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Hospital de Órbigo, Spain

Sanz-Requena R.,Hospital Quiron Valencia | Revert-Ventura A.,Hospital de Manises | Marti-Bonmati L.,Hospital Quiron Valencia | Marti-Bonmati L.,Hospital Universitari i Politecnic la Fe | And 3 more authors.
European Radiology | Year: 2013

Objectives: To evaluate the quantitative parameters obtained from dynamic MR T2*-weighted images as predictors of survival taking into consideration the biasing effects of other survival-related covariates. Methods: Thirty-nine patients (60 ± 14 years; survival 267 ± 191 days) with high-grade gliomas (8 grade III, 31 grade IV) were retrospectively included in the study. Additional data incorporated Karnofsky performance scale, tumour resection extension after surgery and type of treatment. Dynamic T2*-weighted MRI was acquired before treatment. Tumour curves were extracted for each voxel, and several quantitative parameters were obtained from the whole tumour volume and the 10 % maximum values. Additional image covariates included the presence of necrosis, single or multiple lesions, and tumour and oedema volumes. The relationship between quantitative parameters and survival was assessed using clusterisation techniques and the log-rank method. Cox regression analysis was used to evaluate each parameter's predictive value. Results: Only the mean of the 10 % maximum values of the transfer coefficient showed an independent relationship with patient survival (log-rank chi-squared test <0.001, Cox regression P = 0.015), with higher values corresponding to lower survival rates. Conclusions: High maximum transfer coefficient values show an independent statistical relationship with low survival in high-grade glioma patients. This imaging biomarker can be used as a predictor of prognosis. Key Points: • Histological examination is the standard procedure for predicting glioma biological behaviour. • Tumour biopsies may be biased by sample size and location. • Dynamic T2*-weighted MRI quantitative analysis characterises tumour vasculature at the voxel level. • High-transfer constant maximum values are independent predictors of low overall survival. © 2013 European Society of Radiology.

Gisbert J.P.,Hospital Universitario La Paz | Gomollon F.,Hospital Clinico Universitario Of Zaragoza | Hinojosa J.,Hospital de Manises | Roman A.L.S.,Hospital Ramon y Cajal. Madrid. IBDnet
Journal of Crohn's and Colitis | Year: 2010

Background & aims: A European consensus on the management of ulcerative colitis (UC) was recently published; however, there is no adequate evidence about adherence to such guidelines among gastroenterologists. This knowledge would allow the local evaluation of the situation and the adoption of actions to reduce the existent clinical variability. Methods: A cross-sectional survey was conducted in Spain to assess the adherence to the European Crohn's and Colitis Organisation (ECCO) guidelines on mild to moderate UC. We surveyed 700 gastroenterologists, and finally a total of 530 gastroenterologists specialised in inflammatory bowel disease (GSIBDs) and general gastroenterologists (GGs), responded to the survey (76%). Results: Agreement with the guidelines was high; discrepancies included that only 25% of the GGs used the combination of oral and topical 5-aminosalycilic acid (5-ASA) for treating extensive UC vs 45% of the GISBDs. In addition, topical rectal steroids were considered as effective as topical mesalazine by 48% of the GGs vs 31% of the GSIBDs, indefinite treatment with 5-ASA was prescribed by only 26% of the GGs vs 41% of the GSIBDs, and the once daily dosing of 5-ASA was generally used by 46% of the GGs vs 51% of the GSIBDs. Conclusions: The questionnaire showed a high degree of agreement between GGs and GSIBDs. Nevertheless, the GSIBD group showed closer agreement with the ECCO guidelines. Furthermore, some shortcomings were found in the GG group, in which increased maintenance treatment with 5-ASA, the use of a single daily dose of 5-ASA, and the use of combined oral and topical treatment for distal colitis should be advised. © 2010 European Crohn's and Colitis Organisation.

Martorell-Calatayud A.,Hospital de Manises | Sanmartin Jimenez O.,Instituto Valenciano Of Oncologia | Cruz Mojarrieta J.,Instituto Valenciano Of Oncologia | Guillen Barona C.,Instituto Valenciano Of Oncologia
Actas Dermo-Sifiliograficas | Year: 2013

With a lifetime incidence of approximately 10% in the general population, cutaneous squamous cell carcinoma (CSCC) is the second most common type of nonmelanoma skin cancer. Most CSCCs are benign and can be completely eradicated by surgery or other dermatological procedures. There is, however, a subgroup associated with an increased likelihood of lymph node metastases and, therefore, with high morbidity and mortality. This article analyzes the various factors that define aggressive CSCC. We propose a method for defining high-risk SCC on the basis of a series of major and minor criteria. This method will allow better prognostic evaluation and enable personalized management of patients with high-risk SCC, possibly leading to improved overall survival. © 2012 Elsevier España, S.L. y AEDV. Todos los derechos reservados.

Cosin-Roger J.,University of Valencia | Ortiz-Masia D.,University of Valencia | Calatayud S.,University of Valencia | Hernandez C.,FISABIO | And 4 more authors.
PLoS ONE | Year: 2013

Macrophages, which exhibit great plasticity, are important components of the inflamed tissue and constitute an essential element of regenerative responses. Epithelial Wnt signalling is involved in mechanisms of proliferation and differentiation and expression of Wnt ligands by macrophages has been reported. We aim to determine whether the macrophage phenotype determines the expression of Wnt ligands, the influence of the macrophage phenotype in epithelial activation of Wnt signalling and the relevance of this pathway in ulcerative colitis. Human monocyte-derived macrophages and U937-derived macrophages were polarized towards M1 or M2 phenotypes and the expression of Wnt1 and Wnt3a was analyzed by qPCR. The effects of macrophages and the role of Wnt1 were analyzed on the expression of β-catenin, Tcf-4, c-Myc and markers of cell differentiation in a co-culture system with Caco-2 cells. Immunohistochemical staining of CD68, CD206, CD86, Wnt1, β-catenin and c-Myc were evaluated in the damaged and non-damaged mucosa of patients with UC. We also determined the mRNA expression of Lgr5 and c-Myc by qPCR and protein levels of β-catenin by western blot. Results show that M2, and no M1, activated the Wnt signaling pathway in co-culture epithelial cells through Wnt1 which impaired enterocyte differentiation. A significant increase in the number of CD206+ macrophages was observed in the damaged mucosa of chronic vs newly diagnosed patients. CD206 immunostaining co-localized with Wnt1 in the mucosa and these cells were associated with activation of canonical Wnt signalling pathway in epithelial cells and diminution of alkaline phosphatase activity. Our results show that M2 macrophages, and not M1, activate Wnt signalling pathways and decrease enterocyte differentiation in co-cultured epithelial cells. In the mucosa of UC patients, M2 macrophages increase with chronicity and are associated with activation of epithelial Wnt signalling and diminution in enterocyte differentiation. © 2013 Cosín-Roger et al.

Ortiz-Masia D.,University of Valencia | Diez I.,University of Valencia | Calatayud S.,University of Valencia | Hernandez C.,FISABIO | And 4 more authors.
PLoS ONE | Year: 2012

Inflammation is part of a complex biological response of vascular tissue to pathogens or damaged cells. First inflammatory cells attempt to remove the injurious stimuli and this is followed by a healing process mediated principally by phagocytosis of senescent cells. Hypoxia and p38-MAPK are associated with inflammation, and hypoxia inducible factor 1 (HIF-1) has been detected in inflamed tissues. We aimed to analyse the role of p38-MAPK and HIF-1 in the transcriptional regulation of CD36, a class B scavenger receptor, and its ligand thrombospondin (TSP-1) in macrophages and to evaluate the involvement of this pathway in phagocytosis of apoptotic neutrophils. We have also assessed HIF-1α, p38-MAPK and CD36 immunostaining in the mucosa of patients with inflammatory bowel disease. Results show that hypoxia increases neutrophil phagocytosis by macrophages and induces the expression of CD36 and TSP-1. Addition of a p38-MAPK inhibitor significantly reduced the increase in CD36 and TSP-1 expression provoked by hypoxia and decreased HIF-1α stabilization in macrophages. Transient transfection of macrophages with a miHIF-1α-targeting vector blocked the increase in mRNA expression of CD36 and TSP-1 during hypoxia and reduced phagocytosis, thus highlighting a role for the transcriptional activity of HIF-1. CD36 and TSP-1 were necessary for the phagocytosis of neutrophils induced by hypoxic macrophages, since functional blockade of these proteins undermined this process. Immunohistochemical studies revealed CD36, HIF-1α and p38-MAPK expression in the mucosa of patients with inflammatory bowel disease. A positive and significant correlation between HIF-1α and CD36 expression and CD36 and p38-MAPK expression was observed in cells of the lamina propria of the damaged mucosa. Our results demonstrate a HIF-1-dependent up-regulation of CD36 and TSP-1 that mediates the increased phagocytosis of neutrophils by macrophages during hypoxia. Moreover, they suggest that CD36 expression in the damaged mucosa of patients with inflammatory bowel disease depends on p38-MAPK and HIF-1 activity. © 2012 Ortiz-Masià et al.

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