Pierre Quartier

Assistance Publique – Hôpitaux de Paris, Lutetia Parisorum, Île-de-France, France

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Publications (181)735.4 Total impact

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    ABSTRACT: To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers.
    Annals of the rheumatic diseases. 07/2014;
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    ABSTRACT: The efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were previously demonstrated at week 40 of CHERISH, a phase 3 trial in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) (). Here we report the efficacy and safety of TCZ over 104 weeks of treatment in patients with pcJIA. Patients 2 to 17 years old with ≥6 months' active pcJIA who failed methotrexate received open-label TCZ (weight ≥30 kg, 8 mg/kg [n = 119]; weight ≥30 kg, randomly assigned [1:1] to 8 [n = 34] or 10 [n = 35] mg/kg) every 4 weeks for 16 weeks. Patients with ≥JIA American College of Rheumatology (ACR) 30 response at week 16 entered a 24-week, double-blind withdrawal period and were randomly assigned (1:1) to placebo or continuation with TCZ. Patients with JIA ACR30 flare or who completed the withdrawal period entered an open-label extension through week 104. One hundred eighty-eight patients entered the lead-in period, 166 entered the withdrawal period, 160 entered the open-label extension period, and 155 completed 104 weeks. In patients who received continuous TCZ throughout the study (n = 82), JIA ACR responses, improvement in JIA ACR core components, and proportions of patients with inactive disease or remission () were maintained through week 104. JADAS-71 scores were maintained through week 104 (Figure); 73% of patients had JADAS-71 <3.8 (minimal disease activity cutoff), 56% had JADAS-71 <1 (inactive disease cutoff). The safety population comprised 188 patients with 307 patient-years (PY). Rates/100 PY of adverse events (AEs) and serious AEs (SAEs) were 406.5 and 11.1, respectively; infections were the most common AE (151.4) and SAE (5.2). ALT and AST elevations ≥3× upper limit of normal occurred in 6.4% and 2.7% of patients, respectively. Grade 3 lowest neutrophil count and grade 2/3/4 thrombocytopenia occurred in 5.9% and 1.6% of patients, respectively. LDL cholesterol ≥110 mg/dL occurred in 16.2% of patients. [Table: see text] The efficacy of TCZ was maintained through 2 years of treatment in patients with pcJIA, with no change in safety profile from that reported previously ().
    Arthritis & rheumatology (Hoboken, N.J.). 03/2014; 66 Suppl 11:S5-6.
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    ABSTRACT: Abstract Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease and the most common systemic association of uveitis in children. JIA is subdivided into seven clinically more homogeneous subtypes, using the International League of Associations for Rheumatology (ILAR) classification system: systemic arthritis, oligoarthritis, rheumatoid factor (RF)-negative polyarthritis, RF-positive polyarthritis, psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis. Uveitis is very rare in patients with systemic onset JIA and in patients with juvenile-onset rheumatoid arthritis. Patients with early-onset antinuclear antibody (ANA)-positive oligoarticular JIA have the highest risk of developing chronic iridocyclitis. Ocular involvement in enthesitis-related arthritis is characterized by recurrent acute symptomatic iridocyclitis. The diagnosis and differential diagnosis of JIA are based on history, physical examination, and laboratory investigations, including complete blood count, acute-phase reactants, ANA, RF, HLA-B27, and musculoskeletal imaging studies. Recent studies have revealed distinct gene expression profiles that may be useful in the diagnosis, classification, and follow-up of JIA patients.
    Ocular immunology and inflammation 01/2014; · 0.72 Impact Factor
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    ABSTRACT: Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), belongs to the group of ANCA-associated necrotizing vasculitides. This study describes the clinical picture of the disease in a large cohort of GPA paediatric patients. Children with age at diagnosis ≤ 18 years, fulfilling the EULAR/PRINTO/PRES GPA/WG classification criteria were extracted from the PRINTO vasculitis database. The clinical signs/symptoms and laboratory features were analysed before or at the time of diagnosis and at least 3 months thereafter and compared with other paediatric and adult case series (>50 patients) derived from the literature.
    Pediatric rheumatology online journal. 01/2014; 12:18.
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    ABSTRACT: Growth retardation is a frequent complication of severe juvenile idiopathic arthritis (JIA). Biologic treatments may improve growth velocity by controlling systemic inflammation and reducing corticosteroids. Our goals were to compare growth velocity before and after the onset of biologic therapy and to determine whether the JIA subtype, the use of steroids, the requirement of one or several biologic agents, or the disease activity influenced growth velocity. We retrospectively analyzed the growth of children with JIA who never received growth hormone treatment, who started biologic treatment before puberty, and who were followed for at least 6 months afterward. We included 100 children (33 boys). Median patient age was 7.1 years (range: 1.6-15.7) at the onset of biologic treatment and 11.0 years (range: 2.3-19.5) at the latest followup. Forty-six patients had received corticosteroid and 34 had received more than 1 biologic agent. Patient median height expressed as SD score (SDS) was 0.31 (range: -2.47 to 5.46) at disease onset, -0.24 (-3.63 to 2.90) at biologic therapy onset (p < 0.0001), and -0.15 (-4.95 to 3.52) at the latest followup (p = 0.171 compared to biologic treatment onset). Patients who required several biologics and systemic patients had a significantly lower growth velocity after the onset of biologic treatment. At the latest followup, 18% of our study group had low growth velocities and 19% were below -2SD or shorter than genetically programmed. In a subset of patients, particularly systemic JIA patients and patients who required more than 1 biologic, biologic therapy may be insufficient to restore normal growth velocity.
    The Journal of Rheumatology 12/2013; · 3.26 Impact Factor
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    ABSTRACT: Studies on the role of the RNA receptor TLR8 in inflammation have been limited by its different function in human versus rodents. We have generated multiple lines of transgenic mice expressing different levels of human TLR8. The high copy number chimeras were unable to pass germline; developed severe inflammation targeting the pancreas, salivary glands, and joints; and the severity of the specific phenotypes closely correlated with the huTLR8 expression levels. Mice with relatively low expression levels survived and bred successfully but had increased susceptibility to collagen-induced arthritis, and the levels of huTLR8 correlated with proinflammatory cytokines in the joints of the animals. At the cellular level, huTLR8 signaling exerted a DC-intrinsic effect leading to up-regulation of co-stimulatory molecules and subsequent T cell activation. A pathogenic role for TLR8 in human diseases was suggested by its increased expression in patients with systemic arthritis and the correlation of TLR8 expression with the elevation of IL-1β levels and disease status. We found that the consequence of self-recognition via TLR8 results in a constellation of diseases, strikingly distinct from those related to TLR7 signaling, and points to specific inflammatory diseases that may benefit from inhibition of TLR8 in humans.
    Journal of Experimental Medicine 11/2013; · 13.21 Impact Factor
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    Pediatric Rheumatology 11/2013; 11(Suppl1):A216. · 1.47 Impact Factor
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    ABSTRACT: Multicentric carpo-tarsal osteolysis (MCTO) with or without nephropathy is a rare osteolysis disorder beginning in early childhood and involving mainly carpal and tarsal bones. Renal disease appears later in life in the majority of cases and evolves quickly to end stage renal failure. Autosomal dominant (AD) inheritance has been demonstrated, with a high frequency of sporadic cases. Recently, mutations in a highly conserved region of the MAFB gene (v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B) have been identified in MCTO patients by exome sequencing. MafB, known as a regulator of various developmental processes, is essential for osteoclastogenesis and renal development. We report here the molecular screening of MAFB in eight MCTO patients from six families. We identified MAFB mutations in all, including three novel missense mutations clustering within the hot spot mutation region. Among the eight patients, six only presented renal disease. Our report confirms the genetic homogeneity of MCTO and provides data underlying the clinical variability of this disorder. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 08/2013; · 2.30 Impact Factor
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    ABSTRACT: Anakinra pharmacokinetics and pharmacodynamics were investigated in children and adolescents treated for systemic-onset juvenile idiopathic arthritis (SJIA) and autoinflammatory syndromes. Anakinra was given subcutaneously at doses between 2 and 10 mg/kg (maximum 100 mg) per day. Anakinra concentrations were recorded in patients, as well as C-reactive protein (CRP) levels, on different occasions. The data were fitted to a pharmacokinetic-pharmacodynamic model via a population approach using Monolix. A total of 87 children and adolescents, 8 months to 21 years old, were available for pharmacokinetic evaluation. A one compartment model with linear absorption and elimination described the pharmacokinetics. Taking into account bodyweight to explain variations in apparent clearance (CL/F) and distribution volume (V/F) significantly reduced the associated between-subject and between-occasion variabilities. The final estimates were 6.24 L/h/70 kg and 65.2 L/70 kg for CL/F and V/F respectively. A mixture pharmacodynamic model described the CRP level change during anakinra treatment for the SJIA patients with 2 subpopulations, patients with high baseline and large CRP decrease and patients with low baseline and small CRP decrease followed by a re-increase in CRP levels. There was no significant effect of the combined anti-inflammatory treatment. The proportion of patients for which the development of a resistance to treatment was significant was 62% and the corresponding time was approximately 60 days CONCLUSIONS: Based on effects in SJIA, a prospective dosage adjustment was proposed based on a 0.4 mg/L Css target in order to obtain a CRP decrease to 10 mg/L or below.
    BMC pharmacology & toxicology. 08/2013; 14(1):40.
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    ABSTRACT: Germline mutations in the SLC29A3 gene result in a range of recessive, clinically related syndromes: H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome, Faisalabad histiocytosis, and sinus histiocytosis with massive lymphadenopathy. The main symptoms of these diseases are hyperpigmentation with hypertrichosis, sensorineural deafness, diabetes, short stature, uveitis, and Rosai-Dorfman like histiocytosis. Here, we report the case of an 11-month-old boy with early-onset, recurrent episodes of unprovoked fever lasting 7 to 10 days and associated with pericardial effusion, abdominal pain, diarrhea, and inflammation. Physical examination revealed hyperpigmentation with hypertrichosis, dysmorphic features, and spleen and liver enlargement. Failure to thrive, sensorineural deafness, retarded psychomotor development, and a Rosai-Dorfman like cheek lesion developed subsequently. The febrile episodes did not respond to tumor necrosis factor α antagonists and interleukin-1. Sequencing of the SLC29A3 gene revealed a homozygous missense mutation c.1088G>A (p.Arg363Gln). These observations suggest that a newly identified mutation in the SLC29A3 gene may be associated with an autoinflammatory disorder. Genetic defects in SLC29A3 should be considered in patients with autoinflammatory manifestations, recurrent febrile attacks, and 1 or more of the symptoms found in the broad spectrum of SLC29A3-related disorders (especially hyperpigmentation with hypertrichosis).
    PEDIATRICS 03/2013; · 4.47 Impact Factor
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    ABSTRACT: BACKGROUND AND AIM: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations of the MEFV gene. We analyse the impact of ethnic, environmental and genetic factors on the severity of disease presentation in a large international registry. METHODS: Demographic, genetic and clinical data from validated paediatric FMF patients enrolled in the Eurofever registry were analysed. Three subgroups were considered: (i) patients living in the eastern Mediterranean countries; (ii) patients with an eastern Mediterranean ancestry living in western Europe; (iii) Caucasian patients living in western European countries. A score for disease severity at presentation was elaborated. RESULTS: Since November 2009, 346 FMF paediatric patients were enrolled in the Eurofever registry. The genetic and demographic features (ethnicity, age of onset, age at diagnosis) were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. European patients had a lower frequency of the high penetrance M694V mutation and a significant delay of diagnosis (p<0.002). Patients living in eastern Mediterranean countries had a higher frequency of fever episodes/year and more frequent arthritis, pericarditis, chest pain, abdominal pain and vomiting compared to the other two groups. Multivariate analysis showed that the variables independently associated with severity of disease presentation were country of residence, presence of M694V mutation and positive family history. CONCLUSIONS: Eastern Mediterranean FMF patients have a milder disease phenotype once they migrate to Europe, reflecting the effect of environment on the expression of a monogenic disease.
    Annals of the rheumatic diseases 03/2013; · 8.11 Impact Factor
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    Pediatric Rheumatology 02/2013; · 1.47 Impact Factor
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    ABSTRACT: OBJECTIVE: Radiographic damage was recently identified as a feature of poor prognosis in polyarticular juvenile idiopathic arthritis (pJIA). However, most radiographic studies did not differentiate pJIA from other subtypes of JIA and little is known about pJIA persisting into adulthood. We describe radiological peripheral involvement in young adults with pJIA compared to patients with rheumatoid arthritis (RA). METHODS: All consecutive patients with pJIA followed in a transition program were included. Age, sex, disease duration, and medical or surgical treatment information was collected. Laboratory tests and standard radiographs of the hands and wrists, feet, and hips were analyzed by 2 independent radiologists blinded to the diagnosis. One RA control group (age < 55 yrs), matched for sex and disease duration, was recruited. RESULTS: Forty-three patients with pJIA and 59 with RA were included. Radiographs showed hand lesions in 79% of pJIA and 86% of patients with RA, feet lesions in 74% of pJIA and 80% of patients with RA, and hip damage in 35% of pJIA and 17% of patients with RA (p = nonsignificant). Specific to the juvenile forms were lower frequency of proximal interphalangeal joint involvement (51% vs 76%; p = 0.03) and higher risk of bilateral hip damage (86% vs 25%; p < 0.01) than in adult RA. CONCLUSION: Structural peripheral damage is as common and as severe in young adults with pJIA as in adults with RA. The main specific feature of pJIA seems to be a high risk of bilateral hip damage. This requires a particular monitoring of pJIA patients with unilateral hip involvement to detect bilateralization.
    The Journal of Rheumatology 02/2013; · 3.26 Impact Factor
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    ABSTRACT: BACKGROUND: There is sparse knowledge about grading tenosynovitis using MRI. OBJECTIVE: The purpose of this study was to assess the reliability of a tenosynovitis MRI scoring system in juvenile idiopathic arthritis. MATERIALS AND METHODS: Children with juvenile idiopathic arthritis and wrist involvement were enrolled in two paediatric centres, from October 2006 to January 2010. The extensor (compartments II, IV and VI) and flexor tendons were assessed for the presence of tenosynovitis on T1-weighted postcontrast fat-saturated MR images and were scored from 0 (normal) to 2 (moderate to severe) by two observers independently. Intra- and interobserver agreement was assessed. RESULTS: Ninety children (age range: 5-18.5 years) were included, of whom 34 had tenosynovitis involving extensors and 28 had tenosynovitis involving flexors. A total of 360 tendon areas were analysed, of which 114 had tenosynovitis (86/270 extensors and 28/90 flexors). Intra-reader 1 agreement was excellent for the extensors (k = 0.82-0.91) and for the flexors (k = 0.85); intra-reader 2 agreement was moderate to good for the extensors (k = 0.51-0.72) and good for the flexors (k = 0.64). Inter-reader agreement was good for the extensors (k = 0.69-0.73) and moderate for the flexors (k = 0.49). CONCLUSION: The proposed MRI scoring system for the assessment of wrist tenosynovitis in juvenile idiopathic arthritis appears feasible with an observer agreement sufficient for clinical use.
    Pediatric Radiology 02/2013; · 1.57 Impact Factor
  • Pierre Quartier, Romain K Gherardi
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    ABSTRACT: Juvenile dermatomyositis (JDM) is a systemic, inflammatory, idiopathic disease, mainly affecting the skin and the muscles, starting before the age of 16, with an incidence around one case per 1 million children. Some patients display typical features of JDM without skin involvement, or even without muscle involvement; however, both tissues are affected over time in most cases. Diagnosis criteria were established by Bohan and Peter 35 years ago, based on the presence of typical skin rash and proximal muscle involvement. Other conditions have to be ruled out before making a diagnosis of JDM, such as other connective tissue diseases, polymyositis, infectious/postinfectious myositis, genetic diseases, or metabolic or drug-induced myopathies. Unlike adult-onset dermatomyositis, JDM is exceptionally associated with a malignant disease. JDM may also affect several organs, including the lungs and the digestive tract. In a subset of patients, glucose intolerance, lipodystrophia and/or calcinosis develop. Delay in treatment initiation or inadequate treatment may favor diffuse, debilitating calcinosis. JDM patients have to be referred to reference pediatric centers to properly assess disease activity and disease-related damage (including low bone density in most cases), and to define the best treatment. Long-lasting corticosteroid therapy remains the gold standard, together with physiotherapy. Ongoing clinical trials are assessing the effect of several immunosuppressive and immunomodulatory drugs, which may help to control the disease and possibly demonstrate a corticosteroid-sparing effect. Most patients respond to treatment; relapses are frequent but a complete disease remission is achieved in most cases before adulthood.
    Handbook of Clinical Neurology 01/2013; 113:1457-63.
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    ABSTRACT: BACKGROUND: Juvenile dermatomyositis (JDM) is the main cause of chronic idiopathic inflammatory myopathy of autoimmune origin in children. The aim of this multicenter prospective study was to describe respiratory status and treatment of children followed for JDM. METHODS AND PATIENTS: Clinical manifestations, pulmonary function tests (PFT), chest high-resolution computed tomography (HRCT) scan results, and treatments and their adverse effects were analyzed in children followed for JDM. RESULTS: Twenty-one patients (median age: 9.9 years; range: 20 months-18 years) were included. The median of disease duration at the time of the analysis was 3 years (range: 6 months-9 years 4 months). Overall 16 (76%) of 21 children presented with a respiratory involvement related to JDM including interstitial lung disease (n = 3) and/or respiratory muscle involvement (n = 7). Seven patients presented with other nonspecific manifestations. Three children had aspiration pneumonia. A chest HRCT was performed in 15 children, and abnormalities were observed in 12. PFT were performed in 20 of 21 patients. Seven showed functional abnormalities: restrictive ventilatory defect (n = 3) or obstructive ventilatory defect (n = 4). Six patients had abnormal respiratory muscle tests, including three with a restrictive ventilatory defect and one with an obstructive ventilatory defect. One other child with an acute aspiration pneumonia had a clearly muscle respiratory involvement but was too young to perform respiratory muscle tests and confirm this diagnosis. Treatment comprised systemic corticosteroid for all patients and adjuvant immunosuppressive therapy for 11. Adverse effects linked to treatment were reported in eight patients. CONCLUSION: The frequency of lung involvement in children with JDM justifies systematic respiratory assessment with PFT including measures of respiratory muscle strength. We suggest that a chest HRCT scan is indicated in cases of respiratory symptoms and/or PFT abnormalities. Longitudinal studies are needed to assess pediatric characteristics, long-term outcomes, and responses to treatment taking into account the risk-benefit ratio. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.
    Pediatric Pulmonology 12/2012; · 2.38 Impact Factor
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    ABSTRACT: Background Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1β monoclonal antibody, in two trials. Methods In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilogram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. Results At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to placebo (74% of patients in the canakinumab group had no flare, vs. 25% in the placebo group, according to Kaplan-Meier estimates; hazard ratio, 0.36; P=0.003). The average glucocorticoid dose was reduced from 0.34 to 0.05 mg per kilogram per day, and glucocorticoids were discontinued in 42 of 128 patients (33%). The macrophage activation syndrome occurred in 7 patients; infections were more frequent with canakinumab than with placebo. Conclusions These two phase 3 studies show the efficacy of canakinumab in systemic JIA with active systemic features. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT00889863 and NCT00886769 .).
    New England Journal of Medicine 12/2012; 367(25):2396-2406. · 51.66 Impact Factor
  • Biology of Blood and Marrow Transplantation 12/2012; · 3.94 Impact Factor
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    ABSTRACT: We analysed the long term outcomes of paediatric patients registered in the European Group for Blood and Marrow Transplantation (EBMT) database who received hematopoietic stem cell transplantation (HSCT) for severe treatment refractory autoimmune cytopenia. With a median follow-up of 100 months, event free survival was 54% overall, with no significant difference between allogeneic (n=15) andautologous (n=7) HSCT (58% versus 42%, p= 0.5). Despite a trend to failure of response or relapse following autologous compared with allogeneic HSCT, the difference was not significant (43% versus 13%, p=0.3). Treatment related mortality was high in both HSCT groups (29% versus 16%; p= 0.09). Based on the limited numbers in this retrospective analysis, both allogeneic and autologous HSCT may induce complete and persistent responses in around half of pediatric patients with severe refractory autoimmune cytopenia, although treatment related toxicity is high.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2012; · 3.15 Impact Factor

Publication Stats

3k Citations
735.40 Total Impact Points

Institutions

  • 2010–2014
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Hospital General de Niños Pedro de Elizalde
      Buenos Aires, Buenos Aires F.D., Argentina
  • 2009–2014
    • Université René Descartes - Paris 5
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
    • Klinikum Stuttgart
      Stuttgart, Baden-Württemberg, Germany
    • Centre Hospitalier de Dreux
      Dreux, Centre, France
  • 2013
    • Institut Imagine
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • National and Kapodistrian University of Athens
      Athínai, Attica, Greece
    • Universitair Ziekenhuis Leuven
      Louvain, Flanders, Belgium
  • 2011
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
    • CHU de Lyon - Hôpital Femme-Mère-Enfant
      Lyons, Rhône-Alpes, France
  • 2008–2010
    • IRCCS Istituto G. Gaslini
      Genova, Liguria, Italy
  • 2000–2008
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
  • 2005
    • McGill University
      Montréal, Quebec, Canada
    • Imperial College London
      • Department of Medicine
      London, ENG, United Kingdom
  • 2003–2004
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
  • 1999
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France