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Background: There is an urgent need to replace fossil-based fuels and chemicals with bio-based, renewable alternatives. Water content is a critical parameter in these liquid products since water affects their quality and properties. However, currently existing methods for bio-oil water content determination have limitations and thus, there is a need to find methods that are versatile, work for a wide water content and sample consistency range repeatably and reliably and are safe for the user and the environment., Results: In this research, a 17 O NMR spectroscopy protocol for water content determination of pyrolysis and hydrothermal liquefaction (HTL) liquids was developed and compared with the standard method Karl Fischer (KF) titration. The approach showed linearity over a wide concentration range, and the changes to the measurement parameters caused only minor effects to the results (≤0.8 percentage points) indicating robustness. The method is also accurate since the absolute differences between experimental and theoretical water contents varied from 0.08 % to 2.09 %. Additionally, the precision of the method, based on the relative standard deviations (RSD) of the three replicate measurements of pyrolysis and HTL samples, was good (RSD <1.82 %). The method was applied to samples containing 1-98 wt% water. Overall, the 17 O NMR spectroscopy and KF titration results were well aligned with each other suggesting that the 17 O NMR spectroscopy is a potential alternative for the conventional KF titration., Significance: This is the first study on the use of 17 O NMR spectroscopy protocol for water content quantification. The results indicate that the protocol is an accurate, linear, and precise technique for water content determination of a wide range of samples. Furthermore, the method does not require hazardous chemicals or calibration standards, and the sample preparation is straightforward. The non-destructiveness of the method also enables further studies on the sample, e.g. by 1 H NMR spectroscopy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Noora Jokinen reports financial support was provided by Vilho Yrjö and Kalle Väisälä Fund. If there are other authors, they 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies., Methods: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients., Results: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31)., Conclusions: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment., (© 2024. The Author(s).)

Background: With the expanding eligibility for endovascular therapy (EVT) of patients presenting in the late window (6-24 hours after last known well), we aimed to derive a score to predict favorable outcomes associated with EVT versus best medical management., Methods and Results: A multinational observational cohort of patients from the CLEAR (Computed Tomography for Late Endovascular Reperfusion) study with proximal intracranial occlusion (2014-2022) was queried (n=58 sites). Logistic regression analyses were used to derive a 9-point score for predicting good functional outcome (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale score) at 90 days, with sensitivity analyses for prespecified subgroups conducted using bootstrapped random forest regressions. Secondary outcomes included 90-day functional independence (modified Rankin Scale score 0-2), poor outcome (modified Rankin Scale score 5-6), and 90-day survival. The score was externally validated with a single-center cohort (2014-2023). Of the 3231 included patients (n=2499 EVT), a 9-point score included age, early computed tomography ischemic changes, and stroke severity, with higher points indicating a higher probability of a good functional outcome. The areas under the curve for the primary outcome among EVT and best medical management subgroups were 0.72 (95% CI, 0.70-0.74) and 0.87 (95% CI, 0.84-0.90), respectively, with similar performance in the external validation cohort (area under the curve, 0.71 [95% CI, 0.66-0.76]). There was a significant interaction between the score and EVT for good functional outcome, functional independence, and poor outcome (all P interaction <0.001), with greater benefit favoring patients with lower and midrange scores., Conclusions: This score is a pragmatic tool that can estimate the probability of a good outcome with EVT in the late window., Registration: URL: https://www.Clinicaltrials.gov; Unique identifier: NCT04096248.

Background: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well., Methods: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT., Results: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P <0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P =0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P =0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P =0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P =0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well., Conclusions: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248., Competing Interests: Disclosures Drs Demeestere and Lemmens reported institutional research fees from Genentech. Dr Strbian reported consultancy fees from AstraZeneca and Boehringer Ingelheim. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda, Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, Ceretrieve; grants from Cerenovus and Stryker. Dr Nagel reported consultancy for Brainomix; speaker with Boehringer ingelheim and Pfizer. Dr Yamagami reported research grants from Bristol Myers Squibb; lecturer’s fees from Stryker, Medtronic, Johnson & Johnson, Bayer, Daiichi Sankyo, Bristol Myers Squibb, Otuska Pharmaceutical; advisory board for Daiichi Sankyo. Dr Puetz reported lecturer for Daiichi Sankyo. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; Data Safety and Monitoring Board from Jacobs Institute; and stock options in Viz AI. Dr Ribo reported consultancy for Medtronic, MiniMed, Cerenovus, AptaTargets, Stryker, Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Michel reported grants from University of Lausanne and Swiss National Science Foundation (SNF). Dr Marto reported consulting from Amicus Therapeutics, Boehringer Ingelheim; Speaker with Boehringer Ingelheim. Dr Henon reported fees from Novartis and a grant from Sanofi-Aventis. Dr Gutierrez reported consultancy fees from Medtronic, Stryker and Microvention, and a grant from Methinks, Microvention, Stryker and the National Institutes of Health. Dr Siegler reported a grant from Philips and Viz AI. Dr Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, CSL Behring; lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer Ingelheim, Daiichi Sankyo, Bayer and Bristol-Meyers Squibb. Dr Sheth reported consultancy for Imperative Care, Viz AI, Penumbra; compensation from Motif Neurosciences; grants from National Institutes of Health. Dr Dobrocky reported consultancy fees from MicroVention. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Zaidi reported a grant from Genentech. Dr Castonguay reported employment by Medtronic. Dr Uchida reported fees by Bristol Myers Squibb, Daiichi Sankyo, Medtronic and Stryker. Dr Sakai reported research grant from Biomedical Solutions, Medtronic, Terumo, TG Medical; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Daiichi Sankyo, Kaneka, Medtronic, Terumo; advisory board for Johnson & Johnson, Medtronic, Terumo. Dr Toyoda reported lecturer fees from Otsuka, Daiichi Sankyo, Bayer, Novartis, and Bristol-Myers Squibb. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Zaidat reported consultancy fees by Johnson & Johnson, Medtronic and Stryker, Penumbra stock, and a grant from Johson & Johnson, Medtronic, Penumbra and Stryker. Dr Fischer reported research support from SNF, Medtronic, Stryker, Rapid Medical, Penumbra, Phenox; consultancies for Stryker, CSL Behring; advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, Acthera. Dr Nguyen discloses research support from Medtronic to her institution; advisory board for Brainomix, Aruna Bio; Associate Editor Stroke.

Introduction: Present-day computer tomography (CT) scanners have excellent spatial resolution and signal-to-noise ratio and are instrumental detecting early ischemic changes (EIC) in brain. We assessed the temporal changes of EIC based on the recanalization status after thrombectomy., Patients and Methods: The cohort comprises consecutive patients with acute ischemic stroke in anterior circulation treated with thrombectomy in tertiary referral hospital. All baseline and follow-up scans were screened for any ischemic changes and further classified using Alberta Stroke Program Early CT Score (ASPECTS). Generalized linear mixed models were used to analyze the impact of recanalization status using modified Thrombolysis in Cerebral Infarction (mTICI) on temporal evolution of ischemic changes., Results: We included 614 patients with ICA, M1, or M2 occlusions. Median ASPECTS score was 9 (IQR 7-10) at baseline and 7 (5-8) at approximately 24 h. mTICI 3 was achieved in 207 (33.8%), 2B 241 (39.3%), 2A in 77 (12.6%), and 0-1 in 88 (14.3%) patients. Compared to patients with mTICI 3, those with mTICI 0-1 and 2A had less favorable temporal changes of ASPECTS ( p  < 0.001). Effect of recanalization was noted in the cortical regions of ICA/M1 patients, but not in their deep structures or patients with M2 occlusions. All ischemic changes detected at baseline were also present at all follow-up images, regardless of the recanalization status., Conclusions: Temporal evolution of the ischemic changes and ASPECTS are related to the success of the recanalization therapy in cortical regions of ICA/M1 patients, but not in their deep brain structures or M2 patients. In none of the patients did EIC revert in any brain region after successful recanalization., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window., Methods: This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well (TSLW) from January 2014 to May 2022 were included. The primary end point was the 90-day ordinal shift in the modified Rankin Scale (mRS) score. Inverse probability treatment weighting (IPTW) and multivariable methods were used., Results: Of 5,098 patients screened, 839 patients were included, with a median (interquartile range) age of 75 (64-83) years; 455 (54.2%) were women. There were 616 patients selected to undergo EVT by NCCT (73.4%) and 223 (26.6%) who were medically managed. In IPTW analyses, there was a more favorable 90-day ordinal mRS shift in patients selected by NCCT to EVT vs those who were medically managed (odds ratio [OR] 1.99, 95% CI 1.53-2.59; p < 0.001). There were higher rates of 90-day functional independence (mRS 0-2) in the EVT group (40.1% vs 18.4%, OR 3.31, 95% CI 2.11-5.20; p < 0.001). sICH was nonsignificantly higher in the EVT group (8.5% vs 1.4%, OR 3.77, 95% CI 0.72-19.7, p = 0.12). Mortality at 90 days was lower in the EVT vs MM group (23.9% vs 32.3%, OR 0.61, 95% CI 0.45-0.83, p = 0.002)., Discussion: In patients with proximal anterior LVO in the extended time window, there was a lower rate of disability and mortality in patients selected with NCCT and CTA to EVT compared with those who were medically managed. These findings support the use of NCCT as a simpler and more inclusive approach to patient selection in the extended window., Trial Registration Information: This study was registered at ClinicalTrials.gov under NCT04096248., Classification of Evidence: This study provides Class III evidence that for patients with proximal anterior circulation occlusion presenting with ischemic stroke from 6 to 24 hours, compared with medical management, those undergoing thrombectomy based on NCCT have reduced disability and mortality at 90 days.

Background and Purpose: We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability., Methods: In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0-4 and LVO who underwent EVT 6-24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0-2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2-4) and those without (mRS score 0-1)., Results: A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43-1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995)., Conclusion: A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window.

Background: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period., Methods: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR., Results: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR., Conclusions: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women., Competing Interests: Disclosures Dr Castonguay reports employment by Medtronic. Dr Cordonnier reports compensation from the University of Glasgow for data and safety monitoring services; employment by the University of Lille; compensation from Biogen for consultant services. Dr Fischer reports employment by Universität Basel; compensation from Boehringer Ingelheim and Biogen for expert witness services. Dr Dobrocky reported MicroVention consultancy. Dr Haussen reports compensation from Vesalio, Cerenovus, Chiesi USA, Inc, Stryker, Brainomix, and Poseydon Medical for consultant services; stock options in Viz.ai; compensation from Jacobs Institute for data and safety monitoring services. Dr Henon reports grants from Sanofi-Aventis U.S. LLC. Dr Kaesmacher reports grants from Swiss National Science Foundation to other. Dr Kaiser reported grants from Joachim Herz Foundation. Martinez-Majander reported grants from Finnish Medical Foundation. Dr Marto reported consulting from Amicus Therapeutics and Boehringer Ingelheim; Speaker with Boehringer Ingelheim. Dr Michel reports grants from the Swiss National Science Foundation, Swiss Heart Foundation, and the University of Lausanne to other. Dr Möhlenbruch reports grants from Medtronic, MicroVention, Inc, and Stryker to other. Dr Nagel reports compensation from Brainomix for consultant services. Dr Nguyen discloses research support from Medtronic, Society of Vascular, and Interventional Neurology to her institution; advisory board compensation from Idorsia, Brainomix; Associate Editor of Stroke. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda, Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz.ai, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, RapidPulse; stock options Viz.ai, Vesalio, Perfuze, Corindus, Brainomix, Ceretrieve; grants from Cerenovus, Stryker; Dr Nogueira reports compensation from Philips for consultant services; stock holdings in Quantanosis AI; compensation from Synchron for data and safety monitoring services; stock holdings in Piraeus Medical; stock options in Viseon, Inc; compensation from Hybernia for consultant services; stock options in Reist/Q’Apel Medical; stock options in Cerebrotech; compensation from Astrocyte and Cerebrotech for consultant services; stock holdings in Brain4Care; stock options in Truvic. Dr Ortega-Gutierrez reports compensation from MicroVention, Inc, Medtronic, and Stryker for consultant services; grants from Stryker, National Institutes of Health, methinks, Siemens, and MicroVention, Inc; and employment by Carver College of Medicine, University of Iowa. Dr Puetz reported as lecturer for Daiichi Sankyo. Dr Puri reports compensation from Medtronic, Stryker, Johnson & Johnson Health Care Systems, Inc, and MicroVention, Inc, for consultant services. Dr Ribo reports compensation from Philips, Stryker Corporation, Cerenovus, Medtronic MiniMed, Inc, and AptaTargets for consultant services; stock holdings in Anaconda Biomed, Methinks, and Nora. Dr Ringleb reports compensation from Daiichi Sankyo Company and Boehringer Ingelheim for consultant services; employment by Heidelberg University Hospital; travel support from Bristol-Myers Squibb and Bayer Healthcare. Dr Sakai reports compensation from Stryker, Asahi Intecc Co, Ltd, Terumo, Medtronic, Johnson & Johnson Medical Devices & Diagnostics Group, Latin America, L.L.C., Daiichi Sankyo Company Ltd, and Kaneka Medics for other services; grants from Medtronic; grants from Terumo. Dr Sheth reports compensation from Motif Neurosciences for other services; compensation from Viz.ai, Imperative Care, Inc, and Penumbra, Inc, for consultant services; grants from National Institutes of Health; employment by UTHealth McGovern Medical School. Dr Strbian reports employment by Helsingin ja Uudenmaan Sairaanhoitopiiri. Dr Uchida reports compensation from Bristol-Myers Squibb, Stryker, Daiichi Sankyo Company, Ltd, and Medtronic for other services. Dr Wouters reports grants from The Research Foundation-Flanders travel and Remmert Adriaan-Laan-Fonds. Dr Yamagami reports compensation from Otsuka Pharmaceutical Co, Ltd. Medtronic, Daiichi Sankyo Company Ltd, Bristol-Myers Squibb, Johnson and Johnson, Bayer. Daiichi Sankyo Company Ltd, and Stryker for other services; grants from Bristol-Myers Squibb. S. Yoshimura reports compensation from Bristol-Myers Squibb, Johnson & Johnson Medical Devices & Diagnostics Group, Latin America, LLC, Bayer, Kaneka Medics, Boehringer Ingelheim, Medtronic Daiichi Sankyo Company, Stryker, and Terumo for other services. S. Ning discloses research support from Society for Interventional Radiology. Dr Zaidat reports grants from Medtronic, Penumbra, Inc, Johnson and Johnson, Stryker to other; compensation from Medtronic and Johnson & Johnson Health Care Systems, Inc, and Penumbra, Inc, for consultant services; stock holdings in Penumbra Inc. The other authors report no conflicts.

Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs., Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion., Methods and Design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial., Study Outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted., Sample Size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation., Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia., Trial Registrations: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: White matter hypodensities (WMH), a surrogate of small vessel disease, associate with cognitive decline and stroke risk. The impact of WMH on functional outcome after intracerebral hemorrhage (ICH) has differed between studies. We aimed to examine factors associated with the severity of WMH in ICH, and whether there is an independent association between the extent of WMH and outcome., Materials and Methods: This was a prospective study of consented patients with non-traumatic primary ICH, admitted to the Helsinki University Hospital between May 2014 and December 2018. To evaluate the extent of the WMH, modified van Swieten score of the side contralateral to the ICH was obtained. Patients were grouped into 3 categories of the scores. We performed univariate and multivariable analyses to find out factors associated with the severity of WMH, and whether WMH associate with functional outcome and mortality up to 12 months, adjusted for the known major outcome predictors., Results: In our cohort of 417 ICH patients, WMH severity associated with older age, female sex, admission National Institutes of Health Stroke Scale (NIHSS) points, and signs of previous ischemic stroke on CT. We found an independent association between WMH severity and poor functional outcome at 3 months (OR 1.72, 95% CI 1.27-2.33), and 1 year (OR 2.16, 95% CI 1.57-2.95), and mortality at 1 year (OR 1.91, 95% CI 1.29-2.85)., Conclusions: In our ICH patients, vascular comorbidities and older age associated with the presence of WMH, which, in turn, strongly associated with poor functional outcome., Competing Interests: Declaration of Competing Interest HS reports grants from Maire Taponen Foundation, Biomedicum Helsinki Foundation, and The Finnish Medical Foundation. MT reports speaker honoraria from Sanofi Genzyme. LT, NM-M, PV, GS and DS report no disclosures relevant to the manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Oral contraceptives (OCs) are generally safe but vascular risk factors increase OC-associated ischemic stroke risk. We performed a case-control study to evaluate whether a genomic risk score for ischemic stroke modifies OC-associated ischemic stroke risk., Methods: The Genetics of Early-Onset Stroke study includes 332 premenopausal women (136 arterial ischemic stroke cases and 196 controls) with data on estrogen-containing OC use within 30 days before the index event (for cases) or interview (for controls). Using a previously validated genetic risk score (metaGRS) for ischemic stroke based on 19 polygenic risk scores for stroke and stroke-associated risk factors, we stratified our combined case-control sample into tertiles of genomic risk. We evaluated the association between OC use and ischemic stroke within each tertile. We tested if the association between OC use and ischemic stroke depended on the genomic risk of stroke using logistic regression with an OC use × metaGRS interaction term. These analyses were performed with and without adjustment for smoking, hypertension, diabetes, coronary heart disease, and body mass index., Results: After adjustment for vascular risk factors, the odds ratio of OC use was 3.2 (1.7-6.3) overall and increased from the lower, middle, and upper tertile of genomic risk from 1.6 (0.5-5.4) to 2.5 (0.08-8.2) to 13.7 (3.8-67.3) respectively, and a p -value for interaction of 0.001., Conclusions: Our results suggest that genomic profile may modify the OC-associated ischemic stroke risk. Larger studies are warranted to determine whether a genomic risk score could be clinically useful in reducing OC-associated ischemic stroke., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor [MF] declared a past co-authorship with the author [BM]. The author(s) JP and BM declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry 1,2 . Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis 3 , and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach 4 , we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry 5 . Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries., (© 2022. The Author(s).)

Objectives: Selected patients with acute ischemic stroke (AIS) caused by proximal middle cerebral artery (MCA) or internal carotid artery occlusion benefit from endovascular thrombectomy (EVT) in extended time window (6-24 h from last seen well) based on two landmark randomized controlled trials (RCTs) DAWN and DEFUSE-3. We evaluated patients' outcome in the real-life with the focus on adherence to protocol of the two RCTs., Materials and Methods: We included consecutive patients with AIS (excluding basilar artery occlusions) referred to EVT in our stroke center in the extended time window between January 2018 and December 2019 and compared the outcome of patients who fulfilled criteria of the RCTs with those who did not., Results: Of the total of 100 patients, 23 complied with RCT's criteria and 18 presented with minor non-adherence (lower NIHSS score or longer treatment delay), whereas 22 patients had large baseline ischemia (>1/3 MCA), 28 presented with M2 and more distal occlusions, and 9 patients did not undergo perfusion imaging prior to EVT. Good 3-month outcome (modified Rankin Scale 0-2) was observed in 54% of those who either met the RCT criteria or presented with lower NIHSS score or longer treatment delay, but only in 30% of M2 occlusions, and in none of the patients with large baseline ischemia., Conclusions: Our findings highlight the impact of mostly large baseline ischemia but also vessel status when selecting patients for EVT in the extended time window and emphasize the need for further data in these patient subgroups., Competing Interests: Declarations of 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain., Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment., Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0-1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0-5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0-1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4-14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4-5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8-1.7])., Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to-6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively]. Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health., Competing Interests: AR was employed by Centogene AG, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hong, Giese, Schirmer, Bonkhoff, Bretzner, Rist, Dalca, Regenhardt, Etherton, Donahue, Nardin, Mocking, McIntosh, Attia, Benavente, Cole, Donatti, Griessenauer, Heitsch, Holmegaard, Jood, Jimenez-Conde, Roquer, Kittner, Lemmens, Levi, McDonough, Meschia, Phuah, Rolfs, Ropele, Rosand, Rundek, Sacco, Schmidt, Enzinger, Sharma, Slowik, Sousa, Stanne, Strbian, Tatlisumak, Thijs, Vagal, Wasselius, Woo, Zand, McArdle, Worrall, Wu, Jern, Lindgren, Maguire, Tomppo, Golland, Rost and the MRI-GENIE and GISCOME Investigators and the International Stroke Genetics Consortium.)

This study assessed the pyrolysis liquids obtained by slow pyrolysis of industrial hemp leaves, hurds, and roots. The liquids recovered between a pyrolysis temperature of 275-350 °C, at two condensation temperatures 130 °C and 70 °C, were analyzed. Aqueous and bio-oil pyrolysis liquids were produced and analyzed by proton nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and atmospheric pressure photoionization Fourier transform ion cyclotron resonance mass spectrometry (APPI FT-ICR MS). NMR revealed quantitative concentrations of the most abundant compounds in the aqueous fractions and compound groups in the oily fractions. In the aqueous fractions, the concentration range of acetic acid was 50-241 gL -1 , methanol 2-30 gL -1 , propanoic acid 5-20 gL -1 , and 1-hydroxybutan-2-one 2 gL -1 . GC-MS was used to compare the compositions of the volatile compounds and APPI FT-ICR MS was utilized to determine the most abundant higher molecular weight compounds. The different obtained pyrolysis liquids (aqueous and oily) had various volatile and nonvolatile compounds such as acetic acid, 2,6-dimethoxyphenol, 2-methoxyphenol, and cannabidiol. This study provides a detailed understanding of the chemical composition of pyrolysis liquids from different parts of the industrial hemp plant and assesses their possible economic potential.

Background: The genetic basis of lacunar stroke is poorly understood, with a single locus on 16q24 identified to date. We sought to identify novel associations and provide mechanistic insights into the disease., Methods: We did a pooled analysis of data from newly recruited patients with an MRI-confirmed diagnosis of lacunar stroke and existing genome-wide association studies (GWAS). Patients were recruited from hospitals in the UK as part of the UK DNA Lacunar Stroke studies 1 and 2 and from collaborators within the International Stroke Genetics Consortium. Cases and controls were stratified by ancestry and two meta-analyses were done: a European ancestry analysis, and a transethnic analysis that included all ancestry groups. We also did a multi-trait analysis of GWAS, in a joint analysis with a study of cerebral white matter hyperintensities (an aetiologically related radiological trait), to find additional genetic associations. We did a transcriptome-wide association study (TWAS) to detect genes for which expression is associated with lacunar stroke; identified significantly enriched pathways using multi-marker analysis of genomic annotation; and evaluated cardiovascular risk factors causally associated with the disease using mendelian randomisation., Findings: Our meta-analysis comprised studies from Europe, the USA, and Australia, including 7338 cases and 254 798 controls, of which 2987 cases (matched with 29 540 controls) were confirmed using MRI. Five loci (ICA1L-WDR12-CARF-NBEAL1, ULK4, SPI1-SLC39A13-PSMC3-RAPSN, ZCCHC14, ZBTB14-EPB41L3) were found to be associated with lacunar stroke in the European or transethnic meta-analyses. A further seven loci (SLC25A44-PMF1-BGLAP, LOX-ZNF474-LOC100505841, FOXF2-FOXQ1, VTA1-GPR126, SH3PXD2A, HTRA1-ARMS2, COL4A2) were found to be associated in the multi-trait analysis with cerebral white matter hyperintensities (n=42 310). Two of the identified loci contain genes (COL4A2 and HTRA1) that are involved in monogenic lacunar stroke. The TWAS identified associations between the expression of six genes (SCL25A44, ULK4, CARF, FAM117B, ICA1L, NBEAL1) and lacunar stroke. Pathway analyses implicated disruption of the extracellular matrix, phosphatidylinositol 5 phosphate binding, and roundabout binding (false discovery rate <0·05). Mendelian randomisation analyses identified positive associations of elevated blood pressure, history of smoking, and type 2 diabetes with lacunar stroke., Interpretation: Lacunar stroke has a substantial heritable component, with 12 loci now identified that could represent future treatment targets. These loci provide insights into lacunar stroke pathogenesis, highlighting disruption of the vascular extracellular matrix (COL4A2, LOX, SH3PXD2A, GPR126, HTRA1), pericyte differentiation (FOXF2, GPR126), TGF-β signalling (HTRA1), and myelination (ULK4, GPR126) in disease risk., Funding: British Heart Foundation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing., Materials and Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke., Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80)., Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events., Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT., (© European Stroke Organisation 2020.)

Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention., Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features., Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02])., Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant.

Wood chips are extensively utilised as raw material for the pulp and bio-fuel industry, and advanced material analyses may improve the processes in utilizing these products. Electrical impedance spectroscopy (EIS) combined with machine learning was used in order to analyse heartwood content of pine chips and bark content of birch chips. A novel electrode system integrated in a sampling container was developed for the testing using frequency range 42 Hz-5 MHz. Three electrode pairs were used to measure the samples in x-, y- and z-direction. Three machine learning methods were used: K-nearest neighbor (KNN), decision tree (DT) and support vector machines (SVM). The heartwood content of pine chips and bark content of birch chips were classified with an accuracy of 91% using EIS from pure materials combined with a k-nearest neighbour classifier. When using mixed materials and multiple classes, 73% correct classification for pine heartwood content (four groups) and 64% for birch bark content (five groups) were achieved.

Oral mucosal diseases are common health problems that reduce overall wellbeing and increase the risk for several systemic diseases. Due to the limitations of present diagnostics, new non-invasive methods are needed for reliable, affordable, real-time screening and follow-up of oral mucosal lesions. Bioimpedance spectroscopy, spectral camera imaging and other optical methods are promising novel techniques to detect abnormal changes in oral mucosa. In this review, the current status of bioimpedance spectroscopy and autofluorescence utilising spectral camera techniques in the assessment of oral mucosal health is critically evaluated. Scientific publications related to bioimpedance spectroscopy were surveyed using PubMed and Scopus databases. Search was done using a combination of terms "oral mucosa", "oral cancer", "squamous cell cancer", "tissue", "electrical impedance measurement" and "bioimpedance spectroscopy". Publications related to spectral cameras were searched from PubMed with a focus on autofluorescence utilising spectral camera techniques. Search was done using terms "autofluorescence", "oral disease" and "VELscope" publication date restricted from 2008 to date. In this review, we also discuss the future trends and strategies such as combining different methods, e.g. spectral cameras and bioimpedance spectroscopy that could represent a unique multimodality in vivo tool for providing complementary information on the health status of the oral mucosa.

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Background: The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear., Purpose: In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation., Methods: In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke., Results: A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24-2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74-2.04))., Conclusions: After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT ; 53.1% of patients with  HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

Background: The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention., Methods and Results: Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA 2 DS 2 -VASc score >4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke., Conclusions: In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)