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Mistry P.K.,Yale University | Lukina E.,Hematology Research Center | Turkia H.B.,Hopital La Rabta | Amato D.,Mount Sinai Hospital | And 17 more authors.
JAMA - Journal of the American Medical Association | Year: 2015

Importance: Gaucher disease type 1 is characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. A safe, effective oral therapy is needed. Objective: To determine whether eliglustat, a novel oral substrate reduction therapy, safely reverses clinical manifestations in untreated adults with Gaucher disease type 1. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 12 countries from November 2009 to July 2012 among eligible patients with splenomegaly plus thrombocytopenia and/or anemia. Of 72 patients screened, 40 were enrolled. Interventions: Patients were stratified by spleen volume and randomized 1:1 to receive eliglustat (50 or 100mg twice daily; n = 20) or placebo (n = 20) for 9 months. Main Outcomes and Measures: The primary efficacy end pointwas percentage change in spleen volume in multiples of normal from baseline to 9 months; secondary efficacy end points were change in hemoglobin level and percentage changes in liver volume and platelet count. Results: All patients had baseline splenomegaly and thrombocytopenia (mostly moderate or severe), most had mild or moderate hepatomegaly, and 20% had mild anemia. Least-square mean spleen volume decreased by 27.77% (95% CI, -32.57% to -22.97%) in the eliglustat group (from 13.89 to 10.17 multiples of normal) vs an increase of 2.26% (95% CI, -2.54% to 7.06%) in the placebo group (from 12.50 to 12.84 multiples of normal) for an absolute treatment difference of -30.03% (95% CI, -36.82% to -23.24%; P < .001). For the secondary end points, the least-square mean absolute differences between groups all favored eliglustat, with a 1.22-g/dL increase in hemoglobin level (95% CI, 0.57-1.88 g/dL; P < .001), 6.64% decrease in liver volume (95% CI, -11.37% to -1.91%; P = .007), and 41.06% increase in platelet count (95% CI, 23.95%-58.17%; P < .001). No serious adverse events occurred. One patient in the eliglustat group withdrew (non-treatment related); 39 of the 40 patients transitioned to an open-label extension study. Conclusions and Relevance: Among previously untreated adults with Gaucher disease type 1, treatment with eliglustat compared with placebo for 9 months resulted in significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count. The clinical significance of these findings is uncertain, and more definitive conclusions about clinical efficacy and utility will require comparison with the standard treatment of enzyme replacement therapy as well as longer-term follow-up. Trial Registration: clinicaltrials.gov Identifier: NCT00891202. Copyright © 2015 American Medical Association. All rights reserved. Source

Khazzaka A.,Saint - Joseph University | Sarkis R.,Hotel Dieu Of France University Hospital
Surgery for Obesity and Related Diseases | Year: 2013

Background: The purpose of this pilot study was to demonstrate the feasibility and procedural safety of laparoscopic fundoplication combined with mediogastric plication in patients with a body mass index of 32-35 kg/m 2. Methods: Sixteen patients underwent laparoscopic fundoplication combined with mediogastric plication. All procedures were performed with the patient under general anesthesia. The 1-year follow-up results encompassed gastroesophageal reflux disease recovery and excess weight loss. Results: The procedure time varied from 65 to 95 minutes. No serious procedure-related complications occurred. Gastroesophageal reflux disease-related symptoms resolved in all patients (P =.000). The excess weight loss was 10 ± 4 kg (58%) 1 year after the procedure. The 1-year follow-up excess weight was significantly less than the baseline excess weight (P =.000). The average body mass index decreased from 33.8 ± 1.9 kg/m2 at baseline to 27.2 ± 1.7 kg/m2 at 1 year (P =.02). Of the 16 patients, 14 had an excess weight loss of 62%, and 2 sweet-eaters had an excess weight loss of 33%. At 1 year of follow-up, the excess weight in those who smoked (n = 10) was greater than that of nonsmokers (n = 6; P =.02). However, smoking did not seem to significantly affect excess weight loss (P =.065). Conclusion: Fundoplication combined with mediogastric plication produced a total recovery from gastroesophageal reflux disease and an excess weight loss of 62% in 87.5% of patients after 1 year of follow-up. This procedure is technically feasible, and no serious procedure-related complications occurred. The follow-up is ongoing to investigate the efficacy and long-term durability of the procedure. © 2013 American Society for Metabolic and Bariatric Surgery. All rights reserved. Source

Taddei P.J.,University of Houston | Taddei P.J.,American University of Beirut | Jalbout W.,American University of Beirut | Howell R.M.,University of Houston | And 5 more authors.
Physics in Medicine and Biology | Year: 2013

The prediction of late effects after radiotherapy in organs outside a treatment field requires accurate estimations of out-of-field dose. However, out-of-field dose is not calculated accurately by commercial treatment planning systems (TPSs). The purpose of this study was to develop and test an analytical model for out-of-field dose during craniospinal irradiation (CSI) from photon beams produced by a linear accelerator. In two separate evaluations of the model, we measured absorbed dose for a 6 MV CSI using thermoluminescent dosimeters placed throughout an anthropomorphic phantom and fit the measured data to an analytical model of absorbed dose versus distance outside of the composite field edge. These measurements were performed in two separate clinics - the University of Texas MD Anderson Cancer Center (MD Anderson) and the American University of Beirut Medical Center (AUBMC) - using the same phantom but different linear accelerators and TPSs commissioned for patient treatments. The measurement at AUBMC also included in-field locations. Measured dose values were compared to those predicted by TPSs and parameters were fit to the model in each setting. In each clinic, 95% of the measured data were contained within a factor of 0.2 and one root mean square deviation of the model-based values. The root mean square deviations of the mathematical model were 0.91 cGy Gy -1 and 1.67 cGy Gy-1 in the MD Anderson and AUBMC clinics, respectively. The TPS predictions agreed poorly with measurements in regions of sharp dose gradient, e.g., near the field edge. At distances greater than 1 cm from the field edge, the TPS underestimated the dose by an average of 14% ± 24% and 44% ± 19% in the MD Anderson and AUBMC clinics, respectively. The in-field measured dose values of the measurement at AUBMC matched the dose values calculated by the TPS to within 2%. Dose algorithms in TPSs systematically underestimated the actual out-of-field dose. Therefore, it is important to use an improved model based on measurements when estimating out-of-field dose. The model proposed in this study performed well for this purpose in two clinics and may be applicable in other clinics with similar treatment field configurations. © 2013 Institute of Physics and Engineering in Medicine. Source

Farhat F.S.,Bellevue Medical Center | Farhat F.S.,Saida University | Kattan J.,Hotel Dieu Of France University Hospital | Ghosn M.G.,Hotel Dieu Of France University Hospital
Expert Review of Anticancer Therapy | Year: 2010

Gastric cancer is one of the most common cancers and the second leading cause of cancer-related death. So far, the only curative treatment for gastric cancer is surgery. However, approximately half of all patients present with nonoperable tumors. Therefore, combination chemotherapy regimens are being accepted nowadays as first-line treatment for this disease. Despite the numerous efforts of randomized trials on advanced gastric cancer, no globally accepted regimen has yet been established. Historically, the most widely adopted protocols use 5-fluorouracil or platinum-based therapy with a response rate not exceeding 50% in combination therapy with a high rate of toxicity. Recently, many new drugs have emerged on the market and have been used in treating advanced or metastatic gastric cancer allowing the creation of new combination regimens with better clinical benefit. The combination of irinotecan plus capecitabine is one of these new combinations that seem to provide an acceptable response rate and good toxicity profile. In this article, we review the efficacy, tolerability, and feasibility of this combination for the treatment of advanced or metastatic gastric cancer and we summarize the clinical trials using this regimen. © 2010 Expert Reviews Ltd. Source

Stephan F.,Hotel Dieu Of France University Hospital | Haber R.,Hotel Dieu Of France University Hospital | Kechichian E.,Hotel Dieu Of France University Hospital | Kamar F.,Bellevue Medical Center
Indian Journal of Dermatology | Year: 2016

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome or drug-induced hypersensitivity syndrome (DIHS) is a severe adverse drug reaction. It can present with clinical, paraclinical, and histological findings mimicking skin and/or systemic lymphomas. We report the first case of a lamotrigine-induced DRESS with histologic features of a cutaneous CD30+ lymphoma. The patient responded well to a tapering course of oral steroids. This case highlights the atypical presentation of a lamotrigine-induced DRESS/DIHS in the presence of a cutaneous and a lymph node CD30 + lymphocytic infiltrate mimicking systemic lymphoma. Pathologists and clinicians must be aware of this 'lymphomatous' presentation of drug reactions. Source

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