RESUMEN
BACKGROUND: Mechanical thrombectomy has revolutionised the treatment of acute ischaemic stroke due to large vessel occlusion. It is well recognised that patients are more likely to benefit when reperfusion happens quickly, however, there is uncertainty as to how best to deliver this service. OBJECTIVES: To compare outcomes of patients in Northern -Ireland who underwent thrombectomy via direct admission to the single endovascular centre (mothership [MS]) with those transferred from primary stroke centres (drip-and-ship [DS]). METHODS: Analysis was conducted on the records of all patients who underwent thrombectomy from January 2014 to December 2017 inclusive. The primary outcome measure was 3 months functional independence (modified Rankin Score [mRS] 0-2). Secondary outcome measures were full recovery (mRS 0) at 3 months, symptomatic intracranial haemorrhage (sICH) rates and mortality rates. RESULTS: Two hundred fourteen patients underwent thrombectomy (MS 124, DS 90). Patients in the MS group were older (median 73 vs. 70 years, p = 0.026), but there was no significant difference in baseline National Institutes of Health Stroke Scale (median 15 MS vs. 16.5 DS, p = 0.162) or thrombolysis rates (41.9% MS vs. 54.4% DS, p = 0.070) between the groups. Time from stroke onset to arrival at thrombectomy centre was shorter in the MS group (median 71 vs. 218 min, p < 0.001) but door to groin puncture time was shorter in the DS group (median 30 vs. 60 min, p < 0.001). There was no significant difference in 3 months functional independence (51.6% MS vs. 62.2% DS, p = 0.123), or in the secondary outcome measures of full recovery (21.8% MS vs. 12.2% DS, p = 0.071), sICH (MS 0.8%, DS 4.4%, p = 0.082) and mortality (MS 24.2%, DS 20.0%, p = 0.468). CONCLUSIONS: Our analysis showed similar outcomes after thrombectomy in the MS and DS groups. For patients potentially eligible for thrombectomy, rapid access to the endovascular centre is essential to optimise both the number of patients treated and the outcomes achieved.
Asunto(s)
Isquemia Encefálica/terapia , Procedimientos Endovasculares , Admisión del Paciente , Transferencia de Pacientes , Accidente Cerebrovascular/terapia , Trombectomía , Terapia Trombolítica , Tiempo de Tratamiento , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/mortalidad , Isquemia Encefálica/fisiopatología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Irlanda del Norte , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/fisiopatología , Trombectomía/efectos adversos , Trombectomía/mortalidad , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
A chimerized (murine/human) monoclonal antibody (pagibaximab) against lipoteichoic acid (LTA) and protective in animal models for coagulase-negative staphylococci (CONS) and Staphylococcus aureus bacteremia, was developed for prevention of staphylococcal infection in high-risk populations. This open label two-dose study of a single intravenous dose of 3 or 10 mg/kg of pagibaximab evaluated the safety/tolerability, pharmacokinetics, and opsonophagocytic activity of pagibaximab in healthy adults. Eight participants were enrolled (four in each dose group). No infusion, drug, or dose related adverse events occurred. Serum anti-LTA levels were dose-related; mean concentrations peaked at 87.75 and 259.24 microg/mL for 3 and 10 mg/kg groups, respectively. The half-life (beta) of pagibaximab was approximately 33 days. Opsonophagocytic activity of serum samples on a human clinical isolate of Staphylococcus epidermidis in a standard bacterial killing assay was dose-related, and peaked at a mean of 88.5 and 95.5% at 1:90 dilution for 3 and 10 mg/kg groups, respectively. Serum anti-LTA and opsonophagocytic activity levels exhibited statistically significant correlation. The results suggest that pagibaximab at 3 and 10 mg/kg administered as a single intravenous dose in healthy adults appears to: 1) provide preliminary safety and tolerability data, 2) produce dose-related serum anti-LTA and opsonophagocytic activity levels, 3) have a half-life similar to other immunoglobulin G1 antibodies, 4) exhibit statistically significant correlation between serum anti-LTA and opsonophagocytic activity levels. This study supports conducting safety and pharmacokinetic trials of pagibaximab in populations at high-risk of developing CONS infection.