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Vesperini V.,Montpellier University | Lukas C.,Montpellier University | Fautrel B.,Salpetriere Hospital | Le Loet X.,Bois Guillaume Hospital | And 2 more authors.
Arthritis Care and Research | Year: 2013

Objective. To investigate the initial response to treatment and risk of radiographic disease progression in current smokers (S), ex-smokers (EX), and nonsmokers (NS) in a prospective early arthritis cohort and to analyze the influence of smoking cessation on arthritis outcome. Methods. The ESPOIR cohort is a prospective cohort study monitoring clinical, biologic, and radiographic data for patients with inflammatory arthritis lasting 6 weeks to 6 months. We examined the influence of smoking status on disease presentation (baseline characteristics) and therapeutic response at 1 year. Risk of structural progression at 12 months, defined as change in the modified Sharp/van der Heijde score ≥1, was analyzed by multivariate regression adjusted for potential confounders (age, sex, joint erosion at inclusion, educational level, positivity for rheumatoid factor or anti-cyclic citrullinated peptide 2 antibodies, and shared HLA-DRB1 epitope). Results. A total of 813 patients were included; 641 (79%) fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism (EULAR) criteria for rheumatoid arthritis (RA). At inclusion, 138 (21.5%) were S patients, 168 (26.2%) were EX patients, and 335 (52.3%) were NS patients. Baseline acute-phase indicator values were significantly lower for S patients than EX and NS patients (mean ± SD erythrocyte sedimentation rate was 24.2 ± 18.2 mm/hour versus 33.4 ± 28.0 and 31.4 ± 25.0 [P = 0.02], respectively, and mean ± SD C-reactive protein level was 17.7 ± 28.0 mg/dl versus 28.5 ± 42.5 and 21.4 ± 29.0 [P = 0.01], respectively). Smoking status had no influence on Disease Activity Score in 28 joints, Health Assessment Questionnaire score, EULAR response, or use of disease-modifying antirheumatic drugs and biologic therapy in the first 12 months of followup (P > 0.05). The adjusted risk for structural disease progression was associated with active smokers (odds ratio 0.50 [95% confidence interval 0.27-0.93], P = 0.028). Sixteen patients had stopped smoking at 12 months, with no significant difference in observed outcomes from other patients. Conclusion. In this large prospective cohort of patients with early arthritis, smoking status had no significant effect on disease activity and disability but did reduce 1-year radiographic disease progression. The antiinflammatory role of nicotine may explain the lower systemic inflammation and structural disease progression in current smokers with early RA. Copyright © 2013 by the American College of Rheumatology.


Soria J.-C.,Institute Gustave Roussy | Blay J.Y.,Center Leon Berard | Spano J.P.,Salpetriere Hospital | Pivot X.,University Hospital njoz | And 2 more authors.
Annals of Oncology | Year: 2011

The treatment of certain cancers has been revolutionised in recent years by the introduction of novel drugs designed to target specific molecular factors implicated in tumour growth. Notable examples include trastuzumab, a humanised monoclonal antibody (mAb) against human epidermal growth factor receptor (HER)-2 in women with HER2-positive breast cancer; rituximab, an anti-CD20 mAb in patients with non-Hodgkin's lymphoma; imatinib, a tyrosine kinase inhibitor in KIT-positive gastrointestinal stromal tumours and sunitinib, another tyrosine kinase inhibitor, in metastatic renal cell carcinoma. For regulatory reasons, new molecular targeted agents are first evaluated in advanced and metastatic disease, wherein they prolong survival. However, their most profound impact has been observed in the adjuvant setting, where they may contribute to curative therapy rather than mere palliation. Expansion in the use of molecular targeted therapies will have important cost implications for health care systems. Although expensive, on a monthly basis, molecular targeted therapies may not be more costly than treatments for other major chronic diseases, especially considering the contribution of cancer to the global disease burden, the associated socioeconomic costs and the long-term benefits of therapy. Nevertheless, the use of these agents must be optimised, in part using molecular biomarkers associated with drug response. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Papeix C.,Salpetriere Hospital | Depaz R.,Salpetriere Hospital | Tourbah A.,Salpetriere Hospital | Tourbah A.,Reims University Hospital Center | And 3 more authors.
Multiple Sclerosis Journal | Year: 2011

We report the case of a young woman with multiple sclerosis who discontinued natalizumab twice and experienced a severe relapse following each natalizumab withdrawal. The first relapse was successfully treated by intravenous methylprednisolone (IVMP). In contrast the second relapse was unresponsive to IVMP. Subsequent treatment by plasma exchanges (PLEX) was followed by a dramatic neurological worsening. This case suggests that PLEX after natalizumab discontinuation may increase relapse severity. © SAGE Publications 2011.


Vidailhet M.,Groupe Hospitalier Pitie Salpetriere | Vidailhet M.,French Institute of Health and Medical Research | Vidailhet M.,University Pierre and Marie Curie | Vidailhet M.,Salpetriere Hospital | And 7 more authors.
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2013

The few controlled studies that have been carried out have shown that bilateral internal globus pallidum stimulation is a safe and long-term effective treatment for hyperkinetic disorders. However, most recent published data on deep brain stimulation (DBS) for dystonia, applied to different targets and patients, are still mainly from uncontrolled case reports (especially for secondary dystonia). This precludes clear determination of the efficacy of this procedure and the choice of the 'good' target for the 'good' patient. We performed a literature analysis on DBS for dystonia according to the expected outcome. We separated those with good evidence of favourable outcome from those with less predictable outcome. In the former group, we review the main results for primary dystonia (generalised/focal) and highlight recent data on myoclonus-dystonia and tardive dystonia (as they share, with primary dystonia, a marked beneficial effect from pallidal stimulation with good risk/benefit ratio). In the latter group, poor or variable results have been obtained for secondary dystonia (with a focus on heredodegenerative and metabolic disorders). From this overview, the main results and limits for each subgroup of patients that may help in the selection of dystonic patients who will benefit from DBS are discussed.


Bedossa P.,Beaujon Hospital | Bedossa P.,University Paris Diderot | Poitou C.,Salpetriere Hospital | Poitou C.,French Institute of Health and Medical Research | And 14 more authors.
Hepatology | Year: 2012

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and being overweight is a significant risk factor. The aim was to build an algorithm along with a scoring system for histopathologic classification of liver lesions that covers the entire spectrum of lesions in morbidly obese patients. A cohort of 679 obese patients undergoing liver biopsy at the time of bariatric surgery was studied. An algorithm for segregating lesions into normal liver, NAFLD, or nonalcoholic steatohepatitis (NASH) was built based on semiquantitative evaluation of steatosis, hepatocellular ballooning, and lobular inflammation. For each case, the SAF score was created including the semiquantitative scoring of steatosis (S), activity (A), and fibrosis (F). Based on the algorithm, 230 obese patients (34%) were categorized as NASH, 291 (43%) as NAFLD without NASH, and 158 (23%) as not NAFLD. The activity score (ballooning + lobular inflammation) enabled discriminating NASH because all patients with NASH had A ≥ 2, whereas no patients with A < 2 had NASH. This score was closely correlated with both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P < 0.0001, analysis of variance [ANOVA]). Comparison of transaminase levels between patients with normal liver and pure steatosis did not reveal significant differences, thus lending support to the proposal not to include steatosis in the activity score but to report it separately in the SAF score. In the validation series, the interobserver agreement for the diagnosis of NASH was excellent (κ = 0.80) between liver pathologists. There was no discrepancy between the initial diagnosis and the diagnosis proposed using the algorithm. Conclusion: We propose a simple but robust algorithm for categorizing liver lesions in NAFLD patients. Because liver lesions in obese patients may display a continuous spectrum of histologic lesions, we suggest describing liver lesions using the SAF score. © 2012 American Association for the Study of Liver Diseases.


Chiarovano E.,University of Paris Descartes | Zamith F.,Salpetriere Hospital | Vidal P.-P.,University of Paris Descartes | de Waele C.,University of Paris Descartes | de Waele C.,Salpetriere Hospital
Clinical Neurophysiology | Year: 2011

Objective: This study compared the results of ocular and cervical vestibular evoked myogenic potentials (VEMPs) tests for healthy subjects with those for patients suffering from vestibular diseases to try to determine the clinical usefulness of combined ocular and cervical STB VEMP testing. Methods: Thirty-two healthy volunteers and 74 patients with unilateral vestibular dysfunction underwent tests for ocular and cervical VEMPs induced by AC 100. dB nHL 500. Hz STB combined with caloric and audiometric tests. Results: In healthy subjects, the mean P13-N23 peak-to-peak amplitude of cervical VEMPs was much larger than the mean n1-p1 peak-to-peak amplitude of ocular VEMPs. In patients, cervical and ocular VEMPs may be dissociated. The peak-to-peak amplitude of both cervical and ocular tests was abnormally in most of patients suffering from vestibular lesions. No correlations were found between VEMPs, the degree of hearing loss and/or of horizontal canalar paresis. Conclusions: Ocular and cervical VEMPs provide complementary information about saccular and utricular otolithic function. Significance: Testing of ocular and cervical VEMPs allows the crossed vestibulo-ocular reflex and ipsilateral sacculo-collic reflex to be determined. These tests can help describe vestibular lesions and assess the effects of treatment and should therefore be used clinically. © 2011.


Vidailhet M.,Salpetriere Hospital
Handbook of Clinical Neurology | Year: 2013

Symptomatic treatment of cerebral palsy (CP) is difficult, with variable beneficial effect. The choice of therapy is guided by the main clinical features (spasticity, dystonia/choreoathetosis), by the experience of experts, and by the results of open-label trials and a few controlled studies. Treatments of spasticity are not discussed in depth here. From open-label trials and a few controlled studies in dystonia/choreoathetosis CP, it appears that treatment should be started at a low dose and increased slowly, and that more beneficial effects are obtained on upper extremity function, face and jaw dystonia and drooling, and in children. L-Baclofen or antiepileptic drugs are rarely effective and poorly tolerated whereas benzodiazepines may be moderately helpful. Local injections of botulinum toxin help to reduce pain and limit the amplitude of some movements (violent neck movements with high risk of symptomatic radiculomyelopathy). In a rare subtype of dystonia-choreathetosis CP with little spasticity and MRI lesions, bilateral pallidal stimulation (GPi) has shown mild to moderate improvement of dystonia (in open-label small series and in one controlled study) with no cognitive or mood adverse effects. Optimal placement of the leads was a major (but not exclusive) factor for good outcome but results cannot be predicted on an individual basis and larger studies are needed. © 2013 Elsevier B.V.


Khayat D.,Salpetriere Hospital
Cancer | Year: 2012

The costs of cancer care are rising, and spending on expensive innovative anticancer agents is likely to come under scrutiny as health care payers are confronted by the challenge of resource limits in the face of infinite demand. Indirect costs account for the major part of total attributable costs of cancer and are dominated by the cost of mortality in individuals of working age (who therefore do not contribute to economic productivity). Although cancer is a leading cause of morbidity and premature mortality, in 2007, it was estimated that cancer accounted for only around 6% of the total health care costs in Europe. It is estimated that cancer drug costs constitute around 12% of total direct cancer costs and 5% of the costs of all drugs. Countries vary in their uptake of novel anticancer agents. However, even in France-a leading nation for the use of these agents-the costs of innovative anticancer drugs accounted for <0.6% of total health care expenditure in 2006. Population-level data suggest that novel therapies have contributed (together with advances in screening and other aspects of care) to improvements in survival from cancer. If this is the case, then the potential reduction in the associated indirect costs could exceed the direct costs associated with the uptake of innovative drug therapies. Further research is required to establish the costs and benefits of novel agents in routine practice. Copyright © 2011 American Cancer Society.


Lubetzki C.,Salpetriere Hospital | Stankoff B.,Salpetriere Hospital
Handbook of Clinical Neurology | Year: 2014

This review, focused on demyelination in multiple sclerosis, is divided in two parts. The first part addresses the many and not exclusive mechanisms leading to demyelination in the central nervous system. Although the hypothesis that a primary oligodendrocyte or myelin injury induces a secondary immune response in the central nervous system is still a matter of debate, most recent advances underline the influence of a primary immune response against myelin antigen(s), with a diversity of potential targets. Whereas multiple sclerosis was long considered as a T cell-mediated disease, the role of B lymphocytes is now increasingly recognized, and the influence of antibodies on tissue damage actively investigated. The second part of the review describes the axonal consequences of demyelination. Segmental demyelination results in conduction block or slowing of conduction through adaptative responses, notably related to modifications in the distribution of voltage gated sodium channels along the denuded axon. If demyelination persists, these changes, as well as the loss of trophic and metabolic support, will lead to irreversible axonal damage and loss. In this respect, favouring early myelin repair, during a window of time when axonal damage is still reversible, might pave the way for neuroprotection. © 2014 Elsevier B.V.


Baumann N.,Salpetriere Hospital | Turpin J.-C.,Salpetriere Hospital
Neurochemical Research | Year: 2010

Stress is a word that is used very commonly. It is generally employed to design unpleasant phenomena, although it is related to a function necessary to our life. Stress in itself is not a disease. Stress is not an aggression. It is an adaptative response of our body to any demand. Nothing can be done without stress. Stress gives rise to a mobilization of our body to succeed in a group of activities necessary to individual and social life. It favors our dynamism and creativity. But this aptitude can attain its limits, when the solicitations we receive are above what we are able to perform, both in relation to our mental and physical capabilities. The brain controls the systems involved in stress. The main areas are the prefrontal cortex, the limbic system (which comprises the hippocampus and the amygdala) and the hypothalamus. Relations between the prefrontal cortex and the limbic system are important for the planification of action. The main systems of regulation are the sympathetic and parasympathetic systems, the neuro-endocrine system and last but not least the immune system. There is a relation between all our organs and the brain. The genetic aspects and the influences of our past experiences, both during childhood and in adult life, are envisaged. © 2010 Springer Science+Business Media, LLC.

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