Frédéric Pène

Université René Descartes - Paris 5, Lutetia Parisorum, Île-de-France, France

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Publications (112)634.04 Total impact

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    Frédéric Pène · Peter Pickkers · Richard S Hotchkiss

    Preview · Article · Dec 2015 · Intensive Care Medicine

  • No preview · Article · Dec 2015
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    ABSTRACT: Experimental research has always been the cornerstone of pathophysiological and therapeutic advances in critical care medicine, where clinical observations and basic research mutually fed each other in a so-called translational approach. The objective of this review is to address the different aspects of translational research in the field of critical care medicine. We herein highlighted some demonstrative examples including the animal-to-human approach to study host-pathogen interactions, the human-to-animal approach for sepsis-induced immunosuppression, the still restrictive human approach to study critical illness-related neuromyopathy, and the technological developments to assess the microcirculatory changes in critically ill patients. These examples not only emphasize how translational research resulted in major improvements in the comprehension of the pathophysiology of severe clinical conditions and offered promising perspectives in critical care medicine but also point out the obstacles to translate such achievements into clinical practice.
    Full-text · Article · Dec 2015 · Annals of Intensive Care
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    ABSTRACT: Background Cancer patients are at high risk for acute kidney injury (AKI), which is associated with high morbidity and mortality. We sought to appraise the incidence, risk factors, and outcome of AKI in a large multicentre cohort study of critically ill patients with haematological malignancies. Methods We used a retrospective analysis of a prospectively collected database. The study was carried out in 17 university or university-affiliated centres in France and Belgium between 2010 and 2012. AKI was defined according to the Acute Kidney Injury Network (AKIN) definition. Results Of the 1011 patients admitted into the intensive care unit (ICU) during the study period, 1009 were included in this study. According to the AKIN definition, 671 patients (66.5%) developed an AKI during their ICU stay, of which 258 patients (38.4%) were AKI stage 1, 75 patients (11.2%) AKI stage 2 and 338 patients (50.4%) AKI stage 3. After adjustment for confounders, main adverse risk factors of AKI were older age, severity [non-renal Sequential Organ Failure Assessment (SOFA)], history of hypertension, tumour lysis syndrome, exposure to nephrotoxic agents and myeloma. Hospital mortality was 44.3% in patients with AKI and 25.4% in patients without AKI (P < 0.0001). After adjustment for confounders, AKI was independently associated with hospital mortality [OR 1.65 (95% CI 1.19–2.29)]. Overall, 271 patients required renal replacement therapy (RRT), of whom 57.2% died during their hospital stay as compared with 31.2% (P < 0.0001) in those not requiring RRT. Conclusion Two-thirds of critically ill patients with haematological malignancies developed AKI. Hospital mortality in this population of patients developing AKI or requiring RRT is close to that in general ICU population.
    Full-text · Article · Dec 2015 · Nephrology Dialysis Transplantation
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    ABSTRACT: Most studies about septic shock report a crude mortality rate that neither distinguishes between early and late deaths nor addresses the direct causes of death. We herein aimed to determine the modalities of death in septic shock. This was a 6-year (2008-2013) monocenter retrospective study. All consecutive patients diagnosed for septic shock within the first 48 h of intensive care unit (ICU) admission were included. Early and late deaths were defined as occurring within or after 3 days following ICU admission, respectively. The main cause of death in the ICU was determined from medical files. A multinomial logistic regression analysis using the status alive as the reference category was performed to identify the prognostic factors associated with early and late deaths. Five hundred forty-three patients were included, with a mean age of 66 ± 15 years and a high proportion (67 %) of comorbidities. The in-ICU and in-hospital mortality rates were 37.2 and 45 %, respectively. Deaths occurred early for 78 (32 %) and later on for 166 (68 %) patients in the ICU (n = 124) or in the hospital (n = 42). Early deaths were mainly attributable to intractable multiple organ failure related to the primary infection (82 %) and to mesenteric ischemia (6.4 %). In-ICU late deaths were directly related to end-of-life decisions in 29 % of patients and otherwise mostly related to ICU-acquired complications, including nosocomial infections (20.4 %) and mesenteric ischemia (16.6 %). Independent determinants of early death were age, malignancy, diabetes mellitus, no pathogen identification, and initial severity. Among 3-day survivors, independent risk factors for late death were age, cirrhosis, no pathogen identification, and previous corticosteroid treatment. Our study provides a comprehensive assessment of septic shock-related deaths. Identification of risk factors of early and late deaths may determine differential prognostic patterns.
    Full-text · Article · Dec 2015 · Annals of Intensive Care
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    ABSTRACT: In patients with hematological malignancies and acute respiratory failure (ARF), noninvasive ventilation was associated with a decreased mortality in older studies. However, mortality of intubated patients decreased in the last years. In this study, we assess outcomes in those patients according to the initial ventilation strategy. We performed a post hoc analysis of a prospective multicentre study of critically ill hematology patients, in 17 intensive care units in France and Belgium. Patients with hematological malignancies admitted for ARF in 2010 and 2011 and who were not intubated at admission were included in the study. A propensity score-based approach was used to assess the impact of NIV compared to oxygen only on hospital mortality. Among 1011 patients admitted to ICU during the study period, 380 met inclusion criteria. Underlying diseases included lymphoid (n = 162, 42.6 %) or myeloid (n = 141, 37.1 %) diseases. ARF etiologies were pulmonary infections (n = 161, 43 %), malignant infiltration (n = 65, 17 %) or cardiac pulmonary edema (n = 40, 10 %). Mechanical ventilation was ultimately needed in 94 (24.7 %) patients, within 3 [2–5] days of ICU admission. Hospital mortality was 32 % (123 deaths). At ICU admission, 142 patients received first-line noninvasive ventilation (NIV), whereas 238 received oxygen only. Fifty-five patients in each group (NIV or oxygen only) were matched according the propensity score. NIV was not associated with decreased hospital mortality [OR 1.5 (0.62–3.65)]. In hematology patients with acute respiratory failure, initial treatment with NIV did not improve survival compared to oxygen only. Clinical trial.gov number NCT 01172132
    Full-text · Article · Dec 2015 · Annals of Intensive Care
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    ABSTRACT: Background: Daily therapeutic plasma exchange (TPE) and rituximab improved thrombotic thrombocytopenic (TTP) prognosis. In the more severe cases, salvage therapies including twice-daily TPE and/or cyclophosphamide may be proposed and require evaluation. Methods: TTP was defined as a thrombotic microangiopathy (TMA) with severe (< 10%) acquired ADAMTS13 deficiency. Among patients included in the French Reference Center for TMA registry, we considered those with a severe disease (i.e., unresponsive to daily TPE and rituximab) who received twice-daily TPE. Results: 19/289 (6.6%) patients with TTP were treated by twice-daily TPE between 2008 and 2014. Twice-daily TPE were associated with rituximab in 16 cases. The median duration of twice-daily TPE treatment was 3 days (2-22 days). In 6 patients (31.6%), additional treatments (mainly pulses of cyclophosphamide) were performed because of a persistently refractory disease (4 cases) or an exacerbation (2 cases), despite twice-daily TPE. Only one patient (5.3%) died. The other 18 achieved a durable complete remission 25.5 days (13-68 days) after the first TPE. The median follow-up was 14.4 months (7 days-45 months). Conclusions: Twice-daily TPE may be an efficient strategy in the more severe TTP patients with a short term life-threatening disease that could overcome their poor prognosis. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · European Journal Of Haematology
  • Ine Moors · Frédéric Pène · Étienne Lengline · Dominique Benoit
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    ABSTRACT: Purpose of review: Over the past decades, survival of critically ill hematological patients has dramatically improved, and these patients are more frequently referred to the ICU for intensive treatment, including a rising need for administering anticancer-therapy in this setting. Recent findings: The scarce literature on this subject provides evidence for feasibility of administering chemotherapy in the ICU, with expected ICU survival of 60-70%, and one in three patients surviving at least 1 year after discharge. We summarize the recent evidence concerning outcome, dosing and indications of chemotherapy in the ICU, and provide practical guidelines for some special oncological situations. Summary: Anticancer-therapy in the ICU is feasible and no longer futile as long as it is initiated in a selected, well-informed patient population with reasonable prognostic expectations. Accurate recognition of organ failure and early referral to the ICU for both supportive care and timely administration of chemotherapy is recommended before the development of multisystem organ failure.
    No preview · Article · Nov 2015 · Current opinion in critical care

  • No preview · Article · Nov 2015 · Resuscitation
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    ABSTRACT: Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64-15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59-27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications.
    Preview · Article · Oct 2015 · Medicine
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    ABSTRACT: Background: Whether to perform or not an immediate percutaneous coronary intervention (PCI) after out-of-hospital cardiac arrest is still debated. We aimed to evaluate the impact of PCI on short- and long-term survival in out-of-hospital cardiac arrest patients admitted after successful resuscitation. Methods and results: Between 2000 and 2013, all nontrauma out-of-hospital cardiac arrest patients admitted in a Parisian cardiac arrest center after return of spontaneous circulation were prospectively included. The association between immediate PCI and short- and long-term mortality was analyzed using logistic regression and Cox multivariate analysis, respectively. Propensity score-matching method was used to assess the influence of PCI on short- and long-term survival. During the study period, 1722 patients (71.5% male, median age 60 [49.6, 72.2] years) were analyzed: 628 (35.6%) without coronary angiography, 615 (35.7%) with coronary angiography without PCI, and 479 (27.8%) with both. Among these groups, day 30 and year-10 survival rates were 21% and 11.9%, 35% and 29%, 43% and 38%, respectively (P<0.01 for each). PCI as compared with no coronary angiography was associated with a lower day-30 and long-term mortality (adjORcoro with PCI versus no coro 0.71, 95% confidence interval [0.54, 0.92]; P=0.02 and adjHRcoro with PCI versus no coro 0.44, 95% confidence interval [0.27, 0.71]; P<0.01, respectively). PCI remained associated with a lower risk of long-term mortality (adjHR 0.29; 95% confidence interval [0.14, 0.61]; P<0.01) in propensity score-matching analysis. Conclusions: Immediate PCI after out-of-hospital cardiac arrest was associated with significant reduced risk of short- and long-term mortality. These findings should suggest physicians to consider immediate coronary angiography and PCI if indicated in these patients.
    No preview · Article · Oct 2015 · Circulation Cardiovascular Interventions
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    ABSTRACT: Importance Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this indication remains unclear.Objective To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure.Design, Setting, and Participants Multicenter randomized trial conducted among 374 critically ill immunocompromised patients, of whom 317 (84.7%) were receiving treatment for hematologic malignancies or solid tumors, at 28 intensive care units (ICUs) in France and Belgium between August 12, 2013, and January 2, 2015.Interventions Patients were randomly assigned to early noninvasive ventilation (n = 191) or oxygen therapy alone (n = 183).Main Outcomes and Measures The primary outcome was day-28 mortality. Secondary outcomes were intubation, Sequential Organ Failure Assessment score on day 3, ICU-acquired infections, duration of mechanical ventilation, and ICU length of stay.Results At randomization, median oxygen flow was 9 L/min (interquartile range, 5-15) in the noninvasive ventilation group and 9 L/min (interquartile range, 6-15) in the oxygen group. All patients in the noninvasive ventilation group received the first noninvasive ventilation session immediately after randomization. On day 28 after randomization, 46 deaths (24.1%) had occurred in the noninvasive ventilation group vs 50 (27.3%) in the oxygen group (absolute difference, −3.2 [95% CI, −12.1 to 5.6]; P = .47). Oxygenation failure occurred in 155 patients overall (41.4%), 73 (38.2%) in the noninvasive ventilation group and 82 (44.8%) in the oxygen group (absolute difference, −6.6 [95% CI, −16.6 to 3.4]; P = .20). There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays.Conclusions and Relevance Among immunocompromised patients admitted to the ICU with hypoxemic acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce 28-day mortality. However, study power was limited.Trial Registration clinicaltrials.gov Identifier:NCT01915719
    Full-text · Article · Oct 2015 · JAMA The Journal of the American Medical Association
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    Preview · Article · Oct 2015
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    Full-text · Article · Oct 2015
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    ABSTRACT: Compared to many other cardiovascular diseases, there is a paucity of data on the characteristics of successfully resuscitated cardiac arrest (CA) patients with human immunodeficiency virus (HIV) infection. We investigated causes, clinical features and outcome of these patients, and assessed the specific burden of HIV on outcome. Retrospective analysis of HIV-infected patients admitted to 20 French ICUs for successfully resuscitated CA (2000-2012). Characteristics and outcome of HIV-infected patients were compared to those of a large cohort of HIV-uninfected patients admitted after CA in the Cochin Hospital ICU during the same period. 99 patients were included (median CD4 lymphocyte count 233/mm(3), viral load 43 copies/ml). When compared with the control cohort of 1701 patients, HIV-infected patients were younger, with a predominance of male, a majority of in-hospital CA (52%), and non-shockable initial rhythm (80.8%). CA was mostly related to respiratory cause (n=36, including 23 pneumonia), cardiac cause (n=33, including 16 acute myocardial infarction), neurologic cause (n=8) and toxic cause (n=5). CA was deemed directly related to HIV infection in 18 cases. Seventy-one patients died in the ICU, mostly for care withdrawal after post-anoxic encephalopathy. After propensity score matching, ICU mortality was not significantly affected by HIV infection. Similarly, HIV disease characteristics had no impact on ICU outcome. Etiologies of CA in HIV-infected patients are miscellaneous and mostly not related to HIV infection. Outcome remains bleak but is similar to outcome of HIV-negative patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Aug 2015 · International journal of cardiology
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    ABSTRACT: Patients with systemic sclerosis (SSc) are prone to disease-specific or treatment-related life-threatening complications that may warrant intensive care unit (ICU) admission. We assessed the characteristics and current outcome of patients with SSc admitted to the ICU. We performed a single-center retrospective study over 6 years (November 2006-December 2012). All patients with SSc admitted to the ICU were enrolled. Short-term (in-ICU and in-hospital) and longterm (6-mo and 1-yr) mortality rates were studied, and the prognostic factors were analyzed. Forty-one patients with a median age of 50 years [interquartile range (IQR) 40-65] were included. Twenty-nine patients (72.5%) displayed diffuse cutaneous SSc. The time from diagnosis to ICU admission was 78 months (IQR 34-128). Twenty-eight patients (71.7%) previously had pulmonary fibrosis, and 12 (31.5%) had pulmonary hypertension. The main reason for ICU admission was acute respiratory failure in 27 patients (65.8%). Noninvasive ventilation was first attempted in 13 patients (31.7%) and was successful in 8 of them, whereas others required endotracheal intubation within 24 h. Altogether, 13 patients (31.7%) required endotracheal intubation and mechanical ventilation. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 31.8%, 39.0%, 46.4%, and 61.0%, respectively. Invasive mechanical ventilation was the worst prognostic factor, associated with an in-hospital mortality rate of 84.6%. This study provides reliable prognostic data in patients with SSc who required ICU admission. The devastating outcome of invasive mechanical ventilation in patients with SSc requires a reappraisal of indications for ICU admission and early identification of patients likely to benefit from noninvasive ventilation.
    No preview · Article · Jul 2015 · The Journal of Rheumatology
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    ABSTRACT: TLR2 has a prominent role in host defense against a wide variety of pathogens. Stimulation of TLR2 triggers MyD88-dependent signaling to induce NF-κB translocation, and activates a Rac1-PI 3-kinase dependent pathway that leads to transactivation of NF-κB through phosphorylation of the P65 NF-κB subunit. This transactivation pathway involves tyrosine phosphorylations. The role of the tyrosine kinases in TLR signaling is controversial, with discrepancies between studies using only chemical inhibitors and knockout mice. Here, we show the involvement of the tyrosine-kinase Lyn in TLR2-dependent activation of NF-κB in human cellular models, by using complementary inhibition strategies. Stimulation of TLR2 induces the formation of an activation cluster involving TLR2, CD14, PI 3-kinase and Lyn, and leads to the activation of AKT. Lyn-dependent phosphorylation of the p110 catalytic subunit of PI 3-kinase is essential to the control of PI 3-kinase biological activity upstream of AKT and thereby to the transactivation of NF-κB. Thus, Lyn kinase activity is crucial in TLR2-mediated activation of the innate immune response in human mononuclear cells. © The Author(s) 2015.
    No preview · Article · Jun 2015 · Innate Immunity
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    ABSTRACT: Strongyloides stercoralis may lead to overwhelming infestation [Strongyloides hyperinfection syndrome (SHS)]. We aimed at describing a case series of patients admitted in intensive care unit (ICU) with SHS and report a literature review of such cases. Retrospective multicenter study of 11 patients admitted to the ICU of tertiary hospitals with SHS between 2000 and 2013. Literature review with Pubmed retrieved 122 cases. Logistic regression analysis was performed to identify predictive factors of ICU mortality and shock occurrence. 133 patients [median age 53 (39, 64), 72.2 % males] were included. Underlying immunosuppression was present in 127 patients, mostly long-term corticosteroid treatment in 111 (83.5 %) patients. Fever (80.8 %), respiratory (88.6 %), and gastrointestinal (71.2 %) symptoms were common clinical manifestations. Shock occurred in 75 (57.3 %) patients and mechanical ventilation was required in 89 (67.9 %) patients. Hypereosinophilia and a concomitant bacterial infection were observed in 34 (34.3 %) and 51 (38.4 %) patients, respectively. The in-ICU mortality rate was 60.3 %. Predictive factors of ICU mortality were shock occurrence [Odds ratio (OR) 18.1, 95 % confidence interval (95 % CI) 3.03-107.6, p < 0.01] and mechanical ventilation (OR 28.1, 95 % CI 3.6-217, p < 0.01). Hypereosinophilia (OR 0.21, 95 % CI 0.06-0.7, p = 0.01) and a concomitant bacterial infection (OR 4.68, 95 % CI 1.3-16.8, p = 0.02) were independent predictors of shock occurrence. SHS remains associated with a poor outcome, especially when associated with shock and mechanical ventilation. Deterioration to shock is often related to concomitant bacterial infection. The poor outcome of established SHS pleads for a large application of antiparasitic primary prophylaxis in at-risk patients.
    Full-text · Article · May 2015 · Infection
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    ABSTRACT: The number of patients living with hematological malignancies (HMs) has increased steadily over time. This is the result of intensive and effective treatments that also increase the probability of infiltrative, infectious or toxic life threatening event. Over the last two decades, the number of patients with HMs admitted to the ICU increased and their mortality has dropped sharply. ICU patients with HMs require an extensive diagnostic workup and the optimal use of ICU treatments to identify the reason for ICU admission and the nature of the complication that explains organ dysfunctions. Mortality of ARDS or septic shock is up to 50%, respectively. In this review, the authors share their experience with managing critically ill patients with HMs. They discuss the main aspects of the diagnostic and therapeutic management of critically ill patients with HMs and argue that outcomes have improved over time and that many classic determinants of mortality have become irrelevant. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Apr 2015 · Blood Reviews
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    ABSTRACT: Intensive care unit (ICU) admission is associated with high mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Whether mortality has decreased recently is unknown. The 497 adult allogeneic HSCT recipients admitted to three ICUs between 1997 and 2011 were evaluated retrospectively. Two hundred and nine patients admitted between 1997 and 2003 were compared with the 288 patients admitted from 2004 to 2011. Factors associated with 90-day mortality were identified. The recent cohort was characterized by older age, lower conditioning intensity, and greater use of peripheral blood or unrelated-donor graft. In the recent cohort, ICU was used more often for patients in hematological remission (67% vs 44%; P<0.0001) and without GVHD (73% vs 48%; P<0.0001) or invasive fungal infection (85% vs 73%; P=0.0003) despite a stable admission rate (21.7%). These changes were associated with significantly better 90-day survival (49% vs 31%). Independent predictors of hospital mortality were GVHD, mechanical ventilation (MV) and renal replacement therapy (RRT). Among patients who required MV or RRT, survival was 29% and 18%, respectively, but dropped to 18% and 6% in those with GVHD. The use of ICU admission has changed and translated into improved survival, but advanced life support in patients with GVHD usually provides no benefits.Bone Marrow Transplantation advance online publication, 23 March 2015; doi:10.1038/bmt.2015.55.
    No preview · Article · Mar 2015 · Bone marrow transplantation

Publication Stats

2k Citations
634.04 Total Impact Points

Institutions

  • 2005-2015
    • Université René Descartes - Paris 5
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 2006-2014
    • Hôpital Cochin (Hôpitaux Universitaires Paris Centre)
      Lutetia Parisorum, Île-de-France, France
  • 2005-2014
    • Assistance Publique – Hôpitaux de Paris
      • • Département de Biochimie
      • • Department of Cardiology
      Lutetia Parisorum, Île-de-France, France
  • 2004-2014
    • Institut Cochin
      Lutetia Parisorum, Île-de-France, France
  • 2011-2013
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Immunoregulation
      Maryland, United States
  • 2012
    • Hôpital Avicenne – Hôpitaux Universitaires Paris-Seine-Saint-Denis
      Bobigny, Île-de-France, France
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France