Heart Failure (HF) and Diabetes Mellitus (DM) often coexist, and each condition independently increases the likelihood of developing the other. While there has been concern regarding the increasing burden of disease for both conditions individually over the last decade, a comprehensive examination of mortality trends and demographic and regional disparities needs to be thoroughly explored in the United States (US). This study analyzed death certificates from the CDC WONDER database, focusing on mortality caused by the co-occurrence of HF and DM in adults aged 75 and older from 1999 to 2020. Age-adjusted mortality rates (AAMRs) and annual percent changes (APCs) were computed and categorized by year, gender, race, census region, state, and metropolitan status. A total of 663,016 deaths were reported in patients with coexisting HF and DM. Overall, AAMR increased from 154.1 to 186.1 per 100,000 population between 1999 and 2020, with a notable significant increase from 2018 to 2020 (APC: 11.30). Older men had consistently higher AAMRs than older women (185 vs. 135.4). Furthermore, we found that AAMRs were highest among non-Hispanic (NH) American Indian or Alaskan natives and lowest in NH Asian or Pacific Islanders (214.4 vs. 104.1). Similarly, AAMRs were highest in the Midwestern region and among those dwelling in non-metropolitan areas. Mortality from HF and DM has risen significantly in recent years, especially among older men, NH American Indian or Alaska Natives, and those in non-metropolitan areas. Urgent policies need to be developed to address these disparities and promote equitable healthcare access.

Introduction: Malignant neoplasms of bone and articular cartilage, although rare, are associated with substantial morbidity and mortality, posing a serious health burden. Understanding the trends in mortality related to these cancers is crucial for developing targeted interventions and improving patient outcomes. This study aims to analyze long-term mortality trends, identify demographic and geographic disparities, and uncover potential factors driving changes in mortality rates. Methods: This retrospective study analyzed mortality rates among individuals aged 65 and older from 1999 to 2020 using CDC WONDER death certificate data, abstracting demographics, geographic factors, and urban/rural status. Results: From 1999 to 2020, 18,205 adults aged 65 and older died from malignant neoplasms of bone and cartilage. The age-adjusted mortality rate (AAMR) started at 20 per 100,000 in 1999 and steadily declined until 2012 (APC: −1.12). However, from 2012 onwards, there was a notable reversal, with the AAMR rising sharply to 23.8 by 2020 (APC: 4.73). Men had higher mortality rates than women, with NH Black individuals showing the highest rates among races. Southern states and nonmetropolitan areas had elevated AAMRs, suggesting targeted interventions for better outcomes and lower death rates. Conclusion: The findings highlight significant inequities, with Southern states and nonmetropolitan areas showing elevated age-adjusted mortality rates (AAMRs). These geographic disparities underscore the urgent need for targeted public health interventions in these regions to improve cancer outcomes and reduce mortality. Addressing these gaps is essential for achieving more equitable health outcomes, particularly in high-risk populations.

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.

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-β 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.

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.

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.