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Cochin, France

Steib A.,University of Strasbourg | Morel M.H.,University of Limoges | Nathan N.,University of Limoges | Ozier Y.,Groupe Hospitalier Cochin | Treger M.,University of Strasbourg
Journal of Thrombosis and Haemostasis | Year: 2010

Background: After a vitamin K antagonist (VKA) overdose, 1-2 mg of oral vitamin K can lower the International Normalized Ratio (INR) to the therapeutic range. Objective: To establish whether oral vitamin K can substitute for heparin bridging and decrease the INR to ≤ 1.5 before elective surgery. Methods: Patients on long-term VKAs were randomized either to heparin bridging after the last VKA dose on day - 5 before surgery (group H) or to VKA treatment until day - 2, followed by 1 mg of oral vitamin K on the day before surgery (group K). Blood clotting variables were assessed on days -5/-2, 1 and 0, and postoperatively. If the target INR was not achieved 2 h before incision, surgery was deferred or performed after injection of prothrombin complex concentrate (PCC). Results: In 30 of 94 included patients, baseline INR was outside the chosen range (18, INR < 2; 12, INR > 3.5), leaving 34 eligible patients in group H and 30 in group K. The groups were balanced in terms of body mass index, VKA treatment duration and indication, scheduled surgery, preoperative and postoperative hemoglobin, and blood loss. The INR was significantly higher in group K on days - 1 and 0 than in group H. An INR ≤ 1.5 was not achieved in 20 group K patients (66%). Surgery was postponed or performed after PCC injection in 12 of these 20 patients. Conclusions: Oral vitamin K (1 mg) cannot substitute for heparin bridging before surgery. In addition, one-third of patients on VKAs were exposed to a risk of bleeding (overdose) or thrombosis (underdose), thus highlighting the need for new oral anticoagulants. © 2009 International Society on Thrombosis and Haemostasis.

Soufir J.-C.,Groupe Hospitalier Cochin | Meduri G.,Laboratoire Of Genetique Moleculaire | Ziyyat A.,Groupe Hospitalier Cochin | Ziyyat A.,University of Paris Descartes
Human Reproduction | Year: 2011

Background: We previously demonstrated in a small pilot study that oral medroxyprogesterone acetate and percutaneous testosterone (OMP/PT) induce reversible spermatogenesis suppression. The aims of this study were to determine the rate of spermatogenetic inhibition and recovery and to obtain preliminary data on efficacy for a larger population under OMP/PT. Methods: A total of 35 healthy men with normal spermiograms requesting male hormonal contraception were treated with OMP (20 mg/day) and PT (50125 mg/day) for periods up to 18 months. Couples were included in a contraceptive efficacy phase after a value of ≤1 million/ml spermatozoa was reached between 1 and 3 months of treatment. Results: Sperm counts decreased by 47 at 1 month, reaching 90 at 2 months and 98100 between 4 and 8 months. At 3 months, 80 of men had ≤1 million/ml spermatozoa. Follicle-stimulating hormone and luteinizing hormone decreased to 35 of pretreatment levels after 1 month of treatment and to 7580 at 2 and 6 months, respectively. Plasma testosterone and estradiol levels were in the eugonadal range at 3, 6, 9 and 12 months of treatment. Dihydrotestosterone concentrations were 24 times higher than pretreatment values. The rate of spermatogenetic recovery was rapid (73 ± 29.5 days). During the efficacy phase (211 months for 25 couples), one pregnancy attributable to poor compliance of the male partner was observed. Conclusions: OMP/PT efficiently inhibits spermatogenesis in 80 of men, maintains testosterone at physiological levels and avoids the need for parenteral administration, which is poorly accepted by French men. These Results: justify larger studies to define a more adequate dosage of OMP/PT and to confirm its efficacy and safety. © 2011 The Author.

Beuschlein F.,Ludwig Maximilians University of Munich | Weigel J.,University of Wurzburg | Saeger W.,University of Hamburg | Kroiss M.,University of Wurzburg | And 22 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Background: Recurrence of adrenocortical carcinoma (ACC) even after complete (R0) resection occurs frequently. Objective: The aim of this study was to identify markers with prognostic value for patients in this clinical setting. Design, Setting, and Participants: From the German ACC registry, 319 patients with the European Network for the Study of Adrenal Tumors stage I-III were identified. As an independent validation cohort, 250 patients from three European countries were included. Outcome Measurements and Statistical Analysis: Clinical, histological, and immunohistochemical markers were correlated with recurrence-free (RFS) and overall survival (OS). Results: Although univariable analysis within the German cohort suggested several factors with potential prognostic power, upon multivariable adjustment only a few including age, tumor size, venous tumor thrombus (VTT), and the proliferation marker Ki67 retained significance. Among these, Ki67 provided the single best prognostic value for RFS (hazard ratio [HR] for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P < .0001) which was confirmed in the validation cohort. Accordingly, clinical outcome differed significantly between patients with Ki67 <10%, 10-19%, and ≥20% (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs 113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor size, VTT, and Ki67 were established. Although these scores discriminated slightly better between subgroups, there was no clinically meaningful advantage in comparison with Ki67 alone. Conclusion: This largest study on prognostic markers in localized ACC identified Ki67 as the single most important factor predicting recurrence in patients following R0 resection. Thus, evaluation of Ki67 indices should be introduced as standard grading in all pathology reports of patients with ACC. Copyright © 2015 by the Endocrine Society.

Abdelhedi F.,Groupe Hospitalier Cochin | Corcos J.,Groupe Hospitalier Cochin | Cuisset L.,Groupe Hospitalier Cochin | Tsatsaris V.,University of Paris Descartes | And 4 more authors.
American Journal of Medical Genetics, Part A | Year: 2012

We report on a fetus with an isolated short femur detected by ultrasound and a de novo interstitial deletion of chromosome 15. The deletion was diagnosed prenatally by karyotype and further mapped by fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (array-CGH) to bands 15q15.3 to 15q21.3 with a size of 11.11Mb. Fetal autopsy showed characteristic minor anomalies, urinary abnormalities, and delayed bone maturation, but neither craniosynostosis, nor congenital heart defects as observed in previously reported cases. Despite the existence of ultrasound abnormalities, all five cases reported so far were diagnosed after birth. This is the first case of an interstitial deletion involving chromosomal band 15q15.3-q21.3 diagnosed prenatally and characterized at the molecular level. Our observation suggests the absence of imprinted genes in the area of 15q15-q22 and strengthens the hypothesis that a critical region for craniosynostosis may be mapped outside the deleted region in the present patient. © 2012 Wiley Periodicals, Inc.

Lecomte F.,Groupe Hospitalier Cochin | Lecomte F.,University of Paris Descartes | Gault N.,University of Paris Descartes | Kone V.,University of Paris Descartes | And 8 more authors.
American Journal of Emergency Medicine | Year: 2011

Objective: Neuropathic pain (NP) in acute conditions has been poorly investigated. A diagnostic score, the DN4 scale (DN4), has been developed to help physicians to detect and treat NP appropriately. DN4 is a 10-item questionnaire. If you have 4 or more positive responses out of 10 items, the answer to the questionnaire is positive and you have a neuropathic pain. We aimed to determine the prevalence of NP in emergency department (ED) patients and to describe this population. Methods: We used the DN4 in the patients with NP visiting the adult ED of a university hospital. Patients were asked about the characteristics of their pain using a face-to-face questionnaire. Results: Among 533 patients with a DN4 score, 114 (21.4%) had NP. Neuropathic pain was independently negatively associated with age of 65 years of older (odds ratio [OR], 0.2, 95% confidence interval [CI], 0.05-0.8) and positively associated with intense pain (OR, 5.2; 95% CI, 1.5-18.2), located to the limbs (OR, 2.3; 95% CI, 1.2-4.0). Conclusion: Neuropathic pain was common in ED patients and associated to a higher level of pain. © 2011 Elsevier Inc.

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