Significant Reduction In Mortality Research Articles

Effectiveness of treat-to-target cholesterol-lowering interventions on cardiovascular disease and all-cause mortality risk in the community-dwelling population: a target trial emulation.

Little is known about the long-term effectiveness of risk-based treat-to-target cholesterol-lowering interventions on cardiovascular risk. Here, we show the emulated effectiveness of guideline-recommended low-density and non-high-density lipoprotein cholesterol-lowering interventions using the absolute risk reduction (ARR) and the restricted mean event-free time-based number needed to treat (NNT). With 5,375 participants, the 29-year risks for cardiovascular disease (CVD), all-cause mortality, and atherosclerotic CVD were 18.6%, 25.6%, and 17.7%, respectively. Long-term treat-to-target interventions showed significant reductions in CVD (ARR -2.3%, 95%CI -3.4% to -0.8%; NNT 115), all-cause mortality (-3.0%, -4.3% to -1.8%; 95), and atherosclerotic CVD (-2.6%, -3.5% to -1.2%; 104). Such effects appear more pronounced in women, smokers, and those with body mass index < 24 kg/m² or higher adherence rates.

“Effectiveness and safety of negative pressure wound therapy in patients with deep sternal wound infection: a systematic review and meta-analysis”

Background: Deep sternal wound infection (DSWI) is a severe and life-threatening complication following cardiovascular surgery. Negative pressure wound therapy (NPWT) has emerged as a promising therapeutic bridging option for DSWI. In this systematic review and meta-analysis, we aimed to evaluate the impact of NPWT on clinical outcomes in patients with DSWI. Material and Methods: A comprehensive literature search was conducted according to the PRISMA guideline in electronic databases, including PubMed, Embase, and Cochrane Library. Data extraction was performed independently by two reviewers, and risk of bias was assessed by ROBINS-I tool. The primary outcomes assessed were mortality rate and reinfection rate. The secondary outcomes assessed were length of hospital stay and intensive care unit stay. Results: In this systematic review identified a total of 36 studies, comprising 3,681 patients with DSWI who received treatment. The meta-analysis revealed that NPWT was associated with a significant reduction in mortality rate (RR 0.46, 95% CI 0.35-0.61, P&lt;0.000001) and reinfection rate (RR 0.43, 95% CI: 0.25-0.74, P=0.002) compared to conventional wound management. Furthermore, pooling of these studies showed significant difference between the NPWT and conventional treatment groups in length of hospital stay (mean difference: -4.49, 95% CI: -8.14, -0.83; P=0.02) and length of ICU stay (mean difference: -1.11, 95% CI: -2.18, -0.04; P=0.04). Conclusion: This systematic review and meta-analysis provide evidence that NPWT is superior to conventional treatment for patients with DSWI following cardiovascular surgery.

Study protocol: the ‘Endoscope CRC’ cohort, a prospective biobank study on the development and evaluation of diagnostic and prognostic biomarker profiles for colorectal cancer and premalignant lesions

IntroductionEarly detection of colorectal cancer (CRC) and clinically relevant (advanced) adenomas leads to a significant reduction of CRC-related mortality and morbidity. However, the faecal immunochemical test (FIT) suffers from a...

EGS SO29 - Therapeutic Endoluminal Vacuum Therapy (EVT) as first line management for oesophageal and selected gastric and duodenal perforations

Abstract Background Upper gastro-intestinal (GI) perforations and leaks affect roughly 2,800 patients annually in the UK. They can occur spontaneously, as a complication of medical intervention, or be due to trauma. Mortality rates are around 20%, rising to 50% if diagnosis and treatment is delayed. Around a third of cases fall into the delayed category. Traditionally, management of this group of patients involved surgery with long hospital stays and poor outcomes. Our Unit has adopted EVT as first line management for these cases, using an ad-hoc Endoluminal Vacuum Device (EVD), which has significantly improved patient outcomes compared to traditional treatment strategies. Method The primary aim of this study was to assess the successful perforation/ leak healing rate, the overall mortality rate, and the complication rate of EVT. A retrospective analysis of a prospectively collated database for all patients who received EVT between May 2011 to November 2023 was performed. Patients who had oesophageal, gastric or duodenal perforations were included. The ad-hoc EVD was constructed using an open pore sponge (granufoam, KCI) sutured to the end of a nasogastric (NG) tube. This was inserted endoscopically into the site of perforation and with negative pressure (125mmHg) applied using a negative pressure vacuum pump. Results 104 patients received EVT, with a median age of 65years (range 23-92years), and median ASA of 3 (range 1-5) at presentation. Eighty-five cases were oesophageal, 15 gastric and 4 duodenal. Post-operative leaks accounted for 42 cases, 26 were iatrogenic, 30 spontaneous, and 6 traumatic. Leak resolution was achieved in 94 patients (90.4%). Twelve (11.5%) patients died; 7 (6.7%) deaths were due to treatment failure. Seven (6.7%) patients had a significant bleeding event during EVT of which 4 (3.8%) were directly related to the leak because of undrained sepsis. One patient had an oesophageal mucosal injury during EVD removal. Conclusion EVT is a safe and effective treatment for upper GI tract leaks regardless of their cause. It achieves a significant reduction in mortality compared to traditional treatments, especially in patients with delayed presentation. Adequate drainage of surrounding sepsis is essential to ensure therapy success and avoid bleeding complications. Given the improvement in patient outcomes that EVT delivers, it should be considered for first line management in patients with delayed diagnosis and presentation of oesophageal perforation, following anastomotic leak after resectional surgery, as well as in select patients with gastric and duodenal perforations.

HPB SO71 - Meta-Anaylsis of Early Endoscopic Retrograde Cholangiopancreatography versus conservative management for gallstone pancreatitis

Abstract Background Acute pancreatitis is one of the most common gastrointestinal causes of hospital admission. The most common cause is transient blockage of the bile or pancreatic duct (or both) by gallstones. Most of the time, pancreatitis responds to conservative management (CM) comprising intravenous fluid hydration and analgesia. ERCP +/_endoscopic sphincterotomy in acute gallstone pancreatitis has been advocated in the past to decrease the number of complications of this condition. However, the role and timing of this procedure are still contentious and an ongoing debate. Method The aim of this study is to compare the clinical outcomes of early urgent ERCP versus conservative management in biliary pancreatitis but not cholangitis. An online search of Medline, Embase, Science citation index, PubMed and Cochrane database of systematic reviews published between 1988 and 2022 was carried out for relevant studies. Statistical analysis was done using Revman 5.4 and Odds ratio with a 95% Confidence interval was used for outcome estimation. There was 14 studies included in the final study consisting a total of 1756 patients with 877 patients in ERCP group while 879 in CM group. Results With random effects model, data showed no significant reduction in mortality in ERCP group as compared to the CM group (OR 0.59, 95% CI 0.30-1.16; p=0.13). However there were overall more local or systemic complications (OR 0.51, 95% CI 0.36-0.71; p&amp;lt;0.002) in the CM group as compared to ERCP group. No statistically significant difference found amongst groups when comparing complications as renal failure(OR-0.99, 95% CI-0.41-2.41, p=0.98), cardiac failure (OR-0.77 95% CI 0.35-1.69, p=0.51) or biliary sepsis (OR-0.56 95%CI 0.15-2.10, p=0.39) but there was more incidence of pseudocyst in CM group patients(OR-0.47, 95% CI 0.25-0.87, p=0.02). Conclusion The above study did show that the mortality rate was not significantly higher in the CM group as compared to the ERCP group however the early ERCP was beneficial in reducing overall complications in the interventional group. Based on this fact, ERCP considered early in the management of acute pancreatitis despite of still being debatable in practice can be considered in severe pancreatitis cases and further high powered randomized controlled trials can be carried out to assess this point.

Abstract 4145873: Optimal Timing for Coronary Artery Bypass Grafting in NSTEMI Patients: A Retrospective Cohort Analysis of In-Hospital Mortality and Stroke Prevalence Over 2017 to 2021

Background: Recent studies have suggested performing coronary artery bypass grafting (CABG) within 24 hours of acute myocardial infarction increases mortality risk. However, the ideal timing after the first day remains unclear. This study aims to suggest an optimal timing of CABG in NSTEMI patients using the large National Inpatient Sample (NIS) database over a 5-year period. Methods: This retrospective cohort study analyzed survey-weighted NIS data over 2017-2021, including adult-age admissions with NSTEMI as the principal diagnosis who underwent CABG without prior transfer from another hospital. Patients were categorized into eight groups based on days from admission to CABG (0, 1, 2, 3, 4, 5, 6, and ≥7 days). Baseline characteristics were compared across groups. Multivariate regression analysis adjusted for multiple confounders to assess the association between Time-to-CABG and in-hospital mortality and stroke prevalence. Results: Table 1 presents the baseline characteristics across the eight groups, encompassing 142,200 included admissions (mean age 65.24 years; 26.78% female). In-Hospital Mortality: The adjusted odds ratios (OR) were less than one for groups 1 through 7 compared to group 0, indicating that immediate CABG (day 0) is associated with higher mortality risk. While the reduced odds in the day 1 group were not statistically significant, substantial and statistically significant reductions in mortality were observed between days 2 and 5 (OR: 0.624 - 0.609; p&lt;0.05). After day 5, the OR for mortality trended up, reaching 0.667 (p&lt;0.05) on day 6 and 0.692 (p&lt;0.05) for surgeries performed on day 7 or later. Stroke Prevalence: The adjusted ORs for stroke prevalence were significantly lower for groups 1 through 7 compared to the CABG within 24-hour group (all p-values &lt;0.05). The lowest ORs were observed between days 2 and 4 (OR: 0.654 and 0.542, p&lt;0.05, respectively). After day 4, the ORs increased, reaching 0.672 (p&lt;0.05) for surgeries performed on day 5 and 0.609 (p&lt;0.05) on day 7 and beyond. Conclusion: The mortality risk in NSTEMI patients remained higher if CABG was performed in the first 48 hours of admission (end of day 1) compared to later. This risk also increased if CABG was done after day 5. Combined with the possible risk of stroke being increased from day 5, we suggest the optimal time-to-CABG is between admission day 2 and day 4 in NSTEMI patients. Future prospective studies are warranted to confirm these findings and guide clinical practice.

Abstract 4138024: Identifying the Medications with the Greatest Reduction in Mortality in Coronary Artery Dissection

Introduction: Coronary artery dissection (CD) is a potentially fatal complication, usually arising either spontaneously or iatrogenically. Therefore, identifying treatment methods that reduce mortality is of great importance. The American College of Cardiology recommendations stipulate that patients who have experienced CD may benefit from beta-blocker therapy, as beta-blockers have been shown to reduce the incidence of recurrent CD. Currently, there is little published data in support of beta-blockers providing mortality reduction for CD. Given the significant risk of mortality from CD, we aimed to test the veracity of these recommendations using a retrospective multicenter study as well as having a main objective of exploring means to lower mortality in CD. Methods: We conducted a retrospective, multicenter cohort that identified 2,104 patients diagnosed with CD. We extracted the data from across 16 West Florida hospitals in between the years of 2017-2022. Our patients were identified and stratified based on common lab values and cardioprotective medications they were taking. Chi-square and binary logistic regression was used to calculate odds ratios for mortality. The odds ratio estimate for mortality was our primary outcome with attention given to factors that were associated with an increased or decreased likelihood of mortality in patients with CD. Results: Patients on beta-blockers, angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) were the only variables that were statistically significant. Out of 2,104 patients, 1,562 patients were on beta-blockers (74.2%), and 921 were on an ACEi/ARB (43.8%). Our data revealed that the odds ratio for mortality in patients with CD while on beta blockers was 0.375 (p-value 0.0009, confidence interval 0.210-0.669), and while on ACEi/ARBs was 0.447 (p-value 0.0077, confidence interval 0.247-0.808). These results indicate a significant reduction in mortality in patients who are taking beta-blockers and/or ACEi/ARB medications after being diagnosed with CD. Conclusion: Our data can be viewed as supportive of the current recommendation for the primary use of beta-blockers in patients with spontaneous CD, as well as suggesting angiotensin receptor blockers and angiotensin-converting enzyme inhibitors as possible additional therapies

Abstract 4113486: Cardiovascular Benefits of Sotagliflozin in Diabetic Populations: A Meta-Analysis

Background: Sotagliflozin, an inhibitor of both SGLT1 and SGLT2, is under investigation for potential cardioprotective effects in diabetic patients. Aims: This study assesses the efficacy and cardiovascular benefits of sotagliflozin in patients with type 1 or type 2 diabetes at high cardiovascular risk or with diagnosed heart failure. Methods: We systematically searched digital databases including ClinicalTrials.gov, PubMed, Google Scholar, Cochrane, Medline, and Embase, using a PICOS-based strategy and the PRISMA framework for data reporting. Randomized controlled trials comparing sotagliflozin against placebo over a minimum duration of eight weeks were analyzed using Review Manager (RevMan) 5.4.1. Results: Our meta-analysis included 7 studies with 16,315 participants with all studies comparing either 200 or 400 mg sotagliflozin to placebo. The meta analaysis revealed significant improvements in reduction the total number of cardiovascular deaths [OR= 0.70 (95% CI (0.51- 0.95)), p = 0.02]; reduction in Non-fatal MI [OR=0.76 (95% CI (0.70- 0.84)), p &lt; 0.00001]; reduction in the incidence of hospitalizations due to HF [OR=0.54 (95% CI (0.44, 0.66)), p &lt; 0.00001]; reduction In urgent hospitalizations [OR=0.66 (95% CI (0.53, 0.83)), p=0.0004]; improvement in LVEF&gt;50% [ OR= 0.41 (95%CI (0.34, 0.51)), p&lt;0.0001] and reduction in systolic blood pressure mean reduction of -0.81 (95% CI (1.36, -0.25)), p=0.005]. However there was no statistically significant reduction in all cause mortality [0.73 (95% CI (0.42, 1.26)), p=0.26] . Conclusion: Sotagliflozin significantly reduces the incidence of cardiovascular deaths, adverse events, and hospitalizations in diabetic patients at high risk of cardiovascular complications.

Abstract 4121516: Efficacy of Sentinel Cerebral Embolic Protection Device in Transcatheter Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials and Propensity Score Matched Studies

Background: Transcatheter aortic valve replacement (TAVR) is frequently associated with stroke due to debris embolization. Although the risk of stroke with the newer-generation devices is lower, stroke still represents a significant cause of mortality and morbidity after TAVR. The Sentinel cerebral embolic protection (CEP) device (Boston Scientific) is a dual embolic filter device designed to capture debris dislodged during TAVR. The current literature concerning the efficacy of Sentinel CEP in the reduction of stroke in patients undergoing TAVR is limited and inconsistent. Aim: This meta-analysis aimed to compare clinical outcomes with Sentinel CEP device in patients undergoing TAVR. Methods: A comprehensive systematic literature search was performed on PubMed, Embase, Cochrane Library and Clinicaltrial.gov from inception until 1st May 2024 to retrieve randomized controlled trials (RCTs) and propensity-matched studies comparing TAVR with and without the Sentinel CEP device. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using the DerSimonian-Laird random-effects model, with a p-value of &lt;0.05 considered statistically significant. Results: 6 studies with a total of 25,130 patients undergoing TAVR (12608: Sentinel CEP device; 12522: Without Sentinel CEP device) were included in this meta-analysis. The use of the Sentinel CEP device in TAVR was associated with a statistically significant lower risk of acute kidney injury [OR: 0.89; 95% CI: 0.81, 0.97; p=0.01]. The use of Sentinel CEP device in TAVR was associated with a statistically insignificant trend towards reduction in stroke [OR: 0.80; 95% CI: 0.58, 1.10; p=0.18], all-cause mortality [OR: 0.74; 95% CI: 0.51, 1.07; p=0.11], and major vascular complications [OR: 0.74; 95% CI: 0.46, 1.19; p=0.21]. Conclusion: The use of the Sentinel CEP device in patients undergoing TAVR does not lead to a statistically significant reduction in stroke, all-cause mortality, and major vascular complications; however, the risk of acute kidney injury is lower. Large, multicentric RCTs are warranted to corroborate the findings of this meta-analysis.

Abstract 4125999: Elderly patients with HF with reduced ejection fraction and renal failure: are SGLT2i a good option?

SGLT-2 receptor inhibitors (SGLT-2i) have been shown to reduce cardiovascular mortality and hospitalisations for heart failure (HF) in patients with HF with reduced ejection fraction (HFrEF) and to have a nephroprotective role in patients with chronic kidney disease (CKD). However, the available evidence in patients older than 75 years and with CKD is limited. We conducted a retrospective, single-centre study including patients aged &gt;75 years diagnosed with HFrEF (defined as ejection fraction &lt;40%), CKD (eGFR &lt;60mL/min) and with an indication for treatment with SGLT-2i for HF between November 2019 and November 2022. Clinical, analytical, electrocardiographic and echocardiographic variables were collected. A total of 173 patients were included with a mean follow-up of 31.6 months (SD ±13.2). Mean age 84.7 years (SD ±4.9), 66.5% were male, 85.5% were hypertensive, 34.7% diabetic and 39.3% dyslipidaemic. Peripheral vascular disease was present in 11.6%. Mean glomerular filtration rate was 45.9 mL/min and only 2.3% were on haemodialysis. LVEF at inclusion was 29.5% (SD ±7.9), with 53.1% being of ischaemic aetiology and the most frequent functional class being NYHA II (53.2%). Thirty-seven percent had atrial fibrillation and 34.1% had complete left bundle branch block. At the end of follow-up 80.3% were on beta-blockers, 48.6% on ACE inhibitors, 37.6% on aldosterone antagonists, 23.7% on ARNI and only 11% on SGLT-2i. Survival analysis was performed using Cox logistic regression (multivariate analysis), where SGLT-2i was shown to be the only protective factor for all-cause mortality (HR 0.3 [0.1-0.9]). Male sex (HR 2.2 [1.3-3.9]) and diabetes (HR 1.6 [1.0-2.6]) were associated with higher mortality. The attached figure (figure 1) shows the Kaplan-Meier survival curves for total mortality in those patients with and without SGLT-2i (p log-rank 0.05). In our population, SGLT2i showed a significant reduction in total mortality in patients older than 75 years, with HFrEF and CKD. However, the treatment rate in this subgroup of patients is very low. Further implementation of SGLT2i treatment in this type of patient could be of significant clinical and prognostic benefit.

Abstract 4138553: Sodium-Glucose Cotransporter-2 Inhibitors After Acute Myocardial Infarction: A Meta-analysis of Randomized Controlled Trials

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed to treat type 2 diabetes mellitus, but they have also shown benefits in mitigating cardiovascular risk. Given the increasing evidence of their efficacy in diverse disease states and their proposed mechanisms of action, it is plausible that SGLT2i could improve outcomes in patients with acute myocardial infarction (AMI) if administered early after presentation. However, the efficacy and safety of these therapies when used early in the course of acute coronary heart disease remain largely unexplored. Objective: The aim of this current study was to assess the benefit of early initiation of SGLT2i after AMI. Methods: We searched the Cochrane Central Registry of Controlled Trials, PubMed, Embase, Web of Science, and clinicalTrials.gov databases for all randomized controlled trials (RCTs) published up to May 2024 comparing SGLT2 inhibitors to placebo. The primary clinical endpoints included overall mortality, cardiovascular (CV) death, heart failure (HF) hospitalization, and adverse effects. Data were analyzed using a random-effects model to account for potential heterogeneity among the included studies. Significant heterogeneity was defined as an I-squared statistic ≥ 50%; a fixed-effects model was employed if heterogeneity was not significant. The odds ratio (OR) with a 95% confidence interval (CI) was calculated for each endpoint. Results: Four RCTs were included in the analysis, comprising 11,108 patients (SGLT2i, n = 5,561; placebo, n = 5,547) who enrolled with a mean age of 63±9 years and 77% males. SGLT2i were associated with a 28% reduction in risk of HF hospitalization (OR: 0.72 [95% CI, 0.59-0.88]; p = 0.001; I 2 = 0%). However, there was no significant reduction in overall mortality (OR: 1.01 [95% CI, 0.83-1.23]; p = 0.93; I 2 = 27%), CV mortality (OR: 1.04 [95% CI, 0.83-1.30]; p = 0.74; I 2 = 0%), and serious adverse effects (OR: 1.06 [95% CI, 0.87-1.28]; p = 0.59; I 2 = 62%). Conclusion: In patients with AMI, early initiation of SGLT2i was associated with a lower risk of HF hospitalization without increasing the incidence of serious adverse effects when compared to placebo. However, no significant difference was observed in overall mortality and CV deaths.

Peripheral versus central cannulation of VA-ECMO for primary graft dysfunction after heart transplantation: a systematic review and meta-analysis

Severe primary graft dysfunction (PGD) after heart transplantation (HT) is a major cause of death and requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Given the wide between-center variability in cannula configuration, we conducted a systematic review and metanalysis including studies of adult HT recipients who required VA-ECMO for PGD to determine whether a peripheral or central configuration was associated with higher mortality. The primary endpoints were short-term and one-year mortality. Secondary endpoints were VA-ECMO-related complications. Overall, we included 16 studies comprising 874 patients from 33 centers. Using a random effects model, peripheral cannulation was associated with a non-significant reduction in short-term mortality (OR=0.73, 95%CI=0.41–1.28, I2=55.8%) and a significant reduction in one-year mortality (OR=0.60, 95%CI=0.37–0.97, I2=35.9%). Peripheral cannulation decreased risk of bleeding but increased risk of limb ischemia and infection, with similar rates of stroke and need for renal replacement therapy. Overall, certainty of evidence was low.

All-cause and cause-specific mortality risks in individuals with diabetes living alone: A large-scale population-based cohort study

AimsThe rise in one-person households is a global trend. We aimed to investigate mortality risk in individuals with diabetes living alone (IDLA) using a large-scale population-based database. MethodsA total of 2,447,557 adults with type 2 diabetes were identified from the Korean National Health Information Database. One-person households were defined based on the number of registered family members. The risks of all-cause and cause-specific mortalities were estimated using a multivariable Cox proportional hazards regression model. ResultsDuring a median follow-up period of 6.0 years, 191,084 deaths (7.8 %) occurred. IDLA had a higher risk of mortality compared to those not living alone after adjusting for potential confounders (HR 1.20, 95 % CI: 1.18–1.22). This association was more prominent in younger individuals, men, and those with low income, and it was dependent on the duration of living alone. The risks of cause-specific mortality were all significantly higher in the IDLA group compared with the non-IDLA group. Adherence to favorable lifestyle behaviors was associated with a significant reduction in all-cause mortality, particularly in IDLA. ConclusionsThe elevated risk of mortality in IDLA highlights the need for tailored medical interventions and social assistance, particularly for those with unhealthy lifestyles or low income.

Impact of the Coronavirus Disease 2019 [COVID-19] Pandemic on Post-Acute Care of Patients with Heart Failure and the Effectiveness of Vaccine Prevention.

The Heart Failure Post-Acute Care [HF-PAC] program is a specialized healthcare program aimed at providing comprehensive care and support for patients with heart failure [HF] as they transition from acute hospital settings to home. But the impact of the coronavirus disease 2019 [COVID-19] pandemic on the HF-PAC program remains unknown. Furthermore, the effects of the comprehensive COVID-19 vaccination program on these patients with HF-PAC warrants further investigation. A total of 265 patients with acute decompensated HF were admitted to the hospital between May 2020 and October 2022. Of these, 159 patients underwent planned HF-PAC follow-up for 6 months, followed by scheduled follow-up visits every 3 months and unscheduled telephone randomized visits for at least another 6 months. The program completion rate was nearly 92%. COVID-19 significantly impacted patients with HF-PAC, leading to an increased mortality [13.3%] compared to before the pandemic [6.5%]. In our patient cohort, 83% had received at least 1 dose of vaccine and 61% had received > 3 doses. Of these patients with HF-PAC, 34% contracted COVID-19 infection post discharge, and 8.8% died owing to the infection. Of the mortality group, 42.9% patients were not vaccinated, and 28.6% received 1 vaccine dose, and their vaccination rate was lower than in the survival group [p = 0.01]. The COVID-19 pandemic had a significant impact on patients enrolled in the HF-PAC program; receiving more than 3 doses of the COVID-19 vaccine was associated with a significant reduction in mortality rates among these patients.

Neuroprotective effects of GLP-1 receptor agonists in neurodegenerative Disorders: A Large-Scale Propensity-Matched cohort study

BackgroundGLP-1 receptor agonists, traditionally used for treating type 2 diabetes mellitus and obesity, have demonstrated anti-inflammatory properties. However, their potential neuroprotective effects in neurodegenerative disorders remain unclear. ObjectiveTo evaluate the impact of GLP-1 receptor agonists on the risk of developing various neurodegenerative conditions in obese patients. MethodsThis comprehensive retrospective cohort study analyzed data from 5,307,845 obese adult patients across 73 healthcare organizations in 17 countries. Propensity score matching was performed, resulting in 102,935 patients in each cohort. We compared the risk of developing neurodegenerative disorders between obese patients receiving GLP-1 receptor agonist therapy and those who were not. ResultsObese patients treated with GLP-1 receptor agonists showed significantly lower risks of developing Alzheimer’s disease (RR = 0.627, 95 %CI = 0.481–0.817), Lewy body dementia (RR = 0.590, 95 %CI = 0.462–0.753), and vascular dementia (RR = 0.438, 95 %CI = 0.327–0.588). The risk reduction for Parkinson’s disease was not statistically significant overall (RR = 0.784, 95 %CI = 0.580–1.058) but was significant for semaglutide users (RR = 0.574, 95 %CI = 0.369–0.893). Semaglutide consistently showed the most pronounced protective effects across all disorders. Additionally, a significant reduction in all-cause mortality was observed (HR = 0.525, 95 %CI = 0.493–0.558). ConclusionThis study provides evidence that the effects of GLP-1 receptor agonists may extend beyond their known metabolic and cardioprotective benefits to include neuroprotection, associated with a decreased risk of developing various neurodegenerative disorders. These findings suggest the potential for expanding the therapeutic applications of GLP-1 receptor agonists to improve neurocognitive outcomes. Further research is warranted to elucidate the mechanisms underlying these neuroprotective effects and to explore their clinical applications in neurodegenerative disease prevention and treatment.

Assessing the Efficacy and Challenges of Tofacitinib in the Management of COVID-19: A Systematic Review and Meta-analysis of Cohort Studies

Objectives: Global healthcare faces challenges in combating COVID-19, with rising cases despite widespread vaccination. Severe COVID-19 cases, marked by acute respiratory distress and cytokine release syndrome, highlight the importance of managing cytokine storms. Janus kinase (JAK) inhibitors, such as tofacitinib, show promise in this regard. While tofacitinib is recommended for severe cases, challenges include adverse effects, conflicting studies, and the need for further investigation of new virus strains. Overcoming these hurdles is crucial for developing an effective treatment protocol and reducing COVID-19 mortality. Methods: This study conducted a comprehensive search across PubMed, Scopus, and ISI Web of Science for observational studies on tofacitinib treatment in human adults with COVID-19. The search covered a specified period up to 2024. Data extraction, including study characteristics and quality assessment, employed the Newcastle Ottawa Scale and a modified Cochrane tool. Statistical analysis, conducted with Comprehensive Meta-Analysis Software, assessed heterogeneity and significance levels. Results: The meta-analysis of the three studies showed a significant reduction in mortality (Risk Ratio: 0.372, 95% CI: 0.213–0.649, P-value = 0.001) with low heterogeneity (Cochrane P-value = 0.793), while no significant reduction in the need for mechanical ventilation was observed (Cochrane P-value = 0.194). Conclusion: Tofacitinib administration shows a significant reduction in COVID-19 mortality. However, the limited studies on its efficacy highlight the need for cautious interpretation in clinical assessments.

TAKE AN OLD DRUG AND STAY YOUNG? METFORMIN AS AN ANTI-AGING MEDICATION – A LITERATURE REVIEW.

AIMS: Metformin is the main drug used in the treatment of type 2 diabetes mellitus, and the most widely prescribed oral antihyperglycemic medication. Its mechanism of action is still not completely understood and research into new uses for the compound is still ongoing, with one possible novel application of the medication being to combat aging on both the cellular and the macroscopic level. The aim of the study is to evaluate the current state of knowledge on metformin’s potential as a lifespan-extending and anti-senescence drug, present evidence on the matter and assess possible lanes of further study into such effects. METHODS: The literature review was performed using Internet research paper databases (PubMed, Google Scholar, Medline), using articles available in English. RESULTS: Multiple papers suggest tentative support for the notion that metformin may contribute to slowing cellular senescence, as well as to extending the human lifespan. Theoretical knowledge exists that shows possible routes of action of metformin in this regard. CONCLUSIONS: There is ample evidence in the literature for metformin’s possible effects as an anti-aging drug. Numerous cellular pathways by which it could exert lifespan-extending effects have been elucidated, and in vivo studies on some non-human animals have shown a measurable decrease in their production of aging markers, as well as an increase in the lifespan. Studies on diabetic patients have also demonstrated a significant reduction in all-cause mortality in that particular group. However, there is a lack of data and a need for more research that would investigate metformin’s potential as a universal anti-senescence agent more directly. Two large-scale studies (MILES and TAME) in the area are currently underway.

Remote monitoring of implantable cardioverter defibrillators: a systematic review and meta-analysis of randomised controlled trials

Abstract Background Remote monitoring (RM) of implantable cardioverter defibrillators (ICD) has been widely adopted as the standard follow-up strategy [1]. Observational data [2,3] has suggested morbidity and mortality reduction associated with RM compared to traditional in-person ICD follow-up, however, randomised controlled trials (RCTs) demonstrate heterogeneous results. Purpose To assess the impact of RM of ICDs on morbidity and mortality through a systematic review and meta-analysis of RCTs comparing RM versus in-person follow-up. Methods PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and reference lists were searched for RCTs evaluating RM compared to in-person follow-up of patients with ICDs or cardiac resynchronisation therapy with defibrillator (CRT-D) devices. Meta-analyses of all-cause mortality, cardiovascular (CVD) hospitalisation and inappropriate ICD shock rates were performed. Results Literature search identified 1011 relevant publications, out of which 15 RCTs [4-18] involving a total of 7579 patients (13 RCTs reporting mortality rate, 7 RCTs reporting CVD hospitalisation rate, 6 RCTs reporting inappropriate ICD shock rate) met the inclusion criteria. Pooled analyses demonstrated that RM is not associated with a significant reduction in all-cause mortality (OR 0.95; 95% CI 0.78-1.16; p=0.60)(Figure 1, panel a) or odds of CVD hospitalisation (OR 0.95; 95% CI 0.72-1.25; p=0.70) (Figure 1, panel b). RM was, however, shown to be associated with significantly lower odds of receiving an inappropriate ICD shock compared to the control group (OR 0.63; 95% CI 0.46-0.88; p=0.006) (Figure 1, panel c). The IN-TIME study (the only RCT that independently reached statistical significance in terms of RM effect on mortality) enrolled patients exclusively with a Biotronik ICD or CRT-D; this raised the question as to whether the choice of vendor had an impact on mortality. Our subgroup analysis of the Biotronik device studies demonstrated that there was no significant all-cause mortality benefit (OR 0.87, 95% CI 0.59-1.27; p=0.46). Conclusions This meta-analysis of 15 RCTs including 7579 patients suggests that RM of ICDs is associated with a reduction in inappropriate ICD shocks, without a significant reduction in mortality or CVD hospitalisation when compared to in-person follow-up. Further studies comparing different RM processing and alert response models are warranted.

Effect of catheter ablation in atrial fibrillation patients irrespective of their baseline heart failure: An updated meta-analysis

Abstract Introduction Patients with atrial fibrillation (AF) are associated with higher morbidity and mortality. Catheter ablation (CA) is supposed to improve outcomes in these patients. We aimed to update the evidence regarding CA in AF patients irrespective of their baseline heart failure. Methods We searched PubMed, Scopus, WOS, and Cochrane until February 2024 for relevant studies assessing the impact of CA compared to medical regimens in AF patients with and without heart failure. Outcomes of interest were all-cause mortality, cardiovascular mortality, hospitalization for HF, hospitalization for other cardiovascular causes, and stroke. Results 13 studies were included with a total of 18370 patients. In HF patients, irrespective to their ejection fraction, CA was associated with a significant reduction in all-cause mortality (RR 0.40, 95%CI [0.37 to 0.44], cardiovascular mortality (RR 0.36, 95%CI [0.32 to 0.42]), hospitalization from HF (RR 0.65, 95%CI [0.51 to 0.82]), hospitalization from other cardiovascular causes (RR 0.71, 95%CI [0.57 to 0.89]), and the incidence of stroke (RR 0.55, 95%CI [0.50 to 0.62]). Also, six studies with a total of 2015 patients compared CA to medical treatment in AF patients with HFrEF and HFpEF. CA showed a significant reduction in all-cause mortality in HFpEF patients compared to HFrEF (RR 0.46, 95%CI [0.25 to 0.85]) with no significant differences in terms of other studied outcomes. Moreover, six studies compared CA to medical treatment in HF vs no HF with a total of 2931 patients. Patients with AF and no HF had a significant reduction in all-cause mortality (RR .041, 95%CI [0.20 to 0.80]), with no significant differences in stroke or AF recurrence. Conclusion Current evidence supports the use of catheter ablation in atrial fibrillation patients, irrespective of their baseline heart failure, to achieve lower mortality and hospitalization rates.all-cause mortalitycardiovascular mortality

Impact of late reperfusion therapy in patients with inferior ST-segment elevation myocardial infarction and right ventricular dysfunction: one size never fits all

Abstract Background A significant proportion of ST-segment elevation myocardial infarction (STEMI) patients present late to the emergency room with limited evidence of benefit of reperfusion after 12 hours of symptom onset. Inferior myocardial infarction (MI) with right ventricle (RV) dysfunction is associated with high morbidity and mortality, however, the RV has a unique physiology that allows it to withstand ischemia better and recover faster. Purpose To compare adverse in-hospital cardiovascular events in latecomers with inferior STEMI and RV dysfunction admitted to a cardiovascular intensive care unit (CICU) from a low-to-middle-income country, who underwent late reperfusion treatment versus conservative treatment. Methods A retrospective cohort study was conducted from March 2022 to April 2023. Patients with inferior STEMI and RV dysfunction who received late reperfusion treatment were included. RV dysfunction was defined as a TAPSE &amp;lt;17 mm, tricuspid annular systolic velocity on TDI &amp;lt;9.5 cm/s, or a fractional area change &amp;lt;35%. Late reperfusion was defined as primary percutaneous coronary intervention (PCI) performed after 12 hours of symptom onset or rescue PCI after 12 hours of failed fibrinolysis. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were cardiovascular death, reinfarction, stroke, cardiogenic shock, and mechanical complications. Results During the specified period, a total of 106 patients met the inclusion criteria from a total of 1,786 patients admitted to the CICU in our center. Only 60 patients underwent late PCI, accounting for 56% of the cases, with a median time of onset of symptoms to reperfusion of 19.4 hours (IQR: 15.7, 30.2). The average age was 66.5 ± 10.4 years, and 28% were women. Although the all-cause death rate was lower among late PCI group (13.3% vs 26.1%; p=0.096), this difference did not reach statistical significance in the bivariate analysis. Stratified by cardiogenic shock, a lower rate of all-cause mortality was also observed (33% vs 55%, p=0.15). The incidence of reinfarction was significantly lower in the late PCI group (0% vs 13%, p=0.004). In the multivariate analysis, adjusting for those who underwent PCI between 12-48 hours, revascularization of latecomers was independently associated with a significant reduction of mortality (adjusted OR 0.22; 95% CI 0.05-0.92; p=0.038). In a post-hoc analysis, late PCI showed a lower association with the composite outcome of all-cause mortality and reinfarction (adjusted OR 0.16, 95% CI 0.04-0.56; P=0.004). Conclusion(s) Our study demonstrates that implementing a reperfusion strategy in latecomers with inferior STEMI and RV dysfunction significantly reduces the risk of in-hospital mortality and reinfarction. This suggests a potential benefit of expanding the therapeutic window for PCI in this high-risk population. However, prospective studies are needed to conclude these preliminary findings.