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Introduction: Sex differences in stroke incidence, vascular risk factors (VRFs), and etiologies among young adults remain underexplored, particularly regarding age-related patterns., Patients and Methods: We retrospectively analyzed young adults (18-55 years) with first-ever ischemic stroke treated at certified acute stroke units/centers between 2014 and 2022, using Swiss Stroke Registry data. Stroke rates (per 100,000 person-years), VRFs, and etiologies were assessed by age and sex., Results: Among 3,995 stroke patients, stroke rates were similar between sexes until age 35, after which men showed a more pronounced exponential increase. This rise was particularly notable in patients with elevated BMI and ⩾2 VRFs. The proportion of patients with ⩾2 VRFs rose with age (18-35: 22%; 36-50: 48%; 51-55: 63%). While no statistically significant differences in VRF profiles were observed between men and women aged 18-35, men accumulated VRFs about five years earlier than women, leading to a higher prevalence of multiple VRFs in men aged 36-50, with the gap narrowing in the 51-55 group. Stroke etiologies shifted with age: patent foramen ovale and cervical artery dissection predominated in younger patients, while large artery atherosclerosis, small vessel disease, and strokes of undetermined etiology increased with age, with notable sex differences., Discussion and Conclusions: This study highlights sex and age differences in ischemic stroke rates, VRFs, and etiologies among adults under 55 years. After 35, stroke rates rose more sharply in men, paralleling their higher VRF burden. These findings emphasize the importance of early management of VRFs-including overweight-to mitigate stroke risk., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: There are limited therapeutic options in cases of failed reperfusion (modified thrombolysis in cerebral infarction [mTICI] score < 2b) after stent-retriever and/or aspiration based endovascular treatment (EVT) for acute ischemic stroke. Despite the absence of data supporting its use, rescue therapy (balloon angioplasty and/or stent implantation) is often utilized in such cases. Studies are limited to large vessel occlusions, while the outcomes and complications after rescue therapy in medium/distal vessel occlusions (MDVOs) have not been reported. This study aims to report the outcomes of rescue therapy in MDVO stroke patients., Methods: We performed an analysis of the "Blood pressure and Antiplatelet medication management after reScue angioplasty after failed Endovascular treatment in Large and distal vessel occlusions with probable IntraCranial Atherosclerotic Disease" (BASEL ICAD) retrospective registry. All MDVO stroke patients were included in the analysis., Results: Out of the 718 registry patients, 87 (12.1%) presented with an MDVO. Fifty-six patients (64.4%) showed an occlusion of the M2 segment of the middle cerebral artery. Rescue stenting was performed in 78 patients (89.7%) while balloon angioplasty alone was performed in 9 patients (10.3%). Successful reperfusion (mTICI score ⩾ 2b) was achieved in 73 (83.9%) patients after rescue therapy. Symptomatic intracranial hemorrhage (sICH) occurred in 8 patients (9.2%) and post-treatment stent occlusion in 12 patients (13.8%). Ninety days mortality was 20.7%. Twenty-eight patients (32.2%) achieved functional independence at 90 days (modified Rankin Scale 0-2)., Conclusion: Rescue therapy with stenting and/or balloon angioplasty in patients undergoing EVT for isolated MDVO with suspected underlying intracranial atherosclerotic disease is an effective reperfusion strategy but is associated with complications and poor functional outcomes., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Victor Schulze-Zachau: discloses speaker fees from Medtronic Inc. (money paid to institution). V.S.-Z. is recipient of research grants from Basel University, Bangerter-Rhyner- Stiftung Basel and Freiwillige Akademische Gesellschaft Basel.Thanh N Nguyen: discloses Associate Editor of Stroke; advisory board of Aruna Bio, Brainomix.Kazutaka Uchida: reports lecturer’s fees from Daiichi Sankyo, Bristol-Myers Squibb, Stryker, and Medtronic.Marios-Nikos Psychogios : discloses unrestricted grants from Swiss National Science Foundation (SNF), Bangerter-Rhyner Stiftung, Stryker Neurovascular Inc., Phenox GmbH, Medtronic Inc., Rapid Medical Inc., and Penumbra Inc for the DISTAL trial, grant for SPINNERS trial from Siemens Healthineers AG (money paid to institution) and the following speaker fees: Stryker Neurovascular Inc., Medtronic Inc., Penumbra Inc., Acandis GmbH, Phenox GmbH, Rapid Medical Inc. and Siemens Healthineers AG (money paid to institution).Other authors declare that there is no conflict of interest.

Introduction: There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice., Methods: We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model., Results: Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; I 2  = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; I 2  = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; I 2  = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; I 2  = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; I 2  = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated., Conclusions: Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Automated CT perfusion (aCTP) is commonly used to select patients with anterior circulation large vessel occlusion (aLVO) for endovascular treatment (EVT). The equivalence of visually assessed Non-contrast CT Alberta Stroke Program Early CT Scores (ASPECTS) and aCTP based selection in predicting favorable functional outcomes remains uncertain., Patients and Methods: Retrospective multicenter study of adult aLVO patients from the Swiss Stroke Registry (2014-2021) treated with EVT or best medical treatment 6-24 h after stroke onset. We assessed ASPECTS on non-contrast CT visually and ischemic core volumes on aCTP, defining ASPECTS 0-5 and aCTP CBF < 30% volumes ⩾50 mL as large ischemic cores. We used logistic regression to explore the association between CT modalities and favorable functional outcomes (modified Rankin Scale [mRS] score shift toward lower categories) at 3 months. Receiver operating characteristic (ROC) curve analysis compared the predictive accuracy of visually assessed ASPECTS and aCTP ischemic core for favorable outcomes (mRS 0-2) at 3 months., Results: Of 210 patients, 11.4% had ASPECTS 0-5, and 12.9% aCTP core volumes ⩾50 mL. Within the same model, ASPECTS but not aCTP core volumes were associated with favorable outcomes (ASPECTS: acOR 1.85, 95%CI 1.27-2.70, p  = 0.001). The ROC curve analyses showed comparable diagnostic accuracy in predicting favorable functional outcomes (mRS 0-2) at 3 months (ROC areas: ASPECTS 0.80 [95%CI 0.74-0.86] vs aCTP core 0.79 [95%CI 0.72-0.85])., Discussion and Conclusion: In patients with aLVO, visually assessed ASPECTS showed at least comparable accuracy to automatically generated CTP core volumes in predicting functional outcomes at 3 months., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RS received personal grants from UCB-pharma and holds stocks from Novartis, Roche, Alcon, and Johnson&Johnson. MK received funding form the Swiss National Science Foundation, the Swiss Heart Foundation, and USZ-foundation, and received honoraria and consulting fees from Astra Zeneca and BMS/Pfizer, and in-kind contributions from BRAHMS Termofisher Scientific, Roche Diagnostics. LHB received personal fees from Claret Medical and InnovHeart. GMDM received speaker honoraria from Medtronic. The remaining authors report no conflicts relevant to this study.

Introduction: The impact of leptomeningeal collateralization on the efficacy of mechanical thrombectomy (MT) in patients with anterior circulation large vessel occlusion (aLVO) presenting in the 6-24 h time window remains poorly elucidated., Patients and Methods: Retrospective multicenter study of aLVO patients presenting between 6 and 24 h after stroke onset who received MT plus Best Medical Treatment (BMT) or BMT alone. Leptomeningeal collateralization was assessed using single-phase computed tomography angiography (grade 0: no filling; grade 1: filling ⩽50%; grade 2: filling >50% but <100%; grade 3: filling 100% of the occluded territory). Inverse probability of treatment weighted ordinal regression was performed to assess the association between treatment and shift of the modified Rankin Scale (mRS) score toward lower categories at 3 months. We used interaction analysis to explore differential treatment effects on functional outcomes (probabilities for each mRS subcategory at 3 months) at different collateral grades., Results: Among 363 included patients, 62% received MT + BMT. Better collateralization was associated with better functional outcomes at 3 months in the BMT alone group (collateral grade 1 vs 0: acOR 5.06, 95% CI 2.33-10.99). MT + BMT was associated with higher odds of favorable functional outcome at 3 months (acOR 1.70, 95% CI 1.11-2.62) which was consistent after adjustment for collateral status (acOR 1.54, 95% CI 1.01-2.35). Regarding treatment effect modification, patients with absent collateralization had higher probabilities for a mRS of 0-4 and a lower mortality at 3 months for the MT + BMT group., Discussion and Conclusion: In the 6-to-24-h time window, aLVO patients with absent leptomeningeal collateralization benefit most from MT + BMT, indicating potential advantages for this group despite their poorer baseline prognosis., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MK received speaker honoraria from Medtronic. GMK is on a scientific advisory board of Bayer AG. CWC is member of the Medical and Scientific Advisory Boards of iSchemaView. LHB received personal fees from Claret Medical and InnovHeart. GMDM received speaker honoraria from Medtronic. The remaining authors report no conflicts of interests relevant to this study.

Introduction: Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM., Patients and Methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo)., Results: Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p  < 0.01; I 2  = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p  < 0.01; I 2  = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p  < 0.01; I 2  = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p  < 0.01; I 2  = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p  < 0.01; I 2  = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p  = 0.105; I 2  = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p  < 0.01; I 2  = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p  = 0.792; I 2  = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction., Discussion and Conclusion: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Thrombectomy complications remain poorly explored. This study aims to characterize periprocedural intracranial vessel perforation including the effect of thrombolysis on patient outcomes., Patients and Methods: In this multicenter retrospective cohort study, consecutive patients with vessel perforation during thrombectomy between January 2015 and April 2023 were included. Vessel perforation was defined as active extravasation on digital subtraction angiography. The primary outcome was modified Rankin Scale (mRS) at 90 days. Factors associated with the primary outcome were assessed using proportional odds models., Results: 459 patients with vessel perforation were included (mean age 72.5 ± 13.6 years, 59% female, 41% received thrombolysis). Mortality at 90 days was 51.9% and 16.3% of patients reached mRS 0-2 at 90 days. Thrombolysis was not associated with worse outcome at 90 days. Perforation of a large vessel (LV) as opposed to medium/distal vessel perforation was independently associated with worse outcome at 90 days (aOR 1.709, p  = 0.04) and LV perforation was associated with poorer survival probability (HR 1.389, p  = 0.021). Patients with active bleeding >20 min had worse survival probability, too (HR 1.797, p  = 0.009). Thrombolysis was not associated with longer bleeding duration. Bleeding cessation was achieved faster by permanent vessel occlusion compared to temporary measures (median difference: 4 min, p  < 0.001)., Discussion and Conclusion: Vessel perforation during thrombectomy is a severe and frequently fatal complication. This study does not suggest that thrombolysis significantly attributes to worse prognosis. Prompt cessation of active bleeding within 20 min is critical, emphasizing the need for interventionalists to be trained in complication management., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: V. S.-Z. discloses speaker fees from Medtronic Inc. (money paid to institution). M.R.L. discloses unrestricted educational grants from Medtronic and Stryker; consulting for Medtronic, Stereotaxis, Metis Innovative and Aeaean Advisers; equity interest in Proprio, Fluid Biomed, Stroke Diagnostics, Hyperion Surgical, Apertur; editorial board of Journal of NeuroInterventional Surgery; data safety monitoring board of Arsenal Medical. M.-N.P. discloses unrestricted grants from Swiss National Science Foundation (SNF), Bangerter-Rhyner Stiftung, Stryker Neurovascular Inc., Phenox GmbH, Medtronic Inc., Rapid Medical Inc., and Penumbra Inc for the DISTAL trial, grant for SPINNERS trial from Siemens Healthineers AG (money paid to institution) and the following speaker fees: Stryker Neurovascular Inc., Medtronic Inc., Penumbra Inc., Acandis GmbH, Phenox GmbH, Rapid Medical Inc. and Siemens Healthineers AG (money paid to institution).

Background and Aims: Low density lipoprotein (LDL-C) and other atherogenic lipoproteins are coated by apolipoprotein B100 (apoB). The correlation between LDL-C and apoB is usually thight, but in some cases LDL-C underestimates apoB levels and residual cardiovascular risk. We aimed to assess if a discordance of LDL-C-levels with apoB levels is associated with LAA stroke., Methods: We included patients with an acute ischemic stroke from two prospective studies enrolled at the University Hospital Bern, Basel and Zurich, Switzerland. LDL-C and apoB were measured within 24 h of symptom onset. By linear regression, for each LDL-C, we computed the expected apoB level assuming a perfect correlation. Higher-than-expected apoB was defined as apoB level being in the upper residual tertile., Results: Overall, we included 1783 patients, of which 260 had a LAA stroke (15%). In the overall cohort, higher-than-expected apoB values were not associated with LAA. However, a significant interaction with age was present. Among the 738 patients ⩽70 years of age, a higher-than-expected apoB was more frequent in patients with LAA- versus non LAA-stroke (48% vs 36%, p  = 0.02). In multivariate analysis, a higher-than-expected apoB was associated with LAA stroke (aOR = aOR 2.48, 95%CI 1.14-5.38). Among those aged ⩽70 years and with LAA, 11.7% had higher than guideline-recommended apoB despite LDL-C ⩽ 1.8 mmol/L (<70 mg/dl), compared to 5.9% among patients with other stroke etiologies ( p  = 0.04). A triglyceride cut-off of ⩾0.95 mmol/L had, in external validation, a sensitivity of 71% and specificity of 52% for apoB ⩾ 0.65 g/L among patients with LDL-C <1.8 mmol/L., Conclusions: Among patients aged ⩽70 years, a higher-than-expected apoB was independently associated with LAA stroke. Measuring apoB may help identify younger stroke patients potentially benefiting from intensified lipid-lowering therapy., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Gian Marco De Marchis reports a grant from Novartis for the study “Atherogenic Lipoproteins in Stroke.” He reports consultant honoraria by Novartis and Daiichi Sankyo. Industry payments are made to the research fund of the University Hospital Basel. All other authors report no disclosures.

Background: Data on the impact of competing stroke etiologies in stroke patients with atrial fibrillation (AF) are scarce., Methods: We used prospectively obtained data from an observational registry (Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-(NOACISP)-LONGTERM) of consecutive AF-stroke patients treated with oral anticoagulants. We compared the frequency of (i) the composite outcome of recurrent ischemic stroke (IS), intracerebral hemorrhage (ICH) or all-cause death as well as (ii) recurrent IS alone among AF-stroke patients with versus without competing stroke etiologies according to the TOAST classification. We performed cox proportional hazards regression modeling adjusted for potential confounders. Furthermore, the etiology of recurrent IS was assessed., Results: Among 907 patients (median age 81, 45.6% female), 184 patients (20.3%) had competing etiologies, while 723 (79.7%) had cardioembolism as the only plausible etiology. During 1587 patient-years of follow-up, patients with additional large-artery atherosclerosis had higher rates of the composite outcome (adjusted HR [95% CI] 1.64 [1.11, 2.40], p  = 0.017) and recurrent IS (aHR 2.96 [1.65, 5.35 ], p  < 0.001), compared to patients with cardioembolism as the only plausible etiology. Overall 71 patients had recurrent IS (7.8%) of whom 26.7% had a different etiology than the index IS with large-artery-atherosclerosis (19.7%) being the most common non-cardioembolic cause., Conclusion: In stroke patients with AF, causes other than cardioembolism as competing etiologies were common in index or recurrent IS. Concomitant presence of large-artery-atherosclerosis seems to indicate an increased risk for recurrences suggesting that stroke preventive means might be more effective if they also address competing stroke etiologies in AF-stroke patients., Clinical Trial Registration: NCT03826927.

Background: Ischaemic stroke may occur despite antiplatelet therapy (APT). We aimed to investigate frequency, potential causes and outcomes in patients with ischaemic stroke despite APT., Methods: In this cohort study, we enrolled patients with imaging-confirmed ischaemic stroke from the Swiss Stroke Registry (01/2014-07/2022). We determined the frequency of prior APT, assessed stroke aetiology (modified TOAST classification) and determined the association of prior APT with unfavourable functional outcome (modified Rankin Scale score 3-6) and recurrent ischaemic stroke at 3 months using regression models., Results: Among 53,352 patients, 27,484 (51.5%) had no prior antithrombotic treatment, 17,760 (33.3%) were on APT, 7039 (13.2%) on anticoagulation and 1069 (2.0%) were on APT + anticoagulation. In patients with a history of ischaemic stroke/TIA ( n  = 11,948; 22.4%), 2401 (20.1%) had no prior antithrombotic therapy, 6594 (55.2%) were on APT, 2489 (20.8%) on anticoagulation and 464 (3.9%) on APT + anticoagulation. Amongst patients with ischaemic stroke despite APT, aetiology was large artery atherosclerosis in 19.8% ( n  = 3416), cardiac embolism in 23.6% ( n  = 4059), small vessel disease in 11.7% ( n  = 2011), other causes in 7.4% ( n  = 1267), more than one cause in 6.3% ( n  = 1078) and unknown cause in 31.3% ( n  = 5388). Prior APT was not independently associated with unfavourable outcome (aOR = 1.06; 95% CI: 0.98-1.14; p  = 0.135) or death (aOR = 1.10; 95% CI: 0.99-1.21; p  = 0.059) at 3-months but with increased odds of recurrent stroke (6.0% vs 4.3%; aOR 1.26; 95% CI: 1.11-1.44; p  < 0.001)., Conclusions: One-third of ischaemic strokes occurred despite APT and 20% of patients with a history of ischaemic stroke had no antithrombotic therapy when having stroke recurrence. Aetiology of breakthrough strokes despite APT is heterogeneous and these patients are at increased risk of recurrent stroke.

Background: Computed tomography angiography (CTA) of the supraaortic arteries is commonly used for acute stroke workup and may reveal apical pulmonary lesions (APL)., Aim: To determine the prevalence, follow-up algorithms, and in-hospital outcomes of stroke patients with APL on CTA., Methods: We retrospectively included consecutive adult patients with ischemic stroke, transient ischemic attack, or intracerebral hemorrhage and available CTA at a tertiary hospital between January 2014 and May 2021. We reviewed all CTA reports for the presence of APL. APL were classified as malignancy suspicious or benign appearing based on radiological-morphological criteria. We performed regression analyses to investigate the impact of malignancy suspicious APL on different in-hospital outcome parameters., Results: Among 2715 patients, APL on CTA were found in 161 patients (5.9% [95%CI: 5.1-6.9]; 161/2715). Suspicion of malignancy was present in one third of patients with APL (36.0% [95%CI: 29.0-43.7]; 58/161), 42 of whom (72.4% [95%CI: 60.0-82.2]; 42/58) had no history of lung cancer or metastases. When performed, further investigations confirmed primary or secondary pulmonary malignancy in three-quarters (75.0% [95%CI: 50.5-89.8]; 12/16), with two patients (16.7% [95%CI: 4.7-44.8]; 2/12) receiving de novo oncologic therapy. In multivariable regression, the presence of radiologically malignancy suspicious APL was associated with higher NIHSS scores at 24 h (beta = 0.67, 95%CI: 0.28-1.06, p  = 0.001) and all-cause in-hospital mortality (aOR = 3.83, 95%CI: 1.29-9.94, p  = 0.01)., Conclusions: One in seventeen patients shows APL on CTA, of which one-third is malignancy suspicious. Further work-up confirmed pulmonary malignancy in a substantial number of patients triggering potentially life-saving oncologic therapy.

Background: Several molecular biomarkers are available that predict newly detected atrial fibrillation (NDAF). We aimed to identify such biomarkers that predict NDAF after an Ischaemic stroke (IS)/Transient Ischaemic Attack (TIA) and evaluate their performance., Methods: A systematic review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies of patients with IS, TIA, or both, who underwent ECG monitoring for ⩾24 h, which reported molecular biomarkers and frequency of NDAF after electronic searches of multiple databases were included., Results: Twenty-one studies (76% IS, 24% IS and TIA) involving 4640 patients were included. Twelve biomarkers were identified, with cardiac biomarkers evaluated in the majority (75%) of patients. Performance measures were inconsistently reported. Among cohorts selecting high-risk individuals (12 studies), the most studied biomarkers were N-Terminal-Pro Brain Natriuretic Peptide (NT-ProBNP, five studies; C-statistics reported by three studies, 0.69-0.88) and Brain Natriuretic Peptide (BNP, two studies; C-statistics reported in two studies, 0.68-0.77). Among unselected cohorts (nine studies), the most studied biomarker was BNP (six studies; C-statistics reported in five studies, 0.75-0.88). Only BNP was externally validated (two studies) but using different thresholds to categorise risk of NDAF., Conclusion: Cardiac biomarkers appear to have modest to good discrimination for predicting NDAF, although most analyses were limited by small, heterogeneous study populations. Their clinical utility should be explored further, and this review supports the need to assess the role of molecular biomarkers in large prospective studies with standardised selection criteria, definition of clinically significant NDAF and laboratory assays., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JD has obtained honoraria from Medtronic, BI, BMS, Diaicchi Sankyo, Bayer, Pfizer. In addition, research support was also obtained from Pfizer and BMS. AK has obtained honoraria from Medtronic, Bayer and Abbott Inc. AC has received honoraria from BMS, Pfizer, AstraZeneca and Boeringher Ingelheim and research grants from Pfizer., (© European Stroke Organisation 2022.)

Background: Early identification of patients developing symptomatic intracranial hemorrhage and symptomatic brain edema after acute ischemic stroke is essential for clinical decision-making. Astroglial protein S-100B is a marker of blood-brain barrier disruption, which plays an important role in the formation of intracranial hemorrhage and brain edema. In this study, we assessed the prognostic value of serum S-100B for the development of these complications., Methods: Serum S-100B levels were measured within 24 h from symptom onset in 1749 consecutive acute ischemic stroke patients from the prospective, observational, multicenter BIOSIGNAL cohort study (mean age 72.0 years, 58.3% male). To determine symptomatic intracranial hemorrhage or symptomatic brain edema, follow-up neuroimaging was performed in all patients receiving reperfusion therapy or experiencing clinical worsening with an NIHSS increase of ⩾4., Results: Forty six patients (2.6%) developed symptomatic intracranial hemorrhage and 90 patients (5.2%) developed symptomatic brain edema. After adjustment for established risk factors, log 10 S-100B levels remained independently associated with both symptomatic intracranial hemorrhage (OR 3.41, 95% CI 1.7-6.9, p  = 0.001) and symptomatic brain edema (OR 4.08, 95% CI 2.3-7.1, p  < 0.001) in multivariable logistic regression models. Adding S-100B to the clinical prediction model increased the AUC from 0.72 to 0.75 ( p  = 0.001) for symptomatic intracranial hemorrhage and from 0.78 to 0.81 ( p  < 0.0001) for symptomatic brain edema., Conclusions: Serum S-100B levels measured within 24 h after symptom onset are independently associated with the development of symptomatic intracranial hemorrhage and symptomatic brain edema in acute ischemic stroke patients. Thus, S-100B may be useful for early risk-stratification regarding stroke complications., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TH Nothing to report; JS Nothing to report; AB Nothing to report; LW Nothing to report; VS Nothing to report; CI Nothing to report; TP Nothing to report; MA reports honoraria and board involvements outside the submitted work; UF reports grants, consulting fees, honoraria and board involvements, outside the submitted work; LB Nothing to report; GM Nothing to report; KN Nothing to report; TK Nothing to report; CC reports fees outside the submitted work; GK reports grants outside the submitted work; JM Nothing to report; AB Nothing to report; EP Nothing to report; GN Nothing to report; CF reports a patent Use of GFAP for identification of intracerebral Hemorrhage US20150247867 licensed to Banyan Biomarkers; AL reports grants and fees outside the submitted work.; KS Nothing to report; LS Nothing to report; AvE reports grants, fees, honoraria and board involvements, outside the submitted work; MA Nothing to report; MKv reports grants from the Swiss National Science Foundation (142422), the Swiss Heart Foundation, the Göhner Foundation and the Swiss Seaside Foundation as well as non-financial support from Roche diagnostics during the conduct of the study and is involved in the Advisory Board of AstraZeneca, Bayer, Amgen, BMS/Pfizer and Medtronic outside the submitted work., (© European Stroke Organisation 2022.)

Background: We investigated 92 blood biomarkers implicated in the pathophysiological pathways of ischemic injury, inflammation, hemostasis, and regulation of vascular resistance to predict post-stroke mortality., Aim: Based on the most promising markers, we aimed to create a novel Biomarker Panel Index (BPI) for risk stratification., Methods: In this prospective study, we measured 92 biomarkers in 320 stroke patients. The primary outcome measure was mortality within 90 days. We estimated the association of each biomarker using logistic regression adjusting for multiple testing. The most significant 16 biomarkers were used to create the BPI. We fitted regression models to estimate the association and the discriminatory accuracy of the BPI with mortality and stroke etiology., Results: Adjusted for demographic and vascular covariates, the BPI remained independently associated with mortality (odds ratio (OR) 1.68, 95% confidence interval (CI): 1.29-2.18) and cardioembolic stroke etiology (OR 1.38, 95% CI: 1.10-1.74), and improved the discriminatory accuracy to predict mortality (area under the receiver operating characteristic curve (AUC) 0.93, 95% CI: 0.89-0.96) and cardioembolic stroke etiology (AUC 0.70, 95% CI: 0.64-0.77) as compared to the best clinical prediction models alone (AUC 0.89, 95% CI: 0.84-0.94 and AUC 0.66, 95% CI: 0.60-0.73, respectively)., Conclusions: We identified a novel BPI improving risk stratification for mortality after ischemic stroke beyond established demographic and vascular risk factors. Furthermore, the BPI is associated with underlying cardioembolic stroke etiology. These results need external validation., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

Purpose: The microbiological aetiology of pneumonia complicating stroke is poorly characterised. In this second Pneumonia in Stroke ConsEnsuS statement, we propose a standardised approach to empirical antibiotic therapy in pneumonia complicating stroke, based on likely microbiological aetiology, to improve antibiotic stewardship., Methods: Systematic literature searches of multiple databases were undertaken. An evidence review and a round of consensus consultation were completed prior to a final multi-disciplinary consensus meeting in September 2017, held in Barcelona, Spain. Consensus was approached using a modified Delphi technique and defined a priori as 75% agreement between the consensus group members. Findings : No randomised trials to guide antibiotic treatment of pneumonia complicating stroke were identified. Consensus was reached for the following: (1) Stroke-associated pneumonia may be caused by organisms associated with either community-acquired or hospital-acquired pneumonia; (2) Treatment for early stroke-associated pneumonia (<72 h of stroke onset) should cover community-acquired pneumonia organisms; (3) Treatment for late stroke-associated pneumonia (≥72 h and within seven days of stroke onset) should cover community-acquired pneumonia organisms plus coliforms +/- Pseudomonas spp . if risk factors; (4) No additional antimicrobial cover is required for patients with dysphagia or aspiration; (5) Pneumonia occurring after seven days from stroke onset should be treated as for hospital-acquired pneumonia; (6) Treatment should continue for at least seven days for each of these scenarios., Discussion: Consensus recommendations for antibiotic treatment of the spectrum of pneumonia complicating stroke are proposed. However, there was limited evidence available to formulate consensus on choice of specific antibiotic class for pneumonia complicating stroke., Conclusion: Further studies are required to inform evidence-based treatment of stroke-associated pneumonia including randomised trials of antibiotics and validation of candidate biomarkers., (© European Stroke Organisation 2019.)

Background: An increasing proportion of physicians are women, yet they still face challenges with career advancement. In 2014, the European Stroke Organisation established the goal of increasing the number and participation of women within the society using a Top Down and Bottom Up approach. The 'Women's Initiative for Stroke in Europe' was created the same year by a group of women active within the organisation. We aimed to assess the current status of women in European Stroke Organisation, and to explore the change in sex differences after the introduction of focused approaches to address disparities in 2014., Methods: Using organisational records, we collected data on sex differences in core activities from 2008 up to 2017 including membership, participation in conferences, courses and in the official journal of the society, and positions of seniority and leadership. We estimated sex distribution differences in each of the activities from 2014 to date., Results: In 2017, the proportion of female members was 40%, while 24% of fellows, 22% of the executive board and 19% of the editorial board in the official journal of the society were women. From 2014 to 2017, there was a significant increase in the proportion of female members (p = 0.0002) and in women participating in the annual conference as faculty (p = 0.001). There was no significant change in the sex distribution among the faculty members in junior educational activities (≤27%) or fellows., Interpretation: In 2017, the proportion of women holding positions of seniority and leadership is still significantly lower to the proportion of women attending educational activities. Transparent data on sex distribution will assist implementing tailored programmes to achieve progress against sex-based barriers., (© European Stroke Organisation 2019.)