Éditeur(s) : HAL CCSD
Résumé : International audience
o abstract
Revue Des Maladies Respiratoires

hal-01647782
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647782
DOI : 10.1016/j.rmr.2017.07.017
PUBMED : 28939155

Éditeur(s) : HAL CCSD
Résumé : International audience
o abstract
Revue Des Maladies Respiratoires

hal-01647076
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647076
DOI : 10.1016/j.rmr.2017.07.022
PUBMED : 28935495

Éditeur(s) : HAL CCSD
Résumé : International audience
Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.
European Respiratory Journal

hal-01647080
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647080
DOI : 10.1183/13993003.00716-2017
PUBMED : 29074543

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.
ISSN: 1098-3600

hal-01134364
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134364
DOI : 10.1038/gim.2015.29
PUBMED : 25790162

Éditeur(s) : HAL CCSD
Résumé : International audience
Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. Trial registration numbers NCT01746121 and NCT02397824
Journal of Medical Genetics

hal-01272929
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01272929
DOI : 10.1136/jmedgenet-2015-103302
PUBMED : 26502894

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Introduction. - Temocillin is an alternative to treat urinary tract infections with bacteria producing extended spectrum beta-lactamase (ESBL). The objective is to evaluate the use of temocillin in urinary tract infections. Materials and methods. - A systematic review of literature was carried out according to PRISMA criteria. All national and international recommendations have been reviewed regarding the indication of the use of temocillin in urology. Data collection on the use of temocillin in urinary tract infection has been performed from the Cochrane, LILACS and the Medline database. The following keywords were used: temocillin, extended spectrum. beta-lactamase, urinary tract infections, urine, prostate, epididymis, testis, diffusion, pharmacokinetics, pharmacodynamics. The selection was based on the methodology, language of publication (English/French), relevance to the topic and date of publication of the articles collected. The endpoint was to provide exhaustive scientific information allowing urologists to use this antibiotic in febrile urinary infections. Results. - Bacteria producing ESBL has a relatively high susceptible to temocillin, ranging from 61 % to 90 %. These rates would allow its use in probabilistic. The dosage recommended is currently, in the normo-renal patient, 4 g per day by intermittent infusion or continuously after a loading dose of 2g. Some studies argue, particularly in case of difficult clinical situations or obese patients, for administration of high doses (6 g/24 h) rather continuous infusion. There is no evident relationship between high doses and side effects. With an excellent urinary and prostatic diffusion, temocilllin might be recommend for the treatment of ESBL prostatitis. Conclusion. - Temocillin is known to have good urinary and prostatic diffusion. According to our results, this antibiotics is now a reliable alternative for the treatment of documented ESBL urinary tract infections. (C) 2017 Elsevier Masson SAS. All rights reserved.
ISSN: 1166-7087

hal-01659245
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01659245
DOI : 10.1016/j.purol.2017.07.242
PUBMED : 28869169

Éditeur(s) : HAL CCSD
Résumé : International audience
Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.
ISSN: 2168-6211

hal-01258705
http://hal.univ-brest.fr/hal-01258705
PUBMED : 25621457
DOI : 10.1001/jamapediatrics.2014.3351

Éditeur(s) : HAL CCSD
Résumé : International audience
o abstract
Revue Des Maladies Respiratoires

hal-01647079
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647079
DOI : 10.1016/j.rmr.2017.07.019
PUBMED : 28939154

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
o abstract
ISSN: 1166-7087

hal-01477211
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477211
DOI : 10.1016/j.purol.2016.07.209
PUBMED : 27969303

Éditeur(s) : HAL CCSD
Résumé : National audience
Introduction Streptococcus pneumoniae est le microorganisme le plus fréquemment responsable de méningites bactériennes communautaires. Notre objectif était de décrire leur présentation, leur prise en charge et leur pronostic à partir des données de la Cohorte nationale Observationnelle des Méningites Bactériennes communautaires de l’AdulTe (COMBAT).
17es Journées Nationales d’Infectiologie
Lille, France

Droits : info:eu-repo/semantics/OpenAccess
inserm-01413456
http://www.hal.inserm.fr/inserm-01413456
http://www.hal.inserm.fr/inserm-01413456/document
http://www.hal.inserm.fr/inserm-01413456/file/2016%2C%20Tubiana%20-%20NEURO06.pdf
PUBMED : 27495605

Éditeur(s) : HAL CCSD European Respiratory Society
Résumé : IF 8.332
International audience
The respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) have not been studied in detail. In this retrospective multicentre study, EGPA was defined by asthma, eosinophilia and at least one new onset extra-bronchopulmonary organ manifestation of disease. The study population included 157 patients (mean±SD age 49.4±14.1 years), with a mean±SD blood eosinophil count of 7.4±6.4×109 L-1 at diagnosis. There was a mean±SD of 11.8±18.2 years from the onset of asthma to the diagnosis of EGPA, of 1.4±8.4 years from the first onset of peripheral eosinophilia to the diagnosis of EGPA, and of 7.4±6.4 years from EGPA diagnosis to the final visit. Despite inhaled and oral corticosteroid treatment, the severity of asthma increased 3-6 months before the onset of the systemic manifestations. Asthma was severe in 57%, 48%, and 56% of patients at diagnosis, at 3 years, and at the final visit, respectively. Persistent airflow obstruction was present in 38%, 30%, and 46% at diagnosis, at 3 years, and at the final visit, respectively. In EGPA, asthma is severe, antedates systemic manifestations by a mean of 12 years, and progresses to long-term persistent airflow obstruction despite corticosteroids in a large proportion of patients, which affects long-term management and morbidity. Copyright © 2016 ERS.
ISSN: 0903-1936

hal-01406073
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01406073
DOI : 10.1183/13993003.00097-2016
PUBMED : 27587545

Éditeur(s) : HAL CCSD Springer Verlag (Germany)
Résumé : International audience
Tight control of basal cytosolic Ca(2+) concentration is essential for cell survival and to fine-tune Ca(2+)-dependent cell functions. A way to control this basal cytosolic Ca(2+) concentration is to regulate membrane Ca(2+) channels including store-operated Ca(2+) channels and secondary messenger-operated channels linked to G-protein-coupled or tyrosine kinase receptor activation. Orai, with or without its reticular STIM partner and Transient Receptor Potential (TRP) proteins, were considered to be the main Ca(2+) channels involved. It is well accepted that, in response to cell stimulation, opening of these Ca(2+) channels contributes to Ca(2+) entry and the transient increase in cytosolic Ca(2+) concentration involved in intracellular signaling. However, in various experimental conditions, Ca(2+) entry and/or Ca(2+) currents can be recorded at rest, without application of any experimental stimulation. This led to the proposition that some plasma membrane Ca(2+) channels are already open/activated in basal condition, contributing therefore to constitutive Ca(2+) entry. This article focuses on direct and indirect observations supporting constitutive activity of channels belonging to the Orai and TRP families and on the mechanisms underlying their basal/constitutive activities.
ISSN: 0175-7571

hal-01528591
https://hal.archives-ouvertes.fr/hal-01528591
DOI : 10.1007/s00249-017-1216-8
PUBMED : 28516266

Éditeur(s) : HAL CCSD European Respiratory Society
Résumé : International audience
Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis. We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-Associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival. 237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40-60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046). TERT/TERC DAV were associated with specific clinical and biological features and reduced transplantfree survival. ©ERS 2016.
ISSN: 0903-1936

hal-01467555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555/file/Prevalence%20and%20characteristics%20of%20TERT.pdf
DOI : 10.1183/13993003.02115-2015

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND: Mutations in the telomerase complex (TERT and TR) are associated with pulmonary fibrosis and frequent hematologic manifestations. The aim of this study was to characterize the prognosis of lung transplantation in patients with TERT or TR mutations. METHODS: Patients with documented TERT or TR mutations who received a lung transplant between 2007 and 2013 in France were identified via an exhaustive search of the lung transplantation network, one expert genetic laboratory, and the clinical research network on rare pulmonary diseases. RESULTS: There were 9 patients (7 men) with TERT (n = 6) or TR (n = 3) mutations who received a single (n = 8) or a double (n = 1) lung transplant for pulmonary fibrosis. Median age was 50 years (range, 35-61 years) at diagnosis and 52 years (range, 37-62 years) at the time of lung transplantation. Thrombocytopenia was present in 7 patients before lung transplantation. After lung transplantation, 6 patients developed myelodysplasia and/or bone marrow failure, directly contributing to death in 4 cases. Anemia was observed in 9 patients, and neutropenia was observed in 3 patients. The median survival after lung transplantation was 214 days (range, 59-1,709 days). CONCLUSIONS: Patients with mutations of the telomerase complex are at high risk of severe hematologic complications after lung transplantation, in particular, bone marrow failure. Specific recommendations should be developed for appropriate guidance regarding hematologic risk assessment before transplantation and management of the post-transplantation immunosuppressive regimen.
ISSN: 1053-2498

hal-01146848
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146848
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146848/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146848/file/Severe%20hematological%20complications%20after%20lung%20transplantation_accepted.pdf
DOI : 10.1016/j.healun.2014.11.010

Éditeur(s) : HAL CCSD
Résumé : International audience
Objective To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA. Methods Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease. Results The study population included 157 patients (mean age 49.4 ± 14.1), with a follow-up of 7.4 ± 6.4 years. Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glomerulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic vasculitis (p = 0.005) and with the presence of ANCA (p < 0.001). Overall, 59% of patients had polyangiitis as defined by definite vasculitis, strong surrogate of vasculitis, mononeuritis multiplex, and/or ANCA with at least one systemic manifestation other than ENT or respiratory. Patients with polyangiitis had more systemic manifestations including arthralgias (p = 0.02) and renal disease (p = 0.024), had higher peripheral eosinophilia (p = 0.027), and a trend towards less myocarditis (p = 0.057). Using predefined criteria of vasculitis and surrogates of vasculitis, ANCA alone were found to be insufficient to categorise patients with vasculitis features. Conclusion We suggest a revised nomenclature and definition for EGPA and a new proposed entity referred to as hypereosinophilic asthma with systemic (non vasculitic) manifestations. © 2016 Elsevier B.V.
Autoimmunity Reviews

hal-01467544
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467544
DOI : 10.1016/j.autrev.2016.09.018
PUBMED : 27671089

Éditeur(s) : HAL CCSD
Résumé : International audience
Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines.
Eur Respir Rev

hal-01063982
https://hal.archives-ouvertes.fr/hal-01063982
DOI : 10.1183/09059180.00001814
PUBMED : 24881074

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
We aimed to assess the impact of a postoperative drainage after RPN. A retrospective multicentric study included RPN performed at eight centers between 2010 and 2014. Three centers stopped using postoperative drainage early in their RPN experience, whereas other institutions systematically left a drain. Preoperative characteristics, complication rates, need for postoperative imaging or procedure (surgical or radiological) and length of hospital stay were compared between the two groups [drainage (D) and no drainage (ND)]. Among 636 RPNs, 140 were done without drainage (22 %). In the ND group, surgeons were more experienced (> 50 cases: 55.7 vs. 15.1 %; p < 0.0001), and tumors were more complex (RENAL score: 7.6 vs. 6.5; p < 0.0001). Complication rates were similar in both groups (21.9 vs. 20.2 %; p = 0.67). The omission of postoperative drainage did not increase requirement of CT scan (RR = 1.03; 95 % CI 0.64-1.67). Length of hospital stay was shorter in the ND group (4.5 vs. 5.5 days; p = 0.007). There were six urinary fistulas: four in the D group (0.8 %) and two in the ND group (1.4 %; p = 0.49). A CT scan was done to confirm the diagnosis of fistula in every case. In multivariate analysis, the omission of drainage was not associated with increased need of postoperative CT scan or major complications but was a predictor of decreased length of stay. The omission of postoperative drainage does not seem to increase the risk of postoperative complications and could safely be omitted after RPN.
ISSN: 0724-4983

hal-01361502
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01361502
DOI : 10.1007/s00345-015-1721-2
PUBMED : 26511751