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Background: Stroke incidence and case-fatality are reported to decline in high-income countries during the last decades. Epidemiological studies are important for health services to organize prevention and treatment strategies. Aims: The aim of this population-based study was to determine temporal trends of stroke incidence and case-fatality rates of first-ever stroke in Arcadia, a prefecture in southern Greece. Methods: All first-ever stroke cases in the Arcadia prefecture were ascertained using the same standard criteria and multiple overlapping sources in three study periods: from November 1993 to October 1995; 2004; and 2015–2016. Crude and age-adjusted to European population incidence rates were compared using Poisson regression. Twenty-eight days case fatality rates were estimated and compared using the same method. Results: In total, 1315 patients with first-ever stroke were identified. The age-standardized incidence to the European population was 252 per 100,000 person-years (95% CI 231–239) in 1993/1995, 252 (95% CI 223–286) in 2004, and 211 (192–232) in 2015/2016. The overall age- and sex-adjusted incidence rates fell by 16% (incidence rates ratio 0.84, 95% CI: 0.72–0.97). Similarly, 28-day case-fatality rate decreased by 28% (case fatality rate ratio = 0.72, 95% CI: 0.58–0.90). Conclusions: This population-based study reports a significant decline in stroke incidence and mortality rates in southern Greece between 1993 and 2016. © 2021 World Stroke Organization.

Background and Purpose: Chronic inflammatory bowel diseases (IBD) frequently affect extraintestinal organs including the liver. Since limited evidence suggests the presence of liver disease in IBD patients, we studied the frequency of hepatic steatosis and fibrosis in these patients and characterized disease-related factors. Methods: In this retrospective, cross-sectional, hospital-based, single-center study, consecutive patients with Crohn’s disease (CD) and ulcerative colitis (UC) were included who had undergone routine abdominal ultrasound including transhepatic elastography. Hepatic steatosis was diagnosed by hyperechogenicity on B-mode ultrasound and by measuring controlled attenuation parameter (CAP). Hepatic fibrosis was assumed if transhepatic elastography yielded a stiffness > 7 kPa. Results: 132 patients (60% CD) with a median disease duration of 10 years were included. Steatosis assessed by B-mode ultrasound and CAP correlated well. Of the IBD patients, 30.3% had non-alcoholic fatty liver (NAFL). Factors associated with NAFL were age, BMI, duration of disease, as well as serum activities of aspartate-aminotransferase (AST) and gamma-glutamyl-transpeptidase (GGT). In multivariate analysis, only disease duration was independently associated with hepatic steatosis. Hepatic fibrosis was found in 10 (8%) of all IBD patients, predominantly in patients with CD (10/11). Conclusions: Pure hepatic steatosis is common in both CD and UC, whereas hepatic fibrosis occurs predominantly in CD patients. Association of disease duration with NAFLD suggests a contribution of IBD-related pathogenetic factors. Longitudinal studies are needed to better understand the impact of IBD on hepatic disorders. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

The aim of this study was to present the descriptive characteristics of the Stroke Units Necessity for Patients (SUN4P) registry. Methods: The study population derived from the web-based SUN4P registry included 823 patients with first-ever acute stroke. Descriptive statistics were used to present patients' characteristics. Results: The vast majority of patients (80.4%) had an ischemic stroke, whereas 15.4% had a hemorrhagic stroke. Hypertension was the leading risk factor in both patients. The patients with ischemic stroke had higher prevalence of traditional cardiovascular risk factors such as diabetes mellitus, dyslipidemia and smoking and most commonly cryptogenic stroke (39%). National Institutes of Health Stroke Scale (NIHSS) was higher among patients with hemorrhagic in comparison to those with ischemic stroke (10.5 vs 6 respectively). Moreover, all patients had similar rate of disability prior to stroke, as shown by Modified Rankin Scale (mRS=0). Conclusions: These data are in accordance with current evidence and should be thoroughly assessed in order to ensure optimal therapeutic management of stroke patients. © 2022 The authors and IOS Press.

The aim of this study was to calculate the average operational cost per sub-type of stroke patient and to investigate cost drivers (e.g. ALoS, NIHSS score, age) correlated to cost. Methods: Direct medical costs (diagnostic imaging and clinical laboratory exams, overheads/bed cost, pharmaceuticals, ringers and other non-durables and inpatient rehabilitation) per patient were calculated from the providers' (hospitals') perspective. Resource use data derived from the 'SUN4P' web-based registry and unit costs were retrieved from publically available sources and were assigned to resource use. Results: The sample comprised 6,282 inpatient days of 750 patients (mean age: 75.5±13.3 years) admitted from July 2019 to July 2021, in nine public hospitals. Mean length of stay was 8.4±7.6 days and mean total operational cost was calculated to €1,239.4 (from which 45% and 35% related to diagnostic exams and overheads/bed cost respectively). Mean cost related to hemorrhagic stroke patients that were discharged alive was calculated significantly higher compared to mean cost related to ischemic stroke patients who didn't undertake thrombolysis and were also discharged alive from the hospital (€2,155.2 vs. €945.2, p

This document presents the consensus recommendations of the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society for lipid modification in patients with ischemic stroke or transient ischemic attack. This clinical guide summarizes the current literature on lipid management and can be of assistance to the physicians treating stroke patients in clinical practice. © 2020 World Stroke Organization.

Background: Carotid atherosclerosis and likely pathogenic patent foramen ovale (PFO) are two potential embolic sources in patients with embolic stroke of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. Aim: To investigate the relation between carotid atherosclerosis and likely pathogenic PFO in patients with ESUS. We hypothesized that ipsilateral carotid atherosclerotic plaques are less prevalent in ESUS with likely pathogenic PFO compared to patients with likely incidental PFO or without PFO. Methods: The presence of PFO was assessed with transthoracic echocardiography with microbubble test and, when deemed necessary, through trans-oesophageal echocardiography. The presence of PFO was considered as likely incidental if the RoPE (Risk of Paradoxical Embolism) score was 0–6 and likely pathogenic if 7–10. Results: Among 374 ESUS patients (median age: 61years, 40.4% women), there were 63 (49.6%) with likely incidental PFO, 64 (50.4%) with likely pathogenic PFO and 165 (44.1%) with ipsilateral carotid atherosclerosis. The prevalence of ipsilateral carotid atherosclerosis was lower in patients with likely pathogenic PFO (7.8%) compared to patients with likely incidental PFO (46.0%) or patients without PFO (53.0%) (p

Objectives: Coronavirus disease-19 (COVID-19) is associated with various clinical manifestations, ranging from asymptomatic infection to critical illness. The aim of this study is to evaluate the clinical and laboratory characteristics of hospitalised COVID-19 patients and construct a predictive model for the discrimination of patients at risk of disease progression. Methods: A single-centre cohort study was conducted including consecutively patients with COVID-19. Demographic, clinical and laboratory findings were prospectively collected at admission. The primary outcome of interest was the intensive care unit admission. A risk model was constructed by applying a Cox's proportional hazard's model with elastic net penalty. Its diagnostic performance was assessed by receiver operating characteristic analysis and was compared with conventional pneumonia severity scores. Results: From a total of 67 patients 15 progressed to critical illness. The risk score included patients’ gender, presence of hypertension and diabetes mellitus, fever, shortness of breath, serum glucose, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein and fibrinogen. Its predictive accuracy was estimated to be high (area under the curve: 97.1%), performing better than CURB-65, CRB-65 and PSI/PORT scores. Its sensitivity and specificity were estimated to be 92.3% and 93.3%, respectively, at the optimal threshold of 1.6. Conclusions: A10-variable risk score was constructed based on clinical and laboratory characteristics in order to predict critical illness amongst hospitalised COVID-19 patients, achieving better discrimination compared with traditional pneumonia severity scores. The proposed risk model should be externally validated in independent cohorts in order to ensure its prognostic efficacy. © 2020 John Wiley & Sons Ltd

Background and aims: Only a minority of patients with Embolic Stroke of Undetermined Source (ESUS) receive prolonged cardiac monitoring despite current recommendations. The identification of ESUS patients who have low probability of new diagnosis of atrial fibrillation (AF) could potentially support a strategy of more individualized allocation of available resources and hence, increase their diagnostic yield. We aimed to develop a tool that can identify ESUS patients who have low probability of new incident AF. Methods: We performed multivariate stepwise regression in a pooled dataset of consecutive ESUS patients from three prospective stroke registries to identify predictors of new incident AF. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integer-based point scoring system. Results: Among 839 patients (43.1% women, median age 67.0 years) followed-up for a median of 24.3 months (2999 patient-years), 125 (14.9%) had new incident AF. The proposed score assigns 3 points for age ≥ 60 years; 2 points for hypertension; −1 point for left ventricular hypertrophy reported at echocardiography; 2 points for left atrial diameter >40 mm; −3 points for left ventricular ejection fraction 0 (relative risk: 13.7, 95%CI: 5.9--31.5). The area under the curve of the score was 84.8% (95%CI: 79.9--86.9%). The sensitivity and negative predictive value of a score of ≤0 for new incident AF during follow-up were 94.9% (95%CI: 89.3--98.1%) and 98.0% (95%CI: 95.8--99.3%), respectively. Conclusions: The proposed AF-ESUS score has high sensitivity and high negative predictive value to identify ESUS patients who have low probability of new incident AF. Patients with a score of 1 or more may be better candidates for prolonged automated cardiac monitoring. Clinical trial registration: URL: https://www.clinicaltrials.gov/ Unique identifier: NCT02766205. © 2020 World Stroke Organization.

Durability of SARS-CoV-2 Spike antibody responses after infection provides information relevant to understanding protection against COVID-19 in humans. We report the results of a sequential evaluation of anti-SARS-CoV-2 antibodies in convalescent patients with a median follow-up of 14 months (range 12.4-15.4) post first symptom onset. We report persistence of antibodies for all four specificities tested [Spike, Spike Receptor Binding Domain (Spike-RBD), Nucleocapsid, Nucleocapsid RNA Binding Domain (N-RBD)]. Anti-Spike antibodies persist better than anti-Nucleocapsid antibodies. The durability analysis supports a bi-phasic antibody decay with longer half-lives of antibodies after 6 months and antibody persistence for up to 14 months. Patients infected with the Wuhan (WA1) strain maintained strong cross-reactive recognition of Alpha and Delta Spike-RBD but significantly reduced binding to Beta and Mu Spike-RBD. Sixty percent of convalescent patients with detectable WA1-specific NAb also showed strong neutralization of the Delta variant, the prevalent strain of the present pandemic. These data show that convalescent patients maintain functional antibody responses for more than one year after infection, suggesting a strong long-lasting response after symptomatic disease that may offer a prolonged protection against re-infection. One patient from this cohort showed strong increase of both Spike and Nucleocapsid antibodies at 14 months post-infection indicating SARS-CoV-2 re-exposure. These antibodies showed stronger cross-reactivity to a panel of Spike-RBD including Beta, Delta and Mu and neutralization of a panel of Spike variants including Beta and Gamma. This patient provides an example of strong anti-Spike recall immunity able to control infection at an asymptomatic level. Together, the antibodies from SARS-CoV-2 convalescent patients persist over 14 months and continue to maintain cross-reactivity to the current variants of concern and show strong functional properties. Copyright © 2021 Rosati, Terpos, Ntanasis-Stathopoulos, Agarwal, Bear, Burns, Hu, Korompoki, Donohue, Venzon, Dimopoulos, Pavlakis and Felber.

The association of low-density lipoprotein cholesterol lowering with outcomes in embolic stroke of undetermined source (ESUS) patients is unclear. In these patients we aimed to assess the effect of statin on stroke recurrence, major adverse cardiovascular events (MACE) and death rates. Consecutive ESUS patients in the Athens Stroke Registry were prospectively followed-up to 10 years for stroke recurrence, MACE, and death. The Nelson–Aalen estimator was used to estimate the cumulative probability by statin allocation at discharge and cox-regression analyses to investigate whether statin at discharge was a predictor of outcomes. Among 264 ESUS patients who were discharged and followed for 4 years, 89 (33.7%) were treated with statin at discharge. Patients who were discharged on statin had lower rates of stroke recurrence (3.58 vs. 7.23/100 patient-years, HR: 0.48; 95% CI 0.26–0.90), MACE (4.98 vs. 9.89/100 patient-years, HR: 0.49; 95% CI 0.29–0.85), and death (3.93 vs. 8.21/100 patient-years, HR: 0.50; 95% CI: 0.28–0.89). In the multivariate analysis, statin treatment at discharge was an independent predictor of stroke recurrence (adjusted HR: 0.48; 95% CI 0.26–0.91), MACE (adjusted HR: 0.48; 95% CI 0.28–0.82), and death (adjusted HR: 0.50; 95% CI 0.27–0.93). Patients with ESUS discharged on statins have lower rates of stroke recurrence, MACE, and death compared to those not receiving statin therapy. © 2021, Società Italiana di Medicina Interna (SIMI).

Since the onset of the COVID-19 pandemic, a substantial proportion of COVID-19 patients had documented thrombotic complications and ischemic stroke. Several mechanisms related to immune-mediated thrombosis, the renin angiotensin system and the effect of SARS-CoV-2 in cardiac and brain tissue may contribute to the pathogenesis of ischemic stroke in patients with COVID-19. Simultaneously, significant strains on global healthcare delivery, including ischemic stroke management, have made treatment of stroke in the setting of COVID-19 particularly challenging. In this review, we summarize the current knowledge on epidemiology, clinical manifestation, and pathophysiology of ischemic stroke in patients with COVID-19 to bridge the gap from bench to bedside and clinical practice during the most challenging global health crisis of the last decades. © 2021 European Academy of Neurology

COVID-19 is an ongoing pandemic with high morbidity and mortality. Despite meticulous research, only dexamethasone has shown consistent mortality reduction. Convalescent plasma (CP) infusion might also develop into a safe and effective treatment modality on the basis of recent studies and meta-analyses; however, little is known regarding the kinetics of antibodies in CP recipients. To evaluate the kinetics, we followed 31 CP recipients longitudinally enrolled at a median of 3 days post symptom onset for changes in binding and neutralizing antibody titers and viral loads. Antibodies against the complete trimeric Spike protein and the receptor-binding domain (Spike-RBD), as well as against the complete Nucleocapsid protein and the RNA binding domain (N-RBD) were determined at baseline and weekly following CP infusion. Neutralizing antibody (pseudotype NAb) titers were determined at the same time points. Viral loads were determined semi-quantitatively by SARS-CoV-2 PCR. Patients with low humoral responses at entry showed a robust increase of antibodies to all SARS-CoV-2 proteins and Nab, reaching peak levels within 2 weeks. The rapid increase in binding and neutralizing antibodies was paralleled by a concomitant clearance of the virus within the same timeframe. Patients with high humoral responses at entry demonstrated low or no further increases; however, virus clearance followed the same trajectory as in patients with low antibody response at baseline. Together, the sequential immunological and virological analysis of this well-defined cohort of patients early in infection shows the presence of high levels of binding and neutralizing antibodies and potent clearance of the virus. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004–0.36), p: 0.005], significantly better overall survival by Kaplan–Meir analysis (p < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64–348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209). © 2021 by the au-thors. Licensee MDPI, Basel, Switzerland.

Among healthcare workers (HCWs), SARS-CoV-2 vaccine hesitancy may be linked to a higher susceptibility to nocebo effects, i.e., adverse events (AEs) experienced after medical treatments due to negative expectations. To investigate this hypothesis a cross-sectional survey was performed with a self-completed questionnaire that included a tool (Q-No) for the identification of nocebo-prone individuals. A total of 1309 HCWs (67.2% women; 43.4% physicians; 28.4% nurses; 11.5% administrative staff; 16.6% other personnel) completed the questionnaires, among whom 237 (18.1%) had declined vaccination. Q-No scores were ≥15 in 325 participants (24.8%) suggesting nocebo-prone behavior. In a multivariate logistic regression model with Q-No score, age, gender, and occupation as independent variables, estimated odds ratios (ORs) of vaccination were 0.43 (i.e., less likely, p < 0.001) in participants with Q-No score ≥ 15 vs. Q-No score < 15, 0.58 in females vs. males (p = 0.013), and 4.7 (i.e., more likely) in physicians vs. other HCWs (p < 0.001), independent of age, which was not significantly associated with OR of vaccination. At least one adverse effect (AE) was reported by 67.5% of vaccinees, mostly local pain and flu-like symptoms. In a multivariate logistic regression model, with Q-No score, age, gender, and occupation as independent variables, estimated ORs of AE reporting were 2.0 in females vs. males (p < 0.001) and 1.47 in physicians vs. other HCWs (p = 0.017) independently of age and Q-No score, which were not significantly associated with OR of AE. These findings suggest that nocebo-prone behavior in HCWs is associated with SARS-CoV-2 vaccination hesitancy indicating a potential benefit of a campaign focused on nocebo-prone people. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

The new type of coronavirus (COVID-19), SARS-CoV-2 originated from Wuhan, China and has led to a worldwide pandemic. COVID-19 is a novel emerging infectious disease caused by SARS-CoV-2 characterized as atypical pneumonia. As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. The typical manifestations of COVID-19 include fever, sore throat, fatigue, cough, and dyspnoea combined with recent exposure. Most of the patients with COVID-19 have mild or moderate disease, however up to 5–10% present with severe and even life-threatening disease course. The mortality rates are approximately 2%. Therefore, there is an urgent need for effective and specific antiviral treatment. Currently, supportive care measures such as ventilation oxygenation and fluid management remain the standard of care. Several clinical trials are currently trying to identify the most potent drug or combination against the disease, and it is strongly recommended to enroll patients into ongoing trials. Antivirals can be proven as safe and effective only in the context of randomized clinical trials. Currently several agents such as chloroquine, hydroxychloroquine, favipiravir, monoclonal antibodies, antisense RNA, corticosteroids, convalescent plasma and vaccines are being evaluated. The large numbers of therapeutic interventions aim to define the most efficacious regimen. The aim of this article is to describe the treatment strategies that have been used for COVID-19 patients and review all the available literature. © 2020, Springer Nature Switzerland AG.

The first European Stroke Organization (ESO) standard operating procedure (SOP) published in 2015 aimed at the implementation the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to provide evidence-based guidelines for stroke management. This second ESO-SOP is aiming at further increase of the practicability of ESO guidelines and its technical implications. Authors comprised of the members of the ESO guideline Board and ESO Executive Committee. The final document was agreed on by several internal reviews. The second SOP comprises of the following aspects: rational for the SOP, the introduction of expert consensus statements, types of guideline documents, structures involved and detailed description of the guideline preparation process, handling of financial and intellectual conflicts of interest (Col), involvement of ESO members in the guideline process, review process, authorship and publication policy, updating of guidelines, cooperation with other societies, and dealing with falsified data. This second SOP supersedes the first SOP published in 2015.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P

The aim of this study was to assess stroke patients' experiences in regards to hospital stay and during discharge. A cross-sectional study with retrospective data collection was conducted including patients (n=135) with first-ever acute stroke, who were admitted in seven Public Hospitals in Greece ('Stroke Units Necessity for Patients, SUN4P' registry). The translated version of the NHS-Stroke Questionnaire in the Greek was used. 48.2% of patients rated their overall experience from the care they received as very good/excellent. 66% of patients reported that they participated in decision making about their care and 21.5% reported not having received help from the hospital's social services regarding any benefits/aids, thus lowering their overall patient experience score (p=0.017). Decision and policymakers must consider factors affecting stroke patients experiences during their hospitalization. The development of a national stroke patients' experiences database can help prioritize relevant actions and draw up a commonly accepted management and services redesign framework for patients. © 2020 The authors and IOS Press.

Rationale: Cerebrovascular diseases associated with pregnancy and postpartum period are uncommon; however, they can have an important impact on health of both women and foetus or newborn. Aims: To evaluate the frequency, characteristics and management of cerebrovascular events in pregnant/postpartum women, to clarify pathophysiological mechanisms underlying the occurrence of these events including biomolecular aspects, and to assess the short- and long-term cerebrovascular and global cardiovascular outcome of these patients, their predictors and infant outcome. Methods and design: This is an observational, prospective, multicentre, international case–control study. The study will include patients with cerebrovascular events during pregnancy and/or within six months after delivery. For each included case, two controls will be prospectively recruited: one pregnant or puerperal subject without any history of cerebrovascular event and one non-pregnant or non-puerperal subject with a recent cerebrovascular event. All controls will be matched by age, ethnicity and type of cerebrovascular event with their assigned cases. The pregnant controls will be matched also by pregnancy weeks/trimester. Follow-up will last 24 months for the mother and 12 months for the infant. Summary: To better understand causes and outcomes of uncommon conditions like pregnancy/postpartum-related cerebrovascular events, the development of multisite, multidisciplinary registry-based studies, such as the Stroke in Pregnancy and Postpartum study, is needed in order to collect an adequate number of patients, draw reliable conclusions and give definite recommendations on their management. © European Stroke Organisation 2019.

We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD)); and an in-house ELISA detecting antibodies to complete spike, RBD and N in 60 of these donors. Neutralizing antibodies (NAb) were also evaluated in these 60 donors. Analyzed samples were collected at a median time of 62 (14–104) days from the day of first symptoms or positive PCR (for asymptomatic patients). Anti-SARS-CoV-2 antibodies were detected in 88% and 87.8% of donors using the ELISA and the multiplex assay, respectively. The multivariate analysis showed that age ≥50 years (p < 0.001) and need for hospitalization (p < 0.001) correlated with higher antibody titers, while asymptomatic status (p < 0.001) and testing >60 days after symptom onset (p = 0.001) correlated with lower titers. Interestingly, pseudotype virus-neutralizing antibodies (PsNAbs) significantly correlated with spike and with RBD antibodies by ELISA. Sera with high PsNAb also showed a strong ability to neutralize active SARS-CoV-2 virus, with hospitalized patients showing higher titers. Therefore, convalescent plasma donors can be selected based on the presence of high RBD antibody titers. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Importance: The concept of embolic stroke of undetermined source (ESUS) unifies a subgroup of cryptogenic strokes based on neuroimaging, a defined minimum set of diagnostic tests, and exclusion of certain causes. Despite an annual stroke recurrence rate of 5%, little is known about the etiology underlying recurrent stroke after ESUS. Objective: To identify the stroke subtype of recurrent ischemic strokes after ESUS, to explore the interaction with treatment assignment in each category, and to examine the consistency of cerebral location of qualifying ESUS and recurrent ischemic stroke. Design, Setting, and Participants: The NAVIGATE-ESUS trial was a randomized clinical trial conducted from December 23, 2014, to October 5, 2017. The trial compared the efficacy and safety of rivaroxaban and aspirin in patients with recent ESUS (n = 7213). Ischemic stroke was validated in 309 of the 7213 patients by adjudicators blinded to treatment assignment and classified by local investigators into the categories ESUS or non-ESUS (ie, cardioembolic, atherosclerotic, lacunar, other determined cause, or insufficient testing). Five patients with recurrent strokes that could not be defined as ischemic or hemorrhagic in absence of neuroimaging or autopsy were excluded. Data for this secondary post hoc analysis were analyzed from March to June 2019. Interventions: Patients were randomly assigned to receive rivaroxaban, 15 mg/d, or aspirin, 100 mg/d. Main Outcomes and Measures: Association of recurrent ESUS with stroke characteristics. Results: A total of 309 patients (205 men [66%]; mean [SD] age, 68 [10] years) had ischemic stroke identified during the median follow-up of 11 (interquartile range [IQR], 12) months (annualized rate, 4.6%). Diagnostic testing was insufficient for etiological classification in 39 patients (13%). Of 270 classifiable ischemic strokes, 156 (58%) were ESUS and 114 (42%) were non-ESUS (37 [32%] cardioembolic, 26 [23%] atherosclerotic, 35 [31%] lacunar, and 16 [14%] other determined cause). Atrial fibrillation was found in 27 patients (9%) with recurrent ischemic stroke and was associated with higher morbidity (median change in modified Rankin scale score 2 [IQR, 3] vs 0 (IQR, 1]) and mortality (15% vs 1%) than other causes. Risk of recurrence did not differ significantly by subtype between treatment groups. For both the qualifying and recurrent strokes, location of infarct was more often in the left (46% and 54%, respectively) than right hemisphere (40% and 37%, respectively) or brainstem or cerebellum (14% and 9%, respectively). Conclusions and Relevance: In this secondary analysis of randomized clinical trial data, most recurrent strokes after ESUS were embolic and of undetermined source. Recurrences associated with atrial fibrillation were a minority but were more often disabling and fatal. More extensive investigation to identify the embolic source is important toward an effective antithrombotic strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02313909. © 2020 American Medical Association. All rights reserved.

Background and Aim: Rapid and sensitive detection of atrial fibrillation (AF) is of paramount importance for initiation of adequate preventive therapy after stroke. Stroke Unit care includes continuous electrocardiogram monitoring (CEM) but the optimal exploitation of the recorded ECG traces is controversial. In this retrospective single-center study, we investigated whether an automated analysis of continuous electrocardiogram monitoring (ACEM), based on a software algorithm, accelerates the detection of AF in patients admitted to our Stroke Unit compared to the routine CEM. Methods: Patients with acute ischemic stroke or transient ischemic attack were consecutively enrolled. After a 12-channel ECG on admission, all patients received CEM. Additionally, in the second phase of the study the CEM traces of the patients underwent ACEM analysis using a software algorithm for AF detection. Patients with history of AF or with AF on the admission ECG were excluded. Results: The CEM (n = 208) and ACEM cohorts (n= 114) did not differ significantly regarding risk factors, duration of monitoring and length of admission. We found a higher rate of newly-detected AF in the ACEM cohort compared to the CEM cohort (15.8% versus 10.1%, P < .001). Median time to first detection of AF was shorter in the ACEM compared to the CEM cohort [10 hours (IQR 0–23) versus 46.50 hours (IQR 0–108.25), P < .001]. Conclusions: ACEM accelerates the detection of AF in patients with stroke compared with the routine CEM. Further evidences are required to confirm the increased rate of AF detected using ACEM. © 2020

Background: Controversial evidence suggests that right insular stroke may be associated with worse outcomes compared to the left insular ischemic lesion. Objectives: We investigated whether lateralization of insular stroke is associated with early and late outcome in terms of in-hospital complications, stroke recurrence, cardiovascular events, and death. Methods: Data were prospectively collected from the Athens Stroke Registry. Insular cortex involvement was identified based on brain CT scans or MRI images. Patients were followed up prospectively at 1, 3, 6 months after hospital discharge and yearly thereafter up to 5-years or until death. The assessed outcomes were in-hospital complications, functional outcome assessed by the modified Rankin Scale, stroke recurrence, cardiovascular events, and death. Cox-regression analysis was performed to estimate the cumulative probability of each outcome according to the lateralization of insular strokes. Results: Among the 1212 patients, 650 had left insular stroke involvement and 562 had right. New onset of in-hospital atrial fibrillation was similar between right and left insular strokes (11.6% versus 12.9%, P = .484). During the 5-year follow-up sudden death occurred in 21 (3.7%) patients with right insular compared to 30 (4.6%) with left insular stroke (P = .476). There was no difference between left and right insular strokes regarding mortality (adjusted odds ratio [OR]: .92, 95% confidence interval [CI]: .80-1.06), stroke recurrence (4.3% versus 4.9%; adjusted OR: .81 95% CI: .58-1.13), cardiovascular events, and sudden death (adjusted OR: .99, 95% CI: .76-1.29) and on death and dependency (adjusted OR: .88, 95% CI: .75-1.02) during a 5-year follow up. Conclusions: Lateralization of insular ischemic stroke involvement is not associated with stroke outcomes. © 2019 Elsevier Inc.

Background and Purpose - Emboli in embolic stroke of undetermined source (ESUS) may originate from various potential embolic sources (PES), some of which may respond better to anticoagulation, whereas others to antiplatelets. We analyzed whether rivaroxaban is associated with reduction of recurrent stroke compared with aspirin in patients with ESUS across different PES and by number of PES. Methods - We assessed the presence/absence of each PES (atrial cardiopathy, atrial fibrillation, arterial atherosclerosis, left ventricular dysfunction, cardiac valvulopathy, patent foramen ovale, cancer) in NAVIGATE-ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) participants. Prevalence of each PES, as well as treatment effect and risk of event for each PES were determined. Results by number of PES were also determined. The outcomes were ischemic stroke, all-cause mortality, cardiovascular mortality, and myocardial infarction. Results - In 7213 patients (38% women, mean age 67years) followed for a median of 11 months, the 3 most prevalent PES were atrial cardiopathy (37%), left ventricular disease (36%), and arterial atherosclerosis (29%). Forty-one percent of all patients had multiple PES, with 15% having ≥3 PES. None or a single PES was present in 23% and 36%, respectively. Recurrent ischemic stroke risk was similar for rivaroxaban- and aspirin-assigned patients for each PES, except for those with cardiac valvular disease which was marginally higher in rivaroxaban-assigned patients (hazard ratio, 1.8 [95% CI, 1.0-3.0]). All-cause mortality risks were similar across treatment groups for each PES while too few myocardial infarctions and cardiovascular deaths occurred for meaningful assessment. Increasing number of PES was not associated with increased stroke recurrence nor all-cause mortality, and outcomes did not vary between rivaroxaban- and aspirin-assigned patients by number of PES. Conclusions - A large proportion of patients with ESUS had multiple PES which could explain the neutral results of NAVIGATE-ESUS. Recurrence rates between rivaroxaban- and aspirin-assigned patients were similar across the spectrum of PES. Registration - URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909. © 2020 Lippincott Williams and Wilkins. All rights reserved.

OBJECTIVE: To compare the efficacy and safety of oral anticoagulants vs antiplatelets in patients with stroke and atherosclerotic plaques in the aortic arch or cervical or intracranial arteries, collectively described as supracardiac atherosclerosis. METHODS: We searched PubMed and Scopus until August 28, 2019, for randomized trials comparing oral anticoagulants vs antiplatelets in patients with stroke and supracardiac atherosclerosis using the terms "anticoagulant or anticoagulation" and "antiplatelet or aspirin" and "randomized controlled trial or RCT" and "stroke or cerebral ischemia" and "aortic or carotid or vertebrobasilar or intracranial or atherosclerosis or stenosis or arterial." Four outcomes were assessed: recurrent ischemic stroke, major ischemic event or death, major bleeding, and intracranial bleeding. Treatment effects (relative risk [RR] and 95% confidence interval [CI]) were estimated by meta-analysis using random-effects models. RESULTS: Among 1,117 articles identified in the literature search, results from 10 randomized controlled trials involving 6,068 patients with stroke/TIA with supracardiac atherosclerosis were included in the meta-analysis. Recurrent ischemic stroke rates were 2.94 per 100 patient-years in the anticoagulant-assigned patients vs 3.30 per 100 patient-years in the antiplatelet-assigned patients (RR, 0.91; 95% CI, 0.70-1.18 for the SJ estimator, I2 = 26%). Major ischemic event or death rates were 4.39 per 100 patient-years in anticoagulant-assigned patients vs 4.32 in antiplatelet-assigned patients (RR, 1.03; 95% CI, 0.79-1.35; I2 = 54.5%). Major bleeding rates were 2.88 per 100 patient-years in anticoagulant-assigned patients vs 0.82 in antiplatelet-assigned patients (RR, 3.21; 95% CI, 1.96-5.24; I2 = 46%). CONCLUSION: This systematic review and meta-analysis showed that anticoagulant-assigned patients with stroke and supracardiac atherosclerosis were not at different risk of ischemic stroke recurrence and increased risk of major bleeding compared to antiplatelet-assigned patients. © 2020 American Academy of Neurology.

The aim of this study was to evaluate accessibility of stroke patients to optimal healthcare technology in Greece. Methods: The study population consisted of 313 first ever stroke patients derived from the 'Stroke Units Necessity for Patients, SUN4P' registry. Descriptive statistics were used, to present patients' characteristics and resources utilization Results: The vast majority of patients (91.7%) conducted a CT scan during the acute phase (within the first 24hours). Almost, (65%) were admitted to wards of Internal Medicine Departments, whereas only 21% of patients were admitted to a Stroke Unit. Of note, a total of 6.9% of ischemic stroke patients received intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rtPA). Conclusions: Preliminary results from SUN4P underline the urgent necessity for the re-organization of acute stroke care in Greece, as rates of admissions to stroke units and rtPA treatment during the acute phase are currently below optimal. © 2020 The authors and IOS Press.

SUN4Patients is an observational study for the monitoring of patients with first ever acute stroke. For the support of this study, an online platform has been developed which facilitates the collection of various information related to hospital discharge, health services utilization and loss of productivity of the patients. This paper presents the main characteristics of the platform and the methodology followed for its design and implementation. © 2020 The authors and IOS Press.

Background and aims: To reassess the effect of statin-based lipid-lowering therapy on ischemic stroke in primary and secondary prevention trials with regard to achieved levels of low-density lipoprotein-cholesterol in view of the availability of novel potent hypolipidemic agents. Methods: English literature was searched (up to November 2018) for publications restricted to trials with a minimum enrolment of 1000 and 500 subjects for primary and secondary prevention, respectively, meeting the following criteria: adult population, randomized controlled design, and recorded outcome data on ischemic stroke events. Data were meta-analyzed and curve-estimation procedure was applied to estimate regression statistics and produce related plots. Results: Four primary prevention trials and four secondary prevention trials fulfilled the eligibility criteria. Lipid-lowering therapy was associated with a lower risk of ischemic stroke in primary (risk ratio, RR 0.70, 95% confidence interval, CI, 0.60–0.82; p < 0.001) and in the secondary prevention setting (RR 0.80, 95% CI 0.70–0.90; p < 0.001). Curve-estimation procedure revealed a linear relationship between the absolute risk reduction of ischemic stroke and active treatment-achieved low-density lipoprotein-cholesterol levels in secondary prevention (adjusted R-square 0.90) in support of “the lower the better” hypothesis for stroke survivors. On the other hand, the cubic model followed the observed data well in primary prevention (adjusted R-square 0.98), indicating greater absolute risk reduction in high-risk cardiovascular disease-free individuals. Conclusions: Statin-based lipid-lowering is effective both for primary and secondary prevention of ischemic stroke. Most benefit derives from targeting disease-free individuals at high cardiovascular risk, and by achieving low treatment targets for low-density lipoprotein-cholesterol in stroke survivors. © 2019 World Stroke Organization.

Background and Purpose- It is unclear whether treatment with anticoagulants or antiplatelets is the optimal strategy in patients with stroke or transient ischemic attack of undetermined cause and patent foramen ovale that is not percutaneously closed. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare anticoagulant or antiplatelet treatment in this population. Methods- We searched PubMed until July 16, 2019 for trials comparing anticoagulants and antiplatelet treatment in patients with stroke/transient ischemic attack and medically treated patent foramen ovale using the terms: "cryptogenic or embolic stroke of undetermined source" and "stroke or cerebrovascular accident or transient ischemic attack" and "patent foramen ovale or patent foramen ovale or paradoxical embolism" and "trial or study" and "antithrombotic or anticoagulant or antiplatelet." The outcomes assessed were stroke recurrence, major bleeding, and the composite end point of stroke recurrence or major bleeding. We used 3 random-effects models: (1) a reference model based on the inverse variance method with the Sidik and Jonkman heterogeneity estimator; (2) a strict model, implementing the Hartung and Knapp method; and (3) a commonly used Bayesian model with a prior that assumes moderate to large between-study variance. Results- Among 112 articles identified in the literature search, 5 randomized controlled trials were included in the meta-analysis (1720 patients, mean follow-up 2.3±0.5 years). Stroke recurrence occurred at a rate of 1.73 per 100 patient-years in anticoagulant-assigned patients and 2.39 in antiplatelet-assigned patients (hazard ratio, 0.68; 95% CI, 0.32-1.48 for the Sidik and Jonkman estimator). Major bleeding occurred at a rate of 1.16 per 100 patient-years in anticoagulant-assigned patients and 0.68 in antiplatelet-assigned patients (hazard ratio, 1.61; 95% CI, 0.72-3.59 for the Sidik and Jonkman estimator). The composite outcome occurred in 52 anticoagulant-assigned and 54 antiplatelet-assigned patients (odds ratio, 1.05; 95% CI, 0.65-1.70 for the Sidik and Jonkman estimator). Conclusions- We cannot exclude a large reduction of stroke recurrence in anticoagulant-assigned patients compared with antiplatelet-assigned, without significant differences in major bleeding. An adequately powered randomized controlled trial of a non-vitamin K antagonist versus aspirin is warranted.

Patients with ischemic stroke or transient ischemic attack and non-valvular atrial fibrillation have a high risk of recurrent stroke and other vascular events. The aim of this guideline is to provide recommendations on antithrombotic medication for secondary prevention of stroke and other vascular outcomes in these patients. The working group identified questions and outcomes, graded evidence, and developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach and the European Stroke Organisation (ESO) standard operating procedure for guidelines. The guideline was reviewed and approved by the ESO guideline board and the ESO executive committee. In patients with atrial fibrillation and previous stroke or transient ischemic attack, oral anticoagulants reduce the risk of recurrence over antiplatelets or no antithrombotic treatment. Non-vitamin K antagonist oral anticoagulants are preferred over vitamin K antagonists because they have a lower risk of major bleeding and death. Recommendations are weak regarding timing of treatment, (re-)starting oral anticoagulants in patients with previous intracerebral haemorrhage, and treatment in specific patient subgroups of those of older age, with cognitive impairment, renal failure or small vessel disease, because of a lack of strong evidence. In conclusion, for patients with atrial fibrillation and ischemic stroke or transient ischemic attack, non-vitamin K antagonist oral anticoagulants are the preferred treatment for secondary prevention of recurrent stroke or thromboembolism. Further research is required to determine the best timing for initiating oral anticoagulants after an acute ischemic stroke, whether or not oral anticoagulants should be (re)started in patients with a history of intracerebral haemorrhage, and the best secondary preventive treatment in specific subgroups. © European Stroke Organisation 2019.

Background: Stratification of overall vascular risk in patients with ischemic stroke is important as it may guide management decisions. Currently available schemes have only modest prognostic accuracy. The TRA2°P score aids in vascular risk stratification in patients with previous myocardial infarction (MI). Aim: We investigated whether the prognostic performance of TRA2°P can be extended in patients with ischemic stroke and whether it can improve the risk stratification made by CHA2DS2VASc and Essen-Stroke-Risk-Score (ESRS). Methods: We analyzed the Athens Stroke Registry using Kaplan-Meier survival and Cox-regression analyses to assess if TRA2°P (in different categorizations) predicts the composite endpoint of stroke recurrence, MI or cardiovascular death. We compared its incremental predictive value over CHA2DS2-VASc and ESRS and calculated continuous net reclassification indices (cNRI). Results: In 2833 patients (followed for 9278 patient-years) and 776 events, there was decreased survival probability for TRA2°P-based high-risk patients compared to low-risk (log-rank-test P < .001), but the discriminatory power for the occurrence of the composite endpoint was only modest (Harrell's-C:.566, 95% CI:.545-.587). Combined with ESRS, TRA2°P conferred incremental discrimination (Harrell's-C:.544, 95% CI:.513-.574 versus .574, 95% CI:.543-.605 respectively, P = .049) and reclassification value (cNRI = 9.8%, P = .02). Combined with CHA2DS2-VASc, TRA2°P did not improve discrimination (Harell's-C:.578, 95% CI: .547-.608 versus .585, 95% CI:.554-.616, P = .738). Conclusion: The currently available prognostic scores have generally low performance to predict the overall cardiovascular risk in ischemic stroke patients. Further research is needed to improve vascular risk stratification in ischemic stroke patients. © 2019 Elsevier Inc.

Background and Purpose- The sources of emboli in patients with embolic stroke of undetermined source (ESUS) are multiple and may not respond uniformly to anticoagulation. In this exploratory subgroup analysis of patients with carotid atherosclerosis in the NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism)-ESUS trial, we assessed whether the treatment effect in this subgroup is consistent with the overall trial population and investigated the association of carotid atherosclerosis with recurrent ischemic stroke. Methods- Carotid atherosclerosis was analyzed either as the presence of mild (ie, 20%-49%) atherosclerotic stenosis or, separately, as the presence of carotid plaque. Primary efficacy outcome was ischemic stroke recurrence. Safety outcomes were major bleeding and symptomatic intracerebral bleeding. Results- Carotid plaque was present in 40% of participants and mild carotid stenosis in 11%. There was no significant difference in ischemic stroke recurrence between rivaroxaban- and aspirin-treated patients among 490 patients with carotid stenosis (5.0 versus 5.9/100 patient-years, respectively, hazard ratio [HR], 0.85; 95% CI, 0.39-1.87; P for interaction of treatment effect with patients without carotid stenosis 0.78) and among 2905 patients with carotid plaques (5.9 versus 4.9/100 patient-years, respectively, HR, 1.20; 95% CI, 0.86-1.68; P for interaction of treatment effect with patients without carotid stenosis 0.2). Among patients with carotid plaque, major bleeding was more frequent in rivaroxaban-treated patients compared with aspirin-treated (2.0 versus 0.5/100 patient-years, HR, 3.75; 95% CI, 1.63-8.65). Patients with carotid stenosis had similar rate of ischemic stroke recurrence compared with those without (5.4 versus 4.9/100 patient-years, respectively, HR, 1.11; 95% CI, 0.73-1.69), but there was a strong trend of higher rate of ischemic stroke recurrence in patients with carotid plaque compared with those without (5.4 versus 4.3/100 patient-years, respectively, HR, 1.23; 95% CI, 0.99-1.54). Conclusions- In ESUS patients with carotid atherosclerosis, we found no difference in efficacy between rivaroxaban and aspirin for prevention of recurrent stroke, but aspirin was safer, consistent with the overall trial results. Carotid plaque was much more often present ipsilateral to the qualifying ischemic stroke than contralateral, supporting an important etiological role of nonstenotic carotid disease in ESUS.

WOS: 000434263000007, PubMed: 29766772, BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P, BayerBayer AG; Janssen Research and Development, Supported by Bayer and Janssen Research and Development.

This document presents the consensus recommendations of the Hellenic Stroke Organization which can be of assistance to the treating stroke physicians. © 2017, Springer-Verlag GmbH Germany.