Post-event follow-up costs in patients with atherosclerotic cardiovascular disease in Spain.

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is one of the main causes of morbidity and mortality in developed countries and entails high resources use and costs for health systems. The risk of suffering future cardiovascular (CV) events and the consequent resources use is higher in those patients who have already had a previous cardiovascular event. The objective of the study was to determine the average annual cost of patients with a new or recurrent atherosclerotic CV event during the 2 years after the event. Methodology: Retrospective observational study of electronic medical records of patients from the BIG-PAC® database (7 integrated health areas of 7 Autonomous Communities; n = 1.8 million). Patients with a new or recurrent episode of ASCVD (angina, acute myocardial infarction, transient ischemic attack, stroke, or peripheral arterial disease) between 1-Jan-2017 and 31-Dec-2018 were included. The resources use within two years of the diagnosis was estimated in order to estimate the average cost of patient follow-up. Results: A total of 26,976 patients with an ASCVD episode were identified during the recruitment period; Out of them, 6,798 had a recurrent event during the follow-up period and 2,414 died. The average costs per patient were €11,171 during the first year and €9,944 during the second year. Discussion: Patients with ASCVD represent a significant economic burden for the health system and for society. Despite the perception that drug costs in the follow-up of chronic patients imply a high percentage of the costs, these accounted for only one tenth of the total amount. Implementing preventive programs and increasing the control of cardiovascular risk factors may have a significant social and health impact by helping to reduce mortality and costs for the Spanish National Health System. The costs derived from pharmacological treatments were obtained from the NHS pricing nomenclator database (https://www.sanidad.gob.es/profesionales/nomenclator.do).

[Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO) y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventana de oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos del embarazo y riesgo de enfermedad vascular.] / Consensus document of the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Opportunity window: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular disease.

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs), such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational age and/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developing vascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheral vascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOs when assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact, adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the other hand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality. Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOs could strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients. Various healthcare system options exist to improve the transition of care for women with APOs between different healthcare professionals and implement long-term VR reduction strategies. One potential process could involve incorporating the fourth-trimester concept into clinical recommendations and healthcare policies.

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE), tales como son los trastornos hipertensivos, el parto pretérmino, la diabetes gestacional, los defectos en el crecimiento fetal (feto pequeño para la edad gestacional y/o restricción del crecimiento), el desprendimiento de placenta y la pérdida fetal, y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura: cardiopatía coronaria, accidente cerebrovascular, enfermedad vascular periférica e insuficiencia cardíaca. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo y/o postparto y manteniéndolo a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto del cuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.

Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO) y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventana de oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos del embarazo y riesgo de enfermedad vascular / Consensus document of the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Opportunity window: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular disease

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE), tales como son los trastornos hipertensivos, el parto pretérmino, la diabetes gestacional, los defectos en el crecimiento fetal (feto pequeño para la edad gestacional y/o restricción del crecimiento), el desprendimiento de placenta y la pérdida fetal, y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura: cardiopatía coronaria, accidente cerebrovascular, enfermedad vascular periférica e insuficiencia cardíaca. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo y/o postparto y manteniéndolo a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto delcuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.(AU)

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs), such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational age and/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developing vascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheral vascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOs when assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact, adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the other hand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality.Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOs could strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients. Various healthcare system options exist to improve the transition of care for women with APOs between different healthcare professionals and implement longterm VR reduction strategies. One potential process could involve incorporating the fourth-trimester concept into clinical recommendations and healthcare policies.(AU)

Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment: A Phase 1/2 Randomized Clinical Trial.

Importance: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers. Objective: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. Design, Setting, and Participants: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT. Interventions: In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated. Main Outcomes and Measures: The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score). Results: In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:√2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 patients (36%) receiving ApTOLL, 0.05 mg/kg (11 deaths [26.2%], 3 sICH [7.2%], 2 malignant strokes [4.8%], and 2 recurrent strokes [4.8%]); and in 6 of 42 patients (14%) receiving ApTOLL, 0.2 mg/kg (2 deaths [4.8%], 2 sICH [4.8%], and 3 recurrent strokes [7.1%]). ApTOLL, 0.2 mg/kg, was associated with lower NIHSS score at 72 hours (mean difference log-transformed vs placebo, -45%; 95% CI, -67% to -10%), smaller final infarct volume (mean difference log-transformed vs placebo, -42%; 95% CI, -66% to 1%), and lower degrees of disability at 90 days (common odds ratio for a better outcome vs placebo, 2.44; 95% CI, 1.76 to 5.00). Conclusions and Relevance: In acute ischemic stroke, 0.2 mg/kg of ApTOLL administered within 6 hours of onset in combination with EVT was safe and associated with a potential meaningful clinical effect, reducing mortality and disability at 90 days compared with placebo. These preliminary findings await confirmation from larger pivotal trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04734548.

Depression in Major Neurodegenerative Diseases and Strokes: A Critical Review of Similarities and Differences among Neurological Disorders.

Depression and anxiety are highly prevalent in most neurological disorders and can have a major impact on the patient's disability and quality of life. However, mostly due to the heterogeneity of symptoms and the complexity of the underlying comorbidities, depression can be difficult to diagnose, resulting in limited recognition and in undertreatment. The early detection and treatment of depression simultaneously with the neurological disorder is key to avoiding deterioration and further disability. Although the neurologist should be able to identify and treat depression initially, a neuropsychiatry team should be available for severe cases and those who are unresponsive to treatment. Neurologists should be also aware that in neurodegenerative diseases, such as Alzheimer's or Parkinson's, different depression symptoms could develop at different stages of the disease. The treatment options for depression in neurological diseases include drugs, cognitive-behavioral therapy, and somatic interventions, among others, but often, the evidence-based efficacy is limited and the results are highly variable. Here, we review recent research on the diagnosis and treatment of depression in the context of Alzheimer's disease, Parkinson's disease, and strokes, with the aim of identifying common approaches and solutions for its initial management by the neurologist.

Treatment patterns and use of healthcare resources of patients with atherosclerotic cardiovascular disease and hypercholesterolemia and patients with familial hypercholesterolemia in Spain: Protocol of the Reality study.

Background: Atherosclerotic cardiovascular diseases (ASCVD) and dyslipidemia are associated to a higher risk of cardiovascular events, mortality, use of healthcare resources and costs. In Spain, the evidence about the administration of lipid-lowering treatments in clinical practice, and their clinical effectiveness in patients with ASCVD and hypercholesterolemia and patients with FH is scarce. Therefore, a multidisciplinary working group of cardiologists, family physicians, internal medicine specialists and neurologists was gathered for the Reality study. The aim of this study is to describe the demographic and clinical characteristics, comorbidities, and concomitant medication of patients with ASCVD and hypercholesterolemia and of patients with familial hypercholesterolemia (FH). The use of healthcare resources and costs associated to the management of these diseases after their diagnosis were also considered. Methods: This is an observational and retrospective study, based on the BIG-PAC® database, which includes the electronic medical registries (EMRs) of 1.8 million people from 7 Autonomous Communities in Spain (including public primary care centers and hospitals). The study includes patients who had a new or recurrent episode of ASCVD during the recruitment period (from 01/01/2017 to 31/12/2018). The index date will be defined as the date of the ASCVD event, and the follow-up period will be 24 months. According to their first diagnosis in the database, patients will be classified as ASCVD (5 groups: stable/unstable angina, acute myocardial infarction, ischemic stroke, transient ischemic attack, and peripheral arterial disease) or FH. Discussion: This study aims to analyze the treatment patterns and use of healthcare resources of ASCVD and FH in Spain. The prevalence of these disorders will also be estimated. Due to the high morbidity and mortality associated with these diseases, it is expected that our study will provide useful information for healthcare systems and decision makers to improve the management of these disabling diseases.

[Thrombosis with Thrombocytopenia Syndrome following adenovirus vector-based vaccines to prevent COVID-19: epidemiology and clinical presentation in Spain]. / Síndrome de Trombosis con Trombocitopenia asociado a vacunas de adenovirus frente a la COVID-19: epidemiología y presentación clínica de la serie española.

BACKGROUND: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain. METHODS: We included all venous or arterial thrombosis with thrombocytopenia following adenovirus vector-based vaccines (AstraZeneca or Janssen) to prevent COVID-19 disease between February 1st and September 26th, 2021. We describe the crude rate and the standardized morbidity ratio. We assessed the predictors of mortality. RESULTS: Sixty-one cases were reported and 45 fulfilled eligibility criteria, 82% women. The crude TTS rate was 4/1,000,000 doses and 14-15/1,000,000 doses between 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 higher than the expected in patients younger than 49 years. Symptoms started 10 (interquartile range (IQR): 7-14) days after vaccination. Eighty percent (95% confidence interval (CI): 65-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (95% CI: 49-78%) had D-dimer >2000 ng/mL. Patients had multiple location thrombosis in 36% and fatal outcome in 24% cases. A platelet nadir <50,000 /µL (odds ratio (OR): 7.4; CI 95%: 1.2-47.5) and intracranial hemorrhage (OR: 7.9; IC95%: 1.3-47.0) were associated with fatal outcome. CONCLUSION: TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and/or D-dimer increase.

Cav-1 Protein Levels in Serum and Infarcted Brain Correlate with Hemorrhagic Volume in a Mouse Model of Thromboembolic Stroke, Independently of rt-PA Administration.

Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is currently the only FDA-approved drug for acute ischemic stroke. However, its administration is still limited due to the associated increased risk of hemorrhagic transformation (HT). rt-PA may exacerbate blood-brain barrier (BBB) injury by several mechanisms that have not been fully elucidated. Caveolin-1 (Cav-1), a major structural protein of caveolae, has been linked to the endothelial barrier function. The effects of rt-PA on Cav-1 expression remain largely unknown. Here, Cav-1 protein expression after ischemic conditions, with or without rt-PA administration, was analyzed in a murine thromboembolic middle cerebral artery occlusion (MCAO) and in brain microvascular endothelial bEnd.3 cells subjected to oxygen/glucose deprivation (OGD). Our results show that Cav-1 is overexpressed in endothelial cells of infarcted area and in bEnd.3 cell line after ischemia but there is disagreement regarding rt-PA effects on Cav-1 expression between both experimental models. Delayed rt-PA administration significantly reduced Cav-1 total levels from 24 to 72 h after reoxygenation and increased pCav-1/Cav-1 at 72 h in the bEnd.3 cells while it did not modify Cav-1 immunoreactivity in the infarcted area at 24 h post-MCAO. Importantly, tissue Cav-1 positively correlated with Cav-1 serum levels at 24 h post-MCAO and negatively correlated with the volume of hemorrhage after infarction, the latter supporting a protective role of Cav-1 in cerebral ischemia. In addition, the negative association between baseline serum Cav-1 levels and hemorrhagic volume points to a potential usefulness of baseline serum Cav-1 levels to predict hemorrhagic volume, independently of rt-PA administration.

RP11-362K2.2:RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis.

Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 × 10-8) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10-8) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer's disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-ß, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.

Delayed Neurological Improvement After Full Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke.

Background and Purpose: We aimed to determine the prevalence and predictors of delayed neurological improvement (DNI) after complete endovascular reperfusion in anterior circulation acute ischemic stroke (AIS). Methods: Retrospective analysis of an online multicenter prospective reperfusion registry of patients with consecutive anterior circulation AIS treated with endovascular thrombectomy (EVT) from January 2018 to June 2019 in tertiary stroke centers of the NORDICTUS (NORD-Spain Network for Research and Innovation in ICTUS) network. We included patients with AIS with a proximal occlusion in whom a modified Thrombolysis in Cerebral Infarction 3 reperfusion pattern was obtained. DNI was defined if, despite absence of early neurological improvement during the first 24 hours, patients achieved functional independence on day 90. Clinical and radiological variables obtained before EVT were analyzed as potential predictors of DNI. Results: Of 1565 patients with consecutive AIS treated with EVT, 1381 had proximal anterior circulation occlusions, 803 (58%) of whom achieved a modified Thrombolysis in Cerebral Infarction 3. Of these, 628 patients fulfilled all selection criteria and were included in the study. Mean age was 73.8 years, 323 (51.4%) were female, and median baseline National Institutes of Health Stroke Scale was 16. Absence of early neurological improvement was observed in 142 (22.6%) patients; 32 of these (22.5%) achieved good long-term outcome and constitute the DNI group. Predictors of DNI in multivariable-adjusted logistic regression were male sex (odds ratio, 6.4 [95% CI, 2.1­22.3] P=0.002), lower pre-EVT National Institutes of Health Stroke Scale score (odds ratio, 1.4 [95% CI, 1.2­1.5], P<0.001), and intravenous thrombolysis (odds ratio, 9.1 [95% CI, 2.7­30.90], P<0.001). Conclusions: One-quarter of patients with anterior circulation AIS who do not clinically improve within the first 24 hours after complete cerebral endovascular recanalization will achieve long-term functional independence, regardless of the poor early clinical course. Male sex, lower initial clinical severity, and use of intravenous thrombolysis before EVT predicted this clinical pattern.

Single nucleotide variations in ZBTB46 are associated with post-thrombolytic parenchymal haematoma.

Haemorrhagic transformation is a complication of recombinant tissue-plasminogen activator treatment. The most severe form, parenchymal haematoma, can result in neurological deterioration, disability, and death. Our objective was to identify single nucleotide variations associated with a risk of parenchymal haematoma following thrombolytic therapy in patients with acute ischaemic stroke. A fixed-effect genome-wide meta-analysis was performed combining two-stage genome-wide association studies (n = 1904). The discovery stage (three cohorts) comprised 1324 ischaemic stroke individuals, 5.4% of whom had a parenchymal haematoma. Genetic variants yielding a P-value < 0.05 1 × 10-5 were analysed in the validation stage (six cohorts), formed by 580 ischaemic stroke patients with 12.1% haemorrhagic events. All participants received recombinant tissue-plasminogen activator; cases were parenchymal haematoma type 1 or 2 as defined by the European Cooperative Acute Stroke Study (ECASS) criteria. Genome-wide significant findings (P < 5 × 10-8) were characterized by in silico functional annotation, gene expression, and DNA regulatory elements. We analysed 7 989 272 single nucleotide polymorphisms and identified a genome-wide association locus on chromosome 20 in the discovery cohort; functional annotation indicated that the ZBTB46 gene was driving the association for chromosome 20. The top single nucleotide polymorphism was rs76484331 in the ZBTB46 gene [P = 2.49 × 10-8; odds ratio (OR): 11.21; 95% confidence interval (CI): 4.82-26.55]. In the replication cohort (n = 580), the rs76484331 polymorphism was associated with parenchymal haematoma (P = 0.01), and the overall association after meta-analysis increased (P = 1.61 × 10-8; OR: 5.84; 95% CI: 3.16-10.76). ZBTB46 codes the zinc finger and BTB domain-containing protein 46 that acts as a transcription factor. In silico studies indicated that ZBTB46 is expressed in brain tissue by neurons and endothelial cells. Moreover, rs76484331 interacts with the promoter sites located at 20q13. In conclusion, we identified single nucleotide variants in the ZBTB46 gene associated with a higher risk of parenchymal haematoma following recombinant tissue-plasminogen activator treatment.

Impact of Mediterranean Diet prior to Stroke on the Prognosis of Patients Undergoing Endovascular Treatment.

INTRODUCTION: Mediterranean diet (MeDiet) has been associated with lower risk of stroke. Additionally, animal models suggested that some components of MeDiet are associated with better outcomes after ischemic stroke (IS). We aimed to evaluate the association between global adherence to the MeDiet and the consumption of particular components of the MeDiet with stroke outcomes. MATERIAL AND METHODS: Multicenter observational study of consecutive IS patients treated with endovascular therapy. Inclusion criteria were large anterior circulation vessel occlusion and pre-stroke modified Rankin scale (mRS) <2. Adherence to MeDiet prior to stroke was evaluated using MEDAS 14-item scale. We evaluated the total score and also individual components of the scale. Clinical, radiological, and prognostic variables were collected. Good functional prognosis was considered as mRS ≤2 and complete recanalization as thrombolysis in cerebral infarction 3. RESULTS: From January 1 to October 30, 2018, 239 patients were included (mean age 71 years, 48% women, median baseline NIHSS 16). Median MEDAS scale was 8 points (7-10). Patients with a higher adherence to MeDiet had significantly lower total and LDL-cholesterol levels. Total adherence score was not associated with stroke outcomes. In multivariate analyses, consumption of olive oil as the principal source of fat was independently associated with good functional outcome at 3 months, OR 3.2 (1.1-10.1) and daily consumption of wine was independently associated with complete recanalization, OR 2.0 (1.1-3.8). CONCLUSIONS: Our study suggests that some components of MeDiet, such as olive oil and wine consumption, are related to better prognosis after stroke. More studies are needed to confirm these findings.

Blood Biomarker Panels for the Early Prediction of Stroke-Associated Complications.

Background Acute decompensated heart failure (ADHF) and respiratory tract infections (RTIs) are potentially life-threatening complications in patients experiencing stroke during hospitalization. We aimed to test whether blood biomarker panels might predict these complications early after admission. Methods and Results Nine hundred thirty-eight patients experiencing ischemic stroke were prospectively recruited in the Stroke-Chip study. Post-stroke complications during hospitalization were retrospectively evaluated. Blood samples were drawn within 6 hours after stroke onset, and 14 biomarkers were analyzed by immunoassays. Biomarker values were normalized using log-transformation and Z score. PanelomiX algorithm was used to select panels with the best accuracy for predicting ADHF and RTI. Logistic regression models were constructed with the clinical variables and the biomarker panels. The additional predictive value of the panels compared with the clinical model alone was evaluated by receiver operating characteristic curves. An internal validation through a 10-fold cross-validation with 3 repeats was performed. ADHF and RTI occurred in 19 (2%) and 86 (9.1%) cases, respectively. Three-biomarker panels were developed as predictors: vascular adhesion protein-1 >5.67, NT-proBNP (N-terminal pro-B-type natriuretic peptide) >4.98 and d-dimer >5.38 (sensitivity, 89.5%; specificity, 71.7%) for ADHF; and interleukin-6 >3.97, von Willebrand factor >3.67, and d-dimer >4.58 (sensitivity, 82.6%; specificity, 59.8%) for RTI. Both panels independently predicted stroke complications (panel for ADHF: odds ratio [OR] [95% CI], 10.1 [3-52.2]; panel for RTI: OR, 3.73 [1.95-7.14]) after adjustment by clinical confounders. The addition of the panel to clinical predictors significantly improved areas under the curve of the receiver operating characteristic curves in both cases. Conclusions Blood biomarkers could be useful for the early prediction of ADHF and RTI. Future studies should assess the usefulness of these panels in front of patients experiencing stroke with respiratory symptoms such as dyspnea.

Stroke care during the COVID-19 outbreak in Spain: the experience of Spanish stroke units.

BACKGROUND AND PURPOSE: Spain has been heavily affected by COVID-19. Reallocation of resources for managing the outbreak might have caused a disruption in stroke care. This study analyses the impact on stroke care of reorganising the healthcare system in response to the first COVID-19 outbreak peak in Spain and the strategies adopted by Spanish stroke units to deal with this impact. MATERIALS AND METHODS: We obtained data from a structured survey sent to the responsible of stroke units across the country. We recorded the number of strokes, stroke code activations, intravenous thrombolysis treatments and mechanical thrombectomies during February and March 2019 and 2020. We also collected information on the impact on workflow metrics and on the availability of specialised neurological care and rehabilitation treatments, the characteristics of stroke care for patients with SARS-CoV-2 infection and the impact on human resources. We compared the activity data between 2019 and 2020 and the information on activity and impact on stroke care between regions classified according to the disease incidence rate. RESULTS: Fifty-seven (75%) of all stroke units in Spain responded to the survey. There was an overall reduction in admissions for all stroke types during the outbreak's peak and in the number of stroke code activations and intravenous thrombolysis treatments, results that were independent of the COVID-19 incidence rate. Participants reported a delay in workflow metrics and a reduction of admissions to stroke units, outpatient clinics and rehabilitation therapies. Specific pathways and protocols for managing stroke patients with SARS-CoV-2 infection have been established. CONCLUSION: The COVID-19 outbreak has jeopardised all phases of stroke care. As a consequence, some patients with stroke did not receive adequate treatment.

Oral Anticoagulation and Risk of Symptomatic Hemorrhagic Transformation in Stroke Patients Treated With Mechanical Thrombectomy: Data From the Nordictus Registry.

Introduction: We aimed to evaluate if prior oral anticoagulation (OAC) and its type determines a greater risk of symptomatic hemorrhagic transformation in patients with acute ischemic stroke (AIS) subjected to mechanical thrombectomy. Materials and Methods: Consecutive patients with AIS included in the prospective reperfusion registry NORDICTUS, a network of tertiary stroke centers in Northern Spain, from January 2017 to December 2019 were included. Prior use of oral anticoagulants, baseline variables, and international normalized ratio (INR) on admission were recorded. Symptomatic intracranial hemorrhage (sICH) was the primary outcome measure. Secondary outcome was the relation between INR and sICH, and we evaluated mortality and functional outcome at 3 months by modified Rankin scale. We compared patients with and without previous OAC and also considered the type of oral anticoagulants. Results: About 1.455 AIS patients were included, of whom 274 (19%) were on OAC, 193 (70%) on vitamin K antagonists (VKA), and 81 (30%) on direct oral anticoagulants (DOACs). Anticoagulated patients were older and had more comorbidities. Eighty-one (5.6%) developed sICH, which was more frequent in the VKA group, but not in DOAC group. OAC with VKA emerged as a predictor of sICH in a multivariate regression model (OR, 1.89 [95% CI, 1.01-3.51], p = 0.04) and was not related to INR level on admission. Prior VKA use was not associated with worse outcome in the multivariate regression model nor with mortality at 3 months. Conclusions: OAC with VKA, but not with DOACs, was an independent predictor of sICH after mechanical thrombectomy. This excess risk was associated neither with INR value by the time thrombectomy was performed, nor with a worse functional outcome or mortality at 3 months.

Blood biomarkers predictive of epilepsy after an acute stroke event.

OBJECTIVE: Blood biomarkers have not been widely investigated in poststroke epilepsy. In this study, we aimed to describe clinical factors and biomarkers present during acute stroke and analyze their association with the development of epilepsy at long term. METHODS: A panel of 14 blood biomarkers was evaluated in patients with ischemic and hemorrhagic stroke. Biomarkers were normalized and standardized using Z-scores. Stroke and epilepsy-related variables were also assessed: stroke severity, determined by National Institutes of Health Stroke Scale (NIHSS) score, stroke type and cause, time from stroke to onset of late seizures, and type of seizure. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with epilepsy. RESULTS: From a cohort of 1115 patients, 895 patients were included. Mean ± standard deviation (SD) age was 72.0 ± 13.1 years, and 57.8% of patients were men. Fifty-one patients (5.7%) developed late seizures, with a median time to onset of 232 days (interquartile range [IQR] 86-491). NIHSS score ≥8 (P < .001, hazard ratio [HR] 4.013, 95% confidence interval [CI] 2.123-7.586) and a history of early onset seizures (P < .001, HR 4.038, 95% CI 1.802-9.045) were factors independently associated with a risk of developing epilepsy. Independent blood biomarkers predictive of epilepsy were high endostatin levels >1.203 (P = .046, HR 4.300, 95% CI 1.028-17.996) and low levels of heat shock 70 kDa protein-8 (Hsc70) <2.496 (P = .006, HR 3.795, 95% CI 1.476-9.760) and S100B <1.364 (P = .001, HR 2.955, 95% CI 1.534-5.491). The risk of epilepsy when these biomarkers were combined increased to 17%. The area under the receiver-operating characteristic (ROC) curve of the predictive model was stronger when clinical variables were combined with blood biomarkers (74.3%, 95% CI 65.2%-83.3%) than when they were used alone (68.9%, 95% CI 60.3%-77.6%). SIGNIFICANCE: Downregulated S100B and Hsc70 and upregulated endostatin may assist in prediction of poststroke epilepsy and may provide additional information to clinical risk factors. In addition, these data are hypothesis-generating for the epileptogenic process.

¿Va a cambiar la neurología tras la pandemia de Covid-19 en los próximos cinco años?. Estudio de enfoque mediante informadores clave / Will neurological care change over the next 5 years due to the COVID-19 pandemic?

INTRODUCCIÓN: La pandemia de Covid-19 va a conllevar cambios en la asistencia neurológica, que no se pueden prever fácilmente a largo plazo. MATERIAL Y MÉTODOS: A través de un modelo de informadores clave, se busca el consenso siendo los encuestados, jefes de servicio de Neurología con conocimiento amplio de la situación al haber actuado durante la pandemia, de cómo va a ser la especialidad en un plazo de cinco años. RESULTADOS: Aunque se obtiene un grado de acuerdo bajo entre encuestados, si se describen acuerdos por consenso a nivel mayor (85%) y menor (70%). Los principales acuerdos se refieren al incremento de precauciones, al uso de la telemedicina, al mantenimiento de las consultas telefónicas, a la reducción de asistencia a las consultas evitando que hayan salas de espera con un número alto de personas, al desarrollo de técnicas docentes no presenciales y a la adaptación en el desarrollo de ensayos clínicos en relación a la visita de los monitores. Sin embargo, no se acuerda que haya cambios en la indicación de exploraciones complementarias, ni en la propia exploración neurológica. CONCLUSIÓN: El método de informadores clave ha permitido conocer que cambios se pueden prever tras la pandemia

INTRODUCTION: The COVID-19 pandemic will give rise to long-term changes in neurological care, which are not easily predictable. MATERIAL AND METHODS: A key informant survey was used to enquire about the changes expected in the specialty over the next 5 years. The survey was completed by heads of neurology departments with broad knowledge of the situation, having been active during the pandemic. RESULTS: Despite a low level of consensus between participants, there was strong (85%) and moderate consensus (70%) about certain subjects, mainly the increase in precautions to be taken, the use of telemedicine and teleconsultations, the reduction of care provided in in-person consultations to avoid the presence of large numbers of people in waiting rooms, the development of remote training solutions, and the changes in monitoring visits during clinical trials. There was consensus that there would be no changes to the indication of complementary testing or neurological examination. CONCLUSION: The key informant survey identified the foreseeable changes in neurological care after the pandemic

Evaluation of long-term rt-PA effects on bEnd.3 endothelial cells under ischemic conditions; changes in ZO-1 expression and glycosylation of the bradykinin B2 receptor.

Recombinant tissue plasminogen activator (rt-PA) has proven effective in the treatment of acute ischemic stroke, despite the increased risk of hemorrhagic transformation (HT), its major associated complication. Although it is known that HT is related to blood brain barrier (BBB) disruption, the underlying mechanisms are not well established. We assessed time-dependent effects of rt-PA on the bEnd.3 murine brain endothelial cell line subjected either to normoxia or to 2.5 h of oxygen and glucose deprivation (OGD), evaluating a longer period than has previously been done, beyond 6 h post-reoxygenation. Parameters of cell viability, metabolic activity, ionic and transcellular permeability, as well as levels of claudin-5, zonula occludens-1 (ZO-1) and bradykinin B2 receptor (B2R) protein expression were analyzed at 24, 48 and 72 h post-reoxygenation with or without the administration of rt-PA. rt-PA treatment increased both the ionic and transcellular permeability until 72 h and did not modify cell viability or metabolic activity or the expression of claudin-5, ZO-1 and B2R under normoxia at any analyzed time. Under OGD conditions, rt-PA exacerbated OGD effects on metabolic activity from 48 to 72 h, increased transcellular permeability from 24 to 72 h, significantly decreased ZO-1 protein levels at the plasma membrane and increased B2R glycosylation at 72 h post-reoxygenation. Our findings suggest that a long-term analysis is necessary to elucidate time-dependent molecular mechanisms associated to BBB breakdown due to rt-PA administration under ischemia. Thus, protective BBB therapies after ischemic stroke and rt-PA treatment should be explored at least until 72 h after OGD and rt-PA administration.

Validation of an automated ASPECTS method on non-contrast computed tomography scans of acute ischemic stroke patients.

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) is a systematic method of assessing the extent of early ischemic change on non-contrast computed tomography in patients with acute ischemic stroke. Our objective was to validate an automated ASPECTS scoring method we recently developed on a large data set. MATERIALS AND METHODS: We retrospectively collected 602 acute ischemic stroke patients' non-contrast computed tomography scans. Expert ASPECTS readings on non-contrast computed tomography were compared to automated ASPECTS. Statistical analyses on the total ASPECTS, region level ASPECTS, and dichotomized ASPECTS (≤4 vs. >4) score were conducted. RESULTS: In total, 602 scans were evaluated and 6020 (602 × 10) ASPECTS regions were scored. Median time from stroke onset to computed tomography was 114 min (interquartile range: 73-183 min). Total ASPECTS for the 602 patients generated by the automated method agreed well with expert readings (intraclass correlation coefficient): 0.65 (95% confidence interval (CI): 0.60-0.69). Region level analysis showed that the automated method yielded accuracy of 81.25%, sensitivity of 61.13% (95% CI: 58.4%-63.8%), specificity of 86.56% (95% CI: 85.6%-87.5%), and area under curve of 0.74 (95% CI: 0.73-0.75). For dichotomized ASPECTS (≤4 vs. >4), the automated method demonstrated sensitivity 97.21% (95% CI: 95.4%-98.4%), specificity 57.81% (95% CI: 44.8%-70.1%), accuracy 93.02%, and area under the curve of 0.78 (95% CI: 0.74-0.81). For each individual region (M1-6, lentiform, insula, and caudate), the automated method demonstrated acceptable performance. CONCLUSION: The automated system we developed approached the stroke expert in performance when scoring ASPECTS on non-contrast computed tomography scans of acute ischemic stroke patients.