Manasrah, AlMothana

BACKGROUND: Blood pressure management following successful reperfusion with endovascular thrombectomy for acute ischemic stroke due to large vessel occlusion remains debated. This meta-analysis aimed to determine whether intensive systolic blood pressure (SBP) management improves clinical outcomes compared with a standard approach after endovascular thrombectomy. METHODS: We systematically searched PubMed, Scopus, Embase, and Web of Science through October 2025 for relevant randomized controlled trials comparing intensive (SBP target <140 mm Hg) versus standard (SBP target <180 mm Hg) management. The primary efficacy and safety outcomes were functional independence (modified Rankin Scale score, 0–2) and any intracranial hemorrhage, respectively. We performed frequentist and Bayesian random-effects meta-analyses, supplemented by trial sequential analysis. RESULTS: Six randomized controlled trials comprising 1972 patients were included. In frequentist analysis, intensive SBP management was associated with a significantly reduced likelihood of achieving functional independence (risk ratio, 0.83 [95% CI, 0.73–0.93]). Bayesian analysis confirmed this harmful effect (posterior median risk ratio, 0.83 [95% credible interval, 0.7–1.02]), with a posterior probability of benefit of only 3.2%. Furthermore, ordinal shift analysis indicated that intensive SBP management was associated with a significant shift toward worse functional outcomes across the full modified Rankin Scale score distribution (common odds ratio, 1.26 [95% CI, 1.10–1.44]), a finding supported by a low posterior probability of benefit of 2.1%. No significant differences were observed in the risk of any intracranial hemorrhage (risk ratio, 1.05 [95% CI, 0.96–1.16]). The corresponding Bayesian analysis yielded a posterior risk ratio estimate of 1.05 (95% credible interval, 0.90–1.21) for any intracranial hemorrhage, with a posterior probability of benefit of 23%. Trial sequential analysis indicated that the cumulative evidence reached the boundary for harm and futility for the primary efficacy and safety outcomes, respectively. CONCLUSIONS: In patients with acute ischemic stroke following successful endovascular thrombectomy, intensive SBP management was associated with worse functional outcomes and provided no clear safety benefit. These findings support a standard, guideline-based SBP management strategy over an intensive approach.

ABSTRACTBackground and ObjectiveSeladelpar is an oral, once‐daily medication that improves cholestasis through its selective peroxisome proliferator‐activated receptor (PPAR‐δ) agonism. It shows promising efficacy in treating primary biliary cholangitis (PBC) patients.MethodsA systematic review and meta‐analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Cochrane, Scopus, and WOS until July 19th, 2025. Dichotomous outcomes were reported using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI).ResultsThree RCTs with 499 patients were included. Seladelpar was significantly associated with an increased ALP normalization (RR: 21.12 with 95% CI [4.14, 107.58], p < 0.01), biochemical response (RR: 3.06 with 95% CI [2.00, 4.70], p < 0.01), and decreased pruritus NRS score change (MD: −1.47 with 95% CI [−2.73, −0.21], p = 0.02). Seladelpar was also significantly associated with a decreased incidence of pruritus (RR: 0.54 with 95% CI [0.31, 0.94], p = 0.03) but with an increased incidence of headache (RR: 3.37 with 95% CI [1.11, 10.23], p = 0.03). However, there was no significant difference between seladelpar and placebo regarding the incidence of any adverse events (RR: 0.96 with 95% CI [0.87, 1.06], p = 0.43).ConclusionSeladelpar improved liver biomarkers of cholestasis and reduced pruritus in patients with PBC without significantly increasing the adverse effects. This makes seladelpar a promising addition to the treatments available for PBC.Trial Registration: PROSPERO: CRD42024521208

ABSTRACTTransplant‐associated thrombotic microangiopathy (TA‐TMA) is an endothelial dysfunction syndrome observed after allogeneic hematopoietic cell transplant (alloHCT). Our aim was to externally validate the impact of high‐risk features on the clinical outcomes of adult patients meeting the updated TA‐TMA harmonizing criteria. Between 2005 and 2022, 99 patients were diagnosed with TA‐TMA at Mayo Clinic Rochester (incidence 6.2%) after a median of 137 days post alloHCT (IQR: 34–283 days). The development of TA‐TMA was associated with an inferior overall survival posttransplant (HR: 3.8, 95% CI: 2.97–4.72). High‐risk features, including concomitant infection, acute graft‐versus‐host disease (GVHD), and organ dysfunction, were associated with poor survival, while LDH elevation was not associated with inferior outcomes. The most common treatment strategy for TA‐TMA was discontinuation of calcineurin or mTOR inhibitors in 80 (81%) patients. Thirty (37.5%) patients experienced worsening of GVHD with this strategy, of which 26 (86.7%) patients had died at last follow‐up. The most common cause of death among these patients was worsening GVHD (69%; n = 18), followed by infection (11%; n = 3), disease relapse (8%; n = 2), other/unknown causes (8%; n = 2), or TA‐TMA (4%; n = 1). Objective response rate (ORR) to initial treatment for the cohort was 56.6%. Eculizumab was used in 11 patients with an observed ORR of 70%, including 5 complete responses. In conclusion, TA‐TMA remains a significant contributor to non‐relapse mortality and is associated with worse survival following alloHCT. Not all high‐risk features, particularly LDH elevation, have consistently demonstrated a negative impact in adult cohorts. Patients with TA‐TMA may benefit from immune suppression dose adjustment, rather than a discontinuation, and the addition of complement‐directed therapy, particularly among high‐risk patients.

ABSTRACTBackgroundAnemia is frequently observed as a comorbidity in atrial fibrillation (AF), especially in elderly patients and in those on anticoagulation. This has been associated with poor clinical outcomes. We aim to investigate the impact of anemia on clinical outcomes in patients with AF on oral anticoagulation.MethodsWe comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through March 2024 and conducted a prognostic systematic review and meta‐analysis. All analyses were performed using R V. 4.3.1. This meta‐analysis was registered at PROSPERO (CRD42024556023).ResultsWe included 23 studies comprising 286,781 patients for analysis. Anemia had a significant association with an 84% increase in risk of major bleeding (HR: 1.84 with 95% CI [1.59, 2.13], p < 0.01), a 32% increase in the risk of intracranial hemorrhage (HR: 1.32 with 95% CI [1.10, 1.58], p < 0.01), a 98% increase in the risk of gastrointestinal bleeding (HR: 1.98 with 95% CI [1.67, 2.35], p < 0.01), and a 91% increase in the risk of all‐cause mortality (HR: 1.91 with 95% CI [1.46, 2.51], p < 0.01). However, the impact of anemia did not significantly affect the risk of stroke, transient ischemic stroke (TIA), or systemic embolism (HR: 1.07 with 95% CI [0.93, 1.22], p = 0.36).ConclusionAnemia was significantly associated with an increased risk of major bleeding, intracranial hemorrhage, gastrointestinal bleeding, and all‐cause mortality. However, anemia did not significantly impact stroke, TIA, or systemic embolism.

Abstract Background While the cardioprotective effects of glucagon-like peptide -1 (GLP-10) agonists are well-documented in diabetic patients, their impact on cardiovascular outcomes in patients with obesity without diabetes mellitus remains debated. Purpose This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of GLP-1 on cardiovascular outcomes in patients with obesity without diabetes mellitus. Methods A systematic review and meta-analysis synthesizing RCTs were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through December 26th, 2023. Dichotomous data were pooled using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Results We included 19 RCTs with a total of 32,884 patients. There was no difference between GLP-1 agonists and placebo regarding cardiovascular mortality (RR: 0.85, 95% CI [0.71- 1.01], P= 0.07). However, GLP-1 agonists significantly decreased the incidence of all-cause mortality (RR 0.83, 95% CI 0.72 to 0.94, p &lt; 0.0001), non-cardiovascular mortality (RR 0.78, 95% CI 0.63 to 0.96, p = 0.02), and myocardial infarction (RR 0.73, 95% CI 0.62 to 0.87, p &lt; 0.0001). Also, GLP-1 agonists significantly increased the incidence of any adverse events (RR 1.11, 95% CI 1.05 to 1.16, p &lt; 0.0001), with no difference regarding the incidence of serious adverse events. Conclusion GLP-1 agonists not only demonstrated substantial benefits in reducing cardiovascular risks, including all-cause mortality and myocardial infarction, but also effectively promoted weight loss and improved lipid profiles and blood pressure control. However, their use is accompanied by a higher incidence of gastrointestinal adverse effects and heterogeneity in outcomes, highlighting the need for individualized treatment approaches.

Abstract Background Previous studies have suggested that pre-treatment of coronary artery calcification with rotational atherectomy (RA) prior to stent deployment can enhance procedural success, but this does not necessarily translate into improved clinical outcomes. Recently, the Orbital Atherectomy (OA) system has been introduced into clinical practice to enhance lesion preparation. Purpose Our study aims to evaluate the safety and efficacy of both RA and OA as pre-treatment strategies before stent deployment in patients with coronary artery calcification. Methods We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. These were identified through systematic PubMed, Web of Science, Scopus, Embase, and Cochrane searches until January 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using Stata version 17. Results Our analysis included eleven studies encompassing 81,873 patients. No significant difference was observed between RA and OA in terms of major adverse cardiovascular events (MACE) (RR: 0.81 with 95% CI [0.64, 1.02], P= 0.07). However, OA was significantly associated with a decreased incidence of all-cause mortality (RR: 0.60 with 95% CI [0.52, 0.70], P&lt; 0.01), target vessel revascularization (TVR) (RR: 0.43 with 95% CI [0.22, 0.82], P= 0.01), coronary artery bypass grafting (CABG) (RR: 0.78 with 95% CI [0.62, 0.97], P= 0.03), and fluoroscopy time (MD: -3.93 with 95% CI [-7.39, -0.48], P= 0.03). There was no significant difference between RA and OA in cardiac death (RR: 2.65 with 95% CI [0.94, 7.51], P= 0.07), target lesion revascularization (TLR) (RR: 0.57 with 95% CI [0.23, 1.41], P= 0.22), myocardial infarction (RR: 0.79 with 95% CI [0.62, 1.01], P= 0.06), stent thrombosis (RR: 0.33 with 95% CI [0.09, 1.23], P= 0.10), stroke (RR: 0.76 with 95% CI [0.57, 1.01], P= 0.06), re-admission (RR: 0.76 with 95% CI [0.48, 1.19], P= 0.23), vessel closure (RR: 0.78 with 95% CI [0.18, 3.33], P= 0.74), procedural duration (MD: -5.43 with 95% CI [-21.71, 10.84], P= 0.51), length of hospital stay (MD: 0.21 with 95% CI [-0.47, 0.90], P= 0.54), and contrast amount (MD: -3.68 with 95% CI [-9.37, 2.01], P= 0.21). Conclusion Both RA and OA as pre-treatment strategies before stent deployment demonstrate similar outcomes for numerous cardiovascular events. However, OA is associated with lower rates of all-cause mortality, TVR, CABG, and fluoroscopy time.