Sylvie Chevret

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

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Publications (430)2655.33 Total impact

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    ABSTRACT: We analysed the prognostic significance of minimal residual disease (MRD) level in adult patients with acute myeloid leukemia (AML) treated in the randomized gemtuzumab ozogamicin (GO) ALFA-0701 trial. Levels of WT1 and NPM1 gene transcripts were assessed using cDNA-based real-time quantitative PCR in 183 patients with WT1 overexpression and in 77 patients with NMP1 mutation (NPM1mut) at diagnosis. Positive WT1 MRD (defined as > 0.5% in the peripheral blood) after induction and at the end of treatment were both significantly associated with a higher risk of relapse and a shorter overall survival (OS). Positive NPM1mut MRD (defined as > 0.1% in the bone marrow) after induction and at the end of treatment also predicted a higher risk of relapse, but did not influence OS. Interestingly, the achievement of a negative NPM1mut MRD was significantly more frequent in patients treated in the GO arm compared to those treated in control arm (39 % versus 7% (p=0.006) after induction and 91% versus 61% (p=0.028) at the end of treatment). However, GO did not influence WT1 MRD levels. Our study supports the prognostic significance of MRD assessed by WT1 and NPM1mut transcript levels and show that NPM1 MRD is decreased by GO treatment.
    Oncotarget 07/2014; · 6.64 Impact Factor
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    ABSTRACT: Gemtuzumab ozogamicin was the first example of antibody-directed chemotherapy in cancer, and was developed for acute myeloid leukaemia. However, randomised trials in which it was combined with standard induction chemotherapy in adults have produced conflicting results. We did a meta-analysis of individual patient data to assess the efficacy of adding gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia.
    The Lancet Oncology 07/2014; · 25.12 Impact Factor
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    ABSTRACT: Background Kidney transplant recipients are at risk for life-threatening infections, which may affect the long-term prognosis.Methods We retrospectively included all kidney transplant recipients admitted for sepsis, severe sepsis, or septic shock to the medical intensive care unit (ICU) of the Saint-Louis Hospital, Paris, France, between 2000 and 2010. The main objective was to identify factors associated with survival without graft impairment 90 days after ICU discharge.ResultsData were available for 83 of 100 eligible patients. The main sites of infection were the lungs (54%), urinary tract (24%), and bloodstream (22%). Among documented infections (55/83), 80% were bacterial. Fungal infections were more common among patients transplanted after 2005 (5% vs. 23%, P = 0.02). Mechanical ventilation was used in 46 (56%) patients, vasopressors in 39 (47%), and renal replacement therapy (RRT) in 34 (41%). In-hospital and day-90 mortality rates were 20% and 22%, respectively. On day 90, among the 65 survivors, 39 (47%) had recovered their previous graft function and 26 (31%) had impaired graft function, including 16 (19%) who were dependent on RRT. Factors independently associated with day-90 survival and graft function recovery were baseline serum creatinine (odds ratio [OR] for a 10 μmol/L increase 0.94, 95% confidence interval [CI] 0.88–1.00) and cyclosporine therapy (OR 0.30, 95% CI 0.11–0.79).Conclusion Sepsis was chiefly related to bacterial pneumonia or urinary tract infection. Pneumocystis jirovecii was the leading opportunistic agent, with a trend toward an increase over time. Infections often induced severe graft function impairment. Baseline creatinine and cyclosporine therapy independently predicted the outcome.
    Transplant Infectious Disease 06/2014; · 1.98 Impact Factor
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    ABSTRACT: With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by Ig/TCR minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as primary endpoint. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with post-induction MRD level ≥ 10(-4) and unfavorable genetic characteristics (i.e. MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL; and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-ALL). These two factors allowed definition of a new risk classification, which is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL, not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and 2005 trials. Both trials were registered at ClinicalTrials.gov (GRAALL-2003, NCT00222027; GRAALL-2005, NCT00327678).
    Blood 04/2014; · 9.78 Impact Factor
  • Djillali Annane, Sylvie Chevret
    JAMA The Journal of the American Medical Association 03/2014; 311(10):1069-70. · 29.98 Impact Factor
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    ABSTRACT: We recently showed that the addition of fractionated doses of gemtuzumab ozogamicin (GO) to standard chemotherapy improves clinical outcome of acute myeloid leukemia (AML) patients. In the present study, we performed mutational analysis of 11 genes (FLT3, NPM1, CEBPA, MLL, WT1, IDH1/2, RUNX1, ASXL1, TET2, DNMT3A), EVI1 overexpression screening, and 6.0 single-nucleotide polymorphism array (SNP-A) analysis in diagnostic samples of the 278 AML patients enrolled in the ALFA-0701 trial. In cytogenetically normal (CN) AML (n=146), 38% of the patients had at least 1 SNP-A lesion and 89% of the patients had at least 1 molecular alteration. In multivariate analysis, the independent predictors of higher cumulative incidence of relapse were unfavorable karyotype (P = 0.013) and randomization in the control arm (P = 0.007) in the whole cohort, and MLL partial tandem duplications (P = 0.014) and DNMT3A mutations (P = 0.010) in CN-AML. The independent predictors of shorter overall survival (OS) were unfavorable karyotype (P <0.001) and SNP-A lesion(s) (P = 0.001) in the whole cohort, and SNP-A lesion(s) (P = 0.006), DNMT3A mutations (P = 0.042) and randomization in the control arm (P = 0.043) in CN-AML. Interestingly, CN-AML patients benefited preferentially more from GO treatment as compared to AML patients with abnormal cytogenetics (hazard ratio for death, 0.52 versus 1.14; test for interaction, P = 0.04). Although the interaction test was not statistically significant, the OS benefit associated with GO treatment appeared also more pronounced in FLT3 internal tandem duplication positive than in negative patients.
    Oncotarget 01/2014; · 6.64 Impact Factor
  • Jérôme Lambert, Sylvie Chevret
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    ABSTRACT: Assessments of the discriminative performance of prognostic models have led to the development of several measures that extend the concept of discrimination as evaluated by the receiver operating characteristics curve and the area under the receiver operating characteristic curve (AUC) of diagnostic settings. Thus, several time-dependent-receiver operating characteristic curve and AUC(t) have been proposed. One of the most used, the cumulative/dynamic AUC(C,D)(t) is the probability that, given two randomly chosen patients, one having failed before t and the other having failed after t, the prognostic marker will be correctly ranked. In this paper, we propose a weighted AUC(C,D)(t) with time- and data-dependent weights as a summary measure of the mean AUC(C,D)(t), restricted to a finite time range to ensure its clinical relevance. A simulation study shows that estimated restricted mean AUC increased with the strength of association of the covariate with the outcome, with low impact of censoring, and adequate coverage of bootstrap confidence intervals. We illustrate this methodology to two real datasets from two randomized clinical trials to assess the prognostic factors of the overall mortality in patients who have compensated cirrhosis and to assess the prognostic factors of event-free survival in patients who have acute myeloid leukemia.
    Statistical Methods in Medical Research 01/2014; · 2.36 Impact Factor
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    ABSTRACT: Purpose Hypocitrullinemia has been suggested to be a prognostic factor for patients in intensive care. The aim of this ancillary study of the Corticosteroids and Intensive Insulin Therapy for Septic Shock prospective study was to investigate plasma l-citrulline concentrations and its relationship with inflammation and digestive bacterial translocation in patients with septic shock multiorgan failure and without primary intestinal disease or chronic renal failure. Methods Sixteen adult patients were selected. They were studied on day (D) 0 at hours (H) 0, 6, 12, 18, and 24 and on D4 (H96). Selected plasma amino acids and proteins, proinflammatory (tumor necrosis factor α [TNF-α]) and anti-inflammatory (interleukin [IL] 10) cytokine concentrations, and bacterial translocation were measured. Results Eight D14 survivors and 8 D14 nonsurvivors patients were studied. Citrulline was decreased on D0 (H0: 29 ± 10 vs nadir: 18 ± 6 μmol/L; P < .05). The citrulline nadir was lower (P < .01) in patients with digestive bacterial translocation than that in those without. Mean citrulline concentrations at H0 to H96 were not significantly different between survivors and nonsurvivors. In both groups, citrulline was significantly inversely correlated with C-reactive protein (r2 = 0.10, P < .01) on D0. No significant correlations were found between citrulline and albumin, transthyretin, TNF-α, IL-10, or TNF-α/IL-10 ratio. Conclusions At the onset of septic shock, plasma citrulline decreases and varies inversely with C-reactive protein and is lower when digestive bacterial translocation occurs. This finding could reflect an early acute intestinal dysfunction, but measurement of citrulline concentration does not appear to be able to predict the patients' mortality.
    Journal of Critical Care. 01/2014; 29(2):315.e1–315.e6.
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    ABSTRACT: Mantle cell lymphoma (MCL) is usually an aggressive disease. However, a few patients do have an "indolent" evolution (iMCL) defined by a long survival time without intensive therapy. Many studies highlight the prognostic role of additional genetic abnormalities, but these abnormalities are not routinely tested for and do not yet influence the treatment decision. We aimed to evaluate the prognostic impact of these additional abnormalities detected by conventional cytogenetic testing, as well as their relationships with the clinical characteristics and their value in identifying iMCL. All consecutive MCL cases diagnosed between 1995 and 2011 at four institutions were retrospectively selected on the basis of an informative karyotype with a t(11;14) translocation at the time of diagnosis. A total of 125 patients were included and followed for an actual median time of 35 months. The median overall survival (OS) and survival without treatment (TFS) were 73.7 and 1.3 months, respectively. In multivariable Cox models, a high mantle cell lymphoma international prognostic index score, a complex karyotype, and blastoid morphology were independently associated with a shortened OS. Spleen enlargement, nodal presentation, extra-hematological involvement, and complex karyotypes were associated with shorter TFS. A score based on these factors allowed for the identification of "indolent" patients (median TFS 107 months) from other patients (median TFS: 1 month). In conclusion, in this multicentric cohort of MCL patients, a complex karyotype was associated with a shorter survival time and allowed for the identification of iMCL at the time of diagnosis. © 2013 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 01/2014; 53(1):106-16. · 3.55 Impact Factor
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    ABSTRACT: Hypocitrullinemia has been suggested to be a prognostic factor for patients in intensive care. The aim of this ancillary study of the Corticosteroids and Intensive Insulin Therapy for Septic Shock prospective study was to investigate plasma l-citrulline concentrations and its relationship with inflammation and digestive bacterial translocation in patients with septic shock multiorgan failure and without primary intestinal disease or chronic renal failure. Sixteen adult patients were selected. They were studied on day (D) 0 at hours (H) 0, 6, 12, 18, and 24 and on D4 (H96). Selected plasma amino acids and proteins, proinflammatory (tumor necrosis factor α [TNF-α]) and anti-inflammatory (interleukin [IL] 10) cytokine concentrations, and bacterial translocation were measured. Eight D14 survivors and 8 D14 nonsurvivors patients were studied. Citrulline was decreased on D0 (H0: 29 ± 10 vs nadir: 18 ± 6 μmol/L; P < .05). The citrulline nadir was lower (P < .01) in patients with digestive bacterial translocation than that in those without. Mean citrulline concentrations at H0 to H96 were not significantly different between survivors and nonsurvivors. In both groups, citrulline was significantly inversely correlated with C-reactive protein (r(2) = 0.10, P < .01) on D0. No significant correlations were found between citrulline and albumin, transthyretin, TNF-α, IL-10, or TNF-α/IL-10 ratio. At the onset of septic shock, plasma citrulline decreases and varies inversely with C-reactive protein and is lower when digestive bacterial translocation occurs. This finding could reflect an early acute intestinal dysfunction, but measurement of citrulline concentration does not appear to be able to predict the patients' mortality.
    Journal of critical care 11/2013; · 2.13 Impact Factor
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    ABSTRACT: Objective Propensity score matching is typically used to estimate the average treatment effect for the treated while inverse probability of treatment weighting aims at estimating the population average treatment effect. We illustrate how different estimands can result in very different conclusions.Study designWe applied the two propensity score methods to assess the effect of continuous positive airway pressure on mortality in patients hospitalized for acute heart failure. We used Monte Carlo simulations to investigate the important differences in the two estimates.ResultsContinuous positive airway pressure application increased hospital mortality overall, but no continuous positive airway pressure effect was found on the treated. Potential reasons were (1) violation of the positivity assumption; (2) treatment effect was not uniform across the distribution of the propensity score. From simulations, we concluded that positivity bias was of limited magnitude and did not explain the large differences in the point estimates. However, when treatment effect varies according to the propensity score (E[Y(1)-Y(0)|g(X)] is not constant, Y being the outcome and g(X) the propensity score), propensity score matching ATT estimate could strongly differ from the inverse probability of treatment weighting-average treatment effect estimate. We show that this empirical result is supported by theory.Conclusion Although both approaches are recommended as valid methods for causal inference, propensity score-matching for ATT and inverse probability of treatment weighting for average treatment effect yield substantially different estimates of treatment effect. The choice of the estimand should drive the choice of the method.
    Statistical Methods in Medical Research 11/2013; · 2.36 Impact Factor
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    ABSTRACT: IMPORTANCE Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear. OBJECTIVE To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012. INTERVENTIONS Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay. MAIN OUTCOMES AND MEASURES The primary outcome was death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy. RESULTS Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to 2.10] days; P = .03). CONCLUSIONS AND RELEVANCE Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00318942.
    JAMA The Journal of the American Medical Association 10/2013; · 29.98 Impact Factor
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    ABSTRACT: As a result of reporting bias, or frauds, false or misunderstood findings may represent the majority of published research claims. This article provides simple methods that might help to appraise the quality of the reporting of randomized, controlled trials (RCT). This evaluation roadmap proposed herein relies on four steps: evaluation of the distribution of the reported variables; evaluation of the distribution of the reported p values; data simulation using parametric bootstrap and explicit computation of the p values. Such an approach was illustrated using published data from a retracted RCT comparing a hydroxyethyl starch versus albumin-based priming for cardiopulmonary bypass. Despite obvious nonnormal distributions, several variables are presented as if they were normally distributed. The set of 16 p values testing for differences in baseline characteristics across randomized groups did not follow a Uniform distribution on [0,1] (p = 0.045). The p values obtained by explicit computations were different from the results reported by the authors for the two following variables: urine output at 5 hours (calculated p value < 10-6, reported p >= 0.05); packed red blood cells (PRBC) during surgery (calculated p value = 0.08; reported p < 0.05). Finally, parametric bootstrap found p value > 0.05 in only 5 of the 10,000 simulated datasets concerning urine output 5 hours after surgery. Concerning PRBC transfused during surgery, parametric bootstrap showed that only the corresponding p value had less than a 50% chance to be inferior to 0.05 (3,920/10,000, p value < 0.05). Such simple evaluation methods might offer some warning signals. However, it should be emphasized that such methods do not allow concluding to the presence of error or fraud but should rather be used to justify asking for an access to the raw data.
    Annals of intensive care. 09/2013; 3(1):29.
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    ABSTRACT: The best catecholamine regimen for cardiogenic shock has been poorly evaluated. When a vasopressor is required to treat patients with the most severe form of cardiogenic shock, whether inodilators should be added or whether inopressors can be used alone has not been established. The purpose of this study was to compare the impact of these two strategies on short-term mortality in patients with severe cardiogenic shocks. Three observational cohorts of patients with decompensated heart failure were pooled to comprise a total of 1,272 patients with cardiogenic shocks. Of these 1,272 patients, 988 were considered to be severe because they required a vasopressor during the first 24 hours. We developed a propensity-score (PS) model to predict the individual probability of receiving one of the two regimens (inopressors alone or a combination) conditionally on baseline-measured covariates. The benefit of the treatment regimen on the mortality rate was estimated by fitting a weighted Cox regression model. A total of 643 patients (65.1%) died within the first 30 days (inopressors alone: 293 (72.0%); inopressors and inodilators: 350 (60.0%)). After PS weighting, we observed that the use of an inopressor plus an inodilator was associated with an improved short-term mortality (HR: 0.66 [0.55-0.80]) compared to inopressors alone. In the most severe forms of cardiogenic shock where a vasopressor is immediately required, adding an inodilator may improve short-term mortality. This result should be confirmed in a randomized, controlled trial.
    PLoS ONE 08/2013; 8(8):71659-. · 3.73 Impact Factor
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    ABSTRACT: There have been few Bayesian analyses of phase III sequential clinical trials that model divergent expert opinions in a single distribution. We used modeling of experts' opinions to perform additional Bayesian analyses of a randomized clinical trial (designed as a sequential trial), particularly when a bimodal shape is observed. We provide an illustrative example based on a randomized trial conducted in patients aged between 65 and 75 years with multiple myeloma as the case study. The main endpoint of the trial was overall survival (OS). Prior distribution of the log hazard ratio of death in the experimental versus the control arm ($$\theta $$) was constructed based on elicitation of experts using a mixture of normal distributions estimated by the Expectation-Maximisation (EM) algorithm. At each interim and terminal analysis, the posterior probability of $$\theta $$ and the resulting increases in median OS in the experimental arm compared to the control were computed. The results were compared to results obtained using either skeptical, enthusiastic, or a mixture of those priors. Finally, we discuss our results in light of the frequentist approach originally designed for the trial. A total of 39 experts reported their opinion on the median OS in the experimental arm compared to the median control survival of 30 months. The resulting pooled distribution of the log hazard ratios exhibited a bimodal profile. When the prior mixture of the normal distribution was fitted to the data sets from the experts, 44% of the experts' opinions were optimistic and 56% were doubtful. At the final analysis, the percentage of doubting experts dropped to 18%. This corresponded to a posterior probability of an improved OS in the experimental arm compared to the control arm of at least 0.98, regardless of the prior. These findings are in agreement with the original conclusion of the trial regarding the beneficial effect of the experimental treatment in this population. Only 39 experts among the 120 questioned physicians responded to the inquiry. Our approach was hybrid because the prior mixture was estimated using the EM algorithm, and a full Bayesian approach may have been used. Bayesian inference allows the quantification of increased survival in terms of probability distributions and provides investigators with an additional tool in the analysis of a randomized phase III clinical trial. Using a mixture of densities appears to be a promising strategy for incorporating the bimodal profile of prior opinion, with actualization of the two components along the trial as an illustration of the evolution of opinions as data are accumulated.
    Clinical Trials 07/2013; · 2.20 Impact Factor
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    ABSTRACT: Background:Proteoglycans are involved in neo-angiogenesis and transduction of oncogenic signals, two hallmarks of carcinogenesis. Methods:This study sought to assess the prognostic value of serum levels of three proteoglycans (endocan, syndecan-1 and glypican-3) and VEGF in 295 patients with alcoholic cirrhosis: 170 without hepatocellular carcinoma (HCC), 58 with early HCC and 67 with advanced HCC at inclusion. We analyzed the association between proteoglycan levels and prognosis using Kaplan-Meier and Cox methods. Results:Serum levels of the 3 proteoglycans and VEGF were increased in patients with advanced HCC compared to those without HCC or with early HCC. In multivariate analysis, high levelsof serum endocan (>5 ng/ml) were independently associated with death (HR 2.84 [1.18; 6.84] P =0.02), but not with HCC occurrence, in patients without HCC at baseline. High serum endocan (> 5 ng/ml) and syndecan-1 (> 50 ng/ml) levels were significantly associated with greater risk of tumor recurrence (P = 0.025) in patients with early HCC treated by radiofrequency ablation. In patients with advanced HCC, high serum levels of endocan (P =0.004) and syndecan-1 (P =0.006) were significantly associated with less favorable overall survival. However, only a high level of serum syndecan-1 (>50 ng/ml) was independently associated with greater risk of death (HR: 6.21 [1.90; 20.30] P=0.0025). Conclusions:Serum endocan and syndecan-1 are easily assessable prognostic serum biomarkers of overall survival in alcoholic cirrhosis with and without HCC. Impact:These new biomarkers will be useful to manage patients with HCC developed on alcoholic cirrhosis.
    Cancer Epidemiology Biomarkers &amp Prevention 06/2013; · 4.56 Impact Factor
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    ABSTRACT: PURPOSEPatients with hematologic malignancies are increasingly admitted to the intensive care unit (ICU) when life-threatening events occur. We sought to report outcomes and prognostic factors in these patients. PATIENTS AND METHODS Ours was a prospective, multicenter cohort study of critically ill patients with hematologic malignancies. Health-related quality of life (HRQOL) and disease status were collected after 3 to 6 months.ResultsOf the 1,011 patients, 38.2% had newly diagnosed malignancies, 23.1% were in remission, and 24.9% had received hematopoietic stem-cell transplantations (HSCT, including 145 allogeneic). ICU admission was mostly required for acute respiratory failure (62.5%) and/or shock (42.3%). On day1, 733 patients (72.5%) received life-supporting interventions. Hospital, day-90, and 1-year survival rates were 60.7%, 52.5%, and 43.3%, respectively. By multivariate analysis, cancer remission and time to ICU admission less than 24 hours were associated with better hospital survival. Poor performance status, Charlson comorbidity index, allogeneic HSCT, organ dysfunction score, cardiac arrest, acute respiratory failure, malignant organ infiltration, and invasive aspergillosis were associated with higher hospital mortality. Mechanical ventilation (47.9% of patients), vasoactive drugs (51.2%), and dialysis (25.9%) were associated with mortality rates of 60.5%, 57.5%, and 59.2%, respectively. On day 90, 80% of survivors had no HRQOL alterations (physical and mental health similar to that of the overall cancer population). After 6 months, 80% of survivors had no change in treatment intensity compared with similar patients not admitted to the ICU, and 80% were in remission. CONCLUSION Critically ill patients with hematologic malignancies have good survival, disease control, and post-ICU HRQOL. Earlier ICU admission is associated with better survival.
    Journal of Clinical Oncology 06/2013; · 18.04 Impact Factor
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    ABSTRACT: To provide data for future drug evaluation, we analyzed the outcome of 393 patients aged 50 years or older (median, 64 years) with AML in first relapse after treatment in recent ALFA trials. Salvage options were retrospectively classified as follows: best supportive care (BSC), low-dose cytarabine (LDAC), gemtuzumab ozogamicin (GO), intensive chemotherapy (ICT), or ICT combined with GO. Second complete remission (CR2) rate was 31% and median post-relapse survival was 6.8 months (0%, 17%, 42.5%, 53%, 80% and 3.2, 5.6, 8.9, 9, 19.8 months in BSC, LDAC, GO, ICT, and ICT+GO subsets, respectively). Age, performance status, WBC, CR1 duration, and favorable AML karyotype, but not other cytogenetic or molecular features, influenced post-relapse outcome. Multivariate adjustment and propensity score matching showed that intensive salvage (ICT/ICT+GO/GO versus LDAC/BSC) was associated with longer post-relapse survival, at least in patients with CR1 duration ≥ 12 months (P= 0.001 and 0.0005, respectively). Of interest, GO appeared to be as effective as standard ICT, and ICT+GO combination more effective than standard ICT. In conclusion, older patients with CR1 duration ≥ 12 months appeared to benefit from intensive salvage and results observed with GO-containing salvage suggest that GO combination studies should be actively pursued in this setting.
    American Journal of Hematology 06/2013; · 4.00 Impact Factor
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    Critical care (London, England) 05/2013; 17(3):142. · 4.72 Impact Factor
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    ABSTRACT: BACKGROUND:: Previously reported estimates of the ED95 doses for local anesthetics used in brachial plexus blocks vary. The authors used the continual reassessment method, already established in oncology trials, to determine the ED95 dose for 0.5% bupivacaine for the ultrasound-guided supraclavicular block. METHODS:: A double-blind, prospective trial was scheduled for 40 patients of American Society of Anesthesiologists class I-III presenting for upper limb surgery and supraclavicular block. The study dose to be administered was arbitrarily divided into six dose levels (12, 15, 18, 21, 24, and 27ml) with a priori probabilities of success of 0.5, 0.75, 0.90, 0.95, 0.98, and 0.99 respectively. A continual reassessment method statistical program created a dose-response curve, which would shift direction depending on the success or failure of the block. Our starting dose was 21ml and the next allocated dose was reestimated by the program to be the dose level with the updated posterior response probability closest to 0.95. RESULTS:: After recruitment of eight patients, our initial dose levels and associated probabilities were deemed too low to determine the ED95. Updated a prioris were calculated from the statistical program, and the study recommenced with a new starting dose of 30 ml. On completion, the ED95 dose was estimated to be 27 ml (95% CI, 24-28 ml). CONCLUSIONS:: The continual reassessment method trial design provided a credible estimate for the ED95 dose for 0.5% bupivacaine for our technique of supraclavicular block and may be of value as a statistically robust method for dose-finding studies in anesthesiology.
    Anesthesiology 05/2013; · 5.16 Impact Factor

Publication Stats

14k Citations
2,655.33 Total Impact Points

Institutions

  • 2008–2014
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire d'Angers
      • Département de neurologie
      Angers, Pays de la Loire, France
  • 2007–2014
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Intercommunal Creteil
      Créteil, Île-de-France, France
  • 2004–2014
    • Université de Versailles Saint-Quentin
      Versailles, Île-de-France, France
    • Centre Hospitalier Régional Universitaire de Lille
      Lille, Nord-Pas-de-Calais, France
  • 2013
    • University Hospital Estaing of Clermont-Ferrand
      Clermont, Auvergne, France
    • Hôpital Européen Georges-Pompidou (Hôpitaux Universitaires Paris-Ouest)
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Hôpital Saint-Louis (Hôpitaux Universitaires Saint-Louis, Laboisière, Fernand-Widal)
      • Service de Pneumologie
      Paris, Ile-de-France, France
  • 2003–2012
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Clinique Ambroise Paré
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 1992–2012
    • Université René Descartes - Paris 5
      • Faculty of medicine
      Lutetia Parisorum, Île-de-France, France
  • 1991–2012
    • Hôpital Raymond-Poincaré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Île-de-France, France
  • 2011
    • Mercy Hospital St. Louis
      San Luis, Missouri, United States
    • Centre Hospitalier Universitaire de Saint-Étienne
      Saint-Étienne, Rhône-Alpes, France
    • University Joseph Fourier - Grenoble 1
      Grenoble, Rhône-Alpes, France
    • Hôpital Jean-Verdier – Hôpitaux Universitaires Paris-Seine-Saint-Denis
      Bondy, Île-de-France, France
  • 2002–2011
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • University of Franche-Comté
      Becoinson, Franche-Comté, France
    • Hôpital Antoine-Béclère – Hôpitaux universitaires Paris-Sud
      Clamart, Île-de-France, France
  • 2004–2010
    • Centre Hospitalier de Versailles
      • Department of Onco-Hematology
      Versailles, Île-de-France, France
  • 2009
    • Université Paris 13 Nord
      Île-de-France, France
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2006
    • University of Glasgow
      Glasgow, Scotland, United Kingdom
    • Hôpital Avicenne – Hôpitaux Universitaires Paris-Seine-Saint-Denis
      Bobigny, Île-de-France, France
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      Créteil, Île-de-France, France
  • 2005
    • Hôpital Saint-Vincent-de-Paul – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 1992–2002
    • Hôpital Paris Saint Joseph
      Lutetia Parisorum, Île-de-France, France
  • 2001
    • Centre Hospitalier Universitaire de Caen
      Caen, Lower Normandy, France
    • American Hospital of Paris
      Lutetia Parisorum, Île-de-France, France
  • 2000
    • Institut de Cancérologie Gustave Roussy
      Île-de-France, France
  • 1999
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      • Service de Réanimation Médicale et des Maladies Infectieuses
      Lutetia Parisorum, Île-de-France, France
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • Service d’Hépato - Gastro - Entérologie
      Paris, Ile-de-France, France
  • 1996–1997
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France