Inflammatory Response of Ischemic Tolerance in Circulating Plasma : Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)

Ischemic tolerance (IT) refers to a state where cells are resistant to the damaging effects caused by periods of ischemia. In a clinical scenario, the IT phenomenon would be activated by a recent transient ischemic attack (TIA) before an ischemic stroke (IS). The characterization of inflammatory protein expression patterns will contribute to improved understanding of IT. A total of 477 IS patients from nine hospitals, recruited between January 2011 and January 2016, were included in the current study and divided in three groups: 438 (91.9%) patients without previous TIA (group 1), 22 (4.6%) patients who suffered TIA 24 h before IS (group 2), and 17 (3.5%) patients who suffered TIA between 24 h and 7 days prior to IS (group 3). An inflammatory biomarker panel (IL-6, NT-proBNP, hsCRP, hs-Troponin, NSE, and S-100b) on plasma and a cytokine antibody array was performed to achieve the preconditioning signature potentially induced by TIA phenomena. Primary outcome was modified rankin scale (mRs) score at 90 days. Recent previous TIA was associated with better clinical outcome at 90 days (median mRS of group 1: 2.0 [1.0-4.0]; group 2: 2.0 [0.0-3.0]; group 3: 1.0 [0-2.5]; p = 0.086) and smaller brain lesion (group 1: 3.7 [0.7-18.3]; group 2: 0.8 [0.3-8.9]; group 3: 0.6 [0.1-5.5] mL; p = 0.006). All inflammation biomarkers were down regulated in the groups of recent TIA prior to IS compared to those who did not suffer a TIA events. Moreover, a cytokine antibody array revealed 30 differentially expressed proteins between the three groups. Among them, HRG1-alpha (Fold change 74.4 between group 1 and 2; 74.2 between group 1 and 3) and MAC-1 (Fold change 0.05 between group 1 and 2; 0.06 between group 1 and 3) expression levels would better stratify patients with TIA 7 days before IS. These two proteins showed an earlier inflammation profile that was not detectable by the biomarker panel. Inflammatory pathways were activated by transient ischemic attack, however the period of time between this event and a further ischemic stroke could be determined by a protein signature that would contribute to define the role of ischemic tolerance induced by TIA

SF3B1, RUNX1 and TP53 Mutations Significantly Impact the Outcome of Patients With Lower-Risk Myelodysplastic Syndrome

[Introduction] Prognosis of patients with myelodysplastic syndrome (MDS), particularly the group with lower-risk disease (LR-MDS) is very heterogeneous. Several studies have described the prognostic value of recurrent somatic mutations in MDS including all risk categories. Recently, the incorporation of genomic data to clinical parameters defined the new Molecular International Prognostic Scoring System (IPSS-M).[Materials and Methods] In this study, we evaluated the impact of molecular profile in a series of 181 patients with LR-MDS and non-proliferative chronic myelomonocytic leukemia.[Results] Epigenetic regulators (TET2, ASXL1) and splicing (SF3B1) were the most recurrent mutated pathways. In univariate analysis, RUNX1 or TP53 mutations correlated with lower median overall survival (OS). In contrast, SF3B1 mutation was associated with prolonged median OS [95 months (95% IC, 32-157) vs. 33 months (95% CI, 19-46) in unmutated patients (P < 0.01)]. In a multivariate Cox regression model, RUNX1 mutations independently associated with shorter OS, while SF3B1 mutation retained its favorable impact on outcome (HR: 0.24, 95% CI, 0.1-0.5; P = 0.001). In addition, TP53 or RUNX1 mutations were identified as predictive covariates for the probability of leukemic progression (P < 0.001).[Conclusion] Incorporation of molecular testing in LR-MDS identified a subset of patients with expected poorer outcome, either due to lower survival or probability of leukemic progression.Peer reviewe

Impact of the COVID-19 pandemic on the organisation of stroke care. Madrid Stroke Care Plan

La sobrecarga asistencial y los cambios organizativos frente a la pandemia de COVID-19 podrían estar repercutiendo en la atención al ictus agudo en la Comunidad de Madrid. Métodos: Encuesta estructurada en bloques: características del hospital, cambios en infraestructura y recursos, circuitos de código ictus, pruebas diagnósticas, rehabilitación y atención ambulatoria. Análisis descriptivo según el nivel de complejidad en la atención del ictus (disponibilidad o no de unidad de ictus y de trombectomía mecánica). Resultados: De los 26 hospitales del SERMAS que atienden urgencias en adultos, 22 cumplimentaron la encuesta entre el 16 y 27 de abril. El 95% han cedido neurólogos para atender a pacientes afectados por la COVID-19. Se han reducido camas de neurología en el 89,4%, modificado los circuitos en urgencias para ictus en el 81%, con circuitos específicos para sospecha de infección por SARS-CoV2 en el 50%, y en el 42% de los hospitales los pacientes con ictus agudo positivos para SARS-CoV2 no ingresan en camas de neurología. Ha mejorado el acceso altratamiento, con trombectomía mecánica las 24 h en el propio hospital en 10 hospitales, y sehan reducido los traslados interhospitalarios secundarios. Se ha evitado el ingreso de pacientescon ataque isquémico transitorio o ictus leve (45%) y se han incorporado consultas telefónicaspara seguimiento en el 100%.Conclusiones: Los cambios organizativos de los hospitales de la Comunidad de Madrid frente ala pandemia por SARS-Co2 han modificado la dedicación de recursos humanos e infraestructurasde las unidades de neurología y los circuitos de atención del ictus, realización de pruebasdiagnósticas, ingreso de los pacientes y seguimientoThe overload of the healthcare system and the organisational changes made inresponse to the COVID-19 pandemic may be having an impact on acute stroke care in the Regionof Madrid.Methods: We conducted a survey with sections addressing hospital characteristics, changes ininfrastructure and resources, code stroke clinical pathways, diagnostic testing, rehabilitation,and outpatient care. We performed a descriptive analysis of results according to the level ofcomplexity of stroke care (availability of stroke units and mechanical thrombectomy).Results: The survey was completed by 22 of the 26 hospitals in the Madrid Regional HealthSystem that attend adult emergencies, between 16 and 27 April 2020. Ninety-five percent ofhospitals had reallocated neurologists to care for patients with COVID-19. The numbers of neuro-logy ward beds were reduced in 89.4% of hospitals; emergency department stroke care pathwayswere modified in 81%, with specific pathways for suspected SARS-CoV2 infection established in50% of hospitals; and SARS-CoV2-positive patients with acute stroke were not admitted to neu-rology wards in 42%. Twenty-four hour on-site availability of mechanical thrombectomy wasimproved in 10 hospitals, which resulted in a reduction in the number of secondary hospitaltransfers. The admission of patients with transient ischaemic attack or minor stroke was avoi-ded in 45% of hospitals, and follow-up through telephone consultations was implemented in100%.Conclusions: The organisational changes made in response to the SARS-Co2 pandemic in hos-pitals in the Region of Madrid have modified the allocation of neurology department staff andinfrastructure, stroke units and stroke care pathways, diagnostic testing, hospital admissions,and outpatient follow-u

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality

Background and purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P&lt;0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P&lt;0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality.

BACKGROUND AND PURPOSE: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. METHODS: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). RESULTS: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. CONCLUSIONS: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT

Exemple de programme pour la promotion de la santé mentale et neurologique au travail en équateur.

International audienc

Tratamientos de reperfusión en el infarto cerebral agudo por disección de arterias cervicales

Resumen: Introducción: Las disecciones de arteriales cervicales (DAC) provocan hasta el 20% de los ictus isquémicos en menores de 45 años. El beneficio de los tratamientos de reperfusión en fase aguda no está plenamente clarificado. Métodos: Revisión retrospectiva de pacientes con DAC ingresados en un centro terciario de ictus desde 2010 hasta 2015. Recogemos las características basales, clínicas, los tratamientos, el pronóstico funcional y la mortalidad. Resultados: Se registraron 35 DAC (23 carotídeas/12 vertebrales). La edad media fue de 43,5 ± 9,5 años y el 67,7% fueron varones. En 10 casos (32,3%) hubo antecedente de un traumatismo. Los factores de riesgo más frecuentes fueron la hipertensión arterial (29%) y el tabaquismo (35,5%). La presentación clínica más frecuente fue el infarto cerebral en 29 pacientes (93,5%). La mediana de puntuación National Institute of Health Stroke Scale basal fue de 6 (0-41). El método diagnóstico más empleado fue la angio-TC (74,2%), seguido de resonancia magnética (64,5%) y arteriografía cerebral (45,6%). Siete pacientes (22,6%) fueron tratados con fibrinólisis intravenosa y 11 (35,5%) con tratamiento endovascular (TEV) ± fibrinólisis intravenosa. A los 3 meses, la independencia funcional (escala de Rankin 0-2) fue del 57,1% y del 63,6%, respectivamente. Falleció un paciente (3,2%). Conclusiones: La forma de presentación más frecuente de la DAC fue el infarto cerebral. Estos casos pueden beneficiarse de terapias de reperfusión, con un pronóstico similar al resto de enfermos con ictus isquémicos. Se requieren registros más extensos para conocer mejor la respuesta a los tratamientos de reperfusión en fase aguda en este grupo de pacientes. Abstract: Introduction: Cervical artery dissection (CAD) is responsible for up to 20% of all ischaemic strokes in patients younger than 45. The benefits of acute-phase reperfusion therapy in these patients have yet to be confirmed. Methods: We conducted a retrospective review of patients with CAD admitted to a comprehensive stroke centre between 2010 and 2015. We recorded baseline clinical characteristics, treatments, functional outcomes, and mortality. Results: We identified 35 cases of CAD (23 carotid/12 vertebral); mean age was 43.5  ±  9.5 years and 67.7% were men. Ten patients (32.3%) had a history of trauma. The most frequent risk factors were arterial hypertension (29%) and smoking (35.5%). The most common clinical presentation was ischaemic stroke (29 patients, 93.5%). The median baseline National Institute of Health Stroke Scale score was 6 (range, 0-41). The most frequently used diagnostic method was CT angiography (74.2%), followed by MRI (64.5%) and digital subtraction angiography (45.6%). Seven patients (22.6%) were treated with intravenous fibrinolysis and 11 (35.5%) with endovascular treatment plus intravenous fibrinolysis; at 3 months, functional independence (modified Rankin Scale scores 0-2) was achieved by 57.1% and 63.6% of these cases, respectively. One patient died (3.2%). Conclusions: In our sample, the most common form of presentation of CAD was ischaemic stroke. Reperfusion therapy seems to be a safe and effective option for these patients, and outcomes resemble those of other patients with ischaemic stroke. Larger comparative studies are necessary to better assess response to reperfusion therapy in acute ischaemic stroke. Palabras clave: Ictus isquémico, Disección carotídea, Disección vertebral, Disección arterial cervical, Fibrinólisis intravenosa, Tratamiento endovascular, Keywords: Ischaemic stroke, Carotid artery dissection, Vertebral artery dissection, Cervical artery dissection, Intravenous fibrinolysis, Endovascular treatmen

Reperfusion therapy in patients with acute ischaemic stroke caused by cervical artery dissection

Introduction: Cervical artery dissection (CAD) is responsible for up to 20% of all ischaemic strokes in patients younger than 45. The benefits of acute-phase reperfusion therapy in these patients have yet to be confirmed. Methods: We conducted a retrospective review of patients with CAD admitted to a comprehensive stroke centre between 2010 and 2015. We recorded baseline clinical characteristics, treatments, functional outcomes, and mortality. Results: We identified 35 cases of CAD (23 carotid/12 vertebral); mean age was 43.5 ± 9.5 years and 67.7% were men. Ten patients (32.3%) had a history of trauma. The most frequent risk factors were arterial hypertension (29%) and smoking (35.5%). The most common clinical presentation was ischaemic stroke (29 patients, 93.5%). The median baseline National Institute of Health Stroke Scale score was 6 (range, 0-41). The most frequently used diagnostic method was CT angiography (74.2%), followed by MRI (64.5%) and digital subtraction angiography (45.6%). Seven patients (22.6%) were treated with intravenous fibrinolysis and 11 (35.5%) with endovascular treatment plus intravenous fibrinolysis; at 3 months, functional independence (modified Rankin Scale scores 0-2) was achieved by 57.1% and 63.6% of these cases, respectively. One patient died (3.2%). Conclusions: In our sample, the most common form of presentation of CAD was ischaemic stroke. Reperfusion therapy seems to be a safe and effective option for these patients, and outcomes resemble those of other patients with ischaemic stroke. Larger comparative studies are necessary to better assess response to reperfusion therapy in acute ischaemic stroke. Resumen: Introducción: Las disecciones de arteriales cervicales (DAC) provocan hasta el 20% de los ictus isquémicos en menores de 45 años. El beneficio de los tratamientos de reperfusión en fase aguda no está plenamente clarificado. Métodos: Revisión retrospectiva de pacientes con DAC ingresados en un centro terciario de ictus desde 2010 hasta 2015. Recogemos las características basales, clínicas, los tratamientos, el pronóstico funcional y la mortalidad. Resultados: Se registraron 35 DAC (23 carotídeas/12 vertebrales). La edad media fue de 43,5 ± 9,5 años y el 67,7% fueron varones. En 10 casos (32,3%) hubo antecedente de un traumatismo. Los factores de riesgo más frecuentes fueron la hipertensión arterial (29%) y el tabaquismo (35,5%). La presentación clínica más frecuente fue el infarto cerebral en 29 pacientes (93,5%). La mediana de puntuación National Institute of Health Stroke Scale basal fue de 6 (0-41). El método diagnóstico más empleado fue la angio-TC (74,2%), seguido de resonancia magnética (64,5%) y arteriografía cerebral (45,6%). Siete pacientes (22,6%) fueron tratados con fibrinólisis intravenosa y 11 (35,5%) con tratamiento endovascular (TEV) ± fibrinólisis intravenosa. A los 3 meses, la independencia funcional (escala de Rankin 0-2) fue del 57,1% y del 63,6%, respectivamente. Falleció un paciente (3,2%). Conclusiones: La forma de presentación más frecuente de la DAC fue el infarto cerebral. Estos casos pueden beneficiarse de terapias de reperfusión, con un pronóstico similar al resto de enfermos con ictus isquémicos. Se requieren registros más extensos para conocer mejor la respuesta a los tratamientos de reperfusión en fase aguda en este grupo de pacientes. Keywords: Ischaemic stroke, Carotid artery dissection, Vertebral artery dissection, Cervical artery dissection, Intravenous fibrinolysis, Endovascular treatment, Palabras clave: Ictus isquémico, Disección carotídea, Disección vertebral, Disección arterial cervical, Fibrinólisis intravenosa, Tratamiento endovascula

Intervencionismo neurovascular en la fase aguda del infarto cerebral

Resumen: Introducción y objetivos: El intervencionismo neurovascular (INV) en la fase aguda del ictus isquémico es una alternativa válida en los casos en que la trombólisis intravenosa está contraindicada o cuando no ha sido efectiva. Nuestro objetivo es presentar la experiencia inicial del INV en la Comunidad de Madrid. Métodos: Registro prospectivo de ictus isquémicos tratados con INV en la Comunidad de Madrid (2005-2009). Se recogen variables epidemiológicas, factores de riesgo y gravedad del ictus mediante la NIHSS (National Institute of Health Stroke Scale). Registramos el tipo de técnica, la situación funcional a los 3 meses, mediante la escala de Rankin modificada (eRm), complicaciones hemorrágicas y mortalidad. Resultados: Se incluyó a 41 pacientes. La media ± desviación estándar de edad fue 58,6 ± 19,9 años; el 56,1%, varones. Hubo 22 pacientes con ictus de circulación anterior y 19, de circulación posterior. La mediana de la puntuación NIHSS basal fue 17 [intervalo, 2-34]; 7 pacientes recibieron trombólisis intravenosa previa. Las técnicas utilizadas fueron: interrupción mecánica (26 pacientes), trombólisis intraarterial (26 pacientes), angioplastia/stent (5 pacientes), extracción mecánica mediante dispositivo MERCI (Mechanical Embolus Removal in Cerebral Ischemia) (3 pacientes). Se consiguió una recanalización parcial o total en 32 pacientes (78%). Un paciente presentó una transformación hemorrágica sintomática (2,4%). Al cabo de 3 meses el 53,6% de los pacientes eran independientes (eRm ≤ 2) y la mortalidad general fue del 19,5%. Conclusiones: El ictus isquémico es una emergencia médica tratable en las primeras horas. El INV es una alternativa terapéutica factible y útil en los casos de contraindicación o ineficacia de la trombólisis intravenosa. Abstract: Background and purpose: Endovascular therapies in acute ischaemic stroke may offer benefits to patients that are not eligible for standard use of intravenous tissue activator plasminogen (iv t-PA) or when this is not effective. Our aim is to present the initial experience in with endovascular techniques in the Community of Madrid. Methods: We present data from our registry of acute ischaemic strokes treated with endovascular re-perfusion therapies in five University Hospitals in Madrid (Spain) during the period 2005-2009. We recorded demographic data, vascular risk factors, risk severity with the NIHSS (National Institute of Health Stroke Scale), endovascular techniques, complications and mortality rates. Functional outcome and neurological disability at 90 days was defined by the modified Rankin scale (mRs). Results: A total of 41 patients were treated with endovascular therapies. Mean age was 58.6 ± 19.9, and 56.1% were males. Of those 22 patients had an anterior circulation stroke and 19 had a posterior circulation stroke. Baseline NIHSS score was: median, 17 [range, 2-34]; 7 patients had previously received iv t-PA. The following endovascular techniques were performed: mechanical disruption (26 patients), intra-arterial infusion of t-PA (26 patients), angioplasty and stenting (5 patients), mechanical use of MERCI device (3 patients). Partial or total re-canalization was achieved in 32 patients (78%). Only one patient had a symptomatic cerebral haemorrhage. Three months after stroke, 53.6% of the patients were independent (mRs ≤ 2) and overall mortality rate was 19.5%. Conclusions: Acute ischaemic stroke is a potentially treatable medical emergency within the first hours after the onset of symptoms. Stroke endovascular procedures constitute an alternative for patients with iv t-PA exclusion criteria or when this is not effective. Palabras clave: Ictus isquémico, Trombólisis, Intervencionismo neurovascular, Infarto cerebral, Trombólisis intraarterial, Activador del plasminógeno tisular, Keywords: Ischaemic stroke, Thrombolysis, Endovascular procedures, Cerebral infarction, Intra-arterial thrombolysis, Tissue plasminogen activato