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Romero A.,Institute Investigacion Sanitaria Hospital Clinico San Carlos | Garcia-Saenz J.A.,Institute Investigacion Sanitaria Hospital Clinico San Carlos | Fuentes-Ferrer M.,Institute Investigacion Sanitaria Hospital Clinico San Carlos | Lopez Garcia-Asenjo J.A.,Hospital Principe de Asturias | And 6 more authors.
Annals of Oncology | Year: 2013

Background: Measurement of residual disease following neoadjuvant chemotherapy that accurately predicts longterm survival in locally advanced breast cancer (LABC) is an essential requirement for clinical trials development. Several methods to assess tumor response have been described. However, the agreement between methods and correlation with survival in independent cohorts has not been reported. Patients and methods: We report survival and tumor response according to the measurement of residual breast cancer burden (RCB), the Miller and Payne classification and the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in 151 LABC patients. Kappa Cohen's coefficient was used to test the agreement between methods. We assessed the correlation between the treatment outcome and overall survival (OS) and relapse-free survival (RFS) by calculating Harrell's C-statistic (c). Results: The agreement between Miller and Payne classification and RCB classes was very high (= 0.82). In contrast, we found a moderate-to-fair agreement between the Miller and Payne classification and RECIST criteria (= 0.52) and RCB classes and RECIST criteria (= 0.38). The adjusted C-statistic to predict OS for RCB index (0.77) and RCB classes (0.75) was superior to that of RECIST criteria (0.69) (P = 0.007 and P = 0.035, respectively). Also, RCB index (c = 0.71), RCB classes (c = 0.71) and Miller and Payne classification (c = 0.67) predicted better RFS than RECIST criteria (c = 0.61) (P = 0.005, P = 0.006 and P = 0.028, respectively). Conclusions: The pathological assessment of tumor response might provide stronger prognostic information in LABC patients. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Del Rosal T.,Hospital Universitario La Paz | Baquero-Artigao F.,Hospital Universitario La Paz | Blazquez D.,Hospital 12 de Octubre | Noguera-Julian A.,University of Barcelona | And 3 more authors.
Journal of Clinical Virology | Year: 2012

Background: Congenital cytomegalovirus (CMV) is an important cause of sensorineural hearing loss. Ganciclovir treatment in the neonatal period may prevent hearing deterioration in infants with central nervous system (CNS) involvement. However, there are hardly any data regarding antiviral treatment begun beyond the neonatal period. Objectives: To describe the hearing outcome of infants with congenital CMV infection and CNS involvement treated beyond the neonatal period. To assess the tolerability and toxicity of prolonged valganciclovir treatment in these patients. Study design: Retrospective case series of infants with congenital CMV infection and CNS involvement who started antiviral treatment beyond the neonatal period in Spain between 2008 and 2010. Hearing was tested by brainstem-evoked response at the time of diagnosis, 6 and 12 months after the beginning of treatment. Results: Thirteen cases were included. All received oral valganciclovir, and 4 also intravenous ganciclovir. Median valganciclovir treatment duration was 6 months and it was well tolerated. Six patients developed neutropenia, none requiring granulocyte colony-stimulating factor. Eleven children (85%) had hearing defects at baseline, compared to 50% at 12 months. By ears, 18 ears showed hearing loss at baseline (7 mild, 3 moderate, 8 severe). At 12 months, 9 remained stable, 7 had improved and none had worsened. In 8 normal ears at baseline, no deterioration was found at 12 months. Conclusions: Valganciclovir treatment is well tolerated. It may improve or preserve the auditory function of congenitally cytomegalovirus-infected patients treated beyond the neonatal period for at least one year after the beginning of antiviral treatment. © 2012 Elsevier B.V.

Garcia de Lorenzo A.,Hospital Universitario La Paz | Alvarez Hernandez J.,Hospital Principe de Asturias | Planas M.,University of Vic | Burgos R.,Hospital Vall DHebron | Araujo K.,Nestle
Nutricion Hospitalaria | Year: 2011

Rationale: Disease-related malnutrition constitutes a highly prevalent healthcare problem with high costs associated. In Spain, the prevalence of malnutrition in hospitalized patients has been reported from 30% to 50%. Objectives: Main purposes of this consensus document were to establish recommendations that facilitate decision- making and action to prevent and early-diagnose disease-related hospital malnutrition, on the management of nutritional support methods and actions to evaluate nutritional treatment compliance and efficacy. Methods: A systematic bibliographical search of authors was performed, complemented by updated bibliography by author references up to 2010. From this review, some recommendations were defined, modified and critically evaluated by the representatives of scientific societies in a consensus conference (Dec 2010) following a structured brainstorming technique: the Metaplan ® technique. A double validation process was undertaken until final recommendations were obtained. Results: 30 consensus recommendations for the prevention and management of hospital malnutrition are presented in this document. Recommendations cover all clinical care settings as well as prevention, screening, diagnosis, treatment and follow-up of disease-related malnutrition. Conclusions: Nutritional screening is strongly recommended at all clinical settings when nutritional risk factors are identified or there is clinical suspicion of malnutrition. Nutritional assessment should be designed and performed according to centers' resources, but clearly identified protocols should be available.

Barrio S.,Hospital Universitario 12 Of Octubre | Gallardo M.,Hospital Universitario 12 Of Octubre | Gallardo M.,University of Texas M. D. Anderson Cancer Center | Arenas A.,Hospital Universitario 12 Of Octubre | And 8 more authors.
British Journal of Haematology | Year: 2013

This study aimed to assess the antitumour effects, molecular mechanisms of action, and potential synergy of ruxolitinib with sorafenib, KNK437, dasatinib, and perifosine, in Philadelphia-negative chronic myeloproliferative neoplasms (MPN). Cytotoxic and cytostatic effects of the different compounds were determined in the JAK2 V617F-positive cell lines, HEL and Ba/F3 JAK2V617F EPOR, and in primary mononuclear and bone marrow CD34-positive cells from 19 MPN patients. Ruxolitinib [50% inhibitory concentration (IC50)PV = 15 nmol/l], as well as sorafenib (IC50 PV=8μmol/l), KNK437 (IC50 PV=100μmol/l ), and perifosine (IC50 PV=15μmol/l ), were able to inhibit proliferation in cell line models and in primary cells from MPN patients. Dasatinib, KNK437, and sorafenib showed a strong synergistic effect in combination with ruxolitinib [combination index (CI)PV < 0·3]. Western blot confirmed that ruxolitinib blocked ERK, and consequently STAT5 activation, sorafenib inhibited ERK, P38 and STAT5, dasatinib blocked SRC and STAT5, and KNK437 decreased the stability of the JAK2 protein, reducing its expression. Inhibiting JAK2-related proliferative pathways has the potential to inhibit cell proliferation in MPNs. Furthermore, the combination of ruxolitinib with inhibitors that target these pathways has a strong synergistic effect, which may be due to decreased activation of the common effector, STAT5. © 2013 John Wiley & Sons Ltd.

Flores-Chavez M.D.,Institute Salud Carlos III Carlos III Health Institute | Merino F.J.,Hospital Universitario Severo Ochoa | Garcia-Bujalance S.,Hospital Universitario La Paz | Martin-Rabadan P.,Hospital Gregorio Maranon | And 4 more authors.
Eurosurveillance | Year: 2011

One of the most important modes of transmission of Trypanosoma cruzi infection in areas where it is not endemic is vertical transmission: from mother to child. The objective of this report is to assess the efficacy of different programmes of serological screening to monitor infection with T. cruzi in pregnant Latin American women living in Madrid (Spain). To achieve this, a retrospective study was undertaken from January 2008 to December 2010 in seven hospitals in the Autonomous Community of Madrid. Serological screening programmes were classified in two main strategies: a selective one (pregnant women from Bolivia) and a universal one (pregnant women from Latin America). A total of 3,839 pregnant women were tested and the overall prevalence was 3.96%. The rate of congenital transmission was 2.6%. The current monitoring programmes have variable coverage ranging between 26% (selective screening) and 100% (universal screening). Monitoring of pregnant women from Latin America only reaches full coverage if universal screening of pregnant women is carried out at any moment of pregnancy, including at delivery. A common national regulation is necessary in order to ensure homogenous implementation of screening.

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