M Carles

University of Nice-Sophia Antipolis, Nice, Provence-Alpes-Côte d'Azur, France

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Publications (139)329.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The occurrence of peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer and is considered incurable. However, new therapeutic approaches have been proposed, including cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been effective in selected patients, it is not known how HIPEC prolongs a patient's lifespan. Here, we have demonstrated that HIPEC-treated tumor cells induce the activation of tumor-specific T cells and lead to vaccination against tumor cells in mice. We have established that this effect results from the HIPEC-mediated exposure of heat shock protein (HSP) 90 at the plasma membrane. Inhibition or blocking of HSP90, but not HSP70, prevented the HIPEC-mediated antitumoral vaccination. Our work raises the possibility that the HIPEC procedure not only kills tumor cells but also induces an efficient anticancer immune response, therefore opening new opportunities for cancer treatment.Oncogene advance online publication, 13 April 2015; doi:10.1038/onc.2015.82.
    Oncogene 04/2015; DOI:10.1038/onc.2015.82 · 8.56 Impact Factor
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    ABSTRACT: Patients with acute respiratory distress syndrome who retain maximal alveolar fluid clearance (AFC) have better clinical outcomes. The release of endogenous catecholamines associated with shock or the administration of β2-adrenergic receptor (β2AR) agonists enhances AFC via a 3'-5'-cyclic adenosine monophosphate-dependent mechanism. The authors have previously reported that transforming growth factor-β1 (TGF-β1) and interleukin-8 (IL-8), two major mediators of alveolar inflammation associated with the early phase of acute respiratory distress syndrome, inhibit AFC upregulation by β2AR agonists via a phosphoinositol-3-kinase (PI3K)-dependent mechanism. However, whether TGF-β1 and IL-8 cause an additive or synergistic inhibition of AFC is unclear. Thus, the central hypothesis of the study was to determine whether they synergistically inhibit the β2AR-stimulated AFC by activating two different isoforms of PI3K. The effects of TGF-β1 or IL-8 on β2AR agonist-stimulated net alveolar fluid transport were studied using short-circuit current studies. Molecular pathways of inhibition were confirmed by pharmacologic inhibitors and Western blotting of p-Akt, G-protein-coupled receptor kinase 2, protein kinase C-ζ, and phospho-β2AR. Finally, our observations were confirmed by an in vivo model of AFC. Combined exposure to TGF-β1 and IL-8/cytokine-induced neutrophil chemoattractant-1 caused synergistic inhibition of β2AR agonist-stimulated vectorial Cl across alveolar epithelial type II cells (n = 12 in each group). This effect was explained by activation of different isoforms of PI3K by TGF-β1 and IL-8/cytokine-induced neutrophil chemoattractant-1 (n = 12 in each group). Furthermore, the inhibitory effect of TGF-β1 on 3'-5'-cyclic adenosine monophosphate-stimulated alveolar epithelial fluid transport required the presence of IL-8/cytokine-induced neutrophil chemoattractant-1 (n = 12 in each group). Inhibition of cytokine-induced neutrophil chemoattractant-1 prevented TGF-β1-mediated heterologous β2AR downregulation and restored physiologic β2AR agonist-stimulated AFC in rats (n = 6 in each group). TGF-β1 and IL-8 have a synergistic inhibitory effect on β2AR-mediated stimulation of pulmonary edema removal by the alveolar epithelium. This result may, in part, explain why a large proportion of the patients with acute respiratory distress syndrome have impaired AFC.
    Anesthesiology 01/2015; 122(5). DOI:10.1097/ALN.0000000000000595 · 6.17 Impact Factor
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    ABSTRACT: Deregulated expression of glycolytic enzymes contributes not only to the increased energy demands of transformed cells but also plays non-glycolytic roles in tumors. However, the contribution of these non-glycolytic functions in tumor progression remains poorly defined. Here, we show that elevated expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but not of other glycolytic enzymes tested, increased aggressiveness and vascularization of non-Hodgkin's lymphoma. Elevated GAPDH expression was found to promote NF-κB activation via binding to TNF-receptor-associated factor-2 (TRAF2), enhancing the transcription and the activity of HIF-1α. Consistent with this, inactive mutants of GAPDH failed to bind TRAF2, enhance HIF-1 activity, or promote lymphomagenesis. Furthermore, elevated expression of gapdh mRNA in biopsies from diffuse large B cell NHL patients correlated with high levels of hif-1α, vegf-a, nfkbia mRNA and CD31 staining. Collectively, these data indicate that deregulated GAPDH expression promotes NF-κB-dependent induction of HIF-1α and plays a key role in lymphoma vascularization and aggressiveness.Leukemia accepted article preview online, 14 November 2014. doi:10.1038/leu.2014.324.
    Leukemia 11/2014; 29(5). DOI:10.1038/leu.2014.324 · 9.38 Impact Factor
  • Annales Françaises d Anesthésie et de Réanimation 09/2014; 33:A148. DOI:10.1016/j.annfar.2014.07.238 · 0.84 Impact Factor
  • Annales Françaises d Anesthésie et de Réanimation 09/2014; 33:A184-A185. DOI:10.1016/j.annfar.2014.07.320 · 0.84 Impact Factor
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    Annales Françaises d Anesthésie et de Réanimation 09/2014; 33:A241. DOI:10.1016/j.annfar.2014.07.407 · 0.84 Impact Factor
  • Annales Françaises d Anesthésie et de Réanimation 09/2014; 33:A234-A235. DOI:10.1016/j.annfar.2014.07.396 · 0.84 Impact Factor
  • Annales Françaises d Anesthésie et de Réanimation 09/2014; 33:A145. DOI:10.1016/j.annfar.2014.07.233 · 0.84 Impact Factor
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    ABSTRACT: Las técnicas de anestesia local y locorregional de la pared abdominal y del periné permiten realizar un tratamiento multimodal del dolor postoperatorio. Combinadas con las técnicas quirúrgicas mínimamente invasivas, facilitan la convalecencia y limitan la cronificación del dolor. La seguridad en materia de administración de los anestésicos locales pasa por el conocimiento de sus efectos secundarios, en particular de los tóxicos. La cantidad de anestésico local administrado se debe adaptar al peso, evitando dosis acumuladas próximas a las dosis tóxicas (reinyecciones o procedimientos anestésicos en varias localizaciones). Se recomienda el uso de agujas de bisel corto. Estos bloqueos, con la excepción del bloqueo pudendo, son bloqueos sensitivos denominados comúnmente infiltraciones, no accesibles a la neuroestimulación. Clásicamente, una inyección preoperatoria única proporciona una excelente analgesia postoperatoria de varias horas. A nivel abdominal, es posible colocar un catéter subaponeurótico para prolongar la analgesia durante varios días.
    08/2014; 40(3):1–16. DOI:10.1016/S1280-4703(14)68112-3
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    ABSTRACT: Le tecniche di anestesia locale e locoregionale della parete addominale e del perineo consentono una gestione terapeutica multimodale del dolore postoperatorio. Combinate a tecniche chirurgiche mini-invasive, esse facilitano la convalescenza e limitano la cronicizzazione dei dolori. La sicurezza in materia di somministrazione degli anestetici locali passa per la conoscenza dei loro effetti secondari, in particolare tossici. La quantità di anestetico locale somministrata è adeguata al peso, evitando delle dosi cumulative vicine alle dosi tossiche (reiniezioni o procedura anestetica a livello di diversi siti). È raccomandato l’utilizzo di aghi a ugnatura breve. Questi blocchi, a eccezione del blocco pudendo, sono dei blocchi sensitivi comunemente denominati infiltrazioni, non accessibili alla neurostimolazione. Classicamente, un’iniezione preoperatoria unica fornisce un’eccellente analgesia postoperatoria di diverse ore. È possibile, a livello addominale, posizionare un catetere sottoaponeurotico per prolungare l’analgesia per parecchi giorni.
    08/2014; 19(3):1–15. DOI:10.1016/S1283-0771(14)67850-6
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    ABSTRACT: Nous utilisons depuis 2005 un tableau de bord permettant d’analyser notre activité d’hospitalisation, permettant l’observation d’une association non rare entre le diagnostic d’infection ostéoarticulaire (IOA) et celui de bactériémie. Notre objectif était de caractériser ces IOA avec bactériémie, en évaluant l’impact pronostique de cette dernière. Patients et méthode Notre tableau de bord enregistre prospectivement 28 caractéristiques des patients hospitalisés incluant diagnostic, comorbidités, données microbiologiques, antibiothérapie et évolution. Nous avons sélectionné les patients présentant une IOA de juillet 2005 à décembre 2012. L’éventualité d’une fièvre était recherchée rétrospectivement à la lecture du dossier médical. La chronicité de l’IOA était définie par une évolution > 1 mois. L’évolution défavorable était définie par le recours à la réanimation ou le décès. Résultats Parmi les 632 patients avec IOA, 125 présentaient une bactériémie (19,8 %). En analyse multivariée, la bactériémie était associée au diagnostic de spondylodiscite (odds ratio [OR]), 3,97, p < 0,001, l’éthylisme, OR, 2,51, p = 0,010, la fièvre, OR, 2,43, p < 0,001, aux comorbidités neurologiques et/ou psychiatriques, OR, 2,41, p ≤ 0,001, et à Staphylococcus aureus, OR, 2,32, p < 0,001. Une évolution défavorable était observée 23 fois (3,6 %), celle-ci étant associée à la bactériémie OR, 8,00, p < 0,001, à un âge > 60 ans, OR, 4,78, p = 0,018, et à S. aureus, OR, 3,96, p = 0,010. Conclusion Une bactériémie est observée dans près de 20 % des IOA, étant associée avec des comorbidités repérables et constitue le principal facteur de risque d’évolution défavorable.
    Médecine et Maladies Infectieuses 08/2014; 44(8). DOI:10.1016/j.medmal.2014.07.013 · 0.91 Impact Factor
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    ABSTRACT: Arthroscopic Bankart repair alone cannot restore shoulder stability in patients with glenoid bone loss involving more than 20% of the glenoid surface. Coracoid transposition to prevent recurrent shoulder dislocation according to Bristow-Latarjet is an efficient but controversial procedure.
    Clinical Orthopaedics and Related Research 06/2014; 472(8). DOI:10.1007/s11999-014-3691-x · 2.88 Impact Factor
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    ABSTRACT: Introduction Cette étude porte sur une série de patients opérés d’une laxité antérieure chronique associée à une pré-arthrose ou à une arthrose fémoro-tibiale médiale par autogreffe du ligament croisé antérieur (LCA) associée à une ostéotomie tibiale de valgisation (OTV). L’hypothèse était que cette intervention combinée permet la reprise du sport, de stabiliser le genou et de soulager les douleurs médiales. Patients et méthodes L’étude rétrospective portait sur une série continue de 29 patients, 20 hommes et 9 femmes, d’âge moyen 43 ans (25 à 56), 14 ans (2–29) après l’entorse initiale. L’autogreffe du LCA était réalisée avec un transplant os–tendon patellaire–os chez 12 patients et un transplant aux tendons ischio-jambiers chez 17. L’ostéotomie de valgisation par ouverture médiale était réalisée grâce à une plaque à cale asymétrique. Les résultats ont été évalués par les scores IKDC subjectif et objectif, par des radiographies en appui monopodal et schuss, télémétrie, défilé fémoro-patellaire à un recul moyen de 6 ans (25 mois à 12 ans). Résultats Au recul, 23 patients avaient repris une activité sportive, dont 45 % en compétition, 28 ne ressentaient plus d’instabilité et 21 n’avaient plus de douleur. Le score IKDC subjectif était de 77 points (34 à 97) et 70 % des patients avaient un score IKDC objectif global A ou B. L’axe du genou était en valgus de 2,5°. Discussion La greffe du LCA combinée à une OTV permet de soulager les douleurs dans 7 cas sur 10, de restaurer la stabilité du genou et de reprendre le sport dans 8 cas sur 10. Niveau de preuve Niveau IV. Étude rétrospective thérapeutique.
    Revue de Chirurgie Orthopédique et Traumatologique 04/2014; 100(2):166–170. DOI:10.1016/j.rcot.2014.02.004
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    ABSTRACT: Introduction This study reports a series of patients operated on by anterior cruciate ligament (ACL) reconstruction combined with valgus high tibial osteotomy (HTO) for chronic anterior knee instability associated with medial tibiofemoral osteoarthritis. It was hypothesized that the combined surgery would enable return to sport, stabilize the knee and relieve medial pain. Patients and methods A retrospective study enrolled a continuous series of 29 patients (20 males, nine females; mean age, 43 years (range, 25–56 yrs), at a mean 14 years (range, 2–29 yrs) after the initial injury. ACL autograft used a bone-patellar tendon-bone transplant in 12 patients and hamstring tendon transplant in 17. Medial opening wedge HTO used an asymmetric wedge plate. Results were assessed on subjective and objective IKDC scores, monopodal weight-bearing and full-leg radiographs, telemetry and Merchant view at a mean 6 years follow-up (range, 25 months to 12 years). Results At follow-up, 23 patients had resumed sports activities, with 45% in competitive sports; 28 were free of instability and 21 free of pain. Mean subjective IKDC score was 77 (34–97) and 70% had A or B global objective IKDC scores. The knee axis was in 2.5° valgus. Discussion Combined ACL graft and valgus HTO relieved pain in 70% of cases, and restored knee stability enabling return to sport in 80%. Level of evidence Level IV. Retrospective therapeutic study.
    Orthopaedics & Traumatology Surgery & Research 04/2014; DOI:10.1016/j.otsr.2013.11.012 · 1.17 Impact Factor
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    ABSTRACT: The heat-shock response (HSR) protects from insults, such as ischemia-reperfusion injury, by inhibiting signaling pathways activated by sterile inflammation. However, the mechanisms by which the HSR activation would modulate lung damage and host response to a bacterial lung infection remain unknown. HSR was activated with whole-body hyperthermia or by intraperitoneal geldanamycin in mice that had their lungs instilled with Pseudomonas aeruginosa 24 h later (at least six mice per experimental group). Four hours after instillation, lung endothelial and epithelial permeability, bacterial counts, protein levels in bronchoalveolar lavage fluid, and lung myeloperoxidase activity were measured. Mortality rate 24 h after P. aeruginosa instillation was recorded. The HSR effect on the release of interleukin-10 and killing of P. aeruginosa bacteria by a mouse alveolar macrophage cell line and on neutrophil phagocytosis was also examined. HSR activation worsened lung endothelial (42%) and epithelial permeability (50%) to protein, decreased lung bacterial clearance (71%), and increased mortality (50%) associated with P. aeruginosa pneumonia, an effect that was not observed in heat-shock protein-72-null mice. HSR-mediated decrease in neutrophil phagocytosis (69%) and bacterial killing (38%) by macrophages was interleukin-10 dependent, a mechanism confirmed by increased lung bacterial clearance and decreased mortality (70%) caused by P. aeruginosa pneumonia in heat-shocked interleukin-10-null mice. Prior HSR activation worsens lung injury associated with P. aeruginosa pneumonia in mice via heat-shock protein-72- and interleukin-10-dependent mechanisms. These results provide a novel mechanism for the immunosuppression observed after severe trauma that is known to activate HSR in humans.
    Anesthesiology 03/2014; DOI:10.1097/ALN.0000000000000235 · 6.17 Impact Factor
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    ABSTRACT: Arthroscopic Bankart repair and open Latarjet bone block procedure are widely considered mainstays for surgical treatment of recurrent anterior shoulder instability. The choice between these procedures depends mainly on surgeon preference or training rather than published evidence. We compared patients with recurrent posttraumatic anterior shoulder instability treated with arthroscopic Bankart or open Latarjet procedure in terms of (1) frequency and timing of recurrent instability, (2) risk factors for recurrent instability, and (3) patient-reported outcomes. In this retrospective comparative study, we paired 93 patients undergoing open Latarjet procedures with 93 patients undergoing arthroscopic Bankart repairs over the same period for posttraumatic anterior shoulder instability by one of four surgeons at the same center. Both groups were comparable except that patients in the Latarjet group had more glenoid lesions and more instability episodes preoperatively. Minimum followup was 4 years (mean, 6 years; range, 4-10 years). Patients were assessed with a questionnaire, including stability, Rowe score, and return to sports. Recurrent instability was defined as at least one episode of recurrent dislocation or subluxation. Return to sports was evaluated using a 0% to 100% scale that patients completed after recovery from surgery. Various risk factors for recurrent instability were also analyzed. At latest followup, 10% (nine of 93) in the Latarjet group and 22% (20 of 93) in the Bankart group demonstrated recurrent instability (p = 0.026; odds ratio, 0.39; 95% CI, 0.17-0.91). Ten recurrences in the Bankart group (50%) occurred after 2 years, compared to only one (11%) in the Latarjet group. Reoperation rate was 6% and 7% in the Bankart and Latarjet groups, respectively. In both groups, patients younger than 20 years had higher recurrence risk (p = 0.019). In the Bankart group, independent factors predictive for recurrence were practice of competitive sports and shoulder hyperlaxity (ie, passive external rotation > 85° in the contralateral uninjured shoulder). Although return to sports was not different between groups, the mean Rowe score was higher in the Latarjet group (78 versus 68, p = 0.018). Patients who had the open Latarjet procedure had less recurrent instability and better Rowe scores over a mean 6-year followup. We now perform isolated arthroscopic Bankart repair for carefully selected patients, including patients with an Instability Severity Index Score of 3 or less. Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.
    Clinical Orthopaedics and Related Research 03/2014; 472(8). DOI:10.1007/s11999-014-3550-9 · 2.88 Impact Factor
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    ABSTRACT: The medico-legal risk specifically associated with the practice of ambulatory surgery is still not well studied. SHAM insurances are the biggest French provider of medical liability insurances. The study of the insurance claims provided by this insurer is therefore a relevant source of data on the complications related to ambulatory surgery. Objective The aim of this study was to compare the claim rate related to ambulatory surgery with non-ambulatory surgery. Study design We did a retrospective study on insurance claims provided by SHAM insurances between 2007 and 2011 to compare the claim rate related to ambulatory surgery with non-ambulatory surgery. Materials and methods We searched the files in the SHAM database, and then analyzed them. Results On the study period, out of a total of 29565 registered claims, 467 (1.6%) originated from ambulatory surgery. On the total of 29,098 registered claims for non-ambulatory surgery, 2151 (7.4%) led to a condemnation whereas the rate was 7% (33 out of 467 claims) for ambulatory surgery. The condemnations linked to ambulatory surgery amounted to 1.5% of the total (33 out of 2184), for a cost of 1.7 M€ (versus 400,3 M€ for non-ambulatory surgery). The average cost of a compensation is therefore 50,500 € for ambulatory surgery and 186,000 € for non-ambulatory surgery. The medical specialties concerned are primarily ophthalmology, abdominal and orthopedics surgery. The main identified causes were medical errors (n = 16) and nosocomial infections (n = 13). Conclusions The claim rate in ambulatory surgery is proportionally less frequent with compensations three times less and were related to the most frequent type of surgery done in ambulatory settings. These data should help strengthen quality approach in ambulatory surgery.
    Annales francaises d'anesthesie et de reanimation 03/2014; DOI:10.1016/j.annfar.2013.07.667 · 0.84 Impact Factor
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    ABSTRACT: The medico-legal risk specifically associated with the practice of ambulatory surgery is still not well studied. SHAM insurances are the biggest French provider of medical liability insurances. The study of the insurance claims provided by this insurer is therefore a relevant source of data on the complications related to ambulatory surgery. The aim of this study was to compare the claim rate related to ambulatory surgery with non-ambulatory surgery. We did a retrospective study on insurance claims provided by SHAM insurances between 2007 and 2011 to compare the claim rate related to ambulatory surgery with non-ambulatory surgery. We searched the files in the SHAM database, and then analyzed them. On the study period, out of a total of 29565 registered claims, 467 (1.6%) originated from ambulatory surgery. On the total of 29,098 registered claims for non-ambulatory surgery, 2151 (7.4%) led to a condemnation whereas the rate was 7% (33 out of 467 claims) for ambulatory surgery. The condemnations linked to ambulatory surgery amounted to 1.5% of the total (33 out of 2184), for a cost of 1.7 M€ (versus 400,3 M€ for non-ambulatory surgery). The average cost of a compensation is therefore 50,500 € for ambulatory surgery and 186,000 € for non-ambulatory surgery. The medical specialties concerned are primarily ophthalmology, abdominal and orthopedics surgery. The main identified causes were medical errors (n=16) and nosocomial infections (n=13). The claim rate in ambulatory surgery is proportionally less frequent with compensations three times less and were related to the most frequent type of surgery done in ambulatory settings. These data should help strengthen quality approach in ambulatory surgery.
    Annales francaises d'anesthesie et de reanimation 02/2014; 33(3). DOI:10.1016/j.annfar.2013.12.019 · 0.84 Impact Factor
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    ABSTRACT: Chronic bone infection is associated with bone resorption. From animal studies, CD3/CD28 activated T-cells are known to enhance osteoclastogenesis and bone resorption. Since CD28 is constitutively expressed on T-cells and its expression is downregulated by chronic exposure to inflammatory environment, we characterized costimulatory molecule expression on T-cells from chronically infected patients. We used cytofluorometric techniques to phenotypically characterize T-cells, its costimulatory molecules and perforin secretion from infected and non-infected human bones. Chronic bone infection was defined as infection lasting for more than a month. We show a higher T-cell activation (HLA-DR+) in infected bones compared to non-infected: median being 16% versus 7%, p=0.009 for CD4 T-cells, and 33% versus 15%, p=0.038 for CD8 T-cells respectively. However, T-cell proliferation (Ki67+) was lower for CD8 T-cells in infected bones: 26% versus 34%, p=0.045. In contrast, we detected no difference in apoptosis and regulatory T-cells. In infected bone, we found higher CD28 negative CD4+ T-cells compared to non-infected ones: 20% versus 8% respectively (p=0.005); this T-cell subset had higher CD11b expression and perforin secretion. Chronically infected human bones are characterized by an increase of CD28 negative CD4+ T-cells, indicating long-term activated cells with cytotoxic ability. Therefore this alteration of costimulatory molecules may modify interactions with osteoclasts and impact bone resorption.
    Clinical & Experimental Immunology 12/2013; 176(1). DOI:10.1111/cei.12245 · 3.28 Impact Factor
  • Journal of Shoulder and Elbow Surgery 10/2013; 22(10):e28. DOI:10.1016/j.jse.2013.07.013 · 2.37 Impact Factor

Publication Stats

1k Citations
329.75 Total Impact Points

Institutions

  • 1995–2014
    • University of Nice-Sophia Antipolis
      • Faculty of Medicine
      Nice, Provence-Alpes-Côte d'Azur, France
  • 2013
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Centre Hospitalier Universitaire de Nancy
      • Département Anesthésie Réanimation Cardiaque
      Nancy, Lorraine, France
  • 2005–2013
    • Princess Grace Hospital Centre
      Monaco-Ville, Monaco
  • 2012
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
    • French Institute of Health and Medical Research
      • Mediterranean Center for Molecular Medicine C3M
      Lutetia Parisorum, Île-de-France, France
  • 2010–2012
    • University of California, San Francisco
      • Department of Anesthesia and Perioperative Care
      San Francisco, California, United States
    • University of Alabama at Birmingham
      • Department of Anesthesiology
      Birmingham, Alabama, United States
  • 2011
    • L'Institut de Chirurgie Orthopedique et Sportive
      Lutetia Parisorum, Île-de-France, France
  • 1998–2011
    • Centre Hospitalier Universitaire de Nice
      Nice, Provence-Alpes-Côte d'Azur, France
  • 2006–2008
    • Aix-Marseille Université
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2004
    • invivo-AFDIAR
      United States