Search Results (1,088)

Background: Intermediate-risk acute pulmonary embolism (PE) is clinically heterogeneous, and early deterioration may occur despite initial normotension. The Endothelial Activation and Stress Index (EASIX) is a readily available laboratory index reflecting endothelial activation, cellular injury, renal-perfusion stress, and platelet-related thromboinflammatory burden. We investigated whether admission EASIX and echocardiographic right ventricular-pulmonary arterial (RV-PA) coupling assessed by the TAPSE/PASP ratio identify intermediate-risk PE patients at increased risk for an early adverse clinical outcome (EACO). Methods: This retrospective cohort study included 900 consecutive intermediate-risk acute PE patients admitted between 1 January 2020 and 10 June 2025. EASIX was calculated as LDH (U/L) × creatinine (mg/dL)/platelet count (10⁹/L). The primary endpoint was EACO within the first seven days after PE diagnosis during the index hospitalization, including hemodynamic decompensation, vasopressor/inotrope requirement, intensive care unit transfer, rescue reperfusion therapy, ventilatory support, cardiac arrest, or PE-related death. Hierarchical logistic regression, ROC analysis, calibration assessment, bootstrap internal validation, and 10-fold cross-validation were performed. Results: EACO occurred in 110 patients (12.2%). Patients with EACO had higher EASIX (2.28 [1.52–3.27] vs. 1.27 [0.86–2.00], p < 0.001) and lower TAPSE/PASP ratio (0.29 [0.23–0.36] vs. 0.42 [0.33–0.57], p < 0.001). log2-EASIX correlated inversely with TAPSE/PASP (Spearman rho = −0.30, p < 0.001). In the final combined model, log2-EASIX (OR 1.55 per doubling, 95% CI 1.14–2.10, p = 0.005) and TAPSE/PASP per 0.1-unit decrease (OR 1.36, 95% CI 1.10–1.68, p = 0.004) remained independently associated with EACO after adjustment for clinical variables, troponin, lactate, D-dimer, and C-reactive protein-to-albumin ratio. The final model showed higher discrimination than the clinical-laboratory model, although the absolute AUC increment was modest (AUC 0.920 vs. 0.904). Bootstrap optimism-corrected AUC was 0.910 and 10-fold cross-validated AUC was 0.904. Conclusions: Admission EASIX and impaired RV-PA coupling may provide complementary prognostic information for early risk stratification in intermediate-risk acute PE. Because this was a retrospective single-center study without external validation, these findings should be considered hypothesis-generating and should not be used as definitive treatment-escalation triggers before independent external validation. Full article

Background: Intermediate-high and high-risk pulmonary embolism (PE) are associated with substantial mortality despite anticoagulation. While reperfusion therapies may improve outcomes, real-world evidence comparing treatment strategies and identifying predictors of mid-term mortality remains limited. We aimed to evaluate predictors of 90-day mortality and the impact of reperfusion therapy in patients with intermediate-high and high-risk PE managed within a multidisciplinary Pulmonary Embolism Response Team (PERT). Methods: This retrospective cohort study included 114 consecutive patients with intermediate-high or high-risk acute PE admitted to a tertiary referral center between October 2023 and December 2024. Risk stratification was performed according to ESC guidelines, and simplified Pulmonary Embolism Severity Index (sPESI) scores were calculated. Treatment strategies included anticoagulation alone or reperfusion therapy (systemic thrombolysis or catheter-directed therapy). The primary endpoint was all-cause 90-day mortality. Multivariate logistic regression was performed to identify independent predictors of mortality. Results: The mean age was 68 ± 16 years, and 88% had at least one comorbidity. Reperfusion therapy was administered to 27% of patients. Mortality rates were 1% at 24 h, 6% at 7 days, 17% at 30 days, and 25% at 90 days. In multivariate analysis, hemoglobin ≤ 11.7 g/dL (OR 5.06, 95% CI 1.58–16.17, p = 0.006), sPESI > 2 (OR 4.86, 95% CI 1.49–15.84, p = 0.009), prior stroke (OR 11.59, 95% CI 2.08–64.51, p = 0.005), and high 30-day mortality risk classification (OR 14.14, 95% CI 1.19–167.89, p = 0.036) were independent predictors of mortality. Reperfusion therapy was independently associated with a significant reduction in 90-day mortality (OR 0.05, 95% CI 0.003–0.65, p = 0.022). The regression model demonstrated good explanatory power (Nagelkerke R² = 0.487). Conclusions: In this real-world cohort of intermediate-high and high-risk PE, reperfusion therapy was independently associated with lower 90-day mortality and low bleeding risk. In addition to established predictors, sPESI retained strong prognostic value beyond its traditional 30-day timeframe. These findings support risk-adapted reperfusion strategies guided by multidisciplinary teams and reinforce the role of integrated clinical risk assessment in optimizing outcomes. Full article

Ischemia–reperfusion injury (IRI) of the kidney represents a serious medical issue with complex pathological mechanisms that remain poorly elucidated. The development of ischemic acute kidney injury (AKI) may be mediated by NADPH oxidase and angiotensin II type 2 receptors. The aim of our study was to explore the effects of novokinin (NOV), angiotensin II type 2 receptor (AT2R) agonist and apocynin (APO), an NADPH oxidase inhibitor, on kidney structure and function, as well as the level of oxidative stress in spontaneously hypertensive rats (SHR) with induced IRI. Animals were randomly assigned into five experimental groups: the Sham-operated animals (SHAM) group, the AKI group, and AKI groups receiving APO, NOV, or their combination. Slight improvements in renal function were noted across all treated groups; however, only the combined action of APO + NOV led to a significant decrease in kidney injury molecule-1 (KIM-1) levels and markedly reduced oxidative stress compared with the control AKI group. Our results demonstrate that additively targeting NADPH oxidase and AT2R provides new insights in comparison to individual treatments. These findings suggest a potentially promising new therapeutic strategy for managing IRI and improving outcomes in critically ill patients with AKI. Full article

Objective: The present study aimed to investigate the neuroprotective effects of agomelatine in a rat model of cerebral ischemia/reperfusion injury, a major pathological event underlying ischemic stroke. Methods: Male Sprague Dawley rats included in the study were divided into four groups (n = 10/group): sham, CI/R, CI/R + 20 mg/kg Agm and CI/R + 40 mg/kg Agm. Sixty minutes of ischemia was induced in all groups except the sham group. One hour after ischemia, hydroxyethyl cellulose was administered intraperitoneally to the CI/R group, while 20 and 40 mg/kg agomelatine was administered to CI/R + Agm groups. During the three-day reperfusion period, the rats underwent neurological deficit score (NDS), rotarod, adhesive removal, and grip strength tests. At the end of the experiment, animals were decapitated and brain tissues were collected. In the collected brain tissues, infarct area was determined by TTC staining, and levels of apoptosis (Bcl-2, Bax) and autophagy (Beclin-1, ATG5, ATG7, p62) proteins were determined by Western blot. Statistical analysis of the obtained data was performed. Results: Compared with the CI/R group, agomelatine-treated groups showed significantly lower NDSs and adhesive removal times, as well as higher rotarod retention times and grip strength values (p < 0.05). Infarct area was significantly reduced following agomelatine treatment (p < 0.05). Agomelatine increased Bcl-2, Beclin-1, ATG5, and ATG7 protein levels while decreasing Bax and p62 expression compared with the CI/R group (p < 0.05). Conclusions: Agomelatine attenuated neurological deficits and infarct formation following CI/R injury. These neuroprotective effects may be associated with suppression of apoptosis and enhancement of autophagy-related pathways. Full article

Background: Heart transplantation remains the definitive therapy for end-stage heart failure, but its success critically depends on optimal donor heart preservation. Although the University of Wisconsin (UW) solution is the clinical gold standard, its safe storage window for hearts is limited to 4–6 h. Extending this static cold storage (SCS) window represents a critical challenge. We hypothesized that Salvianolic acid B (SalB), a primary bioactive compound in Salvia miltiorrhiza with potent antioxidant and cardioprotective properties, could serve as an effective pharmacological additive to UW solution. Methods: Isolated mouse hearts were subjected to SCS at 4 °C for varying durations (4, 8, and 10 h) in either standard UW solution or UW solution supplemented with 0.8 mg/mL SalB. Myocardial injury was assessed via cardiac enzyme leakage (BNP, CK-MB, LDH), oxidative stress markers, sterile inflammation, and histopathology. The regulatory roles of SalB on apoptosis and autophagic flux were further evaluated, utilizing the autophagy inhibitor 3-methyladenine (3-MA) to establish mechanistic causality. Results: Hearts preserved in SalB-supplemented UW solution exhibited significantly ameliorated histopathological damage, reduced cold ischemia-induced enzyme efflux, and suppressed oxidative stress compared to standard UW solution. Notably, hearts preserved for 8 h with SalB maintained structural and biochemical integrity comparable to those stored for only 4 h in standard UW solution. Mechanistic investigations revealed that SalB treatment orchestrates a pro-survival shift by significantly reducing cardiomyocyte apoptosis and robustly enhancing autophagic flux to maintain cellular homeostasis. The abrogation of autophagy by 3-MA effectively reversed these cardioprotective benefits. Conclusions: Supplementing UW solution with SalB effectively prolongs the structural and biochemical preservation of donor hearts during cold storage up to 8–10 h. By mitigating ischemia–reperfusion injury via the targeted modulation of autophagic flux, SalB highlights its strong translational potential as a robust pharmacological additive for heart transplantation. Full article

Background/Objectives: Microvascular dysfunction is a common early manifestation of connective tissue diseases (CTDs), yet practical non-invasive tools remain limited beyond nailfold capillaroscopy. Flow-mediated skin fluorescence (FMSF), based on changes in nicotinamide adenine dinucleotide (NADH) fluorescence during brachial artery occlusion and reperfusion, is thought to reflect microvascular and mitochondrial function. We investigated whether FMSF differentiates CTD subgroups and how its parameters relate to capillaroscopic findings. Methods: In this exploratory cross-sectional study, we examined 99 adults: 19 with lupus erythematosus (LE), 25 with primary Raynaud phenomenon (PR), 29 within the systemic sclerosis (SSc) spectrum, and 26 healthy controls. FMSF parameters were compared across subgroups and capillaroscopic patterns (normal, nonspecific, scleroderma-like) using false discovery rate (FDR) correction and age adjustment. Results: Ten of 19 FMSF parameters differed among subgroups (all FDR-corrected p ≤ 0.03); after age adjustment, four remained significant (PSD1, endothelial and myogenic oscillations, and hypoxia sensitivity [HS]; all p ≤ 0.023), a gradient driven largely by the SSc spectrum. These differences attenuated to non-significance after excluding vasoactive-treated patients (HS p = 0.29) and when restricted to an overlapping age range (p = 0.06–0.18). Across capillaroscopic patterns, the hyperemic response index and HR max declined toward scleroderma-like patterns (both p = 0.007), but no parameter remained associated with pattern after adjustment for CTD diagnosis. Conclusions: Our pilot study provides valuable, though exploratory findings: the FMSF signal was largely SSc-driven and sensitive to treatment and age, rather than a robust, disease-independent discriminator. Confirmation in larger, longitudinal cohorts is required. Full article

Despite advances in liver machine perfusion (MP), ischemia–reperfusion injury (IRI) remains a major challenge in liver transplantation, with energetic stress and mitochondrial dysfunction recognized as key drivers of damage exacerbation. We investigated whether fractions enriched with extracellular vesicles (EVs) derived from mesenchymal stromal cells can preserve energetic homeostasis in rat livers undergoing normothermic MP (NMP). An established NMP rat model was used (n = 5 per group). After procurement, livers underwent NMP for 4 h, preceded or not by 30 min cold ischemia (CI). EVs (NMP + EVs and CI + NMP + EVs) or saline (NMP and CI + NMP) were randomly administered to the perfusion fluid. Perfusate samples were collected throughout the procedure, and biopsies were taken at the end of NMP. Ischemic livers exhibited succinate accumulation, flavin mononucleotide (FMN) release, activation of reverse electron transport, and adenosine triphosphate (ATP) depletion. EV treatment effectively counteracted these effects, restoring a metabolic profile comparable to that of non-ischemic livers. Moreover, EVs improved adenosine monophosphate/ATP ratios and prevented AMP-activated protein kinase activation, a key energy-stress sensor. Furthermore, EVs reduced oxidative stress markers, cell death mediators, and pro-inflammatory cytokines, indicating a broad cytoprotective and anti-inflammatory effect. These findings support the potential of EVs to preserve mitochondrial function, restore energy balance, and reduce inflammation, thereby improving liver cell viability during NMP. Full article

Background and Clinical Significance: Hyaluronic acid fillers are currently the most widely used materials in aesthetic medicine and represent one of the most frequently performed minimally invasive procedures worldwide. Vascular occlusion is the most severe complication associated with this type if filler injections due to the risk of tissue necrosis and permanent sequelae. Early recognition and precise identification of the affected vascular territory are essential to prevent irreversible damage. Case Presentation: his report describes a case of infraorbital artery occlusion with retrograde extension to the anterior superior alveolar artery and associated gingival ischemia, highlighting the role of high-frequency ultrasound in diagnosis and management. A 60-year-old woman developed vascular occlusion following supraperiosteal HA injection in the medial cheek. Clinical findings included livedo reticularis in the infraorbital and nasal regions, along with ipsilateral gingival anesthesia and mucosal ischemia. High-frequency ultrasound was used to assess the extent and mechanism of vascular involvement. A targeted treatment approach was implemented using low-dose hyaluronidase (100 IU/mL), with 200 IU administered in the infraorbital region and an additional 100 IU delivered under ultrasound guidance to the affected alveolar branch. Ultrasound examination revealed extrinsic compression of the infraorbital artery and secondary occlusion of the anterior superior alveolar artery consistent with retrograde embolization. Following image-guided administration of hyaluronidase, complete reperfusion was achieved, with resolution of both cutaneous and gingival ischemia and no functional or aesthetic sequelae. Conclusions: High-frequency ultrasound provides critical diagnostic information in vascular complications after HA filler injection, allowing for accurate identification of the mechanism and extent of vascular involvement. Ultrasound-guided low-dose hyaluronidase may represent an effective and safe strategy to restore perfusion while minimizing unnecessary enzyme exposure and associated adverse effects. Full article

Background: Scutellaria baicalensis (Scu) extract has been traditionally used in the treatment of stroke-related syndromes, yet its underlying molecular mechanisms, particularly those involving ferroptosis, remain to be fully elucidated. Purpose: This study aims to validate the hypothesis that Scu extract improves cerebral ischemia-reperfusion injury (CIRI) by inhibiting ferroptosis through the PI3K/AKT signaling pathway. Methods: This study employed middle cerebral artery occlusion (MCAO) in male Sprague-Dawley (SD) rats and oxygen–glucose deprivation/reoxygenation (OGD/R) models to evaluate the protective effects of Scu extract against CIRI. Multiple approaches were integrated to elucidate the underlying mechanisms. Furthermore, a range of experimental techniques, including neurological function assessment, TTC staining, histopathological analysis, biochemical assays, qPCR, transmission electron microscopy (TEM), reactive oxygen species (ROS) detection, Western blotting, and immunofluorescence, were used to comprehensively validate its neuroprotective effects. Results: Scu extract significantly improved neurological outcomes and attenuated brain injury in MCAO rats. Proteomic analysis revealed significant enrichment of ferroptosis-related pathways, which was supported by reduced mitochondrial damage, decreased iron accumulation, and restoration of the SLC7A11/GPX4 axis. Subsequently, UPLC/Q-TOF-MS analysis revealed that four major bioactive components were absorbed in MCAO rats. KEGG pathway analysis based on network pharmacology further indicated that the PI3K/AKT signaling pathway is a key regulatory target. Notably, pharmacological inhibition of PI3K with LY294002 markedly abolished the anti-ferroptotic effects of Scu extract, which was further confirmed in vitro. Conclusions: This study demonstrates that Scu extract confers neuroprotection against CIRI in MCAO rats potentially through inhibiting ferroptosis via activation of the PI3K/AKT pathway. Full article

Background: Evidence regarding optimal reperfusion strategies in older patients with acute ischemic stroke remains inconsistent, particularly in real-world settings where patient selection and comorbidity burden differ from randomized trials. Objective: This study evaluates real-world outcomes of ischemic stroke interventions among older adults in a tertiary medical center. Methods: This single-center retrospective cohort study included patients aged ≥ 65 years with acute ischemic stroke admitted between August 2022 and December 2023. Mortality follow-up continued until September 2024. Patients were categorized according to treatment: intravenous thrombolysis (tPA) alone, endovascular thrombectomy (EVT) alone, or combined (tPA + EVT) therapy. Data included demographics, comorbidities, stroke severity (NIHSS), imaging, treatment timing, and mortality outcomes. Results: Among 200 patients (mean age 77.5 years), 66 received tPA, 86 underwent EVT, and 48 received tPA + EVT therapy. Patients treated with tPA alone presented with milder strokes and had low in-hospital and six-month mortality (1.5% and 6.1%, respectively). In contrast, EVT-only patients had substantially higher in-hospital and six-month mortality (21% and 43%, respectively). Patients receiving tPA + EVT therapy had low mortality rates comparable to the tPA group (2.1% and 6.3%, respectively), despite greater stroke severity at presentation. Conclusions: Despite greater stroke severity, patients receiving tPA + EVT therapy had outcomes comparable to those treated with tPA alone, while EVT-only patients experienced substantially higher mortality. These findings underscore the importance of patient selection and suggest that treatment allocation may strongly influence real-world outcomes in older adults. Full article

Background and Objectives: Angiographic no-reflow (NRF) after percutaneous coronary intervention (PCI) reflects impaired microvascular reperfusion despite successful treatment of the epicardial culprit lesion. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in endothelial signaling, platelet biology, inflammation, and angiogenesis. Its relationship with NRF in non-ST-segment elevation myocardial infarction (NSTEMI) remains insufficiently characterized. Materials and Methods: This single-center prospective observational cohort study included 700 consecutive NSTEMI patients undergoing culprit-lesion PCI. Admission serum total BDNF was measured before PCI using a standardized enzyme-linked immunosorbent assay protocol. Angiographic NRF was defined as final thrombolysis in myocardial infarction (TIMI) flow <3 and/or TIMI 3 flow with myocardial blush grade (MBG) 0–1 in the absence of residual stenosis, dissection, severe spasm, or other mechanical obstruction. Four sequential logistic regression models were used to evaluate the stability of the association between BDNF and NRF: Model 1 adjusted for clinical variables; Model 2 further adjusted for laboratory and inflammatory variables; Model 3 further adjusted for cardiac injury and functional variables; and Model 4 further adjusted for angiographic and procedural variables. Discrimination, calibration, reclassification, decision-curve analysis, and internal validation were assessed. Results: NRF occurred in 114 of 700 patients (16.3%). Serum total BDNF was higher in the NRF group than in the reflow group [555 (465–688) vs. 386 (292–496) pg/mL, p < 0.001]. BDNF remained independently associated with NRF across sequential models: Model 1 OR 1.67 per 100 pg/mL (95% CI 1.43–1.96), Model 2 OR 1.49 (95% CI 1.24–1.79), Model 3 OR 1.41 (95% CI 1.16–1.72), and Model 4 OR 1.31 (95% CI 1.07–1.60). The BDNF-only AUC was 0.787, while the final BDNF-enriched Model 4 reached an AUC of 0.866. The optimism-corrected bootstrap AUC was 0.852 and the 10-fold cross-validated AUC was 0.845. Conclusions: Higher admission serum total BDNF was independently associated with angiographic NRF in NSTEMI patients undergoing PCI and improved risk discrimination when added to clinical, biochemical, cardiac, and angiographic predictors. These findings suggest that serum total BDNF may reflect a context-dependent biomarker signal related to acute thrombo-inflammatory, platelet-associated, and microvascular injury pathways; however, the observed incremental value was modest and requires external validation. Full article

Acute ischemic stroke is one of the leading causes of mortality and disability globally, characterized by a complex and temporally structured cascade of cellular and molecular events. Although reperfusion therapies have improved outcomes, their narrow therapeutic window and limited availability leave many patients without effective treatment, highlighting the need for effective neuroprotective strategies capable of targeting multiple interconnected pathways. Melatonin has been proposed as a potential adjunctive neuroprotective agent based on its pleiotropic properties, modulating cellular signaling networks including antioxidant, anti-inflammatory, mitochondrial stabilizing, and BBB-preserving effects. Melatonin regulates key signaling pathways, thereby coordinating cellular responses to injury in multiple stages of ischemic pathophysiology, positioning it as a potential adjunctive therapy. Preclinical studies consistently demonstrate reductions in infarct volume, preservation of neuronal architecture, and improvements in neurological outcomes. However, clinical evidence remains limited to a small number of clinical trials, which suggest safety and possible early neurological benefit but are underpowered to determine long-term efficacy. Importantly, translational gaps persist regarding optimal dosing, duration of administration, and alignment with the temporal dynamics of post-ischemic injury. This review integrates current knowledge on the cellular and molecular mechanisms underlying the potential neuroprotective actions and its role as a pleiotropic modulator of ischemic injury. Full article

Background: Acute focal neurological deficits require rapid differentiation between ischemic stroke and stroke mimics to avoid treatment delays and inappropriate therapy. Seizures, including ictal deficits, status epilepticus, and post-ictal/Todd’s phenomena, are among the most challenging mimics. This review summarizes the role of multimodal neuroimaging in distinguishing acute ischemic stroke from seizure-related deficits. Methods: We performed a focused narrative review of neuroimaging findings in acute stroke mimics, emphasizing non-contrast computed tomography (CT), CT angiography, CT perfusion, magnetic resonance imaging (MRI), including diffusion weighted imaging (DWI), apparent diffusion coefficient (ADC), fluid attenuated inversion recovery (FLAIR), and arterial spin labeling (ASL) sequences. Imaging patterns, diagnostic pitfalls, and practical clues for hyperacute stroke pathways were synthesized. Results: Acute ischemic stroke is typically suggested by vascular-territorial abnormalities, including arterial occlusion or stenosis, territorial hypoperfusion, and congruent DWI/ADC restriction. Seizure-related deficits more often show non-territorial cortical perfusion changes, ictal or status-related hyperperfusion, reversible MRI abnormalities, and absence of arterial occlusion. However, post-ictal hypoperfusion, peri-ictal diffusion restriction, and reperfusion-related hyperperfusion may overlap with ischemic patterns. Conclusions: A multimodal approach integrating vascular imaging, perfusion distribution, DWI/ADC, ASL, clinical timing, and EEG findings can improve diagnostic accuracy in the stroke–seizure differential without delaying treatment in true acute ischemic stroke. Full article

Juvenile intestinal ischemia–reperfusion (JII/R) is a pediatric surgical emergency caused by mesenteric vessel occlusion and has a high mortality rate. Malrotation can cause intestinal ischemia in infants due to midgut volvulus. It affects not only the intestine itself but also other organs, such as cardiac tissue. Therefore, searching for more effective therapeutic solutions is an essential critical need. This directed our thoughts to evaluate the role of ambrisentan (AMB) in a rat model of induced JII/R by clamping the superior mesenteric artery. Forty juvenile male Wistar albino rats (3–4 weeks old) were randomly divided into four experimental groups: control (CON) group, JII/R group, and AMB-treated groups (30, 60 mg/kg) with JII/R. Induction of JII/R results in significant changes in cardiac enzymes, oxidative stress, inflammatory, and apoptotic parameters with high expression of endothelin receptor A (ERA). Also, histopathological changes revealed extensive mucosal damage, loss of intestinal villi, dysregulated and degenerated cardiac fibers with inflammatory cell infiltration, and tissue necrosis. In contrast, AMB administration significantly reduced the elevated levels of cardiac enzymes, malondialdehyde (MDA), nuclear factor kappa B (NF-κB), ERA, and caspase-3 expression. However, AMB treatment increased immune expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), Ki-67, and mammalian target of rapamycin (mTOR) and showed remarkable improvement in the histopathological changes. AMB could be considered as an adjuvant medical treatment for cases of JII/R. Full article

Background and Purpose: Tenecteplase (TNK) within 4.5 h from symptom onset is not inferior to alteplase in treating ischemic stroke. In recent years, some randomized controlled trials (RCTs) have investigated the efficacy of extending the therapeutic window up to 24 h. This updated meta-analysis aims to synthesize the results of these RCTs comparing TNK to the best medical treatment (BMT) with or without endovascular thrombectomy. Methods: In accordance with PRISMA guidelines, all RCTs comparing TNK with BMT in adult patients between 4.5 and 24 h were systematically searched. The primary endpoint was good functional outcome at 90 days (mRS 0–2). Secondary endpoints included excellent outcome (mRS 0–1), symptomatic intracerebral hemorrhage (sICH), 90-day mortality, complete reperfusion at 24 h. Odd and Hazard ratios (ORs; HRs) were pooled using meta-analytic methods. Results: A total of seven RCTs involving 1754 patients were included. The rates of the primary endpoint were higher in TNK-treated patients (HR: 1.15; 95% CI: 1.03–1.27), as were rates of excellent functional outcome (HR: 1.29; 95% CI: 1.08–1.55). In the subgroup receiving intravenous therapy (IVT) alone, the primary endpoint was significantly more frequent in the TNK group than in the BMT group (OR: 1.47; 95% CI: 1.17–1.84; p for heterogeneity < 0.0001). TNK treatment was also associated with higher reperfusion rates compared with BMT, reflecting a greater proportion of saved ischemic penumbra as assessed via perfusion imaging. Although symptomatic intracranial hemorrhage (sICH) occurred more frequently in TNK-treated patients, the difference did not reach statistical significance, and mortality rates were comparable between treatment groups. Conclusions: Tenecteplase administered between 4.5 and 24 h is associated with improved rates of both good and excellent functional outcomes compared with BMT, especially in patients treated with IVT alone. Additionally, TNK is linked to higher rates of reperfusion. Full article