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OBJECTIVE: This study investigates the difference in the rates of bronchopulmonary dysplasia in very low birth weight infants before and after the introduction of neurally adjusted ventilatory assist (NAVA). STUDY DESIGN: A retrospective cohort study comparing rates of Bronchopulmonary dysplasia (BPD) before and after implementation of NAVA. Eligibility criteria included all very low birth weight VLBW neonates needing ventilation. For analysis, each cohort was divided into three subgroups based on gestational age. Changes in the rate of BPD, length of stay, tracheostomy rates, invasive ventilator days, and home oxygen therapy were compared. RESULTS: There were no differences in the incidence of BPD in neonates at 23-25 6/7 weeks' and 29-32 weeks' gestation between the two cohorts. A higher incidence of BPD was seen in the 26-28 5/7 weeks' gestation NAVA subgroup compared to controls (86% vs. 68%, p = 0.05). No significant difference was found for ventilator days, but infants in the 26-28 6/7 subgroup in the NAVA cohort had a longer length of stay (98 ± 34 days vs. 82 ± 24 days, p = 0.02), a higher percentage discharged on home oxygen therapy (45% vs. 18%, respectively, p = 0.006), and higher tracheostomy rates (3/36 vs. 0/60, p = 0.02), compared to the control group. CONCLUSIONS: The NAVA mode was not associated with a reduction in BPD when compared to other modes of ventilation. Unexpected increases were seen in BPD rates, home oxygen therapy rates, tracheostomy rates, and the length of stay in the NAVA subgroup born at 26-28 6/7 weeks' gestation.
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AIMS: Myxomatous mitral valve disease (MMVD) is associated with leaflet thickening, fibrosis, matrix remodelling, and leaflet prolapse. Molecular mechanisms contributing to MMVD, however, remain poorly understood. We tested the hypothesis that increased transforming growth factor-ß (TGF-ß) signalling and reactive oxygen species (ROS) are major contributors to pro-fibrotic gene expression in human and mouse mitral valves. METHODS AND RESULTS: Using qRT-PCR, we found that increased expression of TGF-ß1 in mitral valves from humans with MMVD (n = 24) was associated with increased expression of connective tissue growth factor (CTGF) and matrix metalloproteinase 2 (MMP2). Increased levels of phospho-SMAD2/3 (western blotting) and expression of SMAD-specific E3 ubiquitin-protein ligases (SMURF) 1 and 2 (qRT-PCR) suggested that TGF-ß1 signalling occurred through canonical signalling cascades. Oxidative stress (dihydroethidium staining) was increased in human MMVD tissue and associated with increases in NAD(P)H oxidase catalytic subunits (Nox) 2 and 4, occurring despite increases in superoxide dismutase 1 (SOD1). In mitral valves from SOD1-deficient mice, expression of CTGF, MMP2, Nox2, and Nox4 was significantly increased, suggesting that ROS can independently activate pro-fibrotic and matrix remodelling gene expression patterns. Furthermore, treatment of mouse mitral valve interstitial cells with cell permeable antioxidants attenuated TGF-ß1-induced pro-fibrotic and matrix remodelling gene expression in vitro. CONCLUSION: Activation of canonical TGF-ß signalling is a major contributor to fibrosis and matrix remodelling in MMVD, and is amplified by increases in oxidative stress. Treatments aimed at reducing TGF-ß activation and oxidative stress in early MMVD may slow progression of MMVD.
Assuntos
Matriz Extracelular/metabolismo , Doenças das Valvas Cardíacas/metabolismo , Valva Mitral/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Animais , Antioxidantes/farmacologia , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Fibrose , Regulação da Expressão Gênica , Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Valva Mitral/efeitos dos fármacos , Valva Mitral/patologia , NADPH Oxidase 2 , NADPH Oxidase 4 , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Infection is one of the major limitations to successful long-term support after ventricular assist device implantation. There are limited data specifically examining the incidence and predictors of driveline infections (DLI), with a changing treatment paradigm toward destination therapy (DT) and longer duration of support. METHODS: Between January 2007 and 2011, 143 patients underwent HeartMate II (Thoratec, Pleasanton, CA) implantation, with 87 (61%) as DT. Driveline maintenance strategy included sterile dressing changes with chlorhexidine and saline application, without prophylactic oral antibiotics. RESULTS: DLI developed in 18 patients (12%) at a median of 182 days (range, 26 to 1,138 days) after implantation, among which 12 (66%) were from the DT cohort. Infections were superficial in 15 (82%) and deep in 3 (18%). Trauma was documented in 6 patients (33%). Seven patients (38%) needed readmission for DLI. Surgical debridement was needed in 3 (17%). All patients were managed successfully, without the need for device explantation or urgent cardiac transplantation. No patient required continuous antibiotic prophylaxis after the infection subsided. Risk factor analysis identified duration of support as the only independent predictor of infection (mean. 600 vs 390 days; p = 0.03). The odds of having a DLI rose by 4% for every month of support. CONCLUSIONS: Longer duration of support significantly increased the risk of DLI and hence increased the risk of DLI in patients with DT. DLI may be successfully managed with antibiotics and local wound care. Most of the infections were superficial, and progression to deep pocket or pump infection is rare in our experience.