Rivera C.,Bordeaux University Hospital Center |
Bernard A.,CHU Dijon |
Falcoz P.-E.,CHU Strasbourg |
Thomas P.,Marseille University Hospital Center |
And 4 more authors.
Annals of Thoracic Surgery | Year: 2011
Background: The objective of this study was to better characterize prolonged air leak (PAL), defined as an air leak longer than 7 days, and to develop and validate a predictive model of this complication after pulmonary resection. Methods: All lung resections entered in Epithor, the French national thoracic database (French Society of Thoracic and Cardiovascular Surgery), were analyzed. Data collected between 2004 and 2008 (n = 24,113) were used to build the model using backward stepwise variable selection, and the 2009 data (n = 6,813) were used for external validation. The primary outcome was PAL. Results of the predictive model were used to propose a score: the index of PAL (IPAL). Results: Prevalence of PAL after pulmonary resection was 6.9% (n = 1,655) in the development data set. In the final model, 9 variables were selected: gender, body mass index, dyspnea score, presence of pleural adhesions, lobectomy or segmentectomy, bilobectomy, bulla resection, pulmonary volume reduction, and location on upper lobe. In the development data set, the C-index was 0.71 (95% confidence interval [CI], 0.70 to 0.72). At external validation, the C-index was 0.69 (95% CI, 0.66 to 0.72) and the calibration slope (ie, the agreement between observed outcomes and predictions) was 0.874 (<1). A score chart based on these analyses has been proposed. The formula to calculate the IPAL is the following: gender (F = 0; M = 4) - (body mass index-24) + 2 × dyspnea score + pleural adhesion (no = 0; yes = 4) + pulmonary resection (wedge = 0; lobectomy or segmentectomy = 7; bilobectomy = 11; bulla resection = 2; volume reduction = 14) + location (lower or middle lobe = 0; upper = 4). Conclusions: Surgeons can easily use the well-validated model to determine intraoperative preventive measures of PAL. © 2011 The Society of Thoracic Surgeons.
Boursault L.,Bordeaux University Hospital Center |
Haddad V.,Bordeaux University Hospital Center |
Vergier B.,Bordeaux University Hospital Center |
Cappellen D.,Bordeaux University Hospital Center |
And 4 more authors.
PLoS ONE | Year: 2013
BRAF inhibitors have demonstrated improvement of overall survival in patients with metastatic melanoma and BRAFV600 mutations. In order to evaluate BRAF tumor heterogeneity between primary and metastatic site, we have evaluated the performance of immunohistochemistry (IHC) with an anti-BRAFV600E antibody in both localization by comparison with high resolution melting analysis followed by Sanger sequencing in a parallel blinded study. A total of 230 samples distributed as primary melanoma (n = 88) and different types of metastatic samples (n = 142) were studied in 99 patients with advanced or metastatic melanoma (stage III or IV). The prevalence of each BRAF mutation was c.1799T>A, BRAFV600E (45.2%), c.1799_1800TG>AA, BRAFV600E2 (3.0%), c.1798_1799GT>AA, BRAFV600K (3.0%), c.1801 A>G, BRAFK601E (1.3%), c.1789_1790CT>TC, BRAFL597S (0.4%), c.1780G>A, BRAFD594N (0.9%) respectively. IHC was positive in 109/112 samples harboring BRAFV600E/E2 mutations and negative in other cases. The cytoplasmic staining was either strongly positive in tumor cells of BRAFV600E mutated cases. It appeared strong brown, different from the vesicular grey cytoplasmic pigmentation of melanophages. Concordance between the two techniques was 96.4%. Sensitivity of IHC for detecting the BRAFV600E/E2 mutations was 97.3%, while specificity was 100%. Both our IHC and molecular study demonstrated homogeneity between primary and metastatic sites for BRAF status in melanoma. This study also provides evidence that IHC may be a cost-effective first-line method for BRAFV600E detection. Thereafter, molecular techniques should be used in negative, ambiguous or non-contributive cases. © 2013 Boursault et al.
Nisand I.,CHU Strasbourg
Medecine Therapeutique Medecine de la Reproduction, Gynecologie et Endocrinologie | Year: 2013
This opinion column provides grounds for initiating debate involving the public on new problems created by advances in Reproductive Medicine such as gamete donation, homosexual parenting and surrogacy.
Depienne C.,University Pierre and Marie Curie |
Magnin E.,Besancon University Hospital Center |
Bouteiller D.,University Pierre and Marie Curie |
Stevanin G.,University Pierre and Marie Curie |
And 7 more authors.
Neurology | Year: 2010
Background: Familial cortical myoclonic tremor with epilepsy (FCMTE) is defined by autosomal dominant adult-onset cortical myoclonus (CM) and seizures in 40% of patients. Two loci, 8q23.3-q24.11 (FAME1/FCMTE1) and 2p11.1-q12.2 (FAME2/FCMTE2), were previously reported without an identified gene. Unlinked families argue for a third mutated gene. Methods: A genome-wide scan was performed in a large FCMTE family using Linkage-12 microarrays (Illumina). Refinement of the locus on 5p was performed by genotyping 13 polymorphic microsatellite markers in the 45 available family members. Results: This large French FCMTE family included 16 affected relatives. The first symptoms were CM in 5 patients (31.2%), seizures in 5 patients (31.2%), and both at the same time in 6 patients (37.5%). A total of 12.5% (2/16) had only CM without seizures. The genome-wide scan identified a single region on 5p15.31-p15, with a multipoint lod score of 3.66. Further genotyping of all family members confirmed that the region spans 9.31 Mb between D5S580 and D5S2096, 2-point lod scores reaching 6.3 at θ = 0 for D5S486. Sequencing of the SEMA5A and CTNND2 genes failed to detect mutations. Conclusions: We report the clinical and genetic characteristics of a large familial cortical myoclonic tremor with epilepsy family. The third gene maps to 5p15.31-p15. Identification of the mutated gene is ongoing. Copyright © 2010 by AAN Enterprises, Inc.
Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study
Emery P.,University of Leeds |
Gottenberg J.E.,CHU Strasbourg |
Rubbert-Roth A.,University of Cologne |
Sarzi-Puttini P.,University of Milan |
And 11 more authors.
Annals of the Rheumatic Diseases | Year: 2014
Objectives: To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi. Methods: SWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patient's global health component (DAS28-3)-erythrocyte sedimentation rate (ESR) over 6 months. Results: 604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3-ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least squares mean (SE) change in DAS28-3-ESR at 6 months was significantly greater in rituximab than TNFi patients: -1.5 (0.2) vs -1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (-1.7 vs -1.3; p=0.017) but not intolerance (-0.7 vs -0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3-ESR with rituximab than with TNFi (-1.6 (0.3) vs -1.2 (0.3); p=0.011), particularly those switching because of inefficacy (-1.9 (0.3) vs -1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups. Conclusions: These real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy. © 2014 BMJ Publishing Group Ltd & European League Against Rheumatism.