Marin M.J.D.C.,Hospital Universitario Ramon y Cajal |
Rotes A.S.,Autonomous University of Barcelona |
Ogando A.R.,Hospital Gregorio Maranon |
Soto A.M.,Hospital Universitario 12 Of Octubre |
And 6 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2014
Rationale: There is a lack of knowledge regarding the epidemiology, clinical characterization, and survival in pediatric pulmonary hypertension.Objectives: To describe the epidemiology, outcomes, and risk factors for mortality in pediatric pulmonary hypertension in Spain.Conclusions: In moderate to severe pediatric pulmonary hypertension, the prognosis is better in pulmonary arterial hypertension than in other Nice categories. In pediatric pulmonary hypertension age at diagnosis younger than 2 years is a risk factor for mortality, in addition to the previously established risk factors.Methods: We analyzed data from the Spanish Registry for Pediatric Pulmonary Hypertension. From January 2009 to June 2012, a total of 225 patients diagnosed with pulmonary hypertension in 1998 or after were collected from 21 referral and nonreferral centers. We included all Nice etiologies, estimated incidence and prevalence of pulmonary hypertension in the Spanish pediatric population, and analyzed risk factors for mortality (Nice etiologic group, clinical and hemodynamic variables). Patients were classified as follows: group I, pulmonary arterial hypertension (n = 142; 61%); group II, left heart disease (n = 31; 14%); group III, respiratory disease (n = 41; 18%); group IV, thromboembolic pulmonary hypertension (n = 2; 1%); or group V, mostly inherited metabolic diseases (n = 10; 4.5%). Of the patients studied, 31% had multifactorial pulmonary hypertension.Measurements and Main Results: Mean age at diagnosis was 4.364.9 years (50%,2 yr). Survival rates at 1 and 3 years were 80 and 74% for the whole cohort, and 89 and 85% for patients with pulmonary arterial hypertension. Independent risk factors for mortality included an etiologic group other than pulmonary arterial hypertension (P<0.001), age at diagnosis younger than 2 years old (P<0.001), advanced functional class at diagnosis (P<0.001), and high right atrial pressure at diagnosis (P = 0.002). Copyright © 2014 by the American Thoracic Society.
Martinez-Balibrea E.,Hospital Germans Trias i Pujol |
Martinez-Balibrea E.,Fundacio Institutdinvestigacio En Ciencies Of La Salut Germans Trias I Pujol C Ctra Of Can Ruti |
Abad A.,Hospital Germans Trias i Pujol |
Abad A.,Fundacio Institutdinvestigacio En Ciencies Of La Salut Germans Trias I Pujol C Ctra Of Can Ruti |
And 15 more authors.
British Journal of Cancer | Year: 2010
Background: The impact of thymidylate synthase (TYMS) and UDP-glucoronosyltransferase 1A (UGT1A) germline polymorphisms on the outcome of colorectal cancer (CRC) patients treated with irinotecan plus 5-fluorouracil (irinotecan/5FU) is still controversial. Our objective was to define a genetic-based algorithm to select patients to be treated with irinotecan/5FU. Methods: Genotyping of TYMS (5′TRP and 3′UTR), UGT1A1 28, UGT1A9 22 and UGT1A7 3 was performed in 149 metastatic CRC patients treated with irinotecan/5FU as first-line chemotherapy enrolled in a randomised phase 3 study. Their association with response, toxicity and survival was investigated by univariate and multivariate statistical analysis. Results: TYMS 3TRP/3TRP genotype was the only independent predictor of tumour response (OR5.87, 95% confidence interval (CI)1.68-20.45; P=0.005). UGT1A1 28/28 was predictive for haematologic toxicity (OR=6.27, 95% CI1.09-36.12; P=0.04), specifically for neutropenia alone (OR=6.40, 95% CI=1.11-37.03; P=0.038) or together with diarrhoea (OR18.87, 95% CI2.14-166.67; P=0.008). UGT1A9 1/1 was associated with non-haematologic toxicity (OR=2.70, 95% CI1.07-6.82; P=0.035). Haplotype VII (all non-favourable alleles) was associated with non-haematologic toxicity (OR=2.11, 95% CI1.12-3.98; P=0.02).Conclusion:TYMS and UGT1A polymorphisms influence on tumour response and toxicities derived from irinotecan/5FU treatment in CRC patients. A genetic-based algorithm to optimise treatment individualisation is proposed. © 2010 Cancer Research UK All rights reserved.
Cortes-Gutierrez E.I.,Instituto Mexicano del Seguro Social |
Davila-Rodriguez M.I.,Instituto Mexicano del Seguro Social |
Fernandez J.L.,Complejo Hospitalario Universitario Juan Canalejo |
Lopez-Fernandez C.,Autonomous University of Madrid |
And 2 more authors.
Journal of Histochemistry and Cytochemistry | Year: 2011
The comet assay is a well-established, simple, versatile, visual, rapid, and sensitive tool used extensively to assess DNA damage and DNA repair quantitatively and qualitatively in single cells. The comet assay is most frequently used to analyze white blood cells or lymphocytes in human biomonitoring studies, although other cell types have been examined, including buccal, nasal, epithelial, and placental cells and even spermatozoa. This study was conducted to design a protocol that can be used to generate comets in subnuclear units, such as chromosomes. The new technique is based on the chromosome isolation protocols currently used for whole chromosome mounting in electron microscopy, coupled to the alkaline variant of the comet assay, to detect DNA damage. The results show that migrant DNA fragments can be visualized in whole nuclei and isolated chromosomes and that they exhibit patterns of DNA migration that depend on the level of DNA damage produced. This protocol has great potential for the highly reproducible study of DNA damage and repair in specific chromosomal domains. © The Author(s) 2011.
Lopez-Fernandez C.,Autonomous University of Madrid |
Johnston S.D.,University of Queensland |
Fernandez J.L.,Complejo Hospitalario Universitario Juan Canalejo |
Wilson R.J.,University of Queensland |
Gosalvez J.,Autonomous University of Madrid
Theriogenology | Year: 2010
This study investigated the hypothesis that post-thaw incubation of ram sperm at high concentrations results in a faster rate of DNA fragmentation than when sperm are incubated at a lower concentration. Ejaculates from 10 rams were frozen-thawed, prepared in sperm concentrations of 100, 50, 25, 12, and 6 × 106 sperm/mL, and incubated for 6 h at 37 °C. Sperm DNA fragmentation was assessed using the sperm chromatin dispersion test (Sperm-Halomax®) at 1, 3, 4, and 6 h of incubation at 37 °C. On fitting a binary logistic regression with a cubic over time and treating ram and dilution levels as factors, there were significant effects with respect to the ram, dilution and time (all P-values were very much smaller than 0.001). Therefore, DNA fragmentation dynamics of incubated frozen-thawed ram sperm were not only dependent on the inherent sperm DNA fragmentation expressed immediately after thawing, but also on the concentration of sperm incubated in the sample. Although there was evidence of individual ram variation in SDF during the incubation period, the general finding of the current study was that lower sperm concentrations resulted in a slower rate of DNA fragmentation These findings have important implications for the post-thaw manipulation of ram sperm used for AI and advanced reproductive procedures that use sperm at low concentrations. Our data also emphasised the highly dynamic nature of sperm DNA fragmentation and the importance of conducting the procedure in a standardised manner. © 2010 Elsevier Inc.
PubMed | Complutense University of Madrid, Hospital Universitario Donosti, University of Barcelona, iversitario Gregorio Maranon and 9 more.
Type: Journal Article | Journal: The Journal of infection | Year: 2015
To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery.Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals.A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p < 0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p < 0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery.Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated.
Fernandez-Berges D.,Fundesalud Hospital Don Benito Villanueva |
Bertomeu-Gonzalez V.,Hospital Universitario La Paz |
Sanchez P.L.,Hospitales Universitarios Salamanca y Valladolid |
Cruz-Fernandez J.M.,Hospital Virgen Of Macarena |
And 6 more authors.
International Journal of Cardiology | Year: 2011
Background: Risk stratification of patients with unstable angina or non-ST-segment elevation myocardial infarction (UA/NSTEMI) is problematic given the heterogeneous presentation of the condition. This study was undertaken to compare, in UA/NSTEMI patients, the prognostic value of two clinical risk scores (RS) (i.e. Thrombolysis in Myocardial Infarction (TIMI) and physician's risk assessment (PRA)) and to assess whether serum biomarkers can increase the prognostic accuracy of these RS. Methods: We prospectively assessed 610 consecutive UA/NSTEMI patients, 217 (36%) UA and 393 (64%) NSTEMI. In all patients RS, high sensitivity C-reactive protein, CD40 ligand, IL6, IL10, IL18, E-selectin, P-selectin, white blood cell count, neopterin, myeloperoxidase, fibrinogen and NT proBNP were assessed at study entry. The primary study endpoint was death and non-fatal MI at 30 and 360 days of follow-up. Results: At 1 year, 54 patients (8.9%) had reached the primary study endpoint (26 suffered a cardiac death (4.3%) and 34 (5.6%) a non-fatal MI). For both RS, the study endpoint occurred more commonly in patients at a "higher risk" compared to those classified as being at a "lower risk". Moreover, TIMI and PRA RS had similar discriminatory accuracy. TIMI RS, however, was a better predictor of events than PRA at both 30- and 360-day follow-up. The inflammatory biomarkers assessed in the study did not improve significantly the predictive value of RS. Conclusions: Our study suggests both that TIMI RS is a better marker of risk than PRA RS and inflammatory biomarkers do not increase the predictive value of these clinical risk scores. © 2009 Elsevier Ireland Ltd. All rights reserved.
Guerrero A.,Instituto Valenciano Of Oncologia |
Servitja S.,Hospital Del Mar |
Rodriguez-Lescure A.,Hospital General Universitario Of Elche |
Calvo L.,Complejo Hospitalario Universitario Juan Canalejo |
And 6 more authors.
Anti-Cancer Drugs | Year: 2011
The objective of this phase I/II study was to establish the recommended dose of biweekly vinorelbine and oxaliplatin in patients with metastatic breast cancer and to evaluate the efficacy and safety profile of this schedule as first-line treatment. Four different dose levels of vinorelbine and oxaliplatin were selected for the phase I study: (i) 25 and 80 mg/m2; (ii) 25 and 90 mg/m2; (iii) 25 and 100 mg/m2; and (iv) 30 and 90 mg/m2; respectively. At least three patients were treated at each dose level. Overall, 12 patients were included in the phase I trial. No dose-limiting toxicities occurred at any dose level. Therefore, the fourth dose level (30 mg/m of vinorelbine and 90 mg/m2 of oxaliplatin) every 2 weeks was selected for the phase II trial. In this part, 44 patients were included and 61% completed the eight 2-week cycles of study treatment. On an intention-to-treat basis, overall response rate was 59%, and median progression-free survival and overall survival were 9.2 months (95% confidence interval: 7.6-10.9) and 18.6 months (95% confidence interval: 14.4-22.9), respectively. The main severe toxicities were neutropenia (46%) and fatigue (14%). We conclude that the biweekly combination of vinorelbine and oxaliplatin at doses of 30 mg/m and 90 mg/m2, respectively, is highly active and well tolerated as first-line treatment for patients with metastatic breast cancer. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Song W.,Imperial College London |
Dyer E.,Imperial College London |
Stuckey D.J.,Imperial College London |
Copeland O.,Imperial College London |
And 13 more authors.
Journal of Biological Chemistry | Year: 2011
We generated a transgenic mouse model expressing the apical hypertrophic cardiomyopathy-causing mutation ACTC E99K at 50% of total heart actin and compared it with actin from patients carrying the same mutation. The actin mutation caused a higher Ca 2+ sensitivity in reconstituted thin filaments measured by in vitro motility assay (2.3-fold for mice and 1.3-fold for humans) and in skinned papillary muscle. The mutation also abolished the change in Ca 2+ sensitivity normally linked to troponin I phosphorylation. MyBP-C and troponin I phosphorylation levels were the same as controls in transgenic mice and human carrier heart samples. ACTC E99K mice exhibited a high death rate between 28 and 45 days (48% females and 22% males). At 21 weeks, the hearts of the male survivors had enlarged atria, increased interstitial fibrosis, and sarcomere disarray. MRI showed hypertrophy, predominantly at the apex of the heart. End-diastolic volume and end-diastolic pressure were increased, and relaxation rates were reduced compared with non-transgenic littermates. End-systolic pressures and volumes were unaltered. ECG abnormalities were present, and the contractile response to β-adrenergic stimulation was much reduced. Older mice (29-week-old females and 38-week-old males) developed dilated cardiomyopathy with increased end-systolic volume and continuing increased end-diastolic pressure and slower contraction and relaxation rates. ECG showed atrial flutter and frequent atrial ectopic beats at rest in some ACTC E99K mice. We propose that the ACTC E99K mutation causes higher myofibrillar Ca 2+ sensitivity that is responsible for the sudden cardiac death, apical hypertrophy, and subsequent development of heart failure in humans and mice. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
PubMed | Hospital Comarcal Of Monforte Of Lemos, Hospital Povisa, Complejo Hospitalario Of Pontevedra, Complejo Hospitalario Universitario Of Vigo and 4 more.
Type: Clinical Conference | Journal: Revista de neurologia | Year: 2016
The effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) have been proven in clinical trials. Yet, due to their limitations, it is important to know how it behaves under everyday clinical practice conditions. Hence, the aim of this study is to evaluate the effectiveness and safety of fingolimod after 12 months usage in clinical practice in Galicia. We conducted a retrospective, multi-centre study (n = 8) of patients with RRMS who were treated with one or more doses of fingolimod, 0.5 mg/day. Effectiveness was assessed -annualised relapse rate (ARR), changes in the score on the Expanded Disability Status Scale (EDSS), percentage of patients free from relapses, free from progression of disability and free from activity in resonance- for the total number of patients and according to previous treatment. Safety was assessed based on the percentage of patients who withdrew and presented adverse side effects. After 12 months use, fingolimod reduced the ARR by 87% (1.7 to 0.23; p < 0.0001) and, consequently, 81% of patients were free from relapses. The score was reduced by 9%. In all, 91% of patients were free from progression of disability and 72% were free from resonance activity. No signs of disease activity were found in 43% of the patients. Most of the benefits of fingolimod differed depending on previous treatment. About a third of the patients reported adverse side effects, but only 2% of them withdrew for this reason. In clinical practice, most of the results on the effectiveness of the clinical trials conducted with fingolimod were observed during the first 12 months of treatment. A better safety profile was observed than that reported in the clinical trials.
PubMed | Hospital Universitario Virgen Of Las Nieves, Hospital Universitario Of Gran Canaria Dr Negrin, Hospital Universitario Ramon y Cajal, Complejo Hospitalario Universitario Juan Canalejo and 2 more.
Type: Journal Article | Journal: Revista espanola de anestesiologia y reanimacion | Year: 2015
To determine the protocols used by Spanish anaesthesiologists for thromboprophylaxis and anticoagulant or antiplatelet drugs management in neurosurgical or neurocritical care patients.An online survey with 22 questions, with one or multiple options, launched by the Neuroscience Subcommittee of the Spanish Anaesthesia Society and available between June and October 2012.Of the 73 hospitals included in the National Hospitals Catalogue, a valid response to the online questionnaire was received by 41 anaesthesiologists from 37 sites (response rate 50.7%). Only one response per site was used. A specific protocol was available in 27% of these centres. Mechanical thromboprophylaxis is used, intraoperatively or postoperatively, in 80%, and pharmacological treatment is used by 75% of respondents. Enoxaparin was the most frequent heparin used in craniotomy patients (78%). Craniotomies were performed maintaining acetylsalicylic acid treatment in patients with coronary stents and double anti-platelet treatment in a half of the centres.Mechanical thromboprophylaxis is used more frequently than the pharmacological approach in neurosurgical or neurocritical populations in Spanish hospitals. Management of patients under previous anticoagulant treatment was highly heterogeneous among hospitals included in this survey. Previous antiplatelet treatment is modified depending on primary or secondary prescription.