Papazian L.,Aix - Marseille University |
Forel J.-M.,Aix - Marseille University |
Gacouin A.,Hopital Pontchaillou |
Penot-Ragon C.,Hopital Sainte Marguerite |
And 13 more authors.
New England Journal of Medicine | Year: 2010
BACKGROUND: In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. METHODS: In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. RESULTS: The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P = 0.04), after adjustment for both the baseline PaO 2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P = 0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P = 0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. CONCLUSIONS: In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique-Hôpitaux de Marseille and the Programme Hospitalier de Recherche Clinique Régional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.) Copyright © 2010 Massachusetts Medical Society.
Denys P.,University of Versailles |
Le Normand L.,University of Nantes |
Ghout I.,Hopital Ambroise Pare |
Costa P.,University of Nimes |
And 7 more authors.
European Urology | Year: 2012
Background: In the treatment of patients with idiopathic overactive bladder (iOAB), high doses of botulinum toxin type A (BoNTA) were often associated with complications resulting from high postvoid residuals (PVR), leading to clean intermittent catheterisation (CIC) and urinary tract infections (UTI). Objective: Evaluate the efficacy and tolerability of low doses of onabotulinumtoxinA compared to placebo in patients with iOAB. Design, setting, and participants: Between 2005 and 2009, adults with persistent iOAB were included in a prospective, randomised, double-blind, placebo-controlled comparative trial. Intervention: Patients were randomised to undergo a single intradetrusor injection procedure of either placebo or onabotulinumtoxinA (50 U, 100 U or 150 U). Measurements: The initial evaluations (ie, clinical and urodynamic variables as well as quality of life [QoL]) were repeated at day 8 and months 1, 3, 5, and 6. Results and limitations: Ninety-nine patients were included in the efficacy analysis. Three months after the procedure, we observed >50% improvement versus baseline in urgency and urge urinary incontinence (UUI) in 65% and 56% of patients who respectively received 100 U (p = 0.086) and 150 U (p = 0.261) BoNTA injections and >75% improvement in 40% of patients of both groups (100 U [p = 0.058] and 150 U [p = 0.022]). Complete continence was observed in 55% and 50% patients after 100 U and 150 U BoNTA treatment, respectively, at month 3. Frequency symptoms and QoL improved up to the 6-mo visit. We observed only three patients with a PVR >200 ml in the 150 U group and a few UTIs. Conclusions: 100 U and 150 U BoNTA injections were well tolerated and have both shown to improve symptoms and QoL in patients with iOAB. Nevertheless, 100 U injections showed a reasonable efficacy, with a lower risk of high PVR. Trial registration: ClinicalTrials.gov NCT00231491. © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Conroy T.,University of Lorraine |
Desseigne F.,Center Leon Berard |
Ychou M.,Center Val dAurelle |
Bouche O.,Center Hospitalier University Robert Debre |
And 17 more authors.
New England Journal of Medicine | Year: 2011
BACKGROUND: Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer. METHODS: We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival. RESULTS: The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001). CONCLUSIONS: As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.) Copyright © 2011 Massachusetts Medical Society.
Martetschlager F.,TU Munich |
Martetschlager F.,The Steadman Philippon Research Institute |
Kraus T.M.,Hopital Ambroise Pare |
Hardy P.,Hopital Ambroise Pare |
And 2 more authors.
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2013
Bony deficiency of the anterior glenoid rim may significantly contribute to recurrent shoulder instability. Today, based on clinical and biomechanical data, a bony reconstruction is recommended in patients with bone loss of greater than 20-25 % of the glenoid surface area. Recent advances in arthroscopic instruments and techniques presently allow minimally invasive and arthroscopic reconstruction of glenoid bone defects and osteosynthesis of glenoid fractures. This article underlines the role of glenoid bone deficiency in recurrent shoulder instability, provides an update on the current management regarding this pathology and highlights the modern techniques for surgical treatment. Therefore, it can help orthopaedic surgeons in the treatment and decision-making when dealing with these difficult to treat patients in daily clinical practice. Level of evidence V. © 2012 Springer-Verlag.
O'Shaughnessy J.A.,Baylor Sammons Cancer Center |
Kaufmann M.,University Hospital Frankfurt |
Siedentopf F.,Praxis fur Gynakologie Dr Schoenegg |
Dalivoust P.,Hopital Ambroise Pare |
And 3 more authors.
Oncologist | Year: 2012
The goals of treatment for metastatic breast cancer (MBC) are to prolong overall survival (OS) while maximizing quality of life, palliating symptoms, and delaying tumor progression. For many years, anthracyclines and taxanes have been the mainstay of treatment for MBC, but these agents are now commonly administered earlier in the course of the disease. A recent meta-analysis revealed adverse effects on OS and overall response rates in patients with MBC receiving first-line anthracycline-based chemotherapy following relapse on adjuvant chemotherapy. Noncrossresistant cytotoxic agents and combinations that combine high clinical activity and acceptable tolerability while being convenient for patients are therefore needed for the first-line treatment of MBC patients. Capecitabine has substantial antitumor activity in the first-line treatment of patients with MBC in prospective, randomized, phase II/III clinical trials as monotherapy and in combination with biologic and novel agents. First-line capecitabine monotherapy has a favorable safety profile, lacking myelosuppression and alopecia, and does not compromise the administration of further lines of chemotherapy. Capecitabine is suitable for long-term administration without the cumulative toxicity that can limit the prolonged use of other chemotherapy agents. Here, we review the available data on capecitabine as a single agent for first-line treatment of patients with human epidermal growth factor receptor 2-negative MBC. © AlphaMed Press.
Gineys R.,Service dOphtalmologie |
Bodaghi B.,Service dOphtalmologie |
Carcelain G.,Laboratoire dImmunologie Tissulaire et Cellulaire |
Cassoux N.,Service dOphtalmologie |
And 4 more authors.
American Journal of Ophthalmology | Year: 2011
Purpose: To evaluate the accuracy of QuantiFERON-TB Gold testing in patients with presumptive tuberculosis-ocular inflammation. Design: Prospective nonrandomized case series and clinical laboratory investigation. Methods: Ninety-six consecutive patients presenting with ocular inflammation between January and October 2007 were tested using QuantiFERON-TB Gold. Positive patients received a 6-month anti-tuberculosis treatment. Patient follow-up ranged from 12 months to 24 months. Treatment was considered effective at the end of follow-up, in cases of no or a 2-point decrease of ocular inflammation (SUN criteria) and systemic corticosteroids stopped or tapered to 10 mg/day. Results: Mean age was 51 ± 17 years. Types of ocular inflammation included scleritis (n = 7), panuveitis (n = 34), and posterior (n = 15), intermediate (n = 14), and anterior uveitis (n = 15). QuantiFERON-TB Gold was positive in 42 cases (44%), negative in 51 cases (53%), and undetermined in 3 cases (3%). Among positive QuantiFERON-TB Gold patients, 25 received a full anti-tuberculosis treatment, which was effective in 15 cases (60%). Associated systemic steroids were given to 6 patients and tapered to 10 mg/day or less in all cases. Median QuantiFERON-TB Gold value was significantly higher in the group with a successful therapeutic response (7.67 IU/mL [0.46 to 33.37]) compared to the group with treatment failure (1.22 IU/mL [0.61 to 4.4]), P =.026. Conclusion: Results of anti-tuberculosis treatment were encouraging in QuantiFERON-TB Goldpositive ocular inflammation, especially with values over 2 IU/mL in our study, suggesting that a higher cut-off value than that given by the manufacturer should be considered to better identify ocular inflammation that can benefit from full anti-tuberculosis treatment. © 2011 Elsevier Inc.
Pham-Thi N.,French National Center for Scientific Research |
Bidat E.,HOpital Ambroise Pare
Archives de Pediatrie | Year: 2014
Solid food introduction in childhood suffered in recent decades many changes due to findings of increased allergies with a likely mismatch schemes and a recent reversal of recommendations for delaying the introduction of foods. The advice may still change due to the latest findings on the mechanisms of sensitization. There is little or no certainty on the date and to provide food at the right time. It seems that the introduction of solid foods may be favorable age between 4 and 6months. Delaying the introduction of allergenic potential has not yet demonstrated a preventive effect. It could be preferable to induce an early oral tolerance that cause allergy with transcutaneous sensitization by ingesting any new dietary protein introduced in the environment of the infant. © 2014 Elsevier Masson SAS.
Weraarpachai W.,Montreal Neurological Institute |
Sasarman F.,Montreal Neurological Institute |
Nishimura T.,Montreal Neurological Institute |
Antonicka H.,Montreal Neurological Institute |
And 6 more authors.
American Journal of Human Genetics | Year: 2012
We investigated a family in which the index subject presented with severe congenital lactic acidosis and dysmorphic features associated with a cytochrome c oxidase (COX)-assembly defect and a specific decrease in the synthesis of COX I, the subunit that nucleates COX assembly. Using a combination of microcell-mediated chromosome transfer, homozygosity mapping, and transcript profiling, we mapped the gene defect to chromosome 12 and identified a homozygous missense mutation (c.88G>A) in C12orf62. C12orf62 was not detectable by immunoblot analysis in subject fibroblasts, and retroviral expression of the wild-type C12orf62 cDNA rescued the biochemical phenotype. Furthermore, siRNA-mediated knockdown of C12orf 62 recapitulated the biochemical defect in control cells and exacerbated it in subject cells. C12orf62 is apparently restricted to the vertebrate lineage. It codes for a very small (6 kDa), uncharacterized, single-transmembrane protein that localizes to mitochondria and elutes in a complex of ∼110 kDa by gel filtration. COX I, II, and IV coimmunoprecipated with an epitope-tagged version of C12orf62, and 2D blue-native-polyacrylamide-gel-electrophoresis analysis of newly synthesized mitochondrial COX subunits in subject fibroblasts showed that COX assembly was impaired and that the nascent enzyme complex was unstable. We conclude that C12orf62 is required for coordination of the early steps of COX assembly with the synthesis of COX I. © 2012 The American Society of Human Genetics.
Bidat E.,Hopital Ambroise Pare
Revue Francaise d'Allergologie | Year: 2010
Cow milk allergy is often associated with goat milk or sheep milk allergy, although probably with a lower frequency than usually reported. Goat milk or sheep milk allergy without allergy to cow milk has been recognized recently. These allergies occur more frequently in patients with multiple allergies. Clinical signs are narrower than for other food allergies. It should be noted that this allergy is easy to diagnose in most cases, given a good clinical history and a positive skin prick-test and/or serum IgE assay. It can be difficult to manage because of reactions to very small amounts of goat milk and/or sheep milk hidden in other foods. The proteins involved are goat and sheep alpha(S1)- and alpha(S2)-caseins and β-casein. Therapeutic advances are anticipated, with various forms of immunotherapy. © 2010 Elsevier Masson SAS. All rights reserved.
Lichtenstein D.A.,Hopital Ambroise Pare
Lung Ultrasound in the Critically Ill: The BLUE Protocol | Year: 2015
The tools of the BLUE-protocol:�Basic notions: the indispensable.- Which unit.- Which probe.- Specific notions.- The seven principles of L.U.C.I..- The BLUE-points.- The 10 signatures at a glance.- The pleural line.- The A-profile and the A-line.- The A-profile and lung sliding.- The B-line.- Interstitial syndrome and lung rockets.- The B-profile, the B-profile.- The A-profile and pneumothorax.- PLAPS.- PLAPS and pleural effusion.- PLAPS and lung consolidation. The C-profile.- BLUE-DVT. Deep venous thrombosis in the BLUE-protocol.- Simple emergency cardiac sonography.- The BLUE-protocol in clinical use:�Basic principle of the BLUE-protocol. The 8 profiles. The data.- Excluded patients of the BLUE-protocol.- Frequently asked questions on the BLUE-protocol.- The BLUE-protocol and pneumonia.-�The BLUE-protocol and acute hemodynamic pulmonary edema.- The BLUE-protocol, asthma and COPD.- The BLUE-protocol and pulmonary embolism.-�The BLUE-protocol and pneumothorax.-�The main products derived from the BLUE-protocol:�Pink-protocol (lung ultrasound in ARDS).- The LUCI-FLR project (decrease of medical irradiation).- FALLS-protocol (heart, lung, venous ultrasound in management of acute circulatory failure).-�SESAME-protocol (ultrasound in cardiac arrest).-�Extension of lung ultrasound to specific disciplines, wider settings, various considerations: Lung ultrasound in the neonate.-�All specialties involved in lung ultrasound.-�Critical ultrasound, lung, heart and DVT apart.-�The Extended BLUE-protocol.-�Non critical ultrasound.-�Various considerations.-�How to learn the BLUE-protocol.-�Holistic ultrasound, a new definition - how it can impact critical medicine.-�Lung artifacts from A to Z. © Springer International Publishing Switzerland 2016. All rights are reserved.