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Marseille, France

Bonello L.,Aix - Marseille University | Laine M.,Aix - Marseille University | Kipson N.,UMR MD2 and Institute of Biological Research | Mancini J.,Assistance Publique | And 13 more authors.
Journal of the American College of Cardiology | Year: 2014

Objectives This study aimed to investigate the impact of ticagrelor on adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients. Background Ticagrelor is a direct-acting P2Y12-adenosine diphosphate receptor blocker. The clinical benefit of ticagrelor compared with clopidogrel in ACS patients suggests that the drug has non-platelet-directed properties. Animal and in vitro models suggested that the "pleiotropic" properties of ticagrelor may be related to an interaction with adenosine metabolism. Methods We prospectively randomized 60 ACS patients to receive ticagrelor or clopidogrel. The APC was measured by liquid chromatography. To assess the mechanism of APC variation, we measured adenosine deaminase concentration, adenosine uptake by red blood cells, and cyclic adenosine monophosphate production by cells overexpressing adenosine receptors. The P2Y 12-adenosine diphosphate receptor blockade was assessed by the vasodilator-stimulated phosphoprotein index. Results Patients receiving ticagrelor had significantly higher APC than patients receiving clopidogrel (1.5 μM [interquartile range: 0.98 to 1.7 μM] vs. 0.68 μM [interquartile range: 0.49 to 0.78 μM]; p < 0.01). The APC was not correlated with vasodilator-stimulated phosphoprotein (p = 0.16). Serum-containing ticagrelor inhibited adenosine uptake by red blood cells compared with clopidogrel or controls (p < 0.01 for both comparisons). Adenosine deaminase activity was similar in serum of patients receiving clopidogrel or ticagrelor (p = 0.1). Ticagrelor and clopidogrel had no direct impact on adenosine receptors (p = not significant). Conclusions Ticagrelor increases APC in ACS patients compared with clopidogrel by inhibiting adenosine uptake by red blood cells. Source


Levy M.,Hopitaux de Paris | Rigaudiere F.,Assistance Publique | De Lauzanne A.,Hopitaux de Paris | Koehl B.,Hopitaux de Paris | And 5 more authors.
Pediatric Infectious Disease Journal | Year: 2015

Background: The effects of ethambutol (EMB) on vision are particularly difficult to detect in children less than 5 years of age because of a lack of complaints and objective clinical signs. The aim of this study was to assess the frequency of visual abnormalities and the utility of visual-evoked potentials (VEPs) recordings in monitoring the visual function of children less than 5 years of age who were exposed to EMB during anti-mycobacterial treatment. Methods: We performed a retrospective study in Robert-Debré University Hospital, Paris, France, including all children less than 5 years of age, who were treated with EMB for a mycobacterial infection from January 2002 to December 2012. Results: Fourteen patients were enrolled, including 12 treated for Mycobacterium tuberculosis infection. The sex ratio was 1:1. The median age was 1.65 years (0.3 to 4.7). Five patients had subarachnoid involvement. The median EMB dose was 22 mg/kg/day (15 to 27). Only 11 patients were monitored using VEPs. Three children (27.3%) developed a visual impairment secondary to EMB, with delays of 4, 7 and 36 weeks. One of the 3 patients developed an impairment of the retrochiasmatic visual pathways, and 2 other patients developed classical retrobulbar optic neuritis. In all cases, the discontinuation of EMB resulted in a normalization of these findings. Conclusion: Alterations in visual function related to the use of EMB are not uncommon in young children and are most likely underestimated. Systematic close monitoring using VEPs recordings is needed in young children treated with EMB. © 2015 Wolters Kluwer Health, Inc. Source


Plavk R.,General Faculty Hospital | Simeoni U.,Assistance Publique | Stranak Z.,Maternity Hospital | Mosca F.,University of Milan | And 5 more authors.
Pediatrics | Year: 2010

OBJECTIVE: Early surfactant followed by extubation to nasal continuous positive airway pressure (nCPAP) compared with later surfactant and mechanical ventilation (MV) reduce the need for MV, air leaks, and bronchopulmonary dysplasia. This randomized, controlled trial investigated whether prophylactic surfactant followed by nCPAP compared with early nCPAP application with early selective surfactant would reduce the need for MV in the first 5 days of life. METHODS: A total of 208 inborn infants who were born at 25 to 28 weeks' gestation and were not intubated at birth were randomly assigned to prophylactic surfactant or nCPAP within 30 minutes of birth. Outcomes were assessed within the first 5 days of life and until death or discharge of the infants from hospital. RESULTS: Thirty-three (31.4%) infants in the prophylactic surfactant group needed MV in the first 5 days of life compared with 34 (33.0%) in the nCPAP group (risk ratio: 0.95 [95% confidence interval: 0.64-1.41]; P = .80). Death and type of survival at 28 days of life and 36 weeks' postmenstrual age and incidence of main morbidities of prematurity (secondary outcomes) were similar in the 2 groups. A total of 78.1% of infants in the prophylactic surfactant group and 78.6% in the nCPAP group survived in room air at 36 weeks' postmenstrual age. CONCLUSIONS: Prophylactic surfactant was not superior to nCPAP and early selective surfactant in decreasing the need for MV in the first 5 days of life and the incidence of main morbidities of prematurity in spontaneously breathing very preterm infants on nCPAP. Copyright © 2010 by the American Academy of Pediatrics. Source


Attygalle A.D.,Royal Marsden Hospital | Cabecadas J.,Servico de Anatomia Patologica | Gaulard P.,Assistance Publique | Jaffe E.S.,U.S. National Cancer Institute | And 4 more authors.
Histopathology | Year: 2014

Mature T-cell and T/NK-cell neoplasms are both uncommon and heterogeneous, among the broad category of non-Hodgkin lymphomas. Owing to the lack of specific genetic alterations in the vast majority, most currently defined entities show overlapping morphological and immunophenotypic features, and therefore pose a challenge to the diagnostic pathologist. In the light of recent immunophenotypic, cytogenetic and molecular genetics advances in the field of T-cell and T/NK-cell lymphomas, the focus of the lymphoma workshop of the European Association for Haematopathology/Society for Hematopathology meeting in Lisbon, Portugal, in October 2012 was to refine existing diagnostic criteria and clarify the borders between overlapping entities. The panel reviewed over 200 submitted cases, which were grouped into five categories: (i) angioimmunoblastic T-cell lymphoma and T-follicular-helper-cell-associated lymphomas; (ii) CD30-positive T-cell lymphomas/lymphoproliferative diseases; (iii) extranodal T-cell and NK-cell neoplasms; (iv) EBV-associated T-cell/NK-cell lymphomas/lymphoproliferative diseases; and (v) peripheral T-cell lymphoma, not otherwise specified, post-transplant lymphoproliferative disorders, and mimics. This report summarizes the discussions and conclusions of the workshop, which question current diagnostic criteria and provide recommendations for refining existing classifications. © 2013 John Wiley & Sons Ltd. Source


Buitenkamp T.D.,Pediatric Oncology Hematology | Izraeli S.,Sheba Medical Center | Zimmermann M.,Hannover Medical School | Forestier E.,Umea University | And 30 more authors.
Blood | Year: 2014

Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt- Münster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% ± 2% vs 15% ± 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% ± 1% vs 2.0% ± <1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% ± 2% vs 81% ± 2%, P < .0001) and overall survival (74% ± 2% vs 89% ± 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] = 0.58, P = .002), white blood cell (WBC) count <10 3 109/L (HR = 0.60, P = .005), and ETV6-RUNX1 (HR = 0.14, P = .006) for EFS and age (HR = 0.48, P < .001), ETV6-RUNX1 (HR = 0.1, P = .016) and high hyperdiploidy (HeH) (HR = 0.29, P = .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DSALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups. (Blood. 2014; 123(1):70-77). © 2014 by The American Society of Hematology. Source

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