Systemic biomarker associated with poor outcome after futile reperfusion.

BACKGROUND: Successful recanalization does not lead to complete tissue reperfusion in a considerable percentage of ischemic stroke patients. This study aimed to identify biomarkers associated with futile recanalization. Leukoaraiosis predicts poor outcomes of this phenomenon. Soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK), which is associated with leukoaraiosis degrees, could be a potential biomarker. METHODS: This study includes two cohorts of ischemic stroke patients in a multicentre retrospective observational study. Effective reperfusion, defined as a reduction of ≥8 points in the National Institutes of Health Stroke Scale (NIHSS) within the first 24 h, was used as a clinical marker of effective reperfusion. RESULTS: In the first cohort study, female sex, age, and high NIHSS at admission (44.7% vs. 81.1%, 71.3 ± 13.7 vs. 81.1 ± 6.7; 16 [13, 21] vs. 23 [17, 28] respectively; p < .0001) were confirmed as predictors of futile recanalization. ROC curve analysis showed that leukocyte levels (sensitivity of 99%, specificity of 55%) and sTWEAK level (sensitivity of 92%, specificity of 88%) can discriminate between poor and good outcomes. Both biomarkers simultaneously are higher associated with outcome after effective reperfusion (OR: 2.17; CI 95% 1.63-4.19; p < .0001) than individually (leukocytes OR: 1.38; CI 95% 1.00-1.64, p = .042; sTWEAK OR: 1.00; C I95% 1.00-1.01, p = .019). These results were validated using a second cohort, where leukocytes and sTWEAK showed a sensitivity of 100% and specificity of 66.7% and 75% respectively. CONCLUSIONS: Leukocyte and sTWEAK could be biomarkers of reperfusion failure and subsequent poor outcomes. Further studies will be necessary to explore its role in reperfusion processes.

Prehospital care process and hospital outcomes in stroke-code cases: comparison of basic and advance life support ambulance attendance. / Proceso de atención prehospitalaria y resultados hospitalarios del código ictus: estudio comparativo entre unidades de soporte vital básico y avanzado.

OBJECTIVES: To study prehospital care process in relation to hospital outcomes in stroke-code cases first attended by 2 different levels of ambulance. To analyze factors associated with a satisfactory functional outcome at 3 months. MATERIAL AND METHODS: Prospective multicenter observational cohort study. All stroke-code cases attended by prehospital emergency services from January 2016 to April 2022 were included. Prehospital and hospital variables were collected. The classificatory variable was type of ambulance attending (basic vs advanced life support). The main outcome variables were mortality and functional status after ischemic strokes in patients who underwent reperfusion treatment 90 days after the ischemic episode. RESULTS: Out of 22 968 stroke-code activations, ischemic stroke was diagnosed in 12 467 patients (54.3%) whose functional status was good before the episode. Basic ambulances attended 93.1%; an advanced ambulance was ordered in 1.6% of the patients. Even though there were differences in patient and clinical characteristics recorded during the prehospital process, type of ambulance was not independently associated with mortality (adjusted odds ratio [aOR], 1.1; 95% CI, 0.77-1.59) or functional status at 3 months (aOR, 1.05; 95% CI, 0,72-1,47). CONCLUSION: The percentage of patient complications in stroke-code cases attended by basic ambulance teams is low. Type of ambulance responding was not associated with either mortality or functional outcome at 3 months in this study.

OBJETIVO: Comparar el proceso asistencial prehospitalario y los resultados hospitalarios de los pacientes categorizados como Código Ictus (CI) en función del tipo de ambulancia que realiza la primera valoración, y analizar los factores asociados con un buen resultado funcional y la mortalidad a los 3 meses. METODO: Estudio observacional de cohortes prospectivo multicéntrico. Incluyó todos los CI atendidos por un sistema de emergencias prehospitalario desde enero del 2016 a abril del 2022. Se recogieron variables prehospitalarias y hospitalarias. La variable de clasificación fue el tipo de ambulancia que asiste el CI: unidad de soporte vital básico (USVB) o avanzado (USVA). Las variables de resultado principal fueron la mortalidad y el estado funcional de los ictus isquémicos sometidos a tratamiento de reperfusión a los 90 días del episodio. RESULTADOS: Se incluyeron 22.968 pacientes, de los cuales 12.467 (54,3%) presentaron un ictus isquémico con un buen estado funcional previo. El 93,1% fueron asistidos por USVB y se solicitó una USVA en el 1,6% de los casos. A pesar de presentar diferencias en el perfil clínico del paciente atendido y en los tiempos del proceso CI prehospitalario, el tipo de unidad no mostró una asociación independiente con la mortalidad (OR ajustada 1,1; IC 95%: 0,77- 1,59) ni con el estado funcional a los 3 meses (OR ajustada 1,05; IC 95%: 0,72-1,47). CONCLUSIONES: El porcentaje de complicaciones de los pacientes con CI atendidos por USVB es bajo. El tipo de unidad que asistió al paciente inicialmente no se asoció ni con el resultado funcional ni con la mortalidad a los 3 meses.

Phase 1b Study to Evaluate Safety, Tolerability, and Maximum Tolerated Dose of PF-05230907 for Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: This study aimed to determine the maximum tolerated dose and to evaluate the overall safety and tolerability of single doses of PF-05230907 in subjects with acute intracerebral hemorrhage. METHODS: Individuals presenting with intracerebral hemorrhage were enrolled in a phase 1, multicenter, open-label clinical trial. A Bayesian modified continual reassessment method design based on treatment-emergent thromboembolic or ischemic events was adopted. Sequential dosing, an external data monitoring committee, and prespecified stopping rules were incorporated as safeguards. RESULTS: Twenty-one subjects received PF-05230907. The mean (±SD) age in years and intracerebral hemorrhage volume in mL at baseline were 62 (±9) and 18 (±11), respectively. Two treatment-emergent thromboembolic or ischemic events occurred (deep vein thrombosis and cerebral ischemia), in the 30 µg/kg dose group. There were no other clear drug-related toxicities at dose levels ranging from 5 to 30 µg/kg. At the time of study termination, the maximum tolerated dose was estimated to be 24 µg/kg, with a mean fitted dose-toxicity estimate of 11.9% (95% CI, 1.2%-27.4%). CONCLUSIONS: Single doses of PF-05230907 appeared to be tolerated across a range of doses in the intracerebral hemorrhage population, with thrombotic events observed only at the highest dose level tested. Recruitment within the recommended therapeutic window of opportunity remains a challenge. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02687191.

Independent Validation of the Hematoma Expansion Prediction Score: A Non-contrast Score Equivalent in Accuracy to the Spot Sign.

BACKGROUND AND PURPOSE: The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. METHODS: We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. RESULTS: A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01-1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57-0.71). Youden's method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09-3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61-5.42) were similar to HEP scores ≥ 4. CONCLUSION: The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

Lack of Early Improvement Predicts Poor Outcome Following Acute Intracerebral Hemorrhage.

OBJECTIVES: There are limited data as to what degree of early neurologic change best relates to outcome in acute intracerebral hemorrhage. We aimed to derive and validate a threshold for early postintracerebral hemorrhage change that best predicts 90-day outcomes. DESIGN: Derivation: retrospective analysis of collated clinical stroke trial data (Virtual International Stroke Trials Archive). VALIDATION: retrospective analysis of a prospective multicenter cohort study (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]). SETTING: Neurocritical and ICUs. PATIENTS: Patients with acute intracerebral hemorrhage presenting less than 6 hours. Derivation: 552 patients; validation: 275 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We generated a receiver operating characteristic curve for the association between 24-hour National Institutes of Health Stroke Scale change and clinical outcome. The primary outcome was a modified Rankin Scale score of 4-6 at 90 days; secondary outcomes were other modified Rankin Scale score ranges (modified Rankin Scale, 2-6, 3-6, 5-6, 6). We employed Youden's J Index to select optimal cut points and calculated sensitivity, specificity, and predictive values. We determined independent predictors via multivariable logistic regression. The derived definitions were validated in the PREDICT cohort. Twenty-four-hour National Institutes of Health Stroke Scale change was strongly associated with 90-day outcome with an area under the receiver operating characteristic curve of 0.75. Youden's method showed an optimum cut point at -0.5, corresponding to National Institutes of Health Stroke Scale change of greater than or equal to 0 (a lack of clinical improvement), which was seen in 46%. Early neurologic change accurately predicted poor outcome when defined as greater than or equal to 0 (sensitivity, 65%; specificity, 73%; positive predictive value, 70%; adjusted odds ratio, 5.05 [CI, 3.25-7.85]) or greater than or equal to 4 (sensitivity, 19%; specificity, 98%; positive predictive value, 91%; adjusted odds ratio, 12.24 [CI, 4.08-36.66]). All definitions reproduced well in the validation cohort. CONCLUSIONS: Lack of clinical improvement at 24 hours robustly predicted poor outcome and showed good discrimination for individual patients who would do poorly. These findings are useful for prognostication and may also present as a potential early surrogate outcome for future intracerebral hemorrhage treatment trials.

Intracerebral Hematoma Morphologic Appearance on Noncontrast Computed Tomography Predicts Significant Hematoma Expansion.

BACKGROUND AND PURPOSE: Hematoma expansion in intracerebral hemorrhage is associated with higher morbidity and mortality. The computed tomography (CT) angiographic spot sign is highly predictive of expansion, but other morphological features of intracerebral hemorrhage such as fluid levels, density heterogeneity, and margin irregularity may also predict expansion, particularly in centres where CT angiography is not readily available. METHODS: Baseline noncontrast CT scans from patients enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study were assessed for the presence of fluid levels and degree of density heterogeneity and margin irregularity using previously validated scales. Presence and grade of these metrics were correlated with the presence of hematoma expansion as defined by the PREDICT study on 24-hour follow-up scan. RESULTS: Three hundred eleven patients were included in the analysis. The presence of fluid levels and increasing heterogeneity and irregularity were associated with 24-hour hematoma expansion (P=0.021, 0.003 and 0.049, respectively) as well as increases in absolute hematoma size. Fluid levels had the highest positive predictive value (50%; 28%-71%), whereas margin irregularity had the highest negative predictive value (78%; 71%-85). Noncontrast metrics had comparable predictive values as spot sign for expansion when controlled for vitamin K, antiplatelet use, and baseline National Institutes of Health Stroke Scale, although in a combined area under the receiver-operating characteristic curve model, spot sign remained the most predictive. CONCLUSIONS: Fluid levels, density heterogeneity, and margin irregularity on noncontrast CT are associated with hematoma expansion at 24 hours. These markers may assist in prediction of outcomes in scenarios where CT angiography is not readily available and may be of future help in refining the predictive value of the CT angiography spot sign.

[Stroke units. Project, development, and outcome at a university hospital]. / Unidades de Ictus. Proyecto, desarrollo y resultados en un Hospital Universitario.

After a brief introduction about what an lctus Word is, the authors describe the project for an lctus Ward at the Dr. Josep Trueta University Hospital in Girona. Afterwards, the authors analyze its development and its results during its existence. The authors conclude that there has been a significant increase in benefits for patients since they have received new therapeutic treatments in a specialized ward, furthermore, both doctors and nurses have had the opportunity to develop new research projects.