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The link between heart and brain continues to be a matter of great interest for the scientific community. One of the most established associations between the two is that the heart is a significant source of emboli and is responsible for 20-25% of all ischemic strokes. The most frequent underlying cause of cardioembolic stroke is atrial fibrillation (AF), a disease that affects almost 3 million people in the USA and 4.5 million in Europe. AF increases the risk of ischemic stroke by a factor of 3 to 5 times. It is estimated that AF is responsible for 15% of all strokes worldwide. A more comprehensive understanding of this association and development of intensive stroke prevention measures are needed, as we know that AF incidence and prevalence will increase over the coming years, becoming one of the largest epidemics and public health challenges we face. more...

Background: The association between cholesterol levels and cerebral edema (CED) or hemorrhagic transformation (HT) as an expressions of blood-brain barrier (BBB) dysfunction after ischemic stroke is not well established. The aim of this study is to determine the association of total cholesterol (TC) levels with the incidence of HT and CED after reperfusion therapies. Methods: We analyzed SITS Thrombolysis and Thrombectomy Registry data from January 2011 to December 2017. We identified patients with data on TC levels at baseline. TC values were categorized in three groups (reference group ⩾200 mg/dl). The two primary outcomes were any parenchymal hemorrhage (PH) and moderate to severe CED on follow up imaging. Secondary outcomes included death and functional independence (mRS 0–2) at 3 months. Multivariable logistic regression analysis adjusted for baseline factors including statin pretreatment was used to assess the association between TC levels and outcomes. Results: Of 35,314 patients with available information on TC levels at baseline, 3372 (9.5%) presented with TC levels ⩽130 mg/dl, 8203 (23.2%) with TC 130–200 mg/dl and 23,739 (67.3%) with TC ⩾ 200 mg/dl. In the adjusted analyses, TC level as continuous variable was inversely associated with moderate to severe CED (OR 0.99, 95% CI 0.99–1.00, p = 0.025) and as categorical variable lower TC levels were associated with a higher risk of moderate to severe CED (aOR 1.24, 95% CI 1.10–1.40, p = 0.003). TC levels were not associated with any PH, functional independence, and mortality at 3 months. Conclusions: Our findings indicate an independent association between low levels of TC and higher odds of moderate/severe CED. Further studies are needed to confirm these findings. more...

Resumen Objetivos Analizar los cambios en las tendencias de la mortalidad por enfermedades cerebrovasculares segun comunidad autonoma y sexo en Espana durante el periodo 1980-2016 utilizando modelos de regresion joinpoint. Metodos Los datos de mortalidad se obtuvieron del Instituto Nacional de Estadistica. Para cada comunidad autonoma y sexo se calcularon las tasas brutas y estandarizadas. El analisis de regresion joinpoint se utilizo para identificar los puntos mas adecuados donde se produjo un cambio estadisticamente significativo en la tendencia. Resultados El analisis joinpoint permite diferenciar comunidades en las que las tasas muestran un descenso continuado a lo largo de todo el periodo en ambos sexos (Asturias, Cantabria, Castilla y Leon, Ceuta y Melilla) o solo en los hombres (Extremadura). En los hombres, en las comunidades en las que se observan cambios en la tendencia se aprecia, en todas ellas (excepto en Aragon, Baleares y Murcia, donde las tasas permanecen estables), un primer periodo de descenso, que oscila entre el −3,4% en Cataluna y Extremadura y el −6,0% en Madrid, y un periodo final donde las tasas muestran tendencias divergentes: siguen descendiendo en Andalucia, Aragon, Baleares y Madrid, han comenzado a estabilizarse en Castilla-La Mancha y Murcia y aumentan en Canarias. En las mujeres, en las comunidades en que se observan cambios en la tendencia se aprecia, en todas ellas (excepto en Aragon, Murcia y Pais Vasco, donde las tasas permanecen estables), un primer periodo de descenso, que oscila entre el −3,1% en Cataluna y el −6,4% en Navarra, y un periodo final donde las tasas muestran tendencias divergentes: siguen descendiendo en Andalucia, Aragon, Cataluna, Galicia, Madrid y Pais Vasco, han comenzado a estabilizarse en Extremadura y Murcia, y aumentan en Canarias. Conclusiones Los datos actuales muestran que las tasas de mortalidad por enfermedades cerebrovasculares se han desacelerado (en mujeres en Andalucia), estancado (en ambos sexos en Murcia, en hombres en Castilla-La Mancha y en mujeres en Extremadura) e incluso se han revertido (en hombres y en mujeres en Canarias). Las causas de estas tendencias requieren mas estudios. more...

Background: In-stent thrombosis after mechanical thrombectomy (MT) worsen outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Although an optimal antiplatelet therapy is needed, the best approach to avoid in-stent thrombosis is yet to be elucidated. Hypothesis: Low-dose intravenous tirofiban is superior to intravenous aspirin in avoiding in-stent thrombosis in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Methods: The ATILA-trial is a multicenter, prospective, phase IV, randomized, controlled (aspirin group as control), assessor-blinded clinical trial. Patients fulfilling inclusion criteria (AIS due to TL, ASPECTS ⩾ 6, pre-stroke modified Rankin Scale ⩽2 and onset Outcomes: The primary efficacy outcome is the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. The primary safety outcome is the rate of symptomatic intracranial hemorrhage. Secondary outcomes include functional independence defined as modified Rankin Scale 0–2, proportion of patients undergoing rescue therapy due to in-stent aggregation during MT and carotid reocclusion at 30 days. Discussion: ATILA-trial will be the first clinical trial regarding the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration: NCT0522596. more...

ObjectiveTo test the hypothesis that IV thrombolysis (IVT) treatment before endovascular thrombectomy (EVT) is associated with better outcomes in patients with anterior circulation large artery occlusion (LAO) stroke, we examined a large real-world database, the Safe Implementation of Treatment in Stroke–International Stroke Thrombectomy Register (SITS-ISTR).MethodsWe identified centers recording ≥10 consecutive patients in the SITS-ISTR, with at least 70% available modified Rankin Scale (mRS) scores at 3 months during 2014 to 2019. We defined LAO as intracranial internal carotid artery, first and second segment of middle cerebral artery, and first segment of anterior cerebral artery. Main outcomes were functional independence (mRS score 0–2) and death at 3 months and symptomatic intracranial hemorrhage (SICH) per modified SITS–Monitoring Study. We performed propensity score–matched (PSM) and multivariable logistic regression analyses.ResultsOf 6,350 patients from 42 centers, 3,944 (62.1%) received IVT. IVT + EVT–treated patients had less frequent atrial fibrillation, ongoing anticoagulation, previous stroke, heart failure, and prestroke disability. PSM analysis showed that IVT + EVT–treated patients had a higher rate of functional independence than patients treated with EVT alone (46.4% vs 40.3%,p< 0.001) and a lower rate of death at 3 months (20.3% vs 23.3%,p= 0.035). SICH rates (3.5% vs 3.0%,p= 0.42) were similar in both groups. Multivariate adjustment yielded results consistent with PSM.ConclusionPretreatment with IVT was associated with favorable outcomes in EVT-treated LAO stroke in the SITS-ISTR. These findings, while indicative of international routine clinical practice, are limited by observational design, unmeasured confounding, and possible residual confounding by indication.Classification of EvidenceThis study provides Class II evidence that IVT before EVT increases the probability of functional independence at 3 months compared to EVT alone. more...

This study was supported by a Spanish grant from the Instituto de Salud Carlos III (ISCIII-FIS IP14/00971,2014-2017). The ITRIBIS project (Improving Translational Research Potential at the Institute of Biomedicine of Seville) has the registration number REGPOT-2013-1. Cooperative Cerebrovascular Disease Research Network (INVICTUS+)(RD16/0019/0015). Fernando Mancha is supported by a Rio Hortega contract. Francisco Moniche is PI of PI15/01197 and PI18/01414 grants. This study was partially funded by Abbott (Chicago, IL, USA) and Grifols (Barcelona, Spain) but had no role in the design of the study, interpretation of the data or manuscript approval. more...

Background and Purpose Cerebral edema (CED) in ischemic stroke can worsen prognosis and about 70% of patients who develop severe CED die if treated conservatively. We aimed to describe incidence, risk factors and outcomes of CED in patients with extensive ischemia.Methods Oservational study based on Safe Implementation of Treatments in Stroke-International Stroke Treatment Registry (2003–2019). Severe hemispheric syndrome (SHS) at baseline and persistent SHS (pSHS) at 24 hours were defined as National Institutes of Health Stroke Score (NIHSS) >15. Outcomes were moderate/severe CED detected by neuroimaging, functional independence (modified Rankin Scale 0–2) and death at 90 days.Results Patients (n=8,560) presented with SHS and developed pSHS at 24 hours; 82.2% received intravenous thrombolysis (IVT), 10.5% IVT+thrombectomy, and 7.3% thrombectomy alone. Median age was 77 and NIHSS 21. Of 7,949 patients with CED data, 3,780 (47.6%) had any CED and 2,297 (28.9%) moderate/severe CED. In the multivariable analysis, age 128.5 mg/dL (RR, 1.21), and decreased level of consciousness (RR, 1.14) were associated with moderate/severe CED (for all P more...

[Backgroun] Statins have an important role in stroke prevention, especially in high-risk populations and may also affect the initial stroke severity and outcomes in patients taking them before an ischemic stroke., [Aims] Our aim was to evaluate the association of statin pre-treatment with the severity in acute ischemic stroke (AIS)., [Methods] We analyzed AIS patients received intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT) and recorded in the SITS International Thrombolysis and Thrombectomy Registry from 2011 to 2017. We identified patients with statin information at baseline. The primary outcome was baseline National Institutes of Health Stroke Scale (NIHSS) score. Secondary outcomes were NIHSS score at 24 h, symptomatic intracerebral hemorrhage (SICH) and functional outcome at 90 days after acute intervention. Multivariable linear and logistic regression and propensity score matching (PSM) was used to quantify the effect of statin pre-treatment., [Results] Of 93,849 patients, 23,651 (25.2%) were treated with statins prior the AIS. Statin pre-treatment group was older and had higher comorbidity. Median NIHSS at baseline was similar between groups. In the adjusted and PSM analysis, statin pre-treatment was inversely associated with baseline NIHSS (odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.6–0.99 and OR for PSM 0.73, 95% CI = 0.54–0.99, p = 0.004) and independently associated with mild stroke defined as NIHSS ⩽8 in adjusted and PSM analysis (OR = 1.21, 95% CI = 1.1–1.34, p, [Conclusion] Prior treatment with statins was associated with lower NIHSS at baseline. However, this association did not translate into any difference regarding functional outcome at 90 days. No association was found regarding SICH. These findings indicate the need of further studies to assess the effect on statin pre-treatment on initial stroke severity. more...

Background – A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. There is still conflicting evidence whether reperfusion is associated with a lower risk for CED in acute ischemic stroke. Aim – To investigate the association of reperfusion with development of early CED after stroke thrombectomy. Methods – From the SITS-International Stroke Thrombectomy Registry, we selected patients with occlusion of the intracranial internal carotid or middle cerebral artery (M1 or M2). Successful reperfusion was defined as mTICI ≥2b. Primary outcome was moderate or severe CED, defined as focal brain swelling ≥1/3 of the hemisphere on imaging scans at 24 hours. We used regression methods while adjusting for baseline variables. Effect modification by severe early neurological deficits, as indicators of large infarct at baseline and at 24 hours, were explored. Results – In total, 4640 patients, median age 70 years and median National Institutes of Health Stroke Score (NIHSS) 16, were included. Of these, 86% had successful reperfusion. Moderate or severe CED was less frequent among patients who had reperfusion compared to patients without reperfusion: 12.5% versus 29.6%, p Conclusions – In patients with large artery anterior circulation occlusion stroke who underwent thrombectomy, successful reperfusion was associated with approximately 50% lower risk for early CED. Severe neurological deficit at baseline seems to be a predictor for moderate or severe CED also in patients with successful reperfusion by thrombectomy. more...

Background and Purpose— A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. Reperfusion may cause blood-brain barrier disruption and a risk for cerebral edema and secondary parenchymal hemorrhage (PH). We aimed to investigate the effect of recanalization on development of early CED and PH after recanalization therapy. Methods— From the SITS-International Stroke Treatment Registry, we selected patients with signs of artery occlusion at baseline (either Hyperdense Artery Sign or computed tomography/magnetic resonance imaging angiographic occlusion). We defined recanalization as the disappearance of radiological signs of occlusion at 22 to 36 hours. Primary outcome was moderate to severe CED and secondary outcome was PH on 22- to 36-hour imaging scans. We used logistic regression with adjustment for baseline variables and PH. Results— Twenty two thousand one hundred eighty-four patients fulfilled the inclusion criteria (n=18 318 received intravenous thrombolysis, n=3071 received intravenous thrombolysis+thrombectomy, n=795 received thrombectomy). Recanalization occurred in 64.1%. Median age was 71 versus 71 years and National Institutes of Health Stroke Scale score 15 versus 16 in the recanalized versus nonrecanalized patients respectively. Recanalized patients had a lower risk for CED (13.0% versus 23.6%), adjusted odds ratio (aOR), 0.52 (95% CI, 0.46–0.59), and a higher risk for PH (8.9% versus 6.5%), adjusted odds ratio, 1.37 (95% CI, 1.22–1.55), than nonrecanalized patients. Conclusions— In patients with acute ischemic stroke, recanalization was associated with a lower risk for early CED even after adjustment for higher rate for PH in recanalized patients. more...

Objetivos: evaluar la efectividad del cribado de pulso irregular por el farmaceutico comunitario mediante el pilotaje de una metodologia y procedimiento para una campana de deteccion de pulso irregular en las farmacias comunitarias espanolas. Metodos: estudio descriptivo transversal realizado por farmaceuticos comunitarios socios de SEFAC entre los dias 24 a 29 de noviembre de 2016 y los dias 5 a 11 de junio de 2017. Criterios de inclusion: usuarios ≥40 anos, sin FA o con FA sin tratamiento anticoagulante. Variables principales: pulso (latidos/minuto) y CHA2 DS2 vascular. Resultados: se realizaron 789 mediciones de pulso en ambas campanas, de las cuales se encontro que 41 (5,2 %) participantes presentaban un pulso irregular. 35 (4,3 %) fueron derivados a sus medicos de familia, confirmandose 12 (1,5%) diagnosticos nuevos de FA e iniciando 7 (0,9 %) de ellos tratamiento anticoagulante. Mas del 80 % de los participantes no presentaba ningun sintoma clinico de FA y un 41,9 % padecia HTA. El numero de pacientes con CHA2 DS2 vascular ≥2 y pulso irregular fue de 17 (3,9 %), de los cuales 10 (58,8 %) estaban sin tratamiento; 5 (29,4 %) tenian tratamiento antiagregante y 2 (11,8 %) tratamiento anticoagulante. Conclusiones: tanto el elevado numero de pacientes con FA diagnosticada y sin tratamiento como el numero apreciable de pacientes con pulso irregular y sospecha de FA detectados demuestran la capacidad y eficacia de la farmacia comunitaria en la realizacion del cribado del pulso irregular contribuyendo asi a la deteccion de nuevos casos de FA. more...

Objectives The aim of the HISPANIAS (HyperperfusIon Syndrome Post-carotid ANgIoplasty And Stenting) study was to define CHS rates and develop a clinical predictive model for cerebral hyperperfusion syndrome (CHS) after carotid artery stenting (CAS). Background CHS is a severe complication following CAS. The presence of clinical manifestations is estimated on the basis of retrospective reviews and is still uncertain. Methods The HISPANIAS study was a national prospective multicenter study with 14 recruiting hospitals. CHS was classified as mild (headache only) and moderate-severe (seizure, impaired level of consciousness, or development of focal neurological signs). Results A total of 757 CAS procedures were performed. CHS occurred in 22 (2.9%) patients, in which 16 (2.1%) had moderate-severe CHS and 6 (0.8%) had mild CHS (only headache). The rate of hemorrhages was 0.7% and was associated with high mortality (20%). Pre-operative predictors of moderate-severe CHS in multivariate analysis were female sex (odds ratio [OR]: 3.24; 95% confidence interval [CI]: 1.11 to 9.47; p = 0.03), older patients (OR: 1.09; 95% CI: 1.01 to 1.17; p = 0.02), left carotid artery treated (OR: 4.13; 95% CI: 1.11 to 15.40; p = 0.03), and chronic renal failure (OR: 6.29; 95% CI: 1.75 to 22.57; p = 0.005). The area under the curve of this clinical and radiological model was 0.86 (95% CI: 0.81 to 0.92; p = 0.001). Conclusions The rate of CHS in the HISPANIAS study was 2.9%, with moderate-severe CHS of 2.1%. CHS was independently associated with female sex, older age, history of chronic kidney disease, and a treated left carotid artery. Although further investigations are needed, the authors propose a model to identify high-risk patients and develop strategies to decrease CHS morbidity and mortality in the future. more...

[Background] Atrial fibrillation (AF) has been associated with an increased risk of silent brain infarcts (SBI) and cognitive impairment, even in patients with low embolic risk. We aimed to test the association between 11 blood-biomarkers representing different AF-related pathways, and SBI, white matter hyperintensities (WMH), and cognitive decline in patients with AF and low embolic risk., [Methods] The present study followed a cross-sectional design. 70 patients with a history of AF and CHADS2 score ≤1, and 10 controls with neither AF nor SBI were included. All patients underwent a 3T brain MRI. Cortical and large subcortical ischemic lesions were considered presumed embolic origin lesions. White matter hyperintensities (WMH) were measured according to the Fazekas scale. A subset of patients underwent cognitive evaluation with the MoCA test. Circulating proteins were measured under blind conditions in a laboratory at Roche Diagnostics, Germany., [Results] 45 patients presented SBI in the MRI, and 25 did not. Ang-2, FGF-23, and BMP-10 were increased in patients with SBI. Ang-2 was elevated only in patients with embolic infarcts, whereas FGF-23 and BMP-10 tended to be elevated in patients with both types of infarcts. Ang-2 (OR = 1.56 [0.94-2.59], p = 0.087), and BMP-10 (OR = 4.83 [0.99–23.60], p = 0.052) were the biomarkers that showed the highest association with SBI when entered in a multivariable logistic regression model corrected by age. No biomarker was found associated with WMH or mild cognitive impairment., [Conclusions] BMP-10, and Ang-2 were increased in patients with SBI. Its usefulness to detect SBI in AF patients should be further explored., A Junta de Andalucía grant (PIN-0144-2016) supported partially the study. The Fundación Cajasol contributed to the study. Neurovascular Research Groups at Seville and Barcelona are part of the Spanish Neurovascular Disease Research Network (RICORS-ICTUS, RD21/0006/0007). more...

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[Background and objective] We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS–International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies., [Methods] We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014–2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST., [Results] Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44–47), 46.0% (42–50), 38% (35–41) and 37% (35–41), respectively; death was 19.2% (19–21), 15.3% (12.7–18.4), 29.2% (27–32) and 28.6% (27–31); and SICH was 3.6% (3–4), 4.4% (3.0–6.4), 5.8% (4.7–7.1) and not available., [Conclusion] Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies., SITS (Safe Implementation of Treatment in Stroke) is financed directly and indirectly by grants from Karolinska Institutet, Stockholm County Council, the Swedish Heart-Lung Foundation, the Swedish Order of St. John, Friends of Karolinska Institutet and private donors, as well as from an unrestricted sponsorship from Boehringer Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, Ferrer International and EVER Pharma. SITS is currently conducting studies supported by Boehringer Ingelheim and Biogen, as well as in collaboration with Karolinska Institutet, supported by Stryker, Covidien and Phenox. N Ahmed is supported by grants provided by the Stockholm County Council and the Swedish Heart-Lung Foundation. S Holmin is supported by grants provided by the Söderberg Foundations, the Stockholm County Council, the Erling Persson Foundation, VINNOVA and HMT. Irene Escudero-Martínez has received a grant from ‘Fundación Progreso y Salud, Junta de Andalucía’ (grant EF-0437-2018). RM has been supported by the project no. LQ1605 from the National Program of Sustainability II (MEYS CR). RH has been supported by the grants no. DRO–UHHK 00179906 from the Ministry of Health of the Czech Republic and no. PROGRES Q40 from Charles University, Czech Republic. more...

[Background] Silent brain infarcts (SBI), a finding on neuroimaging, are associated with higher risk of future stroke. Atrial Fibrillation (AF) has been previously identified as a cause of SBI., [Objectives] The aim of this study is to determine the prevalence of and risk factors for SBI in patients with AF and low-to-moderate embolic risk according to CHADS2 and CHA2DS2VASc score., [Methods] Patients with a history of AF based on medical records who scored 0–1 in the CHADS2 score were selected from the Seville urban area using the Andalusian electronic healthcare database (DIRAYA). Demographic and clinical data were collected and a 3T brain MRI was performed on patients older than 50 years and with absence of neurological symptoms., [Results] 66 of the initial 443 patients (14.9%) and 41 of the 349 patients with low risk according to CHA2DS2VASc score (11.7%) presented at least 1 SBI. After adjusted multivariable analysis, an older age (OR 3.84, 95% CI 1.07–13.76) and left atrial (LA) enlargement (OR 3.13, 95% CI 1.15–8.55) were associated with SBI in the whole cohort, while only LA enlargement was associated with SBI in the low-risk cohort (OR 3.19, 95% CI 1.33–7.63)., [Conclusions] LA enlargement on echocardiogram was associated with SBI in patients with AF and low or moderate embolic risk according to CHADS2 and in the low-risk population according to CHA2DS2VASc. Although further studies are needed, a neuroimaging screening might be justified in these patients to guide medical therapies to improve stroke prevention., The Spanish Ministry of Economy, Industry and Competitiveness (Grant RTC-2016-5300-1), the Junta de Andalucía (Grant PIN-0144-2016) and the European Project ITRIBIS supported the study. The Fundación Cajasol also contributed to the study. Neurovascular Research Group is part of the Spanish Neurovascular Disease Research Network (INVICTUS + , RD16/0019/0015). more...

Previous studies have shown the potential of microRNAs (miRNA) in the pathological process of stroke and functional recovery. Bone marrow mononuclear cell (BM-MNC) transplantation improves recovery in experimental models of ischemic stroke that might be related with miRNA modifications. However, its effect on circulating miRNA has not been described in patients with stroke. We aimed to evaluate the circulating levels of miRNAs after autologous BM-MNC transplantation in patients with stroke. We investigate the pattern of miRNA-133b and miRNA-34a expression in patients with ischemic stroke included in a multicenter randomized controlled phase IIb trial (http://www.clinicaltrials.gov; unique identifier: NCT02178657). Patients were randomized to 2 different doses of autologous intra-arterial BM-MNC injection (2×106/kg or 5×106/kg) or control group within the first 7 days after stroke onset. We evaluate plasma concentration of miRNA-113b and miRNA-34a at inclusion and 4, 7, and 90 days after treatment. Thirteen cases (8 with 2×106/kg BM-MNC dose and 5 with 5×106/kg dose) and 11 controls (BM-MNC non-treated) were consecutively included. Mean age was 64.1±12.3 with a mean National Institutes of Health Stroke Scale score at inclusion of 14.5. Basal levels of miRNA were similar in both groups. miR-34a-5p and miR-133b showed different expression patterns. There was a significant dose-dependent increase of miRNA-34a levels 4 days after BM-MNC injection (fold change 3.7, p, This work has been supported by the grants PI15/01197, PI18/01414 and RD16/0019/0015 (INVICTUS+) from the Spanish Ministry of Economy and Competitiveness, cofunded by ISCIII and FEDER funds; Mutua Madrileña grant. FMa is supported by a Rio Hortega contract (CM16/00015). Andalusian Initiative for Advanced Therapies (IATA) is the sponsor of the trial. more...

Background and Purpose— Restenosis after carotid angioplasty (with or without stent) is associated with increased rate of stroke and death. Our aim was to determine risk and predictive factors related to carotid restenosis post carotid angioplasty and its association to recurrent cerebrovascular events. Methods— All consecutive patients with carotid stenosis treated with angioplasty (n=1060) in a single University Hospital were included (from 2002 to 2013). Follow-up was done prospectively evaluating restenosis, ipsilateral stroke, or death. Restenosis was defined as a narrowing of ≥70% of a previously treated vessel evaluated by ultrasonography. Results— Of the 1060 patients treated, 9.2% (97) of patients experienced restenosis during follow up (median 12 [9–32] months). Occurrence of restenosis was associated with ipsilateral stroke during follow-up ( P =0.049). After Cox regression analysis, hypertension (hazard ratio, 6.2 [1.9–19.9]; P =0.002), impaired vasoreactivity (hazard ratio, 1.7 [1.09–2.8]; P =0.019), and angioplasty without stent (hazard ratio, 2.9 [1.2–6.8]; P =0.012) were independent risk predictors of >70% restenosis. Conclusions— Carotid restenosis after carotid angioplasty is associated with ipsilateral stroke occurrence. In our sample, hypertension, angioplasty without stent, and impaired vasoreactivity identify patients at high risk of restenosis and could help to select patients for follow-up ultrasonography imaging. more...

Introduction: In recent decades, mortality rates for cerebrovascular diseases (CVD) have declined significantly in many countries. This study analyses changes in CVD mortality rates in Spain (1980-2011) to determine if previously observed trends remain. Patients and methods: Data on CVD mortality rates and the population data needed for the analysis were provided by Spain's National Statistics Institute. We calculated age-specific mortality rate, age-standardised overall mortality, and age-truncated mortality (35-64 years) using the direct method and standard European population structure. Joinpoint analysis was used to estimate the percentage of annual change in rates and identify significant changes in trends. Results: CVD mortality rate decreased considerably and continuously over the last 32 years in all age groups and in both sexes in Spain. For both sexes, joinpoint analysis identifies a final period with more marked decline: 2005-2011 in women (−6.3%) and 2007-2011 in men (−7.2%). Conclusions: CVD mortality rates displayed a marked and continuous decline in Spain between 1980 and 2011. Due to the ageing of the population, doctors expect an increase in CVD prevalence and therefore its magnitude in terms of disability and healthcare costs, which poses a challenge to our health system. Resumen: Introducción: En las últimas décadas las tasas de mortalidad por enfermedades cerebrovasculares (ECV) han descendido de forma importante en muchos países. En este estudio se analizan los cambios recientes en la evolución de la mortalidad por ECV en España (1980-2011) para verificar si las tendencias observadas previamente continúan. Pacientes y métodos: Los datos de mortalidad por ECV y las poblaciones necesarias para el cálculo de los indicadores fueron facilitados por el Instituto Nacional de Estadística. Se calcularon las tasas específicas por grupos de edad y estandarizadas globales y truncadas (35-64 años) mediante el método directo (población estándar europea). Mediante análisis de regresión «joinpoint» estimamos el porcentaje de cambio anual de las tasas e identificamos puntos de cambio significativos en la tendencia. Resultados: La mortalidad por ECV se ha reducido de forma contundente y sostenida en los últimos 32 años en todos los grupos de edad y sexo en España. En ambos sexos el análisis joinpoint identifica un periodo final de mayor descenso (2005-2011 [−6,3%] en mujeres y 2007-2011 en varones [−7,2%]). Conclusiones: Existe un marcado y continuo descenso en la mortalidad por ECV en España (1980-2011). Teniendo en cuenta el proceso de envejecimiento de la población, es esperable un incremento de la prevalencia y, por ello, de la magnitud de las ECV medida en términos de discapacidad y costes de salud, lo que representará un gran reto para nuestro sistema sanitario. Keywords: Regression analysis, Cerebrovascular diseases, Epidemiology, Spain, Mortality, Trends, Palabras clave: Análisis de regresión, Enfermedad cerebrovascular, Epidemiología, España, Mortalidad, Tendencia more...

Introduction: One of the main limitations in biomarker research for stroke-associated pneumonia (SAP) is the lack of a gold-standard for clinical diagnosis. We aimed to evaluate the diagnostic accuracy of candidate biomarkers related to the features on thoracic high-resolution computed tomography (HRCT). Methods: Patients with ischemic stroke with baseline NIHSS>10 were enrolled between March-2016 and August-2017. Blood samples were collected at baseline, 24 and 48 hours after stroke onset, to determine C-reactive protein (CRP), serum amyloid protein A (SAA), mid-regional proadrenomedullin (MR-proADM), and soluble receptor of urokinase-type plasminogen activator (suPAR). Biomarkers were measured by immunoassays. Pneumonia was diagnosed as the presence of a new consolidation, infectious nodules or ground-glass pattern, in a thoracic HRCT performed 5-7 days after stroke. Results: From 46 included patients, thoracic HRCT was performed in 41 patients. Five (12.5%) were diagnosed as pneumonia and 3 (7.3%) with acute bronchitis. No blood marker was associated with pneumonia on thoracic HRCT at baseline. At 24 hours, a cut-off of MR-proADM>1.023 nmol/L had 80% sensitivity and 72.2% specificity for pneumonia. At 48 hours, both SAA>25.15 mg/dL (60% sensitivity, 85.7% specificity) and suPAR>3.14 ng/mL (80% sensitivity, 57.1% specificity) were associated with infections. The combination of SAA>25.15 mg/dL and suPAR>3.14 ng/mL at 48 hours had 80% sensitivity and 95.8% specificity when both biomarkers were above the cut-off, and 60% sensitivity and 94.1% specificity when one of them was above the cut-off. Conclusions: An objective diagnostic test such as thoracic HRCT could be of interest for future research in SAP. The evaluated biomarkers will require further validation in larger samples. However, these biomarkers represent promising tools to be evaluated in future projects on SAP early diagnosis and guidance on antibiotic therapy. more...

OBJECTIVES To analyse the changes in stroke mortality trends in Spain by autonomous community and by sex during the period 1980-2016, using joinpoint regression models. METHODS Mortality data were obtained from the Spanish National Statistics Institute. Crude and standardised rates were calculated for each Spanish autonomous community, and for each sex. Joinpoint analysis was used to identify the best-fitting points showing a statistically significant change in the trend. RESULTS Joinpoint analysis enabled us to differentiate between communities in which mortality rates showed a continuous decline throughout the study period in both sexes (Asturias, Cantabria, Castile and Leon, Ceuta, and Melilla) or in men only (Extremadura). In men, in all those communities in which changes in the trend were observed (all but Aragon, the Balearic Islands, and Murcia, where rates remained stable), we observed an initial period of decline (ranging from -3.4% in Catalonia and Extremadura, to -6.0% in Madrid) and a final period where the trends diverged: mortality rates continued to fall in Andalusia, Aragon, the Balearic Islands, and Madrid, but began to stabilise in Castile-La Mancha and Murcia and to increase in the Canary Islands. In women, in those communities where changes were observed (all but Aragon, Murcia, and the Basque Country, where rates remained stable), we observed an initial period of decline (ranging from -3.1% in Catalonia to -6.4% in Navarre) and a final period where divergent trends were observed: rates continued to decline in Andalusia, Aragon, Catalonia, Galicia, Madrid, and the Basque Country, but began to stabilise in Extremadura and Murcia and to increase in the Canary Islands. CONCLUSIONS Current data show that stroke mortality rates have decreased (in women in Andalusia), stabilised (in both sexes in Murcia, in men in Castile-La Mancha, and in women in Extremadura), and have even reversed (in both sexes in the Canary Islands). Further study is needed to identify the causes of these trends. more...

Introduction: Traditional predictors of paroxysmal AF (PAF) including left atria size, CHADSVASC score or rate of atria premature beats are inaccurate to predict PAF in elderly stroke patients. We aimed to evaluate the yield of atrial dysfunction markers such as NT-ProBNP and Left atrial deformability in acute elderly cryptogenic stroke patients to predict PAF. Methods: We prospectively evaluated cryptogenic stroke patients Results: Out of 150 cryptogenic stroke patients, one hundred and ten patients fulfilled 4 weeks of Holter monitoring. Median age was 75 years (69-83).The percentage of PAF detection was 24.5%. Age, sex, hypertension, diabetes, CHADSVASC score, NIHSSS, left atria volume, left ventricle ejection fraction and rate of atria premature beats were comparable between patients with and without PAF detection. Admission NT-ProBNP levels were higher (346.9 pg/ml [175-685]) in whom PAF was detected compared to those who did not (203.5 pg/ml [76.75-453.95] (p=0.028). Conversely, LAS was lower 18.66% [13.98-26.71] in PAF compared to no PAF detected patients 27.43% [21.28-36-56] (p=0.003). Both markers were inversely correlated (Spearman Rho -0.31) (p=0.007). The AUC of NT-ProBNP was 0.65 (0-53-0.76) with cut-off point of NT-ProBNP> 102 pg/ml (sensitivity 96%, specificity 33%) and LAS was 0.73 (0.59-0.86) with cut-off point of LAS Conclusions: The combination of both NT-ProBNP and LAS markedly improve the predictive accuracy for PAF detection in elderly cryptogenic stroke patients. more...

The Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN), Age, Atrial Fibrillation, Dysphagia, male sex, and National Institutes of Health Stroke Scale (A2DS2), and acute ischemic stroke-associated pneumonia score (AIS-APS) scores were created to predict stroke-associated pneumonia (SAP), one of the most important medical stroke complications. External validation of all such scores in an acute stroke population was the aim of our study.Patients with ischemic or hemorrhagic stroke were prospectively enrolled in the multicenter Stroke-Induced Pneumonia in Andalucía project between October 2014 and May 2016. Receiver operating characteristic curves and linear regression analyses were used to determine discrimination ability of the scores. The Hosmer-Lemeshow goodness-of-fit test and the plot of observed versus predicted SAP risk were used to assess model calibration.Among 201 included patients, SAP rate was 15.5% (31). Higher ISAN, A2DS2, and AIS-APS scores were related to SAP (all P .001). The C statistic was .83 (95% confidence interval [CI], .76-.91) for the ISAN score, .80 (95% CI, .70-.89) for the A2DS2 score, and .82 (95% CI, .74-.90) for the AIS-APS score, suggesting good discrimination. The ISAN and AIS-APS scores showed good calibration (Cox and Snell RIn our cohort, the external validation of ISAN, A2DS2, and AIS-APS scores have demonstrated their accurate prediction of SAP and the ability of these scores as screening tools to better manage SAP. The AIS-APS score would be recommendable for the development of future clinical trials. more...

Objective/Background In 2006, the American Heart Association recommended that for preference carotid endarterectomy (CEA) or, alternatively, carotid angioplasty and stenting (CAS) for symptomatic carotid artery stenosis should ideally occur within 14 days of an ischaemic event. The aim was to determine the safety of CAS according to those recommendations in daily practice. Methods A retrospective analysis was performed of all consecutive patients (2000–16), with ipsilateral carotid symptoms who underwent CAS for extracranial carotid stenosis ≥70%, who were previously included in a prospective database. Thirty day morbidity was assessed (any stroke without transient ischaemic attack [TIA]/amaurosis fugax), along with mortality of the procedure in the early (≤14 days after stroke onset) and delayed phases (15–180 days after stroke onset). Patients who received CAS and/or mechanical thrombectomy for acute ischaemic stroke treatment were not included. Results In total, 1227 patients with symptomatic carotid stenosis who underwent CAS were identified. Early and delayed CAS was performed in 291 and 936 patients, respectively. Morbidity (any stroke) and mortality was 2.2% (n = 27) in the whole cohort (n = 8 [2.7%] in early vs. n = 19 [2%] in delayed CAS; p = .47). There were no differences in morbidity between early and delayed CAS regarding TIA (n = 15 vs. 36 [5.2% vs. 3.9%]; p = .33), minor stroke (n = 4 vs. 5 [1.4% vs. 0.5%]; p = .14), or major stroke (n = 2 vs. 6 [0.7% vs. 0.6%]; p = .59). Two patients (0.7%) died after early CAS and eight (0.9%) after delayed CAS (p = .56). Conclusion CAS may be safely performed in the early phase after an ischaemic stroke with low clinical complication rates. Further studies are needed to validate CAS safety conducted even earlier in the acute phase of ischaemic stroke. more...

A stroke is a time-dependent medical emergency. Swiftness in its recognition and in the care received by the patients plays a key role in the prognosis.To analyse the medical intervention times, to evaluate possible areas where improvements can be made and to examine the allocation of resources in the centres.The study was based on a prospective register of patients with suspected stroke and stroke code activation treated in eight experienced Spanish stroke units. Onset-to-door, door-to-computed tomography (CT), door-to-needle, CT-to-needle and onset-to-needle times were collected. Information about the means of transport used to get to the hospital, the type of stroke and reperfusion therapies was also collected. With regard to the structural resources of the centres, data were gathered about the nurse-to-patient ratio, bed monitoring, availability of multimodal CT and magnetic resonance, and doing information or training courses.Altogether 197 patients were included, of whom 181 (151 infarctions and 30 brain haemorrhages) were valid. The medians (p25-p75) in minutes were: onset-to-door, 104 (70-188); door-to-CT, 27 (19-41); CT-to-needle, 30 (21-43); door-to-needle, 64 (49-83); and onset-to-needle, 156 (129-202). Reperfusion therapies were applied in 68 patients (45% of the cerebral infarctions), of which 81% were intravenous thrombolyses; 7%, endovascular treatments; and 12%, a combination of the two. The resources available in the centres were in accordance with those recommended by the clinical guidelines. There was a low percentage of patients who were studied by means of magnetic resonance.The percentage of patients treated with thrombolysis was very high and although the times of the in-hospital circuits were good, there is still room for further improvement.Atencion urgente al ictus en hospitales con unidad de ictus. Proyecto Quick.Introduccion. El ictus es una emergencia medica dependiente del tiempo. La rapidez en su reconocimiento y en la atencion que reciben los pacientes es clave en el pronostico. Objetivos. Analizar los tiempos de actuacion medica, evaluar posibles areas de mejora y estudiar la dotacion de recursos de los centros. Pacientes y metodos. Registro prospectivo de pacientes atendidos en ocho unidades de ictus experimentadas españolas con sospecha de ictus y activacion del codigo ictus. Se recogieron los tiempos inicio-puerta, puerta-tomografia computarizada (TC), puerta-aguja, TC-aguja e inicio-aguja. Tambien se recogieron el metodo de trasporte al hospital, el tipo de ictus y las terapias de reperfusion. En cuanto a la dotacion estructural de los centros, se recogieron la ratio de enfermeria, la monitorizacion de camas, la disponibilidad de TC multimodal y resonancia magnetica, y la realizacion de cursos de informacion o formacion. Resultados. Se incluyeron 197 pacientes, de los cuales fueron validos 181 (151 infartos y 30 hemorragias cerebrales). Las medianas (p25-p75) en minutos fueron: inicio-puerta, 104 (70-188); puerta-TC, 27 (19-41); TC-aguja, 30 (21-43); puerta-aguja, 64 (49-83); e inicio-aguja, 156 (129-202). Se aplicaron terapias de reperfusion en 68 pacientes (el 45% de los infartos cerebrales), de los cuales el 81% fueron trombolisis intravenosas; el 7%, tratamientos endovasculares; y el 12%, una combinacion de ambos. Los recursos de los centros estuvieron de acuerdo con lo recomendado por las guias clinicas. Hubo un bajo porcentaje de pacientes estudiados con resonancia magnetica. Conclusion. El porcentaje de pacientes tratados con trombolisis fue muy elevado y los tiempos de los circuitos intrahospitalarios, aunque buenos, tienen margen de mejora. more...

Objectives Genetic background has been identified to be a major predictor of post-clopidogrel platelet inhibition in patients undergoing coronary stenting. However, there is a lack of data on clopidogrel response regarding genotype in patients undergoing carotid artery stenting (CAS). The influence of the most common allelic variants of CYP2C19 phenotypes and genotypes on response to baseline clopidogrel and on the pharmacodynamic effect of dose adjustment (high or standard dose of clopidogrel) in patients with high on-treatment reactivity after CAS was investigated. Methods Platelet reactivity was assessed before and 30 days after carotid stenting using the VerifyNow P2Y12 assay to obtain P2Y12 reactivity unit (PRU) values. Results A total of 209 patients (79.4% male, 44.1% currents smokers) were treated by CAS. Smokers improved responsiveness to clopidogrel ( p = .034). With respect to CYP2C19 enzymatic function, 61 subjects (29.1%) were ultra-rapid metabolizers, 95 patients (45.5%) were extensive metabolizers, 51 (24.4%) were intermediate metabolizers, and two (0.96%) were poor metabolizers. Baseline PRU was significantly higher among intermediate–poor metabolizers compared with ultra-rapid ( p = .001) or extensive metabolizers ( p = .005). At 30 days follow up, in non-responding patients with the intermediate–poor metabolizer phenotype, the PRU value and inhibition percentage were significantly reduced with standard dose ( p = .008; p = .0029) and high dose of clopidogrel ( p = .00 0; p = .000). However, high dose clopidogrel did not achieve a more intense pharmacodynamic effect at 30 days ( p = .994) compared with standard dose. Conclusions In patients undergoing carotid stenting, those with the CYP2C19*2 allele had increased basal PRU values and in fact clopidogrel non-responders increased significantly among intermediate–poor metabolizers. Although high dose and standard dose clopidogrel therapy was effective in lowering the 30 day PRU values in patients with high on-treatment reactivity who are intermediate–poor metabolizers, the use of high dose clopidogrel did not result in statistically significantly greater reductions in reactivity compared with the standard dose. more...

Introduccion. El ictus es una emergencia medica dependiente del tiempo. La rapidez en su reconocimiento y en la atencion que reciben los pacientes es clave en el pronostico. Objetivos. Analizar los tiempos de actuacion medica, evaluar posibles areas de mejora y estudiar la dotacion de recursos de los centros. Pacientes y metodos. Registro prospectivo de pacientes atendidos en ocho unidades de ictus experimentadas espanolas con sospecha de ictus y activacion del codigo ictus. Se recogieron los tiempos inicio-puerta, puerta-tomografia computarizada (TC), puerta-aguja, TC-aguja e inicio-aguja. Tambien se recogieron el metodo de trasporte al hospital, el tipo de ictus y las terapias de reperfusion. En cuanto a la dotacion estructural de los centros, se recogieron la ratio de enfermeria, la monitorizacion de camas, la disponibilidad de TC multimodal y resonancia magnetica, y la realizacion de cursos de informacion o formacion. Resultados. Se incluyeron 197 pacientes, de los cuales fueron validos 181 (151 infartos y 30 hemorragias cerebrales). Las medianas (p25-p75) en minutos fueron: inicio-puerta, 104 (70-188); puerta-TC, 27 (19-41); TC-aguja, 30 (21-43); puerta-aguja, 64 (49-83); e inicio-aguja, 156 (129-202). Se aplicaron terapias de reperfusion en 68 pacientes (el 45% de los infartos cerebrales), de los cuales el 81% fueron trombolisis intravenosas; el 7%, tratamientos endovasculares; y el 12%, una combinacion de ambos. Los recursos de los centros estuvieron de acuerdo con lo recomendado por las guias clinicas. Hubo un bajo porcentaje de pacientes estudiados con resonancia magnetica. Conclusion. El porcentaje de pacientes tratados con trombolisis fue muy elevado y los tiempos de los circuitos intrahospitalarios, aunque buenos, tienen margen de mejora. more...