Tirzepatide: A novel cardiovascular protective agent in type 2 diabetes mellitus and obesity.

Cardiovascular disease (CVD) remains a major global health concern, and obesity and diabetes mellitus have been found to be important risk factors. Tirzepatide a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP1) receptor agonist has been shown to have cardioprotective effects. Noteworthy benefits of Tirzepatide include decreased cardiovascular risk factors in people with Type 2 diabetes mellitus (T2DM). In the SURPASS-4 trial, tirzepatide significant decreased blood pressure, body weight, and HbA1c. Furthermore, the SURMOUNT-1 trial demonstrated the effectiveness of tirzepatide in reducing cardiometabolic risk factors in people with obesity without T2DM. Together, the dual receptor agonism improves lipid profiles, increases insulin secretion, reduces inflammation, and promotes endothelial integrity. Tirzepatide shows promise as a comprehensive therapeutic option for managing cardiovascular risk factors in patients with T2DM and obesity. While further studies are needed to assess the long-term cardiovascular benefits, current evidence supports tirzepatide's potential impact on cardiovascular health beyond its antidiabetic properties.

Temporal and regional trends in adults with diabetics kidney disease in the US from 1999 to 2020.

AIMS: We aim to analyze trends in mortality rates among adults with diabetic kidney disease (DKD) in the US from 1999 to 2020. METHODS: We queried the Centers for Disease Control Wide-Ranging Online Data for Epidemiologic Research database for mortality statistics from 1999 to 2020 associated with DKD in adults aged ≥25 years. Age-adjusted mortality rates (AAMRs) were calculated and trends were analyzed using the Joinpoint Regression Program. RESULTS: From 1999 to 2020, a total of 528,430 deaths were reported among adults with DKD. The mortality rates increased over time with males consistently exhibiting higher AAMR than females. NH American Indian or Alaska Native individuals had the highest AAMR, followed by NH Blacks, Hispanics, NH Whites, and NH Asians. The West region had the highest AAMR, followed by the Midwest, South, and Northeast. Rural regions had higher AAMR than urban areas, and mortality rates increased with age. CONCLUSIONS: This study reveals notable disparities in DKD mortality rates across demographic groups and geographic regions. NH American Indians or Alaska Natives, males, elderly individuals, rural residents, and those in the West region were disproportionately affected. Understanding these trends is crucial for developing targeted interventions to reduce DKD-related mortality and address healthcare disparities.

Disparities in mortality trends of adults with HIV in the USA: A comprehensive examination across 2 decades.

Approximately 38 million people worldwide are affected by human immunodeficiency virus (HIV), with 4000 new infections daily. While literature explores HIV mortality among the elderly in the US, there is an underrepresentation of mortality data for adults. By scrutinizing mortality trends based on demographic factors such as gender, race or ethnicity, age groups, and geographic location, the study seeks to uncover patterns that may facilitate a longitudinal perspective for tailoring interventions and allocating resources effectively. Crude death rates and age-adjusted mortality rates (AAMR) per 100,000 individuals were calculated using HIV mortality data (ICD-10 Codes B20-24) from CDC WONDER database. Permutation test was used to calculate annual percentage changes in AAMR with 95% confidence interval. Average annual percentage changes were computed as weighted average of annual percentage changes. Between 1999 to 2020, US adult HIV deaths totaled 225,396 (AAMR: 5.03), with a significantly decreasing average annual percentage changes (-5.94). Males exhibited a 3-fold higher AAMR (7.50) than females (2.67). Non-Hispanic Blacks had the highest AAMR (21.82), while Non-Hispanic Asians had the lowest (0.67). The South and Northeast regions had the highest AAMRs (6.91 and 6.33, respectively). Notably, the District of Columbia had an alarmingly high mortality rate of 39.9, while North Dakota had the lowest (0.7). Urban regions (5.47) had double the mortality rates of rural regions (2.70). Mortality rate peaked in age groups 45 to 54 (8.65) and 35 to 44 (7.42). While overall HIV mortality is declining, disparities persist among demographics. Targeted interventions are crucial to improve preventive measures and healthcare access for disproportionately affected groups.

Cardiac autonomic plexus neuromodulation for decompensated heart failure: An updated review on the positive inotropic technique based on the DRI2P2S classification.

Current pharmacological regimen is unable to improve adverse outcomes such as mortality post hospitalization for Acutely Decompensated Heart Failure (ADHF) patients. Ongoing research is directed towards managing ADHF patients with Cardiac Autonomic Nervous System (CANS) excitatory interventions having long-term prognosis benefits. Recently, a novel treatment coined as Cardiac Pulmonary Nerve Stimulation (CPNS) has reproducibly shown increased inotropy with no change in heart rate. However, there are some potential limitations associated with the neurostimulation of the parasympathetic component of the CANS plexus. The INOVATE-HF trial involved the vagus nerve only. The early termination of the INOVATE-HF trial gave valuable insights into the cardio-protective effect of simultaneously stimulating the sympathetic and parasympathetic components of the CANS plexus done in CPNS. It is essential to individualize the treatment protocol keeping in mind patient selection. Ongoing trials assessing the efficacy and safety of the CPNS technique in ADHF patients shall set the tone for such innovative techniques in times to come.

Mortality patterns in older adults with infective endocarditis in the US: A retrospective analysis.

BACKGROUND: Infective Endocarditis (IE) has become a significant cause of morbidity and mortality over the last two decades. Despite management advancements, mortality trends in the USA's geriatric population are unexplored. The aim of this study was to assess the trends and regional differences in IE related mortality among geriatric patients in the USA. METHODS: We analyzed death certificates sourced from the CDC WONDER database spanning 1999 to 2020. The research targeted individuals aged 65 and older. Age-adjusted mortality rates (AAMRs) per 100,000 and annual percent change (APC), along with 95% CI, were calculated through joinpoint regression analysis. RESULTS: From 1999 to 2020, infective endocarditis caused 222,573 deaths, showing a declining trend (APC: -0.8361). Males had higher AAMR (26.8) than females (22.2). NH White had the highest AAMR (25.8), followed by NH American Indians or Alaska Natives (19.6). Geographically, the Midwest had the highest AAMR (27.4), followed by the Northeast (25.8). Rural areas consistently had higher AAMRs (26.6) than urban areas (23.6), while 80.16% of deaths occurring in urban settings. North Dakota, Nebraska, and Montana had the highest state AAMRs, approximately double than the states with the lowest mortality rates: Mississippi, Hawaii, California, and Massachusetts. Those aged 85 and above accounted for 42.9% of deaths. CONCLUSION: IE mortality exhibited a clear pattern: rising till 2004, declining from 2004 to 2018, and increasing again till 2020. Key risk factors were male gender, Midwest residence, NH White ethnicity, and age ≥85.Targeted interventions are essential to reduce IE mortality, especially among vulnerable older populations.

Bevacizumab Combination Therapy Versus Standard Chemotherapy for Ovarian Cancer in Shorter and Longer Follow-Up Duration: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer over a shorter and longer follow-up period. METHODS: We searched Medline, Cochrane CENTRAL, Scopus, and Google Scholar for all phase 3 randomized controlled trials (RCTs) that administered bevacizumab to women with ovarian cancer. Review Manager 5.4 was used to calculate risk ratios (RR) and hazard ratios (HR) with 95% CIs. We assessed the quality of the included studies using version 2 of the Cochrane Risk of Bias tool (RoB 2). RESULTS: After screening the titles, abstracts, and full texts, we included nine RCTs in our systematic review and meta-analysis. Four RCTs had a low risk of bias, while 5 had some concerns. Bevacizumab was associated with a progression free survival benefit for <36 months (HR: 0.59, 95% CI: 0.45-0.76, P<0.0001, I2=90%) and >36 months (HR: 0.66, 95% CI: 0.55-0.80, P<0.0001, I2=80%), and an overall survival benefit for <36 months (HR: 0.87, 95% CI: 0.78-0.98, P=0.02, I2=0%) but not for >36 months (HR: 0.98, 95% CI: 0.89-1.09, P=0.77, I2=30%). There was no difference in deaths between intervention and control groups <36 months (RR: 0.95, 95% CI: 0.86-1.04, P=0.26, I2=10%) or >36 months (RR: 1.02, 95% CI: 0.97-1.06, P=0.50, I2=0%). Bevacizumab reduced disease progression <36 months (RR: 0.82, 95% CI: 0.72-0.92, P=0.0008, I2=82%) but not at >36 months (RR: 0.83, 95% CI: 0.58-1.19, P=0.30, I2=94%). The adverse events reported with Bevacizumab use included thrombocytopenia, neutropenia, leukocytopenia, anemia, hypertension, bleeding or hemorrhage, and gastrointestinal, cardiac, and dermatological adverse events. CONCLUSION: Bevacizumab may improve progression-free survival within and after 36 months, overall survival within 36 months, and reduce disease progression within 36 months.

The Efficacy of Ketoconazole Containing Regimens in Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis.

Castration resistant prostate cancer (CRPC) is a challenging subset of prostate cancer associated with an extensive metastatic profile and high mortality. Ketoconazole is a nonselective steroid 17α-hydroxylase/17,20 lyase (CYP17A1) inhibitor and is employed as a second line treatment option for CRPC with an established efficacy profile in patients. The aim of this study is to assess the efficacy of ketoconazole containing regimens for CRPC in terms of prostate specific antigen (PSA) decline rate using a systematic review and meta-analysis. In this review, an electronic search was carried out on PubMed, Cochrane CENTRAL, Scopus, and Google Scholar to find relevant literature. Random effects model was used to assess pooled PSA decline rate and 95% CIs. Publication bias was assessed using the funnel plot symmetry and one-tailed Egger's and Begg's test. In all cases, P-value <.05 was indicative of significant results. The review is registered with PROSPERO: CRD42023466536. A total of 483 articles were retrieved after database searching, out of which 23 studies (having a total of 1315 patients) were included in the review based on prespecified criteria. The PSA decline rate was reported in the 14 observational studies (having 964 patients) and 9 experimental studies (having 351 patients). Pooled results revealed that 48.6% (95% CI 43.1-54.2; P-value <.001; I2 = 73.24%) of participants achieved more than 50% decline in PSA (602/1315 participants). Sensitivity analysis using the leave-one-out method revealed no substantial change in pooled effect estimates; (Risk Ratio) RR 47.2% to RR 49.8% demonstrating the robustness of our results. There was no evidence of publication bias as assessed from the funnel plot symmetry. Ketoconazole containing regimens have shown moderate efficacy in high risk CRPC patients as demonstrated by the pooled results. Hence, a ketoconazole based chemotherapy can be added to patients' regimen if there is a persistent rise in PSA levels after androgen deprivation therapy.

Efficacy of Cisplatin-Containing Chemotherapy Regimens in Patients of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: The relative success of cisplatin-based chemotherapy regimens for PDAC in clinical trials warrants a review of the literature to assess the cumulative results. This study aims to assess the efficacy of cisplatin-containing regimens for PDAC in terms of survival and response outcomes using a systematic review and proportional meta-analysis. METHODS: In this study, an electronic search was conducted on PubMed, Cochrane Library, Scopus, and Google Scholar to find relevant literature. The random effects model was used to assess pooled overall response rate, stable disease rate, progressive disease rate, 1-year overall survival rate, and their 95% CIs. Publication bias was assessed using funnel plot symmetry and the one-tailed Eggers' test. In all cases, p-value < 0.05 was indicative of significant results. The review is registered with PROSPERO: CRD42023459243. RESULTS: A total of 34 studies consisting of 1599 patients were included in this review. All the included studies were of good quality. In total, 906 patients were male, and the median age of the patients was 58-69 years. Overall, 599 patients had cancer of the pancreatic head, 139 had cancer of the pancreatic body, and 102 patients had cancer of the pancreatic tail. The pooled risk ratios (RRs) revealed an overall response rate of 19.2% (95% CI, 14.6-24.2%), a stable disease rate of 42.3% (95% CI, 36.6-48.8), a 1-year overall survival rate of 40% (95% CI, 34.3-45.8), and progressive disease rate of 24.7% (95% CI, 18.8-31.2). Commonly reported adverse events were anemia, thrombocytopenia, abdominal adverse events, neutropenia, fatigue, leukopenia, alopecia, anorexia, mucositis, stomatitis, and hepatobiliary adverse events. CONCLUSION: Cisplatin-containing regimens have shown moderate efficacy with significant improvement in overall survival at 1 year, stable disease rate, and progressive disease rate; however, only a small percentage of patients achieved an overall response rate.