Purpan Hospital

Toulouse, France

Purpan Hospital

Toulouse, France
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Bretagnol F.,Beaujon Hospital | Panis Y.,Beaujon Hospital | Rullier E.,St Andre Hospital | Rouanet P.,Val dAurelle Institute | And 6 more authors.
Annals of Surgery | Year: 2010

Objective: To assess with a single-blinded, multicenter, randomized trial, the postoperative results in patients undergoing sphincter-saving rectal resection for cancer without preoperative mechanical bowel preparation (MBP). Background: The collective evidence from literature strongly suggests that MBP, before elective colonic surgery, is of no benefit in terms of postoperative morbidity. Very few data and no randomized study are available for rectal surgery and preliminary results conclude toward the safety of rectal resection without MBP. Methods: From October 2007 to January 2009, patients scheduled for elective rectal cancer sphincter-saving resection were randomized to receive preoperative MBP (ie, retrograde enema and oral laxatives) or not. Primary endpoint was the overall 30-day morbidity rate. Secondary endpoints included mortality rate, anastomotic leakage rate, major morbidity rate (Dindo III or more), degree of discomfort for the patient, and hospital stay. Results: A total of 178 patients (103 men), including 89 in both groups (no-MBP and MBP groups), were included in the study. The overall and infectious morbidity rates were significantly higher in no-MBP versus MBP group, 44% versus 27%, P = 0.018, and 34% versus 16%, P = 0.005, respectively. Regarding both anastomotic leakage and major morbidity rates, there was no significant difference between no-MBP and MBP group: 19% versus 10% (P = 0.09) and 18% versus 11% (P = 0.69), respectively. Moderate or severe discomfort was reported by 40% of prepared patients. Mortality rate (1.1% vs 3.4%) and mean hospital stay (16 vs 14 days) did not differ significantly between both groups. Conclusions: This first randomized trial demonstrated that rectal cancer surgery without MBP was associated with higher risk of overall and infectious morbidity rates without any significant increase of anastomotic leakage rate. Thus, it suggests continuing to perform MBP before elective rectal resection for cancer. This study is registered with clinicaltrials.gov, number NCT00554892. Copyright © 2010 by Lippincott Williams & Wilkins.

Dougados M.,University of Paris Descartes | Dougados M.,Cochin Hospital | Combe B.,Rheumatology Lapeyronie Hospital | Braun J.,Charité - Medical University of Berlin | And 7 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Objective: Inflammation at the entheses is a distinguishing feature of spondyloarthritis (SpA). Enthesitis at the heel is the most common location and is often chronic, refractory to standard treatment and may have socioeconomic consequences. The objective of this study was to investigate the efficacy of etanercept in refractory heel enthesitis related to SpA. Methods: The present work was a 12-week, randomised, double-blind, placebo-controlled study compared etanercept with placebo in patients with SpA according to Amor's criteria, and heel enthesitis proven by MRI. The primary efficacy end point was the normalised net incremental area under the curve (AUC) between randomisation and week 12 for the patient's global assessment (PGA) of disease activity. Secondary end points included change from baseline in PGA, heel pain, the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) function subscale and improvement in enthesitis as measured by MRI. Results: A total of 24 patients were randomised. Mean normalised net incremental AUC for PGA of disease activity over 12 weeks was significantly greater in the etanercept versus placebo group: -28.5 versus -11.1, respectively (p=0.029). Significant improvements were also reported in the etanercept versus placebo group for PGA, -37.6 versus -11.6 (p=0.007); heel pain, -36.7 versus -13.1 (p=0.022); and WOMAC function, -23.2 versus -7.8 (p=0.024). No significant changes were observed in the MRI findings between groups. No unexpected adverse events or changes in laboratory values or vital signs. Conclusions: This trial is the first randomised placebocontrolled study of an anti-tumour necrosis factor (TNF) agent in refractory heel enthesitis in patients with SpA. It demonstrates that etanercept has a statistically significant and clinically relevant benefit in such patients. ClinicalTrials.gov identifier: NCT00420303.

Meng W.,Queen's University of Belfast | Butterworth J.,Newcastle University | Bradley D.T.,Queen's University of Belfast | Hughes A.E.,Queen's University of Belfast | And 3 more authors.
Investigative Ophthalmology and Visual Science | Year: 2012

Purpose. Myopia is a complex trait affected by both genetic and environmental factors. High myopia is associated with increased risk of sight threatening eye disorders such as retinal detachment. The purpose of this genome-wide association study was to identify susceptibility genes contributing to high myopia in the French population. Methods. High myopic cases were genotyped using Affymetrix SNP 6.0 chips and population controls were selected from the GABRIEL French dataset, in which samples were genotyped by Illumina Human610 quad array. The association study was conducted using 152,234 single nucleotide polymorphisms that were present on both manufacturers' chips in 192 high myopic cases and 1064 controls to identify associated regions. Imputation was performed on peak regions. Results. Associations were found at known myopia locus MYP10 on chromosome 8p23 and MYP15 on chromosome 10q21.1. Rs189798 (8p23), and rs10825992 (10q21.1) showed the strongest associations in these regions (P = 6.32 × 10-7 and P = 2.17 × 10-5, respectively). The imputed results at 8p23 showed two peaks of interest. The first spanned 30 kb including rs189798 between MIR4660 and PPP1R3B with the most significant association at rs17155227 (P = 1.07 × 10-10). The second novel peak was 4 kb in length, encompassing MIR124-1 and the MSRA gene, with the strongest association at rs55864141 (P = 1.30 × 10-7). The peak of imputed data at 10q21.1 was 70 kb in length between ZWINT and MIR3924, with rs3107503 having the lowest P value (P = 1.54 × 10-7). Conclusions. We provide evidence for the association of MYP10 at 8p23 and MYP15 at 10p21.1 with high myopia in the French population and refine these regions of association. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

White P.M.,University of Edinburgh | White P.M.,Western General Hospital | Lewis S.C.,University of Edinburgh | Gholkar A.,Newcastle General Hospital | And 5 more authors.
The Lancet | Year: 2011

Background: Coated coils for endovascular treatment of cerebral aneurysm were developed to reduce recurrence and retreatment rates, and have been in clinical use for 8-9 years without robust evidence to determine their efficacy. We assessed the efficacy and safety of hydrogel-coated coils. Methods: This randomised trial was undertaken in 24 centres in seven countries. Patients aged 18-75 years with a previously untreated ruptured or unruptured cerebral aneurysm of 2-25 mm in maximum diameter were randomly allocated (1:1) to aneurysm coiling with either hydrogel-coated coils or standard bare platinum coils (control). Randomisation was done with a computer-generated sequence, stratified by aneurysm size, shape, and dome-to-neck ratio; intention to use assist device; and by region. Participants and those assessing outcomes were masked to allocation. Analysis was by modified intention to treat (excluding missing data). Primary outcome was a composite of angiographic and clinical outcomes at 18-month follow-up. We also did prespecified subgroup analyses of characteristics likely to be relevant to angiographic outcome. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN30531382. Findings: 249 patients were allocated to the hydrogel coil group and 250 to the control group. In 44 of 467 patients for whom an 18-month composite primary outcome was unavailable, 6-month angiographic results were used. 70 (28) patients in the hydrogel group and 90 (36) control patients had an adverse composite primary outcome, giving an absolute reduction in the proportion of adverse composite primary outcomes with hydrogel of 7·0 (95 CI -1·6 to 15·5), odds ratio (OR) 0·73 (0·49-1·1, p=0·13). In a prespecified subgroup analysis in recently ruptured aneurysms, there were more adverse composite primary outcomes in the control group than in the hydrogel group - OR 2·08 (1·24-3·46, p=0·014). There were 8·6 fewer major angiographic recurrences in patients allocated to hydrogel coils - OR 0·7 (0·4-1·0, p=0·049). There were five cases of unexplained hydrocephalus in not-recently-ruptured aneurysms in the hydrogel coil group and one case in the control group. Interpretation: Whether use of hydrogel coils reduces late aneurysm rupture or improves long-term clinical outcome is not clear, but our results indicate that their use lowers major recurrence. Funding: MicroVention Inc. © 2011 Elsevier Ltd.

Pichenot M.,Hospital of Tourcoing | Deuffic-Burban S.,French Institute of Health and Medical Research | Deuffic-Burban S.,University of Lille Nord de France | Cuzin L.,Purpan Hospital | And 3 more authors.
HIV Medicine | Year: 2012

Objectives: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the overall efficacy of new antiretroviral drugs, as well as the factors associated with increased efficacy. We compared CD4 cell count increases associated with chemokine (C-C motif) receptor 5 (CCR5) inhibitors or other new drugs, using indirect comparison. Methods: We included RCTs published in 2003-2010 that assessed the 48-week immunological and virological efficacy of adding new antiretroviral drugs vs. placebo to optimized background therapy (OBT) in treatment-experienced subjects. These drugs included maraviroc, vicriviroc, enfuvirtide, raltegravir, etravirine, tipranavir and darunavir. We collected baseline descriptive characteristics, CD4 cell count changes and virological suppression proportions (percentage with HIV RNA <50 HIV-1 RNA copies/mL). Results: We identified 10 studies which included a total of 6401 patients. New drugs were associated with increased virological suppression (pooled odds ratio 2.97) and larger CD4 count increases (pooled nonstandardized difference 39cells/μL) compared with placebo. OBT genotypic sensitivity scores (GSSs) were also associated with larger differences in virological suppression (P<0.001 for GSS=0,≤1 and ≤2) and CD4 cell count increase (GSS=0, P<0.001; GSS ≤1, P=0.002; GSS ≤2, P=0.015) between the two groups. CCR5 inhibitors were not associated with significant gains in CD4 cell counts (P=0.22) compared with other new drugs. Conclusions: Our study confirmed the overall immunological and virological efficacy of new antiretroviral drugs in treatment-experienced patients, compared with placebo. The main predictive factor for efficacy was the number of fully active drugs. CCR5 inhibitors did not increase CD4 cell count to a greater extent than other new drugs. © 2011 British HIV Association.

Fischer K.,University Utrecht | Ljung R.,Lund University | Platokouki H.,St Sophia Childrens Hospital | Liesner R.,Great Ormond Street Hospital for Children | And 3 more authors.
Haemophilia | Year: 2014

Haemophilia is a rare disease. To improve knowledge, prospective studies of large numbers of subjects are needed. To establish a large well-documented birth cohort of patients with haemophilia enabling studies on early presentation, side effects and outcome of treatment. Twenty-one haemophilia treatment centres have been collecting data on all children with haemophilia with FVIII/IX levels up to 25% born from 2000 onwards. Another eight centres collected data on severe haemophilia A only. At baseline, details on delivery and diagnosis, gene mutation, family history of haemophilia and inhibitors are collected. For the first 75 exposure days, date, reason, dose and product are recorded for each infusion. Clinically relevant inhibitors are defined as follows: at least two positive inhibitor titres and a FVIII/IX recovery <66% of expected. For inhibitor patients, results of all inhibitor- and recovery tests are collected. For continued treatment, data on bleeding, surgery, prophylaxis and clotting factor consumption are collected annually. Data are downloaded for analysis annually. In May 2013, a total of 1094 patients were included: 701 with severe, 146 with moderate and 247 with mild haemophilia. Gene defect data were available for 87.6% of patients with severe haemophilia A. The first analysis, performed in May 2011, lead to two landmark publications. The outcome of this large collaborative research confirms its value for the improvement of haemophilia care. High-quality prospective observational cohorts form an ideal source to study natural history and treatment in rare diseases such as haemophilia. © 2014 John Wiley & Sons Ltd.

Guell J.L.,Hospital Clinic i Provincial | Guell J.L.,Autonomous University of Barcelona | Morral M.,Hospital Clinic i Provincial | Malecaze F.,Purpan Hospital | And 3 more authors.
Journal of Cataract and Refractive Surgery | Year: 2012

Purpose: To report the long-term results of combined collagen crosslinking (CXL) and toric phakic intraocular lens (pIOL) implantation to correct myopic astigmatism in patients with progressive mild to moderate keratoconus. Setting: Instituto de Microcirugia Ocular, Barcelona, Spain. Design: Case series. Methods: From November 2006 to July 2009, CXL was performed in eyes with proven progressive keratoconus. Once refraction and topography stabilized, toric Artiflex/Artisan pIOL implantation was performed to correct residual myopic astigmatism. A complete ophthalmologic examination, including manifest refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, biomicroscopy, tonometry, fundoscopy, keratometry, corneal tomography, and central endothelial cell count (ECC), was performed before each procedure and postoperatively at 3 months and at yearly intervals up to 5 years. Main outcome measures were accuracy and stability of the spherical equivalent (SE) and cylinder, keratometry, UDVA (efficacy), CDVA (safety), central ECC, and complications. Results: The median follow-up in the 9 patients (17 eyes) was 36.9 months ± 15.0 (SD). The median interval between CXL and pIOL implantation was 3.9 ± 0.7 months. Fourteen eyes (82%) were within ±0.50 diopter (D) of the attempted SE correction and 13 eyes (76%) were within ±1.00 D of the attempted cylinder correction. The mean difference in simulated keratometry between preoperatively and the last follow-up was 0.17 ± 0.45 D (range -0.55 to 1.45 D). The postoperative UDVA was 20/40 or better in 16 eyes (94%). No eye lost lines of CDVA. No significant decrease in central ECC occurred (P>.05). Conclusion: Combined CXL and toric iris-claw pIOL implantation effectively and safely corrected myopic astigmatism in progressive mild to moderate keratoconus. Financial Disclosure: Dr. Güell is a consultant to Ophtec. No other author has a financial or proprietary interest in any material or methods mentioned. © 2012 ASCRS and ESCRS.

Dejean A.S.,University of California at San Diego | Dejean A.S.,Purpan Hospital | Hedrick S.M.,University of California at San Diego | Kerdiles Y.M.,University of California at San Diego | Kerdiles Y.M.,French Institute of Health and Medical Research
Antioxidants and Redox Signaling | Year: 2011

Recent studies have highlighted a fundamental role for Forkhead box O (Foxo) transcription factors in immune system homeostasis. Initial reports designed to dissect function of individual Foxo isoforms in the immune system were based on in vitro overexpression systems, and these experiments suggested that Foxo1 and Foxo3 are important for growth factor withdrawal-induced cell death. Moreover, Foxo factors importantly regulate basic cell cycle progression, and so the implication was that these factors may control lymphocyte homeostasis, including a critical function in the termination and resolution of an immune response. Most recently, cell-type-specific loss mutants for the different Foxo isoforms have revealed unexpected and highly specialized functions in the control of multiple cell types in the immune system, but they have yet to reveal a role in cell death or proliferation. This review will focus on the recent advances made in the understanding of the many ways that Foxo factors regulate the immune system, including a discussion of how the specialized versus redundant functions of Foxo transcription factors impact immune system homeostasis. © 2011 Mary Ann Liebert, Inc.

The aim of our study was to analyze the factors contributing to heterogeneity of prognosis in patients with hyperdiploidy>50 chromosomes (HD>50), a group of B-cell precursor acute lymphoblastic leukemia with favorable outcome. The 541 HD>50 patients registered prospectively in the 58951 European Organisation for Research and Treatment of Cancer (EORTC) Children's Leukemia Group (CLG) trial, identified by karyotype (446 patients) and by DNA index (DI) (490 patients), had a 6-year event-free survival (EFS) of 89.0% (standard error [SE] = 1.5%) and a 6-year overall survival (OS) of 95.9% (SE = 0.9%). The strongest prognostic factor was the modal number of chromosomes (MNC): the 6-year EFS of 51-53, 54-57, and 58-66 MNC groups were 80%, 89%, and 99%, respectively (P < .0001). Ploidy assessed by DI was also a favorable factor: the higher the DI, the better the outcome. The 6-year EFS of the 3 subgroups of DI < 1.16/≥1.16-<1.24/≥1.24 were 83%, 90%, and 95%, respectively (P = .009). All usual combinations of trisomies (chromosomes 4, 10, 17, 18) were significant favorable factors but had lower EFS when MNC was lower than 58. In multivariate analysis, MNC remained the strongest factor. Consequently, the best indicator for excellent outcome was ploidy assessed by karyotype because patients with 58-66 chromosomes stood every chance of being cured (OS of 100% at 6-year follow-up) with less-intensive therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003728. Registered: http://www.eortc.org/, http://clinicaltrials.gov/show/NCT00003728.

Soler V.,Purpan Hospital | Benito A.,University of Murcia | Soler P.,Toulouse Hospital | Triozon C.,Purpan Hospital | And 4 more authors.
American Journal of Ophthalmology | Year: 2011

Purpose: To compare visual and optical outcomes of pupil-centered vs vertex-centered ablation in patients undergoing laser-assisted in situ keratomileusis (LASIK) for hyperopia. Design: Randomized, double-masked, prospective, single-center trial. Methods: Setting: Institutional practice. Study population: Sixty eyes of 30 patients with low and moderate hyperopia. Intervention procedure: Eyes underwent LASIK (Allegretto excimer laser). In 30 eyes, the ablation was centered on the pupil, while in the 30 other eyes the ablation was centered on the corneal reflex. Main outcome measures: Primary outcome measure was the safety index. Main secondary outcome measures were efficacy index, manifest refraction, uncorrected visual acuity, best spectacle-corrected visual acuity (BCVA), and ocular high-order aberrations for a 6-mm pupil size. Results: At 3 months postoperatively, the safety index was 0.99 ± 0.04 in the pupil-centered group and 0.99 ± 0.08 in the vertex-centered group (P =.97). The efficacy index was also similar for both groups: 0.96 ± 0.05 in pupil-centered eyes and 0.93 ± 0.09 in vertex-centered eyes (P =.31). Optical aberrations were similar for pupil-centered and vertex-centered eyes. Considering only eyes showing large pupil decentration, we found a tendency for better visual results in favor of pupil-centered eyes in terms of safety index and a slight but significant increase of coma in vertex-centered eyes. Conclusion: LASIK is an effective procedure for treatment of hyperopia. Pupil-centered and vertex-centered treatments provide similar visual and optical outcomes. However, in eyes showing large temporal pupil decentration, pupil-centered ablation seemed to produce a lower amount of coma and, as a consequence, a reduced loss of BCVA compared with vertex-centered patients. © 2011 Elsevier Inc.

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