RESUMEN
A meta-analysis was performed to assess randomized controlled trials comparing local endovascular therapy (with and without intravenous thrombolysis) versus standard care (intravenous thrombolysis alone when appropriate) for acute ischemic stroke. Local endovascular therapy showed a significant improvement in functional independence versus standard care (odds ratio, 1.779; 95% confidence interval, 1.262-2.507; P < .001). This benefit strengthened further on subgroup analyses of trials in which a majority of cases used stent retrievers, trials with intravenous thrombolysis use in both arms when appropriate, and trials that required preprocedural imaging of all patients. There were no significant differences between arms in terms of mortality, hemicraniectomy, intracranial hemorrhage, and cerebral edema rates (P > .05). In conclusion, in the treatment of acute ischemic stroke, local endovascular therapy leads to improved functional independence compared with standard care.
Asunto(s)
Isquemia Encefálica/terapia , Procedimientos Endovasculares , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/terapia , Terapia Trombolítica , Administración Intravenosa , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidad , Isquemia Encefálica/fisiopatología , Circulación Cerebrovascular , Evaluación de la Discapacidad , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Fibrinolíticos/efectos adversos , Humanos , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/fisiopatología , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/mortalidad , Resultado del TratamientoRESUMEN
New approaches to antimicrobial discovery are needed to address the growing threat of antibiotic resistance. The Streptomyces genus, a proven source of antibiotics, is recognized as having a large reservoir of untapped secondary metabolic genes, many of which are likely to produce uncharacterized compounds. However, most of these compounds are currently inaccessible, as they are not expressed under standard laboratory conditions. Here, we present a novel methodology for activating these "cryptic" metabolites by heterologously expressing a constitutively active pleiotropic regulator. By screening wild Streptomyces isolates, we identified the antibiotic siamycin-I, a lasso peptide that we show is active against multidrug pathogens. We further revealed that siamycin-I interferes with cell wall integrity via lipid II. This new technology has the potential to be broadly applied for use in the discovery of additional "cryptic" metabolites.