizing the need for early monitoring and prevention. Further studies are warranted to understand mechanisms and develop tailored management approaches.

Impact of School-Based Interventions on Pediatric Obesity: A Systematic Review.

Childhood obesity is a global public health problem with significant implications for the health and well-being of children. The prevalence of childhood obesity is increasing every decade, making it a recognized public health concern. This systematic review aims to explore and evaluate the impact of school-based interventions on reducing pediatric obesity among school-aged children. A systematic review of literature according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 was conducted. Google Scholar, PubMed, and Cochrane were the databases used. After screening for bias, inclusion and exclusion criteria, and quality, 27 studies were included in the systematic review, and data were synthesized. The results show that physical activity reduces obesity and improves cardiovascular health. The nutritional change reduces the risk of obesity more than physical activity alone. When blended, the two provide the most benefits for participants. Motivation, self-efficacy, and behavioral change could help maintain the improvements. Schools should adopt a blend of physical activity and nutritional change to reduce prevent, reduce, and manage obesity.

Racial Disparities and Outcomes of Percutaneous Coronary Interventions in Patients Above 65 Years in America: A Systematic Review.

This systematic review aims to examine the racial disparities and outcomes of percutaneous coronary interventions (PCIs) in patients above 65 years in America. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 2020 and includes a comprehensive search strategy, study selection, data extraction, and quality assessment. The search strategy identified 10 relevant articles that were included in the review. The findings indicate that racial disparities exist in access to PCI, door-to-balloon (DTB) time, procedure utilization, and outcomes among elderly patients. African American and Hispanic patients were found to experience longer door-to-balloon time and lower rates of PCI utilization compared to White patients. Moreover, racial and ethnic minorities had worse clinical outcomes, including higher mortality rates and increased risk of major adverse cardiovascular events. The review also highlights the impact of Medicaid expansion on reducing disparities in access, treatment, and outcomes for patients with acute myocardial infarction (AMI). However, limitations in data availability and representation of racial and ethnic minorities in clinical trials were identified. The discussion section provides a robust analysis of the findings, exploring potential underlying factors contributing to the observed disparities. The review concludes that addressing racial disparities in PCI outcomes among elderly patients is crucial for achieving equitable healthcare delivery and improving cardiovascular health outcomes in America.

A Systematic Review of Myocarditis Induced by Immune Checkpoint Inhibitors: How Concerning Is the Most Common Cardiotoxicity of Immune Checkpoint Inhibitors?

Novel cancer therapies have revolutionized the management of various cancers. An immune checkpoint inhibitor (ICI) is one of these antitumor medications. ICIs, which are immune therapies, enhance the immune system's capacity to fight cancer cells. Based on the receptors that they inhibit, such as PD-1, PD-L1, and CTLA-4, ICIs are subdivided. Although this class of drugs is extremely beneficial for cancer patients, their adverse effects can be fatal. Multiple organs, such as the cardiovascular system, may be impacted by immune-related adverse effects (irAEs). These cardiotoxic irAEs can occur at a rate of up to 1% and can be fatal. Myocarditis is the most prevalent of all cardiotoxicities. The purpose of this systematic review is to assess the seriousness of myocarditis, the most prevalent cardiotoxicity of ICIs, and the importance of screening. We chose studies based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 criteria. Therefore, from 2018 to 2023, we gathered articles from databases such as PubMed, ScienceDirect, Web of Science, the Cochrane Library, and Google Scholar. Of the 665 studies identified based on various screening methods and quality assessment tools, 13 were selected for inclusion in the study. This study shows that although the risk of myocarditis in ICI therapy is low and the majority of cases are asymptomatic or mild, some cases can be deadly and disastrous, and physicians should be aware that if myocarditis is suspected based on clinical symptoms, troponin, electrocardiogram, and echocardiogram, treatment should be initiated accordingly.

Which Is Better? Rate Versus Rhythm Control in Atrial Fibrillation: A Systematic Review.

Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and mortality. The optimal approach to managing AF, specifically rate control versus rhythm control, remains a topic of debate in clinical practice. This systematic review aims to compare the rate control and rhythm control strategies based on their clinical outcomes, quality of life, and adverse events associated with them. A comprehensive search was conducted using PubMed, Google Scholar, Science Direct, Research Gate, MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, and Embase (Excerpta Medica dataBASE) databases. A total of 1657 research papers were identified through the search strategy, and after applying the eligibility criteria, 28 studies were selected for the analysis. The studies encompassed a range of methodologies, including randomized controlled trials, observational studies, and meta-analyses. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for study selection, data extraction, and analysis. The outcomes of interest included all: cause mortality, stroke, bleeding events, cardiovascular hospitalizations, quality of life, and adverse effects of treatment. Data were synthesized and presented in tables, charts, and forest plots for meta-analysis where appropriate. The results indicate that both rate control and rhythm control strategies have their own merits and limitations, with the outcomes varying based on patient characteristics and comorbidities. While rhythm control strategies may lead to better symptom control and improved quality of life, rate control strategies may be associated with lower risks of adverse events and complications. This systematic review provides a comprehensive overview of the current evidence regarding rate and rhythm control strategies in AF management, offering insights for clinical decision-making and highlighting the need for individualized treatment approaches.