RESUMEN
BACKGROUND: Biodegradable polymers for release of antiproliferative drugs from drug-eluting stents aim to improve vascular healing. We assessed noninferiority of a novel ultrathin strut drug-eluting stent releasing sirolimus from a biodegradable polymer (Orsiro, O-SES) compared with the durable polymer Xience Prime everolimus-eluting stent (X-EES) in terms of the primary end point in-stent late lumen loss at 9 months. METHODS AND RESULTS: A total of 452 patients were randomly assigned 2:1 to treatment with O-SES (298 patients, 332 lesions) or X-EES (154 patients, 173 lesions) in a multicenter, noninferiority trial. The primary end point was in-stent late loss at 9 months. O-SES was noninferior to X-EES for the primary end point (0.10±0.32 versus 0.11±0.29 mm; difference=0.00063 mm; 95% confidence interval, -0.06 to 0.07; Pnoninferiority<0.0001). Clinical outcome showed similar rates of target-lesion failure at 1 year (O-SES 6.5% versus X-EES 8.0%; hazard ratio=0.82; 95% confidence interval, 0.40-1.68; log-rank test: P=0.58) without cases of stent thrombosis. A subgroup of patients (n=55) underwent serial optical coherence tomography at 9 months, which demonstrated similar neointimal thickness among lesions allocated to O-SES and X-EES (0.10±0.04 mm versus 0.11±0.04 mm; -0.01 [-0.04, -0.01]; P=0.37). Another subgroup of patients (n=56) underwent serial intravascular ultrasound at baseline and 9 months indicating a potential difference in neointimal area at follow-up (O-SES, 0.16±0.33 mm(2) versus X-EES, 0.43±0.56 mm(2); P=0.04). CONCLUSIONS: Compared with durable polymer X-EES, novel biodegradable polymer-based O-SES was found noninferior for the primary end point in-stent late lumen loss at 9 months. Clinical event rates were comparable without cases of stent thrombosis throughout 1 year of follow-up. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01356888.
Asunto(s)
Angioplastia Coronaria con Balón/instrumentación , Fármacos Cardiovasculares/administración & dosificación , Enfermedad de la Arteria Coronaria/terapia , Reestenosis Coronaria/prevención & control , Vasos Coronarios/efectos de los fármacos , Stents Liberadores de Fármacos , Polímeros , Sirolimus/análogos & derivados , Anciano , Angioplastia Coronaria con Balón/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico , Reestenosis Coronaria/diagnóstico , Reestenosis Coronaria/etiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Europa (Continente) , Everolimus , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neointima , Valor Predictivo de las Pruebas , Diseño de Prótesis , Factores de Riesgo , Sirolimus/administración & dosificación , Factores de Tiempo , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
OBJECTIVES: Extramural paratracheal/-bronchial tumors of the mediastinum and the hilum that cannot be seen in bronchoscopy constitute a particular challenge for transbronchial fine needle aspiration cytology. A software prototype was developed as a guidance tool to visualize extramural targets on computed tomography (CT)-bronchoscopy. A phantom study was conducted to evaluate this guidance tool. MATERIAL AND METHODS: For CT-bronchoscopic simulation extramural targets are visualized behind the semitransparent wall in the endoluminal view. An airway phantom with 16 targets was examined by 3 bronchoscopists. In a first pass the targets were bronchoscopically punctured in the conventional way only with knowledge of axial CT-sections. In a second pass guidance by CT-bronchoscopic simulation was used. A postinterventional CT scan of the phantom was conducted to analyze the spatial relationship between the marked puncture sites and the targets. The punctures were classified in hits and failed punctures due to deviation in distance and angle. RESULTS: The total hit rate of the 3 operators was significantly higher with CT-bronchoscopic simulation (32 of 48) than with the conventional method (14 of 48; P < 0.01). Concerning the failed punctures the deviation in distance and angle was significantly smaller with CT-bronchoscopic simulation (P < 0.01, P < 0.05, respectively). CONCLUSION: CT-bronchoscopic simulation significantly increased hit rate of bronchoscopic punctures of extramural lesions compared with conventional orientation using axial CT-sections in this phantom study. These results suggest that CT-bronchoscopic simulation might be a valuable tool for increasing yield and accuracy of bronchoscopic transbronchial fine needle aspiration in patients with mediastinal and hilar masses that are invisible for conventional bronchoscopy.
Asunto(s)
Biopsia con Aguja Fina/métodos , Neoplasias de los Bronquios/diagnóstico , Broncoscopía/métodos , Fantasmas de Imagen , Tomografía Computarizada por Rayos X/métodos , Interfaz Usuario-Computador , Simulación por Computador , Modelos Anatómicos , Programas InformáticosRESUMEN
A hallmark of central nervous system (CNS) pathology is reactive astrocyte production of the chronic glial scar that is inhibitory to neuronal regeneration. The reactive astrocyte response is complex; these cells also produce neurotrophic factors and are responsible for removal of extracellular glutamate, the excitatory neurotransmitter that rises to neurotoxic levels in injury and disease. To identify genes expressed by reactive astrocytes, we employed an in vivo model of the glial scar and differential display PCR and found an increase in the level of Ant1, a mitochondrial ATP/ADP exchanger that facilitates the flux of ATP out of the mitochondria. Ant1 expression in reactive astrocytes is regulated by transforming growth factor-beta1, a pluripotent CNS injury-induced cytokine. The significance of increased Ant1 is evident from the observation that glutamate uptake is significantly decreased in astrocytes from Ant1 null mutant mice while a specific Ant inhibitor reduces glutamate uptake in wild-type astrocytes. Thus, the astrocytic response to CNS injury includes an apparent increase in energy mobilization capacity by Ant1 that contributes to neuroprotective, energy-dependent glutamate uptake.