Allenbach Y.,University Pierre and Marie Curie |
Drouot L.,University of Rouen |
Rigolet A.,University Pierre and Marie Curie |
Charuel J.L.,University Pierre and Marie Curie |
And 34 more authors.
Medicine (United States) | Year: 2014
Necrotizing autoimmune myopathy (NAM) is a group of acquired myopathies characterized by prominent myofiber necrosis with little or no muscle inflammation. Recently, researchers identified autoantibodies (aAb) against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with NAM, especially in statin-exposed patients. Here we report what is to our knowledge the first European cohort of patients with NAM.The serum of 206 patients with suspicion of NAM was tested for detection of anti-HMGCR aAb using an addressable laser bead immunoassay. Forty-five patients were found to be anti-HMGCR positive. Their mean age was 48.9 ± 21.9 years and the group was predominantly female (73.3%). Statin exposure was recorded in 44.4% of patients. Almost all patients had a muscular deficit (97.7%), frequently severe (Medical Research Council [MRC] 5 ≤3 in 75.5%). Subacute onset (<6 mo) was noted for most of them (64.4%). Nevertheless, 3 patients (6.6%) had a slowly progressive course over more than 10 years. Except for weight loss (20%), no extramuscular sign was observed. The mean CK level was high (6941 ± 8802 IU/L) and correlated with muscle strength evaluated by manual muscle testing (r = -0.37, p = 0.03). Similarly, anti-HMGCR aAb titers were correlated with muscular strength (r = -0.31; p = 0.03) and CK level (r = 0.45; p = 0.01). Mean duration of treatment was 34.1 ± 40.8 months, and by the end of the study no patient had been able to stop treatment.This study confirms the observation and description of anti-HMGCR aAb associated with NAM. The majority of patients were statin naive and needed prolonged treatments. Some patients had a dystrophic-like presentation. Anti-HMGR aAb titers correlated with CK levels and muscle strength, suggesting their pathogenic role. Copyright © 2014 by Lippincott Williams & Wilkins.
Dalmay F.,University of Limoges |
Bhalla D.,University of Limoges |
Nicoletti A.,University of Catania |
Cabrera-Gomez J.A.,International Neurological Restoration Center |
And 5 more authors.
Multiple Sclerosis | Year: 2010
Few studies report a protective role of childhood solar exposure to multiple sclerosis. Our objective was to confirm the protective role of childhood solar exposure in multiple sclerosis in Cuba, Martinique and Sicily. This was a matched case- control study, and cases met Poser criteria for clinically, laboratory (definite, probable) multiple sclerosis. Controls were resident population, without neurological disorder, living close to cases (within 100 km), matched for sex, age (±5 years), residence before age 15. We recruited 551 subjects during a 1-year period (193 cases, Cuba n = 95, Sicily n = 50, Martinique n = 48; 358 controls). Some (89%) met definite clinical multiple sclerosis criteria (relapsing remitting form (with and without sequel) (74%), secondary progressive (21%), primary progressive (5%)). Odds ratios in a uni-variate analysis were: family history of multiple sclerosis (5.1) and autoimmune disorder (4.0); wearing shirt (3.5), hat (2.7), pants (2.4); sun exposure causing sunburn (1.8); sun exposure duration (1 h more/day; weekends 0.91, weekdays 0.86); bare-chested (0.6); water sports (0.2). Independent factors in the multivariate analysis were family history of multiple sclerosis (4.8 (1.50-15.10)), wearing pants under sunlight (1.9 (1.10-3.20)), sun exposure duration (1 h more/ day, weekdays 0.90 (0.85-0.98), weekends 0.93 (0.87-0.99)), water sports (0.23 (0.13-0.40)). We conclude that outdoor leisure activities in addition to sun exposure reports are associated with a reduced multiple sclerosis risk, with evidence of dose response. © 2010 The Author(s).
Makinson A.,Hopital Gui de Chauliac |
Makinson A.,Montpellier University |
Tenon J.-C.,Hopital Gui de Chauliac |
Eymard-Duvernay S.,Montpellier University |
And 11 more authors.
Journal of Thoracic Oncology | Year: 2011
Objectives: To describe factors associated with survival in human immunodeficiency virus (HIV)-infected subjects with non-small cell lung cancer (NSCLC) and analyze toxicities induced by cytotoxic chemotherapy and antiretroviral compounds. Design: Retrospective analyses of HIV-infected subjects with NSCLC enrolled in the Dat'Aids cohort. A toxicity substudy included subjects treated by at least one cycle of cytotoxic chemotherapy. Methods: Survival was analyzed using Cox models. In the toxicity substudy, factors associated with grade 4 hematological toxicity of each episode of combination of antiretroviral drugs and cytotoxic chemotherapy were analyzed using marginal logistic regression models. Results: Fifty-two subjects were included in the study: 42 were men, median age was 48 years, 98% were smokers, with a median of 30 pack years, median CD4 was 300 cells/μl, and median survival time was 12 months. CD4 levels ≥200 cells/μl at NSCLC diagnosis (hazard ratio [HR] = 0.29, 95% confidence interval [CI] [0.10-0.89]), performance status less than 2 (HR = 0.32, 95% CI [0.15-0.68]) and highly active antiretroviral therapy (HR = 0.26, 95% CI [0.09-0.74]) were significantly associated with increased survival in the multivariable model. Forty subjects were included in the toxicity substudy, and 14 among 68 different combinations were complicated by a grade 4 hematological toxicity. Protease inhibitor use (odds ratio = 5.22, 95% CI [1.07-25.38]) was significantly associated with grade 4 hematological toxicity in the multivariable analyses. Conclusions: In HIV-infected patients, CD4 levels at NSCLC diagnosis may be a predictive factor of survival. Use of highly active antiretroviral therapy during NSCLC chemotherapy is warranted, but protease inhibitors should be used with caution, as they may enhance severe hematological toxicities. Copyright © 2011 by the International Association for the Study of Lung Cancer.
PubMed | UPMC; AP HP, UPMC; Hopital Tenon, University of Paris Pantheon Sorbonne, Angers University Hospital Center and 8 more.
Type: Journal Article | Journal: Autoimmunity reviews | Year: 2015
Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB.Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies.214 CHB were included: 202 detected in utero at a median term of 23 weeks gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p<0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7-32.7]) and prematurity (p=0.002; HR 17.1 [95%CI 2.8-103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p=0.0157; HR 6.37 [95%CI: 1.25-32.44]), postnatal DCM (p<0.0001; HR 227.58[95%CI: 24.33-2128.46]) and pacemaker implantation (p=0.0035; HR 0.11[95%CI: 0.02-0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB.In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids.
Coman T.,French National Center for Scientific Research |
Bachy E.,Lyon University Hospital Center |
Michallet M.,Lyon University Hospital Center |
Socie G.,Hopital St Louis |
And 18 more authors.
Haematologica | Year: 2013
Optimal salvage treatment for multiple myeloma relapsing after allogeneic stem cell transplantation remains to be determined. Usually, such patients have been heavily pre-treated and present at relapse with a relatively refractory disease. Immunomodulatory properties of lenalidomide may be beneficial by facilitating a graft-versus-myeloma effect after allogeneic stem cell transplantation. However, the safety of such treatment is still under debate. We conducted a multicenter retrospective study and included 52 myeloma patients receiving lenalidomide alone or in combination with dexamethasone as salvage therapy after allogeneic stem cell transplantation. The first aim was to assess the efficacy and tolerance of this drug. The second aim was to evaluate its potential immunomodulatory effects evaluated on the occurrence of acute graft-versus-host disease under treatment. In this cohort, we show that lenalidomide can induce a high response rate of 83% (including 29% complete response). On lenalidomide therapy, 16 patients (31%) developed or exacerbated an acute graft-versus-host disease, which was the only factor significantly associated with an improved anti-myeloma response. Side effects were mostly reversible, whereas 2 deaths (4%) could be attributed to treatment toxicity and to graft-versus-host disease, respectively. With a median follow up of 16.3 months, the median overall and progression free survival were 30.5 and 18 months, respectively, independently of the occurrence of acute graft-versus-host disease under lenalidomide. Lenalidomide can induce high response rates in myeloma relapsing after allogeneic stem cell transplantation at least in part by triggering an allogeneic anti-myeloma response. Induced graft-versus-host disease has to be balanced against the potential benefit in terms of disease control. Further immunological studies would help us understand lenalidomide immunomodulatory activity in vivo. © 2013 Ferrata Storti Foundation.
PubMed | Service dAnatomie Pathologique, Tapion Hospital, CHU Fort de France, Center Hospitalier University Of Martinique and 2 more.
Type: Journal Article | Journal: The West Indian medical journal | Year: 2015
We report here the clinical case of an Afro-Caribbean patient referred for complete atrioventricular block for whom a diagnosis of hereditary cardiac amyloidosis was eventually confirmed. Hereditary cardiac amyloidosis is an emerging threat in the Caribbean, and the main goal of this report is to raise the awareness of the disease among physicians.
Khellaf M.,University Paris Est Creteil |
Michel M.,University Paris Est Creteil |
Quittet P.,Montpellier University Hospital Center |
Viallard J.-F.,CHU Haut Leveque |
And 21 more authors.
Blood | Year: 2011
Romiplostim, a thrombopoietic agent with demonstrated efficacy against immune thrombocytopenia (ITP) in prospective controlled studies, was recently licensed for adults with chronic ITP. Only France has allowed romiplostim compassionate use since January 2008. ITP patients could receive romiplostim when they failed to respond to successive corticosteroids, intravenous immunoglobulins, rituximab, and splenectomy, or when splenectomy was not indicated. We included the first 80 patients enrolled in this program with at least 2 years of follow-up. Primary platelet response (platelet count ≥ 50 × 10 9/L and double baseline) was observed in 74% of all patients. Long-term responses (2 years) were observed in 47 (65%) patients, 37 (79%) had sustained platelet responses with a median platelet count of 106 × 10 9/L (interquartile range, 75-167 × 10 9/L), and 10 (21%) were still taking romiplostim, despite a median platelet count of 38 × 10 9/L (interquartile range, 35-44 × 10 9/L), but with clinical benefit (lower dose and/or fewer concomitant treatment(s) and/or diminished bleeding signs). A high bleeding score and use of concomitant ITP therapy were baseline factors predicting romiplostim failure. The most frequently reported adverse events were: arthralgias (26%), fatigue (13%), and nausea (7%). Our results confirmed that romiplostim use in clinical practice is effective and safe for severe chronic ITP. This trial was registered at www.clinicaltrials.gov as #NCT01013181. © 2011 by The American Society of Hematology.
Rousseau M.,University of Lorraine |
Delattre O.,CHU Fort de France |
Gillet P.,University of Lorraine |
Lopez E.,UMR7208 BOREA
Bio-Medical Materials and Engineering | Year: 2012
The present study was designed to analyze the intra-articular behaviour of nacre, when implanted in the subchondral bone area in the sheep knee. We implanted nacre blocks in sheep's trochlea by replacing the half of the femoral trochlea (nacre group). For comparison we used complete cartilage resection (resection group) down to the subchondral bone. In the "nacre group", implants were well tolerated without any synovial inflammation. In addition, we observed centripetal regrowth of new cartilage after 3 months. In the "resection group", no chondral regrowth was observed, but, in contrast, a thin layer of fibrous tissue was formed. After 6 months, a new tissue covered the nacre implant formed by an osteochondral regrowth. Nacre, as a subchondral implant, exerts benefic potential for osteochondral repair.
Lafont M.,University of Bordeaux 1 |
Fagour C.,CHU Fort de France |
Haissaguerre M.,University of Bordeaux 1 |
Darancette G.,Bordeaux University Hospital Center |
And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015
Context: The per-operative hemodynamic behavior of normotensive incidentally discovered pheochromocytomas is poorly documented. Objective: To compare the per-operative hemodynamic instability and early postoperative outcome of normotensive pheochromocytomas, hypertensive pheochromocytomas, and benign non-pheochromocytoma adrenal incidentalomas (AIs). Design: Retrospective cohort treated in a single center. Patients and Methods: Fifty patients (10 normotensive pheochromocytomas, 24 hypertensive pheochromocytomas, and 16 AIs) were anesthetized and operated on by the same team, using laparoscopy in 78% of cases. Before surgery, 60% of normotensive and 95.8% of hypertensive pheochromocytomas received pretreatment with α-receptor or calcium channel blockers. All of the patients received the same intraoperative hemodynamic monitoring, including continuous direct intra-arterial pressure recording. Results: All the features of hemodynamic instability, with the exception of the diastolic pressure nadir and fluid volume requirements, differed between hypertensive pheochromocytomas and AIs. Conversely, all features of hemodynamic instability were similar in hypertensive and normotensive pheochromocytomas. More specifically, by comparison with AIs, normotensive pheochromocytomas displayed higher maximal systolic pressure; more hypertensive, severe hypertensive, and hypotensive episodes; and a higher minimal heart rate, and also required more interventions to treat undesirable blood pressure elevations. Postoperative complications, all of which were mild, were more frequent in hypertensive pheochromocytomas than in normotensive pheochromocytomas (P < .03). Conclusions: Normotensive pheochromocytomas have roughly comparable per-operative hemodynamic instability to hypertensive pheochromocytomas and differ markedly from non-pheochromocytoma AIs. It is therefore crucial to identify normotensive pheochromocytomas among AIs when surgery is scheduled and to apply the standard of care for pheochromocytoma anesthesia. Copyright © 2015 by the Endocrine Society.
Preuss M.,University of Leipzig |
Preuss M.,Justus Liebig University |
Renner C.,University of Leipzig |
Krupp W.,University of Leipzig |
And 10 more authors.
Child's Nervous System | Year: 2013
Introduction: Whereas in the adult population 5-Aminolevulinic acid (5-ALA) fluorescence guidance has been widely accepted for improving the extent of tumor resection, the application in children remains an off-label use. Even though most pediatric study protocols require a complete resection for improving outcome parameters, only few pediatric patients have been operated with fluorescence guidance, and it remains questionable, whether and which pediatric tumors show useful fluorescence. We present casuistic reports of application of 5-ALA in children collected from three different neurosurgical departments. Patients and methods: In children with suspected malignant intracerebral tumor or recurrence, individual informed consent was obtained in each case from the parents. 5-ALA was administered according to the adult protocol, with 20 mg/kg, 2 h before induction of anesthesia. We retrospectively analyzed 18 patients (13 male, 5 female; age 3-18 years), using the intraoperative neurosurgical protocol, the postoperative MRI results, and the follow-up clinical examinations. Results: The use of 5-ALA fluorescence guidance proved to be safe in our group of pediatric patients. Fluorescence guidance was most useful for recurrent glioblastoma resection. Medulloblastoma tissue displayed fluorescence only inconsistently, and most pilocytic astrocytoma remained without staining. Ganglioglioma showed partial staining in the central tumor areas, without allowing the use for circumferent resection. Conclusion: The off-label use of 5-ALA fluorescence guidance in pediatric patients appears to be most useful in recurrent high-grade gliomas. Fluorescence accumulation in other pediatric brain tumor entities is not predictable and should be evaluated in future clinical studies before being integrated into the current treatment protocols. © 2013 Springer-Verlag Berlin Heidelberg.