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BACKGROUND AND PURPOSE: Selection of the correct flow-diverter size is critical for cerebral aneurysm treatment success, but it remains challenging due to the interplay of device size, anatomy, and deployment. Current convention does not address these challenges well. The goals of this pilot study were to determine whether computational modeling improves flow-diverter sizing over current convention and to validate simulated deployments. MATERIALS AND METHODS: Seven experienced neurosurgeons and interventional neuroradiologists used computational modeling to prospectively plan 19 clinical interventions. In each patient case, physicians simulated 2-4 flow-diverter sizes that were under consideration based on preprocedural imaging. In addition, physicians identified a preferred device size using the current convention. A questionnaire on the impact of computational modeling on the procedure was completed immediately after treatment. Rotational angiography image data were acquired after treatment and compared with flow-diverter simulations to validate the output of the software platform. RESULTS: According to questionnaire responses, physicians found the simulations useful for treatment planning, and they increased their confidence in device selection in 94.7% of cases. After viewing the simulations results, physicians selected a device size that was different from the original conventionally planned device size in 63.2% of cases. The average absolute difference between clinical and simulated flow-diverter lengths was 2.1 mm. In 57% of cases, average simulated flow-diverter diameters were within the measurement uncertainty of clinical flow-diverter diameters. CONCLUSIONS: Physicians found computational modeling to be an impactful and useful tool for flow-diverter treatment planning. Validation results showed good agreement between simulated and clinical flow-diverter diameters and lengths.
Asunto(s)
Implantación de Prótesis Vascular/métodos , Prótesis Vascular , Simulación por Computador , Aneurisma Intracraneal/cirugía , Femenino , Humanos , Masculino , Proyectos Piloto , Programas InformáticosRESUMEN
BACKGROUND AND PURPOSE: Pulmonary vascular dysfunction is a key event in acute lung injury. We recently demonstrated that PGE2 , via activation of E-prostanoid (EP)4 receptors, strongly enhances microvascular barrier function in vitro. The aim of this study was to investigate the beneficial effects of concomitant EP4 receptor activation in murine models of acute pulmonary inflammation. EXPERIMENTAL APPROACH: Pulmonary inflammation in male BALB/c mice was induced by LPS (20 µg per mouse intranasally) or oleic acid (0.15 µL·g-1 , i.v. ). In-vitro, endothelial barrier function was determined by measuring electrical impedance. KEY RESULTS: PGE2 activation of EP4 receptors reduced neutrophil infiltration, pulmonary vascular leakage and TNF-α concentration in bronchoalveolar lavage fluid from LPS-induced pulmonary inflammation. Similarly, pulmonary vascular hyperpermeability induced by oleic acid was counteracted by EP4 receptor activation. In lung function assays, the EP4 agonist ONO AE1-329 restored the increased resistance and reduced compliance upon methacholine challenge in mice treated with LPS or oleic acid. In agreement with these findings, EP4 receptor activation increased the in vitro vascular barrier function of human and mouse pulmonary microvascular endothelial cells and diminished the barrier disruption induced by LPS. The EP2 agonist ONO AE1-259 likewise reversed LPS-induced lung dysfunction without enhancing vascular barrier function. CONCLUSION AND IMPLICATIONS: Our results show that activation of the EP4 receptor strengthens the microvascular barrier function and thereby ameliorates the pathology of acute lung inflammation, including neutrophil infiltration, vascular oedema formation and airway dysfunction. This suggests a potential benefit for EP4 agonists in acute pulmonary inflammation.
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OBJECTIVE: To examine radical-induced DNA damage and its elimination in workers exposed to quartz and in patients with silicosis, and to assess the relationship of these effects to lung function. METHODS: Blood and spontaneous urine samples were obtained from active, quartz-exposed workers without silicosis (n = 63), and from retired workers with silicosis (n = 42). Levels of 8-hydroxydeoxyguanosine (8-OHdG) were determined in peripheral blood leukocyte DNA and urine, by the use of high-performance liquid chromatography coupled with ultra violet- (UV) and electrochemical detection. RESULTS: No significant differences in the mean levels of 8-OHdG in leukocyte DNA and of urinary excretion of 8-OHdG were found between silicosis patients and quartz-exposed healthy workers. However, in the group of silicosis patients with increased oxidative DNA damage the urinary excretion of 8-OHdG was lower than in the corresponding group of active workers without silicosis. In the case of silicosis, urinary 8-OHdG correlated positively, and 8-OHdG in DNA correlated negatively, with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Healthy workers with a personally estimated high dust exposure in the workplace showed higher levels of 8-OHdG in DNA than did workers with moderate dust exposure. No association of 8-OHdG formation and/or elimination with duration of employment, field of activity, smoking or age was found. CONCLUSION: Our findings suggest that a less effective repair of 8-OHdG is associated with a higher degree of pulmonary airway obstruction in patients with silicosis.