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Inhibitory control refers to the ability to suppress cognitive or motor processes. Current neurocognitive models indicate that this function mainly involves the anterior cingulate cortex and the inferior frontal cortex. However, how the communication between these areas influence inhibitory control performance and their functional response remains unknown. We addressed this question by injecting behavioral and electrophysiological markers of inhibitory control recorded during a Go/NoGo task as the 'symptoms' in a connectome-based lesion-symptom mapping approach in a sample of 96 first unilateral stroke patients. This approach enables us to identify the white matter tracts whose disruption by the lesions causally influences brain functional activity during inhibitory control. We found a central role of left frontotemporal and frontobasal intrahemispheric connections, as well as of the connections between the left temporoparietal and right temporal areas in inhibitory control performance. We also found that connections between the left temporal and right superior parietal areas modulate the conflict-related N2 event-related potential component and between the left temporal parietal area and right temporal and occipital areas for the inhibition P3 component. Our study supports the role of a distributed bilateral network in inhibitory control and reveals that combining lesion-symptom mapping approaches with functional indices of cognitive processes could shed new light on post-stroke functional reorganization. It may further help to refine the interpretation of classical electrophysiological markers of executive control in stroke patients., (© 2024. The Author(s).)

Acute stroke triggers extensive changes to myeloid immune cell populations in the brain that may be targets for limiting brain damage and enhancing repair. Immunomodulatory approaches will be most effective with precise manipulation of discrete myeloid cell phenotypes in time and space. Here, we investigate how stroke alters mononuclear myeloid cell composition and phenotypes at single-cell resolution and key spatial patterns. Our results show that multiple reactive microglial states and monocyte-derived populations contribute to an extensive myeloid cell repertoire in post-stroke brains. We identify important overlaps and distinctions among different cell types/states that involve ontogeny- and spatial-related properties. Notably, brain connectivity with infarcted tissue underpins the pattern of local and remote altered cell accumulation and reactivity. Our discoveries suggest a global but anatomically governed brain myeloid cell response to stroke that comprises diverse phenotypes arising through intrinsic cell ontogeny factors interacting with exposure to spatially organized brain damage and neuro-axonal cues., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Carotid artery stenting (CAS) for heavily calcified lesions is controversial due to concern for stent failure and increased perioperative stroke risk. However, the degree to which calcification affects outcomes is poorly understood, particularly in transcarotid artery revascularization (TCAR). With the precipitous increase in TCAR use and its expansion to standard surgical-risk patients, we aimed to determine the impact of lesion calcification on CAS outcomes to ensure its safe and appropriate use., Methods: We identified patients in the Vascular Quality Initiative who underwent first-time transfemoral CAS (tfCAS) and TCAR between 2016 and 2021. Patients were stratified into groups based on degree of lesion calcification: no calcification, 1% to 50% calcification, 51% to 99% calcification, and 100% circumferential calcification or intraluminal protrusion. Outcomes included in-hospital and 1-year composite stroke/death, as well as individual stroke, death, and myocardial infarction outcomes. Logistic regression was used to evaluate associations between degree of calcification and these outcomes., Results: Among 21,860 patients undergoing CAS, 28% patients had no calcification, 34% had 1% to 50% calcification, 35% had 51% to 99% calcification, and 3% had 100% circumferential calcification/protrusion. Patients with 51% to 99% and circumferential calcification/protrusion had higher odds of in-hospital stroke/death (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.02-1.6; P = .034; OR, 1.9; 95% CI, 1.1-2.9; P = .004, respectively) compared with those with no calcification. Circumferential calcification was also associated with increased risk for in-hospital myocardial infarction (OR, 3.5; 95% CI, 1.5-8.0; P = .003). In tfCAS patients, only circumferential calcification/protrusion was associated with higher in-hospital stroke/death odds (OR, 2.0; 95% CI, 1.2-3.4; P = .013), whereas for TCAR patients, 51% to 99% calcification was associated with increased odds of in-hospital stroke/death (OR, 1.5; 95% CI, 1.1-2.2; P = .025). At 1 year, circumferential calcification/protrusion was associated with higher odds of ipsilateral stroke/death (12.4% vs 6.6%; hazard ratio, 1.64; P = .002)., Conclusions: Among patients undergoing CAS, there is an increased risk of in-hospital stroke/death for lesions with >50% calcification or circumferential/protruding plaques. Increasing severity of carotid lesion calcification is a significant risk factor for stroke/death in patients undergoing CAS, regardless of approach., Competing Interests: Disclosures None., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Accumulating evidence indicates that neutrophil activation (NA) contributes to microvascular thromboinflammation in acute ischemic stroke (AIS) due to a large vessel occlusion. Preclinical data have suggested that intravenous thrombolysis (IVT) before endovascular therapy (EVT) could dampen microvascular thromboinflammation. In this study we investigated the association between NA dynamics and stroke outcome, and the impact of IVT on NA in patients with AIS treated with EVT., Methods: A single-center prospective study was carried out, including patients treated with EVT for whom three blood samples (before, within 1 hour, 24 hours post-EVT) were drawn to measure plasma myeloperoxidase (MPO) concentration as a marker of NA. Unfavorable outcome was defined as a modified Rankin score of 3-6 at 3 months., Results: Between 2016 and 2020, 179 patients were included. The plasma MPO concentration peaked significantly 1 hour post-EVT (median increase 21.0 ng/mL (IQR -2.1-150)) and returned to pre-EVT baseline values 24 hours after EVT (median change from baseline -0.8 ng/mL (IQR -7.6-6.7)). This peak was strongly associated with unfavorable outcomes at 3 months (aOR 0.53 (95% CI 0.34 to 0.84), P=0.007). IVT before EVT abolished this 1 hour post-EVT MPO peak. Changes in plasma MPO concentration (baseline to 1 hour post-EVT) were associated with unfavorable outcomes only in patients not treated with IVT before EVT (aOR 0.54 (95% CI 0.33 to 0.88, P=0.013). However, we found no significant heterogeneity in the associations between changes in plasma MPO concentration and outcomes., Conclusions: A peak in plasma MPO concentration occurs early after EVT and is associated with unfavorable outcomes. IVT abolished the post-EVT MPO peak and may modulate the association between NA and outcomes., Competing Interests: Competing interests: MM reports personal fees from Boerhinger Ingelheim, Air Liquide, Acticor Biotech, Amgen, Novonordisk outside the submitted work. JL reports personal fees from Julien Labreuche during the conduct of the study. JMH reports personal fees from Alexion, grants and personal fees from Astra-Zeneca, personal fees from Bayer, personal fees from Boehringer Ingelheim france, personal fees from GSK, personal fees from MSD, personal fees from Novo, personal fees from Sanofi, personal fees from Servier, personal fees from Vifor Fresenius outside the submitted work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Retinal artery occlusion (RAO) may lead to irreversible blindness. For acute RAO, intravenous thrombolysis (IVT) can be considered as treatment. However, due to the rarity of RAO, data about IVT safety and effectiveness is limited., Methods: From the multicenter database ThRombolysis for Ischemic Stroke Patients (TRISP), we retrospectively analyzed visual acuity (VA) at baseline and within 3 months in IVT and non-IVT treated RAO patients. Primary outcome was difference of VA between baseline and follow up (∆VA). Secondary outcomes were rates of visual recovery (defined as improvement of VA ⩾ 0.3 logMAR), and safety (symptomatic intracranial hemorrhage (sICH) according to ECASS II criteria, asymptomatic intracranial hemorrhage (ICH) and major extracranial bleeding). Statistical analysis was performed using parametric tests and a linear regression model adjusted for age, sex and baseline VA., Results: We screened 200 patients with acute RAO and included 47 IVT and 34 non-IVT patients with complete information about recovery of vision. Visual Acuity at follow up significantly improved compared to baseline in IVT patients (∆VA 0.5 ± 0.8, p  < 0.001) and non-IVT patients (∆VA 0.40 ± 1.1, p  < 0.05). No significant differences in ∆VA and visual recovery rate were found between groups at follow up. Two asymptomatic ICH (4%) and one (2%) major extracranial bleeding (intraocular bleeding) occurred in the IVT group, while no bleeding events were reported in the non-IVT group., Conclusion: Our study provides real-life data from the largest cohort of IVT treated RAO patients published so far. While there is no evidence for superiority of IVT compared to conservative treatment, bleeding rates were low. A randomized controlled trial and standardized outcome assessments in RAO patients are justified to assess the net benefit of IVT in RAO., 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: PB: Research funds by the Gottfried and Julia Bangerter-Rhyner Foundation and Swiss Academy of Medical Sciences and funding for travel and conference fees from BMS/Pfizer. SW: Research funds by the Swiss National Science Foundation, the UZH Clinical research priority program (CRPP) stroke, the Swiss Heart foundation, the Zurich Neuroscience Center (ZNZ), speaker honoraria from Springer, Teva Pharma and consultancy fees from Bayer and Novartis. STE has received funding for travel or speaker honoraria from Bayer, Boehringer Ingelheim and Daiichi-Sankyo. He has served on scientific advisory boards for Bayer, Boehringer Ingelheim, BMS/Pfizer, and MindMaze and on the editorial board of Stroke. His institutions have received an educational grant from Pfizer, compensation from Stago for educational efforts and research support from Daiichi-Sankyo, the Science Funds [Wissenschaftsfonds] of the University Hospital Basel, the University Basel, from the “Wissenschaftsfonds Rehabilitation” of the University Department for Geriatric Medicine Felix Platter, the “Freiwillige Akademische Gesellschaft Basel,” the Swiss Heart Foundation, and the Swiss National Science Foundation. PR has received honoraria for advisory board participation from Boehringer Ingelheim and Pfizer and lecture fees from Boehringer Ingelheim, Bayer, Pfizer and Daiichi Sankyo. His institution has received a grant from Boehringer Ingelheim for the ECASS-4 Study. RRL received funding for speaker honoraria from Pfizer, Boehringer Ingelheim, Biogen and Iscehma View. He has served on scientific advisory boards for Novo-Nordisk and Bayer.

CT perfusion imaging is important in the imaging workup of acute ischemic stroke for evaluating affected cerebral tissue. CT perfusion analysis software produces cerebral perfusion maps from commonly noisy spatio-temporal CT perfusion data. High levels of noise can influence the results of CT perfusion analysis, necessitating software tuning. This work proposes a novel approach for CT perfusion analysis that uses physics-informed learning, an optimization framework that is robust to noise. In particular, we propose SPPINN: Spatio-temporal Perfusion Physics-Informed Neural Network and research spatio-temporal physics-informed learning. SPPINN learns implicit neural representations of contrast attenuation in CT perfusion scans using the spatio-temporal coordinates of the data and employs these representations to estimate a continuous representation of the cerebral perfusion parameters. We validate the approach on simulated data to quantify perfusion parameter estimation performance. Furthermore, we apply the method to in-house patient data and the public Ischemic Stroke Lesion Segmentation 2018 benchmark data to assess the correspondence between the perfusion maps and reference standard infarct core segmentations. Our method achieves accurate perfusion parameter estimates even with high noise levels and differentiates healthy tissue from infarcted tissue. Moreover, SPPINN perfusion maps accurately correspond with reference standard infarct core segmentations. Hence, we show that using spatio-temporal physics-informed learning for cerebral perfusion estimation is accurate, even in noisy CT perfusion data. The code for this work is available at https://github.com/lucasdevries/SPPINN., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Henk A. Marquering reports a relationship with Nicolab that includes: equity or stocks. Charles B.L.M. Majoie reports a relationship with Nicolab that includes: equity or stocks., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to demonstrate the safety and functional outcomes of antiplatelet use within 24 hours following mechanical thrombectomy (MT)., Methods: A retrospective review of prospectively collected data for consecutive patients who underwent MT for acute ischemic stroke (AIS) between 2016 and 2020 was performed. Patient demographics, comorbidities, Alberta Stroke Program Early CT Score (ASPECTS), antiplatelet use, neurological status, and tissue plasminogen activator use were collected. Patients were stratified into two groups, early (< 24 hours) or late (> 24 hours), based on when antiplatelet therapy was initiated post-MT. The primary outcome was safety, determined based on the rate of symptomatic intracranial hemorrhage (sICH) and inpatient mortality. The secondary outcome was functional independence (defined as modified Rankin Scale [mRS] score ≤ 2) at discharge and 30 days and 90 days postoperatively. The two cohorts were compared using univariate analysis. Multiple imputations were used to create complete data sets for missing data. Multivariable analysis was used to identify predictors for sICH and functional outcomes., Results: A total of 190 patients met inclusion criteria (95 per group). Significant differences between the early and late groups included sex, preoperative intravenous thrombolysis, angioplasty, stent placement, and thrombectomy site. ICH (symptomatic and asymptomatic) and inpatient mortality were not significantly different between the groups. The mRS score was significantly lower at discharge (p < 0.001), 30 days (p = 0.011), and 90 days (p = 0.024) following MT in the early group. Functional independence was significantly higher in the early antiplatelet group at discharge (p = 0.015) and at 30 days (p = 0.006). Early antiplatelet use was independently associated with significantly increased odds of achieving functional independence at discharge (OR 3.07, p = 0.007) and 30 days (OR 5.78, p = 0.004). Early antiplatelet therapy was not independently associated with increased odds of sICH., Conclusions: Early antiplatelet initiation after MT in patients with AIS was independently associated with significantly increased odds of improved postoperative functional outcomes without increased odds of developing sICH.

Acute ischemic stroke is a sudden neurological event caused by brain ischemia. Patients with large vessel occlusion are at high risk of developing significant cerebral edema, which can lead to rapid neurological decline. The optimal timing for decompressive hemicraniectomy to prevent further brain damage is still uncertain. This study aimed to identify potential predictors of severe brain edema. The data indicate that specific cytokines may help identify patients with a higher risk of developing life-threatening brain swelling in the early phase post-stroke. The association between a positive biomarker and the outcome was calculated, and three biomarkers-S100B protein, MMP-9, and IL-10-were found to be significantly associated with malignant edema. A model was derived for early predicting malignant cerebral edema, including S100B protein and IL-1 beta. These findings suggest that molecular biomarkers related to the ischemic cascade may be a helpful way of predicting the development of malignant cerebral edema in ischemic stroke patients, potentially widening the time window for intervention and assisting in decision-making. In conclusion, this study provides insights into the molecular mechanisms of severe brain edema and highlights the potential use of biomarkers in predicting the course of ischemic stroke., (© 2023. Springer Nature Limited.)

Background: In anterior circulation large vessel occlusion (LVO) in the extended time window, the guidelines recommend advanced imaging (ADVI) to select patients for endovascular therapy (EVT). However, questions remain regarding its availability and applicability in the real world. It is unclear whether an approach to the extended window EVT that does not use ADVI would be equivalent., Methods: In April 2022, a literature search was performed to identified randomized controlled trials (RCT) and observational studies describing 90-day outcomes. We performed a meta-analysis of the proportion of aggregate using a random effect to estimate rates of functional independence, defined as modified Rankin Scale (mRS) score ≤2 at 90 days, mean mRS, mortality and symptomatic intracranial hemorrhage (sICH) stratified by imaging modality., Results: Four RCTs and 28 observational studies were included. The pooled proportion of functional independence among patients selected by ADVI was 44% (95% CI 39% to 48%; I 2 =80%) and 48% (95% CI 41% to 55%; I 2 =75%) with non-contrast CT/CT angiography (NCCT/CTA) (p=0.36). Mean mRS with ADVI was 2.88 (95% CI 2.36 to 3.41; I 2 =0.0%) and 2.79 (95% CI 2.31 to 3.27; I 2 =0.0%) with NCCT (p=0.79). Mortality in patients selected by ADVI was 13% (95% CI 10% to 17%; I 2 =81%) and 16% (95% CI 12% to 22%; I 2 =69%) with NCCT (p=0.29). sICH with ADVI was 4% (95% CI 3% to 7%; I 2 =73%) and 6% with NCCT/CTA (95% CI 4% to 8%; I 2 =6%, p=0.27)., Conclusions: Our study suggests that, in anterior circulation LVO, the rates of functional independence may be similar when patients are selected using ADVI or NCCT for EVT in the extended time window. A simplified triage protocol does not seem to increase mortality or sICH. PROTOCOL REGISTRATION NUMBER: (PROSPERO ID: CRD42021236092)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

In many medical applications, interpretable models with high prediction performance are sought. Often, those models are required to handle semistructured data like tabular and image data. We show how to apply deep transformation models (DTMs) for distributional regression that fulfill these requirements. DTMs allow the data analyst to specify (deep) neural networks for different input modalities making them applicable to various research questions. Like statistical models, DTMs can provide interpretable effect estimates while achieving the state-of-the-art prediction performance of deep neural networks. In addition, the construction of ensembles of DTMs that retain model structure and interpretability allows quantifying epistemic and aleatoric uncertainty. In this study, we compare several DTMs, including baseline-adjusted models, trained on a semistructured data set of 407 stroke patients with the aim to predict ordinal functional outcome three months after stroke. We follow statistical principles of model-building to achieve an adequate trade-off between interpretability and flexibility while assessing the relative importance of the involved data modalities. We evaluate the models for an ordinal and dichotomized version of the outcome as used in clinical practice. We show that both tabular clinical and brain imaging data are useful for functional outcome prediction, whereas models based on tabular data only outperform those based on imaging data only. There is no substantial evidence for improved prediction when combining both data modalities. Overall, we highlight that DTMs provide a powerful, interpretable approach to analyzing semistructured data and that they have the potential to support clinical decision-making., (© 2022 Wiley-VCH GmbH.)

Mental flexibility (MF) refers to the capacity to dynamically switch from one task to another. Current neurocognitive models suggest that since this function requires interactions between multiple remote brain areas, the integrity of the anatomic tracts connecting these brain areas is necessary to maintain performance. We tested this hypothesis by assessing with a connectome-based lesion-symptom mapping approach the effects of white matter lesions on the brain's structural connectome and their association with performance on the trail making test, a neuropsychological test of MF, in a sample of 167 first unilateral stroke patients. We found associations between MF deficits and damage of i) left lateralized fronto-temporo-parietal connections and interhemispheric connections between left temporo-parietal and right parietal areas; ii) left cortico-basal connections; and iii) left cortico-pontine connections. We further identified a relationship between MF and white matter disconnections within cortical areas composing the cognitive control, default mode and attention functional networks. These results for a central role of white matter integrity in MF extend current literature by providing causal evidence for a functional interdependence among the regional cortical and subcortical structures composing the MF network. Our results further emphasize the necessity to consider connectomics in lesion-symptom mapping analyses to establish comprehensive neurocognitive models of high-order cognitive functions., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Ischemic stroke despite a direct oral anticoagulant (DOAC) is increasingly common and portends a high risk of subsequent ischemic stroke. The efficacy and safety of antithrombotic regimens after the condition are unclear. We aimed to compare the outcomes of patients with ischemic stroke despite DOACs with and without an alternative antithrombotic regimen and determine the risk factors of recurrent ischemic stroke while on anticoagulation., Methods: In a population-based, propensity score-weighted, retrospective cohort study, we compared the clinical outcomes of DOAC-to-warfarin switch, DOAC-to-DOAC switch (DOAC switch ), or addition of antiplatelet agents, with those of unchanged DOAC regimen (DOAC same ) among patients with nonvalvular atrial fibrillation (NVAF) who developed the first ischemic stroke despite a DOAC from January 1, 2015, to December 31, 2020, in Hong Kong. The primary outcome was recurrent ischemic stroke. Secondary outcomes were intracranial hemorrhage, acute coronary syndrome, and death. We performed competing risk regression analyses to compare the clinical endpoints and determined the predictors of recurrent ischemic stroke in an unweighted multivariable logistic regression model., Results: During the 6-year study period, among 45,946 patients with AF on a DOAC as stroke prophylaxis, 2,908 patients developed ischemic stroke despite a DOAC. A total of 2,337 patients with NVAF were included in the final analyses. Compared with DOAC same , warfarin (aHR 1.96, 95% CI 1.27-3.02, p = 0.002) and DOAC switch (aHR 1.62, 95% CI 1.25-2.11, p < 0.001) were associated with an increased risk of recurrent ischemic stroke. In the DOAC same group, adjunctive antiplatelet agent was not associated with a reduced risk of recurrent ischemic stroke. Diabetes mellitus, concurrent cytochrome P450/P-glycoprotein (CYP/P-gp) modulators, and large artery atherosclerotic disease (LAD) were predictors of recurrent ischemic stroke., Discussion: In patients with NVAF with ischemic stroke despite a DOAC, the increased risk of recurrent ischemic stroke with switching to warfarin called for caution against such practice, while the increased ischemic stroke with DOAC-to-DOAC switch demands further studies. Adjunctive antiplatelet agent did not seem to reduce ischemic stroke relapse. Because diabetes mellitus, the use of CYP/P-gp modulators, and LAD were predictors of recurrent ischemic stroke, further investigations should evaluate whether strict glycemic control, DOAC level monitoring, and routine screening for carotid and intracranial atherosclerosis may reduce ischemic stroke recurrence in these patients., Classification of Evidence: This study provides Class II evidence that in patients with NVAF experiencing an ischemic stroke while being treated with a DOAC, continuing treatment with that DOAC is more effective at preventing recurrent ischemic stroke than switching to a different DOAC or to warfarin., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Despite evolving treatments, functional recovery in patients with large vessel occlusion stroke remains variable and outcome prediction challenging. Can we improve estimation of functional outcome with interpretable deep learning models using clinical and magnetic resonance imaging data?, Methods: In this observational study, we collected data of 222 patients with middle cerebral artery M1 segment occlusion who received mechanical thrombectomy. In a 5-fold cross validation, we evaluated interpretable deep learning models for predicting functional outcome in terms of modified Rankin scale at 3 months using clinical variables, diffusion weighted imaging and perfusion weighted imaging, and a combination thereof. Based on 50 test patients, we compared model performances to those of 5 experienced stroke neurologists. Prediction performance for ordinal (modified Rankin scale score, 0-6) and binary (modified Rankin scale score, 0-2 versus 3-6) functional outcome was assessed using discrimination and calibration measures like area under the receiver operating characteristic curve and accuracy (percentage of correctly classified patients)., Results: In the cross validation, the model based on clinical variables and diffusion weighted imaging achieved the highest binary prediction performance (area under the receiver operating characteristic curve, 0.766 [0.727-0.803]). Performance of models using clinical variables or diffusion weighted imaging only was lower. Adding perfusion weighted imaging did not improve outcome prediction. On the test set of 50 patients, binary prediction performance between model (accuracy, 60% [55.4%-64.4%]) and neurologists (accuracy, 60% [55.8%-64.21%]) was similar when using clinical data. However, models significantly outperformed neurologists when imaging data were provided, alone or in combination with clinical variables (accuracy, 72% [67.8%-76%] versus 64% [59.8%-68.4%] with clinical and imaging data). Prediction performance of neurologists with comparable experience varied strongly., Conclusions: We hypothesize that early prediction of functional outcome in large vessel occlusion stroke patients may be significantly improved if neurologists are supported by interpretable deep learning models., Competing Interests: Disclosures Dr Heldner reports grants from the Bangerter Foundation, the Swiss National Science Foundation, SITEM (Center for Translational Medicine and Biomedical Entrepreneurship) Support Funds, and the Swiss Heart Foundation, all outside the submitted work. Dr Antonenko reports a grant from the Swiss National Science Foundation. Dr Dobrocky reports consultant fees for MicroVention, Inc. Dr Fischer reports grants from Alexion, CSL Behring, Medtronic, Penumbra, Inc, Phenox, Inc, Rapid Medical, Ltd, and Stryker. Dr Gralla reports interests with Medtronic USA, Inc. Dr Arnold reports consultancy fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Pfizer, Boehringer Ingelheim, Covidien, Medtronic, and Novo Nordisk. Dr Luft reports consultancy fees from Amgen and Moleac, Ltd. Susanne Wegener received research funds by the Swiss National Science Foundation, the UZH Clinical research priority program (CRPP) stroke, the Swiss Heart foundation, the Zurich Neuroscience Center (ZNZ), speaker honoraria from Springer, Teva Pharma, and consultancy fees from Bayer and Novartis. The other authors report no conflicts.

The optimal approach for prevention of cardiovascular events and reduction of bleeding in patients with acute coronary syndrome (ACS) and atrial fibrillation (AF) is still controversial. The aim of our study is to asses our single-center experience with concomitant left atrial appendage occlusion (LAAO) and percutaneous coronary intervention (PCI). 50 patients with ACS without ST elevation and history of AF were randomized after successful PCI to LAAO or conventional medical therapy. The primary endpoints were safety and length of hospitalization. The follow-up period was 30 days. The mean procedural times were 113 ± 23 min PCI + LAAO implantation and 39 ± 19 min of PCI only (p < 0.001), while mean fluoroscopy times were 18 ± 8 min and 12 ± 8 min (p < 0.001), respectively. No procedure-related complications were observed. There was no difference observed for length of hospitalization between two groups. LAAO in patients with ACS and AF undergoing PCI appears safe., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Background: Machine learning tools such as random forests provide important opportunities for modeling large, complex modern data generated in medicine. Unfortunately, when it comes to understanding why machine learning models are predictive, applied research continues to rely on 'out of bag' (OOB) variable importance metrics (VIMPs) that are known to have considerable shortcomings within the statistics community. After explaining the limitations of OOB VIMPs - including bias towards correlated features and limited interpretability - we describe a modern approach called 'knockoff VIMPs' and explain its advantages., Methods: We first evaluate current VIMP practices through an in-depth literature review of 50 recent random forest manuscripts. Next, we recommend organized and interpretable strategies for analysis with knockoff VIMPs, including computing them for groups of features and considering multiple model performance metrics. To demonstrate methods, we develop a random forest to predict 5-year incident stroke in the Sleep Heart Health Study and compare results based on OOB and knockoff VIMPs., Results: Nearly all papers in the literature review contained substantial limitations in their use of VIMPs. In our demonstration, using OOB VIMPs for individual variables suggested two highly correlated lung function variables (forced expiratory volume, forced vital capacity) as the best predictors of incident stroke, followed by age and height. Using an organized analytic approach that considered knockoff VIMPs of both groups of features and individual features, the largest contributions to model sensitivity were medications (especially cardiovascular) and measured medical risk factors, while the largest contributions to model specificity were age, diastolic blood pressure, self-reported medical risk factors, polysomnography features, and pack-years of smoking. Thus, we reach very different conclusions about stroke risk factors using OOB VIMPs versus knockoff VIMPs., Conclusions: The near-ubiquitous reliance on OOB VIMPs may provide misleading results for researchers who use such methods to guide their research. Given the rapid pace of scientific inquiry using machine learning, it is essential to bring modern knockoff VIMPs that are interpretable and unbiased into widespread applied practice to steer researchers using random forest machine learning toward more meaningful results., (© 2023. The Author(s).)

Objective: Recent studies have highlighted that race and socioeconomic status serve as important determinants of disease presentation and perioperative outcomes in carotid artery disease. However, these investigations only focus on individual factors of social disadvantage, and fail to account for community factors that may drive disparities. Area Deprivation Index (ADI) is a validated measure of neighborhood adversity that offers a more comprehensive assessment of social disadvantage. We examined the impact of ADI ranking on carotid artery disease severity, management, and postoperative outcomes., Methods: We identified patients who underwent carotid endarterectomy (CEA), transfemoral carotid artery stenting (tfCAS), and transcarotid artery revascularization (TCAR) in the Vascular Quality Initiative registry between 2016 and 2020. Patients were assigned ADI scores of 1 to 100 based on zip codes and grouped into quintiles, with higher quintiles reflecting increasing adversity. Outcomes assessed included disease presentation, intervention type, and discharge patterns. Logistic regression was used to evaluate independent associations between ADI quintiles and these outcomes., Results: Among 91,904 patients undergoing carotid revascularization, 9811 (10.7%) were in the lowest ADI quintile (Q1), 18,905 (20.6%) in Q2, 25,442 (27.7%) in Q3, 26,099 (28.4%) in Q4, and 11,647 (12.7%) in Q5. With increasing ADI quintiles, patients were more likely to present with symptomatic disease (Q5, 52.1% vs Q1, 46.6%; P < .001), and stroke vs transient ischemic attack (Q5, 63.1% vs Q1, 53.5%; P < .001); they also more frequently underwent CAS vs CEA (Q5, 46.4% vs Q1, 33.9%; P < .001), and specifically tfCAS vs TCAR (Q5, 54.2% vs Q1, 33.9%; P < .001). In adjusted analyses, higher ADI quintiles remained as independent risk factors for presenting with symptomatic disease and stroke and undergoing CAS and tfCAS. Across ADI quintiles, patients were more likely to experience death (Q5, 0.8% vs Q1, 0.4%; P < .001), stroke/death (Q5, 2.1% vs Q1, 1.6%; P = .001), failure to discharge home (Q5, 11.5% vs Q1, 8.0%; P < .001) and length of stay >2 days (Q5, 33.3% vs Q1, 26.3%; P < .001) following revascularization., Conclusions: Among carotid revascularization patients, those with greater neighborhood social disadvantage had greater disease severity and more frequently underwent tfCAS. These patients also had higher rates of death and stroke/death, were less frequently discharged home, and had prolonged hospital stays. Greater efforts are needed to ensure that patients in higher ADI quintiles undergo better carotid surveillance and are treated appropriately for their carotid artery disease., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Aspiration thrombectomy has been associated with an increased risk of stroke, and its routine use is not recommended. Ill-defined procedural techniques for aspiration thrombectomy may provide an explanation for inconsistent outcomes and adverse event rates in trials. Large thrombi can plug the aspiration port of the aspiration catheter and then be dislodged into the central circulation when they are retracted into the guide catheter, or when the aspiration catheter is removed from the Tuohy connector. We report a case of thrombus aspiration where a large distal thrombus was aspirated into the mouth of the aspiration catheter, held there with suction as it was removed and delivered outside the body without being dislodged. We offer several tips for safe removal of coronary thrombi too big to aspirate., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: The risk of symptomatic intracranial hemorrhage (ICH) approaches 5% despite mechanical thrombectomy (MT) efficacy for ischemic stroke secondary to large vessel occlusion. Flat-panel detector CT (FDCT) imaging with Syngo Dyna CT imaging (Siemens Medical Solutions, Malvern, PA) can be used immediately following MT to detect ICH., Purpose: To evaluate the accuracy and reliability of FDCT imaging with Dyna CT compared to conventional post-MT CT and MRI., Methods: Head FDCT (20 second, 70 kV) was performed immediately following MT on 26 consecutive patients; postprocedural CT or MRI was obtained ∼24 hours later. Two blinded, independent neuroradiologists evaluated all imaging, identifying ICH, stroke, and presence of subarachnoid contrast. Cohen's κ statistic was used to assess interrater agreement for each imaging outcome and compared the FDCT to conventional imaging., Results: FDCT for ICH demonstrated a strong degree of interrater reliability (κ = 0.896; 95% confidence interval [CI], 0.734-1.057). Negligible reliability was seen for ischemia determination on immediate post-MT FDCT (κ = 0.149; 95% CI, -0.243 to 0.541). ICH evaluation between FDCT and post-MT conventional CT revealed modest interrater reliability (κ = 0.432; 95% CI, -0.100 to 0.965), which did not reach statistical significance. There was no substantive reliability in the evaluation of ICH between FDCT and post-MT MRI (κ = 0.118, 95% CI, -0.345 to 0.580)., Conclusion: FDCT, such as Dyna CT, immediately post-MT is a promising tool that can expedite the detection of ICH with a high degree of reliability, although the detection of ischemic parenchymal changes is limited., (© 2023 American Society of Neuroimaging.)

Background: Atherosclerotic steno-occlusive cerebrovascular disease includes extracranial carotid occlusive and intracranial atherosclerotic disease. Despite the negative findings in Carotid Occlusion Surgery Study (COSS), many large centers continue to report favorable results for revascularization surgery in select groups of patients. The aim of our study was to perform an updated systematic review to investigate the role of revascularization surgery for atherosclerotic steno-occlusive patients in the modern era., Methods: Five independent reviewers performed Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided literature searches in October 2022 to identify articles reporting clinical outcomes in adult patients undergoing bypass for atherosclerotic steno-occlusive disease. Primary endpoints used were perioperative and long-term ischemic strokes, intracerebral hemorrhage, bypass patency, and favorable clinical outcomes. Study quality was evaluated with Newcastle-Ottawa, JADAD, and the Oxford Center for Evidence-Based Medicine scales., Results: A total of 6709 articles were identified in the initial search. Of these articles, 50 met the inclusion criteria and were included in the systematic review. A notable increase in the proportion of articles published over the past 10 years was observed. There were 6046 total patients with 4447 bypasses performed over the period from 1978 to 2022. The average length of follow-up was 2.75 ± 2.71 years. The average Newcastle-Ottawa was 6.23 out of 9 stars. There was a significant difference in perioperative stroke (odds ratio [OR], 0.65 [0.48-0.87]; P = 0.004), long-term ischemia (OR, 0.32 [0.23-0.44]; P < 0.0001), overall ischemia (OR, 0.36 [0.28-0.44]; P < 0.0001), and favorable outcomes (OR, 3.63 [2.84-4.64]; P < 0.0001) when comparing pre-COSS to post-COSS time frames in favor of post-COSS., Conclusions: Based on a systematic review of 50 articles, the existing literature indicates that long-term stroke rates and favorable outcomes for surgical revascularization for steno-occlusive disease have improved over time and are lower than previously reported. Improved patient selection, perioperative care, and surgical techniques may contribute to improved outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Patients presenting to the emergency department (ED) with acute vertigo or dizziness represent a diagnostic challenge. Neuroimaging has variable indications and yield. We aimed to conduct a systematic review and meta-analysis of the diagnostic test accuracy of neuroimaging for patients presenting with acute vertigo or dizziness., Methods: An electronic search was designed following patient-intervention-control-outcome (PICO) question-(P) adult patients with acute vertigo or dizziness presenting to the ED; (I) neuroimaging including computed tomography (CT), CT angiography (CTA), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and ultrasound (US); (C) MRI/clinical criterion standard; and (O) central causes (stroke, hemorrhage, tumor, others) versus peripheral causes of symptoms. Articles were assessed in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to assess certainty of evidence in pooled estimates., Results: We included studies that reported diagnostic test accuracy. From 6309 titles, 460 articles were retrieved, and 12 were included: noncontrast CT scan-six studies, 771 patients, pooled sensitivity 28.5% (95% confidence interval [CI] 14.4%-48.5%, moderate certainty) and specificity 98.9% (95% CI 93.4%-99.8%, moderate certainty); MRI-five studies, 943 patients, sensitivity 79.8% (95% CI 71.4%-86.2%, high certainty) and specificity 98.8% (95% CI 96.2%-100%, high certainty); CTA-one study, 153 patients, sensitivity 14.3% (95% CI 1.8%-42.8%) and specificity 97.7% (95% CI 93.8%-99.6%), CT had higher sensitivity than CTA (21.4% and 14.3%) for central etiology; MRA-one study, 24 patients, sensitivity 60.0% (95% CI 26.2%-87.8%) and specificity 92.9% (95% CI 66.1%-99.8%); US-three studies, 258 patients, sensitivity ranged from 30% to 53.6%, specificity from 94.9% to 100%., Conclusions: Noncontrast CT has very low sensitivity and MRI will miss approximately one in five patients with stroke if imaging is obtained early after symptom onset. The evidence does not support neuroimaging as the only tool for ruling out stroke and other central causes in patients with acute dizziness or vertigo presenting to the ED., (© 2022 Society for Academic Emergency Medicine.)

Background: History and physical examination are key features to narrow the differential diagnosis of central versus peripheral causes in patients presenting with acute vertigo. We conducted a systematic review and meta-analysis of the diagnostic test accuracy of physical examination findings., Methods: This study involved a patient-intervention-control-outcome (PICO) question: (P) adult ED patients with vertigo/dizziness; (I) presence/absence of specific physical examination findings; and (O) central (ischemic stroke, hemorrhage, others) versus peripheral etiology. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was assessed., Results: From 6309 titles, 460 articles were retrieved, and 43 met the inclusion criteria: general neurologic examination-five studies, 869 patients, pooled sensitivity 46.8% (95% confidence interval [CI] 32.3%-61.9%, moderate certainty) and specificity 92.8% (95% CI 75.7%-98.1%, low certainty); limb weakness/hemiparesis-four studies, 893 patients, sensitivity 11.4% (95% CI 5.1%-23.6%, high) and specificity 98.5% (95% CI 97.1%-99.2%, high); truncal/gait ataxia-10 studies, 1810 patients (increasing severity of truncal ataxia had an increasing sensitivity for central etiology, sensitivity 69.7% [43.3%-87.9%, low] and specificity 83.7% [95% CI 52.1%-96.0%, low]); dysmetria signs-four studies, 1135 patients, sensitivity 24.6% (95% CI 15.6%-36.5%, high) and specificity 97.8% (94.4%-99.2%, high); head impulse test (HIT)-17 studies, 1366 patients, sensitivity 76.8% (64.4%-85.8%, low) and specificity 89.1% (95% CI 75.8%-95.6%, moderate); spontaneous nystagmus-six studies, 621 patients, sensitivity 52.3% (29.8%-74.0%, moderate) and specificity 42.0% (95% CI 15.5%-74.1%, moderate); nystagmus type-16 studies, 1366 patients (bidirectional, vertical, direction changing, or pure torsional nystagmus are consistent with a central cause of vertigo, sensitivity 50.7% [95% CI 41.1%-60.2%, moderate] and specificity 98.5% [95% CI 91.7%-99.7%, moderate]); test of skew-15 studies, 1150 patients (skew deviation is abnormal and consistent with central etiology, sensitivity was 23.7% [95% CI 15%-35.4%, moderate] and specificity 97.6% [95% CI 96%-98.6%, moderate]); HINTS (head impulse, nystagmus, test of skew)-14 studies, 1781 patients, sensitivity 92.9% (95% CI 79.1%-97.9%, high) and specificity 83.4% (95% CI 69.6%-91.7%, moderate); and HINTS+ (HINTS with hearing component)-five studies, 342 patients, sensitivity 99.0% (95% CI 73.6%-100%, high) and specificity 84.8% (95% CI 70.1%-93.0%, high)., Conclusions: Most neurologic examination findings have low sensitivity and high specificity for a central cause in patients with acute vertigo or dizziness. In acute vestibular syndrome (monophasic, continuous, persistent dizziness), HINTS and HINTS+ have high sensitivity when performed by trained clinicians., (© 2022 Society for Academic Emergency Medicine.)

Purpose: To evaluate and compare which factors are relevant to the diagnostic decision-making and imaging workup of intracerebral hemorrhages in large, specialized European centers., Methods: Expert neuroradiologists from ten large, specialized centers (where endovascular stroke treatment is routinely performed) in nine European countries were selected in cooperation with the European Society of Neuroradiology (ESNR). The experts were asked to describe how and when they would investigate specific causes in a patient who presented with an acute, atraumatic, intracerebral hemorrhage for two given locations: (1) basal ganglia, thalamus, pons or cerebellum; (2) lobar hemorrhage. Answers were collected, and decision trees were compared., Results: Criteria that were considered relevant for decision-making reflect recommendations from current guidelines and were similar in all participating centers. CT Angiography or MR angiography was considered essential by the majority of centers regardless of other factors. Imaging in clinical practice tended to surpass guideline recommendations and was heterogeneous among different centers, e.g., in a scenario suggestive of typical hypertensive hemorrhage, recommendations ranged from no further follow-up imaging to CT angiography and MR angiography. In no case was a consensus above 60% achieved., Conclusion: In European clinical practices, existing guidelines for diagnostic imaging strategies in ICH evaluation are followed as a basis but in most cases, additional imaging investigation is undertaken. Significant differences in imaging workup were observed among the centers. Results suggest a high level of awareness and caution regarding potentially underlying pathology other than hypertensive disease., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

CT perfusion imaging is commonly used for infarct core quantification in acute ischemic stroke patients. The outcomes and perfusion maps of CT perfusion software, however, show many discrepancies between vendors. We aim to perform infarct core segmentation directly from CT perfusion source data using machine learning, excluding the need to use the perfusion maps from standard CT perfusion software. To this end, we present a symmetry-aware spatio-temporal segmentation model that encodes the micro-perfusion dynamics in the brain, while decoding a static segmentation map for infarct core assessment. Our proposed spatio-temporal PerfU-Net employs an attention module on the skip-connections to match the dimensions of the encoder and decoder. We train and evaluate the method on 94 and 62 scans, respectively, using the Ischemic Stroke Lesion Segmentation (ISLES) 2018 challenge data. We achieve state-of-the-art results compared to methods that only use CT perfusion source imaging with a Dice score of 0.46. We are almost on par with methods that use perfusion maps from third party software, whilst it is known that there is a large variation in these perfusion maps from various vendors. Moreover, we achieve improved performance compared to simple perfusion map analysis, which is used in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Henk A. Marquering reports a relationship with Nicolab that includes: equity or stocks. Charles B.L.M. Majoie reports a relationship with Nicolab that includes: equity or stocks., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Conflict of interest: The authors have provided declaration of interest information for all relationships that might be perceived as real or potential sources of conflicts of interest. The full disclosures can be viewed in the supplementary material for this article, available online at https://doi.org/10.1093/europace/euac144.

Background and Purpose: An early understanding of stroke mechanism may improve treatment and outcome in patients presenting with large vessel occlusion stroke (LVOS) treated with mechanical thrombectomy (MT). We aimed to investigate whether spontaneous external carotid artery (ECA) embolism detection during MT is associated with stroke etiology and clinical outcome., Methods: We retrospectively reviewed our prospectively maintained institutional database including consecutive patients with anterior circulation LVOS treated with MT between January 2015 and August 2020., Results: An ECA embolus was detected in 68 of 1298 patients (5.2%). The kappa coefficient for interobserver agreement was 0.89 (95% confidence interval [CI] 0.82-0.95). ECA embolism was significantly associated with intracranial internal carotid artery (ICA) occlusion (p < 0.001), cardioembolic etiology (p < 0.001) and a lower clot burden score (p < 0.001). Day-1 variation of National Institutes of Health Stroke Scale score (adjusted odds ratio [OR] -2.7, 95% CI -4.9 to 0.3; p = 0.021) and delta Alberta Stroke Program Early Computed Tomography Score (adjusted OR 0.9, 95% CI 0.2 to 1.5; p = 0.004) were worse among patients with ECA emboli. There was no significant difference in 90-day functional outcome between groups (adjusted OR 0.8, 95% CI 0.42 to 1.52; p = 0.50)., Conclusion: In patients with anterior circulation LVOS treated with MT, ECA embolism was significantly associated with cardioembolic etiology, high thrombus burden and proximal intracranial ICA occlusions. This underexplored angiographic pattern might provide a valuable etiologic clue to the underlying cause of anterior circulation LVOS and may also help determine the appropriate revascularization strategy., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Women and men with chronic coronary syndrome (CCS) have different clinical features and management, and studies on mid-term prognosis have reported conflicting results. Our objective was to investigate the impact of the female sex in the prognosis of the disease in the very long term. Methods and Results: We investigated differential features and very long-term prognosis in 1268 consecutive outpatients with CCS (337 [27%] women and 931 [73%] men). Women were older than men, more likely to have hypertension, diabetes, angina, and atrial fibrillation, and less likely to be exsmoker/active smoker and to have been treated with coronary revascularization ( p  < 0.05 for all). The prescription of statins, antiplatelets, and betablockers was similar in both groups. After up to 17 years of follow-up (median = 11 years, interquartile range = 4-15 years), cumulative incidences of acute myocardial infarction (10.2% vs. 11.8%) or stroke (11% vs. 10%) at median follow-up were similar, but the risks of major cardiovascular events (acute myocardial infarction, stroke, or cardiovascular death, 41.2% vs. 33.6%), hospital admission for heart failure (20.9% vs. 11.9%), or cardiovascular death (32.3% vs. 22.1%) were significantly higher for women ( p  < 0.0005), with a nonsignificant trend to higher overall mortality (45.2% vs. 39.1%, p  = 0.07). However, after multivariate adjustment, all these differences disappeared. Conclusion: Although women and men with CCS presented a different clinical profile, and crude rates of major cardiovascular events, heart failure and cardiovascular death were higher in women, female sex was not an independent prognostic factor in this study with up to 17 years of follow-up.

Objectives: Ischemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population., Materials and Methods: Retrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE., Results: Medical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors., Conclusions: The variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Moyamoya disease is a chronic, progressive cerebrovascular disease involving occlusion or stenosis of the terminal portion of the internal carotid artery. We conducted an updated systematic review and meta-analysis to investigate clinical and angiographic outcomes comparing direct, combined, and indirect bypass for the treatment of moyamoya disease in adults., Methods: Two independent authors performed Preferred Reporting Items for Systematic reviews and Meta-Analyses guided literature searches in December 2021 to identify articles reporting clinical/angiographic outcomes in adult moyamoya disease patients undergoing bypass. Primary end points used were ischemic and hemorrhagic strokes, clinical outcomes, and angiographic revascularization. Study quality was evaluated with Newcastle-Ottawa and the Oxford Center for Evidence-Based Medicine scales., Results: Four thousand four hundred fifty seven articles were identified in the initial search; 143 articles were analyzed. There were 3827 direct, 3826 indirect, and 3801 combined bypasses. Average length of follow-up was 3.59±2.93 years. Pooled analysis significantly favored direct (odds ratio [OR], 0.62 [0.48-0.79]; P <0.0001; OR, 0.44 [0.32-0.59]; P <0.0001; OR, 0.56 [0.42-0.74]; P <0.0001; OR, 3.1 [2.5-3.8]; P =0.0001) and combined (OR, 0.53 [0.41-0.69]; P <0.0001; OR, 0.28 [0.2-0.41]; P <0.0001; OR, 0.41 [0.3-0.56]; P <0.0001; OR, 3.1 [2.8-4.3]; P =0.0001) over indirect bypass for early stroke, late stroke, late intracerebral hemorrhage, and favorable outcomes, respectively. Indirect bypass was favored over combined (OR, 3.1 [1.7-5.6]; P <0.0001) and direct (OR, 4.12 [2.34-7.25]; P <0.0001) for early intracerebral hemorrhage. The meta-analysis significantly favored direct (OR, 0.37 [0.23-0.60]; P <0.001; OR, 0.49 [0.31-0.77]; P =0.002) and combined (OR, 0.23 [0.12-0.43]; P <0.00001; OR, 0.30 [0.18-0.49]; P <0.00001) bypass over indirect bypass for late stroke and late hemorrhage, respectively. Combined bypass was favored over indirect bypass for favorable outcomes (OR, 2.06 [1.18-3.58]; P =0.01)., Conclusions: Based on combined meta-analysis (43 articles) and pooled analysis (143 articles), the existing literature indicates that combined and direct bypasses have significant benefits for patients suffering from late stroke and hemorrhage versus indirect bypass. Combined bypass was favored over indirect bypass for favorable outcomes. This is a strong recommendation based on low-quality evidence when utilizing the Grades of Recommendation, Assessment, Development, and Evaluation system. These findings have important implications for bypass strategy selection.

Background: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with large vessel occlusion is unknown. Perfusion imaging may identify subsets of large vessel occlusion-related minor stroke patients with distinct response to bridging therapy., Methods: We conducted a multicenter international observational study of consecutive IVT-treated patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) who had an anterior circulation large vessel occlusion and perfusion imaging performed before IVT, with a subset undergoing immediate thrombectomy. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month modified Rankin Scale score 0 to 1. We searched for an interaction between treatment group and mismatch volume (critical hypoperfusion-core volume)., Results: Overall, 569 patients were included (172 and 397 in the bridging therapy and IVT groups, respectively). After propensity-score weighting, the distribution of baseline variables was similar across the 2 groups. In the entire population, bridging was associated with lower odds of achieving modified Rankin Scale score 0 to 1: odds ratio, 0.73 [95% CI, 0.55-0.96]; P =0.03. However, mismatch volume modified the effect of bridging on clinical outcome ( P interaction =0.04 for continuous mismatch volume); bridging was associated with worse outcome in patients with, but not in those without, mismatch volume <40 mL (odds ratio, [95% CI] for modified Rankin Scale score 0-1: 0.48 [0.33-0.71] versus 1.14 [0.76-1.71], respectively). Bridging was associated with higher incidence of symptomatic intracranial hemorrhage in the entire population, but this effect was present in the small mismatch subset only ( P interaction =0.002)., Conclusions: In our population of large vessel occlusion-related minor stroke patients, bridging therapy was associated with lower rates of good outcome as compared with IVT alone. However, mismatch volume was a strong modifier of the effect of bridging therapy over IVT alone, notably with worse outcome with bridging therapy in patients with mismatch volume ≤40 mL. Randomized trials should consider adding perfusion imaging for patient selection.

Background: Intensive care unit (ICU) acquired weakness is associated with reduced physical function, increased mortality and reduced quality of life, and affects about 43% of survivors of critical illness. Lacking therapeutic options, the prevention of known risk factors and implementation of early mobilization is essential. Robotic assistance devices are increasingly being studied in mobilization., Objective: This qualitative review synthesizes the evidence of early mobilization in the ICU and focuses on the advantages of robotic assistance devices., Results: Active mobilization should begin early during critical care. Interventions commencing 72 h after admission to the ICU are considered early. Mobilization interventions during critical care have been shown to be safe and reduce the time on mechanical ventilation in the ICU and the length of delirious episodes. Protocolized early mobilization interventions led to more active mobilization and increased functional independence and mobility at hospital discharge. In rehabilitation after stroke, robot-assisted training increases the chance of regaining independent walking ability, especially in more severely impaired patients, seems to be safe and increases muscle strength and quality of life in small trials., Conclusion: Early mobilization improves the outcome of the critically ill. Robotic devices support the gait training after stroke and are the subject of ongoing studies on early mobilization and verticalization in the intensive care setting., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

BACKGROUND: Medication adherence and persistence is fundamental for drug effectiveness, which is also true for the prevention of strokes in patients with atrial fibrillation (AF). Adherence to direct oral anticoagulants (DOACs) as first-line agents is often high in the early posthospital period. However, adherence often sharply declines (or eventually leads to nonpersistence) in the post-discharge ambulatory period, rendering stroke prevention ineffective. If patients at high risk of nonpersistence or nonadherence could be identified early, they could be offered early intervention measures to improve adherence and/or persistence. OBJECTIVE: To develop and internally validate a predictive model for medication nonadherence and nonpersistence to DOAC treatment in patients with AF after discharge using health insurance claims data. METHODS: We selected health insurance claims data between 2011 and 2016 from 8,055 patients with AF who were newly treated with rivaroxaban or apixaban after a hospital admission for stroke, transient ischemic attack, or AF. In the post-discharge ambulatory period, medication adherence was derived as the proportion of days covered, calculated from drug dispensation data. A maximum permissible 90-day gap between the end of a prescription and the next dispensation was used to estimate persistence. Candidate predictors were either derived from the index hospital admission or summarized from the previous year (eg, comorbidities or medication adherence to long-term treatments, such as ß-blockers, renin-angiotensin system inhibitors, statins, and thyroid hormones). A regularized logistic regression model was fitted using the least absolute shrinkage and selection operator in a split-sample approach (66.7% training data; 33.3% test data) to predict a composite of medication nonadherence/nonpersistence. Discrimination performance was assessed using the area under the receiver operating characteristic curve, the maximum sensitivity/specificity, and the scaled Brier score. A calibration curve fitted by linear regression was used to evaluate model calibration. RESULTS: The average age of the study participants was 79.7 years, 62% were female, and 3,515 patients (44%) were adherent and persistent (median follow-up of 185 days). Medication adherence to previous long-term treatments showed strong predictive properties. The developed model discriminated well (concordance statistic: 0.755), was well calibrated, and showed a scaled Brier score of 0.202 for identification of patients at risk. CONCLUSIONS: The model successfully predicted medication non-adherence/nonpersistence to DOAC treatment after discharge. Such a model could help ensure that targeted interventions are already in place at the time of hospital discharge, potentially preventing strokes and reducing costs. DISCLOSURES: Mr Wirbka is funded by the German Innovation Funds according to § 92a (2) Volume V of the Social Insurance Code (§ 92a Abs. 2, SGBV-Fünftes Buch Sozialgesetzbuch), grant number: 01VSF18019. Dr Haefeli received financial support from Daiichi-Sankyo, app development (https://www.easydoac.de/), and Bayer. He also received personal speaker fees from Bristol Myers-Squibb and Daiichi-Sankyo Online Seminar. Dr Meid is funded by the Physician-Scientist Programme of the Medical Faculty of Heidelberg University.

Background: For patients with symptomatic atrial fibrillation (AF), physicians typically offer AF ablation for symptom relief; however, patients often anticipate/expect a life free from anticoagulation. This belief puts patients at increased risk of stroke due to the potential for asymptomatic AF postablation if anticoagulation is ceased contrary to clinical guidelines. Although the WATCHMAN device has been FDA-approved to decrease the risk of thromboembolism from the left atrial appendage (LAA) in patients with an appropriate rationale to avoid oral anticoagulation, it has not been well-studied following AF ablation. Additionally, there are limited data comparing the WATCHMAN device to direct oral anticoagulants. The OPTION study will investigate whether LAA closure with the WATCHMAN FLX device is a reasonable alternative to oral anticoagulation following percutaneous catheter ablation for nonvalvular AF., Trial Design: OPTION is a multinational, multicenter, prospective randomized clinical trial. Patients with a CHA 2 DS 2 -VASc of ≥2 in men or ≥3 in women and who underwent a AF catheter ablation procedure between 90 and 180 days prior to randomization (sequential) or are planning to have catheter ablation within 10 days of randomization (concomitant) will be randomized in a 1:1 allocation of WATCHMAN FLX vs control. Control patients will start or continue market-approved oral anticoagulation for the duration of the trial. A total of 1600 patients were randomized from 130 global investigational sites. Follow-up for both device and control patients will occur at 3, 12, 24, and 36 months. The primary effectiveness noninferiority endpoint is stroke (ischemic or hemorrhagic), all-cause death, or systemic embolism at 36 months. The primary safety superiority endpoint is nonprocedural bleeding through 36 months (International Society on Thrombosis and Haemostasis [ISTH] major bleeding or clinically relevant nonmajor bleeding). The secondary noninferiority endpoint is ISTH major bleeding through 36 months (including procedural bleeding)., Conclusions: This trial will assess the safety and efficacy of WATCHMAN FLX in a postablation contemporary clinical AF patient population at risk of stroke., (Copyright © 2022. Published by Elsevier Inc.)

Background: While aortic valve replacement (AVR) is indicated for symptomatic severe aortic stenosis (AS), the appropriate management of asymptomatic severe AS remains unclear. We conducted an updated meta-analysis to compare the outcomes of surgical AVR (SAVR) versus conservative treatment in patients with asymptomatic severe AS., Methods: We searched PubMed, EMBASE, Cochrane, clinicaltrials.gov, and Google Scholar for studies comparing outcomes of SAVR versus conservative treatment in asymptomatic severe AS. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each individual study. Outcomes included all-cause mortality, cardiovascular and non-cardiovascular mortality, 30-day operative mortality, sudden cardiac death (SCD), heart failure hospitalization (HFH), myocardial infarction (MI), and stroke., Results: A total of 8 studies with 2685 patients were included. The mean age was above 60 years, and the median follow-up duration was 4 years. Compared to conservative treatment, SAVR was associated with significantly lower all-cause mortality (RR 0.39; 95% CI 0.23-0.64) and HFH rates (RR 0.18; 95% CI 0.05-0.71). There were no significant differences in cardiovascular mortality (RR 0.24; 95% CI 0.03-1.67), non-cardiovascular mortality (RR 0.49; 95% CI 0.23-1.03), 30-day operative mortality (RR 0.48; 95% CI 0.10-2.32), SCD (RR 0.37; 95% CI 0.05-2.89), MI (RR 0.48; 95% CI 0.04-5.52), and stroke rates (RR 1.20; 95% CI 0.35-4.11) between the two strategies., Conclusions: In patients with asymptomatic severe AS, SAVR is associated with significantly lower all-cause mortality and HFH compared to conservative treatment. While SAVR is a promising option for asymptomatic severe AS, most studies were observational and nonrandomized; randomized trials are needed to establish a clear benefit., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Machine learning has immense novel but also disruptive potential for medicine. Numerous applications have already been suggested and evaluated concerning cardiovascular diseases. One important aspect is the detection and management of potentially thrombogenic arrhythmias such as atrial fibrillation. While atrial fibrillation is the most common arrhythmia with a lifetime risk of one in three persons and an increased risk of thromboembolic complications such as stroke, many atrial fibrillation episodes are asymptomatic and a first diagnosis is oftentimes only reached after an embolic event. Therefore, screening for atrial fibrillation represents an important part of clinical practice. Novel technologies such as machine learning have the potential to substantially improve patient care and clinical outcomes. Additionally, machine learning applications may aid cardiologists in the management of patients with already diagnosed atrial fibrillation, for example, by identifying patients at a high risk of recurrence after catheter ablation. We summarize the current state of evidence concerning machine learning and, in particular, artificial neural networks in the detection and management of atrial fibrillation and describe possible future areas of development as well as pitfalls. Typical data flow in machine learning applications for atrial fibrillation detection., (© 2022. The Author(s).)

Background: Left atrial appendage occlusion (LAAO) provides an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). In patients with a long-term or permanent contraindication for OAC randomized controlled trial (RCT) data is lacking., Study Objectives: To assess the efficacy and safety of LAAO in AF patients who are ineligible to use OAC. The co-primary efficacy endpoint is (1) time to first occurrence of stroke (ischemic, hemorrhagic, or undetermined) and (2) time to first occurrence of the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). The primary safety endpoint is the 30-day rate of peri-procedural complications., Study Design: This is a multicenter, investigator-initiated, open-label, blinded endpoint (PROBE), superiority-driven RCT. Patients with AF, a CHA₂DS₂-VASc score ≥2 for men and ≥3 for women and a long-term or permanent contraindication for OAC will be randomized in a 2:1 fashion to the device- or control arm. Patients in the device arm will undergo percutaneous LAAO and will receive post-procedural dual antiplatelet therapy (DAPT) per protocol, while those in the control arm will continue their current treatment consisting of no antithrombotic therapy or (D)APT as deemed appropriate by the primary responsible physician. In this endpoint-driven trial design, assuming a 50% lower stroke risk of LAAO compared to conservative treatment, 609 patients will be followed for a minimum of 1 and a maximum of 5 years. Cost-effectiveness and budget impact analyses will be performed to allow decision-making on reimbursement of LAAO for the target population in the Netherlands., Summary: The COMPARE LAAO trial will investigate the clinical superiority in preventing thromboembolic events and cost-effectiveness of LAAO in AF patients with a high thromboembolic risk and a contraindication for OAC use., Nct Trial Number: NCT04676880., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To emphasize treatment speed for time-sensitive conditions, emergency medicine has developed not only the concept of the golden hour, but also the platinum half-hour. Patients with acute stroke treated within the first half-hour of onset have not been previously characterized., Methods: In this cohort study, we analyzed patients enrolled in the FAST-MAG (Field Administration of Stroke Therapy-Magnesium) trial, testing paramedic prehospital start of neuroprotective agent ≤2 hours of onset. The features of all acute cerebral ischemia, and intracranial hemorrhage patients with treatment starting at ≤30 m of last known well were compared with later-treated patients., Results: Among 1680 patients, 203 (12.1%) received study agents within 30 minutes of last known well. Among platinum half-hour patients, median onset-to-treatment time was 28 minutes (interquartile range, 25-30), and final diagnoses were acute cerebral ischemia in 71.8% (ischemic stroke, 61.5%, TIA 10.3%); intracranial hemorrhage in 26.1%; and mimic in 2.5%. Clinical features among platinum half-hour patients were largely similar to later-treated patients and included age 69 (interquartile range, 57-79), 44.8% women, prehospital Los Angeles Motor Scale median 4 (3-5), and early-postarrival National Institutes of Health Stroke Scale deficit 8 (interquartile range, 3-18). Platinum half-hour acute cerebral ischemia patients did have more severe prehospital motor deficits and younger age; platinum half-hour intracranial hemorrhage patients had more severe motor deficits, were more often female, and less often of Hispanic ethnicity. Outcomes at 3 m in platinum half-hour patients were comparable to later-treated patients and included freedom-from-disability (modified Rankin Scale score, 0-1) in 35.5%, functional independence (modified Rankin Scale score, 0-2) in 53.2%, and mortality in 17.7%., Conclusions: Prehospital initiation permits treatment start within the platinum half-hour after last known well in a substantial proportion of acute ischemic and hemorrhagic stroke patients, accounting for more than 1 in 10 enrolled in a multicenter trial. Hyperacute platinum half-hour patients were largely similar to later-treated patients and are an attainable target for treatment in prehospital stroke trials.

Objective: To report the 3-year experience of endovascular revascularization of acute arterial mesenteric ischemia (AMI) from an intestinal stroke center unit (ISCU)., Method: All data from patients admitted to the ISCU between January 2016 and January 2019 for arterial AMI who underwent endovascular recanalization were prospectively acquired and retrospectively analyzed. Patient demographics, clinical and laboratory characteristics at presentation, and CT scans were reviewed. The type (thrombolysis, thrombectomy, stenting) and the outcome of endovascular procedures (technical success or failure, complications) were noted. Care pathways were described focusing on post-procedural treatments (surgical revascularization, bowel resection) and the mortality rate was evaluated in subgroups., Results: Fifty-eight patients (34 men [59%], mean 69 ± 29 years) were included. Endovascular revascularization was technically successful in 51/58 (88%) patients, and 10 (17%) patients had post-procedural complications. Stenting and in situ thrombolysis were performed in most patients (n = 33 and n = 19, respectively). Thirty-two patients (55%) were recurrence-free and required no further treatment after the procedure, while 9 (16%), 5 (9%), and 5 (9%) patients underwent 2nd-line bowel resection, surgical revascularization, or both. Overall, 46 (79%), 45 (78%), and 34 patients (63%) were alive at 3 months, 1 year, and 3 years. No significant difference in survival was found in care pathways or baseline characteristics., Conclusion: Endovascular revascularization is highly feasible for the treatment of arterial AMI, and is associated with an acceptable rate of complications. Results of endovascular revascularization shall only be interpreted as part of a multidisciplinary patient management strategy., Key Points: • Endovascular revascularization is highly feasible for the treatment of arterial AMI, and is associated with an acceptable rate of complications. • Several techniques are available to perform endovascular revascularization, and their use depends on the cause, the location, and the quality of underlying arteries of patients. • Results of endovascular revascularization shall only be interpreted in relation to its role in an integrated multidisciplinary and patient management strategy., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Decision making for the "best" treatment is particularly challenging in situations in which individual patient response to drugs can largely differ from average treatment effects. By estimating individual treatment effects (ITEs), we aimed to demonstrate how strokes, major bleeding events, and a composite of both could be reduced by model-assisted recommendations for a particular direct oral anticoagulant (DOAC)., Methods: In German claims data for the calendar years 2014-2018, we selected 29 901 new users of the DOACs rivaroxaban and apixaban. Random forests considered binary events within 1 y to estimate ITEs under each DOAC according to the X-learner algorithm with 29 potential effect modifiers; treatment recommendations were based on these estimated ITEs. Model performance was evaluated by the c-for-benefit statistics, absolute risk reduction (ARR), and absolute risk difference (ARD) by trial emulation., Results: A significant proportion of patients would be recommended a different treatment option than they actually received. The stroke model significantly discriminated patients for higher benefit and thus indicated improved decisions by reduced outcomes (c-for-benefit: 0.56; 95% confidence interval [0.52; 0.60]). In the group with apixaban recommendation, the model also improved the composite endpoint (ARR: 1.69 % [0.39; 2.97]). In trial emulations, model-assisted recommendations significantly reduced the composite event rate (ARD: -0.78 % [-1.40; -0.03])., Conclusions: If prescribers are undecided about the potential benefits of different treatment options, ITEs can support decision making, especially if evidence is inconclusive, risk-benefit profiles of therapeutic alternatives differ significantly, and the patients' complexity deviates from "typical" study populations. In the exemplary case for DOACs and potentially in other situations, the significant impact could also become practically relevant if recommendations were available in an automated way as part of decision making.HighlightsIt was possible to calculate individual treatment effects (ITEs) from routine claims data for rivaroxaban and apixaban, and the characteristics between the groups with recommendation for one or the other option differed significantly.ITEs resulted in recommendations that were significantly superior to usual (observed) treatment allocations in terms of absolute risk reduction, both separately for stroke and in the composite endpoint of stroke and major bleeding.When similar patients from routine data were selected (precision cohorts) for patients with a strong recommendation for one option or the other, those similar patients under the respective recommendation showed a significantly better prognosis compared with the alternative option.Many steps may still be needed on the way to clinical practice, but the principle of decision support developed from routine data may point the way toward future decision-making processes.

Background White matter hyperintensity (WMH) has been linked to poor clinical outcomes after acute ischemic stroke. Purpose To assess whether the WMH burden on pretreatment MRI scans is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) or poor functional outcome in patients with acute ischemic stroke treated with endovascular thrombectomy (EVT). Materials and Methods In this retrospective study, consecutive patients treated with EVT for anterior circulation acute ischemic stroke at a comprehensive stroke center (where MRI was the first-line pretreatment imaging strategy; January 2015 to December 2017) were included and analyzed. WMH volumes were assessed with semiautomated volumetric analysis at fluid-attenuated inversion recovery MRI by readers who were blinded to clinical data. The associations of WMH burden with sICH and 3-month functional outcome (modified Rankin Scale [mRS] score) were assessed. Results A total of 366 patients were included (mean age, 69 years ± 19 [SD]; 188 women [51%]). Median total WMH volume was 3.61 cm 3 (IQR, 1.10-10.83 cm 3 ). Patients demonstrated higher mRS scores with increasing WMH volumes (odds ratio [OR], 1.020 [95% CI: 1.003, 1.037] per 1.0-cm 3 increase for each mRS point increase; P = .018) after adjustment for patient and clinical variables. There were no significant associations between WMH severity and 90-day mortality (OR, 1.007 [95% CI: 0.990, 1.024]; P = .40) or the occurrence of sICH (OR, 1.001 [95% CI: 0.978, 1.024]; P = .94). Conclusion Higher white matter hyperintensity burden was associated with increased risk for poor 3-month functional outcome after endovascular thrombectomy for large-vessel occlusive stroke. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Mossa-Basha and Zhu in this issue.

Introduction: Donor hepatic artery thrombosis (dHAT) identified during liver procurement and backtable is a rare and little-reported event that can make liver transplants unfeasible., Methods: This is a retrospective study of dHAT identified during liver grafts procurements or backtable procedures. All grafts were recovered from brain-dead donors. The demographic characteristics of the donors and the incidence of dHAT were analyzed. The data were also compared to a cohort of donors without dHAT., Results: There was a total of 486 donors during the study period. The incidence of dHAT was 1.85% (n = 9). The diagnosis of dHAT was made during procurement in 5 cases (55.5%) and during the backtable in 4 (44.4%). Most donors were female (n = 5), with an average BMI of 28.14 ± 6.9 kg/m 2 , hypertensive (n = 5), and with stroke as cause of brain death (n = 8). The most prevalent site of dHAT was a left hepatic artery originating from the left gastric artery (n = 4). Of the 9 cases reported, 2 livers were used for transplantation, and 7 were discarded. Comparing those cases to a cohort of 260 donors without dHAT, we found a higher incidence of anatomic variations in the hepatic artery (P = .01) and of stroke as cause of brain death (P = .05)., Conclusion: The occurrence of dHAT before liver procurement is a rare event, however it may become a treacherous pitfall if the diagnosis is late. Grafts with anatomic variations recovered from women with brain death due to stroke and with past history of hypertension seem to be at a higher risk of presenting dHAT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Neurological manifestations are frequent during COVID-19 but have been poorly studied as prognostic markers of COVID-19., Objectives: The aim of this study was to assess whether neurological manifestations are associated with a poor prognosis of COVID-19, and which patient and COVID-19 characteristics were associated with encephalopathy., Methods: This was a retrospective cohort study and included patients admitted with COVID-19 in four hospitals from Recife, Brazil. Data were collected by reviewing medical records., Results: 613 were included; 54.6% were male, the median age was 54 (41-68) years, 26.4% required mechanical ventilation, and 24.1% died. The neurological symptoms presented were: myalgia (25.6%), headache (22%), fatigue (22%), drowsiness (16%), anosmia (14%), disorientation (8.8%), ageusia (7.3%), seizures (2.8%), and dizziness (1.5%). Twelve patients (2%) had strokes (ischemic strokes: 9) and 149 (24.3%), encephalopathy. Older age, a prolonged hospitalization, diabetes mellitus, a previous history of stroke and having epileptic seizures during hospitalization were significantly associated with the occurrence of encephalopathy. Older age, smoking and requiring mechanical ventilation were associated with prolonged hospitalization. Older patients, those requiring mechanical ventilation and those with encephalopathy presented a significantly higher risk, while those who had anosmia presented a significantly lower risk of dying., Conclusions: Neurological symptoms are frequent among patients with COVID-19. Encephalopathy was the most frequent neurological complication and was associated with a higher mortality. Those with anosmia had a lower mortality., (© 2021. Belgian Neurological Society.)

Background: Prehospital automated large vessel occlusion (LVO) detection in Mobile Stroke Units (MSUs) could accelerate identification and treatment of patients with LVO acute ischemic stroke. Here, we evaluate the performance of a machine learning (ML) model on CT angiograms (CTAs) obtained from 2 MSUs to detect LVO., Methods: Patients evaluated on MSUs in Houston and Los Angeles with out-of-hospital CTAs were identified. Anterior circulation LVO was defined as an occlusion of the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or anterior cerebral artery vessels and determined by an expert human reader. A ML model to detect LVO was trained and tested on independent data sets consisting of in-hospital CTAs and then tested on MSU CTA images. Model performance was determined using area under the receiver-operator curve statistics., Results: Among 68 patients with out-of-hospital MSU CTAs, 40% had an LVO. The most common occlusion location was the middle cerebral artery M1 segment (59%), followed by the internal carotid artery (30%), and middle cerebral artery M2 (11%). Median time from last known well to CTA imaging was 88.0 (interquartile range, 59.5-196.0) minutes. After training on 870 in-hospital CTAs, the ML model performed well in identifying LVO in a separate in-hospital data set of 441 images with area under receiver-operator curve of 0.84 (95% CI, 0.80-0.87). ML algorithm analysis time was under 1 minute. The performance of the ML model on the MSU CTA images was comparable with area under receiver-operator curve 0.80 (95% CI, 0.71-0.89). There was no significant difference in performance between the Houston and Los Angeles MSU CTA cohorts., Conclusions: In this study of patients evaluated on MSUs in 2 cities, a ML algorithm was able to accurately and rapidly detect LVO using prehospital CTA acquisitions.

Background: Left atrial appendage occlusion (LAAO) is recommended for patients with atrial fibrillation at increased stroke risk, where effective long-term oral anticoagulation (OAC) is not feasible. In order to assess long-term safety of LAAO with aspirin monotherapy or no therapy, we aimed to report on patients with the Watchman LAAO device (Boston Scientific) once postimplantation intensified antiplatelet or anticoagulation therapy is discontinued., Methods: A total of 1025 patients scheduled for elective LAAO therapy prospectively consented for participation in the EWOLUTION registry; 1005 patients received a successful implant and were followed for 2 years. We identified 766 patients in EWOLUTION on single-antiplatelet therapy (SAPT; n = 639) or no therapy (n = 127) for ≥1 year following LAAO., Results: Three to 6 months after LAAO, 766 patients were switched to SAPT or no therapy and were followed for at least 1 year until the study's conclusion or with events while on SAPT/ no therapy; mean time on SAPT/no therapy was 536.56 ± 177.59 days. Patients experienced 1.4 ischemic strokes per 100 patient years (PY) despite a CHA2DS2-VASC score of 4.3 ± 1.6. Major nonprocedural bleeding rates were low, with 1.3 major bleeds per 100 PY with a mean HAS-BLED score of 2.2 ± 1.2. Furthermore, the ischemic stroke rate in the SAPT/no-therapy subgroup was similar to the whole EWOLUTION collective and high-risk subgroups; the bleeding rate was even lower. When analyzed separately, strokes (2.1/100 PY) and bleedings (1.4/100 PY) of the no-therapy subgroup were similar to patients on SAPT (strokes 0.7/100 PY [P=.70]; bleedings 1.4/100 PY [P=.90])., Conclusions: Outcome data of patients on SAPT/no therapy for ≥1 year following Watchman implantation in the EWOLUTION registry suggest the efficacy and safety of LAAO.

Background: Resistance to fibrinolysis, levels of procoagulant/antifibrinolytic neutrophil extracellular traps (NETs), and the severity of acute ischemic stroke (AIS) are increased by COVID-19. Whether NETs are components of AIS thrombi from COVID-19 patients and whether COVID-19 impacts the susceptibility of these thrombi to thrombolytic treatments remain unknown, however., Objectives: We aimed to characterize AIS thrombi from COVID-19 patients by immunohistology and to compare their response to thrombolysis to that of AIS thrombi from non-COVID-19 patients., Patients/methods: For this monocentric cohort study, 14 thrombi from COVID-19 AIS patients and 16 thrombi from non-COVID-19 patients, all recovered by endovascular therapy, were analyzed by immunohistology or subjected to ex vivo thrombolysis by tissue-type plasminogen (tPA)/plasminogen., Results: COVID-19 AIS thrombi were rich in neutrophils and contained NETs, but not spike protein. Thrombolysis assays revealed a mean resistance profile to tPA/plasminogen of COVID-19 AIS thrombi similar to that of non-COVID-19 AIS thrombi. The addition of DNase 1 successfully improved thrombolysis by potentiating fibrinolysis irrespective of COVID-19 status. Levels of neutrophil, NETs, and platelet markers in lysis supernatants were comparable between AIS thrombi from non-COVID-19 and COVID-19 patients., Conclusions: These results show that COVID-19 does not impact NETs content or worsen fibrinolysis resistance of AIS thrombi, a therapeutic hurdle that could be overcome by DNase 1 even in the context of SARS-CoV-2 infection., (© 2022 International Society on Thrombosis and Haemostasis.)

Background: Advanced age and type 2 diabetes (T2D) are common in patients with nonvalvular atrial fibrillation (NVAF). We evaluated the impact of age on the effectiveness and safety of rivaroxaban versus warfarin in this population., Methods: We analyzed electronic health record data from November 2010, to December 2019 including adults with NVAF and T2D, newly started on rivaroxaban or warfarin. Propensity score-overlap weighted hazard ratios (HRs) for stroke/systemic embolism (SSE), hospitalization for major or clinically relevant nonmajor bleeding (CRNMB), vascular death, major adverse limb events (MALE), major bleeding, and intracranial hemorrhage (ICH) were calculated for older (≥80 years) and younger (<80 years) cohorts., Results: We included 32 078 rivaroxaban and 83 971 warfarin users (6606 rivaroxaban and 25,335 warfarin patients were aged ≥80 years). No significant interaction for rivaroxaban versus warfarin by age was observed for any outcome, including SSE (HR = 1.05 vs 0.95), hospitalization for major or CRNMB (HR = 1.06 vs 0.90), vascular death (HR = 0.92 vs 0.90), MALE (HR = 0.80 vs 0.76), major bleeding or ICH., Conclusions: The effectiveness and safety of rivaroxaban versus warfarin remained consistent across patient age subgroups.

Aims: A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers., Methods: A cost-utility analysis estimated the impact of non-adherence over a 20-year horizon, for a patient cohort with a mean age of 77 years, based on data from the Stockholm Healthcare database of NVAF patients with incident stroke between 2011 and 2018. Adherence was defined using a medication possession ratio (MPR) cut-off of 90%; primary outcomes were the number of ischemic strokes and associated incremental cost-utility ratio., Results: Hypothetical comparisons between cohorts of 1,000 patients with varying non-adherence levels and full adherence (MPR >90%) predicted an additional number of strokes ranging from 117 (MPR = 81-90%) to 866 (MPR <60%), and years of life lost ranging from 177 (MPR = 81- 90%) to 1,318 (MPR < 60%; discounted at 3%). Chronic disease co-management intervention occurring during each DOAC prescription renewal and patient education intervention at DOAC initiation will be cost-saving to the health system if its cost is below SEK 143 and SEK 4,655, and cost-effective if below SEK 858 and SEK 28,665, respectively., Conclusion: Adherence improving interventions for NVAF patients on DOACs such as chronic disease co-management and patient education can be cost-saving and cost-effective, within a range of costs that appear reasonable to the Swedish healthcare system.

Purpose: Acute ischemic stroke (AIS) secondary to a basilar artery occlusion (BAO) carries a poor prognosis, especially in cases of severe symptoms, such as coma at presentation. Despite a lack of evidence, mechanical thrombectomy (MT) is often performed as the procedural risks are felt to be minimal compared to the natural history. We sought to evaluate MT efficacy and safety in comatose BAO patients., Methods: We performed a retrospective analysis of a multicenter prospective cohort of consecutive AIS patients with BAO who underwent MT. We compared baseline characteristics between comatose and noncomatose BAO patients, as well as clinical outcomes (modified Rankin scale, mRS 0-3 at 3 months). Using a multivariate logistic regression, we examined the population of comatose patients for baseline predictive factors of mortality., Results: We included 269 patients, 72 (27%) comatose and 197 (73%) non-comatose. Despite similar recanalization rates between comatose and non-comatose patients (83% vs. 90% p = 0.221), comatose patient long-term outcomes were dramatically worse (11% mRS 0-3 vs. 54%, p < 0.0001) and mortality was higher (64% vs. 34%, p < 0.0001). Baseline predictors of mortality at 3 months among comatose BAO patients after multivariate analysis were the following: male sex (odds ratio, OR 31.20, 2.57-378.52, p = 0.007), older age (OR 1.13, 1.04-1.24, p = 0.007) and higher serum glucose levels (OR 1.54, 1.07-2.21, p = 0.019)., Conclusion: Thrombectomy is technically effective for BAO patients presenting with coma; however, the long-term favorable outcome remains poor. Male sex, old age and hyperglycemia were predictors of mortality in these patients., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Heart failure predisposes to intracardiac thrombus (ICT) formation. There are limited data on the prevalence and impact of preexisting ICT on postoperative outcomes in left ventricular assist device patients. We examined the risk for stroke and death in this patient population., Methods and Results: We retrospectively studied patients who were implanted with HeartMate (HM) II or HM3 between February 2009 and March 2019. Preoperative transthoracic echocardiograms, intraoperative transesophageal echocardiograms and operative reports were reviewed to identify ICT. There were 525 patients with a left ventricular assist device (median age 60.6 years, 81.8% male, 372 HMII and 151 HM3) included in this analysis. An ICT was identified in 44 patients (8.4%). During the follow-up, 43 patients experienced a stroke and 55 died. After multivariable adjustment, presence of ICT increased the risk for the composite of stroke or death at 6-month (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.00-3.33, P = .049). Patients with ICT were also at higher risk for stroke (HR 2.45, 95% CI 1.14-5.28, P = .021) and death (HR 2.36, 95% CI 1.17-4.79 P = .016) at 6 months of follow-up., Conclusions: The presence of ICT is an independent predictor of stroke and death at 6 months after left ventricular assist device implantation. Additional studies are needed to help risk stratify and optimize the perioperative management of this patient population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A 62-year old man attended accident and emergency in June 2020 with dense right sided weakness, aphasia and confusion. Investigations revealed a left middle cerebral artery infarct, and he was admitted under the stroke team for ongoing inpatient rehabilitation. He was discharged home in September 2020 and received community stroke rehabilitation from physiotherapy, nursing, occupational therapy and speech and language therapy. He is now working towards a graded discharge from the Community Stroke and Neuro Rehab Team, after achieving his rehabilitation goals. In this case, the multidisciplinary team adopted different ways of working to accommodate the patients' priorities while also negotiating the COVID-19 pandemic. This included taking a transdisciplinary approach to rehabilitation and considering alternative supported self-management strategies. This case highlighted several learning points, particularly the potential benefits of shared goal setting for patients with communication difficulties and transdisciplinary approaches to community stroke rehabilitation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Targeted eloquence-based tissue reperfusion within the primary motor cortex may have a differential effect on disability as compared with traditional volume-based (thrombolysis in cerebral infarction, TICI) reperfusion after endovascular thrombectomy (EVT) in the setting of acute ischemic stroke (AIS)., Methods: We explored the impact of eloquent reperfusion (ER) within primary motor cortex (PMC) on clinical outcome (modified Rankin Scale, mRS) in AIS patients undergoing EVT. ER-PMC was defined as presence of flow on final digital subtraction angiography (DSA) within four main cortical branches, supplying the PMC (middle cerebral artery (MCA) - precentral, central, postcentral; anterior cerebral artery (ACA) - medial frontal branch arising from callosomarginal or pericallosal arteries) and graded as absent (0), partial (1), and complete (2). Prospectively collected data from two centers were analyzed. Multivariate analysis was conducted to assess the impact of ER-PMC on 90-day disability (mRS) among patients with anterior circulation occlusion who achieved partial reperfusion (TICI 2a and 2b)., Results: Among the 125 patients who met the study criteria, ER-PMC distribution was: absent (0) in 19/125 (15.2%); partial (1) in 52/125 (41.6%), and complete (2) in 54/125 (43.2%). TICI 2b was achieved in 102/125 (81.6%) and ER-PMC was substantially higher in those patients (P<0.001). In multivariate analysis, in addition to age and symptomatic intracranial hemorrhage, ER-PMC had a profound independent impact on 90-day disability (OR 6.10, P=0.001 for ER-PMC 1 vs 0 and OR 9.87, P<0.001 for ER-PMC 2 vs 0), while the extent of total partial reperfusion (TICI 2b vs 2a) was not related to 90-day mRS., Conclusions: Eloquent PMC-tissue reperfusion is a key determinant of functional outcome, with a greater impact than volume-based (TICI) degree of partial reperfusion alone. PMC-targeted revascularization among patients with partial reperfusion may further diminish post-stroke disability after EVT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)