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.

Histotripsy: an innovative approach for minimally invasive tumour and disease treatment.

Histotripsy is a noninvasive medical technique that uses high-intensity focused ultrasound (HIFU) to treat liver tumours. The two main histotripsy methods are boiling histotripsy and cavitation cloud histotripsy. Boiling histotripsy uses prolonged ultrasound pulses to create small boiling bubbles in the tissue, which leads to the breakdown of the tissue into smaller subcellular fragments. Cavitation cloud histotripsy uses the ultrasonic cavitation effect to disintegrate target tissue into precisely defined liquefied lesions. Both methods show similar treatment effectiveness; however, boiling histotripsy ensures treatment stability by producing a stable boiling bubble with each pulse. The therapeutic effect is ascribed to mechanical damage at the subcellular level rather than thermal damage. This article discusses the mechanisms, treatment parameters, and potential of histotripsy as a minimally invasive procedure that provides precise and controlled subcellular damage.

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.

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.

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.

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.

Evaluating the safety and efficacy of zuranolone in the management of major depressive disorder and postpartum depression, with or without concurrent insomnia: a rigorous systematic review and meta-analysis.

Introduction: Major depressive disorder (MDD), postpartum depression (PPD), and insomnia are neuropsychological conditions in which zuranolone is used to improve symptoms and prognosis of the disorder. This meta-analysis aimed to determine the efficacy of zuranolone in comparison to other drugs used for treating these conditions. Methods: This meta-analysis included patients aged between 18 and 75 years who were diagnosed with major depressive disorder and postpartum depression with or without insomnia and were administered zuranolone for treatment. Only randomized controlled trials (RCTs) were included, and animal studies were excluded. The databases used were PubMed, Scopus, Cochrane, and Clinicaltrials.gov, with MeSH terms and relevant keywords for (Zuranolone) and (Depression). The Cochrane risk of bias tool was used for quality assessment. Results: The meta-analysis included eight RCTs that analyzed data from 2031 patients. The meta-analysis revealed statistically significant changes in the Hamilton Depression Rating Scale (HAM-D), Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and treatment-emergent adverse effects (TEAE) scores in the PPD subgroup. HAM-D and TEAEs scores were also significant in the MDD subgroup, but the changes in the MADRS, HAM-A, and Bech-6 scores were insignificant. Serious adverse events were insignificant in all subgroups. Conclusion: Meta-analysis found a significant improvement in depressive symptoms with zuranolone treatment, especially on day 15. This suggests that zuranolone is a promising therapeutic option for patients with MDD and PPD with or without insomnia. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459554, identifier CRD42023459554.

Safety and efficacy of antithrombotics in outpatients with symptomatic COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease (COVID-19) is a global health emergency, with well over six hundred million infections and over six million deaths to date. Besides other ramifications, it is also associated with inflammation and an augmented risk of thromboembolic complications. Despite this, the risks and benefits of antithrombotic drugs in patients with mild to moderate COVID-19 have not been well-established and remain controversial. OBJECTIVES: To evaluate the safety and efficacy of antithrombotic drugs on mild to moderate symptomatic COVID-19 patients by performing an updated systematic review and meta-analysis. METHODS: We queried electronic databases (PubMed, Cochrane Central, Scopus, and Embase) from their inception up to September 2022 for randomized controlled trials comparing antithrombotic drugs against placebo. The outcomes of interest were the need for hospital care, mortality, and thromboembolic events in the enrolled participants. Dichotomous outcomes were presented as risk ratio (RR) with 95 % confidence intervals (CIs) and were consolidated using random-effects model. MAIN RESULTS: Five eligible studies (Rivaroxaban/Apixaban, two; enoxaparin, two; Sulodexide, one), consisting of 2,005 participants with mild to moderate COVID-19, were included. Pooled results show that antithrombotics, when compared to placebo, do not significantly reduce all-cause mortality (RR 0.51, 95 % CI 0.15-1.68; P = 0.27; I2 = 0), thromboembolic events (RR 0.78, 95 % CI 0.17-3.51; P = 0.74; I2 = 0), need for hospitalization (RR 0.73, 95 % CI 0.51-1.03; P = 0.08; I2 = 0), nor significantly increase clinically relevant non-major bleeding events (RR 2.36, 95 % CI 0.56-9.89; P = 0.24; I2 = 0). However, when Sulodexide was compared independently to other antithrombotics, it significantly reduced the need for hospitalization (RR 0.60, 95 % CI 0.37-0.95; P = 0.03). CONCLUSIONS: Our pooled analysis was not able to establish statistically significant benefits or risks of using antithrombotic drugs in mild to moderate COVID-19 patients. To further improve our understanding of the efficacy, safety and risk profile of such a therapy, large sample randomized clinical trials are required on a wide scale.

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.

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.

Meta-analysis of Molteno glaucoma implants and Ahmed glaucoma valves: insights into efficacy and safety for complex glaucoma.

Background: Glaucoma is a leading cause of irreversible blindness globally and for decades, Molteno and Ahmed glaucoma implants, operating on different mechanisms, have been used to treat complicated glaucoma with varying success. Objective: To assess the safety and efficacy of the Molteno glaucoma implant (MGI) versus the Ahmed glaucoma valve (AGV) in patients with complicated glaucoma. Methods: We comprehensively searched PubMed, Google Scholar, Cochrane Library and Science Direct) from inception till July 2023 and studies comparing patients with MGI and those with AGV in patients with complicated glaucoma. The primary outcome was intra-ocular pressure reduction at different time intervals. Secondary outcomes included surgical success rate, hypertensive phase, anti-glaucoma medication (AGM) and total complications. Results: In this meta-analysis, four studies were included with a patient population of 257 with refractory, neovascular or advanced uncontrolled glaucoma. Postoperative intra-ocular pressure reduction did not show significant difference between the two groups (MD: -1.34, 95% CI [-2.78, 0.09]). From the secondary outcomes, surgical success rate (RR: 0.88, 95% CI [0.51,1.53]), hypertensive phase (RR: 0.74, 95% CI [0.39,1.40]) were insignificant. Postoperative anti-glaucoma medication (MD: -0.07, 95% CI [-0.79, -0.65] and total complications (RR:1.36, 95% CI [1.07, 1.72]) were significant. Conclusion: No significant difference was observed between the patients with MGI and AGV for the primary outcome. From the secondary outcome, AGV was associated with reduced anti-glaucoma medication use and significantly lowered the number of complications. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=475539, identifier CRD42023475539.