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Isidor B.,Nantes University Hospital Center | Lindenbaum P.,Nantes University Hospital Center | Lindenbaum P.,French Institute of Health and Medical Research | Lindenbaum P.,University of Nantes | And 26 more authors.
Nature Genetics | Year: 2011

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner. © 2011 Nature America, Inc. All rights reserved.


Pidhorz L.,Center hospitalier du Mans | Alligand-Perrin P.,Center hospitalier du Mans | De Keating E.,Center hospitalier du Mans | Fabre T.,Service dorthopedie traumatologie | Mansat P.,Institut Universitaire de France
Orthopaedics and Traumatology: Surgery and Research | Year: 2013

Introduction: Conservative treatment is exceptional in fracture of the distal extremity of the humerus in patients over 65 years of age. In a selected population, however, it may be an attractive option. Materials and methods: One prospective and one retrospective study included a total of 56 patients, with a mean age of 84.7 years (range, 68-100 yrs). All were managed by 6 to 8 weeks' brachial-antebrachial-palmar immobilization, without fracture reduction. Fractures were AO type A in 18 cases, type B in 8 cases and type C in 30 cases. Results: At a mean 20.2 months' follow-up in the retrospective and 8.6 months in the prospective series, mean MEPS score was 83 and 86 points with 75% and 83% satisfactory results respectively and mean Quick-DASH 31.3 and 34.4 points respectively. There were 3 non-unions. There was extra-articular malunion in 70% and intra-articular malunion in 65% of cases in the retrospective series, versus 16% intra-articular malunion in the prospective series. The rate of osteoarthritis increased over time, with more than 50% grade 2 or 3 in the retrospective series at end of follow-up. There were 3 complications: 2 hematomas and 1 skin lesion (localized pressure ulcer). There were 3 fracture displacements, not requiring change in management. Discussion: Conservative treatment for fracture of the distal extremity of the humerus in patients over 65 years of age is exceptional, but conserves patient's independence and provides satisfactory clinical results, with no significant joint stiffness or elbow instability. Non-anatomic results on X-ray, however, have to be accepted. Level of evidence: Level IV. © 2013 Elsevier Masson SAS.


Cappuzzo F.,Ospedale Civile di Livorno | Ciuleanu T.,Institute of Oncology Ion Chiricuta | Stelmakh L.,St. Petersburg State Medical University | Cicenas S.,Vilnius University | And 9 more authors.
The Lancet Oncology | Year: 2010

Background: First-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) is usually limited to four to six cycles. Maintenance therapy can delay progression and prolong survival. The oral epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib has proven efficacy and tolerability in second-line NSCLC. We designed the phase 3, placebo-controlled Sequential Tarceva in Unresectable NSCLC (SATURN; BO18192) study to assess use of erlotinib as maintenance therapy in patients with non-progressive disease following first-line platinum-doublet chemotherapy. Methods: Between December, 2005, and May, 2008, 1949 patients were included in the run-in phase (four cycles of platinum-based chemotherapy). At the end of the run-in phase, 889 patients who did not have progressive disease were entered into the main study, and were randomly allocated using a 1:1 adaptive randomisation method through a third-party interactive voice response system to receive erlotinib (150 mg/day; n=438) or placebo (n=451) until progression or unacceptable toxicity. Patients were stratified by EGFR immunohistochemistry status, stage, Eastern Cooperative Oncology Group performance status, chemotherapy regimen, smoking history, and region. Co-primary endpoints were progression-free survival (PFS) in all analysable patients irrespective of EGFR status, and PFS in patients whose tumours had EGFR protein overexpression, as determined by immunohistochemistry. This study is registered with www.ClinicalTrials.gov, number NCT00556712. Findings: 884 patients were analysable for PFS; 437 in the erlotinib group and 447 in the placebo group. After a median follow-up of 11·4 months for the erlotinib group and 11·5 months for the placebo group, median PFS was significantly longer with erlotinib than with placebo: 12·3 weeks for patients in the erlotinib group versus 11·1 weeks for those in the placebo group (HR 0·71, 95% CI 0·62-0·82; p<0·0001). PFS was also significantly longer in patients with EGFR-positive immunohistochemistry who were treated with erlotinib (n=307) compared with EGFR-positive patients given placebo (n=311; median PFS 12·3 weeks in the erlotinib group vs 11·1 weeks in the placebo group; HR 0·69, 0·58-0·82; p<0·0001). The most common grade 3 or higher adverse events were rash (37 [9%] of 443 patients in the erlotinib group vs none of 445 in the placebo group) and diarrhoea (seven [2%] of 443 patients vs none of 445). Serious adverse events were reported in 47 patients (11%) on erlotinib compared with 34 patients (8%) on placebo. The most common serious adverse event was pneumonia (seven cases [2%] with erlotinib and four [<1%] with placebo). Interpretation: Maintenance therapy with erlotinib for patients with NSCLC is well tolerated and significantly prolongs PFS compared with placebo. First-line maintenance with erlotinib could be considered in patients who do not progress after four cycles of chemotherapy. Funding: F Hoffmann-La Roche Ltd. © 2010 Elsevier Ltd.


Falandry C.,University of Lyon | Weber B.,Center Alexis Vautrin | Savoye A.-M.,Institute Jean Godinot | Tinquaut F.,Hygee Center | And 8 more authors.
Annals of Oncology | Year: 2013

Two previous GINECO elderly specific studies in advanced ovarian cancer (AOC) patients highlighted the prognostic value of geriatric covariates for overall survival (OS). Patients and methods: This open-label prospective trial was designed to identify the impact of geriatric covariates on OS in AOC patients ≥70 years treated with first-line carboplatin. Results: Geriatric covariates of the 111 patients included median age 79 years (≥80 years: 41%); performance status (PS) ≥2: 47%; ≥3 major comorbidities: 24%; ≥4 comedications: 68%; activities of daily living (ADL) score <6: 55%; instrumental activities of daily living (IADL) score <25: 69%; Hospital Anxiety and Depression Scale (HADS) >14: 37%. The median OS was 17.4 months. Overall, 74% of patients completed the six planned chemotherapy cycles. Grade 3-4 haematological toxic effects were frequent (50%) but manageable. Grade 3-4 non-haematological toxicities included fatigue (15%), anorexia (12%), infections (9%) and thrombosis (2%). A survival score = exp(0.327*GVS) was developed, where the geriatric vulnerability score (GVS) is the sum of the following (each assigned a value of one): albuminaemia <35 g/l; ADL score <6; IADL score <25; lymphopaenia <1 G/l; and HADS >14. With a cut-off ≥3, GVS discriminated two groups with significantly different OS, treatment completion, severe adverse events and unplanned hospital admissions rates. Conclusions: The GVS is a valuable tool for identifying vulnerable patients when treating an elderly AOC population. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology All rights reserved.


Laribi K.,Center Hospitalier Le Mans | Denizon N.,Center Hospitalier Le Mans | Ghnaya H.,Center Hospitalier Le Mans | Atlassi M.,Center Hospitalier Le Mans | And 4 more authors.
European Journal of Haematology | Year: 2014

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy which was first included as an independent cutaneous lymphoma in the 2008 World Health Organisation (WHO) classification (1). BPDCN usually has an extremely poor prognosis, with quick relapses after chemotherapy (2; 3). Here, we report two cases of patients diagnosed in 2011 with BPDCN and myelodysplasia, and who were treated for the first time with 5-azacytidine (5-Aza); a drug approved by the Food and Drug Administration (FDA) and mainly used in the treatment of myelodysplastic syndrome (Kaminskas E, et al. 2005 Clin Cancer Res, 11, 3604-8). The first case was an 81-year-old man who presented with unusual CD10+, CD56- immunohistochemistry and 45X, -Y abnormality using fluorescent in situ hybridization (FISH) analysis. The second case was a 78-year-old woman who manifested monosomy 13 and chromosome instability due to D13S319 locus deletion in 13q14 as determined by FISH. Both patients showed excellent responses of their skin lesions after one cycle of chemotherapy, and their hematological disease was stabilized; however, pulmonary sepsis set in, followed by neutropenia after the fourth and the fifth cycle of treatment, that is, eight and 9 months postdiagnosis, respectively, leading to patient death. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Baroudjian B.,University Paris Diderot | Viguier M.,University Paris Diderot | Battistella M.,University Paris Diderot | Beneton N.,Center Hospitalier du Mans | And 4 more authors.
British Journal of Dermatology | Year: 2014

Idiopathic CD4+ lymphocytopenia (ICL) is a rare immunodeficiency syndrome of unknown origin for which the increased risks of opportunistic infections and of malignancies have been well established; however, skin dysimmune diseases, including psoriasis, have been scarcely reported up to now. We report herein the severe course of psoriasis in four patients with ICL, and show evidence for a defect in the skin recruitment of regulatory CD4 +FoxP3+ T cells. These data raise the apparent paradigm of the occurrence of a severe immunomediated disease together with a profound T-cell defect, a model that might also apply to other immune deficiencies associated with psoriasis. What's already known about this topic? While the risk of opportunistic infections and of malignancies has been previously stressed in idiopathic CD4+ T-cell lymphocytopenia (ICL), the association with skin dysimmune disorders, mainly psoriasis, has been poorly addressed so far. What does this study add? We report four cases of severe psoriasis in patients with ICL and discuss the contribution of a regulatory T-cell defect to the pathogenesis of psoriasis in this setting. © 2014 British Association of Dermatologists.


Pidhorz L.,Center hospitalier du Mans
Orthopaedics and Traumatology: Surgery and Research | Year: 2015

Humeral shaft fractures account for up to 5% of all fractures. Many of these fractures are still being treated conservatively using functional (Sarmiento) bracing or a hanging arm cast. Union is achieved in 10weeks in more than 94% of cases. Angulation of less than 30° varus or valgus and less than 20° flessum or recurvatum can be tolerated by the patient from a functional and esthetic point of view. The ideal candidate for this treatment is a patient with an isolated fracture. Plate and screw fixation of the fracture results in union in 11 to 19weeks. Reported complications include non-union (2.8-21%), secondary radial nerve palsy (6.5-12%) and infection (0.8-2.4%). Anterograde or retrograde locked intramedullary nailing requires knowledge of nailing techniques and regional anatomy to avoid the complications associated with the technique. Union is obtained in 10-15weeks. Reported complications consist of non-union (2-17.4%), infection (0-4%) and secondary radial nerve palsy (2.7-5%). Hackethal bundle nailing is still used for fracture fixation, despite an elevated complication rate (5-24% non-union and 6-29% pin migration) because of its low cost and simple instrumentation. Union is achieved in 8-9weeks. Controversy remains about the course to follow when the radial nerve is injured initially. If the fracture is open, significantly displaced, associated with a vascular injury or requires surgical treatment, the nerve must be explored. In other cases, the recommended approach varies greatly. Conservative treatment is inexpensive and has a low complication rate. Humeral shaft fractures are increasingly being treated surgically, at a greater cost and higher risk of complications. © 2015 Elsevier Masson SAS.


Vetel J.-M.,Center Hospitalier du Mans
Revue de Geriatrie | Year: 2011

Knee osteoarthritis is a painful and disabling pathology characterized by relapses and remissions with progressive cartilage destruction. Pain relief is the main goal of treatment, which is essentially medical. A pharmacologic arsenal is available, however not devoid of side effects. This article reviews drugs that can be used in the treatment of this condition as well as their advantages and risks. The associated physical therapy is not considered. © La Revue de Gériatrie.


Grimbert P.,Center Hospitalier du Mans | Lebreton O.,Nantes University Hospital Center | Weber M.,Nantes University Hospital Center
Journal Francais d'Ophtalmologie | Year: 2014

Introduction To evaluate the anatomical and functional consequences of internal limiting membrane (ILM) peeling in epiretinal membrane (ERM) surgery. Methods Retrospective single-center study including consecutive patients operated on for idiopathic ERM. The integrity of the ILM was assessed by ILM Blue® staining after removal of the ERM: either the peeling was spontaneous (group 1) or a complementary peeling was required (group 2). Pre- and post-operatively (1 and 6 months), all patients were analyzed using visual acuity, SD-OCT (Spectralis HRA OCT, Heidelberg, Germany) and microperimetry (OPKO/OTI, Miami, USA). Results Twenty-one eyes of 21 patients were included: 12 "active ILM peelings" and 9 "spontaneous peelings". In both groups, visual acuity increased significantly after surgery. Microperimetry revealed more microscotomata at 1 and 6 months for active peeling (P < 0.05). Their location corresponded more often to the site where the ERM or ILM was grasped, based on surgical videos (P < 0.05), and with the appearance of inner retinal defects using en face OCT. Discussion ILM peeling is frequently performed to reduce ERM recurrence. Despite lack of effect on visual acuity, active ILM peeling increases the incidence of microscotomas related to the site where the ERM or ILM is grasped. Conclusion Active ILM peeling may be responsible for postoperative visual discomfort related to microscopic trauma during peeling. © 2014 Elsevier Masson SAS. Tous droits réserv és.


PubMed | Center hospitalier du Mans
Type: Journal Article | Journal: Revue de l'infirmiere | Year: 2017

The socially interactive therapeutic robot Paro is presented in the form of a soft toy. It can benefit patients suffering from Alzheimers as well as nurses.

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