Explore the vast range of titles available.

Background: Among the currently approved antiobesity medications, the glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, and the dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes. Objectives: The objective of this study was to evaluate the cardio- and neuroprotective potential of these novel agents in the nondiabetic overweight/obese adult population. Data sources and methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate the risk of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality in overweight or obese adults without diabetes treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Secondary outcomes included the risk of myocardial infarction (MI) and stroke. Results: Sixteen RCTs (13 and 3 on GLP-1 RAs and tirzepatide, respectively) comprising 28,168 participants were included. GLP-1 or GIP/GLP-1 RAs reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71–0.89; p < 0.01; I2 = 0) and all-cause mortality (OR: 0.80; 95% CI: 0.70–0.92; p < 0.01; I2 = 0), while there was a trend toward lower cardiovascular-mortality (OR: 0.84; 95% CI: 0.71–1.01; p = 0.06; I2 = 0%) compared to placebo. Additionally, GLP-1 or GIP/GLP-1 RAs reduced the odds of MI (OR: 0.72; 95% CI: 0.61–0.86; p < 0.01; I2 = 0%) and nonfatal-MI (OR: 0.72; 95% CI: 0.61–0.85; p < 0.01; I2 = 0%); while no associations between antiobesity treatment and fatal-MI, stroke, nonfatal, or fatal stroke were uncovered. Conclusion: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and all-cause mortality in overweight or obese adults without diabetes. Additionally, GLP-1 RAs and GIP/GLP-1 RAs attenuate the risk of MI. Since data on stroke are still limited, future RCTs are warranted to evaluate the neuroprotective potential of these novel antiobesity agents. Trial registration: PROSPERO CRD42024515966.

Stroke is a leading cause of disability and the second cause of death in adults. Moreover, the incidence of stroke is continuously rising. Acute reperfusion therapies (ARTs) have revolutionized stroke medicine and have altered the natural course of acute ischemic stroke. However, these treatments are ultimately offered to only a minority of acute ischemic stroke (AIS) patients, primarily due to delays in presentation. The use of advanced imaging has partially increased eligibility for ART; nevertheless, a large proportion of AIS patients remain untreated. In addition, many stroke centers lack readily available advanced imaging, sometimes lacking even computed tomography angiography. In these settings, several recent studies have sought to simplify the imaging prerequisites and criteria for the administration of ARTs. In this review, we discuss the possible treatment options for AIS patients presenting in different time points, according to type of imaging availability and mechanical thrombectomy availability. Our aim is to provide evidence-based recommendations, but also to analyze emerging data supporting the individualized, off-label use of ART without the aid of advanced imaging.

Endovascular thrombectomy (EVT) has become standard of care for large vessel occlusion strokes but current guidelines exclude a large proportion of patients from this highly effective treatment. This review therefore focuses on expanding indications for EVT in several borderline indications such as patients in the extended time window, patients with extensive signs of infarction on admission imaging, elderly patients and patients with pre-existing deficits. It also discusses the current knowledge on intravenous thrombolysis as an adjunct to EVT and EVT as primary therapy for distal vessel occlusions, for tandem occlusions, for basilar artery occlusions and in pediatric patients. We provide clear recommendations based on current guidelines and further literature.

Intravenous thrombolysis (IVT) represents the only systemic reperfusion therapy able to reverse neurological deficit in patients with acute ischemic stroke (AIS). Despite its effectiveness in patients with or without large vessel occlusion, it can be offered only to a minority of them, because of the short therapeutic window and additional contraindications derived from stringent but arbitrary inclusion and exclusion criteria used in landmark randomized controlled clinical trials. Many absolute or relative contraindications lead to disparities between the official drug label and guidelines or expert recommendations. Based on recent advances in neuroimaging and evidence from cohort studies, off-label use of IVT is increasingly incorporated into the daily practice of many stroke centers. They relate to extension of therapeutic time windows, and expansion of indications in co-existing conditions originally listed in exclusion criteria, such as use of alternative thrombolytic agents, pre-treatment with antiplatelets, anticoagulants or low molecular weight heparins. In this narrative review, we summarize recent randomized and real-world data on the safety and efficacy of off-label use of IVT for AIS. We also make some practical recommendations to stroke physicians regarding the off-label use of thrombolytic agents in complex and uncommon presentations of AIS or other conditions mimicking acute cerebral ischemia. Finally, we provide guidance on the risks and benefits of IVT in numerous AIS subgroups, where equipoise exists and guidelines and treatment practices vary.

The clinical manifestations of proximal (extracranial) internal carotid artery occlusions (pICAOs) may range from asymptomatic to acute, large, and devastating ischemic strokes. The etiology and pathophysiology of the occlusion, intracranial collateral status and patient’s premorbid status are among the factors determining the clinical presentation and outcome of pICAOs. Rapid and accurate diagnosis is crucial and may be assisted by the combination of carotid and transcranial duplex sonography, or a computed tomography/magnetic resonance angiography (CTA/MRA). It should be noted that with either imaging modalities, the discrimination of a pseudo-occlusion of the extracranial internal carotid artery (ICA) from a true pICAO may not be straightforward. In the absence of randomized data, the management of acute, symptomatic pICAOs remains individualized and relies largely on expert opinion. Administration of intravenous thrombolysis is reasonable and probably beneficial in the settings of acute ischemic stroke with early presentation. Unfortunately, rates of recanalization are rather low and acute interventional reperfusion therapies emerge as a potentially powerful therapeutic option for patients with persistent and severe symptoms. However, none of the pivotal clinical trials on mechanical thrombectomy for acute ischemic stroke randomized patients with isolated extracranial large vessel occlusions. On the contrary, several lines of evidence from non-randomized studies have shown that acute carotid endarterectomy, or endovascular thrombectomy/stenting of the ICA are feasible and safe, and pοtentially beneficial. The heterogeneity in the pathophysiology and clinical presentation of acute pICAOs renders patient selection for an acute interventional treatment a complicated decision-making process. The present narrative review will outline the pathophysiology, clinical presentation, diagnostic challenges, and possible treatment options for pICAOs.

Background: The literature on endovascular treatment (EVT) for large-vessel occlusion (LVO) acute ischaemic stroke (AIS) has been rapidly increasing after the publication of positive randomized-controlled clinical trials (RCTs) and a plethora of systematic reviews (SRs) showing benefit compared to best medical therapy (BMT) for LVO. Objectives: An overview of SRs (umbrella review) and meta-analysis of primary RCTs were performed to summarize the literature and present efficacy and safety of EVT. Design and methods: MEDLINE via Pubmed, Embase and Epistemonikos databases were searched from January 2015 until 15 October 2023. All SRs of RCTs comparing EVT to BMT were included. Quality was assessed using Risk of Bias in Systematic Reviews scores and the RoB 2 Cochrane Collaboration tool, as appropriate. GRADE approach was used to evaluate the strength of evidence. Data were presented according to the Preferred Reporting Items for Overviews of Reviews statement. The primary outcome was 3-month good functional outcome [modified Rankin scale (mRS) score 0–2]. Results: Three eligible SRs and 4 additional RCTs were included in the overview, comprising a total of 24 RCTs, corresponding to 5968 AIS patients with LVO (3044 randomized to EVT versus 2924 patients randomized to BMT). High-quality evidence shows that EVT is associated with an increased likelihood of good functional outcome [risk ratio (RR) 1.78 (95% confidence interval (CI): 1.54–2.06); 166 more per 1000 patients], independent ambulation [mRS-scores 0–3; RR 1.50 (95% CI: 1.37–1.64); 174 more per 1000 patients], excellent functional outcome [mRS-scores 0–1; RR 1.90 (95% CI: 1.62–2.22); 118 more per 1000 patients] at 3 months. EVT was associated with reduced 3-month mortality [RR 0.81 (95% CI: 0.74–0.88); 61 less per 1000 patients] despite an increase in symptomatic intracranial haemorrhage [sICH; RR 1.65 (95% CI: 1.23–2.21); 22 more per 1000 patients]. Conclusion: In patients with AIS due to LVO in the anterior or posterior circulation, within 24 h from symptom onset, EVT improves functional outcomes and increases the chance of survival despite increased sICH risk. Registration: PROSPERO Registration Number CRD42023461138.

Assessing ischemic etiology and mechanism during the acute phase of an ischemic stroke is crucial in order to tailor and monitor appropriate treatment and determine prognosis. Cervical Duplex Ultrasound (CDU) has evolved since many years as an excellent screening tool for the evaluation of extracranial vasculature. CDU has the advantages of a low cost, easily applicable, bed side examination with high temporal and spatial resolution and without exposing the patients to any significant complications. It represents an easily repeatable test that can be performed in the emergency room as a first-line examination of cervical artery pathology. CDU provides well validated estimates of the type of the atherosclerotic plaque, the degree of stenosis, as well as structural and hemodynamic information directly about extracranial vessels (e.g., subclavian steal syndrome) and indirectly about intracranial circulation. CDU may also aid the diagnosis of non-atherosclerotic lesions of vessel walls including dissections, arteritis, carotid-jugular fistulas and fibromuscular dysplasias. The present narrative review outlines all potential applications of CDU in acute stroke management and also highlights its potential therapeutic implications.

Background: Patients with atrial fibrillation (AF) who survive spontaneous intracerebral hemorrhage (ICH) face competing risks of thromboembolism and recurrent bleeding. Objectives: To evaluate the safety and efficacy of initiating oral anticoagulants versus avoiding anticoagulation in adults with AF after spontaneous ICH. Design: Systematic review and meta-analysis of randomized-controlled clinical trials (RCTs). Data sources and methods: We searched MEDLINE, Scopus, and ClinicalTrials.gov up to August 28, 2025, for eligible RCTs randomizing adults with AF and prior spontaneous ICH to start oral anticoagulation versus avoid anticoagulation. Efficacy outcomes included the occurrence of new ischemic stroke (primary) and ischemic major adverse cardiovascular events (MACE; secondary). Safety outcomes included recurrent ICH (primary), hemorrhagic-MACE, all-cause mortality at follow-up, and cardiovascular death (secondary). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Results: Six RCTs were included, comprising 403 patients in the anticoagulation group and 395 in the avoid-anticoagulation group. Anticoagulants reduced the rates of new ischemic stroke (RR = 0.20; 95% CI: 0.06–0.72; I2 = 60%; number needed to treat = 9) and ischemic-MACE (RR = 0.41; 95% CI: 0.23–0.75; I2 = 32%). Anticoagulants were associated with higher rates of recurrent ICH (RR = 3.14; 95% CI: 1.41–7.01; I2 = 0%; number needed to harm = 19) and hemorrhagic-MACE (RR = 2.35; 95% CI: 1.32–4.21; I2 = 1%). All-cause mortality at 90 days (RR = 1.06; 95% CI: 0.69–1.64; I2 = 28%) and cardiovascular death (RR = 0.98; 95% CI: 0.34–2.87; I2 = 63%) did not differ between the two groups. Leave-one-out sensitivity analyses supported the overall direction of effects, with some attenuation when individual trials were omitted. Conclusion: In AF survivors of spontaneous ICH, restarting oral anticoagulation lowers ischemic events but raises risks of recurrent ICH and major bleeding, without a clear early mortality difference. Potential benefits may outweigh risks in selected patients within a multidisciplinary framework. Adequately powered RCTs are needed to refine agent choice, timing, and patient selection. Trial registration: PROSPERO CRD420251135299 (registered August 27, 2025).

Acute ischemic stroke (AIS) remains a major cause of long-term disability and death worldwide, posing significant challenges to healthcare systems. Timely diagnosis is crucial, as acute phase therapeutic options are highly time-sensitive and most effective when administered early in the disease course. In this context, serum biomarkers have emerged as a promising and complementary tool to aid in the rapid and accurate diagnosis, prognosis, and therapeutic monitoring of AIS. This narrative review aims to provide a comprehensive overview of the current landscape of serum biomarkers relevant to AIS. These biomarkers are categorized based on the underlying pathophysiological mechanisms they reflect, including markers of inflammation and oxidative stress, neuronal and endothelial injury, and those related to hemostasis and fibrinolysis. Their biological significance is evaluated through the spectrum of their diagnostic sensitivity and specificity and their potential integration into clinical practice. In addition, many of these biomarkers offer prognostic insights, helping to predict the likelihood of complications, recurrent stroke, or poor functional recovery. Furthermore, their role as a potential tool for the differential diagnosis of patients presenting with minor or nonspecific neurological symptoms and therapeutic monitoring is emphasized. Despite the promising potential of these biomarkers, their translation into routine clinical use remains limited.

Background and aims: Tenecteplase has recently emerged as an alternative thrombolytic agent in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO), possibly superior in achieving early reperfusion compared with alteplase. We aimed to compare the safety and efficacy of intravenous tenecteplase with intravenous alteplase for AIS patients with LVO in everyday clinical practice settings. Methods: We prospectively evaluated patients with AIS due to LVO, treated with intravenous thrombolysis (IVT) with or without mechanical thrombectomy in two tertiary stroke centers. Patients were treated with standard-dose alteplase (0.9 mg/kg) or 0.25 mg/kg tenecteplase. Safety outcomes included prevalence of symptomatic intracranial hemorrhage (sICH) and mortality. Efficacy outcomes included averted thrombectomy, major neurological improvement at 24 h (defined as decrease in baseline NIHSS score of 8 points or greater) and functional status on discharge and on 3 months assessed by modified Rankin Scale (mRS). Results: Nineteen AIS patients with LVO received tenecteplase and 39 received alteplase. We observed a non-significant higher rate of averted thrombectomies (32% versus 18%, p = 0.243) and a non-significant higher rate of sICH (16% versus 5%, p = 0.201) in the tenecteplase group. The rate of 24 h major neurological improvement was higher in the tenecteplase group (64% versus 33%, p = 0.046) but this was marginally attenuated in multivariable analyses (adjusted OR 10.22, 95% CI: 0.73–142.98; p = 0.084). Discharge mRS, 3-months mRS, and 3-month functional independence (mRS scores of 0–2) did not differ (p > 0.2) between the two groups. The rates of 3-month mortality (11% versus 18%, p = 0.703) were similar in the two groups. No independent association between thrombolytic agent and safety or efficacy outcomes emerged in multivariable regression analyses. Conclusion: The present pilot observational study highlights that AIS patients with LVO treated with 0.25 mg/kg bolus administration of tenecteplase had increased likelihood to achieve early neurological improvement compared with AIS patients treated with alteplase, but this association was attenuated after adjustment for potential confounders. There were no significant differences in 3-month functional or safety outcomes between the two groups. This preliminary real-world observation requires independent confirmation in larger, multicenter studies.