PubMed | University of Bordeaux 1, Uppsala University, Lyon University Hospital Center, Montpellier University and 12 more.
Type: Journal Article | Journal: Journal of human genetics | Year: 2016
Otopalatodigital spectrum disorders (OPDSD) constitute a group of dominant X-linked osteochondrodysplasias including four syndromes: otopalatodigital syndromes type 1 and type 2 (OPD1 and OPD2), frontometaphyseal dysplasia, and Melnick-Needles syndrome. These syndromes variably associate specific facial and extremities features, hearing loss, cleft palate, skeletal dysplasia and several malformations, and show important clinical overlap over the different entities. FLNA gain-of-function mutations were identified in these conditions. FLNA encodes filamin A, a scaffolding actin-binding protein. Here, we report phenotypic descriptions and molecular results of FLNA analysis in a large series of 27 probands hypothesized to be affected by OPDSD. We identified 11 different missense mutations in 15 unrelated probands (n=15/27, 56%), of which seven were novel, including one of unknown significance. Segregation analyses within families made possible investigating 20 additional relatives carrying a mutation. This series allows refining the phenotypic and mutational spectrum of FLNA mutations causing OPDSD, and providing suggestions to avoid the overdiagnosis of OPD1.
PubMed | Cochin Hospital, Center Hospitalier Bretagne Atlantique, Catherine Of Sienne Center, University of Nantes and 13 more.
Type: Journal Article | Journal: The Lancet. Haematology | Year: 2016
Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated radioimmunotherapy using anti-CD22 We did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals. Eligible patients were aged 60-80 years with bulky stage 2-3 or stage 3-4 CD20-positive diffuse large B-cell lymphoma, previously untreated, and not eligible for transplantation. Patients received six cycles of R-CHOP (rituximab [375 mg/mBetween Oct 22, 2008, and Dec 16, 2010, we recruited 75 patients, of whom four (5%) were excluded after central pathology review; hence, 71 (95%) patients were included in the analysis. All patients started induction treatment; 57 (80%) received radioimmunotherapy. With a median follow-up of 37 months (IQR 30-44), the estimated 2 year event-free survival was 75% (95% CI 63-84). Radioimmunotherapy toxicity consisted of grade 3-4 thrombocytopenia in 48 (84%) of 57 patients and neutropenia in 45 (79%) of 57 patients. One patient developed myelodysplastic syndrome 28 months after receiving radioimmunotherapy and one patient developed acute myeloid leukaemia 5 months after receiving radioimmunotherapy.Fractionated radioimmunotherapy with Immunomedics, Amgen, Cancerople Grand Ouest, the GOELAMS/LYSA group and the French National Agency for Research (Investissements dAvenir).
PubMed | Center hospitalier Bretagne Atlantique, Rennes University Hospital Center and University of Rennes 1
Type: Journal Article | Journal: Journal de gynecologie, obstetrique et biologie de la reproduction | Year: 2016
To assess the use of French Cancer Institute recommendations for the diagnosis and treatment of endometrial cancer.Retrospective observational study involving 137patients with endometrial cancer between 2011 and 2013.Both MRI and pathological assessment with correct report as recommended were used for 66.4% of patients with endometrial cancer. For patients with correct preoperative assessment, 44.9% of patients were uncorrectly classified and upgraded on final pathological analysis of hysterectomy concerning lymph node involvement risk. These patients did not have confident surgical assessment, according this risk.To improve relevance of preoperative assessment in endometrial cancer, radiological and pathological expertise is required. However, even performed optimally, preoperative assessment does not allow correct risk stratification of lymph node involvement in endometrial cancer. This ineffective stratification leads to propose sentinel lymph node biopsy with hysterectomy in case of preoperative low risk endometrial cancer assessment.
PubMed | University of Nantes, Hoffmann-La Roche and Center Hospitalier Bretagne Atlantique
Type: Journal Article | Journal: BMC cancer | Year: 2016
Mantle Cell Lymphoma (MCL) is often associated with progression, temporary response to therapy and a high relapse rate over time resulting in a poor long-term prognosis. Because MCL is classified as an incurable disease, therapeutic resistance is of great interest. However, knowledge about the biological mechanisms underlying resistance associated with MCL therapies and about associated predictors remains poor. The REFRACT-LYMA Cohort, a multicenter prospective cohort of patients with MCL, is set up to address this limitation. We here describe the study background, design and methods used for this cohort.The REFRACT-LYMA Cohort Study aims at including all patients (>18years old) who are diagnosed with MCL in any stage of the disease and treated in specialized oncology centers in three public hospitals in Northwestern France. Any such patient providing a signed informed consent is included. All subjects are followed up indefinitely, until refusal to participate in the study, emigration or death. The REFRACT-LYMA follow-up is continuous and collects data on socio-economic status, medical status, MCL therapies and associated events (resistance, side effects). Participants also complete standardized quality of life (QOL) questionnaires. In addition, participants are asked to donate blood samples that will support ex vivo analysis of expression and functional assays required to uncover predictive biomarkers and companion diagnostics. If diagnostic biopsies are performed during the course of the disease, extracted biological samples are kept in a dedicated biobank.To our knowledge, the REFRACT-LYMA Cohort Study is the first prospective cohort of patients with MCL for whom real-life medical, epidemiological and QOL data is repeatedly collected together with biological samples during the course of the disease. The integrative cohort at mid-term will be unique at producing a large variety of data that can be used to conceive the most effective personalized therapy for MCL patients. Additionally, the REFRACT-LYMA Cohort puts the medical care of MCL patients in a health and pharmacoeconomic perspective.
PubMed | Institute Mutualiste Montsouris, Hopital Ambroise Pare, systemIC, University of Paris Descartes and 2 more.
Type: | Journal: Rheumatology (Oxford, England) | Year: 2016
Granulomatosis with polyangiitis (GPA) mainly affects white Europeans, but rarely GPA may also affect non-Europeans. This study aimed to describe GPA clinical-biological presentation and outcome in black sub-Saharan Africans and Afro-Caribbeans and in North Africans.Among 914 GPA patients included in the French Vasculitis Study Group database, geographic origin and ethnicity were known for 760. Clinical-biological presentations and outcomes of white Europeans vs black sub-Saharans and Afro-Caribbeans and vs North Africans were analysed.Among the 760 patients, 689 (91%) were white Europeans, 33 (4.3%) were North Africans and 22 (2.9%) were sub-Saharans (n = 8) or Afro-Caribbeans (French West Indies, n = 14). Black sub-Saharans and Afro-Caribbeans, compared with white Europeans, were significantly younger at GPA diagnosis (P = 0.003), had more frequent central nervous system involvement (P = 0.02), subglottic stenosis (P = 0.002) and pachymeningitis (P = 0.009), and tended to have more frequent chondritis and retroorbital tumour. Median serum creatinine levels and Birmingham Vasculitis Activity Score were significantly lower in sub-Saharans and Afro-Caribbeans (P = 0.002 and P = 0.003, respectively). In contrast, in comparison with white Europeans, North Africans had only less frequent arthralgias (P = 0.004). Time to relapse was shorter for black sub-Saharans and Afro-Caribbeans compared with white Europeans [adjusted HR = 1.96 (95% CI: 1.09, 3.51) (P = 0.02)], and did not differ for North Africans. In contrast, overall survival was not significantly different according to ethnicity.Our findings indicated different GPA clinical presentations in white Europeans and sub-Saharans and Afro-Caribbeans, with black patients having more frequent severe granulomatous manifestations. In addition, time to relapse was significantly shorter for black sub-Saharans and Afro-Caribbeans compared with white Europeans.
Edouard S.,French National Center for Scientific Research |
Subramanian G.,French National Center for Scientific Research |
Lefevre B.,Center Hospitalier Bretagne Atlantique |
Dos Santos A.,Center Hospitalier Bretagne Atlantique |
And 4 more authors.
Vector-Borne and Zoonotic Diseases | Year: 2013
Here we report a case of co-infection with Orientia tsutsugamushi, the causative agent of scrub typhus, and Arsenophonus nasoniae in a woman with a rash and an eschar who returned from a trip to Southeast Asia. A. nasoniae was previously considered to be a secondary insect and tick endosymbiont of unknown pathogenicity in humans. We amplified both O. tsutsugamushi and A. nasoniae DNA from a skin eschar with qPCR, and a seroconversion for O. tsutsugamushi and A. nasoniae was observed with immunofluorescence assays and western blotting for this patient. And we used 2-D western blotting with an A. nasoniae antigen and polyclonal mouse anti-A. nasoniae antibodies produced in our laboratory to detect the specific antigenic A. nasoniae proteins. © Copyright 2013, Mary Ann Liebert, Inc. 2013.
Le Floc'h M.,Center hospitalier Bretagne Atlantique |
Poirier P.,Center hospitalier Bretagne Atlantique
Medecine Palliative | Year: 2014
In a society of hypermodernity that thrives Homo consumericus, the place of the psychologist driven by psychoanalysis in palliative care training should be questioned. Contemporary discourse contaminates the hospital institution and generates effects on training requests that emerge. A quest for satisfaction is expressed. On the scene of training, requests are nevertheless ambivalent. By not supporting the gadgetry, the psychoanalytic orientation allows to question the place of the truth in palliative care, but at the cost of discomfort. © 2014 Elsevier Masson SAS.
Keesmann K.,Center hospitalier Bretagne Atlantique
Medecine Palliative | Year: 2012
A semi-structured survey conducted among caregivers of a regional hospital in France reveals a confusion between anxiolysis and sedation in some situations of terminal illness. Analysis of the results reveals that this confusion is due to the difficulty in clearly identifying anxiety, the absence of a reassessment of treatment and finally from a trivialization of vigilance disorders at the end of life. Added the difficulty of the notion of refractory symptom and of modulation of sedation's depth. Furthermore the molecule used for sedation has also an indication as anxiolytic and has, for some caregivers, a symbolic connotation of " serene end of life" , as its name suggests, " hypno-well" , good sleep. All this contributes to the confusion. These findings lead to proposals for trainings, tools, places of listening and exchanges. The reflection about the use of a single molecule for two different indications, anxiolysis and sedation, seems to be useful. © 2011 Elsevier Masson SAS.
Le Floc'h M.,Center hospitalier Bretagne Atlantique
Medecine Palliative | Year: 2012
In palliative care services, we meet patients who are waiting for death, for whom death is already there. These are bodies in suspense, watched and locked up in a death sentence. Everything about their relations with others appears to be closed, at the risk of being a tragedy. It's a strange place, a strange time for a meeting where, at a time when everything seems to be passing away, something unexpected can appear. It's an unexpected event that will reveal desire. © 2011 Elsevier Masson SAS.
Righini M.,University of Geneva |
Jobic C.,French Institute of Health and Medical Research |
Boehlen F.,University of Geneva |
Broussaud J.,Center Hospitalier Bretagne Atlantique |
And 4 more authors.
Haematologica | Year: 2013
The assessment of clinical probability represents an important step in the diagnostic strategy of patients with suspected deep vein thrombosis. The recently derived LEFt clinical prediction rule for pregnant women combines three variables: symptoms in the left leg (L), calf circumference difference of 2 centimeters or over (E for edema) and first trimester presentation (Ft) but is lacking an external validation. The LEFt rule was computed among pregnant women with suspected deep vein thrombosis who were included in a multicenter prospective diagnostic management outcome study. We calculated the proportion of women and the prevalence of deep vein thrombosis in each probability group, along with the diagnostic performances of the LEFt rule. All variables needed to compute the rule could be retrieved in 157 of the 167 pregnant women with suspected deep vein thrombosis. The prevalence of confirmed deep vein thrombosis was 13 of 157 (8.3%). The LEFt rule was negative in 46 (29%) women. A deep vein thrombosis was diagnosed in 13 of 111 (11.7%, 95% Confidence Interval (CI): 8.3-20.9%) of women with at least one of the LEFt criteria, as compared with none of 46 (0.0%, 95%CI: 0.0-7.9%) of women with none of the LEFt criteria. These results suggest that a negative LEFt rule accurately identifies pregnant women in whom the proportion of confirmed deep vein thrombosis appears to be very low. The rule should not be used as stand-alone test for excluding DVT during pregnancy, but might rather be implemented in a diagnostic strategy in association with D-dimer measurement and compression ultrasonography. The original trial was registered at clinicaltrials.gov (NCT 00740454). © 2013 Ferrata Storti Foundation.