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Romero-Gomez M.,University of Seville | Berenguer M.,University of Valencia | Molina E.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Calleja J.L.,Autonomous University of Madrid
Journal of Hepatology | Year: 2013

The addition of protease inhibitors, boceprevir or telaprevir, to peginterferon + ribavirin (PegIFN/RBV) increases the frequency as well as the severity, and hence, clinical relevance of anemia, which has now become one of the major complications associated with triple therapy. Most significant factors associated with anemia in patients receiving triple therapy include older age, lower body mass index (BMI), advanced fibrosis, and lower baseline hemoglobin. The variability in inosine triphosphate pyrophosphatase (ITPA) gene, which encodes a protein that hydrolyses inosine triphosphate (ITP), has been identified as an essential genetic factor for anemia both in dual and triple therapy. The correct management of anemia is based on anticipation, characterization and therapeutic management. Basically, anemia can be characterized in 3 types: ferropenic (mostly in fertile women), thalassemic type hemolytic anemia, and anemia from chronic processes. Functional deficit of iron should also be excluded in patients with normal ferritin and lower saturation of transferrin. Ribavirin dose reduction and epoetin, sequentially, are indicated in the management of anemia. Epoetin non-response can be caused by lack of time, type of anemia, functional iron deficit or erythropoietin resistance. In the transplantation setting, adding a protease inhibitor to PegIFN/RBV results in a significant increase in the incidence and severity of anemia and, as a consequence, a greater need for epoetin, transfusions, and ribavirin dose reductions. Packed red cell transfusions are utilized when hemoglobin decreases to less than 7.5 g/dl and/or there are clinical symptoms and/or there is no response to other therapeutic measures. © 2013 European Association for the Study of the Liver. Published.


Maneiro J.R.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Salgado E.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Gomez-Reino J.J.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Gomez-Reino J.J.,University of Santiago de Compostela | And 2 more authors.
Seminars in Arthritis and Rheumatism | Year: 2012

Objective: To evaluate the safety, efficacy, and effectiveness of TNF antagonists in patients with sarcoidosis. Methods: A descriptive study of a case series registered in BIOBADASER and a systematic review was performed. The search strategy of articles published between 1998 and July 2011 in Medline, Embase, and the Cochrane Library included synonyms of sarcoidosis and synonyms of TNF antagonists. Results: Seven patients treated with infliximab (IFX) and 1 with etanercept (ETN) switched to IFX for inefficacy were registered in BIOBADASER 2.0. In 3, treatment is still ongoing. Reasons for discontinuation were serious adverse events in 2 cases, inefficacy in 2 cases, and complete clinical response in 2 cases. Eight serious adverse events were reported. In the selected 69 of 2262 reports and 1 abstract of the review, 232 patients (89.9%) were treated with IFX and 26 (10.0%) were treated with ETN. In 2 randomized clinical trials, favorable response of the lung disease was reported with IFX. In other randomized clinical trials, no improvement of ocular manifestations was reported with ETN. In the cases series, results were diverse. Mean weighted rates of adverse events, infections, serious infections, and malignancy were 39.9, 22.1, 5.9, and 1.0 per 100 patient-years, respectively. Conclusions: There is insufficient evidence to ensure the efficacy of TNF antagonists in sarcoidosis. Nevertheless, IFX may be effective in selected manifestations of the disease. Before starting treatment of sarcoidosis with IFX, a careful evaluation of the benefit/risk ratio must be considered on an individual basis. © 2012 Elsevier Inc.


Andujar-Plata P.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Pi-Sunyer X.,Roosevelt University | Laferrere B.,Roosevelt University
Diabetes Research and Clinical Practice | Year: 2012

Metformin is a cornerstone in the treatment of type 2 diabetes. Although its mechanism of action is not well understood, there is new evidence about its possible role in cancer. A Pubmed search from 1990 to 2011 was done using the terms metformin, cancer, mechanism of action, diabetes treatment and prevention. We found more than one thousand articles and reviewed studies that had assessed the efficacy of metformin in treatment and prevention of type 2 diabetes and its mechanisms of actions, as well as articles on its antitumoral effects. We found that the United Kingdom Prospective Diabetes Study and the Diabetes Prevention Program have demonstrated the efficacy of metformin in terms of treatment and prevention of type 2 diabetes; metformin is safe, cost effective and remains the first line of diabetes therapy with diet and exercise. The mechanisms of action include a decrease of hepatic insulin resistance, change in bile acids metabolism, incretins release and decreased amyloid deposits. The AMP-activated protein kinase seems to be an important target for these effects. Epidemiological retrospective studies point out a possible association between metformin and decreased cancer risk, data supported by in vitro and animal studies. These data should trigger randomized controlled trials to prove or disprove this additional benefit of metformin. © 2011 Elsevier Ireland Ltd.


Maneiro R.J.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Salgado E.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Carmona L.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Carmona L.,Camilo José Cela University | And 2 more authors.
Seminars in Arthritis and Rheumatism | Year: 2013

Objective: To identify if rheumatoid factor (RF) is predictor of response to rituximab (RTX), abatacept (ABT), and tocilizumab (TCZ) in rheumatoid arthritis (RA). Methods: Systematic review and meta-analysis of clinical trials and observational studies based on a sensitive search. Meta-regression was used to explore causes of heterogeneity. Unpublished data of clinical trials provided by the authors were also included. Results: The electronic search captured 3221 references and 422 meeting abstracts. By hand search, four additional articles were also identified. A total of 23 studies meet the purpose of the study and were included in the review. RF positivity at starting predicts better ACR20 [OR, 1.95 (1.24, 3.08)], ACR50 [OR, 5.38 (2.50, 11.60)] and EULAR response [OR, 3.52 (1.66, 7.45)] in 14 studies with RTX, and better ACR20 [OR, 1.51 (1.21, 1.90)] in 6 studies with TCZ. In 3 studies with ABT, no association was found between response and RF [OR 1.36 (0.97, 1.90)]. No asymmetries in the funnel plots or significant variables were found in the meta-regression. Conclusion: In RA, RF positivity predicts better response to RTX and TCZ but not to ABT. © 2012 Elsevier Inc.


Alvarez E.,University of Santiago de Compostela | Rodino-Janeiro B.K.,University of Santiago de Compostela | Ucieda-Somoza R.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Gonzalez-Juanatey J.R.,University of Santiago de Compostela
Journal of Cardiovascular Pharmacology | Year: 2010

Endothelial dysfunction has been linked to reactive oxygen species (ROS) production by nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase. Angiotensin II (ANG), which levels are elevated in some cardiovascular diseases, can stimulate this enzyme, whereas statins have been demonstrated pleiotropic effects related with the restoration of endothelial function. Therefore, our purpose was to study the mechanism of the possible beneficial effects of pravastatin on ANG-activated human umbilical vein endothelial cells (HUVEC). ANG induced an increase in the extracellular superoxide anion produced by NADPH oxidase but had no effect in the intracellular ROS production. Pravastatin, which alone did not have any effect on ROS production, totally blocked the stimulating effects of ANG when combined with it. These effects were not due to a direct action of ANG or pravastatin on the activity of NADPH oxidase measured in HUVEC lisates. On the contrary, the results correlated well with other effects of ANG: a Nox4 and p22phox upregulated expression and an enhanced Nox4 translocation to the cell membrane. All these effects were inhibited by pravastatin, which had no effect when incubated alone. These data reveal for the first time that pravastatin interrupts the signaling pathway activated by ANG that leads to an enhanced NADPH oxidase activity at the cell membrane of HUVEC. For that, pravastatin inhibits ANG-induced upregulation of catalytic NADPH oxidase subunits and blocks the migration of them to the endothelial cell membrane. © 2010 by Lippincott Williams & Wilkins.


Maneiro J.R.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Salgado E.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Gomez-Reino J.J.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Gomez-Reino J.J.,University of Santiago de Compostela
JAMA Internal Medicine | Year: 2013

IMPORTANCE Knowledge of the immunogenicity of biologic agents may be helpful for the development of strategies for treatment of chronic immune-mediated inflammatory diseases. OBJECTIVE To summarize the influence of antibodies against biologic agents (AABs [seropositivity]) on efficacy and safety in immune-mediated inflammatory diseases. DATA SOURCES MEDLINE, EMBASE, Cochrane Library, and theWeb of Knowledge were searched for articles published in English, Spanish, French, Italian, or Portuguese between 2000 and March 2012. The search strategy focused on synonyms of diseases, immunogenicity, and biologic agents. Abstracts from 2001 to 2011 of the European League Against Rheumatism and American College of Rheumatology congresses were also included. STUDY SELECTION The selection criteria were (1) observational or interventional studies in rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, spondyloarthritis, and psoriasis; (2) studies including patients who received biologic agents; and (3) studies collecting data on AABs. DATA EXTRACTIONANDSYNTHESIS Data collected included publication details, study design, characteristics of patients and treatments, presence of antibodies, and definition of response. MAIN OUTCOMES AND MEASURES The primary end pointwas the association of AABs with response to treatment. Secondary end points were the association of AABs with safety, the association of AABs with concentration of the drug, and the influence of use of concomitant immunosuppressive therapy in the formation of AABs. RESULTS The search captured 10 728 articles and abstracts. By hand and reverse search, 31 articleswere additionally included. After evaluation of the full reports, 60 referenceswere selected. They included 59 studies of anti-tumor necrosis factor monoclonal antibodies: 1 with etanercept, 2 with rituximab, and 2 with abatacept. In rheumatoid arthritis but not in inflammatory bowel disease or spondyloarthritis, seropositive patients presented worse clinical response at 6 months or less (odds ratio [OR],0.03; 95%CI,0.01-0.21), and at 6 months or more (0.03; 0.00-0.30) by meta-analysis. In rheumatoid arthritis, discontinuation of the biologic agent for all reasonswas more common in seropositive patients (OR, 3.53; 95%CI, 1.60-7.82). In all conditions, seropositive patients had a higher risk of hypersensitivity reactions (OR, 3.97; 95%CI, 2.36-6.67).Overall, concomitant treatment with disease-modifying antirheumatic drugs, including azathioprine, decreased the risk of seropositivity (OR,0.32; 95%CI,0.25-0.42). CONCLUSIONS AND RELEVANCE Presence of antibodies against anti-tumor necrosis factor monoclonal antibodies confers a risk of discontinuation of treatment in rheumatoid arthritis and a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases. The combined use of anti-tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks. Information on other biologic agents is fragmentary.


Rios M.,University of Santiago de Compostela | Foretz M.,University of Paris Descartes | Viollet B.,University of Paris Descartes | Prieto A.,Complejo Hospitalario Universitario Of Santiago Of Compostela | And 3 more authors.
Cancer Research | Year: 2013

50-AMP-activated protein kinase (AMPK) is an energy sensor that controls cell metabolism, and it has been related to apoptosis and cell-cycle arrest. Although its role in metabolic homeostasis is well documented, its function in cancer is much less clear. In this study, we examined the role of AMPK in a mouse model of astrocytoma driven by oncogenic H-RasV12 and/or with PTEN deletion based on the common constitutive activation of the Raf/MEK/ERK and PI3K/AKT cascades in human astrocytomas. We also evaluated the activity and role of AMPK in human glioblastoma cells and xenografts. AMPK was constitutively activated in astrocytes expressing oncogenic H-RasV12 in parallel with high cell division rates. Genetic deletion of AMPK or attenuation of its activity in these cells was sufficient to reduce cell proliferation. The levels of pAMK were always related to the levels of phosphorylated retinoblastoma (Rb) at Ser804, which may indicate an AMPKmediated phosphorylation of Rb. We confirmed this AMPK-Rb relationship in human glioblastoma cell lines and xenografts. In clinical specimens of human glioblastoma, elevated levels of activated AMPK appeared especially in areas of high proliferation surrounding the blood vessels. Together, our findings indicate that the initiation and progression of astrocytic tumors relies upon AMPK-dependent control of the cell cycle, thereby identifying AMPK as a candidate therapeutic target in this setting. © 2013 American Association for Cancer Research.


Perez-Fentes D.,Complejo Hospitalario Universitario Of Santiago Of Compostela
Archivos Espanoles de Urologia | Year: 2016

The insertion of a double J catheter (DJ) has widespread, becoming a usual procedure and standard of care in urology. Despite its relative simplicity it is not free from intraoperative risks or problems during the weeks after the implant. Conversely, despite great advances in design of these catheters the ideal material has not been discovered yet, one that is perfectly biocompatible with urine and avoids completely the advent of complications. The range of problems associated with DJs is variable: from mild self-limited dysuria or hematuria to more complex situations with higher risk, such as catheter migration, complete calcification, breakage, obstruction and renal unit loss. The treatment of theses complications must combine maximal efficacy for their resolution with the least possible surgical aggression. Accordingly, the different options of endourological approach become very important and they are the cornerstone for the treatment of the complications associated with ureteral catheters. The objective of this review is to present the main complications derived from the insertion of a DJ, their diagnosis, prevention and treatment, focusing mainly in the different endourological techniques.


Olmos M.A.M.,Complejo Hospitalario Universitario Of Santiago Of Compostela
Nutricion Hospitalaria | Year: 2015

Telemedicine represents the union of information technology and telecommunication services in health. This allows the improvement of health care, especially in underserved areas, bringing professionals working in continuing education and improving patient care at home. The application of telemedicine in various hospital complexes, clinics and health centers, has helped to provide a better service, within the parameters of efficiency, effectiveness, cost-benefit, with increasing satisfaction of medical staff and patients. The development and application of various types of telemedicine, the technological development of audio, text, video and data, and constant improvement of infrastructure in telecommunications, have favored the expansion and development of telemedicine in various medical specialties. The use of electronic health records by different health professionals can have a positive impact on the care provided to patients. This should also be supported by the development of better health policies, legal security and greater awareness in health professionals and patients regarding the potential benefits. Regarding the clinical activity in Nutrition, new technologies also provide an opportunity to improve in various educational, preventive, diagnostic and treatment aspects, including shared track between Nutrition Units and Primary Care Teams, for patients who need home nutritional care at, with shared protocols, providing teleconsultation in required cases and avoiding unnecessary travel to hospital. © 2015, Grupo Aula Medica S.A. All rights reserved.


Rodino-Janeiro B.K.,University of Santiago de Compostela | Gonzalez-Peteiro M.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Ucieda-Somoza R.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Gonzalez-Juanatey J.R.,University of Santiago de Compostela | Alvarez E.,University of Santiago de Compostela
Diabetes/Metabolism Research and Reviews | Year: 2010

Background Hyperglycaemia induces non-enzymatic glycation reactions in proteins which generate Amadori products and advanced glycation end- products; the latter are thought to participate in the vascular complications of diabetic patients. However, the exact mechanisms concerning the effects of glycated proteins on vascular tissue remain to be determined. Therefore, the effects of glycated human serum albumin on human umbilical vein endothelial cells were studied. Methods Reactive oxygen species production was measured by the cytochrome C reduction method and by 5(6)-carboxy-2′,7′-dichlorofluorescein diacetate (c-DCF-DA) fluorescence after treating human umbilical vein endothelial cells with glycated human serum albumin (6-200 μg/mL). The expression of Nox4 and p22phox mRNAs were analysed by reverse transcription-quantitative polymerase chain reactions and the levels of their proteins were measured by immunofluorescence. Results Low concentrations of glycated human serum albumin enhanced reactive oxygen species production in human umbilical vein endothelial cells after 4 h of treatment at both extracellular and intracellular sites. This enhanced production was sustained, although to a lesser extent, after 6 and 12 h of treatment. The gene expression study revealed that Nox4 and p22phox mRNA levels were elevated after 4 h of treatment with glycated human serum albumin. This mRNA elevation and enhanced reactive oxygen species production correlated with an increased expression of the Nox4 protein. Conclusions The results revealed that a circulating and abundant modified glycated human serum albumin protein in diabetic patients induced a sustained reactive oxygen species production in human endothelial cells. This effect may have been due to an up-regulation of Nox4, the main subunit of NADPH oxidase in the endothelium. © 2010 John Wiley & Sons, Ltd.

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