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Saint-Sauveur-en-Rue, France

Van Belle E.,Heart Catheterization Laboratory | Van Belle E.,Lille University | Juthier F.,Heart Catheterization Laboratory | Juthier F.,Lille University | And 23 more authors.

BACKGROUND-: Significant postprocedural aortic regurgitation (AR) is observed in 10% to 20% of cases after transcatheter aortic valve replacement (TAVR). The prognostic value and the predictors of such a complication in balloon-expandable (BE) and self-expandable (SE) TAVR remain unclear. METHODS AND RESULTS-: TAVR was performed in 3195 consecutive patients at 34 hospitals. Postprocedural transthoracic echocardiography was performed in 2769 (92%) patients of the eligible population, and these patients constituted the study group. Median follow-up was 306 days (Q1-Q3=178-490). BE and SE devices were implanted in 67.6% (n=1872) and 32.4% (n=897). Delivery was femoral (75.3%) or nonfemoral (24.7%). A postprocedural AR≥grade 2 was observed in 15.8% and was more frequent in SE (21.5%) than in BE-TAVR (13.0%, P=0.0001). Extensive multivariable analysis confirmed that the use of a SE device was one of the most powerful independent predictors of postprocedural AR≥grade 2. For BE-TAVR, 8 independent predictors of postprocedural grade 2 were identified including femoral delivery (P=0.04), larger aortic annulus (P=0.0004), and smaller prosthesis diameter (P=0.0001). For SE-TAVR, 2 independent predictors were identified including femoral delivery(P=0.0001). Aortic annulus and prosthesis diameter were not predictors of postprocedural AR for SE-TAVR. A postprocedural AR≥grade 2, but not a postprocedural AR=grade 1, was a strong independent predictor of 1-year mortality for BE (hazard ratio=2.50; P=0.0001) and SE-TAVR (hazard ratio=2.11; P=0.0001). Although postprocedural AR≥grade 2 was well tolerated in patients with AR grade 2 at baseline (1-year mortality=7%), it was associated with a very high mortality in other subgroups: renal failure (43%), AR Source

Marie I.,University of Rouen | Leroi A.-M.,University of Rouen | Menard J.-F.,CHU Rouen | Levesque H.,University of Rouen | And 2 more authors.
Autoimmunity Reviews

Fecal calprotectin (FC) is a simple, non-invasive and reproducible test, which has been described to be highly elevated in patients with active inflammatory bowel diseases. Recently, few authors have reported increased levels of FC in SSc patients, although the relationship between FC levels and the degree of gastrointestinal involvement has not yet been determined in patients with SSc. Thus, this prospective study aimed to: 1) determine the prevalence of increased fecal calprotectin (FC) levels in unselected patients with systemic sclerosis (SSc); 2) make prediction about which SSc patients exhibit increased levels of FC; and 3) evaluate the correlation between increased levels of FC and digestive symptoms, and gastrointestinal involvement, including the presence of small intestinal bacterial overgrowth (SIBO) using glucose H2/CH4 breath test.125 consecutive patients with SSc underwent FC levels and glucose H2/CH4 breath test. All of the patients with SSc also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated.93 (74.4%) patients had abnormal levels of FC (>50μg/g); 68 patients (54.4%) exhibited highly elevated levels of FC (>200μg/g). A marked correlation was found between abnormal FC levels and GSS score of digestive symptoms, esophageal involvement and delayed gastric emptying. Moreover, we found a strong association between abnormal levels of FC and the presence of SIBO on glucose H2/CH4 breath test, with the higher correlation between the presence of SIBO and the level of FC ≥275μg/g with an area under the receiver operating characteristic curve of 0.97±0.001 (CI: 0.93-0.99; p<10-6); the sensitivity of FC level ≥275μg/g for predicting SIBO was as high as 0.93, while the specificity was 0.95. Finally, eradication of SIBO was obtained in 52.4% of the SSc patients with a significant improvement of intestinal symptoms. Finally, after 3months of rotating courses of alternative antibiotic therapy, eradication of SIBO was associated with significant decrease of FC levels in SSc patients.The current study underscores that abnormal FC levels were correlated with gastrointestinal impairment, especially SIBO. Because FC levels ≥. 275. μg/g were markedly associated with the presence of SIBO, our findings suggest that FC may be a helpful test in identifying the group of SSc patients at high risk for SIBO requiring glucose breath test to detect SIBO. Finally, we also suggest that FC levels may be helpful in SSc patients to assess SIBO eradication, as long-term antibiotic therapy is costly and carries risks such as the onset of pseudo-membranous colitis and SIBO-related antibiotic resistance. © 2014 Elsevier B.V. Source

Mescam-Mancini L.,Grenoble University Hospital Center | Lantuejoul S.,Grenoble University Hospital Center | Lantuejoul S.,French Institute of Health and Medical Research | Moro-Sibilot D.,Grenoble University Hospital Center | And 11 more authors.
Lung Cancer

Objectives: ROS1 proto-oncogene translocations define a new molecular subgroup in non-small cell lung cancers (NSCLC) and are associated with a response to the MET/ALK inhibitor, crizotinib. These rearrangements are described in 0.9-1.7% NSCLC, in wild-type EGFR, KRAS and ALK ("triple negative") lung adenocarcinomas. Rapid and efficient identification of these alterations is thus becoming increasingly important. Materials and methods: In this study, 121 triple negative lung adenocarcinomas were screened by both IHC with the ROS1 D4D6 antibody, and FISH using two commercially available ROS1 break-apart probes. To address a possible cross-reactivity of the ROS1 antibody with other protein kinase receptors, we screened 80 additional cases with known EGFR, KRAS, PI3KCA, BRAF, HER2 mutations or ALK-rearrangement. Results: We diagnosed 9 ROS1-rearranged adenocarcinomas, with both a positive FISH result (51-87% rearranged nuclei) and a positive IHC staining (2+/3+ cytoplasmic staining). Only one of the ROS1-positive FISH cases was characterized by a classical split pattern, the others showed a variant pattern, most commonly involving a loss of the 5' telomeric probe. Considering a positivity threshold of 2+ stained cells, the sensitivity of the ROS1 D4D6 antibody compared to FISH was 100% and the specificity 96.9%, as two HER2-mutated tumors were positive with D4D6 antibody, without any translocation in FISH. All the ROS1-positive cases were at an advanced stage, arising in never or light smokers. They were mainly solid cribriform and acinar adenocarcinomas, with signet ring cells noted in 5 cases, and calcifications in 3 cases. One positive case was an invasive mucinous carcinoma. Conclusion: Our results show that a screening algorithm based on an IHC detection of ROS1 fusion proteins, confirmed if positive or doubtful by a ROS1 break-apart FISH assay, is pertinent in advanced "triple negative" lung adenocarcinomas, since the prevalence of ROS1-positive cases in this selected population reaches 7.4% in our series. © 2013 Elsevier Ireland Ltd. Source

Marie I.,University of Rouen | Gehanno J.-F.,CHU Rouen
Seminars in Immunopathology

Systemic sclerosis (SSc) has a complex pathogenesis. Although, there is a growing evidence that environmental factors have an impact on alterations and modulation of epigenetic determinants, resulting in SSc onset and progression. A marked correlation has thus been found between SSc onset and occupational exposure to crystalline silica and the following organic solvents: white spirit, aromatic solvents, chlorinated solvents, trichloroethylene, and ketones; the risk associated with high cumulative exposure to silica and organic solvents further appears to be strongly increased in SSc. Altogether, occupational exposure should be systematically checked in all SSc patients at diagnosis, as (1) exposed patients seem to develop more severe forms of SSc and (2) the identification of the occupational agents will allow its interruption, which may lead to potential improvement of SSc outcome. By contrast, based on current published data, there is insufficient evidence that exposure to other chemical agents (including notably pesticides as well as personal care such as silicone and hair dye), physical agents (ionizing radiation, ultraviolet radiation, electric and magnetic fields), and biological agents (infections and diet, foods, and dietary contaminants) is a causative factor of SSc. Further investigations are still warranted to identify other environmental factors that may be associated with SSc onset and progression. © 2015, Springer-Verlag Berlin Heidelberg. Source

Resection of pancreatic adenocarcinoma is the only chance for cure giving a survival for resectable tumors between 20 and 30 months after adjuvant therapy. The primary driver of clinical management is the feasability of surgical resection. To guide surgical indications, resectability criteria have been defined, but the literature and published data are heterogeneous. Several groups have formulated their criteria to describe pancreatic tumors in terms of operability, each focusing on the anatomic interface between the tumor and its surrounding critical structures. These include the MD Anderson Cancer Center (MDACC), American Hepato Pancreato Biliary Assocation (AHPBA) and National Comprehensive Cancer Network (NCCN) criteria. These systems define resectable disease, borderline resectable disease and locally advanced unresectable disease. These classification systems are based on standardized CT-scan analysis. American recommandations have been updated in early 2014. Although these classifications are informative, they should not be used without analysis of clinical and laboratory data which are required for therapeutic decision Recent advances in terms of chemotherapy based on FOLFIRINOX and nabpaclitaxel suggest the interest of sequential management for unresectable disease with firstly neoadjuvant treatment, secondly repeated monitoring and evaluation of resectability and thirdly surgery for well selected candidates. The evaluation of tumor's resectability is currently the key criteria guiding oncological management according to the tumoral stage. Source

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