Didier Samuel

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (590)2578.51 Total impact

  • Journal of the European Academy of Dermatology and Venereology 09/2014; · 2.69 Impact Factor
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    ABSTRACT: Intensive care information systems (ICIS) implemented in intensive care unit (ICU) were shown to improve patient safety, reduce medical errors and increase the time devolved by medical/nursing staff to patients care. Data on the real impact of ICIS on patient outcome are scarce. This study aimed to evaluate the effects of ICIS on the outcome of critically-ill patients. From January 2004 to August 2006, 1,397 patients admitted to our ICU were enrolled in this observational study. This period was divided in two phases: before the implementation of ICIS (BEFORE) and after implementation of ICIS (AFTER). We compared standard ICU patient's outcomes: mortality, length of stay in ICU, hospital stay, and the re-admission rate depending upon BEFORE and AFTER. Although patients admitted AFTER were more severely ill than those of BEFORE (SAPS II: 32.1 ± 17.5 vs. 30.5 ± 18.5, p = 0.014, respectively), their ICU length of stay was significantly shorter (8.4 ± 15.2 vs. 6.8 ± 12.9 days; p = 0.048) while the re-admission rate and mortality rate were similar (4.4 vs. 4.2 %; p = 0.86, and 9.6 vs 11.2 % p = 0.35, respectively) in patients admitted AFTER. We observed that the implementation of ICIS allowed shortening of ICU length of stay without altering other patient outcomes.
    Journal of clinical monitoring and computing. 06/2014;
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    ABSTRACT: Abstract BACKGROUND & AIMS: Acute-on Chronic Liver Failure (ACLF) is a frequent syndrome (30% prevalence) characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality. This study develops and validates a specific prognostic score for ACLF patients. METHODS: Data from 1,349 patients included in the CANONIC study were used. First, a simplified organ function scoring system (CLIF-Consortium Organ Failure score, CLIF-C OFs) to diagnose ACLF was developed using data from all patients. Subsequently, in 275 patients with ACLF, CLIF-C OFs and two other independent predictors of mortality (age and white-cell count) were combined to develop a specific prognostic score for ACLF (CLIF CONSORTIUM score for ACLF, CLIF-C ACLFs). Concordance index (C-index) was used to compare the discrimination abilities of CLIF-C ACLFs, MELD (MELDs), MELD-Sodium (MELD-Nas) and Child-Pugh (CPs) scores. CLIF-C ACLFs was validated in an external cohort and assessed for sequential use. RESULTS: CLIF-C ACLFs showed a significantly higher predictive accuracy than MELDs, MELD-Nas and CPs, reducing (19-28%) the corresponding prediction error rates at all the main time-points after ACLF diagnosis (28, 90, 180 and 365 days) in both the CANONIC and the external validation cohort. CLIF-C ACLFs computed at 48 hours, 3-7 days and 8-15 days after ACLF diagnosis predicted 28-day mortality significantly better than at diagnosis. CONCLUSIONS: CLIF-C ACLFs at ACLF diagnosis is superior to MELDs and MELD-Nas in predicting mortality. CLIF-C ACLFs is a clinically relevant, validated scoring system that can be used sequentially to stratify the risk of mortality in ACLF patients.
    Journal of Hepatology 06/2014; · 9.86 Impact Factor
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    ABSTRACT: Reducing the incidence of hepatocellular carcinoma (HCC) in HIV-infected patients has become a serious problem when managing these patients. There are many explanations for this disease evolution, which notably include their longer survival under effective antiviral therapy and also the more rapid evolution of chronic liver disease. Despite recent advances in the management of hepatitis B (HBV) and hepatitis C (HCV) viral diseases, which will probably increase the number of patients achieving a virological response, HIV-infected patients with cirrhosis are still at risk of the onset of HCC. This evolution to HCC is also correlated to other comorbidities such as excessive alcohol consumption and nonalcoholic steatohepatitis (NASH). HCC thus remains a public health issue in this population. The poor prognosis and aggressiveness of HCC have been fully demonstrated, but the mechanisms underlying this aggressiveness are not yet well defined. As well as underlying mechanisms that contribute to accelerating hepatocarcinogenesis in HIV-infected patients, there are other reasons why HIV-infected patients should be considered a higher risk population. This review discusses the principal epidemiological determinants; the mechanisms of pathogenesis; and the treatment of HCC in HIV/HBV and HIV/HCV coinfected patients. It also discusses the probable need to develop a specific screening policy for HCC in this population in order to prevent the rapid development and to make them more amenable to a curative treatment.
    AIDS (London, England) 04/2014; · 4.91 Impact Factor
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    ABSTRACT: We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis. In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n=299) or boceprevir (n=212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy (SVR12) and safety. This observational study did not allow for direct comparison of the 2 regimens. Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count >100,000/mm(3). Severe adverse events occurred in 49.9% of cases, including liver decompensation or severe infections in 10.4% and death in 2.2%. In multivariate analysis, baseline serum albumin <35 g/L and baseline platelet counts ≤100,000/mm(3) predicted severe side effects or death. Relatively high percentages of real-life, treatment-experienced, patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe side. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. ClinicalTrials.gov number, NCT01514890.
    Gastroenterology 04/2014; · 12.82 Impact Factor
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    ABSTRACT: Recurrent hepatitis C after liver transplantation (LT) is associated with rapid fibrosis progression. The aim of this study was to evaluate the cumulative risk for severe fibrosis and the factors influencing it. Two hundred and fifty LT patients were included 1 to 15years after LT. Recurrence of chronic hepatitis C on liver graft was classified according to Metavir score. Kaplan-Meyer estimates for actuarial progression to severe fibrosis (Metavir>F3) showed a probability of 15.2% and 44.5% at 5 and 10years, respectively. Predictive factors for progression to severe fibrosis were: use of tacrolimus as main CNI, recipient age at time of biopsy<55, donor age ≥45, graft HCV re-infection<3months, biologically suspected graft re-infection and lack of response to antiviral treatment after LT. Multivariate analysis disclosed that only donor age ≥45 (hazard ratio 2.243, 95%CI 1.264-3.983, P=0.0058) and lack of response to antiviral treatment (hazard ratio 2.816, 95%CI 1.227-6.464, P=0.0146) were associated to severe fibrosis. Our study confirms that donor age ≥45 and lack of response to antiviral treatment after LT are major predictive factors of progression of HCV recurrence on liver graft.
    Gastroentérologie Clinique et Biologique 03/2014; · 0.80 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) infection is one of the leading causes of end-stage liver disease and the main indication for liver transplantation (LT) in most countries. All patients who undergo LT with detectable serum HCV RNA experience graft reinfection. Between 20 and 30% of patients have developed cirrhosis at 5 years post-LT. The outcome of transplant patients with cirrhosis on the graft is severe, with a rate of decompensation at 1 year of approximately 40%. To date, retransplantation is the only option in patients with decompensated liver disease. Until 2011, standard antiviral therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV), was the only effective therapy. Obtaining a sustained virological response (SVR) in patients with LT greatly improves overall and graft survival but this only occurs in 30% of transplanted patients. Direct acting antivirals (DAAs) such as protease inhibitors (PI), polymerase or other non-structural proteins inhibitors represent a new era in HCV associated liver disease. Although their use in the field of LT will certainly be essential there are some limitations because of safety and tolerance. One limitation is the potential interaction with calcineurin inhibitors. We describe the results of triple therapy with boceprevir (BOC) or telaprevir (TVR) for efficacy and safety and comment on future therapeutic strategies in liver transplant recipients.
    Liver international: official journal of the International Association for the Study of the Liver 02/2014; 34 Suppl 1:46-52. · 3.87 Impact Factor
  • The Lancet 01/2014; 383(9913):218. · 39.06 Impact Factor
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    ABSTRACT: Introduction Mortality rate of patients with cirrhosis admitted to the intensive care unit (ICU) and requiring mechanical ventilation varies between 60 and 91%. The aim of our study is to assess the prognosis of these patients, their 1-year outcome and to analyze predictive factors of long-term mortality. Methods From May 2005 to May 2011, we studied 246 consecutive patients with cirrhosis requiring mechanical ventilation either at admission or during their ICU stay. Results Alcohol was the most common etiology of the cirrhosis (69%). Bleeding related to portal hypertension (30%) and severe sepsis (33%) were the most common reasons for admission. ICU and hospital mortality were respectively 65.9% and 70.3%. Prognostic severity scores, the need for other organ support therapy, infection, and total bilirubin value at ICU admission were significantly associated with ICU mortality. Eighty-four patients (34.1%) were discharged from the ICU. Among these patients, the one-year survival was only of 32%. Logistic regression analysis, using survival at one year as the endpoint, identified two independent risk factors: the length of ventilation (odds ratio [OR] = 1.1; 95% CI, 1.0–1.2; p = 0.02) and total bilirubin at ICU discharge (OR = 1.3; 95% CI, 1.1–1.5; p = 0.006). Conclusion Patients with cirrhosis admitted to the liver ICU and who required mechanical ventilation have a poor prognosis with a 1-year mortality of 89%. At ICU discharge, a total bilirubin level higher than 64.5 μmol/L and length of ventilation higher than 9 days could help the hepatologists to identify patients at risk of death in the year following the ICU discharge.
    Journal of Hepatology. 01/2014; 60(3):570–578.
  • Bruno Roche, Didier Samuel
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    ABSTRACT: Antiviral therapy using newer nucleos(t)ide analogues with lower resistance rates such as entecavir or tenofovir could suppress hepatitis B virus (HBV) replication, improve liver function, delay or obviate the need for liver transplantation in some patients, and reduce the risk of HBV recurrence. The combination of long-term antiviral and low-dose hepatitis B immune globulin (HBIG) can effectively prevent HBV recurrence in more than 90% of transplant recipients. Some form of HBV prophylaxis needs be continued indefinitely after transplantation. However, in patients with a low risk of HBV recurrence (i.e. HBV DNA levels undetectable before transplantation), it is possible to discontinue HBIG and maintain long-term antiviral therapy. A more cautious approach to prophylaxis regimen is necessary for those patients with high pretransplant HBV DNA levels, those with limited antiviral options if HBV recurrence occurs (i.e. HIV or HDV coinfection, preexisting drug resistance), those with a high risk of hepatocellular carcinoma recurrence, and those with a risk of noncompliance to antiviral therapy. © 2014 S. Karger AG, Basel.
    Intervirology 01/2014; 57(3-4):196-201. · 1.89 Impact Factor
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    ABSTRACT: Solid cancers are a major adverse outcome of liver transplantation. Recent reassessments have revealed insights into causal factors, primarily centering on modulations of the natural killer (NK) cell compartment in liver transplant recipients. In the presence of cytomegalovirus, the clonal expansion of differentiated NK cells could restrict the diversity of the NK repertoire favoring the development of certain tumors.
    Oncoimmunology. 01/2014; 3:e28782.
  • Transplantation 12/2013; 96(11):e79-81. · 3.78 Impact Factor
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    ABSTRACT: Solid cancers are a major adverse outcome of orthotopic liver transplantation (OLT). Although the use of chronic immunosuppression is known to play a role in T cell impairment, recent insights into the specificities of NK cells led us to reassess the potential modulation of this innate immune cell compartment after transplantation. Our extensive phenotypic and functional study reveals that the development of specific de novo noncutaneous tumors post-OLT is linked to unusual NK cell subsets with maturation defects and to uncommon cytokine production associated with the development of specific cancers. Remarkably, in CMV(+) patients, the development de novo head/neck or colorectal tumors is linked to an aberrant expansion of NK cells expressing NKG2C and a high level of intracellular TNF-α, which impact on their polyfunctional capacities. In contrast, NK cells from patients diagnosed with genitourinary tumors possessed a standard immature signature, including high expression of NKG2A and a robust production of IFN-γ. Taken together, our results suggest that under an immunosuppressive environment, the interplay between the modulation of NK repertoire and CMV status may greatly hamper the spectrum of immune surveillance and thus favor outgrowth and the development of specific de novo tumors after OLT.
    The Journal of Immunology 12/2013; · 5.52 Impact Factor
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    ABSTRACT: Mortality rate of patients with cirrhosis admitted to the Intensive Care Unit (ICU) and requiring mechanical ventilation varies between 60 and 91%. The aim of our study is to assess the prognosis of these patients, their 1-year outcome and to analyze predictive factors of long-term mortality. from May 2005 to May 2011, we studied 246 consecutive patients with cirrhosis requiring mechanical ventilation either at admission or during their ICU stay. Alcohol was the most common etiology of the cirrhosis (69%). Bleeding related to portal hypertension (30%) and severe sepsis (33%) were the most common reasons for admission. ICU and hospital mortality were respectively 65.9% and 70.3%. Prognostic severity scores, the need for other organ support therapy, infection and total bilirubin value at ICU admission were significantly associated with ICU mortality. Eighty-four patients (34,1%) were discharged from the ICU. Among these patients, the one-year survival was only of 32%. Logistic regression analysis, using survival at one year as the endpoint, identified two independent risk factors: the length of ventilation (odds ratio [OR] = 1.1; 95% CI, 1.0-1.2; p=0.02) and total bilirubin at ICU discharge (OR=1.3; 95% CI, 1.1-1.5; p=0.006). Patients with cirrhosis admitted to the liver ICU and who required mechanical ventilation have a poor prognosis with a 1-year mortality of 89%. At ICU discharge, a total bilirubin level higher than 64.5 and length of ventilation higher than 9 days could help the hepatologists to identify patientsat risk of death in the year following the ICU discharge.
    Journal of Hepatology 11/2013; · 9.86 Impact Factor
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    ABSTRACT: Liver transplantation (LT) is the therapeutic option for severe complications of Wilson's disease (WD). To report on the long-term outcome of WD patients following LT. The medical records of 121 French patients transplanted for WD between 1985 and 2009 were reviewed retrospectively. Seventy-five patients were adults (median age: 29 yrs, (18-66)) and 46 were children (median age: 14 yrs, (7-17)). The indication for LT was (1) fulminant/subfulminant hepatitis (n=64, 53%), median age = 16 yrs (7-53), (2) decompensated cirrhosis (n=50, 41%), median age = 31.5 yrs (12-66) or (3) severe neurological disease (n= 7, 6%), median age = 21.5 yrs (14.5-42). Median post-transplant follow-up was 72 months (0-23.5). Actuarial patient survival rates were 87% at 5, 10 and 15 years. Male gender, pre-transplant renal insufficiency, non elective procedure and neurological indication were significantly associated with poorer survival rate. None of these factors remained statistically significant under multivariate analysis, In patients transplanted for hepatic indications, the prognosis was poorer in case of fulminant or subfulminant course, non elective procedure, pre-transplant renal insufficiency and in patients transplanted before 2000. Multivariate analysis disclosed that only recent period of LT was associated with better prognosis. At last visit, the median calculated glomerular filtration rate was 93 mL/min (33-180); 11/93 patients (12%) had stage II renal insufficiency and none had stage III. Liver failure associated with WD is a rare indication for LT (<1%) which achieves an excellent long-term outcome, including renal function.
    Journal of Hepatology 11/2013; · 9.86 Impact Factor
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    ABSTRACT: Chinese translation BACKGROUND: Albumin dialysis with the Molecular Adsorbent Recirculating System (MARS) (Gambro, Lund, Sweden), a noncell artificial liver support device, may be beneficial in acute liver failure (ALF). To determine whether MARS improves survival in ALF. Randomized, controlled trial. (ClinicalTrials.gov: NCT00224705) SETTING: 16 French liver transplantation centers. 102 patients with ALF. Conventional treatment (n = 49) or MARS with conventional treatment (n = 53), stratified according to whether paracetamol caused ALF. 6-month survival and secondary end points, including adverse events. 102 patients (mean age, 40.4 years [SD, 13]) were in the modified intention-to-treat (mITT) population. The per-protocol analysis (49 conventional, 39 MARS) included patients with at least 1 session of MARS of 5 hours or more. Six-month survival was 75.5% (95% CI, 60.8% to 86.2%) with conventional treatment and 84.9% (CI, 71.9% to 92.8%) with MARS (P = 0.28) in the mITT population and 75.5% (CI, 60.8% to 86.2%) with conventional treatment and 82.9% (CI, 65.9% to 91.9%) with MARS (P = 0.50) in the per-protocol population. In patients with paracetamol-related ALF, the 6-month survival rate was 68.4% (CI, 43.5% to 86.4%) with conventional treatment and 85.0% (CI, 61.1% to 96.0%) with MARS (P = 0.46) in the mITT population. Sixty-six of 102 patients had transplantation (41.0% among paracetamol-induced ALF; 79.4% among non-paracetamol-induced ALF) (P < 0.001). Adverse events did not significantly differ between groups. The short delay from randomization to liver transplantation (median, 16.2 hours) precludes definitive efficacy or safety evaluations. This randomized trial of MARS in patients with ALF was unable to provide definitive efficacy or safety conclusions because many patients had transplantation before administration of the intervention. Acute liver failure not caused by paracetamol was associated with greater 6-month patient survival. Assistance Publique-Hôpitaux de Paris.
    Annals of internal medicine 10/2013; 159(8):522-531. · 13.98 Impact Factor
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    Didier Samuel
    Journal of Hepatology 10/2013; · 9.86 Impact Factor
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    ABSTRACT: Objectives: To correlate human herpesvirus 6 (HHV-6) viral load with pathologic features in graft acute hepatitis of unknown origin. Methods: Liver frozen samples from 26 patients with graft hepatitis of unknown origin were available for HHV-6 DNA quantification. Results: In 10 (38.5%) of 26 liver samples, HHV-6 DNA was detectable, with a median viral load of 3.84 log10 copies/10(6) cells. Confluent periportal necrosis was observed in 4 of 10 patients and associated with high viral load. These 4 patients responded to antiviral therapy. Mild unspecific hepatitis was observed in 4 patients with low intragraft viral load and in 2 patients with high viral load in a context of deep immunosuppression. Patients with HHV-6-negative graft hepatitis disclosed lobular necrotico-inflammatory activity without periportal necrosis. Conclusions: Our study provides data supporting the pathogenic role of HHV-6 for liver allografts. The presence of confluent periportal necrosis could be a clue for prompt diagnosis of HHV-6-induced graft hepatitis.
    American Journal of Clinical Pathology 09/2013; 140(3):403-9. · 2.88 Impact Factor
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    ABSTRACT: Autoimmune hepatitis (AIH) after liver transplantation has been defined histologically as a "hepatitic" pattern of injury, characterized by lymphoplasmacytic inflammation with necroinflammatory activity (NIA), comparable with findings seen in native livers. This definition, however, is difficult to apply in practice because specific histologic criteria are not clearly delineated. This study aimed to determine which histologic features correlated best with clinical and serologic features of dAIH. Index liver biopsies from patients with autoimmune-like hepatitis transplanted for non-AIH in two centers (n=35 and 20) were reviewed. Histologic features were correlated with the clinical diagnosis of AIH based on a retrospective review of clinical and serologic data, including therapeutic response. A clinical diagnosis of AIH was retrospectively assigned to 24 of 35 (68%) and 18 of 20 (90%) patients, respectively (P=0.10). In multivariate analysis, centrilobular NIA and centrilobular plasma cell (PC) ratio of 30% to 50% were independently discriminating for a clinical diagnosis of AIH (P=0.04 and 0.05, respectively). The best level of predictability (99.6%) was mathematically achieved when severe centrilobular NIA and centrilobular PC ratio of 30% to 50% were both present. A histologic pattern of centrilobular injury including increased NIA and increased PC infiltration correlates with measurements of autoimmunity in liver recipients. It could be used to segregate cases for further study and introduced into the AIH scoring systems when applied in the context of liver transplantation.
    Transplantation 08/2013; · 3.78 Impact Factor

Publication Stats

9k Citations
2,578.51 Total Impact Points

Institutions

  • 2007–2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Baylor College of Medicine
      • Department of Surgery
      Houston, TX, United States
  • 1997–2014
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • University of Valencia
      Valenza, Valencia, Spain
    • King's College London
      Londinium, England, United Kingdom
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 1991–2013
    • Université Paris-Sud 11
      • Faculty of Medicine
      Orsay, Île-de-France, France
  • 1990–2013
    • Hôpital Paul-Brousse – Hôpitaux universitaires Paris-Sud
      Île-de-France, France
    • Groupe Hospitalier Paul Guiraud
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France
  • 1999–2012
    • French Institute of Health and Medical Research
      • Center of Biomedical Research Bichat-Beaujon
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud)
      Lutetia Parisorum, Île-de-France, France
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2009
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      Créteil, Île-de-France, France
  • 2005
    • University of California, San Francisco
      San Francisco, California, United States
    • Centre Hospitalier Universitaire de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
  • 2001
    • CHU de Lyon - Hôpital de la Croix-Rousse
      Lyons, Rhône-Alpes, France
  • 1996
    • Osaka Medical College
      Takatuki, Ōsaka, Japan
  • 1995
    • Hadassah Medical Center
      • Department of Medicine
      Jerusalem, Jerusalem District, Israel
  • 1993
    • University of Florence
      • Dipartimento di Medicina Sperimentale e Clinica
      Florens, Tuscany, Italy
  • 1990–1993
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France