Bruno Mégarbane

Paris Diderot University, Lutetia Parisorum, Île-de-France, France

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Publications (339)1136 Total impact

  • B. Mégarbane
    06/2015; 27(2). DOI:10.1016/j.toxac.2015.04.011
  • B. Megarbane
    06/2015; 27(2). DOI:10.1016/j.toxac.2015.03.022
  • 06/2015; 27(2). DOI:10.1016/j.toxac.2015.03.009
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    ABSTRACT: -Targeted temperature management is recommended after out-of-hospital cardiac arrest (OHCA). Whether advanced internal cooling is superior to basic external cooling remains presently unknown. The aim of this multicenter controlled trial was to evaluate the benefit of endovascular versus basic surface cooling. -Inclusion criteria were: age 18-79, OHCA related to a presumed cardiac cause, time to return of spontaneous circulation (ROSC) <60min, delay between ROSC and inclusion <240min, unconscious patient after ROSC and prior to start cooling. Exclusion criteria were: terminal disease, pregnancy, known coagulopathy, uncontrolled bleeding, temperature on admission <30°C, in-hospital CA, immediate need for extracorporeal life support or hemodialysis. Patients were randomized between two cooling strategies: endovascular femoral devices (Icy catheter, Coolgard(TM), Zoll, formerly Alsius, USA, n=203) or basic external cooling using fans, a home-made tent, and ice packs (n=197). The primary endpoint, i.e. favorable outcome evaluated by survival without major neurological damages (Cerebral Performance Categories 1-2) at day 28, was not significantly different between groups (odds ratio 1.41 [0.93-2.16], P=0.107). Improvement of favorable outcome at day 90 in favor of endovascular group did not reach significance (odds ratio 1.51 [0.96-2.35], P=0.07). Time to target temperature (33°C) was significantly shorter, and target hypothermia was more strictly maintained in the endovascular versus the surface group (P<0.001). Minor side effects directly related to the cooling method were more frequently observed in the endovascular group (P=0.009). -Despite better hypothermia induction and maintenance, endovascular cooling was not significantly superior to basic external cooling regarding favorable outcome. Clinical Trial Registration Identifier: NCT00392639.
    Circulation 06/2015; DOI:10.1161/CIRCULATIONAHA.114.012805 · 14.95 Impact Factor
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    ABSTRACT: Intravenous lipid emulsion (ILE) therapy is a novel treatment that was discovered in the last decade. Despite unclear understanding of its mechanisms of action, numerous and diverse publications attested to its clinical use. However, current evidence supporting its use is unclear and recommendations are inconsistent. To assist clinicians in decision-making, the American Academy of Clinical Toxicology created a workgroup composed of international experts from various clinical specialties, which includes representatives of major clinical toxicology associations. Rigorous methodology using the Appraisal of Guidelines for Research and Evaluation or AGREE II instrument was developed to provide a framework for the systematic reviews for this project and to formulate evidence-based recommendations on the use of ILE in poisoning. Systematic reviews on the efficacy of ILE in local anesthetic toxicity and non-local anesthetic poisonings as well as adverse effects of ILE are planned. A comprehensive review of lipid analytical interferences and a survey of ILE costs will be developed. The evidence will be appraised using the GRADE system. A thorough and transparent process for consensus statements will be performed to provide recommendations, using a modified Delphi method with two rounds of voting. This process will allow for the production of useful practice recommendations for this therapy.
    Clinical Toxicology 06/2015; DOI:10.3109/15563650.2015.1052498 · 3.12 Impact Factor
  • Critical care medicine 06/2015; 43(6):e211-e212. DOI:10.1097/CCM.0000000000001006 · 6.15 Impact Factor
  • 06/2015; 27(2):S57-S58. DOI:10.1016/j.toxac.2015.03.089
  • 06/2015; 27(2):S51-S52. DOI:10.1016/j.toxac.2015.03.077
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    ABSTRACT: To characterize etiology, clinical course and outcomes of patients in prolonged refractory status epilepticus (PRSE) and looking for prognostic factors. Retrospective study conducted in patients hospitalized from January 1, 2001 to December 31, 2011 in 19 polyvalent intensive care units in French university and general hospitals. Patients were adults with a generalized convulsive refractory status epilepticus that lasted more than seven days, despite treatment including an anesthetic drug and mechanical ventilation. Patients with anoxic encephalopathy were excluded. Follow-up phone call was used to determine functional outcome using modified Rankin Scale (mRS) with mRS 0-3 defining good and mRS 4-6 poor outcome. 78 patients (35 female) were included. Median age was 57 years. Causes of status epilepticus were various, mainly including prior epilepsy (14.1%), CNS infection (12.8%), and stroke (12.8%). No etiology was found in 27 (34.6%) patients. PRSE was considered controlled in only 53 (67.9%) patients after a median duration of 17 (IQR 12-26) days. The median length of ICU stay was 28 (19-48) days. Forty-one (52.5%) patients died in the ICU, 26 from multiple organ failure, 8 from care withdrawal, 2 from sudden cardiac arrest, 1 from brain death and 4 from unknown causes. PRSE was previously resolved in 20 patients who died in the ICU. At one-year follow-up, there were 12 patients with good outcome and 58 with poor outcome and 8 lost of follow-up. On multivariate analysis, only vasopressor use was a predictor of poor outcome (OR 6.54; 95%CI 1.09-39.29; p = 0.04). Poor outcome was observed in about 80% of this population of PRSE. Most patients died from systemic complications linked to their ICU stay. Some patients can recover satisfactorily over time though we did not identify any robust factor of good outcome.
    Critical care (London, England) 04/2015; 19(1):199. DOI:10.1186/s13054-015-0914-9
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    ABSTRACT: There is currently no validated strategy for the timing of renal replacement therapy (RRT) for acute kidney injury (AKI) in the intensive care unit (ICU) when short-term life-threatening metabolic abnormalities are absent. No adequately powered prospective randomized study has addressed this issue to date. As a result, significant practice heterogeneity exists and may expose patients to either unnecessary hazardous procedures or undue delay in RRT. This is a multicenter, prospective, randomized, open-label parallel-group clinical trial that compares the effect of two RRT initiation strategies on overall survival of critically ill patients receiving intravenous catecholamines or invasive mechanical ventilation and presenting with AKI classification stage 3 (KDIGO 2012). In the 'early' strategy, RRT is initiated immediately. In the 'delayed' strategy, clinical and metabolic conditions are closely monitored and RRT is initiated only when one or more events (severity criteria) occur, including: oliguria or anuria for more than 72 hours after randomization, serum urea concentration >40 mmol/l, serum potassium concentration >6 mmol/l, serum potassium concentration >5.5 mmol/l persisting despite medical treatment, arterial blood pH <7.15 in a context of pure metabolic acidosis (PaCO2 < 35 mmHg) or in a context of mixed acidosis with a PaCO2 ≥ 50 mmHg without possibility of increasing alveolar ventilation, acute pulmonary edema due to fluid overload despite diuretic therapy leading to severe hypoxemia requiring oxygen flow rate >5 l/min to maintain SpO2 > 95% or FiO2 > 50% under invasive or noninvasive mechanical ventilation. The primary outcome measure is overall survival, measured from randomization (D0) until death, regardless of the cause. The minimum follow-up duration for each patient will be 60 days. Two interim analyses are planned, blinded to group allocation. It is expected that there will be 620 subjects in all. The AKIKI study will be one of the very few large randomized controlled trials evaluating mortality according to the timing of RRT in critically ill patients with AKI classification stage 3 (KDIGO 2012). Results should help clinicians decide when to initiate RRT. NCT01932190 .
    Trials 04/2015; 16(1):170. DOI:10.1186/s13063-015-0718-x · 2.12 Impact Factor
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    ABSTRACT: New psychoactive substances (NPS) have completely modified the drug scene and the current landscape of addiction. Synthetic substances, such as substituted or synthetic cathinones, also known as « legal highs », are often produced and used to mimic the effects of controlled drugs such as cocaine, methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine. The overwhelming majority of synthetic cathinones are produced in China and South East Asian countries. The Internet has emerged as the new marketplace for NPS, playing a major role in providing information on acquisition, synthesis, extraction, identification, and substance use. All these compounds are intentionally mislabeled and sold on-line under slang terms such as bath salts, plant food, plant feeders and research chemicals. They are sometimes labeled « not for human use » or « not tested for hazards or toxicity ». The rapid spread of NPS forces member countries of the European Union to adapt their response to the potential new dangers that may cause. To date, not only health actors but also the general public need to be clearly informed and aware of dangers resulting from NPS spread and use. Here, we review the major clinical effects of synthetic cathinones to highlight their impact on public health. A literature search was conducted from 2009 to 2014 based on PubMed, Google Scholar, Erowid, and governmental websites, using the following keywords alone or in combination: “new psychoactive substances”, “synthetic cathinones”, “substituted cathinones”, “mephedrone”, “methylone”, “MDPV”, “4-MEC”, “addiction”, and “substance use disorder”.
    Current Neuropharmacology 04/2015; 13(1). DOI:10.2174/1570159X13666141210224137 · 2.35 Impact Factor
  • La Presse Médicale 01/2015; 44(4). DOI:10.1016/j.lpm.2014.09.020 · 1.17 Impact Factor
  • SRLF; 01/2015
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    ABSTRACT: Context. A position paper on the use of whole bowel irrigation (WBI) was first published in 1997 by the American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) and updated in 2004. The aims of this paper are to briefly summarize the content of the 2004 Position Paper and to present any new data and recommendations. Methods. A systematic review of the literature from January 2003 to February 28, 2013 was conducted using multiple online databases for articles concerning WBI for gastrointestinal decontamination. An evidence table was created for applicable articles. The authors produced the initial draft that was reviewed by AACT and EAPCCT. Results. The literature search produced 60 articles with the possibility of applicable human data. Based mainly on volunteer studies, WBI can be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs particularly for those patients presenting later than 2 h after drug ingestion when activated charcoal is less effective. WBI can be considered for patients who have ingested substantial amounts of iron, lithium, or potassium as the morbidity is high and there is a lack of other potentially effective options for gastrointestinal decontamination. WBI can be considered for removal of ingested packets of illicit drugs in "body packers." However, controlled data documenting improvement in clinical outcome after WBI are lacking. WBI is contraindicated in patients with bowel obstruction, perforation, or ileus, and in patients with hemodynamic instability or compromised unprotected airways. WBI should be used cautiously in debilitated patients and in patients with medical conditions that might be further compromised by its use. The concurrent administration of activated charcoal and WBI might decrease the effectiveness of the charcoal. The clinical relevance of this interaction is uncertain. Conclusion. WBI can facilitate removal of select toxicants from the gastrointestinal tract in some patients, but there is no convincing evidence from clinical studies that it improves the outcome of poisoned patients. There is no new evidence that would require a major revision of the conclusions of the 2004 position statement.
    Clinical Toxicology 12/2014; 53(1):1-8. DOI:10.3109/15563650.2014.989326 · 3.12 Impact Factor
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    ABSTRACT: Methanol poisoning can induce death and disability. Treatment includes the administration of antidotes (ethanol or fomepizole and folic/folinic acid) and consideration of extracorporeal treatment for correction of acidemia and/or enhanced elimination. The Extracorporeal Treatments in Poisoning workgroup aimed to develop evidence-based consensus recommendations for extracorporeal treatment in methanol poisoning. Utilizing predetermined methods, we conducted a systematic review of the literature. Two hundred seventy-two relevant publications were identified but publication and selection biases were noted. Data on clinical outcomes and dialyzability were collated and a two-round modified Delphi process was used to reach a consensus. Recommended indications for extracorporeal treatment: Severe methanol poisoning including any of the following being attributed to methanol: coma, seizures, new vision deficits, metabolic acidosis with blood pH ≤7.15, persistent metabolic acidosis despite adequate supportive measures and antidotes, serum anion gap higher than 24 mmol/L; or, serum methanol concentration 1) greater than 700 mg/L (21.8 mmol/L) in the context of fomepizole therapy, 2) greater than 600 mg/L or 18.7 mmol/L in the context of ethanol treatment, 3) greater than 500 mg/L or 15.6 mmol/L in the absence of an alcohol dehydrogenase blocker; in the absence of a methanol concentration, the osmolal/osmolar gap may be informative; or, in the context of impaired kidney function. Intermittent hemodialysis is the modality of choice and continuous modalities are acceptable alternatives. Extracorporeal treatment can be terminated when the methanol concentration is <200 mg/L or 6.2 mmol/L and a clinical improvement is observed. Extracorporeal Treatments in Poisoning inhibitors and folic/folinic acid should be continued during extracorporeal treatment. General considerations: Antidotes and extracorporeal treatment should be initiated urgently in the context of severe poisoning. The duration of extracorporeal treatment extracorporeal treatment depends on the type of extracorporeal treatment used and the methanol exposure. Indications for extracorporeal treatment are based on risk factors for poor outcomes. The relative importance of individual indications for the triaging of patients for extracorporeal treatment, in the context of an epidemic when need exceeds resources, is unknown. In the absence of severe poisoning but if the methanol concentration is elevated and there is adequate alcohol dehydrogenase blockade, extracorporeal treatment is not immediately required. Systemic anticoagulation should be avoided during extracorporeal treatment because it may increase the development or severity of intracerebral hemorrhage. Extracorporeal treatment has a valuable role in the treatment of patients with methanol poisoning. A range of clinical indications for extracorporeal treatment is provided and duration of therapy can be guided through the careful monitoring of biomarkers of exposure and toxicity. In the absence of severe poisoning, the decision to use extracorporeal treatment is determined by balancing the cost and complications of extracorporeal treatment to that of fomepizole or ethanol. Given regional differences in cost and availability of fomepizole and extracorporeal treatment, these decisions must be made at a local level.
    Critical Care Medicine 12/2014; 43(2). DOI:10.1097/CCM.0000000000000708 · 6.15 Impact Factor
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    ABSTRACT: Il existe plusieurs modes d’intoxication par la colchicine : aiguë par dose unique, chronique lors d’une insuffisance rénale ou un blocage du métabolisme hépatique. L’intoxication aiguë peut engager le pronostic vital. Les défaillances d’organe conduisant au décès sont connues. À la phase précoce, il s’agit le plus fréquemment d’un choc cardiogénique et plus rarement d’un SDRA. L’assistance circulatoire périphérique (ACP) a été récemment proposée. Nous rapportons une cohorte de 4 intoxications faisant état de l’échec de l’ACP artério-veineuse (a-v).
    12/2014; 26(4). DOI:10.1016/j.toxac.2014.09.006
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    ABSTRACT: L’oxygénation par membrane extracorporelle (ECMO) avec circulation extracorporelle veinoveineuse ou veinoartérielle offrent désormais un espoir thérapeutique supplémentaire aux patients souffrant de défaillance respiratoire ou cardiaque réfractaire aux moyens thérapeutiques usuels optimisés, qu’ils soient pharmacologiques ou non. Malgré l’absence d’un service de chirurgie cardiaque au sein de l’hôpital, le service de réanimation médicale et toxicologique de l’hôpital Lariboisière a développé la technique d’ECMO, il y a environ dix ans, en raison de son recrutement spécifique de patients gravement intoxiqués par cardiotropes. L’équipe médicale et paramédicale s’est longuement formée à la canulation fémorale, au monitorage du patient en ECMO et au sevrage de cette assistance. Ce développement a été rendu possible grâce à une étroite collaboration avec les services de chirurgie cardiaque de l’hôpital universitaire de Caen et de l’hôpital de la Pitié-Salpêtrière à Paris. Par la suite, les indications ont été élargies, aux arrêts cardiaques réfractaires et aux chocs cardiogéniques non toxiques pour l’ECMO veinoartérielle et au traitement des syndromes de détresse respiratoire aiguë, essentiellement dans le cadre d’infections pulmonaires virales ou bactériennes, pour l’ECMO veinoveineuse. La canulation fémorale chirurgicale ou percutanée reste un geste technique invasif, complexe et non dénué de risques significatifs. À défaut d’un apprentissage solide et d’une expérience importante, comme en ont bénéficié les médecins de notre équipe, il est à réserver aux chirurgiens vasculaires ou cardiothoraciques, voire à des réanimateurs très entraînés, y compris dans le cadre d’une équipe mobile d’assistance circulatoire qui se déplace au lit du patient en réanimation. La décision de mise en place, le monitorage puis la décision de sevrage d’une ECMO font appel à des connaissances théoriques et à une expérience importantes et nécessitent des procédures d’organisation pratique pour les équipes médicales et paramédicales, à développer en collaboration étroite avec un service de chirurgie cardiaque. De nombreuses complications peuvent néanmoins survenir, mettant en jeu la vie du patient traité par ECMO. Un nombre minimal de patients traités par cette technique par an par centre semble donc requis pour garder une équipe motivée et entraînée. C’est pourquoi, fort de notre expérience, il nous semble que la réalisation d’une ECMO, ce d’autant plus qu’elle est veinoartérielle, doit rester l’apanage d’équipes médicochirurgicales multidisciplinaires spécialisées et entraînées. Abstract Venovenous and veno-arterial extracorporeal membrane oxygenation (ECMO) offers an additional life-saving therapeutic intervention in patients presenting acute respiratory or cardiac failure refractory to the usual management including pharmacological and non-pharmacological optimized therapies. Despite the absence of cardiac surgery department in the hospital, the medical and toxicological intensive care unit (ICU) in Lariboisière Hospital has developed ECMO since 10 years to manage severe poisonings with cardiotoxicants. Our ICU physicians and care givers have been trained at femoral cannulation as well as ECMO-treated patient monitoring and weaning. This training required a tight collaboration with the departments of cardiac surgery of Caen University Hospital and Pitié-Salpêtrière University Hospital in Paris. Once available in our ICU, ECMO indications have been extended to treat patients with refractory cardiac arrest and non-toxic cardiogenic shock (using veno-arterial ECMO) and patients with acute respiratory distress syndrome, mainly resulting from viral and bacterial pneumonitis (using venovenous ECMO). Surgical as well as percutaneous femoral cannulation represents an invasive and complex intervention, with significant risks of life-threatening complications. In the absence of robust training and prolonged experience, as reached by the physicians in our team, femoral cannulation should be only performed by vascular surgeons, cardiac surgeons or trained intensivists, including within a mobile ECMO team at the patient’s bedside in the ICU. Decision to cannulate, for ECMO monitoring, and to wean ECMO require theoretical knowledge and prolonged experience. Practical procedures should be set-up by the ICU physicians and care-givers, in collaboration with a cardiac surgery department. However, several significant complications may occur, compromising ECMO-treated patient’s survival. A minimal number of ECMO-treated patients per year per center seem requested to maintain a motivated and trained ICU team. Thus, based on our large experience, we recommend that ECMO should only be performed by trained multidisciplinary specialized medicosurgical teams.
    Réanimation 12/2014; 22(S3):643-653. DOI:10.1007/s13546-014-0887-8
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    ABSTRACT: Chloroquine, a well-known anti-malarial drug may be lethal when ingested in large amount. We report the case of a 45 year-old patient who ingested 10 g of chloroquine in a suicidal attempt, 3 h prior to presentation. Despite aggressive management, the patient died on the third day. The ingested dose (> 4 g), the QRS duration (> 0.10 sec), and the onset of hypotension (systolic blood pressure < 100 mmHg) are the established prognosticators. The delay in management, the blood chloroquine concentration on admission, and the onset of cardiovascular complications also influence the final outcome. The treatment consists in tracheal intubation, mechanical ventilation, epinephrine and diazepam in the presence of any bad prognostic factor as well as 8.4% sodium bicarbonate in case of QRS complex enlargement on EKG. The chloroquine is not dialyzable nor hemofiltrated. extracorporeal membrane oxygenation (ECMO) might be helpful in the most severe case refractory to the pharmacological treatments.
  • 11/2014; 32. DOI:10.1016/j.toxac.2014.09.005
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    ABSTRACT: Lithium-induced neurotoxicity may be life-threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg-Li2CO3 in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg-Li2CO3 in rats receiving 800 mg/l-Li2CO3 in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg-Li2CO3 during 5 days in rats with 15 mg/kg-K2Cr2O7-induced renal failure). Delayed absorption (4.03 vs. 0.31 h), increased plasma elimination (0.65 vs. 0.37 l/kg/h) and shorter half-life (1.75 vs. 2.68 h) were observed in acute-on-chronically compared to acutely poisoned rats. Erythrocyte and cerebrospinal fluid kinetics paralleled plasma kinetics in both models. Brain lithium distribution was rapid (as early as 15 min), inhomogeneous and with delayed elimination (over 78h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-the-curve of brain concentrations (379±41 vs. 295±26, P<0.05) and brain-to-plasma ratio (45±10 vs. 8±2, P<0.0001) at 54h]. Moreover, brain lithium distribution was increased in chronically compared to acute-on-chronically poisoned rats (brain-to-plasma ratio: 9±1 vs. 3±0, P<0.01). In conclusion, prolonged rat exposure results in brain lithium accumulation, which is more marked in the presence of renal failure. Our data suggest that differences in plasma and brain kinetics may at least partially explain the observed variability between human intoxication patterns.
    Toxicological Sciences 10/2014; 52(4). DOI:10.1093/toxsci/kfu224 · 4.48 Impact Factor

Publication Stats

3k Citations
1,136.00 Total Impact Points


  • 2007–2015
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
    • University of Washington Seattle
      Seattle, Washington, United States
  • 2014
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
    • Hôpital Lariboisière - Fernand-Widal (Hôpitaux Universitaires Sant-Louis, Lariboisière, Fernand-Widal)
      Lutetia Parisorum, Île-de-France, France
  • 2006–2014
    • Université René Descartes - Paris 5
      • Faculté des Sciences Pharmaceutiques et Biologiques de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2004–2014
    • Hôpital Ambroise Paré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Billancourt, Île-de-France, France
  • 2013
    • Groupe Hospitalier Saint Vincent
      Strasburg, Alsace, France
    • Brussels University Association
      Bruxelles, Brussels Capital, Belgium
  • 2002–2012
    • Assistance Publique – Hôpitaux de Paris
      • • Department of Cardiology
      • • Service d'Accueil des Urgences
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • University Hospital Brussels
      Bruxelles, Brussels Capital Region, Belgium
  • 2010
    • University of Nebraska Medical Center
      • Department of Pathology and Microbiology
      Omaha, Nebraska, United States
  • 2003–2010
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2008
    • University of Paris-Est
      La Haye-Descartes, Centre, France
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2005–2007
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2000–2005
    • Hôpital Antoine-Béclère – Hôpitaux universitaires Paris-Sud
      Clamart, Île-de-France, France