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Spear R.,French Institute of Health and Medical Research | Boytard L.,French Institute of Health and Medical Research | Blervaque R.,French Institute of Health and Medical Research | Chwastyniak M.,French Institute of Health and Medical Research | And 9 more authors.
International Journal of Molecular Sciences | Year: 2015

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology. © 2015 by the authors; licensee MDPI, Basel, Switzerland. Source


Mourah S.,French Institute of Health and Medical Research | Denis M.G.,University of Nantes | Narducci F.E.,Lille Regional University Hospital | Solassol J.,Montpellier University | And 9 more authors.
PLoS ONE | Year: 2015

Vemurafenib is approved for the treatment of metastatic melanoma in patients with BRAF V600 mutation. In pivotal clinical trials, BRAF testing has always been done with the approved cobas 4800 BRAF test. In routine practice, several methods are available and are used according to the laboratories usual procedures. A national, multicenter, non-interventional study was conducted with prospective and consecutive collection of tumor samples. A parallel evaluation was performed in routine practice between the cobas 4800 BRAF V600 mutation test and home brew methods (HBMs) of 12 national laboratories, labelled and funded by the French National Cancer Institute (INCa). For 420 melanoma samples tested, the cobas method versus HBM showed a high concordance (93.3%; kappa = 0.86) in BRAF V600 genotyping with similar mutation rates (34.0% versus 35.7%, respectively). Overall, 97.4%and 98.6% of samples gave valid results using the cobas and HBM, respectively. Of the 185 samples strictly fulfilling the cobas guidelines, the concordance rate was even higher (95.7%; kappa = 0.91; 95%CI [0.85; 0.97]). Out of the 420 samples tested, 28 (6.7%) showed discordance between HBM and cobas. This prospective study shows a high concordance rate between the cobas 4800 BRAF V600 test and home brew methods in the routine detection of BRAF V600E mutations. © 2015 Mourah et al. Source


Puymirat E.,Assistance Publique Hopitaux de Paris AP HP | Puymirat E.,University of Paris Descartes | Puymirat E.,French Institute of Health and Medical Research | Schiele F.,University Hospital Jean Minjoz | And 18 more authors.
International Journal of Cardiology | Year: 2014

Background Improved early outcome in non-ST elevation myocardial infarction (NSTEMI) patients has been mainly attributed to a broader use of invasive strategies. Little is known about the impact of other changes in early management.Methods We aimed to assess 15-year trends in one-year mortality and their determinants in NSTEMI patients. We used data from 4 one-month French registries, conducted 5 years apart from 1995 to 2010 including 3903 NSTEMI patients admitted to intensive care units.Results From 1995 to 2010, no major change was observed in patient characteristics, while therapeutic management evolved considerably. Early use of antiplatelet agents, β-blockers, ACE-inhibitors and statins increased over time (P < 0.001); use of newer anticoagulants (low-molecular-weight heparin, bivalirudin or fondaparinux) increased from 40.8% in 2000 to 78.9% in 2010 (P < 0.001); percutaneous coronary intervention (PCI) ≤ 3 days of admission rose from 7.6% to 48.1% (P < 0.001). One-year death decreased from 20% to 9.8% (HR adjusted for baseline parameters, 2010 vs. 1995 = 0.47, 95% CI: 0.35-0.62). Early PCI (HR = 0.67; 95% CI: 0.49-0.90), use of newer anticoagulants (HR = 0.62; 95% CI: 0.48-0.78) and early use of evidence based medical therapy (HR = 0.54; 95% CI: 0.40-0.72) were predictors of improved one year-survival.Conclusions One-year mortality of NSTEMI patients decreased by 50% in the past 15 years. Our data support current guidelines recommending early invasive strategies and use of newer anticoagulants for NSTEMI, and also show a strong positive association between early use of appropriate medical therapies and one-year survival, suggesting that these medications should be used from the start. © 2014 Elsevier Ireland Ltd. All rights reserved. Source


Goldstein P.,Lille Regional University Hospital | Grieco N.,Hospital Niguarda Ca Granda Milan | Ince H.,University of Rostock | Danchin N.,European Hospital Georges Pompidou | And 3 more authors.
Vascular Health and Risk Management | Year: 2016

Aim: MULTIPRAC was designed to provide insights into the use and outcomes associated with prehospital initiation of antiplatelet therapy with either prasugrel or clopidogrel in the context of primary percutaneous coronary intervention. After a previous report on efficacy and safety outcomes during hospitalization, we report here the 1-year follow-up data, including cardiovascular (CV) mortality. Methods and results: MULTIPRAC is a multinational, prospective registry of patients with ST-elevation myocardial infarction (STEMI) from 25 hospitals in nine countries, all of which had an established practice of prehospital start of dual antiplatelet therapy in place. The key outcome was CV death at 1 year. Among 2, 036 patients followed-up through 1 year, 49 died (2.4%), 10 during the initial hospitalization and 39 within 1 year after hospital discharge. The primary analysis was based on the P2Y12-inhibitor, used from prehospital loading dose through hospital discharge. Prasugrel (n=824) was more commonly used than clopidogrel (n=425). The observed 1-year rates for CV death were 0.5% with prasugrel and 2.6% with clopidogrel. After adjustment for differences in baseline characteristics, treatment with prasugrel was associated with a significantly lower risk of CV death than treatment with clopidogrel (odds ratio 0.248; 95% confidence interval 0.06–0.89). Conclusion: In STEMI patients from routine practice undergoing primary angioplasty, who were able to start oral antiplatelet therapy prehospital, treatment with prasugrel as compared to clopidogrel was associated with a lower risk of CV death at 1-year follow-up. © 2016 Goldstein et al. Source


Nanhoe-Mahabier W.,Radboud University Nijmegen | Delval A.,Lille Regional University Hospital | Snijders A.H.,Radboud University Nijmegen | Weerdesteyn V.,Radboud University Nijmegen | And 2 more authors.
Movement Disorders | Year: 2012

Background: Under carefully controlled conditions, rhythmic auditory cueing can improve gait in patients with Parkinson's disease (PD). In complex environments, attention paid to cueing might adversely affect gait, for example when a simultaneous task-such as avoiding obstacles-has to be executed. We primarily examined whether concurrent auditory cueing interferes with an obstacle avoidance task in patients with PD. The secondary aim was to study differences between patients with and without freezing of gait. Methods: Nineteen patients with PD (8 with freezing) were examined on a treadmill in 4 conditions: normal walking; walking with auditory cueing; walking with an obstacle avoidance task; and walking with auditory cueing and obstacle avoidance. Outcome measures included kinematic gait parameters and obstacle crossing parameters. Results: Auditory cueing improved gait in PD, without negative effects on concurrent obstacle avoidance. Additionally, freezers avoided obstacles less efficiently than non-freezers. Conclusions: PD patients are able to successfully execute an obstacle avoidance task, when auditory cueing is administered simultaneously. The different obstacle avoidance behavior in freezers may contribute to their higher fall risk. © 2012 Movement Disorder Society. Source

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