Hospital Universitario 12 Octubre

Madrid, Spain

Hospital Universitario 12 Octubre

Madrid, Spain
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Nelson M.,Chelsea and Westminster Hospital | Rubio R.,Hospital Universitario 12 Octubre | Lazzarin A.,San Raffaele Scientific Institute | Romanova S.,State Research Center Institute of Biophysics | And 6 more authors.
Journal of Interferon and Cytokine Research | Year: 2017

To evaluate the efficacy and safety of pegylated interferon-lambda-1a (Lambda)/ribavirin (RBV)/daclatasvir (DCV) for treatment of patients coinfected with chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Treatment-naive patients were assigned to cohort A [HCV genotype (GT)-2 or -3] or cohort B [HCV GT-1(a or b) or -4]. All patients received Lambda/RBV/DCV for the first 12 weeks; cohort A received Lambda/RBV for an additional 12 weeks, followed by 24 weeks of follow-up, and cohort B received responseguided therapy. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post-treatment week 12 (SVR12). In cohort A (n = 104), 84.6% achieved SVR12 (95.0% in GT-2; 83.1% in GT-3). In cohort B (n = 196), 76.0% achieved SVR12 (71.7% in GT-1a; 86.0% in GT-1b; 70.7% in GT-4). Rates of discontinuation due to adverse events (AEs) (3.8% and 6.1%) and serious AEs (5.8% and 6.1%) were low in cohorts A and B, respectively. In addition, treatment with Lambda/RBV/DCV had little impact on CD4 counts. SVR12 rates with Lambda/RBV/DCV in an HCV/HIV-coinfected population ranged from 71.7% to 95.0%. Treatment was generally well tolerated, with a low proportion of patients discontinuing due to AEs. Clinical trial registration NCT01866930. © Mary Ann Liebert, Inc.


Garcia-Romero A.,IE University | Estrada-Lorenzo J.M.,Hospital Universitario 12 Octubre
Scientometrics | Year: 2014

Plagiarism is one of the most important current debates among scientific stakeholders. A separate but related issue is the use of authors’ own ideas in different papers (i.e., self-plagiarism). Opinions on this issue are mixed, and there is a lack of consensus. Our goal was to gain deeper insight into plagiarism and self-plagiarism through a citation analysis of documents involved in these situations. The Déjà vu database, which comprises around 80,000 duplicate records, was used to select 247 pairs of documents that had been examined by curators on a full text basis following a stringent protocol. We then used the Scopus database to perform a citation analysis of the selected documents. For each document pair, we used specific bibliometric indicators, such as the number of authors, full text similarity, journal impact factor, the Eigenfactor, and article influence. Our results confirm that cases of plagiarism are published in journals with lower visibility and thus tend to receive fewer citations. Moreover, full text similarity was significantly higher in cases of plagiarism than in cases of self-plagiarism. Among pairs of documents with shared authors, duplicates not citing the original document showed higher full text similarity than those citing the original document, and also showed greater overlap in the references cited in the two documents. © 2014, Akadémiai Kiadó, Budapest, Hungary.


Sanchez-Fructuoso A.,Hospital Clinico San Carlos | Guirado L.,Fundacion Puigvert | Ruiz J.C.,Hospital Universitario Marques Of Valdecilla | Torregrosa V.,Hospital Clinic i Provincial | And 3 more authors.
Transplantation Proceedings | Year: 2010

Background Kidney transplant, the gold standard treatment for chronic kidney disease (CKD), is increasingly complicated by anemia. Once-monthly dosing of methoxy polyethylene glycol-epoetin beta provides stable, sustained hemoglobin levels in CKD patients. The present study evaluated anemia control in recipients treated with methoxy polyethylene glycol-epoetin beta to correct or as conversion treatment from other erythropoiesis-stimulating agents (ESAs). Patients and Methods This observational, retrospective study included kidney transplant patients treated with methoxy polyethylene glycol-epoetin beta according to investigators' clinical practice. Information about demographics, CKD, anemia, blood analyses, treatment, and adverse events were collected from patients' medical charts at baseline as well as months 1, 3, and 6. Results From October 2009 to March 2010, the 285 patients in the study included: an overall mean age of 52.8 ± 13.9 years with 146 females (51.2%) and 152 patients (55.1%) in stage 3 CKD. Forty-five patients (15.8%) were in the immediate posttransplant period; 51, nave- treatment (17.9%) and 189, converted subjects (66.3%). Eighty-two of the converted patients (48.0%) had previously received darbepoietin; 81 (47.4%), epoetin beta; and 8 (4.7%), epoetin alfa. The mean doses of methoxy polyethylene glycol-epoetin beta at baseline were 75.0 ± 22.4 μg per month, 95.8 ± 45.5 μg per month, and 118.9 ± 58.9 μg per month among nave, converted, and immediate posttransplant patients, respectively. Mean hemoglobin content varied from baseline to month 6, namely 10.2 ± 0.7 versus 11.8 ± 0.9 g/dL in nave (P < .001) and 11.4 ± 1.3 versus 12.0 ± 1.2 g/dL in converted patients (P = .001). Patients in the immediate posttransplant period showed mean hemoglobin values maintained between 10.4 ± 1.7 g/dL at baseline and 11.5 ± 1.2 g/dL at month 3. The only study-drugrelated adverse event was hypertension. No patient died during the study. Conclusion These preliminary results suggested that hemoglobin stability can be achieved and maintained after correction or conversion to once-monthly methoxy polyethylene glycol-epoetin beta in kidney recipients. It was well tolerated; the safety profile was that expected and comparable with shorter acting ESAs. © 2010 Elsevier Inc.


Pepke-Zaba J.,Papworth Hospital | Delcroix M.,University Hospital Gasthuisberg | Lang I.,Medical University of Vienna | Mayer E.,Kerckhoff Heart and Lung Center | And 18 more authors.
Circulation | Year: 2011

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is often a sequel of venous thromboembolism with fatal natural history; however, many cases can be cured by pulmonary endarterectomy. The clinical characteristics and current management of patients enrolled in an international CTEPH registry was investigated. METHODS AND RESULTS-: The international registry included 679 newly diagnosed (≤6 months) consecutive patients with CTEPH, from February 2007 until January 2009. Diagnosis was confirmed by right heart catheterization, ventilation-perfusion lung scintigraphy, computerized tomography, and/or pulmonary angiography. At diagnosis, a median of 14.1 months had passed since first symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable, and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%- 60.9% across countries) underwent surgery. Operable patients did not differ from nonoperable patients relative to symptoms, New York Heart Association class, and hemodynamics. A history of acute pulmonary embolism was reported for 74.8% of patients (77.5% operable, 70.0% nonoperable). Associated conditions included thrombophilic disorder in 31.9% (37.1% operable, 23.5% nonoperable) and splenectomy in 3.4% of patients (1.9% operable, 5.7% nonoperable). At the time of CTEPH diagnosis, 37.7% of patients initiated at least 1 pulmonary arterial hypertension-targeted therapy (28.3% operable, 53.8% nonoperable). Pulmonary endarterectomy was performed with a 4.7% documented mortality rate. CONCLUSIONS-: Despite similarities in clinical presentation, operable and nonoperable CTEPH patients may have distinct associated medical conditions. Operability rates vary considerably across countries, and a substantial number of patients (operable and nonoperable) receive off-label pulmonary arterial hypertension-targeted treatments. © 2011 American Heart Association, Inc.


PubMed | Hospital Universitario Miguel Servet, Hospital Universitario Infanta Cristina, Hospital Universitario 12 Octubre, Hospital Universitario 12 Of Octubre and Hospital Universitario Of Cruces
Type: Case Reports | Journal: Immunobiology | Year: 2015

Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency caused by impaired Fas/FasL-mediated apoptosis of lymphocytes and is characterized by chronic nonmalignant or benign lymphoproliferation, autoimmune manifestations and expansion of double negative (DN) T-cells (TCR+CD4-CD8-). Most cases of ALPS are associated with germline (ALPS-FAS) or somatic (ALPS-sFAS) heterozygous FAS mutations or a combination of both. Here we report three unrelated patients with ALPS-sFAS. Only one of them showed impaired Fas function in PHA-activated T-cells. In this patient, the genetic analysis of the caspase-10 gene (CASP10) identified a heterozygous germline change in exon 9 (c.1337A>G) causing Y446C substitution in the caspase-10 protein. In addition, this patient had a dysregulated T- and B-cell phenotype; circulating lymphocytes showed expansion of T effector memory CD45RA+ (TEMRA) CD4 T-cells, effector memory CD8 T-cells, CD21(low) B-cells and reduced memory switched B-cells. Additionally, this patient showed altered expression in T-cells of several molecules that change during differentiation from nave to effector cells (CD27, CD95, CD57 and perforin). Molecular alterations in genes of the Fas pathway are necessary for the development of ALPS and this syndrome could be influenced by the concurrent effect of other mutations hitting different genes involved in Fas or related pathways.


von Minckwitz G.,Neu Isenburg and University Womens Hospital | Puglisi F.,University of Udine | Cortes J.,University of Barcelona | Vrdoljak E.,University of Split | And 13 more authors.
The Lancet Oncology | Year: 2014

Background: Combining bevacizumab with first-line or second-line chemotherapy improves progression-free survival in HER2-negative locally recurrent or metastatic breast cancer. We assessed the efficacy and safety of further bevacizumab therapy in patients with locally recurrent or metastatic breast cancer whose disease had progressed after treatment with bevacizumab plus chemotherapy. Methods: In this open-label, randomised, phase 3 trial, we recruited patients who had HER2-negative locally recurrent or metastatic breast cancer that had progressed after receiving 12 weeks or more of first-line bevacizumab plus chemotherapy from 118 centres in 12 countries. Patients were randomly assigned (1:1) by use of a central interactive voice response system using a block randomisation schedule (block size four) stratified by hormone receptor status, first-line progression-free survival, selected chemotherapy, and lactate dehydrogenase concentration, to receive second-line single-agent chemotherapy either alone or with bevacizumab (15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks). Second-line therapy was continued until disease progression, unacceptable toxicity, or consent withdrawal. At progression, patients randomly assigned to chemotherapy alone received third-line chemotherapy without bevacizumab; those randomly assigned to bevacizumab continued bevacizumab with third-line chemotherapy. The primary endpoint was progression-free survival from randomisation to second-line progression or death in the intention-to-treat population. This trial is ongoing, and registered with ClinicalTrials.gov, number NCT01250379. Findings: Between Feb 17, 2011, and April 3, 2013, 494 patients were randomly assigned to treatment (247 in each group). The median duration of follow-up at the time of this prespecified primary progression-free survival analysis was 15·9 months (IQR 9·1-21·7) in the chemotherapy-alone group and 16·1 months (10·6-22·7) in the combination group. Progression-free survival was significantly longer for those patients treated with bevacizumab plus chemotherapy than for those with chemotherapy alone (median: 6·3 months [95% CI 5·4-7·2] vs 4·2 months [3·9-4·7], respectively, stratified hazard ratio [HR] 0·75 [95% CI 0·61-0·93], two-sided stratified log-rank p=0·0068). The most common grade 3 or more adverse events were hypertension (33 [13%] of 245 patients receiving bevacizumab plus chemotherapy vs 17 [7%] of 238 patients receiving chemotherapy alone), neutropenia (29 [12%] vs 20 [8%]), and hand-foot syndrome (27 [11%] vs 25 [11%]). Grade 3 proteinuria occurred in 17 (7%) of 245 patients receiving combination therapy and one (<1%) of 238 patients receiving chemotherapy alone. Serious adverse events were reported in 61 (25%) of 245 patients receiving bevacizumab plus chemotherapy versus 44 (18%) of 238 patients receiving chemotherapy alone. Interpretation: These results suggest that continued VEGF inhibition with further bevacizumab is a valid treatment option for patients with locally recurrent or metastatic HER2-negative breast cancer whose disease was stabilised or responded to first-line bevacizumab with chemotherapy. Funding: F Hoffmann-La Roche. © 2014 Elsevier Ltd.


PubMed | University of Split, Instituto Nazionale Tumori Fondazione G Pascale, Neu Isenburg and University Womens Hospital, University of Barcelona and 10 more.
Type: Clinical Trial, Phase III | Journal: The Lancet. Oncology | Year: 2014

Combining bevacizumab with first-line or second-line chemotherapy improves progression-free survival in HER2-negative locally recurrent or metastatic breast cancer. We assessed the efficacy and safety of further bevacizumab therapy in patients with locally recurrent or metastatic breast cancer whose disease had progressed after treatment with bevacizumab plus chemotherapy.In this open-label, randomised, phase 3 trial, we recruited patients who had HER2-negative locally recurrent or metastatic breast cancer that had progressed after receiving 12 weeks or more of first-line bevacizumab plus chemotherapy from 118 centres in 12 countries. Patients were randomly assigned (1:1) by use of a central interactive voice response system using a block randomisation schedule (block size four) stratified by hormone receptor status, first-line progression-free survival, selected chemotherapy, and lactate dehydrogenase concentration, to receive second-line single-agent chemotherapy either alone or with bevacizumab (15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks). Second-line therapy was continued until disease progression, unacceptable toxicity, or consent withdrawal. At progression, patients randomly assigned to chemotherapy alone received third-line chemotherapy without bevacizumab; those randomly assigned to bevacizumab continued bevacizumab with third-line chemotherapy. The primary endpoint was progression-free survival from randomisation to second-line progression or death in the intention-to-treat population. This trial is ongoing, and registered with ClinicalTrials.gov, number NCT01250379.Between Feb 17, 2011, and April 3, 2013, 494 patients were randomly assigned to treatment (247 in each group). The median duration of follow-up at the time of this prespecified primary progression-free survival analysis was 159 months (IQR 91-217) in the chemotherapy-alone group and 161 months (106-227) in the combination group. Progression-free survival was significantly longer for those patients treated with bevacizumab plus chemotherapy than for those with chemotherapy alone (median: 63 months [95% CI 54-72] vs 42 months [39-47], respectively, stratified hazard ratio [HR] 075 [95% CI 061-093], two-sided stratified log-rank p=00068). The most common grade 3 or more adverse events were hypertension (33 [13%] of 245 patients receiving bevacizumab plus chemotherapy vs 17 [7%] of 238 patients receiving chemotherapy alone), neutropenia (29 [12%] vs 20 [8%]), and hand-foot syndrome (27 [11%] vs 25 [11%]). Grade 3 proteinuria occurred in 17 (7%) of 245 patients receiving combination therapy and one (<1%) of 238 patients receiving chemotherapy alone. Serious adverse events were reported in 61 (25%) of 245 patients receiving bevacizumab plus chemotherapy versus 44 (18%) of 238 patients receiving chemotherapy alone.These results suggest that continued VEGF inhibition with further bevacizumab is a valid treatment option for patients with locally recurrent or metastatic HER2-negative breast cancer whose disease was stabilised or responded to first-line bevacizumab with chemotherapy.F Hoffmann-La Roche.


Romero Otero J.,Hospital Universitario 12 Octubre | Garcia Gomez B.,Hospital Universitario 12 Octubre | Campos Juanatey F.,Hospital Universitario 12 Octubre | Campos Juanatey F.,Hospital Universitario Marques Of Valdecilla | And 2 more authors.
Urologic Oncology: Seminars and Original Investigations | Year: 2014

Many aspects of prostate cancer diagnosis and treatment could be greatly advanced with new, effective biomarkers. Prostate-specific antigen (PSA) has multiple weaknesses as a biomarker, such as not distinguishing well between cancer and benign prostatic hyperplasia or between indolent and aggressive cancers, thus leading to overtreatment, especially unnecessary biopsies. PSA also often fails to indicate accurately which patients are responding to a given treatment. Yet PSA is the only prostate cancer biomarker routinely used by urologists. Here, we provide updated information on the most relevant of the other biomarkers currently in use or in development for prostate cancer.Recent research shows improvement over using PSA alone by comparing total PSA (tPSA) or free PSA (fPSA) with new, related markers, such as prostate cancer antigen (PCA) 3, the individual molecular forms of PSA (proPSA, benign PSA, and intact PSA), and kallikreins other than PSA. Promising results have also been seen with the use of the fusion gene TMPRSS2:ERG and with various forms of the urokinase plasminogen activation receptor. Initially, there were high hopes for early PCA, but those data were not reproducible and thus research on early PCA has been abandoned.Much work remains to be done before any of these biomarkers are fully validated and accepted. Currently, the only markers discussed in this paper with Food and Drug Administration-approved tests are PCA 3 and an isoform of proPSA, [-2]proPSA. Assays are in development for most of the other biomarkers described in this paper. While the biomarker validation process can be long and filled with obstacles, the rewards will be great-in terms of both patient care and costs to the health care system. © 2014 Elsevier Inc.


Moncada I.,Hospital La Zarzuela | de Bethencourt F.R.,Hospital Universitario La Paz | Lledo-Garcia E.,Hospital General Universitario Gregorio Maranon | Romero-Otero J.,Hospital Universitario 12 Octubre | And 4 more authors.
World Journal of Urology | Year: 2014

Purpose We report time to erectile function (EF)-recovery data from a multicenter, randomized, double-blind, double-dummy, placebo-controlled trial evaluating tadalafil started after bilateral nerve-sparing radical prostatectomy (nsRP). Methods Patients ≤68 years were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg once daily (OaD), 20 mg tadalafil on demand ("pro-re-nata"; PRN), or placebo, followed by 6-week drug-free washout (DFW) and 3-month open-label OaD treatment. Secondary outcome measures included Kaplan-Meier estimates of time to EF-recovery (IIEF-EF ≥ 22) during DBT (Cox proportional hazard model adjusting for treatment, age, and country). Results A total of 423 patients were randomized to tadalafil OaD (N = 139), PRN (N = 143), and placebo (N = 141); 114/122/155 completed DBT. The proportion of patients achieving IIEF-EF ≥22 at some point during DBT with OaD, PRN, and placebo was 29.5, 23.9, and 18.4 %, respectively. DBT was too short to achieve EF-recovery (IIEF-EF ≥ 22) in >50 % of patients; median time to EF-recovery was non-estimable. Time for 25 % of patients to achieve EF-recovery (95 % CI) was 5.8 (4.9, 9.2) months for OaD versus 9.0 (5.5, 9.2) and 9.3 (9.0, 9.9) months for PRN and placebo, respectively. Showing a significant overall treatment effect (p = 0.038), the probability for EF-recovery was significantly higher for OaD versus placebo [hazard ratio (HR); 95 % CI 1.9; 1.2, 3.1; p = 0.011], but not for PRN versus placebo (p = 0.140). Of 57 OaD patients (41.0 %) with ED improved (by ≥1 IIEF-EF severity grade) at the end of DBT, 16 (28.1 % of 57) maintained this improvement through DFW and 27 (47.4 %) declined but maintained improvement from baseline after DFW. Conclusions Data suggest that the use of tadalafil OaD can significantly shorten the time to EF-recovery post-nsRP compared with placebo. © 2014 The Author(s).


PubMed | Sloan Kettering Cancer Center and Hospital Universitario 12 Octubre
Type: Journal Article | Journal: Urologic oncology | Year: 2014

Many aspects of prostate cancer diagnosis and treatment could be greatly advanced with new, effective biomarkers. Prostate-specific antigen (PSA) has multiple weaknesses as a biomarker, such as not distinguishing well between cancer and benign prostatic hyperplasia or between indolent and aggressive cancers, thus leading to overtreatment, especially unnecessary biopsies. PSA also often fails to indicate accurately which patients are responding to a given treatment. Yet PSA is the only prostate cancer biomarker routinely used by urologists. Here, we provide updated information on the most relevant of the other biomarkers currently in use or in development for prostate cancer. Recent research shows improvement over using PSA alone by comparing total PSA (tPSA) or free PSA (fPSA) with new, related markers, such as prostate cancer antigen (PCA) 3, the individual molecular forms of PSA (proPSA, benign PSA, and intact PSA), and kallikreins other than PSA. Promising results have also been seen with the use of the fusion gene TMPRSS2:ERG and with various forms of the urokinase plasminogen activation receptor. Initially, there were high hopes for early PCA, but those data were not reproducible and thus research on early PCA has been abandoned. Much work remains to be done before any of these biomarkers are fully validated and accepted. Currently, the only markers discussed in this paper with Food and Drug Administration-approved tests are PCA 3 and an isoform of proPSA, [-2]proPSA. Assays are in development for most of the other biomarkers described in this paper. While the biomarker validation process can be long and filled with obstacles, the rewards will be great-in terms of both patient care and costs to the health care system.

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