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Objective: Given the high disease and cost burden of ischemic stroke, evaluating the clinical efficacy and cost-effectiveness of new approaches to prevent and treat ischemic stroke is critical. Effective ischemic stroke management depends on timely administration of thrombolytics after stroke onset. This study evaluates the cost-effectiveness associated with the use of mobile stroke units (MSUs) to expedite tissue plasminogen activator (tPA) administration, as compared with standard management through emergency medical services (EMS)., Methods: This study is a prospective, multicenter, alternating-week, cluster-controlled trial of MSU versus EMS. One-year and life-time cost-effectiveness analyses, using the incremental cost-effectiveness ratio (ICER) method, were performed from the perspective of CMS's Medicare. Quality-adjusted life years (QALYs) estimated using patient-reported EQ-5D-5L data were used as the effectiveness measure. Health care utilizations were converted to costs using average national Medicare reimbursements. ICERs excluding patients with pre-existing disability, and limited to stroke-related costs were also calculated., Results: The first-year ICER for all tPA-eligible patients using total cost differences between MSU and EMS groups was $238,873/QALY; for patients without pre-existing disability was $61,199/QALY. The lifetime ICERs for all tPA-eligible patients and for those without pre-existing disability were $94,710 and $31,259/QALY, respectively. All ICERs were lower when restricted to stroke-related costs and were highly dependent on the number of patients treated per year in an MSU., Interpretation: MSUs' cost-effectiveness is borderline if we consider total first-year costs and outcomes in all tPA-eligible patients. MSUs are cost-effective to highly cost-effective when calculations are based on patients without pre-existing disability, patients' lifetime horizon, stroke-related costs, and more patients treated per year in an MSU. ANN NEUROL 2024., (© 2024 American Neurological Association.)

Background: Cancer is associated with an increased risk of atrial fibrillation. Whether cancer is also associated with atrial cardiopathy, another atrial pathology associated with heightened ischemic stroke risk, is uncertain., Methods: We conducted a retrospective cross-sectional study among consecutive patients hospitalized with acute ischemic stroke at a quaternary care center in New York, United States from 2011 through 2016. The study exposure was active cancer. The study outcome was atrial cardiopathy, defined as a left atrial volume index ≥35 mL/m 2 on echocardiography. We used multivariable logistic regression, adjusting for baseline characteristics, to evaluate the relationship between cancer (active or historical) and atrial cardiopathy. We performed a subgroup analysis among patients with embolic stroke of undetermined source (ESUS)., Results: The final cohort included 1104 patients with acute ischemic stroke, of whom 10 % had active cancer and 47 % had atrial cardiopathy. Patients with atrial cardiopathy, compared to those without, were older (median age, 77 versus 68 years), and more frequently had hypertension, coronary disease, and atrial fibrillation. Active cancer was present in 9.6 % of patients with atrial cardiopathy (n = 50/520) and 10.4 % of patients without (n = 61/584). There was no association between active cancer and atrial cardiopathy among the overall ischemic stroke cohort (adjusted odds ratio [OR], 0.91; 95 % confidence interval [CI], 0.60-1.37) nor in patients with ESUS (aOR, 0.64; 95 % CI, 0.30-1.36). When the cancer exposure was broadened to include any history of cancer (n = 236, 21.4 %), there still was no significant association with atrial cardiopathy (aOR, 0.93; 95 % CI, 0.68-1.25)., Conclusions: When defining atrial cardiopathy by left atrial volume, we did not find an association between cancer and atrial cardiopathy in patients with ischemic stroke, including among those with ESUS. Future studies, evaluating other atrial cardiopathy biomarkers and settings, are needed to further investigate any potential link between cancer and atrial cardiopathy., Competing Interests: Declaration of competing interest Dr. Beyeler has received research support from the University of Bern, Switzerland. Dr. Navi has received personal fees for serving on an adjudication committee for MindRhythm Inc. Dr. Kamel reports serving as a PI for the ARCADIA trial (NIH/NINDSU01NS095869), which received in-kind study drug from the BMS-Pfizer Alliance for Eliquis® and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, U01NS106513); serving as Deputy Editor for JAMA Neurology; serving on clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; serving on endpoint adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. The other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to estimate the incidence, timing, and type of new cancer diagnosis among patients with cryptogenic stroke., Methods: We used data from the ARCADIA trial, which enrolled patients with cryptogenic stroke and atrial cardiopathy. Participants were prospectively followed, and serious adverse events were assessed every 3 months or sooner if investigators were alerted between visits to an event. Kaplan-Meier statistics were used to estimate the cumulative incidence of a cancer diagnosis within the first year after randomization., Results: Among 878 participants without baseline history of cancer, 13 (1.5%) were diagnosed with incident cancer in the year after randomization, comprising 12 solid cancers (3 prostate, 2 breast, 2 gastrointestinal, and 5 other primary sites) and 1 hematologic cancer (non-Hodgkin lymphoma). The cumulative incidences of a cancer diagnosis were 0% at 3 months, 0.6% (95% CI 0.2%-1.5%) at 6 months, and 2.0% (95 CI 1.1%-3.4%) at 1 year. The median time from index stroke to cancer diagnosis was 261 days (interquartile range 183-358)., Discussion: In a multicenter cryptogenic stroke cohort with prospective follow-up, the 1-year cumulative incidence of a cancer diagnosis was 2%. This rate may be an underestimation because of the clinical trial population and exclusion of cancers diagnosed immediately after stroke., Trial Registration Information: ClinicalTrials.gov Identifier: NCT03192215. Registered June 20, 2017. First patient enrolled February 1, 2018.

Multiple randomized controlled trials have demonstrated that dual antiplatelet therapy (DAPT) significantly reduces the risk of subsequent stroke as compared to aspirin monotherapy after high-risk transient ischemic attack (TIA) or minor ischemic stroke. We sought to evaluate the uptake of DAPT after high-risk TIA at a single center. We conducted a retrospective cohort study of consecutive TIA patients admitted via the Emergency Department (ED) of Bern University Hospital (1/1/2018-12/31/2019). We use descriptive statistics to detail cohort characteristics and compared patients treated with DAPT to those not treated. Statistical significance was set at α = 0.05 and all tests of comparison were two-sided. A total of 383 TIA patients were seen during the study period, 247 were eligible for DAPT. Among those eligible for DAPT, mean age was 72 years and 51% were female. A total of 49 (19.8%) eligible TIA patients were treated with DAPT; use of DAPT significantly increased from 2018 to 2019. Patients admitted to the stroke unit or intensive care unit (n = 33) had a significantly higher proportion of DAPT treatment as compared to those admitted to the general neurology ward or discharged to home from the ED. DAPT use was also significantly higher in patients with large artery atherosclerotic disease (n = 23) as compared to other etiological subtypes and significantly higher among patients who arrived to the ED within 24 h of symptom onset (n = 178). In conclusion, we found that only 2 out of every 10 high-risk TIA patients received DAPT in the years following its introduction in the clinical practice. Our results suggest that strategies to improve the uptake of new, evidence-based secondary stroke prevention treatment after high-risk TIA are needed., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background and Objectives: Cancer is associated with an increased risk of acute ischemic stroke (AIS) and venous thromboembolism. The role of a cardiac right-to-left shunt (RLS) as a surrogate parameter for paradoxical embolism in cancer-related strokes is uncertain. We sought to investigate the relationship between the presence of an RLS and cancer in AIS patients., Methods: We included consecutive AIS patients hospitalized at our tertiary stroke center between January 2015 and December 2020 with available RLS status as detected on transesophageal echocardiography (TEE). Active cancers were retrospectively identified and the association with RLS was assessed with multivariable logistic regression and inverse probability of treatment weighting to minimize the ascertainment bias of having a TEE obtained., Results: Of the 2236 AIS patients included, 103 (4.6%) had active cancer, of whom 24 (23%) were diagnosed with RLS. An RLS was present in 774 out of the 2133 AIS patients without active cancer (36%). After adjustment and weighting, the absence of RLS was associated with active cancer (adjusted odds ratio (aOR) 2.29; 95% confidence interval (CI), 1.14-4.58). When analysis was restricted to patients younger than 60 years of age or those with a high-risk RLS (Risk of Paradoxical Embolism Score ⩾ 6), there was no association between RLS and cancer (aOR, 3.07; 95% CI, 0.79-11.88 and aOR, 0.56; 95% CI, 0.10-3.10, respectively)., Conclusion: RLS was diagnosed less frequently in AIS patients with cancer than in cancer-free patients, suggesting that arterial sources may play a larger role in cancer-related strokes than paradoxical venous embolization. Future studies are needed to validate these findings and evaluate potential therapeutic implications, such as the general indication, or lack thereof, for patent foramen ovale (PFO) closure in this patient population., 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: Mo.B. reports research support from the Department of Neurology, Inselspital, Bern University Hospital and the University of Bern, Switzerland.None of the other authors report any conflicts of interest in relation with this study.

Background: Early diagnosis of previously unknown cancer (i.e., occult cancer) after an acute ischemic stroke (AIS) could result in faster initiation of cancer therapy and potentially improve clinical outcomes. Our study aimed to compare mortality rates between AIS patients with occult cancer diagnosed during the index stroke hospitalization versus those diagnosed after hospital discharge., Methods: Among consecutive AIS patients treated at our stroke center from 2015 through 2020, we identified new cancer diagnoses made within the year after the AIS. We used multivariable Cox regression analyses to evaluate the association between the timing of occult cancer diagnosis (during the AIS hospitalization versus after discharge) and long-term survival., Results: Of 3894 AIS patients with available long-term follow-up data, 59 (1.5 %) were diagnosed with a new cancer within one year after index stroke. Of these, 27 (46 %) were diagnosed during the index hospitalization and 32 (54 %) were diagnosed after discharge. During a median follow-up of 406 days (interquartile range, 89-1073), 70 % (n = 19) of patients whose cancer was diagnosed during hospitalization had died, compared to 63 % (n = 20) of patients whose cancer was diagnosed after discharge (p= 0.58). In our main multivariable model, there was no difference in long-term mortality between patient groups (adjusted hazard ratio, 1.16; 95 % confidence interval, 0.53-2.52; p= 0.71)., Conclusions: In this analysis, timing of a new cancer diagnosis after AIS did not seem to influence patients' long-term survival. Given the fairly small number of included patients with previously occult cancer, larger multicenter studies are needed to confirm our results., Competing Interests: Declaration of competing interest Morin Beyeler reports research support from the “Kurt und Senta Hermann-Stiftung”, the Department of Neurology, Inselspital, Bern University Hospital and the University of Bern, Switzerland. None of the other authors report any conflicts of interest in relation with this study., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Case reports describe arterial thrombosis including ischemic stroke associated with severe ovarian hyperstimulation syndrome (OHSS), but the prevalence of major ischemic events during or shortly after OHSS is unknown., Methods: Using publicly available administrative datasets in the United States between 2015 and 2020, we conducted two separate cross-sectional studies of patients with OHSS. We included all patients with OHSS. Our study outcome was any hospitalization for acute ischemic stroke, acute myocardial infarction, cerebral venous sinus thrombosis, pulmonary embolism, or acute deep venous thrombosis during the index hospitalization or within 90 days of OHSS diagnosis., Results and Conclusions: We found very few major ischemic events in patients with OHSS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Miller and Dr. Navi have received personal fees for serving as neurology expert witnesses. 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 Elsevier Inc. All rights reserved.)

Background: Previous cohort studies of hospitalized patients with a delayed diagnosis of ischemic stroke found that these patients often had an initial emergency department (ED) diagnosis of a fall. We sought to evaluate whether ED visits for a fall resulting in discharge to home (ie, treat-and-release visits) were associated with increased short-term ischemic stroke risk., Methods: A case-crossover design was used to compare ED visits for falls during case periods (0-15, 16-30, 31-90, and 91-180 days before stroke) and control periods (equivalent time periods exactly 1 year before stroke) using administrative data from the Healthcare Cost and Utilization Project on all hospital admissions and ED visits across 10 states from 2016 to 2020. To identify ED treat-and-release visits for a fall and patients hospitalized for acute ischemic stroke, we used previously validated International Classification of Diseases, Tenth Revision, Clinical Modification codes. Odds ratios and 95% CIs were calculated using conditional logistic regression., Results: Among 90 592 hospitalized patients with ischemic stroke, 5230 (5.8%) had an ED treat-and-release visit for a fall within 180 days before their stroke. Patients with an ED treat-and-release visit for a fall were older (mean age, 74.7 [SD, 14.6] versus 70.8 [SD, 15.1] years), more often female (61.9% versus 53.4%), and had higher rates of vascular comorbidities than other patients with stroke. ED treat-and-release visits for a fall were significantly more common in the 15 days before stroke compared with the 15-day control period 1 year earlier (odds ratio, 2.7 [95% CI, 2.4-3.1]). The association between stroke and a preceding ED treat-and-release visit for a fall decreased in magnitude with increasing temporal distance from stroke., Conclusions: ED treat-and-release visits for a fall are associated with significantly increased short-term ischemic stroke risk. These visits may be opportunities to improve stroke diagnostic accuracy and treatment in the ED., Competing Interests: Dr Navi has received personal fees for medicolegal consulting and for serving on an adjudication committee for MindRhythm Inc. Dr Kamel reports: PI for the ARCADIA trial ([Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy]; National Institutes of Health [NIH]/National Institute of Neurological Disorders and Stroke U01NS095869), which receives in-kind study drug from the BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, and U01NS106513); Deputy Editor for JAMA Neurology; clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; end point adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. The other authors report no conflicts.

Objective: Approximately half of ischemic strokes (IS) in cancer patients are cryptogenic, with many presumed cardioembolic. We evaluated whether there were specific miRNA and mRNA transcriptome architectures in peripheral blood of IS patients with and without comorbid cancer, and between cardioembolic versus noncardioembolic IS etiologies in comorbid cancer., Methods: We studied patients with cancer and IS (CS; n = 42), stroke only (SO; n = 41), and cancer only (n = 28), and vascular risk factor-matched controls (n = 30). mRNA-Seq and miRNA-Seq data, analyzed with linear regression models, identified differentially expressed genes in CS versus SO and in cardioembolic versus noncardioembolic CS, and miRNA-mRNA regulatory pairs. Network-level analyses identified stroke etiology-specific responses in CS., Results: A total of 2,085 mRNAs and 31 miRNAs were differentially expressed between CS and SO. In CS, 122 and 35 miRNA-mRNA regulatory pairs, and 5 and 3 coexpressed gene modules, were associated with cardioembolic and noncardioembolic CS, respectively. Complement, growth factor, and immune/inflammatory pathways showed differences between IS etiologies in CS. A 15-gene biomarker panel assembled from a derivation cohort (n = 50) correctly classified 81% of CS and 71% of SO participants in a validation cohort (n = 33). Another 15-gene panel correctly identified etiologies for 13 of 13 CS-cardioembolic and 11 of 11 CS-noncardioembolic participants upon cross-validation; 11 of 16 CS-cryptogenic participants were predicted cardioembolic., Interpretation: We discovered unique mRNA and miRNA transcriptome architecture in CS and SO, and in CS with different IS etiologies. Cardioembolic and noncardioembolic etiologies in CS showed unique coexpression networks and potential master regulators. These may help distinguish CS from SO and identify IS etiology in cryptogenic CS patients. ANN NEUROL 2024;96:565-581., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke., Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke., Design, Setting, and Participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024., Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined., Main Outcomes and Measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage., Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%])., Conclusions and Relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin., Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Background and Objectives: A better understanding of the factors influencing D-dimer levels in code stroke patients is needed to guide further investigations of concomitant thrombotic conditions. This study aimed to investigate the impact of time from symptom onset and other factors on D-dimer levels in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA)., Methods: Data on consecutive AIS and TIA patients treated at our tertiary-care stroke center between January 2015 and December 2020 were retrospectively assessed. Patients with available D-dimer levels were evaluated for eligibility. Multivariable non-linear regression analyses were performed., Results: In total, 2467 AIS patients and 708 TIA patients were included. The median D-dimer levels differed between the AIS and TIA groups (746 µg/L [interquartile range 381-1468] versus 442 µg/L [interquartile range 244-800], p<0.001). In AIS patients, an early increase in D-dimer levels was demonstrated within the first 6 h (standardized beta coefficient [β] 0.728; 95% confidence interval [CI] 0.324-1.121). This was followed by an immediate decrease (β -13.022; 95% CI -20.401 to -5.643) and then by a second, late increase after 35 h (β 11.750; 95% CI 4.71-18.791). No time-dependent fluctuation in D-dimer levels was observed in TIA patients., Conclusion: The time from symptom onset may affect D-dimer levels in patients with AIS but not those with TIA. Further studies confirming these findings and validating time-specific variations are needed to enable D-dimer levels to be used efficiently as an acute stroke and thrombotic risk biomarker., Competing Interests: Declaration of competing interest Dr. Arnold reports personal fees from Bayer, Bristol-Myers Squibb, Medtronic, Amgen, Daiichi Sankyo, Nestlé Health Sciences, Boehringer Ingelheim, and Covidien during the conduct of the study. Dr. Jung reports grants from the Swiss National Science Foundation and the Swiss Heart Foundation. Dr. Beyeler reports research support from the Department of Neurology, Inselspital, Bern University Hospital and the University of Bern, Switzerland. None of the other authors report any conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Chronic hypertension is an established long-term risk factor for major adverse cardiovascular events (MACEs). However, little is known about short-term MACE risk after hypertensive urgency, defined as an episode of acute severe hypertension without evidence of target-organ damage. We sought to evaluate the short-term risk of MACE after an emergency department (ED) visit for hypertensive urgency resulting in discharge to home., Methods: We performed a case-crossover study using deidentified administrative claims data. Our case periods were 1-week intervals from 0 to 12 weeks before hospitalization for MACE. We compared ED visits for hypertensive urgency during these case periods versus equivalent control periods 1 year earlier. Hypertensive urgency and MACE components were all ascertained using previously validated International Classification of Diseases , Tenth Revision Clinical Modification codes. We used McNemar test for matched data to calculate risk ratios., Results: Among 2 225 722 patients with MACE, 1 893 401 (85.1%) had a prior diagnosis of hypertension. There were 4644 (0.2%) patients who had at least 1 ED visit for hypertensive urgency during the 12 weeks preceding their MACE hospitalization. An ED visit for hypertensive urgency was significantly more common in the first week before MACE compared with the same chronological week 1 year earlier (risk ratio, 3.5 [95% CI, 2.9-4.2]). The association between hypertensive urgency and MACE decreased in magnitude with increasing temporal distance from MACE and was no longer significant by 11 weeks before MACE (risk ratio, 1.2 [95% CI, 0.99-1.6])., Conclusions: ED visits for hypertensive urgency were associated with a substantially increased short-term risk of subsequent MACE., Competing Interests: Disclosures J. Razzak serves as primary investigator for the National Institutes of Health (NIH)–funded grants R21HD103049, D43TW007292, and R21TW012210. B.B. Navi and A.Z. Segal have received personal fees for serving as a neurology expert witness. S.S. Bruce is supported by National Center for Advancing Translational Sciences research grant KL2TR2385. H. Kamel reports: PI for the ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke) trial (NIH/NINDS U01NS095869), which receives in-kind study drug from the Bristol-Myers Squibb-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, U01NS106513); deputy editor for JAMA Neurology; clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; end point adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. The other authors report no conflicts.

Introduction: Atrial fibrillation (AF) and cancer are each associated with worse outcomes in patients with acute ischemic stroke (AIS). Few studies have evaluated the impact of AF on outcomes of cancer-related stroke., Patients and Methods: We conducted a retrospective cross-sectional study using the 2016-2019 National Inpatient Sample, identifying all hospitalizations with diagnosis codes for cancer and AIS. The primary exposure was a diagnosis of AF. The primary outcome was in-hospital mortality. The secondary outcomes were length-of-stay and discharge to non-home locations. We used multiple logistic and linear regression models, adjusted for age, gender, race-ethnicity, and the Charlson Comorbidity Index, to examine the association between AF and study outcomes., Results: Among 150,200 hospitalizations with diagnoses of cancer and AIS (mean age 72 years, 53% male), 40,084 (26.7%) included comorbid AF. Compared to hospitalizations without AF, hospitalizations with AF had higher rates of in-hospital mortality (14.8% [95% CI, 14.0%-15.6%] vs 12.1% [95% CI, 11.6%-12.5%]) and non-home discharge disposition (83.5% [95% CI, 82.7%-84.3%] vs 75.1% [95% CI, 74.5%-75.7%]) as well as longer mean length-of-stay (8.4 days [95% CI, 8.2-8.6 days] vs 8.2 days [95% CI, 8.0-8.3 days]). In multivariable analyses, AF remained independently associated with higher odds of in-hospital mortality (adjusted odds ratio [aOR], 1.34; 95% CI, 1.24-1.46), non-home discharge disposition (aOR, 1.32; 95% CI, 1.23-1.42), and longer length-of-stay (adjusted mean difference, 13.7%; 95% CI, 10.9%-16.7%)., Discussion and Conclusion: In cancer-related AIS, comorbid AF is associated with worse short-term outcomes, including higher odds for in-hospital mortality, poor discharge disposition, and longer hospital stays., 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: Dr. Navi has received personal fees for serving on an adjudication committee for MindRhythm Inc and for serving as a neurology expert witness. Dr. Kamel reports serving as a PI for the ARCADIA trial (NIH/NINDS U01NS095869), which received in-kind study drug from the BMS-Pfizer Alliance for Eliquis® and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, U01NS106513); serving as Deputy Editor for JAMA Neurology; serving on clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; serving on endpoint adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. The other authors declare that there is no conflict of interest.

Background and Aims: Most cancer patients require surgery for diagnosis and treatment. This study evaluated whether cancer is a risk factor for perioperative arterial ischaemic events., Methods: The primary cohort included patients registered in the National Surgical Quality Improvement Program (NSQIP) between 2006 and 2016. The secondary cohort included Healthcare Cost and Utilization Project (HCUP) claims data from 11 US states between 2016 and 2018. Study populations comprised patients who underwent inpatient (NSQIP, HCUP) or outpatient (NSQIP) surgery. Study exposures were disseminated cancer (NSQIP) and all cancers (HCUP). The primary outcome was a perioperative arterial ischaemic event, defined as myocardial infarction or stroke diagnosed within 30 days after surgery., Results: Among 5 609 675 NSQIP surgeries, 2.2% involved patients with disseminated cancer. The perioperative arterial ischaemic event rate was 0.96% among patients with disseminated cancer vs. 0.48% among patients without (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.90-2.13). In Cox analyses adjusting for demographics, functional status, comorbidities, surgical specialty, anesthesia type, and clinical factors, disseminated cancer remained associated with higher risk of perioperative arterial ischaemic events (HR, 1.37; 95% CI, 1.28-1.46). Among 1 341 658 surgical patients in the HCUP cohort, 11.8% had a diagnosis of cancer. A perioperative arterial ischaemic event was diagnosed in 0.74% of patients with cancer vs. 0.54% of patients without cancer (HR, 1.35; 95% CI, 1.27-1.43). In Cox analyses adjusted for demographics, insurance, comorbidities, and surgery type, cancer remained associated with higher risk of perioperative arterial ischaemic events (HR, 1.31; 95% CI, 1.21-1.42)., Conclusion: Cancer is an independent risk factor for perioperative arterial ischaemic events., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cirrhosis is associated with an increased risk of hemorrhagic stroke. Liver fibrosis, typically a silent condition, is antecedent to cirrhosis. The objective of this study was to test the hypothesis that elevated Fibrosis-4 (FIB-4) index, indicating a high probability of liver fibrosis, is associated with an increased risk of hemorrhagic stroke., Methods: We performed a cohort analysis of the prospective United Kingdom Biobank cohort study. Participants 40-69 years old were enrolled between 2007 and 2010 and had available follow-up data until March 1, 2018. We excluded participants with prevalent hemorrhagic stroke or thrombocytopenia. High probability of liver fibrosis was defined as having a value >2.67 of the validated FIB-4 index. The primary outcome was hemorrhagic stroke (intracerebral or subarachnoid hemorrhage), defined based on hospitalization and death registry data. Secondary outcomes were intracerebral and subarachnoid hemorrhage, separately. We used Cox proportional hazards models to evaluate the association of FIB-4 index >2.67 with hemorrhagic stroke while adjusting for potential confounders including hypertension, alcohol use, and antithrombotic use., Results: Among 452,994 participants (mean age, 57 years; 54% women), approximately 2% had FIB-4 index >2.67, and 1241 developed hemorrhagic stroke. In adjusted models, FIB-4 index >2.67 was associated with an increased risk of hemorrhagic stroke (HR, 2.0; 95% CI, 1.6-2.6). Results were similar for intracerebral hemorrhage (HR, 2.0; 95% CI, 1.5-2.7) and subarachnoid hemorrhage (HR, 2.2; 95% CI, 1.5-3.5) individually., Conclusions: Elevated FIB-4 index was associated with an increased risk of hemorrhagic stroke., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Drs. Parikh and Navi have received personal compensation for medicolegal consulting on stroke. Dr. Parikh is now employed by Alnylam Pharmaceuticals, Inc.; his contribution to this work occurred while employed at Weill Cornell Medicine and does not reflect the views of his current employer. Dr. Murthy reports research support from the NIH outside the submitted work, and has received personal compensation for medicolegal consulting on neurological disorders and stroke. Dr. Bruce reports research support from the NIH (KL2-TR-2385) outside the submitted work. Dr. Liberman reports research support from the NIH outside the submitted work. Dr. Kamel serves as a PI for the NIH-funded ARCADIA trial (NINDS U01NS095869) which receives in-kind study drug from the BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics, serves as Deputy Editor for JAMA Neurology, serves as a steering committee member of Medtronic’s Stroke AF trial, serves on a trial executive committee for Janssen, and serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim. Dr. Iadecola serves on the Scientific Advisory Board of Broadview Ventures.

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Rates of dual antiplatelet therapy (DAPT) after high-risk transient ischemic attack or minor ischemic stroke (TIAMIS) are suboptimal. We performed a cost-effectiveness analysis to characterize the parameters of a quality improvement (QI) intervention designed to increase DAPT use after TIAMIS., Methods and Results: We constructed a decision tree model that compared current national rates of DAPT use after TIAMIS with rates after implementing a theoretical QI intervention designed to increase appropriate DAPT use. The base case assumed that a QI intervention increased the rate of DAPT use to 65% from 45%. Costs (payer and societal) and outcomes (stroke, myocardial infarction, major bleed, or death) were modeled using a lifetime horizon. An incremental cost-effectiveness ratio <$100 000 per quality-adjusted life year was considered cost-effective. Deterministic and probabilistic sensitivity analyses were performed. From the payer perspective, a QI intervention was associated with $9657 in lifetime cost savings and 0.18 more quality-adjusted life years compared with current national treatment rates. A QI intervention was cost-effective in 73% of probabilistic sensitivity analysis iterations. Results were similar from the societal perspective. The maximum acceptable, initial, 1-time payer cost of a QI intervention was $28 032 per patient. A QI intervention that increased DAPT use to at least 51% was cost-effective in the base case., Conclusions: Increasing DAPT use after TIAMIS with a QI intervention is cost-effective over a wide range of costs and proportion of patients with TIAMIS treated with DAPT after implementation of a QI intervention. Our results support the development of future interventions focused on increasing DAPT use after TIAMIS.

Ischemic stroke is an important cause of morbidity and mortality in cancer patients. The underlying mechanisms linking cancer and stroke are not completely understood. Long-standing and more recent evidence suggests that cancer-associated prothrombotic states, along with treatment-related vascular toxicity, such as with chemotherapy and immunotherapy, contribute to an increased risk of ischemic stroke in cancer patients. Novel biomarkers, including coagulation, platelet and endothelial markers, cell-free DNA, and extracellular vesicles are being investigated for their potential to improve risk stratification and patient selection for clinical trials and to help guide personalized antithrombotic strategies. Treatment of cancer-related stroke poses unique challenges, including the need to balance the risk of recurrent stroke and other thromboembolic events with that of bleeding associated with antithrombotic therapy. In addition, how and when to restart cancer treatment after stroke remains unclear. In this review, we summarize current knowledge on the mechanisms underlying ischemic stroke in cancer, propose an etiological classification system unique to cancer-related stroke to help guide patient characterization, provide an overview of promising biomarkers and their clinical utility, and discuss the current state of evidence-based management strategies for cancer-related stroke. Ultimately, a personalized approach to stroke prevention and treatment is required in cancer patients, considering both the underlying cancer biology and the individual patient's risk profile., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Infertility treatment with assisted reproductive technologies (ARTs) has been associated with adverse vascular events in some but not all previous studies. Endothelial damage, prothrombotic factor release, and a higher prevalence of cardiovascular risk factors in those receiving ART have been invoked to explain this association. We sought to explore the relationship between ART and stroke risk using population-level data., Methods: We conducted a retrospective cohort study using data from the National Inpatient Sample registry from 2015 to 2020, including all delivery hospitalizations for patients aged 15 to 55 years. The study exposure was use of ART. The primary end point was any stroke defined as ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, or cerebral venous thrombosis during index delivery hospitalization. Individual stroke subtypes (ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral venous thrombosis) were evaluated as secondary end points. Standard International Classification of Diseases, Tenth Revision , Clinical Modification algorithms were used to define study exposure, comorbidities, and prespecified end points. In addition to reporting population-level estimates, propensity score adjustment by inverse probability weighting was used to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between ART and non-ART users., Results: Among 19 123 125 delivery hospitalizations identified, patients with prior ART (n=202 815, 1.1%) experienced significantly higher rates of any stroke (27.1/100 000 versus 9.1/100 000), ischemic stroke (9.9/100 000 versus 3.3/100 000), subarachnoid hemorrhage (7.4/100 000 versus 1.6/100 000), intracerebral hemorrhage (7.4/100 000 versus 2.0/100 000), and cerebral venous thrombosis (7.4/100 000 versus 2.7/100 000) in comparison to non-ART users (all P <0.001 for all unadjusted comparisons). Following inverse probability weighting analysis, ART was associated with increased odds of any stroke (adjusted odds ratios, 2.14 (95% CI, 2.02-2.26); P <0.001)., Conclusions: Using population-level data among patients hospitalized for delivery in the United States, we found an association between ART and stroke after adjustment for measured confounders., Competing Interests: Disclosures Dr Liberman is supported by National Institute for Neurological Disorders and Stroke (NINDS) research grant K23NS10764. Dr Navi has received personal fees for serving as a neurology expert witness. Dr Kamel reports PI for the ARCADIA trial (NIH/NINDS U01NS095869), which receives in-kind study drug from the BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, U01NS106513); Deputy Editor for JAMA Neurology; clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; end point adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. Dr Seitz has stock in Colgate-Palmolive Company and had stock (sold December 2022) in Baxter International, Inc, Bristol Myers Squibb Company, CVS Health Corporation, Johnson & Johnson, Eli Lilly, and Company, Proctor & Gamble Company, UnitedHealth Group Incorporated, Walgreen Boots Alliance, Inc, and White Mountains Insurance.

Background and Purpose: Demographics, clinical characteristics, stroke mechanisms and long-term outcomes were compared between acute ischaemic stroke (AIS) patients with active cancer (AC) versus non-cancer patients., Methods: Using data from 2003 to 2021 in the Acute STroke Registry and Analysis of Lausanne, a retrospective cohort study was performed comparing patients with AC, including previously known and newly diagnosed cancers, with non-cancer patients. Patients with inactive cancer were excluded. Outcomes were the modified Rankin Scale (mRS) score at 3 months, death and cerebrovascular recurrences at 12 months before and after propensity score matching., Results: Amongst 6686 patients with AIS, 1065 (15.9%) had a history of cancer. After excluding 700 (10.4%) patients with inactive cancer, there were 365 (5.5%) patients with AC and 5621 (84%) non-cancer AIS patients. Amongst AC patients, 154 (42.2%) strokes were classified as cancer related. In multivariable analysis, patients with AC were older (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00-1.03), had fewer vascular risk factors and were 48% less likely to receive reperfusion therapies (aOR 0.52, 95% CI 0.35-0.76). Three-month mRS scores were not different in AC patients (aOR 2.18, 95% CI 0.96-5.00). At 12 months, death (adjusted hazard ratio 1.91, 95% CI 1.50-2.43) and risk of cerebrovascular recurrence (sub-distribution hazard ratio 1.68, 95% CI 1.22-2.31) before and after propensity score matching were higher in AC patients., Conclusions: In a large institutional registry spanning nearly two decades, AIS patients with AC had less past cerebrovascular disease but a higher 1-year risk of subsequent death and cerebrovascular recurrence compared to non-cancer patients. Antithrombotic medications at discharge may reduce this risk in AC patients., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: This study was undertaken to examine averted stroke in optimized stroke systems., Methods: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis., Results: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution., Interpretation: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361., (© 2023 American Neurological Association.)

Background: Few data exist on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. A recent trial of mobile stroke units (MSUs) demonstrated faster treatment and improved outcomes, and included PD patients., Aim: To determine outcomes with tissue plasminogen activator (tPA), and benefit of MSU versus management by emergency medical services (EMS), for PD patients., Methods: Primary outcomes were utility-weighted modified Rankin Scale (uw-mRS). Linear and logistic regression models compared outcomes in patients with versus without PD, and PD patients treated by MSU versus standard management by EMS. Time metrics, safety, quality of life, and health-care utilization were compared., Results: Of the 1047 tPA-eligible ischemic stroke patients, 254 were with PD (baseline mRS 2-5) and 793 were without PD (baseline mRS 0-1). Although PD patients had worse 90-day uw-mRS, higher mortality, more health-care utilization, and worse quality of life than non-disabled patients, 53% returned to at least their baseline mRS, those treated faster had better outcome, and there was no increased bleeding risk. Comparing PD patients treated by MSU versus EMS, 90-day uw-mRS was 0.42 versus 0.36 (p = 0.07) and 57% versus 46% returned to at least their baseline mRS. There was no interaction between disability status and MSU versus EMS group assignment (p = 0.67) for 90-day uw-mRS., Conclusion: PD did not prevent the benefit of faster treatment with tPA in the BEST-MSU study. Our data support inclusion of PD patients in the MSU management paradigm., 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: J.C. Grotta has received grants from Patient-Centered Outcomes Research Institute (PCORI), NIH, Genentech, CSL Behring, and Chiesi; is a consultant for Frazer, advison the scientific advisory board for Haemonetics and Acticor, and on the DSMB for Prolong Pharma. J.L. Saver receives contracted hourly payments from Bayer, Biogen, Roche, Genentech, Medtronic, Novo Nordisk, and Occlutech for service on clinical trial steering committees and DSMBs. The remaining authors have no disclosures.

Objective: Generation of automated clinical notes has been posited as a strategy to mitigate physician burnout. In particular, an automated narrative summary of a patient's hospital stay could supplement the hospital course section of the discharge summary that inpatient physicians document in electronic health record (EHR) systems. In the current study, we developed and evaluated an automated method for summarizing the hospital course section using encoder-decoder sequence-to-sequence transformer models., Materials and Methods: We fine-tuned BERT and BART models and optimized for factuality through constraining beam search, which we trained and tested using EHR data from patients admitted to the neurology unit of an academic medical center., Results: The approach demonstrated good ROUGE scores with an R-2 of 13.76. In a blind evaluation, 2 board-certified physicians rated 62% of the automated summaries as meeting the standard of care, which suggests the method may be useful clinically., Discussion and Conclusion: To our knowledge, this study is among the first to demonstrate an automated method for generating a discharge summary hospital course that approaches a quality level of what a physician would write., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background Cerebrovascular dysregulation syndromes, posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), are challenging to diagnose because they are rare and require advanced neuroimaging for confirmation. We sought to estimate PRES/RCVS misdiagnosis in the emergency department and its associated factors. Methods and Results We conducted a retrospective cohort study of PRES/RCVS patients using administrative claims data from 11 states (2016-2018). We defined patients with a probable PRES/RCVS misdiagnosis as those with an emergency department visit for a neurological symptom resulting in discharge to home that occurred ≤14 days before PRES/RCVS hospitalization. Proportions of patients with probable misdiagnosis were calculated, characteristics of patients with and without probable misdiagnosis were compared, and regression analyses adjusted for demographics and comorbidities were performed to identify factors affecting probable misdiagnosis. We identified 4633 patients with PRES/RCVS. A total of 210 patients (4.53% [95% CI, 3.97-5.17]) had a probable preceding emergency department misdiagnosis; these patients were younger (mean age, 48 versus 54 years; P <0.001) and more often female (80.4% versus 69.3%; P <0.001). Misdiagnosed patients had fewer vascular risk factors except prior stroke (36.3% versus 24.2%; P <0.001) and more often had comorbid headache (84% versus 21.4%; P <0.001) and substance use disorder (48.8% versus 37.9%; P <0.001). Facility-level factors associated with probable misdiagnosis included smaller facility, lacking a residency program (62.2% versus 73.7%; P <0.001), and not having on-site neurological services (75.7% versus 84.3%; P <0.001). Probable misdiagnosis was not associated with higher likelihood of stroke or subarachnoid hemorrhage during PRES/RCVS hospitalization. Conclusions Probable emergency department misdiagnosis occurred in ≈1 of every 20 patients with PRES/RCVS in a large, multistate cohort.

Background and Aim: Paraneoplastic coagulopathy can present as stroke and is associated with specific biomarker changes. Identifying paraneoplastic coagulopathy can help guide secondary prevention in stroke patients, and early cancer detection might improve outcomes. However, unlike ischemic stroke, it remains unclear whether paraneoplastic coagulopathy is associated with transient ischemic attacks (TIA). This study assessed the presence of cancer-related biomarkers in TIA patients and evaluated long-term mortality rates in patients with and without active cancer., Methods: Active cancer was retrospectively identified in consecutive TIA patients treated at a comprehensive stroke center between 2015 and 2019. An association between the presence of cancer and cancer-related biomarkers was assessed using multivariable logistic regression. Long-term mortality after TIA was analyzed using multivariable Cox regression., Results: Among 1436 TIA patients, 72 had active cancer (5%), of which 17 were occult (1.2%). Cancer-related TIA was associated with male gender (adjusted odds ratio [aOR] 2.29, 95% CI 1.12-4.68), history of smoking (aOR 2.77, 95% CI 1.34-5.7), elevated D-dimer (aOR 1.77, 95% CI 1.26-2.49), lactate dehydrogenase (aOR 1.003, 95% CI 1.00-1.005), lower leukocyte count (aOR 1.20, 95% CI 1.04-1.38), and lower hemoglobin (aOR 1.02, 95% CI 1.00-1.04). Long-term mortality was associated with both active cancer (adjusted hazard ratios [aHR] 2.47, 95% CI 1.58-3.88) and occult cancer (aHR 3.08, 95% CI 1.30-7.32)., Conclusion: Cancer-related TIA is not uncommon. Biomarkers known to be associated with cancer-related stroke also seem to be present in TIA patients. Early identification would enable targeted treatment strategies and could improve outcomes in this patient population., Competing Interests: MB reports research support from the Kurt und Senta Hermann-Stiftung. JK reports grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern during the conduct of the study. UF reports grants during the conduct of the study from Medtronic, Stryker, and CSL Behring, unrelated to the submitted work. MA reports personal fees from Bayer, Bristol-Myers Squibb, Medtronic, Amgen, Daiichi Sankyo, Nestlé Health Sciences, Boehringer Ingelheim, and Covidien during the conduct of the study. TM reports research support from the Bangerter Rhyner Foundation, Swiss National Foundation, and the Swiss Heart Foundation. MH reports research grants from SITEM Research Support Funds and Swiss National Science Foundation, Swiss Heart Foundation, not directly related to this manuscript. BN reports grants from the United States National Institutes of Health during the conduct of this study. SJ reports grants from the Swiss National Science Foundation and the Swiss Heart Foundation. 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. The author(s) 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., (Copyright © 2023 Beyeler, Castigliego, Baumann, Ziegler, Kielkopf, Mueller, Bauer-Gambelli, Mujanovic, Meinel, Horvath, Fischer, Kaesmacher, Heldner, Seiffge, Arnold, Pabst, Berger, Navi, Jung and Bücke.)

Objectives: Comorbid cancer with stroke is a complex situation with multiple factors affecting quality of life (QoL). No specific questionnaire exists to assess current drivers of QoL and future concerns and priorities in patients with cancer-related stroke., Methods: After developing a structured survey instrument, we prospectively interviewed patients with recent ischemic stroke and active cancer to assess views about their condition, factors currently impacting QoL, concerns for the future, and preferences regarding antithrombotic treatment strategy., Results: In 2021-2022, at two quaternary-care stroke and cancer centers, we surveyed 50 patients with cancer-related stroke (mean age 70 years, 42% women). Most (87%) had solid cancers with lung, prostate, and breast cancers being the most prevalent. The most frequent adverse feelings were sadness and anxiety about another stroke. Disability from stroke, pain from cancer, and dependency were the items rated to have the highest current effect on patients' QoL and were ranked as the number one effector on QoL in 25%, 23%, and 16% of surveys, respectively; bleeding was ranked the lowest. Cognitive/memory impairment (ranked first in 28% of surveys), dependency on others (ranked first in 18%), and speech disturbance (ranked first in 16%) were the highest ranked future concerns; bleeding and pain were ranked the lowest. When questioned about antithrombotic treatment preferences to prevent further stroke, 50% favored a more aggressive approach with anticoagulant therapy, 16% favored a less aggressive approach with antiplatelet therapy, and 34% were neutral/unsure., Conclusions: Patients with cancer-related stroke reported that stroke disability and cancer pain were their most impactful current issues, while long-term cognitive impairment, functional dependence, and speech disturbance were their most important future concerns. These patients seemed to be more concerned about future stroke than bleeding events and tended to prefer a more aggressive antithrombotic strategy, although considerable variability existed., Competing Interests: Declaration of Competing Interest The authors declare no conflicting or competing interest in the subject matter of this manuscript, (Copyright © 2023. Published by Elsevier Inc.)

Background and Objectives: Patients with a new diagnosis of cancer carry an increased risk of acute ischemic stroke (AIS), and this risk varies depending on age, cancer type, stage, and time from diagnosis. Whether patients with AIS with a new diagnosis of neoplasm represent a distinct subset from those with a previously known active malignancy remains unclear. We aimed to estimate the rate of stroke in patients with newly diagnosed cancer (NC) and previously known active cancer (KC) and to compare the demographic and clinical features, stroke mechanisms, and long-term outcomes between groups., Methods: Using 2003-2021 data from the Acute STroke Registry and Analysis of Lausanne registry, we compared patients with KC with patients with NC (cancer identified during AIS hospitalization or within the following 12 months). Patients with inactive and no history of cancer were excluded. Outcomes were the modified Rankin scale (mRS) score at 3 months and mortality and recurrent stroke at 12 months. We used multivariable regression analyses to compare outcomes between groups while adjusting for important prognostic variables., Results: Among 6,686 patients with AIS, 362 (5.4%) had active cancer (AC), including 102 (1.5%) with NC. Gastrointestinal and genitourinary cancers were the most frequent cancer types. Among all patients with AC, 152 (42.5%) AISs were classified as cancer related, with nearly half of these cases attributed to hypercoagulability. In multivariable analysis, patients with NC had less prestroke disability (adjusted odds ratio [aOR] 0.62, 95% CI 0.44-0.86) and fewer prior stroke/transient ischemic attack events (aOR 0.43, 95% CI 0.21-0.88) than patients with KC. Three-month mRS scores were similar between cancer groups (aOR 1.27, 95% CI 0.65-2.49) and were predominantly driven by the presence of newly diagnosed brain metastases (aOR 7.22, 95% CI 1.49-43.17) and metastatic cancer (aOR 2.19, 95% CI 1.22-3.97). At 12 months, mortality risk was higher in patients with NC vs patients with KC (hazard ratio [HR] 2.11, 95% CI 1.38-3.21), while recurrent stroke risk was similar between groups (adjusted HR 1.27, 95% CI 0.67-2.43)., Discussion: In a comprehensive institutional registry spanning nearly 2 decades, 5.4% of patients with AIS had AC, a quarter of which were diagnosed during or within 12 months after the index stroke hospitalization. Patients with NC had less disability and prior cerebrovascular disease, but a higher 1-year risk of subsequent death than patients with KC., (© 2023 American Academy of Neurology.)

Background: Patients with cancer have an increased risk for arterial thromboembolism (ATE). Scant data exist about the impact of cancer-specific genomic alterations on the risk for ATE., Objectives: The aim of this study was to determine whether individual solid tumor somatic genomic alterations influence the incidence of ATE., Methods: A retrospective cohort study was conducted using tumor genetic alteration data from adults with solid cancers who underwent Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets testing between 2014 and 2016. The primary outcome, ATE, was defined as myocardial infarction, coronary revascularization, ischemic stroke, peripheral arterial occlusion, or limb revascularization and identified through systematic electronic medical record assessments. Patients were followed from date of tissue-matched blood control accession to first ATE event or death, for up to 1 year. Cause-specific Cox proportional hazards regression was used to determine HRs of ATE for individual genes adjusted for pertinent clinical covariates., Results: Among 11,871 eligible patients, 74% had metastatic disease, and there were 160 ATE events. A significantly increased risk for ATE independent of tumor type was noted for the KRAS oncogene (HR: 1.98; 95% CI: 1.34-2.94; multiplicity-adjusted P  = 0.015) and the STK11 tumor suppressor gene (HR: 2.51; 95% CI: 1.44-4.38; multiplicity-adjusted P  = 0.015)., Conclusions: In a large genomic tumor-profiling registry of patients with solid cancers, alterations in KRAS and STK11 were associated with an increased risk for ATE independent of cancer type. Further investigation is needed to elucidate the mechanism by which these mutations contribute to ATE in this high-risk population., Competing Interests: This research was supported by a National Cancer Institute Cancer Center Support Grant (P30 CA008748). Dr Willeit was supported by a Dr. Johannes and Hertha Tuba Grant. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.PerspectivesCOMPETENCY IN MEDICAL KNOWLEDGE: ATE is an important cause of mortality in patients with solid cancer. Tumor somatic alterations in KRAS and STK11 were associated with an increased risk for arterial events. This effect was independent of cancer type and other cardiovascular disease risk factors. TRANSLATIONAL OUTLOOK: A better understanding of the genomic determinants of cancer-associated ATE could contribute to improved risk stratification and primary prophylaxis., (© 2023 The Authors.)

Objective: Patients with posterior reversible encephalopathy syndrome (PRES) can develop seizures during the acute phase. We sought to determine the long-term risk of seizure after PRES., Methods: We performed a retrospective cohort study using statewide all-payer claims data from 2016-2018 from nonfederal hospitals in 11 US states. Adults admitted with PRES were compared to adults admitted with stroke, an acute cerebrovascular disorder associated with long-term risk of seizure. The primary outcome was seizure diagnosed during an emergency room visit or hospital admission after the index hospitalization. The secondary outcome was status epilepticus. Diagnoses were determined using previously validated ICD-10-CM codes. Patients with seizure diagnoses before or during the index admission were excluded. We used Cox regression to evaluate the association of PRES with seizure, adjusting for demographics and potential confounders., Results: We identified 2095 patients hospitalized with PRES and 341,809 with stroke. Median follow-up was 0.9 years (IQR, 0.3-1.7) in the PRES group and 1.0 years (IQR, 0.4-1.8) in the stroke group. Crude seizure incidence per 100 person-years was 9.5 after PRES and 2.5 after stroke. After adjustment for demographics and comorbidities, patients with PRES had a higher risk of seizure than patients with stroke (HR, 2.9; 95% CI, 2.6-3.4). Results were unchanged in a sensitivity analysis that applied a two-week washout period to mitigate detection bias. A similar relationship was observed for the secondary outcome of status epilepticus., Interpretation: PRES was associated with an increased long-term risk of subsequent acute care utilization for seizure compared to stroke., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Smoking cessation rates after stroke and transient ischemic attack are suboptimal, and smoking cessation interventions are underutilized. We performed a cost-effectiveness analysis of smoking cessation interventions in this population., Methods: We constructed a decision tree and used Markov models that aimed to assess the cost-effectiveness of varenicline, any pharmacotherapy with intensive counseling, and monetary incentives, compared with brief counseling alone in the secondary stroke prevention setting. Payer and societal costs of interventions and outcomes were modeled. The outcomes were recurrent stroke, myocardial infarction, and death using a lifetime horizon. Estimates and variance for the base case (35% cessation), costs and effectiveness of interventions, and outcome rates were imputed from the stroke literature. We calculated incremental cost-effectiveness ratios and incremental net monetary benefits. An intervention was considered cost-effective if the incremental cost-effectiveness ratio was less than the willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY) or when the incremental net monetary benefit was positive. Probabilistic Monte Carlo simulations modeled the impact of parameter uncertainty., Results: From the payer perspective, varenicline and pharmacotherapy with intensive counseling were associated with more QALYs (0.67 and 1.00, respectively) at less total lifetime costs compared with brief counseling alone. Monetary incentives were associated with 0.71 more QALYs at an additional cost of $120 compared with brief counseling alone, yielding an incremental cost-effectiveness ratio of $168/QALY. From the societal perspective, all 3 interventions provided more QALYs at less total costs compared with brief counseling alone. In 10 000 Monte Carlo simulations, all 3 smoking cessation interventions were cost-effective in >89% of runs., Conclusions: For secondary stroke prevention, it is cost-effective and potentially cost-saving to deliver smoking cessation therapy beyond brief counseling alone.

Background and Aim: Identification of paraneoplastic hypercoagulability in stroke patients helps to guide investigations and prevent stroke recurrence. A previous study demonstrated an association between the absence of the susceptibility vessel sign (SVS) on brain MRI and active cancer in patients treated with mechanical thrombectomy. The present study aimed to confirm this finding and assess an association between the absence of the hyperdense vessel sign (HVS) on head CT and active cancer in all stroke patients., Methods: SVS and HVS status on baseline imaging were retrospectively assessed in all consecutive stroke patients treated at a comprehensive stroke center between 2015 and 2020. Active cancer, known at the time of stroke or diagnosed within 1 year after stroke (occult cancer), was identified. Adjusted odds ratios (aOR) and their 95% confidence interval (CI) for the association between the thrombus imaging characteristics and cancer were calculated using multivariable logistic regression., Results: Of the 2,256 patients with thrombus imaging characteristics available at baseline, 161 had an active cancer (7.1%), of which 36 were occult at the time of index stroke (1.6% of the total). The absence of SVS was associated with active cancer (aOR 3.14, 95% CI 1.45-6.80). No significance was reached for the subgroup of occult cancer (aOR 3.20, 95% CI 0.73-13.94). No association was found between the absence of HVS and active cancer (aOR 1.07, 95% CI 0.54-2.11)., Conclusion: The absence of SVS but not HVS could help to identify paraneoplastic hypercoagulability in stroke patients with active cancer and guide patient care., Competing Interests: 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., (Copyright © 2023 Beyeler, Grunder, Göcmen, Steinauer, Belachew, Kielkopf, Clénin, Mueller, Silimon, Kurmann, Meinel, Bücke, Seiffge, Dobrocky, Piechowiak, Pilgram-Pastor, Mattle, Navi, Arnold, Fischer, Pabst, Gralla, Berger, Jung and Kaesmacher.)

Background: Administrative data can be useful for stroke research but have historically lacked data on stroke severity. Hospitals increasingly report the National Institutes of Health Stroke Scale (NIHSS) score using an International Classification of Diseases , Tenth Revision ( ICD-10 ) diagnosis code, but this code's validity remains unclear., Methods: We examined the concordance of ICD-10 NIHSS scores versus NIHSS scores recorded in CAESAR (Cornell Acute Stroke Academic Registry). We included all patients with acute ischemic stroke from October 1, 2015, when US hospitals transitioned to ICD-10 , through 2018, the latest year in our registry. The NIHSS score (range, 0-42) recorded in our registry served as the reference gold standard. ICD-10 NIHSS scores were derived from hospital discharge diagnosis code R29.7xx, with the latter 2 digits representing the NIHSS score. Multiple logistic regression was used to explore factors associated with availability of ICD-10 NIHSS scores. We used ANOVA to examine the proportion of variation ( R 2 ) in the true (registry) NIHSS score that was explained by the ICD-10 NIHSS score., Results: Among 1357 patients, 395 (29.1%) had an ICD-10 NIHSS score recorded. This proportion increased from 0% in 2015 to 46.5% in 2018. In a logistic regression model, only higher registry NIHSS score (odds ratio per point, 1.05 [95% CI, 1.03-1.07]) and cardioembolic stroke (odds ratio, 1.4 [95% CI, 1.0-2.0]) were associated with availability of the ICD-10 NIHSS score. In an ANOVA model, the ICD-10 NIHSS score explained almost all the variation in the registry NIHSS score ( R 2 =0.88). Fewer than 10% of patients had a large discordance (≥4 points) between their ICD-10 and registry NIHSS scores., Conclusions: When present, ICD-10 codes representing NIHSS scores had excellent agreement with NIHSS scores recorded in our stroke registry. However, ICD-10 NIHSS scores were often missing, especially in less severe strokes, limiting the reliability of these codes for risk adjustment.

Background: Treatment of patients with acute ischemic stroke on mobile stroke units (MSUs) improves outcomes compared with management by standard emergency medical services ambulances and is associated with more patients treated with intravenous tPA (tissue-type plasminogen activator) in the first golden hour after last known normal. We explored the predictors and outcomes of first-hour treatment (FHT) compared with later treatment in an alternating-week cluster-controlled trial of MSUs., Methods: We analyzed all patients treated with intravenous tPA in the BEST-MSU Study (Benefits of Stroke Treatment Delivered by a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services). After stratifying by treatment timeframe, we identified factors associated with FHT. We performed adjusted analyses of the association between FHT and clinical outcome and modeled the shape of the relationship between last known normal-to-treatment time and excellent outcome., Results: Among 941 tPA-treated patients, 206 (21.8%) had lytic started within 60 minutes. Treatment on the MSU, older age, male sex, alert by 911, faster arrival on-scene and imaging, more severe stroke, atrial fibrillation, and absence of heart failure and pretreatment antihypertensive treatment were associated with FHT. Compared with later treatment, FHT was associated with higher adjusted odds ratio for 90-day modified Rankin Scale score of 0 to 1 (odds ratio, 1.87 [95% CI, 1.25-2.84]; P =0.003). Among FHT patients, 68% achieved a 90-day modified Rankin Scale of 0 or 1 or returned to their baseline status. FHT was not associated with higher risk of hemorrhage and was associated with reduced risk of treating neurovascular mimics., Conclusions: FHT almost doubles the odds of excellent clinical outcome without increased risk compared with later treatment, which supports the use of MSUs.

Objective: Severe hypertension can accompany neurological symptoms without obvious signs of target organ damage. However, acute cerebrovascular events can also be a cause and consequence of severe hypertension. We therefore use US population-level data to determine prevalence and clinical characteristics of patients with severe hypertension and neurological complaints., Methods: We used nationally representative data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) collected in 2016-2019 to identify adult ED patients with severely elevated blood pressure (BP) defined as systolic BP ≥ 180 mmHg and/or diastolic BP ≥120 mmHg. We used ED reason for visit data fields to define neurological complaints and used diagnosis data fields to define acute target organ damage. We applied survey visit weights to obtain national estimates., Results: Based on 5083 observations, an estimated 40.4 million patients (95% CI: 37.5-43.0 million) in EDs nationwide from 2016 to 2019 had severe hypertension, equating to 6.1% (95% CI: 5.7-6.5%) of all ED visits. Only 2.8% (95% CI: 2.0-3.9%) of ED patients with severe hypertension were diagnosed with acute cerebrovascular disease; hypertensive urgency was diagnosed in 92.0% (95% CI: 90.3-93.4%). Neurological complaints were frequent in both patients with (75.6%) and without (19.9%) cerebrovascular diagnoses. Hypertensive urgency patients with neurological complaints were more often older, female, had prior stroke/TIA, and had neuroimaging than patients without these complaints. Non-migraine headache and vertigo were the most common neurological complaints recorded., Conclusion: In a nationally representative survey, one-in-sixteen ED patients had severely elevated BP and one-fifth of those patients had neurological complaints., Competing Interests: Declaration of Competing Interest Dr. Liberman is supported by NINDS research grant K23NS10764. Dr. Kamel serves as a PI for the NIH-funded ARCADIA trial (NINDS U01NS095869), which receives in-kind study drug from the BMS-Pfizer Alliance for Eliquis® and ancillary study support from Roche Diagnostics; as Deputy Editor for JAMA Neurology; on clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; and on endpoint adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim. He has an ownership interest in TETMedical, Inc. Dr. Navi has received personal compensation for medicolegal consulting on stroke. Dr. Parikh is supported by the NIH/NIA (K23 AG073524), the Leon Levy Neuroscience Fellowship, the Florence Gould Endowment for Discovery in Stroke, research support from the New York State Empire Clinical Research Investigator Program, and personal compensation for medicolegal consulting on neurological disorders. Dr. Merkler has received personal compensation for medicolegal consulting on neurological disorders. Dr. Razzak serves as PI for the NIH-funded R21HD103049, D43TW007292 and R21TW012210., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Posterior reversible encephalopathy syndrome (PRES) can cause short-term cerebrovascular complications, such as brain infarction and hemorrhage. We hypothesized that PRES is also associated with an increased long-term risk of stroke., Methods: We performed a retrospective cohort study in the United States using statewide all-payer claims data from 2016 to 2018 on all admissions to nonfederal hospitals in 11 states. Adults with PRES were compared with adults with renal colic (negative control) and transient ischemic attack (TIA; positive control). Any stroke and the secondary outcomes of ischemic and hemorrhagic stroke were ascertained using International Classification of Diseases, Tenth Revision, Clinical Modification codes . We excluded prevalent stroke. We used time-to-event statistics to calculate incidence rates and Cox proportional hazards analyses to evaluate the association between PRES and stroke, adjusting for demographics and stroke risk factors. In a sensitivity analysis, outcomes within 2 weeks of index admission were excluded., Results: We identified 1606 patients with PRES, 1192 with renal colic, and 38 216 with TIA. Patients with PRES had a mean age of 56±17 years; 72% were women. Over a median follow-up of 0.9 years, the stroke incidence per 100 person-years was 6.1 (95% CI, 5.0-7.4) after PRES, 1.0 (95% CI, 0.62-1.8) after renal colic, and 9.7 (95% CI, 9.4-10.0) after TIA. After statistical adjustment for patient characteristics and risk factors, patients with PRES had an elevated risk of stroke compared with renal colic (hazard ratio [HR], 2.3 [95% CI, 1.7-3.0]), but lower risk than patients with TIA (HR, 0.67 [95% CI, 0.54-0.82]). In secondary analyses, compared with TIA, PRES was associated with hemorrhagic stroke (HR, 2.0 [95% CI, 1.4-2.9]). PRES was associated with ischemic stroke when compared with renal colic (HR, 1.9 [95% CI, 1.4-2.7]) but not when compared with TIA (HR, 0.49 [95% CI, 0.38-0.63]). Results were similar with 2-week washout., Conclusions: Patients with PRES had an elevated risk of incident stroke.

Objective: To evaluate whether patients discharged to home after an emergency department (ED) visit for headache face a heightened short-term risk of stroke., Background: Stroke hospitalizations that occur soon after ED visits for headache complaints may reflect diagnostic error., Methods: We conducted a retrospective cohort study using statewide administrative claims data for all ED visits and admissions at nonfederal hospitals in Florida 2005-2018 and New York 2005-2016. Using standard International Classification of Diseases (ICD) codes, we identified adult patients discharged to home from the ED (treat-and-release visit) with a benign headache diagnosis (cohort of interest) as well as those with a diagnosis of renal colic or back pain (negative controls). The primary study outcome was hospitalization within 30 days for stroke (ischemic or hemorrhagic) defined using validated ICD codes. We assess the relationship between index ED visit discharge diagnosis and stroke hospitalization adjusting for patient demographics and vascular comorbidities., Results: We identified 1,502,831 patients with an ED treat-and-release headache visit; mean age was 41 (standard deviation: 17) years and 1,044,520 (70%) were female. A total of 2150 (0.14%) patients with headache were hospitalized for stroke within 30 days. In adjusted analysis, stroke risk was higher after headache compared to renal colic (hazard ratio [HR]: 2.69; 95% confidence interval [CI]: 2.29-3.16) or back pain (HR: 4.0; 95% CI: 3.74-4.3). In the subgroup of 26,714 (1.78%) patients with headache who received brain magnetic resonance imaging at index ED visit, stroke risk was only slightly elevated compared to renal colic (HR: 1.47; 95% CI: 1.22-1.78) or back pain (HR: 1.49; 95% CI: 1.24-1.80)., Conclusion: Approximately 1 in 700 patients discharged to home from the ED with a headache diagnosis had a stroke in the following month. Stroke risk was three to four times higher after an ED visit for headache compared to renal colic or back pain., (© 2022 American Headache Society.)

Background: Patients with cancer and acute ischemic stroke (AIS) face high rates of recurrent thromboembolism or death., Objectives: To examine whether hematologic and embolic biomarkers soon after AIS are associated with subsequent adverse clinical outcomes., Methods: We prospectively enrolled 50 adults with active solid tumor cancer and AIS at two hospitals from 2016 to 2020. Blood was collected 72-120 h after stroke onset. A 30-min transcranial Doppler (TCD) microemboli detection study was performed. The exposure variables were hematologic markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of TCD microemboli. The primary outcome was a composite of recurrent arterial/venous thromboembolism or death. We used Cox regression to evaluate associations between biomarkers and subsequent outcomes., Results: During an estimated median follow-up time of 48 days (IQR, 18-312), 43 (86%) participants developed recurrent thromboembolism or death, including 28 (56%) with recurrent thromboembolism, of which 13 were recurrent AIS (26%). In unadjusted analysis, D-dimer (HR 1.6; 95% CI 1.2-2.0), P-selectin (HR 1.9; 95% CI 1.4-2.7), sICAM-1 (HR 2.2; 95% CI 1.6-3.1), sVCAM-1 (HR 1.6; 95% CI 1.2-2.1), and microemboli (HR 2.2; 95% CI 1.1-4.5) were associated with the primary outcome, whereas thrombin-antithrombin and thrombomodulin were not. D-dimer was the only marker associated with recurrent AIS (HR 1.2; 95% CI 1.0-1.5). Results were generally consistent in analyses adjusted for important prognostic variables., Conclusions: Markers of hypercoagulability and embolic disease may be associated with adverse clinical outcomes in cancer-related stroke., (© 2022 International Society on Thrombosis and Haemostasis.)

Background: In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH., Methods: We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale)., Results: Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, P =0.001) and early neurological deterioration (31 versus 17%, P =0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, P <0.001) and 24 hours (14 versus 38mL, P <0.001). Unadjusted 90-day outcome was worse in lobar compared with deep ICH (median modified Rankin Scale score 5 versus 4, P =0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38-0.89]; P =0.01)., Conclusions: In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.

Objectives: To derive models that identify patients with COVID-19 at high risk for stroke., Materials and Methods: We used data from the AHA's Get With The Guidelines® COVID-19 Cardiovascular Disease Registry to generate models for predicting stroke risk among adults hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our models, we used data on demographics, comorbidities, medications, and vital sign and laboratory values at admission. The outcome was a cerebrovascular event (stroke, TIA, or cerebral vein thrombosis). First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable and multivariable analyses. Then, we assigned points for each variable based on corresponding coefficients to create a prediction score. Second, we used machine learning techniques to create risk estimators using all available covariates., Results: Among 21,420 patients hospitalized with COVID-19, 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created/validated a COVID-19 stroke risk score with a C-statistic of 0.66 (95% CI, 0.60-0.72). The CANDLE score assigns 1 point each for prior cerebrovascular disease, afebrile temperature, no prior pulmonary disease, history of hypertension, leukocytosis, and elevated systolic blood pressure. CANDLE stratified risk of an acute cerebrovascular event according to low- (0-1: 0.2% risk), medium- (2-3: 1.1% risk), and high-risk (4-6: 2.1-3.0% risk) groups. Machine learning estimators had similar discriminatory performance as CANDLE: C-statistics, 0.63-0.69., Conclusions: We developed a practical clinical score, with similar performance to machine learning estimators, to help stratify stroke risk among patients hospitalized with COVID-19., Competing Interests: Declaration of Competing Interest Alexander Merkler and Babak Navi report an institutional research grant from Weill Cornell Medicine to examine stroke risk in patients with COVID-19. Costantino Iadecola serves on the scientific advisory board for Broadview Ventures. Mitchell Elkind receives study drug in kind from Bristol Myers Squibb-Pfizer alliance for Eliquis and ancillary research funding from Roche for an NIH-funded stroke prevention trial; he also reports royalties from UpToDate for chapters on COVID-19 and neurological disease and is an uncompensated officer of the American Heart Association. Hooman Kamel serves as co-PI for the NIH-funded ARCADIA trial which receives in-kind study drug from the BMS-Pfizer Alliance and in-kind study assays from Roche Diagnostics, serves as Deputy Editor for JAMA Neurology, serves as a steering committee member of Medtronic's Stroke AF trial (uncompensated), serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim, and has served on an advisory board for Roivant Sciences related to Factor XI inhibition. The other authors have no disclosures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mobile stroke units (MSUs) are specialized ambulances equipped with the personnel, equipment, and imaging capability to diagnose and treat acute stroke in the prehospital setting. Over the past decade, MSUs have proliferated throughout the world, particularly in European and US cities, culminating in the formation of an international consortium. Randomized trials have demonstrated that MSUs increase stroke thrombolysis rates and reduce onset-to-treatment times but until recently it was uncertain if these advantages would translate into better patient outcomes. In 2021, 2 pivotal, large, controlled clinical trials, B&#95;PROUD and BEST-MSU, demonstrated that as compared with conventional emergency care, treatment aboard MSUs was safe and led to improved functional outcomes in patients with stroke. Further, the observed benefit of MSUs appeared to be primarily driven by the higher frequency of ultra-early thrombolysis within the golden hour. Nevertheless, questions remain regarding the cost-effectiveness of MSUs, their utility in nonurban settings, and optimal infrastructure. In addition, in much of the world, MSUs are currently not reimbursed by insurers nor accepted as standard care by regulatory bodies. As MSUs are now established as one of the few proven acute stroke interventions with an effect size that is comparable to that of intravenous thrombolysis and stroke units, stroke leaders and organizations should work with emergency medical services, governments, and community stakeholders to determine how MSUs might benefit individual communities, and their optimal organization and financing. Future research to explore the effect of MSUs on intracranial hemorrhage and thrombectomy outcomes, cost-effectiveness, and novel models including the use of rendezvous transports, helicopters, and advanced neuroimaging is ongoing. Recommended next steps for MSUs include reimbursement by insurers, integration with ambulance networks, recognition by program accreditors, and inclusion in registries that monitor care quality.

Background: Continued smoking after stroke is associated with a high risk of stroke recurrence and other cardiovascular disease. We sought to comprehensively understand the epidemiology of smoking cessation in stroke survivors in the United States. Furthermore, we compared smoking cessation in stroke and cancer survivors because cancer is another smoking-related condition in which smoking cessation is prioritized., Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System, an annual, nationally representative health survey. Using pooled data from 2013 to 2019, we identified stroke and cancer survivors with a history of smoking. We used survey procedures to estimate frequencies and summarize quit ratios with attention to demographic and geographic (state-wise and rural-urban) factors for stroke survivors. The quit ratio is conventionally defined as the proportion of ever smokers who have quit. Then, we used multivariable logistic regression to compare quit ratios in stroke and cancer survivors while adjusting for demographics and smoking-related comorbidities., Results: Among 4 434 604 Americans with a history of stroke and smoking, the median age was 68 years (interquartile range, 59-76), and 45.4% were women. The overall quit ratio was 60.8% (95% CI, 60.1%-61.6%). Quit ratios varied by age group, sex, race and ethnicity, and several geographic factors. There was marked geographic variation in quit ratios, ranging from 48.3% in Kentucky to 71.5% in California. Furthermore, compared with cancer survivors, stroke survivors were less likely to have quit smoking (odds ratio, 0.72 [95% CI, 0.67-0.79]) after accounting for differences in demographics and smoking-related comorbidities., Conclusions: There were considerable demographic and geographic disparities in smoking quit ratios in stroke survivors, who were less likely to have quit smoking than cancer survivors. A targeted initiative is needed to improve smoking cessation for stroke survivors.

Objectives: Cancer can present as stroke. Several cancer types have established screening guidelines. We investigated adherence to guideline-recommended cancer screening in stroke survivors versus the general population., Materials and Methods: We performed a cross-sectional analysis using 2012-2018 data from the CDC's Behavioral Risk Factor Surveillance System (BRFSS) survey. BRFSS is a nationally-representative telephone survey of non-institutionalized Americans that collects data about health conditions and behaviors, including cancer screening. We defined guideline-recommended colorectal, lung, and breast cancer screening based on the U.S. Preventive Services Task Force recommendations. We used survey-specific methods to estimate up-to-date screening rates for those with and without prior stroke. We used logistic regression to estimate the odds of up-to-date screening in stroke survivors compared to those without history of stroke after adjustment for potential confounders., Results: Among 1,018,440 respondents eligible for colorectal cancer screening, 66% were up-to-date. Among 6,880 respondents eligible for lung cancer screening, 16% were up-to-date. Among 548,434 women eligible for breast cancer screening, 78% were up-to-date. After adjustment for demographics and confounders, stroke survivors were more likely to have up-to-date colorectal cancer screening (OR, 1.10; 95% CI, 1.05-1.16), equally likely to undergo lung cancer screening (OR, 0.99; 95% CI, 0.62-1.59), and less likely to undergo breast cancer screening (OR, 0.87; 95% CI, 0.80-0.94)., Conclusions: In a nationwide analysis, stroke survivors had similar suboptimal adherence to guideline-recommended cancer screening as the general population., Competing Interests: Declaration of Competing Interest Hooman Kamel serves as co-PI for the NIH-funded ARCADIA trial which receives in-kind study drug from the BMS-Pfizer Alliance and in-kind study assays from Roche Diagnostics, serves as Deputy Editor for JAMA Neurology, serves as a steering committee member of Medtronic's Stroke AF trial (uncompensated), and serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim. Neal Parikh has received personal fees for medicolegal consulting on stroke. Babak Navi has received personal fees for medicolegal consulting on stroke. The other authors have no disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)