Clinical relevance of circulating angiogenic cells in patients with ischemic stroke.

BACKGROUND: Endothelial progenitor cells (EPCs) are circulating angiogenic cells with endothelial features associated with risk for stroke. We aimed to delve into their functional characteristics. EPCs were isolated and cultured from Ischemic Stroke (IS) patients and predictors of their variance evaluated. METHODS: This is a single-center observational study evaluating 187 consecutively hospitalized patients with IS. EPCs were isolated from blood samples. The number of circulating angiogenic cells (CACs), colony-forming units (CFU-ECs) and the emergence of late outgrowths endothelial cells (LOECs) were counted. We collected clinical variables and measured the stromal cell-derived factor 1 alpha (SDF1α) serum levels. We also examined the relative telomere length and the expression of osteogenic gene markers in CACs. RESULTS: CACs counts and CFU-ECs colony numbers were positively correlated (rho = 0.41, p < 0.001, n = 187). We found significant differences according to whether thrombolytic treatment was performed in the distribution of CFU-ECs (odds ratio (OR) = 2.5; 95% confidence interval (CI) 1.01-6.35; p = 0.042) and CACs (OR = 4.45; 95% IC 1.2-15.5; p = 0.012). The main determinants of CACs variation were the number of risks factors, thrombolysis treatment, arterial hypertension, LOECs occurrence, and the vascular endothelial growth factor expression, whereas CFU-ECs variations depended on hemoglobin content and the relative reduction in the National Institutes of Health Stroke Scale (NIHSS) criteria. The main predictors of LOECs appearance were thrombolysis and length of hospital stay. CONCLUSIONS: Our study supports the relevance of patient risk factors and treatments in the analysis of the functional properties of EPCs.

Novel High-Quality Sonographic Methods to Diagnose Muscle Wasting in Long-Stay Critically Ill Patients: Shear Wave Elastography, Superb Microvascular Imaging and Contrast-Enhanced Ultrasound.

Novel ultrasound (US) methods are required to assess qualitative changes in the quadriceps rectus femoris (QRF) muscle when evaluating mechanically ventilated, long-stay ICU patients with suspected neuromuscular acquired weakness (ICUAW). Our aim was to analyze novel US muscle assessment methods in these patients versus healthy controls by carrying out a prospective observational study. Shear wave elastography (SWE) showed, with a receiver operating characteristic (ROC) curve of 0.972 (95% confidence interval (CI) = 0.916-1.000), that patients increased muscle stiffness associated with muscle fibrosis when diagnosed with ICUAW. We also performed, for the first time, superb microvascular imaging (SMI), which is an innovative US technique designed for imaging microvascularization unseen with color Doppler US, and observed that 53.8% of cases had significantly lower QRF muscle microvascular angiogenic activity than controls (p < 0.001). Finally, we used contrast-enhanced ultrasound (CEUS) to analyze maximum and minimum QRF muscle perfusion and obtained a ROC curve of 0.8, but when used as markers for SMI, their diagnostic capacity increased to 0.988 (CI = 0.965-1) and 0.932 (CI = 0.858-1), respectively. These findings show, for the first time, that these novel sonographic muscle methods should be used for their diagnostic capacity when assessing sarcopenic processes associated with this group of critically ill patients.

Assessment of Muscle Wasting in Long-Stay ICU Patients Using a New Ultrasound Protocol.

There is currently no standardized procedure to assess sarcopenia in long-stay catabolic patients. Our aim is to analyze a novel ultrasound muscle assessment protocol in these patients versus healthy controls, by carrying out a prospective observational study. We designed a new ultrasound protocol that assesses quadriceps rectus femoris (QRF) muscle quality in real-time B-mode, color-Doppler, and M-mode ultrasound, and evaluates QRF intramuscular central tendon thickness, cross-sectional area, and muscle thickness in ultrasound B-mode. Logistic regression was performed as a multivariable analysis on 29 cases and 19 controls. The QRF muscle area and thickness were shown to significantly decrease (p ≤ 0.001), and the central tendon thickness significantly increased (p = 0.047) in cases versus controls. The QRF muscle echogenicity and angiogenic activity fasciculations, subcutaneous edema, and intramuscular fluid were also significantly different between the two groups (p < 0.001). The selected variables in the multivariate logit analysis were the muscle area (OR per cm² = 0.07; 95% confidence interval (CI) = 0.012⁻0.41) and the central tendon thickness (OR per mm 1.887; 95% CI = 2.66⁻13.38).

Sonographic evaluation of atherosclerosis burden in carotid arteries of ischemic stroke patients and its relation to paraoxonase 1 and 2, MTHFR and AT1R genetic variants.

OBJECTIVE: Common variants of the Paraoxonase (PON), 5-Methyl-Tetrahydrofolate-Reductase (MTHFR) and Angiotensin-II receptor 1 (AT1R) genes have been associated with ischemic stroke (IS) risk. Moreover, carotid atherosclerosis is a common cause of IS. The aim of this study is to explore whether variants in these genes associate with the severity of ultrasonographic determined atherosclerosis assessed in carotid arteries. PATIENTS AND METHODS: Etiologic subtype of cerebral ischemia was determined according to the TOAST classification. Genotypes were detected by PCR and restriction analysis. An ultrasonographic supra-aortic trunks study was performed to all patients to assess their atherosclerotic involvement based on predefined criteria. RESULTS: In IS patients, none of the analyzed gene distributions differed concerning the stenosis degree. Nevertheless, a trend was observed for the rs662 and rs7493 variants of the PON1 and PON2 genes respectively. When evaluated the results based on different inheritance models, a significant contribution of rs7493 variant according to a dominant (OR=2.397, 95% CI (1.001-5.376); p=0.045) and log-additive inheritance forms (OR=1.85, 95% CI (1.07-3.2); p=0.03) was observed. Only rs7493 reached statistical significance (p=0.013), when genotype distribution was analyzed according to carotid intima-media thickness (cIMT) and remain significant in multivariate logistic regression analysis (OR=2.66, 95% CI (1.1 to 6.4); p=0.03). CONCLUSION: In IS patients of the north area of the Gran Canaria island the PON2 (rs7493) gene variant associates with a worse ultrasonographic profile. Conversely, the Cys311Cys homozygosis of the rs7493 variant was also related to a better ultrasonographic profile in our study.

Edema angioneurótico tras trombólisis intravenosa / Orolingual angioedema after thrombolytic treatment

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Paraoxonase 1 and 2 gene variants and the ischemic stroke risk in Gran Canaria population: an association study and meta-analysis.

PURPOSE OF THE STUDY: The present study aims to evaluate the relationship between rs662 (Gln(Q)192Arg(R)) and rs854560 (L55M) and the rs7493 (S311C) in the paraoxonase genes and ischemic stroke (IS) in the population of Gran Canaria (Canary Islands). The association with stroke was also evaluated using systematic review and meta-analysis. METHODS: A total of 129 IS patients and 176 age and gender matched controls were enrolled. For meta-analysis, eligible studies were identified through search in public databases. RESULTS: In multivariate regression analysis only the PON2 S311C variant showed to be an independent predictor of IS (OR = 0.093, 95% CI: 0.014-0.627). Overall, no significant association was found between L55M and IS when all studies were pooled nor by subgroup analysis by ethnicity. Gln192Arg showed a modest risk for IS in the global and in Asian population but with high heterogeneity among studies. A modest risk under a dominant inheritance model was found for the S311C variant with an overall random effect OR of 1.004 (95% CI: 1.00-1.35). There was strong evidence of heterogeneity among studies ( p = 0.0097, I2 = 25.35%) which did not disappear after stratification by ethnicity. CONCLUSIONS: The overall analysis shows a significant contribution of the rs662 variant to IS risk. We found that the CC genotype of the PON2 S311C polymorphism is a risk factor for IS. Results of the meta-analysis partially support this conclusion.

Actualización en la genética del ictus / Update on the genetics of stroke

El ictus es una enfermedad que conlleva unas importantes repercusiones en términos de morbimortalidad, además de costes personales y sociales. Se trata de una entidad compleja en cuya patogenia intervienen múltiples factores ambientales y genéticos; a estos últimos se les atribuye un papel hasta en el 50% de los ictus. El objetivo de la revisión es analizar los métodos disponibles para el diagnóstico genético que incluyen estudios de ligamiento, de variación en número de copias, aproximaciones a genes-candidatos, y de genoma completo (GWAS) y de los polimorfismos asociados a su patogenia. Describimos diversos single nucleotide polymorphisms (SNP, «polimorfismos de un solo nucleótido») relacionados con el ictus en los estudios de asociación y GWAS. Se describen SNP del sistema renina-angiotensina-aldosterona, paraoxonasas, óxido nítrico, sistema de coagulación-fibrinólisis, entre otros. Por otra parte, se recoge el papel de ciertos polimorfismos en el fenotipo de la placa carotídea, en los aneurismas intracraneales o en los hematomas lobulares. También se describen aspectos de farmacogenómica, en los que los SNP afectan a la respuesta y seguridad en el uso de distintos fármacos diversos SNP contribuyen significativamente al riesgo de ictus. El advenimiento de técnicas como GWAS ha contribuido a la comprensión de la genética y de la farmacogenómica del ictus (AU)

Stroke is a disease with significant morbidity, mortality, and economic and social impacts. It is a complex entity whose pathogenesis involves multiple environmental and genetic factors, with the latter having a role in up to 50% of strokes. The objective of the review is to analyze the available methods for the genetic diagnosis including linkage studies of variation in copy number, gene - candidate approximations, or whole genome (GWAS) and polymorphisms associated with its pathogenesis. We describe several single nucleotide polymorphisms (SNPs) associated with stroke in association studies and GWAS such as SNPs of angiotensin, the aldosterone system, paraoxonases, nitric oxide, coagulation, and fibrinolysis system, among others. We also analyze the role of certain polymorphisms in the phenotype of the carotid plaque, intracranial aneurysms and lobar hemorrhages. Pharmacogenomic aspects in which SNPs affect the response and safety regarding the use of different drugs are also described. Several SNPs that significantly contribute to the risk of stroke are also described. The advent of techniques like GWAS has contributed to the understanding of genetics and pharmacogenomics of stroke (AU)

[Update on the genetics of stroke]. / Actualización en la genética del ictus.

Stroke is a disease with significant morbidity, mortality, and economic and social impacts. It is a complex entity whose pathogenesis involves multiple environmental and genetic factors, with the latter having a role in up to 50% of strokes. The objective of the review is to analyze the available methods for the genetic diagnosis including linkage studies of variation in copy number, gene - candidate approximations, or whole genome (GWAS) and polymorphisms associated with its pathogenesis. We describe several single nucleotide polymorphisms (SNPs) associated with stroke in association studies and GWAS such as SNPs of angiotensin, the aldosterone system, paraoxonases, nitric oxide, coagulation, and fibrinolysis system, among others. We also analyze the role of certain polymorphisms in the phenotype of the carotid plaque, intracranial aneurysms and lobar hemorrhages. Pharmacogenomic aspects in which SNPs affect the response and safety regarding the use of different drugs are also described. Several SNPs that significantly contribute to the risk of stroke are also described. The advent of techniques like GWAS has contributed to the understanding of genetics and pharmacogenomics of stroke.

Guía para el tratamiento preventivo del ictus isquémico y AIT (II). Recomendaciones según subtipo etiológico / Guidelines for the preventive treatment of ischaemic stroke and TIA (II). Recommendations according to aetiological sub-type

FUNDAMENTO Y OBJETIVO: Actualizar las guías terapéuticas del Comité ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN en el tratamiento preventivo de ictus isquémico (II) y ataque isquémico transitorio (AIT). MÉTODOS: Revisión de evidencias disponibles sobre la prevención del ictus isquémico y AIT en función del subtipo etiológico. Los niveles de evidencia y grados de recomendación se han basado en la clasificación del Centro de Medicina Basada en la Evidencia. RESULTADOS: En el II de origen aterotrombótico reducen el riesgo de recurrencias el tratamiento antiagregante y los procedimientos revascularizadores en casos seleccionados de estenosis carotidea ipsilateral (70-99%). La prevención de II de origen cardioembólico (fibrilación auricular, valvulopatías, prótesis valvulares y en infarto de miocardio con trombo mural) se basa en el uso de anticoagulantes orales. En el II de origen inhabitual, las terapias preventivas dependerán de la etiología; en la trombosis venosa cerebral la anticoagulación oral es eficaz. CONCLUSIONES: Se concluye con recomendaciones de práctica clínica en prevención de ictus isquémico y AIT adaptadas al subtipo etiológico de II que ha presentado el paciente

BACKGROUND AND OBJECTIVE: To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and Transient Ischaemic Attack (TIA). METHODS: We reviewed the available evidence on ischaemic stroke and TIA prevention according to aetiological subtype. Levels of evidence and recommendation levels are based on the classification of the Centre for Evidence-Based Medicine. RESULTS: In atherothrombotic IS, antiplatelet therapy and revascularization procedures in selected cases of ipsilateral carotid stenosis (70%-90%) reduce the risk of recurrences. In cardioembolic IS (atrial fibrillation, valvular diseases, prosthetic valves and myocardial infarction with mural thrombus) prevention is based on the use of oral anticoagulants. Preventive therapies for uncommon causes of IS will depend on the aetiology. In the case of cerebral venous thrombosis oral anticoagulation is effective. CONCLUSIONS: We conclude with recommendations for clinical practice in prevention of IS according to the aetiological subtype presented by the patient

Trombólisis en el síndrome de alarma capsular / Thrombolysis in capsular warning syndrome

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Tratamiento combinado con antitrombóticos en la prevención secundaria del ictus isquémico: [revisión] / Combined treatment with antithrombotics in secondary prevention of the isquemic stroke: [review]

El ictus isquémico constituye un problema sanitario de primer orden debido a su alto riesgo de recurrencia. La búsqueda de estrategias eficaces y seguras para la prevención de eventos vasculares en los pacientes con un ictus isquémico debe ser una prioridad, con el objetivo de disminuir la mortalidad y discapacidad asociada con el mismo. Diversos estudios han analizado el tratamiento combinado con antitrombóticos para intentar mejorar la eficacia de estos fármacos en la prevención secundaria de eventos vasculares tras un primer ictus isquémico. En este trabajo se revisa el estado actual de la evidencia científica en cuanto a la terapia combinada con antitrombóticos en pacientes con un primer ictus isquémico...

Ischemic stroke constitutes a fundamental health issue due to its high level of recurrence. Developing efficient and safe strategies to prevent vascular episodes in patients with ischemic stroke must be a top priority, with the purpose of diminishing associated mortality and disability. Several studies have examined combined antithrombotic therapy in depth, trying to improve its efficacy in secondary prevention of vascular events after a first ischemic stroke. This work reviews the current state of clinical evidence related to combined antithrombotic therapy in patients presenting a first ischemic stroke...

[Risk factors, etiology and prognosis in patients older than 80 years old with ischemic stroke]. / Factores de riesgo, etiología y pronóstico en pacientes mayores de 80 años con accidente cerebrovascular.

INTRODUCTION: The aim of this study was to analyze differences between patients aged 80 years or less and those aged more than 80 years old a hospital series of ischemic stroke. MATERIAL AND METHODS: We performed a retrospective review of all patients with ischemic stroke or transient ischemic attack requiring admission to the Neurology Service of the Dr. Negrín University Hospital of Gran Canaria (Spain) between January 1, 2004 and December 31, 2006. Data were gathered on hypertension, diabetes mellitus (DM), hyperlipidemia, ischemic cardiopathy (IC), atrial fibrillation (AF), the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, as well as the National Institutes of Health (NIH) scale and the modified Rankin scale (mRS) at discharge. RESULTS: A total of 850 patients were included. Age was >80 years in 106 (12.4%) and was <80 years in 744 (87.6%). In the group aged>80 years, 43.4% were men and 56.6% were women (64.1% men and 35.9% women in the group aged<80 years). Hypertension was present in 81.1% of patients aged>80 years (68.1% in those aged<80 years); previous DM was found in 29.2% (39.3% in the group aged<80 years); hyperlipidemia was present in 26.4% (40.2% in the group aged<80); IC was found in 16.9% (15.8% in the group aged<80); AF was found in 40% (20.9% in the group aged<80 years). In the group of patients aged>80 years, 23.6% had atherothrombotic stroke (19.3% in those aged<80 years); 38.7% were cardioembolic (19.3% in the group aged<80 years); 10.4% were lacunar (22.6% in the group aged<80 years); and 24.5% was of undetermined origin (28.6% in the group aged<80 years). The mRS at discharge was 80 years. CONCLUSIONS: Ischemic stroke in patients over 80 years old leads to certain differences in relation to risk factors, stroke etiology and stroke severity.