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Background: We assessed the efficacy and safety of mechanical thrombectomy (MT) in adult stroke patients with anterior circulation large vessel occlusion presenting in the late time window not fulfilling the DEFUSE-3 (Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging trial) and DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct trial) inclusion criteria. Methods: Cohort study of adults with anterior circulation large vessel occlusion admitted between 6 and 24 hours after last-seen-well at 5 participating Swiss stroke centers between 2014 and 2021. Mismatch was assessed by computer tomography or magnetic resonance imaging perfusion with automated software (RAPID or OLEA). We excluded patients meeting DEFUSE-3 and DAWN inclusion criteria and compared those who underwent MT with those receiving best medical treatment alone by inverse probability of treatment weighting using the propensity score. The primary efficacy end point was a favorable functional outcome at 90 days, defined as a modified Rankin Scale score shift toward lower categories. The primary safety end point was symptomatic intracranial hemorrhage within 7 days of stroke onset; the secondary was all-cause mortality within 90 days. Results: Among 278 patients with anterior circulation large vessel occlusion presenting in the late time window, 190 (68%) did not meet the DEFUSE-3 and DAWN inclusion criteria and thus were included in the analyses. Of those, 102 (54%) received MT. In the inverse probability of treatment weighting analysis, patients in the MT group had higher odds of favorable outcomes compared with the best medical treatment alone group (modified Rankin Scale shift: acOR, 1.46 [1.02–2.10]; P =0.04) and lower odds of all-cause mortality within 90 days (aOR, 0.59 [0.37–0.93]; P =0.02). There were no significant differences in symptomatic intracranial hemorrhage (MT versus best medical treatment alone: 5% versus 2%, P =0.63). Conclusions: Two out of 3 patients with anterior circulation large vessel occlusion presenting in the late time window did not meet the DEFUSE-3 and DAWN inclusion criteria. In these patients, MT was associated with higher odds of favorable functional outcomes without increased rates of symptomatic intracranial hemorrhage. These findings support the enrollment of patients into ongoing randomized trials on MT in the late window with more permissive inclusion criteria.

Introduction: Measures of cerebral small vessel disease (cSVD), such as white matter hyperintensities (WMH) and cerebral microbleeds (CMB), are associated with an unfavorable clinical course in stroke patients on oral anticoagulation (OAC) for atrial fibrillation (AF). Here, we investigated whether similar findings can be observed for global cortical atrophy (GCA). Methods: Registry-based prospective observational study of 320 patients treated with OAC following AF stroke. Patients underwent magnetic resonance imaging (MRI) allowing assessment of GCA. Using the simplified visual Pasquier scale, the severity of GCA was categorized as follows: 0: no atrophy, 1: mild atrophy; 2: moderate atrophy, and 3: severe atrophy. Using adjusted logistic and Cox regression analysis, we investigated the association of GCA using a composite outcome measure, comprising: (i) recurrent acute ischemic stroke (IS); (ii) intracranial hemorrhage (ICH); and (iii) death. Results: In our time to event analysis after adjusting for potential confounders (i.e., WMH, CMB, age, sex, diabetes, arterial hypertension, coronary heart disease, hyperlipidemia, and antiplatelet use), GCA was associated with an increased risk for the composite outcome in all three degrees of atrophy (grade 1: aHR 3.95, 95% CI 1.34–11.63, p = 0.013; grade 2: aHR 3.89, 95% CI 1.23–12.30, p = 0.021; grade 3: aHR 4.16, 95% CI 1.17–14.84, p = 0.028). Conclusion: GCA was associated with our composite outcome also after adjusting for other cSVD markers (i.e., CMB, WMH) and age, indicating that GCA may potentially serve as a prognostic marker for stroke patients with atrial fibrillation on oral anticoagulation.

BACKGROUND Data on the impact of competing stroke etiologies in stroke patients with atrial fibrillation (AF) are scarce. METHODS We used prospectively obtained data from an observational registry (Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-(NOACISP)-LONGTERM) of consecutive AF-stroke patients treated with oral anticoagulants. We compared the frequency of (i) the composite outcome of recurrent ischemic stroke (IS), intracerebral hemorrhage (ICH) or all-cause death as well as (ii) recurrent IS alone among AF-stroke patients with versus without competing stroke etiologies according to the TOAST classification. We performed cox proportional hazards regression modeling adjusted for potential confounders. Furthermore, the etiology of recurrent IS was assessed. RESULTS Among 907 patients (median age 81, 45.6% female), 184 patients (20.3%) had competing etiologies, while 723 (79.7%) had cardioembolism as the only plausible etiology. During 1587 patient-years of follow-up, patients with additional large-artery atherosclerosis had higher rates of the composite outcome (adjusted HR [95% CI] 1.64 [1.11, 2.40], p = 0.017) and recurrent IS (aHR 2.96 [1.65, 5.35 ], p

Introduction: Rapid treatment of acute ischemic stroke (AIS) depends on sufficient staffing which differs between Stroke Centers and Stroke Units in Switzerland. We studied the effect of admission time on performance measures of AIS treatment and related temporal trends over time. Patients and methods: We compared treatment rates, door-to-image-time, door-to-needle-time, and door-to-groin-puncture-time in stroke patients admitted during office hours (Monday–Friday 8:00–17:59) and non-office hours at all certified Stroke Centers and Stroke Units in Switzerland, as well as secular trends thereof between 2014 and 2019, using data from the Swiss Stroke Registry. Secondary outcomes were modified Rankin Scale and mortality at 3 months. Results: Data were eligible for analysis in 31,788 (90.2%) of 35,261 patients. Treatment rates for IVT/EVT were higher during non-office hours compared with office hours in Stroke Centers (40.8 vs 36.5%) and Stroke Units (21.8 vs 18.5%). Door-to-image-time and door-to-needle-time increased significantly during non-office hours. Median (IQR) door-to-groin-puncture-time at Stroke Centers was longer during non-office hours compared to office hours (84 (59–116) vs 95 (66–130) minutes). Admission during non-office hours was independently associated with worse functional outcome (1.11 [95%CI: 1.04–1.18]) and increased mortality (1.13 [95%CI: 1.01–1.27]). From 2014 to 2019, median door-to-groin-puncture-time improved and the treatment rate for wake-up strokes increased. Discussion and Conclusion: Despite differences in staffing, patient admission during non-office hours delayed IVT to a similar, modest degree at Stroke Centers and Stroke Units. A larger delay of EVT was observed during non-office hours, but Stroke Centers sped up delivery of EVT over time. Patients admitted during non-office hours had worse functional outcomes, which was not explained by treatment delays.

Supplemental material, sj-docx-1-eso-10.1177_23969873231185220 for The impact of competing stroke etiologies in patients with atrial fibrillation by Annaelle Zietz, Alexandros A Polymeris, Fabrice Helfenstein, Sabine Schaedelin, Lisa Hert, Benjamin Wagner, David J Seiffge, Christopher Traenka, Valerian L Altersberger, Tolga Dittrich, Josefin Kaufmann, Flavia Ravanelli, Joachim Fladt, Urs Fisch, Sebastian Thilemann, Gian Marco De Marchis, Henrik Gensicke, Leo H Bonati, Mira Katan, Urs Fischer, Philippe Lyrer, Stefan T Engelter and Nils Peters in European Stroke Journal

Supplemental material, sj-doc-2-eso-10.1177_23969873231151488 for Apical pulmonary lesions suspected of malignancy visible on neck CT angiography performed for acute stroke: Prevalence, treatment, and clinical implications – the PLEURA study by Tolga D Dittrich, Mara Aujesky, Salome Rudin, Annaelle Zietz, Benjamin Wagner, Alexandros Polymeris, Valerian L Altersberger, Tim Sinnecker, Henrik Gensicke, Stefan T Engelter, Philippe Lyrer, Viviane Hess, Raoul Sutter, Christian H Nickel, Leo H Bonati, Urs Fischer, Marios Psychogios, Mira Katan and Gian Marco De Marchis in European Stroke Journal

Supplemental material, sj-docx-1-eso-10.1177_23969873231151488 for Apical pulmonary lesions suspected of malignancy visible on neck CT angiography performed for acute stroke: Prevalence, treatment, and clinical implications – the PLEURA study by Tolga D Dittrich, Mara Aujesky, Salome Rudin, Annaelle Zietz, Benjamin Wagner, Alexandros Polymeris, Valerian L Altersberger, Tim Sinnecker, Henrik Gensicke, Stefan T Engelter, Philippe Lyrer, Viviane Hess, Raoul Sutter, Christian H Nickel, Leo H Bonati, Urs Fischer, Marios Psychogios, Mira Katan and Gian Marco De Marchis in European Stroke Journal

Supplemental material, sj-docx-1-eso-10.1177_23969873231185895 for Safety and effectiveness of IV Thrombolysis in retinal artery occlusion: A multicenter retrospective cohort study by Philipp Baumgartner, Lucas Kook, Valerian L Altersberger, Henrik Gensicke, Elena Ardila-Jurado, Georg Kägi, Alexander Salerno, Patrik Michel, Kiran M Gopisingh, Paul J Nederkoorn, Jan F Scheitz, Christian H Nolte, Mirjam R Heldner, Marcel Arnold, Charlotte Cordonnier, Lucie Della Schiava, Christian Hametner, Peter A. Ringleb, Ronen R Leker, Hamza Jubran, Andreas R Luft, Stefan T Engelter and Susanne Wegener in European Stroke Journal

Background: The DEFUSE-3 and DAWN trials showed that mechanical thrombectomy (MT) improves the outcome of selected patients with anterior circulation large vessel occlusions (LVO) up to 24 h after stroke onset. However, it is unknown whether only those patients fulfilling the trial inclusion criteria benefit, or whether benefit is seen in a broader range of patients presenting between 6 and 24 h. Aims: We determined whether fulfilling the DEFUSE-3 and DAWN selection criteria affects outcomes in MT patients in clinical practice. Methods: We reviewed adult patients with LVO treated with MT between 6 and 24 h after stroke onset at five Swiss stroke centers between 2014 and 2021. We compared two groups: (1) patients who satisfied neither DEFUSE-3 nor DAWN criteria (NDND) and (2) those who satisfied DEFUSE-3 or DAWN criteria (DOD). We used logistic regression to examine the impact of trial eligibility on two safety outcomes (symptomatic intracranial hemorrhage [sICH] and all-cause mortality at 3 months) and two efficacy outcomes (modified Rankin Score [mRS] shift toward lower categories and mRS of 0–2 at 3 months). Results: Of 174 patients who received MT, 102 (59%) belonged to the NDND group. Rates of sICH were similar between the NDND group and the DOD group (3% vs. 4%, p = 1.00). Multivariable regression revealed no differences in 3-month all-cause mortality (aOR 2.07, 95% CI 0.64–6.84, p = 0.23) or functional outcomes (mRS shift: acOR 0.81, 95% CI 0.37–1.79, p = 0.60; mRS 0–2: aOR 0.91, 95% CI 0.31–2.57, p = 0.85). Conclusion: Among adult patients with LVO treated with MT between 6 and 24 h, safety and efficacy outcomes were similar between DEFUSE-3/DAWN eligible and ineligible patients. Our data provide a compelling rationale for randomized trials with broader inclusion criteria for MT.

The meibomian glands (MGs) within the eyelids produce a lipid-rich secretion that forms the superficial layer of the tear film. Meibomian gland dysfunction (MGD) results in excessive evaporation of the tear film, which is the leading cause of dry eye disease (DED). To develop a research model similar to the physiological situation of MGs, we established a new 3D organotypic slice culture (OSC) of

Background: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. Methods: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those Results: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratio adjusted 1.14 [0.83–1.57]) did not differ significantly between both groups. However, the probability of death (odds ratio adjusted 3.77 [3.14–4.53]) and poor functional outcome (odds ratio adjusted 2.63 [2.13–3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. Conclusions: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Supplemental Digital Content is available in the text., Background and Purpose: Timely reperfusion is an important goal in treatment of eligible patients with acute ischemic stroke. However, during the coronavirus disease 2019 (COVID-19) pandemic, prehospital and in-hospital emergency procedures faced unprecedented challenges, which might have caused a decline in the number of acute reperfusion therapy applied and led to a worsening of key quality measures for this treatment during lockdown. Methods: This prospective multicenter cohort study used data from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry of patients with acute ischemic stroke treated with reperfusion therapies, that is, intravenous thrombolysis or endovascular therapy. We compared prehospital and in-hospital time-based performance measures (stroke-onset-to-admission, admission-to-treatment, admission-to-image, and image-to-treatment time) during the first 6 weeks after announcement of lockdown (lockdown period) with the same period in 2019 (reference period). Secondary outcomes included stroke severity (National Institutes of Health Stroke Scale) after 24 hours and occurrence of symptomatic intracranial hemorrhage (following the ECASS [European-Australasian Acute Stroke Study]-II criteria). Results: Across 20 stroke centers, 540 patients were treated with intravenous thrombolysis/endovascular therapy during lockdown period compared with 578 patients during reference period (−7% [95% CI, 5%–9%]). Performance measures did not change significantly during the lockdown period (2020/2019 minutes median: onset-to-admission 133/145; admission-to-treatment 51/48). Same was true for admission-to-image (20/19) and image-to-treatment (31/30) time in patients with available time of first image (n=871, 77.9%). Median National Institutes of Health Stroke Scale on admission (2020/2019: 11/11) and after 24 hours (2020/2019: 6/5) and percentage of symptomatic intracranial hemorrhage (2020/2019: 6.2/5.7) did not differ significantly between both periods. Conclusions: The COVID-19 pandemic lockdown resulted in a mild decline in the number of patients with stroke treated with acute reperfusion therapies. More importantly, the solid stability of key quality performance measures between the 2020 and 2019 period may indicate resilience of acute stroke care service during the lockdown, at least in well-established European stroke centers.

Introduction Alterations in haemoglobin levels are frequent in stroke patients. The prognostic meaning of anaemia and polyglobulia on outcomes in patients treated with intravenous thrombolysis is ambiguous. Patients and methods In this prospective multicentre, intravenous thrombolysis register-based study, we compared haemoglobin levels on hospital admission with three-month poor outcome (modified Rankin Scale 3–6), mortality and symptomatic intracranial haemorrhage (European Cooperative Acute Stroke Study II-criteria (ECASS-II-criteria)). Haemoglobin level was used as continuous and categorical variable distinguishing anaemia (female: 15.5 g/dl; male: >17 g/dl). Anaemia was subdivided into mild and moderate/severe (female/male: Results Among 6866 intravenous thrombolysis-treated stroke patients, 5448 (79.3%) had normal haemoglobin level, 1232 (17.9%) anaemia – of those 903 (13.2%) had mild and 329 (4.8%) moderate/severe anaemia – and 186 (2.7%) polyglobulia. Anaemia was associated with poor outcome (ORadjusted 1.25 (1.05–1.48)) and mortality (ORadjusted 1.58 (1.27–1.95)). In anaemia subgroups, both mild and moderate/severe anaemia independently predicted poor outcome (ORadjusted 1.29 (1.07–1.55) and 1.48 (1.09–2.02)) and mortality (ORadjusted 1.45 (1.15–1.84) and ORadjusted 2.00 (1.46–2.75)). Each haemoglobin level decrease by 1 g/dl independently increased the risk of poor outcome (ORadjusted 1.07 (1.02–1.11)) and mortality (ORadjusted 1.08 (1.02–1.15)). Anaemia was not associated with occurrence of symptomatic intracranial haemorrhage. Polyglobulia did not change any outcome. Discussion The more severe the anaemia, the higher the probability of poor outcome and death. Severe anaemia might be a target for interventions in hyperacute stroke. Conclusion Anaemia on admission, but not polyglobulia, is a strong and independent predictor of poor outcome and mortality in intravenous thrombolysis-treated stroke patients.

Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to selected centers or lack 3-month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3-month outcomes of patients with IS and COVID-19 in a nationwide stroke registry. From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID-19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3-month outcome of SARS-CoV-2 polymerase chain reaction-positive (PCR+) IS patients to SARS-CoV-2 PCR- and/or asymptomatic non-tested IS patients. Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08-5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14-0.99, p = 0.049). COVID-19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS-adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96-3.58, p = 0.07). In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multi-territory stroke and less often cryptogenic stroke, and their 3-month functional outcome tended to be worse.

Background: Data on the safety and effectiveness of once-daily (QD) versus twice-daily (BID) direct oral anticoagulants (DOAC) in comparison to vitamin K antagonists (VKA) and to one another in patients with atrial fibrillation (AF) and recent stroke are scarce. Patients and methods: Based on prospectively obtained data from the observational registry Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients(NOACISP)-LONGTERM (NCT03826927) from Basel, Switzerland, we compared the occurrence of the primary outcome – the composite of recurrent ischemic stroke, major bleeding, and all-cause death – among consecutive AF patients treated with either VKA, QD DOAC, or BID DOAC following a recent stroke using Cox proportional hazards regression including adjustment for potential confounders. Results: We analyzed 956 patients (median age 80 years, 46% female), of whom 128 received VKA (13.4%), 264 QD DOAC (27.6%), and 564 BID DOAC (59%). Over a total follow-up of 1596 patient-years, both QD DOAC and BID DOAC showed a lower hazard for the composite outcome compared to VKA (adjusted HR [95% CI] 0.69 [0.48, 1.01] and 0.66 [0.47, 0.91], respectively). Upon direct comparison, the hazard for the composite outcome did not differ between patients treated with QD versus BID DOAC (adjusted HR [95% CI] 0.94 [0.70, 1.26]). Secondary analyses focusing on the individual components of the composite outcome revealed no clear differences in the risk-benefit profile of QD versus BID DOAC. Discussion and conclusion: The overall benefit of DOAC over VKA seems to apply to both QD and BID DOAC in AF patients with a recent stroke, without clear evidence that one DOAC dosing regimen is more advantageous than the other.

Supplemental material, sj-docx-1-wso-10.1177_17474930221140793 for Mechanical thrombectomy for large vessel occlusion between 6 and 24 h: outcome comparison of DEFUSE-3/DAWN eligible versus non-eligible patients by Tolga D Dittrich, Peter B Sporns, Lilian F Kriemler, Salome Rudin, Anh Nguyen, Annaelle Zietz, Alexandros A Polymeris, Christopher Tränka, Sebastian Thilemann, Benjamin Wagner, Valerian L Altersberger, Ines Piot, Filip Barinka, Martin Hänsel, Henrik Gensicke, Stefan T Engelter, Philippe A Lyrer, Raoul Sutter, Christian H Nickel, Mira Katan, Nils Peters, Lars Michels, Zsolt Kulcsár, Grzegorz M Karwacki, Marco Pileggi, Carlo Cereda, Susanne Wegener, Leo H Bonati, Urs Fischer, Marios Psychogios and Gian Marco De Marchis in International Journal of Stroke

Supplemental material, sj-docx-1-eso-10.1177_23969873221094408 for Effect of admission time on provision of acute stroke treatment at stroke units and stroke centers—An analysis of the Swiss Stroke Registry by Valerian L Altersberger, Patrick R Wright, Sabine A Schaedelin, Gian Marco De Marchis, Henrik Gensicke, Stefan T Engelter, Marios Psychogios, Timo Kahles, Martina Goeldlin, Thomas R Meinel, Pasquale Mordasini, Johannes Kaesmacher, Alexander von Hessling, Jochen Vehoff, Johannes Weber, Susanne Wegener, Stephan Salmen, Rolf Sturzenegger, Friedrich Medlin, Christian Berger, Ludwig Schelosky, Susanne Renaud, Julien Niederhauser, Christophe Bonvin, Michael Schaerer, Marie-Luise Mono, Biljana Rodic, Guido Schwegler, Nils Peters, Manuel Bolognese, Andreas R Luft, Carlo W Cereda, Georg Kägi, Patrick Michel, Emmanuel Carrera, Marcel Arnold, Urs Fischer, Krassen Nedeltchev and Leo H Bonati in European Stroke Journal

Supplemental material, sj-docx-2-wso-10.1177_17474930221140793 for Mechanical thrombectomy for large vessel occlusion between 6 and 24 h: outcome comparison of DEFUSE-3/DAWN eligible versus non-eligible patients by Tolga D Dittrich, Peter B Sporns, Lilian F Kriemler, Salome Rudin, Anh Nguyen, Annaelle Zietz, Alexandros A Polymeris, Christopher Tränka, Sebastian Thilemann, Benjamin Wagner, Valerian L Altersberger, Ines Piot, Filip Barinka, Martin Hänsel, Henrik Gensicke, Stefan T Engelter, Philippe A Lyrer, Raoul Sutter, Christian H Nickel, Mira Katan, Nils Peters, Lars Michels, Zsolt Kulcsár, Grzegorz M Karwacki, Marco Pileggi, Carlo Cereda, Susanne Wegener, Leo H Bonati, Urs Fischer, Marios Psychogios and Gian Marco De Marchis in International Journal of Stroke

Supplemental material, sj-docx-1-eso-10.1177_23969873221099477 for Once versus twice daily direct oral anticoagulants in patients with recent stroke and atrial fibrillation by Alexandros A Polymeris, Annaelle Zietz, Fabian Schaub, Louisa Meya, Christopher Traenka, Sebastian Thilemann, Benjamin Wagner, Lisa Hert, Valerian L Altersberger, David J Seiffge, Flurina Lyrer, Tolga Dittrich, Ines Piot, Josefin Kaufmann, Lea Barone, Ludvig Dahlheim, Sophie Flammer, Nikolaos S Avramiotis, Nils Peters, Gian Marco De Marchis, Leo H Bonati, Henrik Gensicke, Stefan T Engelter and Philippe A Lyrer in European Stroke Journal

Background: Progressive multifocal leukoencephalopathy (PML) is the main safety concern for dimethyl fumarate (DMF) treatment in persons with multiple sclerosis (pwMS). Risk stratification under DMF is currently based on age above 50 years and prolonged lymphopenia below 500 cells/μL. Objective: To report a case of PML under DMF without severe lymphopenia or immunosenescence. Methods: Case report. Results: A 39-year-old female pwMS developed DMF-associated oligosymptomatic PML. The patient had not experienced any repeated lymphocyte counts below 800 cells/μL and was 15 years younger than previously described cases. Conclusion: Despite risk stratification, vigilance for PML is advised in all pwMS under DMF. Severe CD8-lymphopenia is a common feature of all published DMF-associated cases.

Background and Purpose: Data on the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with stroke attributable to atrial fibrillation (AF) who were dependent on the daily help of others at hospital discharge are scarce. Methods: Based on prospectively obtained data from the observational Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-longterm registry from Basel, Switzerland, we compared the occurrence of the primary outcome—the composite of recurrent ischemic stroke, major bleeding, and all-cause death—among consecutive patients with AF-stroke treated with either VKAs or DOACs between patients dependent (defined as modified Rankin Scale score, 3–5) and patients independent at discharge. We used simple, adjusted, and weighted Cox proportional hazards regression to account for potential confounders. Results: We analyzed 801 patients (median age 80 years, 46% female), of whom 391 (49%) were dependent at discharge and 680 (85%) received DOACs. Over a total follow-up of 1216 patient-years, DOAC- compared to VKA-treated patients had a lower hazard for the composite outcome (hazard ratio [HR], 0.58 [95% CI, 0.42–0.81]), as did independent compared to dependent patients (HR, 0.54 [95% CI, 0.40–0.71]). There was no evidence that the effect of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome differed between dependent (HR dependent , 0.68 [95% CI, 0.45–1.01]) and independent patients (HR independent , 0.44 [95% CI, 0.26–0.75]) in the simple model ( P interaction =0.212). Adjusted (HR dependent , 0.74 [95% CI, 0.49–1.11] and HR independent , 0.51 [95% CI, 0.30–0.87]; P interaction =0.284) and weighted models (HR dependent , 0.79 [95% CI, 0.48–1.31] and HR independent , 0.46 [95% CI, 0.26–0.81]; P interaction =0.163) yielded concordant results. Secondary analyses focusing on the individual components of the composite outcome were consistent to the primary analyses. Conclusions: The benefits of DOACs in patients with atrial fibrillation with a recent stroke were maintained among patients who were dependent on the help of others at discharge. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03826927.

Non

Supplemental material, ESO889468 Supplementary material for Effect of haemoglobin levels on outcome in intravenous thrombolysis-treated stroke patients by Valerian L Altersberger, Lars Kellert, Abdulaziz S Al Sultan, Nicolas Martinez-Majander, Christian Hametner, Ashraf Eskandari, Mirjam R Heldner, Sophie A van den Berg, Andrea Zini, Visnja Padjen, Georg Kägi, Alessandro Pezzini, Alexandros Polymeris, Gian M DeMarchis, Marjaana Tiainen, Silja Räty, Stefania Nannoni, Simon Jung, Thomas P Zonneveld, Stefania Maffei, Leo Bonati, Philippe Lyrer, Gerli Sibolt, Peter A Ringleb, Marcel Arnold, Patrik Michel, Sami Curtze, Paul J Nederkoorn, Stefan T Engelter, Henrik Gensicke and for the Thrombolysis in Stroke Patients (TRISP) collaborators in European Stroke Journal