Piard J.,University of Franche Comte |
Collet C.,Center Hospitalier University Lariboisiere |
Arbez-Gindre F.,University of Franche Comte |
Nirhy-Lanto A.,Center Hospitalier Intercommunal Of La Haute Saone |
Van Maldergem L.,University of Franche Comte
European Journal of Medical Genetics
We describe a multiple malformation syndrome comprising coronal craniosynostosis, unilateral radial ray hypoplasia and diaphragmatic hernia in a 33w female fetus born to a 46 y-old male with an alleged personal and family history of Crouzon syndrome. By identifying an already described c.445C>T TWIST missense mutation, we were able to reassign the diagnosis of the family condition to Saethre-Chötzen syndrome. The present report illustrates clinical variability of a dominantly inherited TWIST mutation and provides a third example of Baller-Gerold/Saethre-Chötzen overlapping phenotype. We also add diaphragmatic hernia in the spectrum of TWIST-related malformations, although we couldn't prove the co-occurrence is not coincidental. © 2012 Elsevier Masson SAS. Source
Taillibert S.,University Pierre and Marie Curie |
Vicaut E.,Center Hospitalier University Lariboisiere |
Le Rhun E.,Breast Unit |
Guillamo J.-S.,Caen University Hospital Center |
And 5 more authors.
TLR-9 agonists are immunostimulating agents that have antitumor effects in animal models. A phase I trial was conducted to define the safety profile of subcutaneous injections, combined with intrathecally administration of CpG-28, a TRL 9 agonist, in patients with neoplastic meningitis (NM). Cohorts of 3-6 patients with NM were treated for 5 weeks with escalating doses of CpG-28. The primary endpoint was tolerance. Secondary endpoints were progression free survival (PFS) and overall survival (OS). Twenty-nine patients were treated with CpG-28. The primary cancers were malignant glioma, lung carcinoma, breast cancer, melanoma or melanocytoma, ependymoma, and colorectal cancer. The median age was 56 years and median Karnovsky Performance status (KPS) was 70%. The treatment was well tolerated. Adverse effects that were possibly or probably related to the studied drug were grade 2 lymphopenia, anemia and neutropenia, local erythema at injection sites, fever and seizure. There were five serious adverse events: two confusions, two infections of ventricular devices and one grade 4 thrombopenia and neutropenia. The median PFS was 7 weeks and median OS was 15 weeks. Interestingly, the median survival was slightly (but not significantly) higher in the eight patients who were concomitantly treated with bevacizumab (19 weeks vs 15 weeks; P = 0.11). CpG-28 was well tolerated at doses up to 0.3 mg/kg subcutaneously and 18 mg intrathecally. Additional trials are warranted. © 2015 Japanese Cancer Association. Source
Perruche F.,Hopital Cochin |
Elie C.,University of Paris Descartes |
D'Ussel M.,Hopital Cochin |
Ray P.,University Paris Diderot |
And 9 more authors.
Emergency Medicine Journal
Objective: To assess the sensitivity and specificity of emergency physicians in detecting anxiety and depression in patients requiring admission to the emergency department (ED) observation care unit for complementary investigations/treatment. Methods: 339 consecutive patients admitted to the emergency observation care unit of 14 EDs were interviewed with standardised questionnaires. The characteristics of the patients, EDs and attending ED physicians were collected. Patients' anxiety and depression were identified using the Hospital Anxiety and Depression Scale (HADS), a self-administered questionnaire. ED physicians were blind to the HADS score and were asked to declare whether they perceived anxiety and depression in each patient. The judgement of ED physicians and the HADS score were compared using sensitivity, specificity, positive and negative likelihood ratios. Results: The HADS questionnaire was correctly completed by 310 patients who comprised the study population. HADS detected symptoms of anxiety in 148 patients (47%) and symptoms of depression in 70 patients (23%). ED physicians determined the presence or absence of anxiety with a sensitivity of 48% (95% CI 40% to 56%) and a specificity of 69% (95% CI 61% to 75%). Positive and negative likelihood ratios were 1.54 (95% CI 1.16 to 2.06) and 0.75 (95% CI 1.28 to 3.28) for anxiety. They detected the presence or absence of depression with a sensitivity of 39% (95% CI 28% to 51%) and a specificity of 78% (95% CI 72% to 83%). Positive and negative likelihood ratios were 1.75 (95% CI 1.20 to 2.56) and 0.78 (95% CI 1.26 to 3.87) for depression. Conclusion: Although patients presenting to the ED often experience anxiety and depression, these symptoms are poorly detected by ED physicians. Source
Cayla G.,Institut Universitaire de France |
Cayla G.,University of Nimes |
Silvain J.,Institut Universitaire de France |
Barthelemy O.,Institut Universitaire de France |
And 8 more authors.
Aim: To determine the incidence, type and possible association with mortality of major bleeding in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with an invasive strategy using predominantly the radial approach and triple antiplatelet therapy. Methods: In the multicentre randomised ABOARD Study, 352 patients with NSTE-ACS were randomised to an 'immediate percutaneous coronary intervention (PCI)' strategy or a strategy of PCI on the 'next working day'. Radial access was predominantly used in this study population. The present subanalysis evaluated the occurrence of major bleeding complications and their association with mortality at 1 month. Results: Patients were treated with a triple antiplatelet therapy using high loading and maintenance doses of clopidogrel and abciximab in 99% of patients receiving PCI. The trans-radial approach was used in the vast majority of patients (84%). During the first 30 days, major bleeding complications (STEEPLE definition) occurred in 5.4% of patients (n=19), with no difference between immediate and delayed intervention. The most common bleeding complications were occult bleeding (36.8% of bleeding, n=7/19) and overt gastrointestinal bleeding (21% of bleeding, n=4/19). Patients with major bleeding had a higher peak concentration of creatinine during hospitalisation (mean±SD, 170±169 vs 97±57 μmol/l; p=0.005) and a 1-month mortality of 26.3%, much higher than patients without bleeding (0.6%, p<0.0001). Major bleeding was strongly associated with 30-day mortality (OR 50.3; 95% CI 10.1 to 249.7; p<0.0001). Conclusion: Despite the predominant use of the radial approach, major bleeding (essentially occult and gastrointestinal) remains a common complication, which is highly associated with mortality in patients with NSTE-ACS treated with optimal antithrombotic therapy. Source
Bruno A.,Paris-Sorbonne University |
Bruno A.,French Institute of Health and Medical Research |
Bruno A.,French National Center for Scientific Research |
Boisselier B.,Paris-Sorbonne University |
And 25 more authors.
Little is known about the genomic basis of primary central nervous system lymphoma (PCNSL) tumorigenesis. To investigate the mutational profile of PCNSL, we analyzed nine paired tumor and germline DNA samples from PCNSL patients by high throughput exome sequencing. Eight genes of interest have been further investigated by focused resequencing in 28 additional PCNSL tumors to better estimate their incidence. Our study identified recurrent somatic mutations in 37 genes, some involved in key signaling pathways such as NFKB, B cell differentiation and cell cycle control. Focused resequencing in the larger cohort revealed high mutation rates for genes already described as mutated in PCNSL such as MYD88 (38%), CD79B (30%), PIM1 (22%) and TBL1XR1 (19%) and for genes not previously reported to be involved in PCNSL tumorigenesis such as ETV6 (16%), IRF4 (14%), IRF2BP2 (11%) and EBF1 (11%). Of note, only 3 somatically acquired SNVs were annotated in the COSMIC database. Our results demonstrate a high genetic heterogeneity of PCNSL and mutational pattern similarities with extracerebral diffuse large B cell lymphomas, particularly of the activated B-cell (ABC) subtype, suggesting shared underlying biological mechanisms. The present study provides new insights into the mutational profile of PCNSL and potential targets for therapeutic strategies. Source