RESUMEN
Purpose: Odatroltide (LT3001), a novel small synthetic peptide molecule designed to recanalize occluded blood vessels and reduce reperfusion injury, is safe and efficacious in multiple embolic stroke animal models. This study aimed to investigate the safety and tolerability of intravenous administration of odatroltide in patients with acute ischemic stroke within 24 hours of onset. Patients and Methods: Patients with National Institutes of Health Stroke Scale (NIHSS 4-30) who were untreated with intravenous thrombolysis or endovascular thrombectomy were randomized (2:1) to receive a single dose of odatroltide (0.025 mg/kg) or placebo within 24 hours of stroke symptom onset. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) occurrence within 36 hours. Results: Twenty-four patients were enrolled and randomized; of these 16 and 8 received intravenous odatroltide infusion and placebo, respectively. sICH did not occur in both groups, and other safety measures were comparable between the groups. The rate of excellent functional outcome (modified Rankin Scale score, 0-1, at 90 days) was 21% and 14% in the odatroltide and placebo groups, respectively. Furthermore, 47% and 14% of patients in the odatroltide and placebo groups, respectively, showed major neurological improvement (NIHSS improvement ≥4 points from baseline to 30 days). Among the 9 odatroltide-treated patients with baseline NIHSS ≥6, 78% showed major neurological improvement. Conclusion: Compared with placebo, treatment with intravenous odatroltide within 24 hours following onset of ischemic stroke appears to be safe and may be associated with better neurological and functional outcomes. However, the efficacy and safety of odatroltide requires further confirmation in the next phase of clinical trials. Clinical Trial Registration: Clinicaltrials.gov identifier: NCT04091945.
Asunto(s)
Accidente Cerebrovascular Isquémico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Administración Intravenosa , Isquemia Encefálica/tratamiento farmacológico , Método Doble Ciego , Infusiones Intravenosas , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Factores de Tiempo , Resultado del TratamientoRESUMEN
The incidence of new-onset seizures, which we defined as de novo seizures occurring within 4 weeks of receiving any of the US Food and Drug Administration-approved COVID-19 vaccinations as reported in patient-reported data compiled in the US Centers for Disease Control and Prevention Vaccine Adverse Events Reporting System Data (CDC VAERS), has not been explored. The VAERS database contains de-identified patient-reported adverse events following vaccination and represents post-marketing surveillance and analysis of vaccine safety. After adjusting for time at risk, this resulted in estimated incidence rates of 3.19 seizures per 100 000 persons per year for the COVID-19 vaccine and 0.090 seizures per 100 000 persons per year for the influenza vaccines. A data-driven, individualized dataset that is comprehensive and coupled with a longitudinal follow-up in larger numbers of vaccinated individuals is needed to expand on our preliminary findings of vaccine-related seizures.
Asunto(s)
COVID-19 , Vacunas contra la Influenza , Gripe Humana , Sistemas de Registro de Reacción Adversa a Medicamentos , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Vacunas contra la Influenza/efectos adversos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Convulsiones/inducido químicamente , Convulsiones/epidemiología , Estados Unidos/epidemiología , Vacunación/efectos adversosRESUMEN
INTRODUCTION: The Cincinnati Prehospital Stroke Severity scale (C-STAT), Los Angeles Motor Scale (LAMS), Rapid Arterial Occlusion Evaluation (RACE) score, and Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scales were designed to aid emergency responder identification of patients with stroke related to large vessel occlusion (LVO). We hypothesized that the addition of a known history of atrial fibrillation (AF) without anticoagulation to currently used scales would improve LVO detection. METHODS: Medical records of patients admitted to a Comprehensive Stroke Center with acute ischemic stroke in 2014-2015 were reviewed. LVO identification using the C-STAT, LAMS, RACE, and FAST-ED scores and the AF variable were compared using univariable analyses. The areas under the receiver operating curves (AUCs) were then compared for each score, the AF variable, and each score with the addition of the AF variable. RESULTS: The sample included 233 patients without and 188 patients with an LVO. A history of known AF, history of AF with no anticoagulation, and the C-STAT, LAMS, RACE, and FAST-ED scores were each associated with LVO in univariable analyses. The AUCs for C-STAT, LAMS, RACE, and FAST-ED were similar. The addition of the known AF and no anticoagulation variable did not appreciably change these AUCs. CONCLUSION: Although known AF with no anticoagulation was associated with LVO in patients with acute ischemic stroke, this historic feature did not improve the accuracy of existing LVO detection scales.
Asunto(s)
Fibrilación Atrial/complicaciones , Isquemia Encefálica/diagnóstico , Técnicas de Apoyo para la Decisión , Embolia Intracraneal/diagnóstico , Accidente Cerebrovascular/diagnóstico , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Isquemia Encefálica/etiología , Isquemia Encefálica/fisiopatología , Femenino , Humanos , Embolia Intracraneal/etiología , Embolia Intracraneal/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/fisiopatologíaRESUMEN
Methionine (Met) loading increases total plasma homocysteine (tHcy) and assesses homocysteine metabolism. We tested the hypothesis that pre- or post-Met tHcy will predict recurrent stroke or coronary artery disease (CAD) in a subgroup analysis of the Vitamin Intervention for Stroke Prevention (VISP) trial. VISP subjects with non-disabling stroke underwent measurement of tHcy at baseline (fasting pre- and post-Met load) and were randomized to high/low-dose B-vitamin therapy for prevention of recurrent stroke or CAD. In the sample cohort of 2124 subjects, mean+/-S.D. tHcy levels in micromol/l were pre-Met 13.2+/-4.3, post-Met 30.4+/-9.76, and pre/post-Met Delta 17.1+/-8.3. The hazard ratio (HR) for recurrent stroke was 1.16 (p=0.026) for 1 S.D. higher pre-Met tHcy and 1.15 (p=0.054) for 1 S.D. higher post-Met tHcy. For CAD, the HR for 1 S.D. higher pre-Met tHcy was 1.27 (p=0.001) and was 1.00 (p=0.99) for post-Met tHcy. In survival analyses using pre- or post-Met as covariates, the coefficient of pre/post-Met Delta was not significant for stroke and was only marginally significant for CAD (p<0.08), but was negative. We conclude that fasting, pre-Met tHcy is as effective as post-Met tHcy or pre/post-Met Delta in predicting the risk for stroke and CAD.