The use and abuse of survival analysis and Kaplan-Meier curves in surgical trials.

BACKGROUND: Survival analysis based on Cox regression and Kaplan-Meier curves, initially devised for oncology trials, have frequently been used in other contexts where fundamental statistical assumptions (such as a constant hazard ratio) are not satisfied. This is almost always the case in trials that compare surgery with medical management. METHODS: We review a trial that compared extracranial-intracranial bypass surgery (EC-IC bypass) with medical management (MM) of patients with symptomatic occlusion of the carotid or middle cerebral artery, where it was claimed that surgery was of no benefit. We discuss a hypothetical study and review other neurovascular trials which have also used survival analysis to compare results. RESULTS: The trial comparing EC-IC bypass and MM did not satisfy the fundamental proportional hazard assumption necessary for valid analyses. This was also the case for two prior EC-IC bypass trials, as well as for other landmark neurovascular studies, such as the trials comparing endarterectomy with MM for carotid stenoses, or for the trial that compared intervention and MM for unruptured brain arteriovenous malformations. While minor deviations may have little effect on large trials, it may be impossible to show the benefits of surgery when trial size is small and deviations large. CONCLUSION: Survival analyses are inappropriate in RCTs comparing surgery with conservative management, unless survival is calculated after the postoperative period. Alternative ways to compare final clinical outcomes, using for example a fixed follow-up period, should be planned for preventive surgical trials that compare intervention with conservative management.

Outcome of patients with multivessel occlusion stroke after endovascular treatment.

INTRODUCTION: Little is known about the implications of multivessel occlusions (MVO) in large vessel occlusion stroke patients who undergo endovascular treatment (EVT). PATIENTS AND METHODS: We report data from the MR CLEAN Registry: a prospective, observational study on all stroke patients who underwent EVT in the Netherlands (March 2014-November 2017). We included patients with an intracranial target occlusion in the anterior circulation. An MVO was defined as an MCA occlusion (M1/M2) or intracranial ICA/ICA-T occlusion, with a concurrent second occlusion in the ACA or PCA territory confirmed on baseline CTA. To compare outcomes, we performed a 10:1 propensity score matching analysis with a logistic regression model including potential confounders. Outcome measures included 90-day functional outcome (modified Rankin Scale, mRS) and mortality. RESULTS: Of 2946 included patients, 71 patients (2.4%) had an MVO (87% concurrent ACA occlusion, 10% PCA occlusion, 3% ⩾3 occlusions). These patients were matched to 71 non-MVO patients. Before matching, MVO patients had a higher baseline NIHSS (median 18 vs 16, p = 0.001) and worse collateral status (absent collaterals: 17% vs 6%, p < 0.001) compared to non-MVO patients. After matching, MVO patients had worse functional outcome at 90 days (median mRS 5 vs 3, cOR 0.39; 95%CI 0.25-0.62). Mortality was higher in MVO patients (46% vs 27%, OR 2.11, 95%CI 1.24-3.57). DISCUSSION AND CONCLUSION: MVOs on baseline imaging were uncommon in LVO stroke patients undergoing EVT, but were associated with poor functional outcome.

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction / Asociación de niveles sanguíneos de caspasa-8 y mortalidad de pacientes con infarto maligno de la arteria cerebral media

Objective High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). Design Observational prospective study. Setting Five Intensive Care Units (ICU). Patients Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. Interventions Determination of serum caspase-8 levels when MMCAI was diagnosed. Main variables of interest Mortality at 30 days and time until this event. Results Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%–91%; p<0.001) by serum caspase-8 levels. Kaplan–Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4–28.4; p<0.001). Conclusions The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study (AU)

Objetivo Se han encontrado altas concentraciones de caspasa-8 (principal caspasa iniciadora de la vía extrínseca de apoptosis) en el tejido cerebral de pacientes con traumatismo craneoencefálico y en la sangre de pacientes con diferentes enfermedades. Sin embargo, no hay datos sobre las concentraciones sanguíneas de caspasa-8 en pacientes con ictus isquémico. Por tanto, el objetivo de este estudio fue determinar si existe una asociación entre las concentraciones sanguíneas de caspasa-8 y la probabilidad y velocidad de mortalidad a 30días en pacientes con infarto maligno de la arteria cerebral media (MMCAI). Diseño Observacional y prospectivo. Ámbito Cinco unidades de cuidados intensivos (UCI). Pacientes Pacientes con MMCAI grave definido como infarto agudo en más del 50% de ese territorio y escala de coma de Glasgow (GCS)<9. Intervenciones Determinación de niveles séricos de caspasa-8 cuando se diagnosticó el MMCAI grave. Variables de interés principal Mortalidad hasta los 30dias y tiempo hasta este evento. Resultados Los pacientes fallecidos (n=28) en comparación con los supervivientes (n=28) mostraron mayores concentraciones séricas de caspasa-8 (p<0,001), menor recuento plaquetario (p=0,01) y menor GCS (p=0,002). Encontramos un área bajo la curva para la predicción de mortalidad del 78% (IC 95%: 65-91%; p<0,001) por los niveles séricos de caspasa-8. El análisis de Kaplan-Meier encontró una mayor tasa de mortalidad en pacientes con niveles séricos de caspasa-8>62,8ng/mL (hazard ratio: 11,2; IC 95%: 4,4-28,4; p<0,001). Conclusiones La asociación de elevadas concentraciones sanguíneas de caspasa-8 con la tasa y velocidad de mortalidad a 30días en pacientes con MMCAI es el principal hallazgo nuevo de nuestro estudio (AU)

Mortality after large artery occlusion acute ischemic stroke.

Despite randomized trials showing a functional outcome benefit in favor of endovascular therapy (EVT), large artery occlusion acute ischemic stroke is associated with high mortality. We performed a retrospective analysis from a prospectively collected code stroke registry and included patients presenting between November 2016 and April 2019 with internal carotid artery and/or proximal middle cerebral artery occlusions. Ninety-day mortality status from registry follow-up was corroborated with the Social Security Death Index. A multivariable logistic regression model was fitted to determine demographic and clinical characteristics associated with 90-day mortality. Among 764 patients, mortality rate was 26%. Increasing age (per 10 years, OR 1.48, 95% CI 1.25-1.76; p < 0.0001), higher presenting NIHSS (per 1 point, OR 1.05, 95% CI 1.01-1.09, p = 0.01), and higher discharge modified Rankin Score (per 1 point, OR 4.27, 95% CI 3.25-5.59, p < 0.0001) were independently associated with higher odds of mortality. Good revascularization therapy, compared to no EVT, was independently associated with a survival benefit (OR 0.61, 95% CI 0.35-1.00, p = 0.048). We identified factors independently associated with mortality in a highly lethal form of stroke which can be used in clinical decision-making, prognostication, and in planning future studies.

Serum Levels of B-cell Lymphoma-2 Anti-Apoptotic Protein and Malignant Middle Cerebral Artery Infarction Mortality.

INTRODUCTION AND GOAL: There is scarce and contradictory data on B-cell lymphoma 2 (Bcl2), member of the Bcl-2 antiapoptotic molecules family of intrinsic apoptosis pathway, in ischemic stroke patients. The objective of this study was to determine whether there is an association between blood Bcl2 concentrations and mortality of ischemic stroke patients. MATERIAL AND METHODS: Five Intensive Care Units participated in this prospective and observational study of patients with severe malignant middle cerebral artery infarction (MMCAI). Severe MMCAI was diagnosed when acute infarction was present in 50% or more of said region and with a Glasgow Coma Scale (GCS) score of less than 9 points. Serum samples were collected at the time of MMCAI diagnosis. FINDINGS: Higher serum Bcl2 concentrations (p = 0.001), lower platelet count (p = 0.01) and lower GCS (p = 0.002) were found in non-survivors (n = 28) than in MMCAI survivors (n = 28). Serum Bcl2 levels had an area under the curve for mortality prediction of 75% (95% CI = 62%-88%; p < 0.001). Patients with serum Bcl2 levels > 43.6 ng/mL had higher mortality rate according to Kaplan-Meier analysis (Hazard ratio=10.0; 95% CI = 3.4-29.5; p < 0.001). Multiple logistic regression showed an association between serum Bcl2 and mortality at 30 days (OR = 1.041; 95% CI = 1.006-1.077; p = 0.02) controlling for GCS and platelet count. CONCLUSIONS: This study reports for the first time the higher blood Bcl2 concentrations in non-surviving ischemic stroke patients than in survivors and the association between elevated blood Bcl2 and mortality in ischemic stroke patients.

DNA and RNA oxidative damage are associated to mortality in patients with cerebral infarction / El daño oxidativo del ADN y ARN se asocian con la mortalidad en los pacientes con inf0arto cerebral

OBJECTIVE: Secondary injury due to oxidation may occur during ischemic stroke, possibly leading to oxidative damage to deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Higher blood concentrations of 8-hydroxy-2′-deoxyguanosine (8-OHdG) (through the oxidation of guanosine from DNA) have been found in ischemic stroke patients than in healthy subjects, and in patients with versus without post-ischemic stroke depression. The present study was carried out to explore the possible association between serum DNA and RNA oxidative damage and mortality in patients with cerebral infarction. METHODS: A prospective, multicenter observational study was carried out in the Intensive Care Units of 6 Spanish hospitals. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as ischemic changes evidenced by computed tomography in more than 50% of the middle cerebral artery territory and a Glasgow Coma Score (GCS)<9. Serum concentrations of the three oxidized guanine species (OGS) (8-hydroxyguanine from DNA or RNA, 8-hydroxyguanosine from RNA, and 8-OHdG from DNA) on the day of MMCAI diagnosis were determined. The study endpoint was 30-day mortality. RESULTS: We found higher serum OGS levels (p < 0.001) in non-surviving (n=34) than in surviving patients (n=34). Logistic regression analyses showed serum OGS levels to be associated to 30-day mortality controlling for lactic acid, GCS and platelet count (OR=1.568; 95%CI=1.131-2.174; p = 0.01). CONCLUSIONS: The novel observation in this study is the association between global serum OGS concentration and mortality in ischemic stroke patients

OBJETIVO: En el infarto cerebral puede aparecer una lesión cerebral secundaria debido a la oxidación del ácido desoxirribonucleico (ADN) y del ácido ribonucleico (ARN). Se han encontrado concentraciones sanguíneas de 8-hidroxi-2'-desoxiguanosina (8-OHdG) (por la oxidación de la guanosina del ADN) más altas en pacientes con infarto cerebral que en individuos sanos, y en pacientes con depresión tras un infarto cerebral. El objetivo de nuestro estudio fue determinar si existe una asociación entre el daño oxidativo del ADN y del ARN, y la mortalidad de los pacientes con infarto cerebral. MÉTODOS: Estudio prospectivo, observacional y multicéntrico realizado en unidades de cuidados intensivos de 6 hospitales españoles. Se incluyeron pacientes con un infarto maligno grave de la arteria cerebral media (MMCAI), definido como la presencia de cambios isquémicos en la tomografía en más del 50% del territorio de la arteria cerebral media y menos de 9 puntos en la escala Glasgow Coma Scale (GCS). Se determinaron los niveles séricos de las 3 especies oxidadas de la nucleobase guanina (OGS) (8-hidroxiguanina del ADN o ARN, 8-hidroxiguanosina del ARN y 8-OHdG del ADN) en el día del diagnóstico del MMCAI. La variable principal fue la mortalidad a 30 días. RESULTADOS: Encontramos concentraciones séricas de OGS (p < 0,001) más altas en los pacientes fallecidos (n=34) que en los supervivientes (n=34). La regresión logística mostró que los niveles séricos de OGS se asociaban con la mortalidad a los 30 días controlando por ácido láctico, GCS y recuento plaquetario (odds ratio=1,568; IC 95%=1,131-2,174; p = 0,01). CONCLUSIONES: El nuevo hallazgo de nuestro estudio fue la asociación entre los niveles séricos de OGS globales y la mortalidad de los pacientes con infarto cerebral

Effect of Recanalization on Cerebral Edema, Long-Term Outcome, and Quality of Life in Patients with Large Hemispheric Infarctions.

OBJECTIVES: Space-occupying cerebral edema is the main cause of mortality and poor functional outcome in patients with large cerebral artery occlusion (LVO). We aimed to determine whether recanalization of LVO would augment cerebral edema volume and the impact on functional outcome and quality of life (QoL). MATERIALS AND METHODS: Prospectively, 43 patients with large middle cerebral artery territory infarction or NIHSS ≥ 12 on admission were enrolled. The degree of recanalization (partial and complete versus no recanalization) was assessed by computed tomography (CT)-angiography or Duplex ultrasound more than 24 h after symptom onset. Cerebral edema volume was measured on follow up CTs by computer-based planimetry. Mortality, functional outcome (by modified Ranking Scale (mRS) and Barthel Index (BI)) were assessed at discharge and 12 months, and QoL (by SF-36 and EQ-5D-3L) at 12 months. RESULTS: Mean cerebral edema volume was 333±141 ml without recanalization (n=13, group 1) and 276±140 ml with partial or complete recanalization (n=30, group 2, p= 0.23). There were no significant differences in mortality at discharge (38% versus 23%), at 12 months (58% versus 48%), in functional outcome at discharge (mRS 0-3: 0% both; mRS 4-5: 62% versus 77%) and at 12 months (mRS 0-3: 0% versus 11%; mRS 4-5: 42% versus 41%). The BI improved significantly from discharge to 12 months only in group 2 (p=0.001). Mean physical component score in SF-36 was 25.6±6.4, psychological component score was 41.9±14.1. In the EQ-5D-3L, most patients reported problems with activities of daily living, reduced mobility, and selfcare. CONCLUSIONS: Recanalization of a large cerebral artery occlusion in the anterior circulation territories is not associated with amplification of post-ischemic cerebral edema but may be correlated with better long-term functional outcome. QoL was low and mainly dependent on physical disability. The association between recanalization, collateral status and development of cerebral edema after LVO and the effect on functional outcome and quality of life should be explored in a larger patient population.

M2 segment thrombectomy is not associated with increased complication risk compared to M1 segment: A meta-analysis of recent literature.

INTRODUCTION: Recent clinical comparisons of M1 and M2 segment endovascular thrombectomy have reached incongruous results in rates of complication and functional outcomes. This study aims to clarify the controversy surrounding this rapidly advancing technique through literature review and meta-analysis. METHODS: A Pubmed search was performed (January 2015-September 2019) using the following keywords: "M2 AND ("stroke" OR "occlusion") AND ("thrombectomy" OR "endovascular")". Safety and clinical outcomes were compared between segments via weighted Student's t-test, Chi-square and odds ratio while study heterogeneity was analyzed using Cochran Q and I2 tests. RESULTS: Pubmed identified 208 articles and eleven studies were included after full-text analysis, comprising 2,548 M1 and 758 M2 mechanical thrombectomy segment cases. Baseline National Institutes of Health Stroke Scale scores were comparatively lower in patients experiencing an M2 occlusion (16 ± 1.25 vs 13.6 ± 0.96, p < 0.01). Patients who underwent M2 mechanical thrombectomy were more likely to experience both good clinical outcomes (modified Rankin Scale 0-2) (48.6% vs 43.5% respectively, OR 1.24; CI 1.05-1.47, p = 0.01) and excellent clinical outcomes (modified Rankin Scale 0-1) (34.7% vs. 26.5%%, OR 1.6; CI 1.28-1.99, p < 0.01) at 90 days compared to M1 mechanical thrombectomy. Neither recanalization rates (75.3% vs 72.8%, OR 0.92, CI 0.75-1.13, p = 0.44) nor symptomatic intracranial hemorrhage rates (5.6% vs 4.9%, OR 0.92; CI 0.61-1.39, p= 0.7) were significantly different between M1 and M2 cohorts. Mortality was less frequent in the M2 cohort compared to M1 (16.3% vs 20.7%, OR 0.73; CI 0.57-0.94, p = 0.01). M1 and M2 cohorts did not differ in symptom onset-to-puncture (238.1 ± 46.7 vs 239.8 ± 43.9 min respectively, p=0.488) nor symptom onset-to recanalization times (318.7 ± 46.6 vs 317.7 ± 71.1 min respectively, p = 0.772), though mean operative duration was shorter in the M2 cohort (61.8 ± 25.5 vs 54.6 ± 24 min, p < 0.01). CONCLUSIONS: Patients who underwent M2 mechanical thrombectomy had a higher prevalence of good and excellent clinical outcomes compared to the M1 mechanical thrombectomy cohorts. Additionally, our data suggest lower mortality rates in the M2 cohort and symptomatic intracranial hemorrhage rates that are similar to the M1 cohort. Therefore, M2 segment thrombectomy likely does not pose a significantly elevated operative risk and may have a positive impact on patient outcomes.

The intranasal administration of Carthamus tinctorius L. extract/phospholipid complex in the treatment of cerebral infarction via the TNF-α/MAPK pathway.

Carthamus tinctorius L.(Safflower), a herbal formula from Traditional Chinese Medicine (TCM), has been widely used for the treatment of cardio-cerebrovascular diseases, particularly cerebral infarction (CI) or cerebral ischemia-reperfusion injury. However, we know very little about the specific mechanisms associated with the therapeutic effect of Safflower on CI. In this study, we used a network pharmacology-based approach, together with rat model of CI, to gain more insight into of such mechanisms. Our analysis showed that Safflower contains 52 active compounds that target 247 genes, which were also cross-referenced with 299 genes associated with CI. Consequently, we identified 52 target genes in Safflower that were associated with CI. These 52 target genes were analyzed by gene ontology (GO) enrichment analysis, leading to the identification of 1491 biological process items, 90 molecular function items and 19 cell assembly items. Eighty-nine pathways were generated by KEGG enrichment (P < 0.05). Next, we investigated the effect of the extract of safflower (ES) and Safflower extract phospholipid complex (ESPC), delivered via the nasal route, on an animal model of the middle cerebral artery occlusion (MCAO). Our data confirmed that Safflower was able to treat CI by the regulating the TNF-α/MAPK pathway via CASP3. The therapeutic effect of ES and ESPC on CI acts by improving the circulation of blood in the central nervous system, reducing the inflammatory reaction, inhibiting apoptosis, and by protecting brain nerve cells from injury.

Intranasal Dexamethasone Reduces Mortality and Brain Damage in a Mouse Experimental Ischemic Stroke Model.

Neuroinflammation triggered by the expression of damaged-associated molecular patterns released from dying cells plays a critical role in the pathogenesis of ischemic stroke. However, the benefits from the control of neuroinflammation in the clinical outcome have not been established. In this study, the effectiveness of intranasal, a highly efficient route to reach the central nervous system, and intraperitoneal dexamethasone administration in the treatment of neuroinflammation was evaluated in a 60-min middle cerebral artery occlusion (MCAO) model in C57BL/6 male mice. We performed a side-by-side comparison using intranasal versus intraperitoneal dexamethasone, a timecourse including immediate (0 h) or 4 or 12 h poststroke intranasal administration, as well as 4 intranasal doses of dexamethasone beginning 12 h after the MCAO versus a single dose at 12 h to identify the most effective conditions to treat neuroinflammation in MCAO mice. The best results were obtained 12 h after MCAO and when mice received a single dose of dexamethasone (0.25 mg/kg) intranasally. This treatment significantly reduced mortality, neurological deficits, infarct volume size, blood-brain barrier permeability in the somatosensory cortex, inflammatory cell infiltration, and glial activation. Our results demonstrate that a single low dose of intranasal dexamethasone has neuroprotective therapeutic effects in the MCAO model, showing a better clinical outcome than the intraperitoneal administration. Based on these results, we propose a new therapeutic approach for the treatment of the damage process that accompanies ischemic stroke.

Ataque cerebrovascular isquémico agudo de territorio anterior: Tratamiento endovascular / Acute ischemic stroke in anterior territory: endovascular treatment

La terapia endovascular (TEV) es el tratamiento estándar del ataque cerebrovascular isquémico (ACVi) con oclusión de gran vaso (OGVC). Aún no se conoce si esos resultados pueden generalizarse a la práctica diaria. Se describen los resultados de la TEV en pacientes con ACVi por OGVC dentro de las 24 horas, en un análisis retrospectivo entre enero 2013 y diciembre 2017 que incluyó 139 casos consecutivos con ACVi y OGVC en arteria cerebral media (ACM), hasta 24 horas del inicio de los síntomas, que recibieron TEV en nuestra institución. El resultado primario medido fue la escala de Rankin modificada (mRS) ≤ 2 a 90 días. Se evaluaron también: reperfusión exitosa, según la escala modificada de trombólisis en infarto cerebral (mTICI) 2b/3, hemorragia intracraneal sintomática (HIS) y mortalidad a 90 días. La edad media: 67.5 ± 15.0, siendo el 51.8% mujeres. La mediana basal de National Institute of Health Stroke Scale (NIHSS) fue 14 (IIC 8-18); la mediana del tiempo desde inicio de síntomas hasta punción inguinal: 331 min (IIC 212-503). El 45.3%, 63 pacientes, fueron tratados > 6 horas después del inicio de síntomas. La tasa de mRS ≤ 2 fue 47.5%. Se logró una reperfusión exitosa en el 74.8%. La tasa de mortalidad a 90 días fue del 18.7% y la HIS del 7.9%. Nuestro registro de pacientes de la vida real con ACVi por OGVC tratados con TEV dentro de las 24 horas mostró altas tasas de reperfusión, buenos resultados funcionales y pocas complicaciones, acorde con las recomendaciones internacionales.

Endovascular treatment (EVT) has become the standard of care for acute ischemic stroke (AIS) with proximal large vessel occlusions (LVO). However, it is still unknown whether these results can be generalized to clinical practice. We aimed to perform a retrospective review of patients who received EVT up to 24 hours, and to assess safety and efficacy in everyday clinical practice. We performed a retrospective analysis, from January 2013 to December 2017, on 139 consecutive patients with AIS for anterior circulation LVO strokes up to 24 h from symptoms onset, who received EVT in our institution. The primary outcome measured was a modified Rankin scale (mRS) ≤ 2 at 90 days. Secondary outcomes included successful reperfusion, defined as a modified Thrombolysis in Cerebral Infarction (mTICI) scale 2b/3, mortality rate at 90 days and symptomatic intracranial hemorrhage (sICH). The mean age was 67.5 ± 15.0, with 51.8% female patients. Median baseline National Institute of Health Stroke Scale (NIHSS) was 14 (IQR 8-18); median time from symptom onset to groin puncture was 331 min (IQR 212-503). Sixty-three patients (45.3%) were treated beyond 6 hours after symptoms onset. The rate of mRS ≤ 2 was 47.5%. Successful reperfusion was achieved in 74.8 %. Mortality rate at 90 days was 18.7 % and sICH was 7.9 %. Our registry of real-life patients with AIS due to LVO who received EVT within 24 hours showed high reperfusion rates, and good functional results with few complications, according to international recommendations.

Distal arterial occlusions in patients with mild strokes - is endovascular therapy superior to thrombolysis alone?

BACKGROUND AND PURPOSE: Safety and efficacy of endovascular thrombectomy (EVT) in patients with mild stroke syndromes is unclear, especially in distal vessel occlusions. METHODS: We analysed in our stroke database (HeiReKa) between 2002 and April 2019 safety and efficacy of EVT compared to intravenous thrombolysis (IVT) in patients with occlusions distal to the M1 segment of the middle cerebral artery and the top of the basilar artery who presented with a National Institute of Health Stroke Scale (NIHSS) below 6. Excellent (good) outcome was defined as modified rankin scale (mRS) 0-1 (0-2) or return to baseline mRS (good) after 3 months. Safety endpoints were mortality after 3 months and intracranial hemorrhage according to the Heidelberg Bleeding Classification (HBC). RESULTS: Of 4167 patients 94 met the inclusion criteria. Sixty-four patients were allocated to the IVT group and 30 to the EVT group of which 15 also received IVT; three patients (4.6%) in the IVT group received rescue EVT. Baseline characteristics did not differ but more M2 occlusions were found in the EVT group (93.3% vs. 64.1%, p = 0.02). Intracranial bleeding occurred more often in EVT patients (HBC class 2: 13.3% vs. 1.6%, p = 0.01). Excellent and good outcome were not significantly different (75% vs. 70%, p = 0.65 and 87.5% vs. 73.3%, p = 0.14). Mortality was significantly lower in IVT patients (1.6% vs. 13.3%, p = 0.04). CONCLUSION: Rates of excellent and good outcome after IVT or EVT were almost similar, but safety parameters were increased after EVT. EVT may be considered in selected patients after careful risk/benefit analysis.

[Acute ischemic stroke in anterior territory: endovascular treatment]. / Ataque cerebrovascular isquémico agudo de territorio anterior. Tratamiento endovascular.

Endovascular treatment (EVT) has become the standard of care for acute ischemic stroke (AIS) with proximal large vessel occlusions (LVO). However, it is still unknown whether these results can be generalized to clinical practice. We aimed to perform a retrospective review of patients who received EVT up to 24 hours, and to assess safety and efficacy in everyday clinical practice. We performed a retrospective analysis, from January 2013 to December 2017, on 139 consecutive patients with AIS for anterior circulation LVO strokes up to 24 h from symptoms onset, who received EVT in our institution. The primary outcome measured was a modified Rankin scale (mRS) = 2 at 90 days. Secondary outcomes included successful reperfusion, defined as a modified Thrombolysis in Cerebral Infarction (mTICI) scale 2b/3, mortality rate at 90 days and symptomatic intracranial hemorrhage (sICH). The mean age was 67.5 ± 15.0, with 51.8% female patients. Median baseline National Institute of Health Stroke Scale (NIHSS) was 14 (IQR 8-18); median time from symptom onset to groin puncture was 331 min (IQR 212-503). Sixty-three patients (45.3%) were treated beyond 6 hours after symptoms onset. The rate of mRS = 2 was 47.5%. Successful reperfusion was achieved in 74.8 %. Mortality rate at 90 days was 18.7 % and sICH was 7.9 %. Our registry of real-life patients with AIS due to LVO who received EVT within 24 hours showed high reperfusion rates, and good functional results with few complications, according to international recommendations.

La terapia endovascular (TEV) es el tratamiento estándar del ataque cerebrovascular isquémico (ACVi) con oclusión de gran vaso (OGVC). Aún no se conoce si esos resultados pueden generalizarse a la práctica diaria. Se describen los resultados de la TEV en pacientes con ACVi por OGVC dentro de las 24 horas, en un análisis retrospectivo entre enero 2013 y diciembre 2017 que incluyó 139 casos consecutivos con ACVi y OGVC en arteria cerebral media (ACM), hasta 24 horas del inicio de los síntomas, que recibieron TEV en nuestra institución. El resultado primario medido fue la escala de Rankin modificada (mRS) = 2 a 90 días. Se evaluaron también: reperfusión exitosa, según la escala modificada de trombólisis en infarto cerebral (mTICI) 2b/3, hemorragia intracraneal sintomática (HIS) y mortalidad a 90 días. La edad media: 67.5 ± 15.0, siendo el 51.8% mujeres. La mediana basal de National Institute of Health Stroke Scale (NIHSS) fue 14 (IIC 8-18); la mediana del tiempo desde inicio de síntomas hasta punción inguinal: 331 min (IIC 212-503). El 45.3%, 63 pacientes, fueron tratados > 6 horas después del inicio de síntomas. La tasa de mRS = 2 fue 47.5%. Se logró una reperfusión exitosa en el 74.8%. La tasa de mortalidad a 90 días fue del 18.7% y la HIS del 7.9%. Nuestro registro de pacientes de la vida real con ACVi por OGVC tratados con TEV dentro de las 24 horas mostró altas tasas de reperfusión, buenos resultados funcionales y pocas complicaciones, acorde con las recomendaciones internacionales.

Assessment of Collateral Circulation Using Perfusion CT in Middle Cerebral Artery Thrombectomy-Treated Patients.

INTRODUCTION: The prognostic value of leptomeningeal collateral circulation in thrombectomy-treated patients remains unclear. We evaluated the construct validity of assessing leptomeningeal collateral circulation using a new regional perfusion CT source image-based approach, the Perfusion Acquisition for THrombectomy Scale (PATHS). We also compared the prognostic value of PATHS with a further 6 scales based on various techniques: CT-angiography, perfusion CT, and digital subtraction angiography. Additionally, we studied the relationship between the scores for the different scales. PATIENTS AND METHODS: We performed a retrospective study of consecutive patients with stroke and M1/terminal carotid occlusion treated with thrombectomy in our center. Leptomeningeal collateral circulation was prospectively evaluated using 7 scales: Tan and Miteff (CT Angiography); Calleja, Cao, American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology, and PATHS (perfusion); and Christoforidis (Digital Subtraction Angiography). Correlations were studied using the Spearman method. RESULTS: The study population comprised 108 patients. All scales predicted the modified Rankin Scale at 3 months (P ≤ .02) and all but 1 (Christoforidis) correlated with 24-hour brain infarct volume (P ≤ .02). These correlations were higher with PATHS (rho = -0.47, P < .001 for 3-month modified Rankin Scale; rho = -0.35, P < .001 for follow-up infarct volume). The multivariate analysis showed PATHS to be an independent predictor of modified Rankin Scale at 3 months less than equal to 2. A crosscorrelation analysis revealed a better correlation between scales that used the same techniques. CONCLUSIONS: PATHS can be used to assess leptomeningeal collateral circulation. PATHS had better prognostic value than other scales; therefore, it might be considered for assessment of leptomeningeal collateral circulation in candidates for thrombectomy. The moderate correlation between scales suggests that scores are not interchangeable.

Predictors of outcome in 1-month survivors of large middle cerebral artery infarcts treated by decompressive hemicraniectomy.

BACKGROUND: Decompressive hemicraniectomy (DH) increases survival without severe dependency in patients with large middle cerebral artery (LMCA) infarcts. The objective was to identify predictors of 1-year outcome after DH for LMCA infarct. METHODS: We conducted this study in consecutive patients who underwent DH for LMCA infarcts, in a tertiary stroke centre. Using multivariable logistic regression analyses, we evaluated predictors of (1) 30-day mortality and (2) poor outcome after 1 year (defined as a modified Rankin Scale score of 4-6) in 30-day survivors. RESULTS: Of 212 patients (133 men, 63%; median age 51 years), 35 (16.5%) died within 30 days. Independent predictors of mortality were infarct volume before DH (OR 1.10 per 10 mL increase, 95% CI 1.04 to 1.16), delay between symptom onset and DH (OR 0.41, 95% CI 0.23 to 0.73 per 12 hours increase) and midline shift after DH (OR 2.59, 95% CI 1.09 to 6.14). The optimal infarct volume cut-off to predict death was 210 mL or more. Among the 177 survivors, 77 (43.5%) had a poor outcome at 1 year. Independent predictors of poor outcome were age (OR 1.08 per 1 year increase, 95% CI 1.03 to 1.12) and weekly alcohol consumption of 300 g or more (OR 5.30, 95% CI 2.20 to 12.76), but not infarct volume. CONCLUSION: In patients with LMCA infarcts treated by DH, stroke characteristics (infarct volume before DH, midline shift after DH and early DH) predict 30-day mortality, while patients' characteristics (age and excessive alcohol intake) predict 1-year outcome survivors.

Management of the Patient with Malignant Hemispheric Stroke.

Malignant hemispheric stroke occurs in 10% of ischemic strokes and has one of the highest mortality and morbidity rates. This stroke, also known as malignant middle cerebral artery stroke, may cause ischemia to an entire hemisphere causing edema, herniation, and death. A collaborative interdisciplinary team approach is needed to manage these complex stroke patients. The nurse plays a vital role in bedside management and support of the patient and family through this complex course of care. This article discusses malignant middle cerebral artery stroke pathophysiology, techniques to predict patients at risk for herniation, collaborative care strategies, and nursing care.

High serum substance P levels and mortality after malignant middle cerebral artery infarction.

PURPOSE: Previously our team found higher serum substance P concentrations at day 1 of a malignant middle cerebral artery infarction (MMCAI) in non-surviving than in surviving patients. Thus, the objective of this study was to determine whether serum substance P levels during the first week of MMCAI could predict mortality. METHODS: We included patients with MMCAI defined as computed tomography findings of acute infarction in at least of 50% of the territory and Glasgow Coma Scale ≤8. We determined serum concentrations of substance P on days 1, 4 and 8 of MMCAI. Thirty-day mortality was the study end-point. RESULTS: Serum substance P concentrations at days 1 (p < .001), 4 (p < .001), and 8 (p = .001) of MMCAI in non-surviving (n = 34) were higher than in surviving patients (n = 34). Receiver operating characteristic analyses showed that serum substance P concentrations at days 1, 4, and 8 of MMCAI had an area under curve (95% confidence intervals) to predict 30-day mortality of 0.77 (0.66-0.87; p < .001), 0.82 (0.69-0.91; p < .001) and 0.85 (0.72-0.94; p < .001) respectively. CONCLUSIONS: The two new findings of our study are that non-surviving MMCAI patients showed higher serum substance P levels at day 1, 4 and 8 than surviving, and that those levels could predict 30-day mortality.

Decompressive hemicraniectomy versus medical treatment of malignant middle cerebral artery infarction: a systematic review and meta-analysis.

OBJECTIVES: To estimate evidence for decompressive hemicraniectomy (DHC) versus medical treatment effects on survival rate and favorable functional recovery among patients of malignant middle cerebral artery infarction (MMCAI) in randomized controlled trials (RCTs). DESIGN: The present study is a systematic review and meta-analysis of RCTs. SETTING: The MEDLINE/PubMed, EMBASE, Springer, Cochrane Collaboration database, China National Knowledge Infrastructure (CNKI) database, and Wanfang database were comprehensively searched for RCTs regarding the effects of DHC versus medical treatment among patients of MMCAI in these English and Chinese electronic databases from inception to 1 June 2019. Two reviewers independently retrieved RCTs and extracted relevant information. The methodological quality of the included trials was estimated using the Cochrane risk of bias tool. Review Manager5.3.5 software was used for statistical analyses. The statistical power of meta-analysis was estimated by Power and Precision, version 4 software. PARTICIPANTS: Nine RCTs with a total of 425 patients with MMCAI, containing 210 cases in the DHC group and 215 cases in the medical treatment group, met the inclusion criteria were included. Primary outcomes were measured by survival rate, defined as modified Rankin scale (mRS) score 0-5 and favorable functional recovery as mRS score 0-3. The follow-up time of all studies was at 6-12months. RESULTS: First, compared with the medical treatment group, DHC was associated with a statistically significant increase survival rate (RR: 1.96, 95%CI 1.61-2.38, P < 0.00001) and favorable functional recovery (RR: 1.62, 95%CI 1.11-2.37, P = 0.01). Second, subgroup analysis: (1) Compared with the medical treatment group among patients age ≤60 years, DHC was associated with a statistically significant increase survival rate (RR = 2.20, 95%CI 1.60-3.04, P < 0.00001); (2) Compared with the medical treatment group among patients of age >60 years, DHC was also associated with a statistically significant increase survival rate (RR: 1.93, 95%CI 1.45-2.59, P < 0.00001); (3) Compared with the medical treatment group, the time of DHC was preformed within 48 h from the onset of stroke that could statistically significant increase survival rate (RR: 2.16, 95%CI 1.69-2.75, P < 0.00001). Third, sensitivity analyses that measured the results were consistent, indicating that the results were stable. Fourth, the results of statistical power analysis were ≥80%. Finally, the funnel plot of the survival rate included nine RCTs showed no remarkable publication bias. CONCLUSIONS: Our study results indicated that DHC could increase survival rate and favorable functional recovery among patients age ≤60 or >60 years. The optimal time for DHC might be no more than 48 h from the onset of symptoms. However, due to the limitations of this research, it is necessary to design high quality, large-scale RCTs to further evaluate these findings.

Mechanical Thrombectomy of the Middle Cerebral Artery - Neither Segment nor Diameter Matter.

OBJECTIVES: The aim of this study was to explore the role of the vessel diameter at the site of middle cerebral artery (MCA) occlusion in acute ischemic stroke patients who underwent mechanical thrombectomy (MT) regarding technical aspects, safety, and clinical outcomes. METHODS: In a retrospective analysis, cerebral artery diameters were measured using digital subtraction angiography in patients with isolated M1 or M2 occlusions undergoing MT. Associations between occluded vessel, occlusion diameter and outcomes were analyzed using logistic regression models adjusting for prespecified prognostic factors. RESULTS: 168 patients with M1 occlusions and 98 patients with M2 occlusions who underwent MT were included. Mean vessel diameters at M1 and M2 occlusion sites differed significantly (2.15 +/- .36 1.55 +/- .38, P < .001). Vessel diameters at the occlusion site and occluded vessel segment did not predict good functional outcome (aOR 1.2 CI .28-5.26, P = .659; aOR .84 CI .35-2.03, P = .841) or mortality (aOR .21 CI .04-1.01, P = .215; aOR 1.36 CI .55-3.37, P = .676). No significant differences in successful recanalization, good functional outcome, mortality, procedural complications, and intracranial hemorrhages between M1 and M2 occlusions was observed. CONCLUSIONS: In this study no significant effect of the MCA vessel diameter on successful recanalization, good functional outcome, or mortality of acute ischemic stroke patients treated with MT could be detected. However, these findings need to be confirmed in further studies.

A nomogram for predicting the in-hospital mortality after large hemispheric infarction.

BACKGROUND: Large hemispheric infarction (LHI) is a severe form of stroke with high mortality and disability rates. The purpose of this study was to explore predictive indicators of the in-hospital mortality of LHI patients treated conservatively without decompressive hemicraniectomy. METHOD: We performed a retrospective study of 187 consecutive patients with LHI between January 1, 2016 to May 31, 2019. The receiver operating curves were preformed to evaluate predictive performance of demographics factors, biomarkers and radiologic characteristics. Significant prognostic factors were combined to build a nomogram to predict the risk of in-hospital death of individual patients. RESULT: One hundred fifty-eight patients with LHI were finally enrolled, 58 of which died. Through multivariate logistic regression analysis, we identified that independent prognostic factors for in-hospital death were age (adjusted odds ratio [aOR] = 1.066; 95% confidence interval [CI], 1.025-1.108; P = 0.001), midline shift (MLS, aOR = 1.330, 95% CI, 1.177-1.503; P <  0.001), and neutrophil-to-lymphocyte ratio (NLR, aOR = 3.319, 95% CI, 1.542-7.144; P = 0.002). NLR may serve as a better predictor than white blood count (WBC) and neutrophil counts. Lastly, we used all of the clinical characteristics to establish a nomogram for predicting the prognosis, area under the curve (AUC) of this nomogram was 0.858 (95% CI, 0.794-0.908). CONCLUSION: This study shows that age, MLS, and admission NLR value are independent predictors of in-hospital mortality in patients with LHI. Moreover, nomogram, serve as a precise and convenient tool for the prognosis of LHI patients.