Marthey L.,University Paris - Sud |
Cadiot G.,Robert Debre University Hospital |
Seksik P.,Paris-Sorbonne University |
Pouderoux P.,University of Nimes |
And 20 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2014
Background Recently, a new enteropathy has been described: olmesartan-associated enteropathy. However, the association has been questioned: a phase 3 trial and a cohort study found no association between gastrointestinal events and olmesartan.Aim To collect French cases of sartan-associated enteropathy to describe further this entity, confirm or refute causality, and determine if the association exists with other sartans.Methods French gastroenterologists were invited to report cases of sartan-associated enteropathy and collect clinical, biological and histological data. Patients with diarrhoea and histological duodenal abnormalities were included.Results Thirty-six patients with olmesartan-associated enteropathy were reported, including 32 with villous atrophy and four without. There was only one patient with irbesartan-associated enteropathy. None of the patients died. Patients with villous atrophy had diarrhoea, vomiting, renal failure, hypokalaemia, body weight loss and hypoalbuminaemia. Thirty-one patients were hospitalised; four required intensive care. Anti-transglutaminase and anti-enterocyte antibodies were negative; anti-nuclear antibodies were positive (9/11). Endoscopic duodenal biopsies showed villous atrophy (32/32) and polyclonal intra-epithelial CD3+CD8+ lymphocytosis (11/11). Exactly, 14/15 patients responded to steroids and/or immunosuppressants, prescribed because of suspected autoimmune enteropathy. Ten olmesartan interruptions were followed by reintroductions before steroids or immunosuppressants. Interruptions were followed by remissions (9/10), but reintroductions were followed by relapses (9/ 9). Twenty-nine patients were in remission since olmesartan interruption, including 26 without immunosuppressants. Patients with normal villi had similar clinical characteristics, but mild histological abnormalities (intra-epithelial lymphocytosis and lamina propria lymphocytic infiltration).Conclusions Olmesartan causes a severe and immune-mediated enteropathy, with or without villous atrophy. Enteropathy associated with other sartans seems to be very rare. © 2014 John Wiley & Sons Ltd. Source
Anderson A.F.,Tennessee Orthopaedic Alliance |
Irrgang J.J.,University of Pittsburgh |
Dunn W.,Vanderbilt University |
Beaufils P.,Versailles Hospital |
And 16 more authors.
American Journal of Sports Medicine | Year: 2011
Background: Consistency of arthroscopic evaluation and documentation in meniscal tears between investigators is essential to the validity of multicenter studies. A group of experts developed a classification of meniscal tears that may be used internationally. Hypothesis: The International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) classification of meniscal tears provides sufficient interobserver reliability for pooling of data from international clinical trials designed to evaluate the outcomes of treatment for meniscal tears. Study Design: Cohort study (diagnosis); Level of evidence, 1. Methods: A pilot study was performed by having 8 members of the committee grade 10 arthroscopic videos for classification of tear depth, rim width, location, tear pattern, and quality of the tissue. The results of the pilot study were used to change the instruction sheet and evaluation form. International interobserver reliability was determined by having 8 orthopaedic surgeons who practice in different countries evaluate 37 arthroscopic videos selected to represent different meniscal tear characteristics. The Spearman ρ correlation coefficient was used to compare the area of the meniscus excised, as drawn on the diagram, with the numeric percentage of meniscus excised. Results: There was an 87% agreement for anterior-posterior location of the tear (κ =.65); 79% agreement for tear pattern (κ =.72); 88% agreement for tear depth (κ =.52); 68% agreement for anterior, middle, and posterior location of the tear (κ =.46); and 72% agreement for tissue quality (κ =.47). There was 54% agreement for the rim width (κ =.25) and 67% agreement if the tear was central to the popliteal hiatus (κ =.36). Based on the Landis and Koch criteria for κ coefficients, there was substantial agreement for anterior-posterior location of the tear and tear pattern; moderate agreement for tear depth, anterior, middle, and posterior location of the tear, and tissue quality; and fair agreement for rim width and if the tear was central to the popliteal tear. Interobserver reliability based on the intraclass correlation coefficient (ICC) was good for tear length (ICC =.83) and moderate for percentage of meniscus that was excised (ICC =.65). The mean ρ for all raters was.92 (95% confidence interval [CI],.89-.94) comparing the values for percentage of meniscus excised with the area on the diagrams. Conclusion: The ISAKOS classification of meniscal tears provides sufficient interobserver reliability for pooling of data from international clinical trials designed to evaluate the outcomes of treatment for meniscal tears. © 2011 The Author(s). Source
Beaufils P.,Versailles Hospital |
Verdonk R.,Ghent University
The Meniscus | Year: 2010
This clinical guide provides a special focus on the normal meniscal mechanism, body and function. Meniscal pathology and therapy are depicted in detail, followed by the presentation of long-term experience of meniscal transplantation and a look into the future of meniscal surgery. During the last few decades, as the management of meniscal trauma has evolved, and knowledge gained on meniscal function, the orthopaedic surgeon has attempted to preserve the meniscus whenever possible. Arthroscopic meniscal repair has become the treatment of choice when the tear is located in the peripheral rim. Partial meniscectomy has become limited to such an extent that the deleterious effect of total meniscectomy is avoided. Meniscal allograft replacement, which has been available for the last two decades, is used when the patient is confronted with a painful total meniscectomy. Future research and experiments may suggest that partial meniscal replacement might be indicated in the presence of a painful knee compartment after failed meniscal repair or partial meniscectomy. © Springer-Verlag Berlin Heidelberg 2010. All rights are reserved. Source
Renneville A.,Biology and Pathology Center |
Renneville A.,University of Lille Nord de France |
Renneville A.,Cancer Research Institute of Lille |
Boissel N.,University Paris Diderot |
And 22 more authors.
Leukemia | Year: 2012
Recently, DNA methyltransferase 3A (DNMT3A) mutations have been identified in acute myeloid leukemia (AML), the highest frequency being found within cytogenetically normal (CN) AML. In this study, diagnostic samples from 123 adults younger than 60 years with primary CN-AML homogeneously treated in the Acute Leukemia French Association-9801 and-9802 trials were screened for mutations in DNMT3A-conserved domains by direct sequencing. Patients were also assessed for the presence of FLT3 (fms-like tyrosine kinase receptor-3), NPM1 (nucleophosmin), CEBPA, WT1 (Wilms tumor 1), IDH1 (isocitrate dehydrogenase 1) and IDH2 mutations. Thirty-eight mutations were detected in 36 patients (29%): 36 nucleotide substitutions, mostly affecting amino-acid residue R882 and two frameshift deletions. DNMT3A mutations were significantly associated with the French-American-British subtypes M4/M5 and the presence of NPM1 mutations. In the whole cohort, DNMT3A mutated patients had a shorter event-free survival (5-year EFS: 13% vs 32%, P0.02) and overall survival (5-year OS: 23% vs 45%, P0.02) compared with DNMT3A wild-type patients. In multivariate analysis including age, white blood cell count, NPM1/FLT3-internal tandem duplication/CEBPA risk group and DNMT3A mutational status, the presence of a DNMT3A mutation remained an independent adverse prognostic factor for EFS and OS, suggesting that testing for DNMT3A mutations could help further improve risk stratification in CN-AML. © 2012 Macmillan Publishers Limited. Source
Verdonk P.,Ghent University |
Beaufils P.,Versailles Hospital |
Bellemans J.,University Hospitals Leuven |
Djian P.,Institute Of Lappareil Locomoteur Nollet |
And 5 more authors.
American Journal of Sports Medicine | Year: 2012
Background: A novel, biodegradable, polyurethane scaffold was designed to fulfill an unmet clinical need in the treatment of patients with painful irreparable partial meniscal defects.Hypothesis: The use of an acellular polyurethane scaffold for new tissue generation in irreparable partial meniscal defects provides both pain relief and improved functionality.Study Design: Case series; Level of evidence, 4.Methods: Fifty-two patients with irreparable partial meniscal defects (34 medial and 18 lateral, 88% with 1-3 previous surgeries on the index meniscus) were implanted with a polyurethane scaffold in a prospective, single-arm, multicenter, proof-of-principle study. Safety was assessed by the rate of scaffold-related serious adverse events (SAEs) and the International Cartilage Repair Society articular cartilage scoring system comparing magnetic resonance imaging (MRI) at 24 months to MRI at baseline (1 week). Kaplan-Meier time to treatment failure distributions were performed. Clinical outcomes were measured comparing visual analog scale, International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score (KOOS), and Lysholm scores at 24 months from baseline (entry into study).Results: Clinically and statistically significant improvements (P <.0001) compared with baseline were reported in all clinical outcome scores (baseline/24 months): visual analog scale (45.7/20.3), International Knee Documentation Committee (45.4/70.1), KOOS symptoms (64.6/78.3), KOOS pain (57.5/78.6), KOOS activities of daily living (68.8/84.2), KOOS sports (30.5/59.0), KOOS quality of life (33.9/56.6), and Lysholm (60.1/80.7), demonstrating improvements in both pain and function. The incidence of treatment failure was 9 (17.3%) patients, of which 3 patients (8.8%) had medial meniscal defects and 6 patients (33.3%) had lateral meniscal defects. There were 9 SAEs requiring reoperation. Stable or improved International Cartilage Repair Society cartilage grades were observed in 92.5% of patients between baseline and 24 months.Conclusion: At 2 years after implantation, safety and clinical outcome data from this study support the use of the polyurethane scaffold for the treatment of irreparable, painful, partial meniscal defects. © 2012 The Author(s). Source