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Le Touquet – Paris-Plage, France

Kupers E.M.,Hypertension Unit | Amar L.,Hypertension Unit | Raynaud A.,Georges Pompidou European Hospital | Plouin P.-F.,Hypertension Unit | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Adrenal venous sampling is recommended to assess whether aldosterone hypersecretion is lateralized in patients with primary aldosteronism. However, this procedure is invasive, poorly standardized, and not widely available. Objective: Our goal was to identify patients' characteristics that can predict unilateral aldosterone hypersecretion in some patients who could hence bypass adrenal venous sampling before surgery. Design and Setting: A cross-sectional diagnostic study was performed from February 2009 to July 2010 at a single center specialized in hypertension care. Patients: A total of 101 consecutive patients with primary aldosteronism who underwent adrenal venous sampling participated in the study. The autonomy of aldosterone hypersecretion was assessed with the saline infusion test. Intervention: Adrenal venous sampling was performed without ACTH infusion but with simultaneous bilateral sampling. Main Outcome Measures: Variables independently associated with a lateralized adrenal venous sampling in multivariate logistic regression were used to derive a clinical prediction rule. Results: Adrenal venous sampling was successful in 87 patients and lateralized in 49. All 26 patients with a typical Conn's adenoma plus serum potassium of less than 3.5 mmol/liter or estimated glomerular filtration rate of at least 100 ml/min/1.73 m2 (or both) had unilateral primary aldosteronism; this rule had 100% specificity (95% confidence interval, 91-100) and 53% sensitivity (95% confidence interval, 38-68). Conclusions: If our results are validated on an independent sample, adrenal venous sampling could be omitted before surgery in patients with a typical Conn's adenoma if they meet at least one of two supplementary biochemical characteristics (serum potassium <3.5 mmol/liter or estimated glomerular filtration rate ≥100 ml/min/1.73 m2). Copyright © 2012 by The Endocrine Society.

Lefaucheur C.,Nephrology and Kidney Transplantation | Duong-Van-Huyen J.-P.,French Institute of Health and Medical Research | Suberbielle C.,University of Paris Descartes | Anglicheau D.,University of Paris Descartes | And 11 more authors.
The Lancet | Year: 2013

Background Rejection of allografts has always been the major obstacle to transplantation success. We aimed to improve characterisation of diff erent kidney-allograft rejection phenotypes, identify how each one is associated with anti-HLA antibodies, and investigate their distinct prognoses. Methods Patients who underwent ABO-compatible kidney transplantations in Necker Hospital and Saint-Louis Hospital (Paris, France) between Jan 1, 1998, and Dec 31, 2008, were included in our population-based study. We assessed patients who provided biopsy samples for acute allograft rejection, which was defi ned as the association of deterioration in function and histopathological lesions. The main outcome was kidney allograft loss-ie, return to dialysis. To investigate distinct rejection patterns, we retrospectively assessed rejection episodes with review of graft histology, C4d in allograft biopsies, and donor-specifi c anti-HLA antibodies. Findings 2079 patients were included in the main analyses, of whom 302 (15%) had acute biopsy-proven rejection. We identifi ed four distinct patterns of kidney allograft rejection: T cell-mediated vascular rejection (26 patients [9%]), antibody-mediated vascular rejection (64 [21%]), T cell-mediated rejection without vasculitis (139 [46%]), and antibodymediated rejection without vasculitis (73 [24%]). Risk of graft loss was 9.07 times (95 CI 3.62-19.7) higher in antibody-mediated vascular rejection than in T cell-mediated rejection without vasculitis (p<0.0001), compared with an increase of 2.93 times (1.1-7.9; P=0.0237) in antibody-mediated rejection without vasculitis and no signifi cant rise in T cell-mediated vascular rejection (hazard ratio [HR] 1.5, 95% CI 0.33-7.6; p=0.60). Interpretation We have identifi ed a type of kidney rejection not presently included in classifi cations: antibodymediated vascular rejection. Recognition of this distinct phenotype could lead to the development of new treatment strategies that could salvage many kidney allografts.

Halabi S.,Duke University | Lin C.-Y.,Duke University | Small E.J.,University of California at San Francisco | Armstrong A.J.,Duke Prostate Center and the Duke Cancer Institute | And 7 more authors.
Journal of the National Cancer Institute | Year: 2013

Background Several prognostic models for overall survival (OS) have been developed and validated in men with metastatic castration-resistant prostate cancer (mCRPC) who receive first-line chemotherapy. We sought to develop and validate a prognostic model to predict OS in men who had progressed after first-line chemotherapy and were selected to receive second-line chemotherapy. Methods Data from a phase III trial in men with mCRPC who had developed progressive disease after first-line chemotherapy (TROPIC trial) were used. The TROPIC was randomly split into training (n = 507) and testing (n = 248) sets. Another dataset consisting of 488 men previously treated with docetaxel (SPARC trial) was used for external validation. Adaptive least absolute shrinkage and selection operator selected nine prognostic factors of OS. A prognostic score was computed from the regression coefficients. The model was assessed on the testing and validation sets for its predictive accuracy using the time-dependent area under the curve (tAUC). Results The nine prognostic variables in the final model were Eastern Cooperative Oncology Group performance status, time since last docetaxel use, measurable disease, presence of visceral disease, pain, duration of hormonal use, hemoglobin, prostate specific antigen, and alkaline phosphatase. The tAUCs for this model were 0.73 (95% confidence interval [CI] = 0.72 to 0.74) and 0.70 (95% CI = 0.68 to 0.72) for the testing and validation sets, respectively. Conclusions A prognostic model of OS in the postdocetaxel, second-line chemotherapy, mCRPC setting was developed and externally validated. This model incorporates novel prognostic factors and can be used to provide predicted probabilities for individual patients and to select patients to participate in clinical trials on the basis of their prognosis. Prospective validation is needed. © The Author 2013.

Loupy A.,Necker Hospital | Hill G.S.,Georges Pompidou European Hospital | Jordan S.C.,Cedars Sinai Medical Center
Nature Reviews Nephrology | Year: 2012

Despite improvements in outcomes of renal transplantation, kidney allograft loss remains substantial, and is associated with increased morbidity, mortality and costs. Identifying the pathologic pathways responsible for allograft loss, and the attendant development of therapeutic interventions, will be one of the guiding future objectives of transplant medicine. One of the most important advances of the past decade has been the demonstration of the destructive power of anti-HLA alloantibodies and their association with antibody-mediated rejection (ABMR). Compelling evidence exists to show that donor-specific anti-HLA antibodies (DSAs) are largely responsible for the chronic deterioration of allografts, a condition previously attributed to calcineurin inhibitor toxicity and chronic allograft nephropathy. The emergence of sensitive techniques to detect DSAs, together with advances in the assessment of graft pathology, have expanded the spectrum of what constitutes ABMR. Today, subtler forms of rejection-such as indolent ABMR, C4d-negative ABMR, and transplant arteriopathy-are seen in which DSAs exert a marked pathological effect. In addition, arteriosclerosis, previously thought to be a bystander lesion related to the vicissitudes of aging, is accelerated in ABMR. Advances in our understanding of the pathological significance of DSAs and ABMR show their primacy in the mediation of chronic allograft destruction. Therapies aimed at B cells, plasma cells and antibodies will be important therapeutic options to improve the length and quality of kidney allograft survival. © 2012 Macmillan Publishers Limited. All rights reserved.

Riquet M.,Georges Pompidou European Hospital
Annals of Thoracic Surgery | Year: 2010

Background Lung cancer may invade the pericardium (T3) and the intrapericardial pulmonary veins and left atrium (T4). Our purpose was to analyze the characteristics of this invading process in search of the reasons explaining its poor prognosis. Methods The clinical records of 4,668 patients who underwent surgery for lung cancer between January 1983 and December 2006 in two thoracic surgery centers were retrospectively reviewed. The epidemiology, pathology, and prognostic characteristics of the tumors invading the pericardium alone (T3) or with pulmonary veins and atrium (T4) were analyzed and compared with all other tumors. Results There were 75 male and 16 female patients, with 85 pneumonectomies and 6 lobectomies that proved R0 in 59.3% of patients, and contained 69 squamous cell cancers, 11 adenocarcinomas, and 13 miscellaneous tumors; 12 were N0 (13.2%), 31 were N1 (34.1%), and 48 were N2 (52.8%). Pericardium alone was invaded in 32 patients (35.2%), and with pulmonary vein and atrium in 34 (37.3%) and 25 (27.5%), respectively. Patient characteristics were similar in each group. Five-year and 10-year survival rates were 15.1% and 10.4%, respectively. Frequency of pneumonectomy, R1-2 resection, and N1-2 involvement were significantly more important compared with noninvading tumors (p < 10-6). Conclusions Reports on T3 and T4 cancer with pericardial involvement are few, but also stress that pulmonary vein and left atrium invasion does not worsen the prognosis more than pericardial invasion alone. The rich pericardial lymph drainage might enhance the spread of tumor cells, explaining excessively high N1-N2 rates and pericardial invasion-related poor prognosis. © 2010 The Society of Thoracic Surgeons.

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