Citations

ABSTRACT Background and Aims Out‐of‐hospital cardiac arrest stands as the primary cause of worldwide mortality. Therefore, all healthcare workers must comprehensively understand and practically apply cardiopulmonary resuscitation (CPR). To address the paucity of literature on this subject, we conducted a nationwide survey among healthcare professionals in Pakistan. Methods This nationwide cross‐sectional study was based on an online questionnaire. The sample pool comprised healthcare professionals and medical students from all over Pakistan. The survey comprised 18 questions aimed to assess the comprehension of CPR, determine the source of their basic life support (BLS) training, and evaluate their competence in performing CPR in real‐life situations. Results The sample size consisted of 951 participants from Pakistan. A total of 712 responders (75%) reported having received CPR or CPR with an Automated External Defibrillator (AED) course, and the same percentage reported that their respective universities had organized the course. The responders reported that the BLS course was made mandatory in only 60% of cases. Most of the respondents were first‐year medical students (21%) and postgraduates (21%). Most of the respondents (78%) professed that the courses had been theoretical as well as practical, and 66% felt confident enacting CPR in out‐of‐hospital settings. Overall, no province was able to achieve a score of greater than 50% when assessed about their knowledge regarding cardiac arrest and CPR. Conclusion This study provides a detailed insight into Pakistan healthcare workers' CPR knowledge and perceptions belonging to different provinces, institutes, designations, and specialties. The participants reported being confident in performing CPR but demonstrated gaps when assessed regarding the revised guidelines and their performance in different scenarios. There is room for further research in overcoming the language barriers and other discrepancies faced by this study.

e20593 Background: Tislelizumab, an anti-PD-1 antibody, is emerging as a promising immunotherapy agent and has demonstrated clinical benefit and acceptable tolerability in recent lung cancer trials. This study aims to assess the safety and efficacy of Tislelizumab, as monotherapy or combined with chemotherapy (Group 1), as a superior treatment alternative for lung cancer compared to standard chemotherapy (Group 2) in improving patient outcomes. Methods: Following PRISMA guidelines, a systematic search was conducted through MEDLINE, Embase, Scopus, Science Direct, Cochrane (CENTRAL), and ClinicalTrials.gov from inception to December 2024 to identify Randomized Control Trials (RCTs). Hazards ratio (HRs) and risk ratios (RRs) were generated, by employing a Random-effects model with a 95% confidence interval (CI). Statistical analysis was performed using RevMan 5.4, with statistical significance set at p<0.05. Our outcomes of interest were Progression Free Survival (PFS), Overall Survival (OS), Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of response (DOR), and treatment-related adverse Events. Results: A total of 6 RCTs involving 2107 patients were included for analysis. Pooled analysis demonstrated that Group 1 significantly improved PFS, OS, and DOR with HRs of 1.85 (95% CI: 1.71-1.99; p <0.00001, I² = 0%), 2.01 (95% CI: 1.75-2.29; p <0.00001, I² = 0%) and 2.14 (95% CI: 1.52-3.03; p <0.0001, I² = 39%), respectively. Group 1 has better DCR and ORR compared to Group 2 with RRs of 1.52 (95% CI: 1.12-2.07; p= 0.007, I² = 97%) and 1.50 (95% CI: 1.20-1.86; p= 0.0003, I² = 83%), respectively. The high heterogeneity observed in the pooled analysis of DCR (I² = 97%) and ORR (I² = 83%) likely reflects variability in study populations, treatment protocols, and response assessment criteria across the included RCTs. Subgroup or sensitivity analyses could help identify contributing factors. Despite the heterogeneity, the pooled effect sizes indicate a statistically significant improvement in DCR and ORR with Tislelizumab, with caution warranted when generalizing these findings. Group 1 significantly reduced all-cause mortality compared to Group 2 (RR = 0.89; 95% CI: 0.83–0.95; p = 0.0003), with no heterogeneity (I² = 0%). No significant differences were found in adverse events, except for ALT elevations. (RR = 1.36; 95% CI: 1.14–1.61; p = 0.0006, I² = 25%). Conclusions: Tislelizumab, with or without chemotherapy, demonstrates greater PFS and OS benefits compared to chemotherapy alone in patients with lung cancer. There was a significantly reduced all-cause mortality in the intervention group; however, the observed increase in the risk of ALT elevation underscores the need for vigilant liver function monitoring. When combined with chemotherapy, Tislelizumab presents a promising treatment option for lung cancer.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Background/objective: HCM is a structural disorder of the myocardium that leads to sudden cardiac death in young adults. We synthesized an updated understanding of the role of Cardiac Myosin Inhibitors (CMIs) in HCM by pooling data from RCTs. Methods: We identified six published RCTs, involving 826 participants. Data were extracted pertaining to study characteristics; primary outcomes of interest–(1) change from baseline in resting left ventricular outflow tract (LVOT) peak gradient, (2) change from baseline in Valsalva LVOT peak gradient, and (3) improvement of ≥1 NYHA class–and secondary outcomes. These were pooled using Review Manager 5.4, employing a random-effects model, and reported as odds ratios (ORs) or mean differences (MDs). Results: We found statistically significant between-group difference favoring CMIs in change from baseline in LVOT peak gradient: at rest (MD −39.33; −53.01 to −25.64), post-Valsalva (MD −48.99; −53.96 to −44.03), and post-exercise (MD −37.11; −44.34 to −29.87); ≥1 NYHA class improvement (OR 4.10; 2.79–6.02), change from baseline in peak oxygen uptake (MD −37.11; −44.34 to −29.87), LVOT gradient ≤30 mm hg (RR 14.89; 7.47–29.67), participants eligible for septal reduction therapy (RR 0.26; 0.18–0.36), and change from baseline in KCCQ-CSS score (MD 8.54; 5.36–11.71). Subgrouping by intervention type (mavacamten vs. aficamten) revealed non-significant results for all primary outcomes. Conclusions: CMIs can contribute to improving key efficacy outcomes for patients with HCM while reducing incidence of SRT.

Abstract Background Thromboembolic stroke risk remains a clinical challenge in cardiac amyloidosis (CA) patients with atrial fibrillation because of the increased prevalence of left atrial appendage thrombi irrespective of CHA2DS2-VASc score and a higher prevalence of factors that increase the risk of bleeding with anticoagulation. Left atrial appendage closure (LAAC) is an effective option in patients with atrial fibrillation and high bleeding risk; however, data describing a LAAC strategy for stroke prevention in patients with CA is limited. Among non-CA patients, procedural success and serious complication rates are around 98% and 3% respectively. Purpose In this multicenter retrospective study, we aimed to investigate whether left atrial appendage closure (LAAC) could reduce the risk of bleeding complications and ischemic cerebrovascular events in patients with CA. Methods In an international multi-center retrospective study, patients with CA that underwent LAAC were included. The diagnosis of CA was established on the basis of histologic confirmation or advanced multimodality cardiac imaging as per current consensus statements. Results A total of 28 patients (93% male; 87% ATTR-CA; 13% AL-CA; mean age 80 years) met inclusion criteria. At baseline, mean CHA2DS2-VASc and HAS-BLED scores were 4 and 3 respectively, mean left ventricular ejection fraction was 50%, and mean indexed left atrial volume was 58 mL/m2. 21% of patients had a prior history of ischemic stroke, 14% prior history of hemorrhagic stroke, 7% prior transient ischemic attack, and 54% had a prior history of major or minor bleeding. Procedural success was achieved in 26 patients (93%) with procedural complications occurring in 2 patients (vascular access site bleeding and cardiac tamponade). Regarding in-hospital and follow-up complications, 0% ischemic stroke, 0% hemorrhagic stroke, and major or minor bleeding in 4% of patients. During follow up, device thrombosis occurred in only 1 patient. Conclusion LAAC is a feasible and effective alternative to anticoagulation in patients with CA and excessive bleeding risk, with procedural success and complication rates similar to reported studies of non-CA patients.

Acute kidney injury (AKI) frequently complicates the repair of Stanford type A aortic dissection (TAAD). This systematic review, meta-analysis, and meta-regression analysis aimed to elucidate the prognostic impact of AKI in these patients. A literature search in PubMed, EMBASE, and Google Scholar identified relevant studies on the predictors and outcomes of AKI following TAAD repair. The primary endpoint was 30-day mortality; secondary endpoints included stroke, dialysis/continuous renal replacement therapy (CRRT), and other complications. Random-effects meta-analyses were used, with significance set at P < 0.05. Twenty-one studies (10 396 patients) were analyzed. AKI was associated with higher risks of 30-day mortality (risk ratio = 3.98), stroke (risk ratio = 2.05), dialysis/CRRT (risk ratio = 32.91), cardiovascular (risk ratio = 2.85) and respiratory complications (risk ratio = 2.13), sepsis (risk ratio = 4.92), and re-exploration for bleeding (risk ratio = 2.46). No significant differences were noted in sternal wound infection, tracheostomy, paraplegia, or hepatic failure. AKI significantly increases mortality, morbidity, hospital, and ICU stay duration in TAAD repair patients.

Background Optimal duration and choice of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention remain controversial. Methods and Results Digital databases (PubMed, Cochrane, and Embase) were queried to select all randomized controlled trials on a post–percutaneous coronary intervention population with acute coronary syndrome. Dual‐antiplatelet therapy (DAPT) with aspirin and clopidogrel for 12 months was compared with 4 major strategies: high‐potency, high‐ to low‐potency, low‐dose, and short‐duration DAPT. A network meta‐analysis was performed to compare the safety and efficacy of different antiplatelet strategies. This study was the second updated manuscript under the International Prospective Register of Systematic Review registration (CRD42021286552). Thirty‐two randomized controlled trials comprising 103 459 (51 750 experimental, 51 709 control) patients were included. Compared with DAPT with aspirin and clopidogrel for 12 months, high‐ to low‐potency DAPT (risk ratio [RR], 0.69 [95% CI, 0.52–0.92]) and aspirin+prasugrel containing DAPT for 12 months (RR, 0.84 [95% CI, 0.72–0.98]) had a significantly lower, whereas DAPT for 1 month followed by clopidogrel only (RR, 1.59 [95% CI, 1.06–2.39]) had a higher, incidence of major adverse cardiovascular events at 1 year (median follow‐up). Prasugrel (RR, 1.35 [95% CI, 1.09–1.66]) and ticagrelor (RR, 1.38 [95% CI, 1.17–1.62]) containing DAPT for 12 months had significantly higher rates, whereas high‐ to low‐potency DAPT (RR, 0.85 [95% CI, 0.63–1.15]) had no significant risk of major bleeding. Conclusions Aspirin and ticagrelor for 3 months, followed by aspirin and clopidogrel for the remaining duration, can be considered the optimal strategy for treating post–percutaneous coronary intervention patients with acute coronary syndrome because of a significantly reduced risk of major adverse cardiovascular events without increasing the risk of bleeding.

BACKGROUND: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by KCNH2 . Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance. Here we sought to test whether variant-specific information, primarily from high-throughput functional assays, could improve both classification and cardiac event risk stratification in a large, harmonized cohort of KCNH2 missense variant heterozygotes. METHODS: We quantified cell-surface trafficking of 18 796 variants in KCNH2 using a multiplexed assay of variant effect (MAVE). We recorded KCNH2 current density for 533 variants by automated patch clamping. We calibrated the strength of evidence of MAVE data according to ClinGen guidelines. We deeply phenotyped 1458 patients with KCNH2 missense variants, including QTc, cardiac event history, and mortality. We correlated variant functional data and Bayesian long QT syndrome penetrance estimates with cohort phenotypes and assessed hazard ratios for cardiac events. RESULTS: Variant MAVE trafficking scores and automated patch clamping peak tail currents were highly correlated (Spearman rank-order ρ=0.69; n=433). The MAVE data were found to provide up to pathogenic very strong evidence for severe loss-of-function variants. In the cohort, both functional assays and Bayesian long QT syndrome penetrance estimates were significantly predictive of cardiac events when independently modeled with patient sex and corrected QT interval (QTc); however, MAVE data became nonsignificant when peak tail current and penetrance estimates were also available. The area under the receiver operator characteristic curve for 20-year event outcomes based on patient-specific sex and QTc (area under the curve, 0.80 [0.76–0.83]) was improved with prospectively available penetrance scores conditioned on MAVE (area under the curve, 0.86 [0.83–0.89]) or attainable automated patch clamping peak tail current data (area under the curve, 0.84 [0.81–0.88]). CONCLUSIONS: High-throughput KCNH2 variant MAVE data meaningfully contribute to variant classification at scale, whereas long QT syndrome penetrance estimates and automated patch clamping peak tail current measurements meaningfully contribute to risk stratification of cardiac events in patients with heterozygous KCNH2 missense variants.

Abstract Objective The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs). Design This is a single-center cohort study. Methods Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016. Results Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P &lt; .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P &lt; .0001), ≥1 cm growth (OR = 15.3, P &lt; .0001), and higher postdexamethasone cortisol (OR = 6.6 for &gt;5 vs &lt;1.8 μg/dL, P = .002). Conclusions Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.