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Le Touquet – Paris-Plage, France

Roupret M.,Hopital de la Pitie Salpetriere
Nature Reviews Urology | Year: 2016

Outcome prediction in patients with bladder cancer has improved through the development of nomograms and predictive models. However, integration of further characteristics such as lymphovascular invasion (LVI) might increase the accuracy and clinical utility of these instruments. Assessment and reporting of LVI in specimens from transurethral resection of the bladder tumour (TURBT) or biopsy in patients with non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) might enable improved staging, prognostication and clinical decision-making. In NMIBC, presence of LVI in TURBT and biopsy samples seems to be associated with understaging and increased risks of disease recurrence and progression. In MIBC, presence of LVI is associated with features of aggressive disease and predicts recurrence and survival. Integration of LVI status into predictive models might aid clinical decision-making regarding intravesical instillation schedules and regimens, early radical cystectomy in patients with high-grade T1 disease and perioperative chemotherapy. However, LVI assessment is hampered by insufficient reproducibility and reliability, lack of routine evaluation and limited concordance between findings in TURBT and radical cystectomy specimens. Standardization of the pathological criteria defining LVI is warranted to improve its reporting in routine clinical practice and its utility as a care-changing prognostic marker. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Inborn errors of metabolism (IEMs) are caused by deficiencies in enzymes and other proteins involved in cell metabolism. Numerous IEMs are curable and thus diagnosis is mandatory before the occurrence of any irreversible neurological injury. IEMs may be responsible for intensive care unit (ICU) admission of patients with unexplained coma or encephalopathy, at any age from infancy to late adulthood. These acute late-onset presentations are often triggered by apparently non-specific external factors including benign fever episodes, prolonged exercise, prolonged fasting, and surgery. Disorders of energy metabolism and "endogenous intoxications" (syndromes leading to hyperammonemia, hyperhomocysteinemia, porphyria, aminoacidopathy, and organic aciduria) represent the two major categories of IEMs. In these settings, in addition to brain magnetic resonance imaging, the most useful metabolic investigations are measurements of blood concentrations of lactate, pyruvate, and ammonia, followed by plasma concentrations of aminoacids and homocystein as well as urine concentrations of organic acids, porphyrins, and porphobilinogen. Interpretation of these biochemical tests and the consequent treatments of assessed metabolic abnormalities require specific expertise found in reference centers. © SRLF et Springer-Verlag France 2012.

Moriarty P.M.,University of Kansas Medical Center | Jacobson T.A.,Emory University | Bruckert E.,Hopital de la Pitie Salpetriere | Thompson P.D.,Hartford Hospital | And 3 more authors.
Journal of Clinical Lipidology | Year: 2014

Background Statin intolerance has been a major limitation in the use of statins, especially at higher doses. New effective treatments are needed for lowering low-density lipoprotein cholesterol (LDL-C) in patients who cannot tolerate daily statin doses. Objective ODYSSEY ALTERNATIVE (NCT01709513) evaluates efficacy and safety of alirocumab, a fully human proprotein convertase subtilisin/kexin type 9 monoclonal antibody, in patients with well-documented statin intolerance and moderate to very high cardiovascular risk. Methods This is a phase 3, multicenter, randomized, double-blind, double-dummy study in statin-intolerant patients. Intolerance was defined as inability to take at least 2 different statins because of muscle-related adverse events (AEs), 1 at the lowest approved starting dose. Patients first received single-blind subcutaneous and oral placebo for 4 weeks, and were withdrawn if they developed muscle-related AEs after the placebo treatment. Continuing patients were randomized (2:2:1 ratio) to alirocumab 75 mg self-administered via single 1 mL prefilled pen every 2 weeks or ezetimibe 10 mg/day or atorvastatin 20 mg/day (statin rechallenge), for 24 weeks. Alirocumab dose was increased to 150 mg every 2 weeks (also 1 mL) at week 12 depending on week 8 LDL-C level. The primary endpoint is percent change in LDL-C from baseline to week 24 by intent-to-treat analysis. Muscle-related AEs were assessed by spontaneous patient reports and clinic queries. Results A total of 314 patients have been randomized. Conclusions This is the first and only study of a new class of LDL-C-lowering agents in patients selected with a rigorously documented intolerance to statins, using a placebo run-in and statin control arm. © 2014 National Lipid Association.

Echaniz-Laguna A.,Hopitaux Universitaires | Dubourg O.,Institute Of Myologie | Carlier P.,Hopital de la Pitie Salpetriere | Carlier R.-Y.,APHP | And 7 more authors.
Neurology | Year: 2014

Objective: To clarify the phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathies. Methods: We screened for TRPV4 mutations in 169 French unrelated patients with inherited axonal peripheral neuropathy. Ninety-five patients had dominant Charcot-Marie-Tooth type 2 (CMT2) disease, and 74 patients, including 39 patients with distal hereditary motor neuropathy, 14 with congenital spinal muscular atrophy and arthrogryposis, 13 with CMT2, and 8 with scapuloperoneal spinal muscular atrophy, presented with additional vocal cord paralysis and/or skeletal dysplasia. Results: No deleterious TRPV4 mutation was identified in the 95 patients with "pure" CMT2 (0/95). In contrast, 12 of 74 patients (16%) with neuropathy and vocal cord paralysis and/or skeletal dysplasia presented pathogenic TRPV4 mutations, including 7 patients with distal hereditary motor neuropathy, 2 with scapuloperoneal spinal muscular atrophy, 2 with congenital spinal muscular atrophy and arthrogryposis, and one with CMT2. Investigation of affected relatives allowed us to study 17 patients. All patients had childhood-onset motor neuropathy and showed a variety of associated findings, including foot deformities (100% of cases), kyphoscoliosis (100%), elevated serum creatine kinase levels (100%), vocal cord paralysis (94%), scapular winging (53%), respiratory insufficiency (29%), hearing loss (24%), skeletal dysplasia (18%), and arthrogryposis (12%). Eight missense mutations were observed in these 12 families, including 2 previously unreported. Six mutations were de novo events, and 2 asymptomatic carriers were identified. Conclusion: With 16% of patients affected in our series, this study demonstrates that TRPV4 mutations are a major cause of inherited axonal neuropathy associated with a large spectrum of additional features. © 2014 American Academy of Neurology.

Seisen T.,Hopital de la Pitie Salpetriere | Colin P.,Hopital Prive de la Louviere | Roupret M.,Hopital de la Pitie Salpetriere
Nature Reviews Urology | Year: 2015

The conservative management of upper tract urothelial carcinoma (UTUC) was traditionally restricted to patients with imperative indications only. However, current recommendations suggest selected patients with normal, functioning contralateral kidneys should also be considered for such an approach. A risk-adapted strategy to accurately select patients who could benefit from kidney-sparing surgery without compromising their oncological safety has been advocated. A number of kidney-sparing surgical procedures are available. Despite the advent of ureteroscopic management, segmental ureterectomy and the percutaneous approach both have specific indications for use that predominantly depend on the tumour location and progression risk. These kidney-sparing procedures are cost-effective, and when used to treat patients with low-risk UTUC, are associated with oncological outcomes similar to radical nephroureterectomy. Systematic second-look endoscopy combined with upper tract instillations of topical chemotherapeutic agents after ureteroscopic or percutaneous surgery and a single early intravesical instillation of mitomycin C after any kidney-sparing procedure might decrease the risks of local recurrence and progression. Meticulous and stringent endoscopic monitoring of the upper and lower urinary tract is a key component of the conservative management of UTUC. Local recurrences are often suitable for repeat conservative therapy, whereas disease progression should be treated with delayed radical nephroureterectomy.

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