MicroRNAs as promising biomarkers and potential therapeutic agents in breast cancer management: a comprehensive review.

Breast cancer (BC), a complex and varied ailment, poses a significant global health burden. MicroRNAs (miRNAs) have emerged as vital regulators in BC progression, with potential implications for diagnosis and treatment. This review aims to synthesize current insights into miRNA dysregulation in BC. MiRNAs, small RNA molecules, govern gene expression post-transcriptionally and are implicated in BC initiation, metastasis, and therapy resistance. Differential expression of specific miRNAs in BC tissues versus normal breast tissue sheds light on underlying molecular mechanisms. MiRNAs also offer promise as diagnostic biomarkers due to their stable nature, accessibility in bodily fluids, and altered expression patterns in early-stage disease, augmenting conventional diagnostic methods. Beyond diagnosis, miRNAs also hold promise as therapeutic targets in BC. By modulating the expression of specific dysregulated miRNAs, it may be possible to restore normal cellular functions and overcome treatment resistance. However, several challenges need to be addressed before miRNA-based therapies can be translated into clinical practice, including the development of efficient delivery systems and rigorous evaluation through preclinical and clinical trials. MiRNAs represent a promising avenue in BC research, offering potential applications in diagnosis, prognosis, and therapeutic interventions. As our understanding of miRNA biology deepens and technology advances, further research and collaborative efforts are needed to fully exploit the diagnostic and therapeutic potential of miRNAs in BC management. Ultimately, the integration of miRNA-based approaches into clinical practice may lead to more personalized and effective strategies for combating this devastating disease.

Evaluating the Effectiveness and Safety of Evinacumab in Treating Hypercholesterolemia and Hypertriglyceridemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk. Familial hypercholesterolemia (FH) further complicates its management, necessitating additional lipid-lowering therapies. Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, has emerged as a potential treatment, particularly for patients with FH, by effectively reducing LDL-C and triglyceride levels. This meta-analysis aimed to evaluate the efficacy and safety of evinacumab across diverse patient populations. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, relevant randomized controlled trials (RCTs) were systematically retrieved from multiple databases until November 24, 2023. The inclusion criteria were studies comparing evinacumab (at doses of 5 and 15 mg) to placebo, with outcomes focusing on lipid levels and adverse events. Standardized protocols were employed for data extraction and quality assessment, and statistical analysis was conducted using RevMan software. RESULTS: Four RCTs, involving 270 patients, were included in the analysis. The analysis revealed significant reductions in lipid markers, particularly with the 15-mg dose of evinacumab, including triacylglycerols (standard mean difference [SMD] = -6.09, 95% confidence interval [CI] - 14.53 to 2.36, P = 0.16), total cholesterol (SMD = - 6.20, 95% CI - 11.53 to - 0.88, P = 0.02), high-density lipoprotein cholesterol (SMD = - 0.79, 95% CI - 1.27 to - 0.31, P = 0.001), LDL-C (SMD = - 4.58, 95% CI - 9.13 to - 0.03, P = 0.05), apolipoprotein (Apo) B (SMD = - 4.01, 95% CI - 7.53 to - 0.46, P = 0.03), and Apo C3 (SMD = - 7.67, 95% CI - 12.94 to - 2.41, P = 0.004). Adverse event analysis revealed no significant association, indicating good tolerability. CONCLUSION: High-dose evinacumab (15 mg) consistently demonstrated efficacy in reducing cholesterol and other lipid markers, with favorable tolerability. Further research is warranted to comprehensively assess its safety and clinical effectiveness, emphasizing the need for additional data to support its use in managing cardiovascular disease.

Unraveling disparities: Probing gender, race, and geographic inequities in pulmonary heart disease mortality in the United States: An extensive longitudinal examination (1999-2020) leveraging CDC WONDER data.

This comprehensive study delves into the epidemiological landscape of Pulmonary Heart Disease (PHD) mortality in the United States from 1999 to 2020, leveraging the extensive CDC WONDER database. PHD encompasses conditions affecting the right side of the heart due to lung disorders or elevated pressure in the pulmonary arteries, including pulmonary hypertension, pulmonary embolism, and chronic thromboembolic pulmonary hypertension (CTEPH). Analyzing data from death certificates, demographic characteristics, and geographical segmentation, significant trends emerge. The age-adjusted mortality rates (AAMRs) for PHD-related deaths show a fluctuating pattern, initially decreasing from 1999 to 2006, followed by a steady increase until 2020. Male patients consistently exhibit higher AAMRs than females, with notable disparities observed among racial/ethnic groups and geographic regions. Non-hispanic (NH) Black or African American individuals, residents of specific states like Colorado and the District of Columbia, and those in the Midwest region demonstrate elevated AAMRs. Furthermore, nonmetropolitan areas consistently manifest higher AAMRs than metropolitan areas. These findings underscore the urgent need for intensified prevention and treatment strategies to address the rising mortality associated with PHD, particularly among vulnerable populations. Insights from this study offer valuable guidance for public health initiatives aimed at reducing PHD-related mortality and improving outcomes nationwide.

Safety and efficacy revisited: a systematic review and meta-analysis of glue versus tack mesh fixation in laparoscopic inguinal herniorrhaphy.

Background: This analysis addresses the uncertainty surrounding the efficacy of glue mesh fixation (GMF) compared with tack mesh fixation (TMF) in laparoscopic herniorrhaphy. Our meta-analysis incorporates recently conducted randomized controlled trials (RCTs) to enhance the reference for assessing the efficacy and safety of GMF. Methods: PubMed Central, Google Scholar, Science Direct, and Cochrane Library were extensively reviewed for articles in the English language performed from inception to May 2023 using the keywords "Glue mesh repair," "Tack mesh repair," "Inguinal Hernia," "Herniorrhaphy," "Laparoscopic," "Mesh Fixation," and "Randomized controlled trials." Results: In this meta-analysis, we incorporated a total of 20 randomized controlled trials, evaluating each article individually using quality ratings. Compared with TMF, GMF demonstrated a significant reduction in the incidence of chronic pain [RR: 0.40, (0.23, 0.68)] and pain scores on postoperative day 1 [MD: -1.07, (-1.90, -0.25)]. We also used funnel plots and Egger's regression to test for publication bias. Conclusion: In summary, this meta-analysis establishes the significance of GMF in reducing chronic pain and postoperative day 1 pain compared with TMF. However, no statistically significant difference was noted between the GMF and TMF groups concerning hematoma, seroma, operation time, recurrence rate, and total complications. Nonetheless, given the small number of cases in this study, the findings must be validated in the future by multicenter, large-sample, high-quality RCTs.

Insights into Covid-19 mortality: A comprehensive study of cardiovascular sensitivity, gender, race, and geography trends in the United States (2020-2023).

This investigation meticulously explores the evolving landscape of Covid-19-related mortality in the United States from 2020 to 2023. Leveraging the comprehensive CDC WONDER database, the study conducts a detailed analysis of age-adjusted mortality rates (AAMRs), considering various demographic and regional parameters. The identified pattern illustrates an initial surge in AAMRs from 2020 to 2021, followed by a subsequent decline until 2023. Notably, there is a discernible reduction in AAMRs for both the elderly (85 years and older) and infants (below one year). Within specific demographic segments, heightened AAMRs are observed among NH American Indian or Alaska Native individuals, men, and residents in particular states and regions. Emphasizing the significant impact of Covid-19 on cardiovascular health, the study underscores increased mortality rates associated with the cardiovascular and respiratory systems. AAMR rates were standardized per 100,000 population, providing a comparative metric. Noteworthy states with elevated AAMRs include Mississippi, Oklahoma, Kentucky, New Mexico, and Alabama, with the Southern region exhibiting the highest AAMR. The research sheds light on demographic and regional disparities in Covid-19-related mortality, calling for intensified efforts in prevention and treatment strategies. These findings, offering nuanced insights, serve as a guide for strategic public health initiatives to mitigate the multifaceted repercussions of the pandemic, especially among vulnerable populations.

Trends in substance-induced cardiomyopathy-related mortality among older adults in the United States from 1999 to 2020.

In this retrospective study, spanning from 1999 to 2020, we examined mortality trends related to SICM (substance-induced cardiomyopathy) among individuals aged 75 and older. A total of 473,408 SICM-related deaths were identified, with detailed data on the place of death available for 454,632 cases, revealing that a significant proportion occurred in medical facilities (45.43 %), nursing homes (24.67 %), hospices (4.21 %), and at home (25.69 %). Our analysis of age-adjusted mortality rates (AAMR) showed an overall decline from 1999 to 2020, decreasing from 14.5 to 7.7 per 10,000 population, with an initial increase from 1999 to 2001 followed by a subsequent decline. Gender-based analysis indicated consistently higher AAMRs for elderly men compared to elderly women. Moreover, we observed variations in AAMRs based on race and ethnicity, with NH Black or African American individuals having the highest AAMRs. Geographic disparities were notable, with states like Delaware having AAMRs twice as high as Utah. The Southern region consistently exhibited the highest AAMR, followed by the Midwestern, Northeastern, and Western regions. Furthermore, metropolitan areas consistently had higher AAMRs than nonmetropolitan areas, although both showed declining trends over the study period. These findings provide valuable insights into SICM-related mortality patterns among the elderly population, emphasizing the importance of considering demographic and geographic factors in public health planning and interventions.

Beyond the surface: analyzing etomidate and propofol as anesthetic agents in electroconvulsive therapy-A systematic review and meta-analysis of seizure duration outcomes.

Background: Electroconvulsive therapy (ECT) is a widely used treatment for severe psychiatric disorders such as schizophrenia, depression, and mania. The procedure involves applying brief electrical stimulation to induce a seizure, and anesthesia is used to ensure sedation and muscle relaxation. Finding the right anesthetic agent with minimal side effects, especially on seizure duration, is crucial for optimal outcomes because seizure duration is an important factor in the effectiveness of ECT, but the anesthetic agents used can affect it. Objective: This systematic review and meta-analysis aimed to pool the results of all relevant studies comparing the two induction agents, etomidate and propofol, for motor and electroencephalogram (EEG) seizure duration outcomes. Methods: A comprehensive literature search was conducted in the PubMed, Medline, and Cochrane Library databases to identify the relevant articles. The primary outcome measures were motor and EEG seizure durations. Statistical power was ensured by performing heterogeneity, publication bias, sensitivity analysis, and subgroup analysis. Standard mean difference and 95% confidence intervals were calculated for continuous outcomes, and a random-effects model was used. Results: A total of 16 studies were included in this meta-analysis, comprising 7 randomized control trials (RCTs), 7 crossover trials, and 2 cohorts. The overall motor seizure duration was statistically significantly longer with etomidate than with propofol. The overall result for EEG seizure duration was also longer with the use of etomidate over propofol and was statistically significant. In addition, subgrouping was performed based on the study design for both outcomes, which showed insignificant results in the cohort's subgroup for both outcomes, while the RCTs and crossover subgroups supported the overall results. Heterogeneity was assessed through subgrouping and sensitivity analysis. Conclusion: Our meta-analysis found that etomidate is superior to propofol in terms of motor and EEG seizure duration in ECT, implying potentially better efficacy. Hence, etomidate should be considered the preferred induction agent in ECT, but larger studies are needed to further validate our findings.

Temporal trends in hypertension related end stage renal disease mortality rates: an analysis of gender, race/ethnicity, and geographic disparities in the United States.

Background: According to one USA Renal Data System report, 57% of end-stage renal disease (ESRD) cases are attributed to hypertensive and diabetic nephropathy. Yet, trends in hypertension related ESRD mortality rates in adults ≥ 35 years of age have not been studied. Objectives: The aim of this retrospective study was to analyze the different trends hypertension related ESRD death rates among adults in the United States. Methods: Death records from the CDC (Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research) database were analyzed from 1999 to 2020 for hypertension related ESRD mortality in adults ≥ 35 years of age. Age-Adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change (APC) were calculated and stratified by year, sex, race/ethnicity, place of death, and geographic location. Results: Hypertension-related ESRD caused a total of 721,511 deaths among adults (aged ≥ 35 years) between 1999 and 2020. The overall AAMR for hypertension related ESRD deaths in adults was 9.70 in 1999 and increased all the way up to 43.7 in 2020 (APC: 9.02; 95% CI: 8.19-11.04). Men had consistently higher AAMRs than woman during the analyzed years from 1999 (AAMR men: 10.8 vs women: 9) to 2020 (AAMR men: 52.2 vs women: 37.2). Overall AAMRs were highest in Non-Hispanic (NH) Black or African American patients (45.7), followed by NH American Indian or Alaska Natives (24.7), Hispanic or Latinos (23.4), NH Asian or Pacific Islanders (19.3), and NH White patients (15.4). Region-wise analysis also showed significant variations in AAMRs (overall AAMR: West 21.2; South: 21; Midwest: 18.3; Northeast: 14.2). Metropolitan areas had slightly higher AAMRs (19.1) than nonmetropolitan areas (19). States with AAMRs in 90th percentile: District of Columbia, Oklahoma, Mississippi, Tennessee, Texas, and South Carolina, had roughly double rates compared to states in 10th percentile. Conclusions: Overall hypertension related ESRD AAMRs among adults were seen to increase in almost all stratified data. The groups associated with the highest death rates were NH Black or African Americans, men, and populations in the West and metropolitan areas of the United States. Strategies and policies targeting these at-risk groups are required to control the rising hypertension related ESRD mortality.