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Le Touquet – Paris-Plage, France

Coriat R.,University of Paris Descartes | Coriat R.,Center for Research on Angiogenesis Inhibitors | Alexandre J.,University of Paris Descartes | Alexandre J.,Center for Research on Angiogenesis Inhibitors | And 14 more authors.
Journal of Clinical Investigation | Year: 2014

Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer. Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ≤2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir. Results. Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles, neurotoxicity was downgraded to grade ≤2 in 6 of 7 patients. Prior to enrollment, patients received an average of 880 ± 239 mg/m2 oxaliplatin. Patients treated with mangafodipir tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin. Serum AOPPs were lower in responders compared with those in nonresponders. Conclusion. Our study suggests that mangafodipir can prevent and/or relieve oxaliplatin-induced neuropathy in cancer patients. Trial registration. Clinicaltrials.gov NCT00727922. Funding. Universite Paris Descartes, Ministere de la Recherche et de lEnseignement Superieur, and Assistance Publique-Hopitaux de Paris. Source


Grimaldi D.,Medical Intensive Care Unit | Grimaldi D.,French Institute of Health and Medical Research | Grimaldi D.,French National Center for Scientific Research | Grimaldi D.,University of Paris Descartes | And 23 more authors.
Resuscitation | Year: 2013

Aims: Gut dysfunction is suspected to play a major role in the pathophysiology of post-resuscitation disease through an increase in intestinal permeability and endotoxin release. However this dysfunction often remains occult and is poorly investigated. The aim of this pilot study was to explore intestinal failure biomarkers in post-cardiac arrest patients and to correlate them with endotoxemia. Methods: Following resuscitation after cardiac arrest, 21 patients were prospectively studied. Urinary intestinal fatty acid-binding protein (IFABP), which marks intestinal permeability, plasma citrulline, which reflects the functional enterocyte mass, and whole blood endotoxin were measured at admission, days 1-3 and 6. We explored the kinetics of release and the relationship between IFABP, citrulline and endotoxin values. Results: IFABP was extremely high at admission and normalized at D3 (6668pg/mL vs 39pg/mL, p=0.01). Lowest median of citrulline (N=20-40μmol/L) was attained at D2 (11μmol/L at D2 vs 24μmol/L at admission, p=0.01) and tended to normalize at D6 (21μmol/L). During ICU stay, 86% of patients presented a detectable endotoxemia. Highest endotoxin level was positively correlated with highest IFABP level (R2=0.31, p=0.01) and was inversely correlated with lowest plasma citrulline levels (R2=0.55, p<0.001). Endotoxin levels increased between admission and D2 in patients with post-resuscitation shock, whereas it decreases in patients with no shock (median +0.33 EU vs -0.19 EU, p=0.03). Highest endotoxin level was positively correlated with D3 SOFA score (R2=0.45, p=0.004). Conclusion: Biomarkers of intestinal injury are altered after cardiac arrest and are associated with endotoxemia. This could worsen post-resuscitation shock and organ failure. © 2012 Elsevier Ireland Ltd. Source


Flaujac C.,Groupe Hospitalier Broca Cochin Hotel Dieu | Guinet C.,Biomnis Ivry sur Seine | Samama M.M.,Groupe Hospitalier Broca Cochin Hotel Dieu
Bio Tribune Magazine | Year: 2011

Biological monitoring of low molecular weight heparins (LMWH) or fondaparinux involves the measurement of anti-Xa activity, with a result in IU of anti-Xa activity/ml. New anticoagulants as rivaroxaban (Xarelto®) have been recently commercialised. This new anticoagulant has a specific and direct effect on factor Xa (independent of the presence of antithrombin). Currently, there is no indication for routine biological monitoring of these new products but there is still an interest to measure the plasmatic concentration of these products. Therefore, standard tests for measuring anti-Xa activity have limitations and should be adapted. The development of tests for measuring anti-Xa activity based on principles similar to those we know and able to give plasma concentrations in ng/ml is on track. Future studies should help to provide better interpretation of laboratory results and to demonstrate their clinical relevance. © 2011 Springer Verlag France. Source


Guinard-Barbier S.,Groupe Hospitalier Broca Cochin Hotel Dieu | Guinard-Barbier S.,University of Paris Descartes | Grabar S.,University of Paris Descartes | Chenevier-Gobeaux C.,Hospital Cochin | And 14 more authors.
Biomarkers | Year: 2011

Introduction: Mid-regional pro-atrial natriuretic peptide (MRproANP) increases during systemic infections and could possibly correlate with bacteremia. Methods: We determined the characteristics of MRproANP for accuracy to detect positive blood culture. Results: Bacteremia was positive in 58 (15%) of 347 patients. MRproANP levels increased in patients with bacteremia (98.4 pmol/L [interquartile range (IQR) 68.2-153.1] vs. 66.4 pmol/L [IQR 51.0-90.3], p<0.01). Performance of MRproANP to predict bacteremia [AUC=0.69, 95%CI: 0.61-0.77] was equivalent to C-reactive protein (0.66 [95%CI: 0.59-0.74], p=0.53) but less accurate than procalcitonin (0.78 [95%CI: 0.72-0.84], p<0.001). Conclusion: Although MRproANP increased in bacteremic patients with acute pyelonephritis, results of likelihood ratios discarded its use at bedside to predict bacteremia. © 2011 Informa UK, Ltd. Source


Giraud C.,Groupe Hospitalier Broca Cochin Hotel Dieu | Giraud C.,University of Paris Descartes | Giraud C.,French Institute of Health and Medical Research | Manceau S.,Groupe Hospitalier Broca Cochin Hotel Dieu | And 13 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

During the 2009 H1N1 influenza pandemics, the concentrations of oseltamivir (O) and its active metabolite (oseltamivir carboxylate [OC]) were determined in 11 children (1 month to 16 years of age) admitted to intensive care units for presumed severe H1N1 infection. They received oseltamivir phosphate (OP) nasogastrically at doses between 1.5 and 6.8 mg/kg of body weight. High OC concentrations were found, with a mean level of 678 ± 535 μg/liter. The mean OP concentration was 27 ± 52 μg/liter. No marked side effect was reported. Copyright © 2011, American Society for Microbiology. All Rights Reserved. Source

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