Hospital Germans Trias Pujol

Badalona, Spain

Hospital Germans Trias Pujol

Badalona, Spain
SEARCH FILTERS
Time filter
Source Type

Audi L.,Hospital Vall dHebron | Fernandez-Cancio M.,Hospital Vall dHebron | Carrascosa A.,Hospital Vall dHebron | Andaluz P.,Hospital Vall dHebron | And 39 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Background: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). Objective: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. Setting: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. Methods: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. Results: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. Conclusions: AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel. Copyright © The Endocrine Society.


Fernandez-Cancio M.,Autonomous University of Barcelona | Audi L.,Autonomous University of Barcelona | Andaluz P.,Autonomous University of Barcelona | Toran N.,Hospital Vall dHebron | And 14 more authors.
International Journal of Andrology | Year: 2011

One hundred and forty-six index patients with 46,XY DSD in whom gonads were confirmed as testes were consecutively studied for a molecular diagnosis during the period 2002-2010. AR gene was analysed in all patients as the first candidate gene, yielding a mutation in 42.5% of cases and SRD5A2 gene was analysed as the second candidate gene, resulting in the characterization of 10 different mutations (p.Y91D, p.G115D, p.Q126R, p.R171S, p.Y188CfsX9, p.N193S, p.A207D, p.F219SfsX60, p.R227Q and p.R246W) in nine index patients (6.2% of the total number of 46,XY DSD patients). One of the mutations (p.Y188CfsX9) has never been reported. In addition, we genotyped SRD5A2 gene p.V89L and c.281+15T>C polymorphisms in 46,XY DSD and in 156 normal adult males and found that patients with SRD5A2 mutations or without a known molecular diagnosis presented a higher frequency of homozygous p.L89, homozygous TT and combined CCTT genotypes compared with controls. This result suggests that 46,XY DSD patient phenotypes may be influenced by SRD5A2 polymorphism genotypes. SRD5A2 gene mutations may not be as infrequent as previously considered in 46,XY DSD patients with variable degrees of external genitalia virilization at birth and normal T production and appears to be the second aetiology in our series. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.


Wick W.,University of Heidelberg | Wick W.,German Cancer Research Center | Gorlia T.,European Organisation for Research and Treatment of Cancer EORTC | Bady P.,Swiss Institute of Bioinformatics | And 25 more authors.
Clinical Cancer Research | Year: 2016

Purpose: EORTC 26082 assessed the activity of temsirolimus in patients with newly diagnosed glioblastoma harboring an unmethylated O6 methylguanine-DNA-methyltransferase (MGMT) promoter. Experimental Design: Patients (n = 257) fulfilling eligibility criteria underwent central MGMT testing. Patients with MGMT unmethylated glioblastoma (n = 111) were randomized 1:1 between standard chemo-radiotherapy with temozolomide or radiotherapy plus weekly temsirolimus (25 mg). Primary endpoint was overall survival at 12 months (OS12). A positive signal was considered >38 patients alive at 12 months in the per protocol population. A noncomparative reference arm of 54 patients evaluated the assumptions on OS12 in a standard-treated cohort of patients. Prespecified post hoc analyses of markers reflecting target activation were performed. Results: Both therapies were administered per protocol with a median of 13 cycles of maintenance temsirolimus. Median age was 55 and 58 years in the temsirolimus and standard arms, the WHO performance status 0 or 1 for most patients (95.5%). In the per protocol population, 38 of 54 patients treated with temsirolimus reached OS12. The actuarial 1-year survival was 72.2% [95% confidence interval (CI), 58.2-82.2] in the temozolomide arm and 69.6% (95% CI, 55.8-79.9) in the temsirolimus arm [hazard ratio (HR) 1.16; 95% CI, 0.77-1.76; P = 0.47]. In multivariable prognostic analyses of clinical and molecular factors, phosphorylation of mTORSer2448 in tumor tissue (HR 0.13; 95% CI, 0.04-0.47; P = 0.002), detected in 37.6%, was associated with benefit from temsirolimus. Conclusions: Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter. Phosphorylation of mTORSer2448 in the pretreatment tumor tissue may define a subgroup benefitting from mTOR inhibition. Clin Cancer Res; 22(19); 4797-806. © 2016 American Association for Cancer Research.


PubMed | University of Bristol, Ospedale Bellaria, Netherlands Cancer Institute, University of Lausanne and 15 more.
Type: Journal Article | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016

EORTC 26082 assessed the activity of temsirolimus in patients with newly diagnosed glioblastoma harboring an unmethylated O6 methylguanine-DNA-methyltransferase (MGMT) promoter.Patients (n = 257) fulfilling eligibility criteria underwent central MGMT testing. Patients with MGMT unmethylated glioblastoma (n = 111) were randomized 1:1 between standard chemo-radiotherapy with temozolomide or radiotherapy plus weekly temsirolimus (25 mg). Primary endpoint was overall survival at 12 months (OS12). A positive signal was considered >38 patients alive at 12 months in the per protocol population. A noncomparative reference arm of 54 patients evaluated the assumptions on OS12 in a standard-treated cohort of patients. Prespecified post hoc analyses of markers reflecting target activation were performed.Both therapies were administered per protocol with a median of 13 cycles of maintenance temsirolimus. Median age was 55 and 58 years in the temsirolimus and standard arms, the WHO performance status 0 or 1 for most patients (95.5%). In the per protocol population, 38 of 54 patients treated with temsirolimus reached OS12. The actuarial 1-year survival was 72.2% [95% confidence interval (CI), 58.2-82.2] in the temozolomide arm and 69.6% (95% CI, 55.8-79.9) in the temsirolimus arm [hazard ratio (HR) 1.16; 95% CI, 0.77-1.76; P = 0.47]. In multivariable prognostic analyses of clinical and molecular factors, phosphorylation of mTORSer2448 in tumor tissue (HR 0.13; 95% CI, 0.04-0.47; P = 0.002), detected in 37.6%, was associated with benefit from temsirolimus.Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter. Phosphorylation of mTORSer2448 in the pretreatment tumor tissue may define a subgroup benefitting from mTOR inhibition. Clin Cancer Res; 22(19); 4797-806. 2016 AACR.


Rubinat E.,Hospital Universitari Arnau Of Vilanova | Rubinat E.,University of Lleida | Marsal J.R.,Institute Universitari nvestigacio encio Primaria Jordi Gol IA Jordi Gol | Marsal J.R.,Hospital Universitari Vall ebron | And 11 more authors.
Journal of Cardiovascular Nursing | Year: 2016

Background: Subjects with type 2 diabetes mellitus are considered to be at high risk for cardiovascular disease. The identification of carotid atherosclerosis is a validated surrogate marker of cardiovascular disease. Nurses are key professionals in the improvement and intensification of cardiovascular preventive strategies. Aims: The aim is to study the presence of carotid atherosclerosis in a group of asymptomatic subjects with type 2 diabetes mellitus and no previous clinical cardiovascular disease. Methods: A total of 187 patients with type 2 diabetes mellitus and 187 age-And sex-matched subjects without type 2 diabetes mellitus were studied in this cross-sectional, observational, cohort study. Standard operational procedures were applied by the nursing team regarding physical examination and carotid ultrasound assessment. Common, bulb, and internal carotid arteries were explored by measuring intima-media thickness and identifying atherosclerotic plaques. Results: Carotid intima-media thickness (c-IMT) and carotid plaque prevalence were significantly greater in diabetic subjects than in the control group. Carotid plaques and c-IMT were more frequent in men than in women and increased with increasing age. In the multivariate analysis, age, gender, waist circumference, systolic blood pressure, and hypercholesterolemia were positively associated with c-IMT, whereas age, gender, and weight were positively associated with carotid plaque. Conclusion: The current nurse-led study shows that subjects with type 2 diabetes mellitus have a high prevalence of subclinical atherosclerosis that is associated with cardiovascular risk factors. © Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.


Alcubierre N.,University of Lleida | Rubinat E.,University of Lleida | Traveset A.,University of Lleida | Martinez-Alonso M.,University of Lleida | And 4 more authors.
Health and Quality of Life Outcomes | Year: 2014

Background: To assess quality of life and treatment satisfaction in patients with type 2 diabetes mellitus with diabetic retinopathy (DR) using validated instruments, with comparison to patients without DR. Methods: A prospective cross-sectional study was designed to assess the influence of retinopathy on quality of life and treatment satisfaction in patients with type 2 diabetes mellitus who do not have any other advanced late complications that could interfere with these outcomes. We included 148 patients with DR and 149 without DR, all without other advanced diabetic complications. Quality of life was assessed using the Audit of Diabetes Dependent Quality of Life (ADDQoL) questionnaire, and treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Clinical and treatment variables related to diabetes were also collected. The degree of DR was classified according to the International Clinical Classification System. Multivariate linear regression models were used to model the ADDQoL and DTSQ scores according to sociodemographical and clinical characteristics, and to model the adjusted relationship of DTSQ with ADDQoL. In DR patients, a subanalysis assessed the relationship of these scores with the degree of retinopathy, severity of macular edema, and previous photocoagulation treatment. Results: DR was associated with significantly lower quality of life (p < 0.001), when examining the two general quality of life items and most of the specific domains. Concerning DTSQ, no difference was found in the total score, and only two domains that assess the perception of glycemic control (hyper- and hypoglycemia) showed a worse score in DR (p < 0.001 and p = 0.008, respectively). Quality of life was significantly affected by the severity of DR, and treatment satisfaction was significantly affected by the severity of macular edema. In the multivariate analysis, a significant effect of the interaction between diabetes duration, insulin therapy, and the presence of DR was found for both, ADDQoL and DTSQ. Conclusion: In the absence of other major complications, DR has a negative impact on quality of life in patients with type 2 diabetes. Further, treatment satisfaction was not affected by the presence of DR. © 2014 Alcubierre et al.; licensee BioMed Central Ltd.

Loading Hospital Germans Trias Pujol collaborators
Loading Hospital Germans Trias Pujol collaborators