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Gomez-Doblas J.J.,Hospital Clinico Universitario Virgen Of La Victoria | Muniz J.,University of La Coruña | Martin J.J.A.,Hospital Universitario Of Fuenlabrada | Awamleh P.,Hospital Universitario Of Fuenlabrada | And 4 more authors.
Revista Espanola de Cardiologia | Year: 2014

Introduction and objectives Atrial fibrillation is associated with substantial morbidity and mortality and both its incidence and prevalence are high. Nevertheless, comprehensive data on this condition in Spain are lacking. The aim of this study was to estimate the prevalence of atrial fibrillation in Spain. Methods A cross-sectional study was conducted in the general Spanish population older than 40 years. Two-stage random sampling was used, in which first-stage units were primary care physicians randomly selected in every Spanish province and second-stage units were 20 randomly selected persons drawn from each participating physician's assigned population. The reported prevalence was standardized for the age and sex distribution of the Spanish population. The electrocardiogram recordings were read centrally. Results Overall, 8343 individuals were evaluated. The mean age was 59.2 years (95% confidence interval, 58.6-59.8 years), and 52.4% of the participants were female. The overall age-adjusted prevalence of atrial fibrillation was 4.4% (95% confidence interval, 3.8-5.1). Prevalence was similar in both sexes, men 4.4% (3.6-5.2) and women 4.5% (3.6-5.3), rising with increasing age older than 60 years. In patients older than 80 years, the prevalence was 17.7% (14.1-21.3). In 10% of patients an unknown atrial fibrillation was diagnosed. Conclusions The prevalence of atrial fibrillation in the general Spanish population older than 40 years is high, at 4.4%. The prevalence is similar in both sexes and rises steeply above 60 years of age. It is estimated that there are over 1 million patients with atrial fibrillation in the Spanish population, of whom over 90 000 are undiagnosed. Full English text available from: www.revespcardiol.org/en.


Jerez J.M.,University of Malaga | Molina I.,University of Malaga | Garcia-Laencina P.J.,Technical University of Cartagena | Alba E.,Hospital Clinico Universitario Virgen Of La Victoria | And 3 more authors.
Artificial Intelligence in Medicine | Year: 2010

Objectives: Missing data imputation is an important task in cases where it is crucial to use all available data and not discard records with missing values. This work evaluates the performance of several statistical and machine learning imputation methods that were used to predict recurrence in patients in an extensive real breast cancer data set. Materials and methods: Imputation methods based on statistical techniques, e.g., mean, hot-deck and multiple imputation, and machine learning techniques, e.g., multi-layer perceptron (MLP), self-organisation maps (SOM) and k-nearest neighbour (KNN), were applied to data collected through the "El Álamo-I" project, and the results were then compared to those obtained from the listwise deletion (LD) imputation method. The database includes demographic, therapeutic and recurrence-survival information from 3679 women with operable invasive breast cancer diagnosed in 32 different hospitals belonging to the Spanish Breast Cancer Research Group (GEICAM). The accuracies of predictions on early cancer relapse were measured using artificial neural networks (ANNs), in which different ANNs were estimated using the data sets with imputed missing values. Results: The imputation methods based on machine learning algorithms outperformed imputation statistical methods in the prediction of patient outcome. Friedman's test revealed a significant difference (p=0.0091) in the observed area under the ROC curve (AUC) values, and the pairwise comparison test showed that the AUCs for MLP, KNN and SOM were significantly higher (p=0.0053, p=0.0048 and p=0.0071, respectively) than the AUC from the LD-based prognosis model. Conclusion: The methods based on machine learning techniques were the most suited for the imputation of missing values and led to a significant enhancement of prognosis accuracy compared to imputation methods based on statistical procedures. © 2010 Elsevier B.V.


Fernandez I.F.,University of Salamanca | Blanco S.,University of Salamanca | Blanco S.,Wellcome Trust Center for Stem Cell Research | Lozano J.,University of Malaga | And 2 more authors.
Molecular and Cellular Biology | Year: 2010

The epidermal growth factor (EGF)-ErbB-mitogen-activated protein kinase (MAPK) transcription signaling pathway is altered in many types of carcinomas, and this pathway can be regulated by new protein-protein interactions. Vaccinia-related kinase (VRK) proteins are Ser-Thr kinases that regulate several signal transduction pathways. In this work, we study the effect of VRK2 on MAPK signaling using breast cancer as a model. High levels of VRK2 inhibit EGF and ErbB2 activation of transcription by the serum response element (SRE). This effect is also detected in response to H-Ras(G12V) or B-Raf(V600E) oncogenes and is accompanied by a reduction in phosphorylated extracellular signal-regulated kinase (ERK) levels, p90RSK levels, and SRE-dependent transcription. Furthermore, VRK2 knockdown has the opposite effect, increasing the transcriptional response to stimulation with EGF and leading to increased levels of ERK phosphorylation. The molecular mechanism lies between MAPK/ERK kinase (MEK) and ERK, since MEK remains phosphorylated while ERK phosphorylation is blocked by VRK2A. This inhibition of the ERK signaling pathway is a consequence of a direct protein-protein interaction between VRK2A, MEK, and kinase suppressor of Ras 1 (KSR1). Identification of new correlations in human cancer can lead to a better understanding of the biology of individual tumors. ErbB2 and VRK2 protein levels were inversely correlated in 136 cases of human breast carcinoma. In ErbB2+ tumors, there is a significant reduction in the VRK2 level, suggesting a role for VRK2A in ErbB2-MAPK signaling. Thus, VRK2 downregulation in carcinomas permits signal transmission through the MEK-ERK pathway without affecting AKT signaling, causing a signal imbalance among pathways that contributes to the phenotype of breast cancer. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Vicente Delgado A.,Hospital Virgen Of La Salud | Gomez Enterria P.,Hospital Universitario Central Of Asturias | Tinahones Madueno F.,Hospital Clinico Universitario Virgen Of La Victoria
Endocrinologia y Nutricion | Year: 2011

Endocrinology and Clinical Nutrition are branches of Medicine that deal with the study of physiology of body glands and hormones and their disorders, intermediate metabolism of nutrients, enteral and parenteral nutrition, promotion of health by prevention of diet-related diseases, and appropriate use of the diagnostic, therapeutic, and preventive tools related to these disciplines. Development of Endocrinology and Clinical Nutrition support services requires accurate definition and management of a number of complex resources, both human and material, as well as adequate planning of the care provided. It is therefore essential to know the services portfolio of an ideal Department of Endocrinology and Clinical Nutrition because this is a useful, valid and necessary tool to optimize the available resources, to increase efficiency, and to improve the quality of care. © 2010 SEEN.


Fumoleau P.,Center Georges Francois Leclerc | Trigo J.M.,Hospital Clinico Universitario Virgen Of La Victoria | Isambert N.,Center Georges Francois Leclerc | Semiond D.,Sanofi S.A. | And 2 more authors.
BMC Cancer | Year: 2013

Background: Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary objectives were to report dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were secondary objectives. Methods: Cabazitaxel was administered weekly (1-hour intravenous infusion at 1.5-12 mg/m2 doses) for the first 4 weeks of a 5-week cycle in patients with solid tumours. Monitoring of DLTs was used to determine the MTD and the recommended weekly dose. Results: Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m2, which was declared the MTD. Gastrointestinal disorders were the most common adverse event. Eight patients developed neutropenia (three ≥ Grade 3); one occurrence of febrile neutropenia was reported. There were two partial responses (in breast cancer) and 13 patients had stable disease (median duration of 3.3 months). Increases in Cmax and AUC0-t were dose proportional for the 6-12 mg/m2 doses. Conclusion: The MTD of weekly cabazitaxel was 12 mg/m2 and the recommended weekly dose was 10 mg/m2. The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens.Trial registration: The study was registered with ClinicalTrials.gov as NCT01755390. © 2013 Fumoleau et al.; licensee BioMed Central Ltd.


Oliver J.A.,University of Granada | Ortiz R.,University of Granada | Ortiz R.,University of Jaén | Melguizo C.,University of Granada | And 3 more authors.
BMC Cancer | Year: 2014

Background: New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments. O6-methylguanine DNA methyltransferase (MGMT) methylation and protein expression have been related to colorectal cancer treatment failure and tumor progression. Moreover, the presence in these tumors of cancer stem cells, which are characterized by CD133 expression, has been associated with chemoresistance, radioresistance, metastasis, and local recurrence. The objective of this study was to determine the prognostic value of CD133 and MGMT and their possible interaction in colorectal cancer patients.Methods: MGMT and CD133 expression was analyzed by immunohistochemistry in 123 paraffin-embedded colorectal adenocarcinoma samples, obtaining the percentage staining and intensity. MGMT promoter methylation status was obtained by using bisulfite modification and methylation-specific PCR (MSP). These values were correlated with clinical data, including overall survival (OS), disease-free survival (DFS), tumor stage, and differentiation grade.Results: Low MGMT expression intensity was significantly correlated with shorter OS and was a prognostic factor independently of treatment and histopathological variables. High percentage of CD133 expression was significantly correlated with shorter DFS but was not an independent factor. Patients with low-intensity MGMT expression and ≥50% CD133 expression had the poorest DFS and OS outcomes.Conclusions: Our results support the hypothesis that MGMT expression may be an OS biomarker as useful as tumor stage or differentiation grade and that CD133 expression may be a predictive biomarker of DFS. Thus, MGMT and CD133 may both be useful for determining the prognosis of colorectal cancer patients and to identify those requiring more aggressive adjuvant therapies. Future studies will be necessary to determine its clinical utility. © 2014 Oliver et al.; licensee BioMed Central Ltd.


von Minckwitz G.,Neu Isenburg and Universitats Frauenklinik Frankfurt | Martin M.,Hospital Universitario Gregorio Maranon | Wilson G.,Christie Hospital | Alba E.,Hospital Clinico Universitario Virgen Of La Victoria | And 3 more authors.
Critical Reviews in Oncology/Hematology | Year: 2013

The first-generation taxanes, conventional paclitaxel and docetaxel, are established treatment options for adjuvant and metastatic breast cancer (MBC). However, these agents have limitations, including primary/secondary resistance and harsh toxicities. The introduction of paclitaxel albumin represents a significant advance in taxane therapy as the first of a new generation of taxanes. This agent utilizes albumin pathways to achieve enhanced and targeted drug delivery to the tumour. The lack of solvent also means that it is well tolerated, despite the lack of premedications. Paclitaxel albumin is licensed in the United States and Europe as ≥2nd-line therapy in MBC (260mg/m2 once every three weeks), but emerging evidence suggests it has activity in various settings as weekly therapy and in combination with other agents. Additional strategies to optimize taxane-based therapy are also being evaluated, including the possibility of tailoring treatment according to patient/disease characteristics, identifying predictive biomarkers and evaluating other novel taxanes. © 2012 Elsevier Ireland Ltd.


Lastra-Aras E.,Complejo Asistencial Universitario Of Burgos | Robles-Diaz L.,Hospital Universitario Doce Of Octubre | Guillen-Ponce C.,Hospital Universitario Ramon y Cajal | Alba E.,Hospital Clinico Universitario Virgen Of La Victoria | Cruz J.-J.,Hospital Universitario Of Salamanca
Clinical and Translational Oncology | Year: 2013

Introduction: Approximately 5 % of all cancer cases are hereditary. Cancer genetic counseling assesses individual and family risks of cancer, conducts genetic studies, interprets results, and advises patients regarding strategies for prevention and risk reduction. Currently, many networks of hereditary cancer genetic counseling units (HCGCUs) are integrated in the medical oncology services of most Spanish hospitals, which are comprised of multidisciplinary teams and offer high-quality care for the treatment of hereditary cancer. Materials and methods: The Spanish Society of Medical Oncology (SEOM) analyzed key issues involving the integration of HCGCUs into the National Health Service. These included basic compliance issues by these units regarding their operation and organization, as well as prerequisites in quality control thereof. Results: This document describes the specific roles and clinical processes performed in HCGCUs in addition to basic services provided by molecular diagnostic laboratories. It also provides a summary on the coordination of care across different levels for patients and families with hereditary cancers. Finally, this document describes the human and material resources needed for the organization of HCGCUs. Conclusions: SEOM has been a pioneer in the creation and development of HCGCUs. This paper seeks to ensure high-quality care to individuals and families with inherited susceptibility to cancer in Spain. © 2012 Federación de Sociedades Españolas de Oncología (FESEO).


Sevilla Garcia M.I.,Hospital Clinico Universitario Virgen Of La Victoria
Revisiones en Cancer | Year: 2012

Neuroendocrine tumors are usually slow growing tumors. Resection of liver metastasis, alone or combined with radiofrequency ablation is the treatment of choice. In patients where surgery is not possible liver embolization or chemoembolization or systemic treatment should be used. Liver transplantation should be reserved for highly selected patients. Copyright ©2012 Aran Ediciones, s. l.


Contreras Molina P.,Hospital Clinico Universitario Virgen Of La Victoria | Flores Carmona E.,Hospital Clinico Universitario Virgen Of La Victoria | Munoz Palza C.A.,Hospital Clinico Universitario Virgen Of La Victoria | Tenor Serrano R.L.,Hospital Clinico Universitario Virgen Of La Victoria
Acta Otorrinolaringologica Espanola | Year: 2012

The abuse of inhaled cocaine causes chemical sinus pathology by secondary midfacial destruction and necrosis. When midfacial necrosis is already established, other complications may occur related to the proximity of structures such as the orbit or optic nerve. We present the evolution of a young cocaine addict with midfacial destruction, who has had a subperiosteal abscess and optic neuritis over the course of the years. Differential diagnosis and management of these complications are also discussed. © 2010 Elsevier España, S.L.

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