San Carlos Clinical Hospital

Villanueva de San Carlos, Spain

San Carlos Clinical Hospital

Villanueva de San Carlos, Spain
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News Article | April 18, 2017
Site: www.eurekalert.org

Scientists at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) have discovered a new mechanism of action of metoprolol, a drug that can reduce the damage produced during a heart attack if administered early. The team led by Dr. Borja Ibáñez, Clinical Research Director at the CNIC and cardiologist at the Fundación Jiménez Díaz University Hospital Health Research Institute (IIS-FJD), has identified the mechanism that explains why this drug is so beneficial: rapid administration of metoprolol during a heart attack directly inhibits the inflammatory action of neutrophils, a type of blood cell. The reduced inflammation translates into a smaller area of damaged tissue in the post-infarcted heart. The finding, published in Nature Communications, opens the way to new applications for this cheap, safe, and simple drug. Acute myocardial infarction is a serious disease that affects more than 50 000 people a year in Spain. Treatment has advanced a great deal in recent years, especially in the extensive use of coronary angioplasty, in which a catheter is used to re-establish blood flow through the blocked coronary artery. Nevertheless, many heart attack survivors have seriously impaired heart function that limits their long-term health and generates major costs to the health system. The search for treatments to limit the irreversible damage caused by a heart attack is an extremely important research area in terms of both patient care and health policy. Neutrophils are white blood cells that target and fight infections. In noninfectious diseases, neutrophils mount an excessive response, and after a myocardial infarction these cells attack the heart, contributing to the long-term injury and impaired function. "In an infarction," explained Dr. Ibañez "the most important thing is to re-establish blood flow as soon as possible. But unfortunately the incoming blood sets off an inflammatory process, started by neutrophils, that causes additional, permanent damage to the heart." This additional damage due to blood flow restoration is known as reperfusion injury, and has been regarded as a necessary evil because it is essential to unblock the coronary artery as rapidly as possible. Metoprolol is a beta-blocker that has been in clinical use for more than 30 years and is a cheap drug (costing less than €2 per dose) of little commercial interest. In 2013, the METOCARD-CNIC clinical trial, led and coordinated by the same CNIC research team, showed that administration of metoprolol very early after an infarction reduces the size of the cardiac injury and improves long-term health. It has taken the team 7 years to determine why this simple and cheap pharmacological strategy is so effective. The study published today in Nature Communications shows that early administration of metoprolol protects the heart by acting directly on neutrophils. "Metoprolol stuns the blood neutrophils, altering their behavior and limiting their injurious inflammatory action on cardiac muscle," explained first author Jaime García-Prieto. When coronary blood flow is re-established, neutrophils launch a complex and organized inflammatory reaction, with negative consequences. According to García-Prieto, "when neutrophils enter the infarcted heart tissue after the restoration of blood flow, they act disproportionately, inducing the death of cells that, while weakened, have survived the infarction." As Andrés Hidalgo, CNIC scientist and expert on neutrophils, explained, "neutrophil tissue invasion is intimately related to their interactions with platelets. Metoprolol blocks these interactions, drastically limiting the number of neutrophils arriving in the infarcted tissue." Moreover, impeding neutrophil invasion also prevents the formation of blood-cell aggregates that block the microcirculation in the post-infarction heart. Dr. Antonio Fernández-Ortiz, study co-author and a cardiologist at the Hospital Clínico San Carlos, clarified that "we knew that platelets were an important factor in the clotting that causes an infarct, but until now we could not be certain that they also act together with neutrophils to magnify injury after blood flow restoration." Dr. Ibañez concluded that "the priority after a heart attack remains the restoration of blood flow as soon as possible, but we need to prepare the heart for this by administering metoprolol." Also an author on the study is Dr. Valentín Fuster, CNIC General Director and Physician in Chief at the Mount Sinai Hospital in New York. Commenting on the study, he emphasized that "the imaging technology at the CNIC has allowed us to rapidly determine the status of a patient's heart after a heart attack, and this has enabled us to discover a new mechanism of action of this drug that we have been using for decades." The study, coordinated by the CNIC, is an example of multidisciplinary networked collaboration involving not only the CNIC and the IIS-FJD but also the San Carlos Clinical Hospital, the Quirón Madrid University Hospital, Asturias Central Hospital, the Ruber Juan Bravo Hospital Complex, Basurto Hospital, and Mount Sinai Hospital in New York. Most of these centers are members of the recently created CIBER research network on cardiovascular diseases (CIBERCV) within the group led by Dr. Ibáñez. The study is the fruit of collaboration among cardiologists, ambulance emergency service staff, veterinarians, biochemists, physicists, and engineers, all of them participants in the CIBERCV consortium.


Perez de Diego R.,University Institute of La Paz | Sanchez-Ramon S.,San Carlos Clinical Hospital | Lopez-Collazo E.,University Institute of La Paz | Martinez-Barricarte R.,Rockefeller University | And 4 more authors.
The Journal of allergy and clinical immunology | Year: 2015

Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.


van Steenbergen H.W.,Leiden University | Rodriguez-Rodriguez L.,San Carlos Clinical Hospital | Berglin E.,Umeå University | Zhernakova A.,University of Groningen | And 7 more authors.
Arthritis Research and Therapy | Year: 2015

Introduction: The severity of joint damage progression in rheumatoid arthritis (RA) is heritable. Several genetic variants have been identified, but together explain only part of the total genetic effect. Variants in Interleukin-6 (IL-6), Interleukin-10 (IL-10), C5-TRAF1, and Fc-receptor-like-3 (FCRL3) have been described to associate with radiographic progression, but results of different studies were incongruent. We aimed to clarify associations of these variants with radiographic progression by evaluating six independent cohorts. Methods: In total 5,895 sets of radiographs of 2,493 RA-patients included in six different independent datasets from the Netherlands, Sweden, Spain and North-America were studied in relation to rs1800795 (IL-6), rs1800896 (IL-10), rs2900180 (C5-TRAF1) and rs7528684 (FCRL3). Associations were tested in the total RA-populations and in anti-citrullinated peptide antibodies (ACPA)-positive and ACPA-negative subgroups per cohort, followed by meta-analyses. Furthermore, the associated region C5-TRAF1 was fine-mapped in the ACPA-negative Dutch RA-patients. Results: No associations were found for rs1800795 (IL-6), rs1800896 (IL-10) and rs7528684 (FCRL3) in the total RA-population and after stratification for ACPA. Rs2900180 in C5-TRAF1 was associated with radiographic progression in the ACPA-negative population (P-value meta-analysis=5.85×10-7). the minor allele was associated with more radiographic progression. Fine-mapping revealed a region of 66Kb that was associated. the lowest P-value was for rs7021880 in TRAF1. The P-value for rs7021880 in meta-analysis was 6.35×10-8. Previous studies indicate that the region of rs7021880 was associated with RNA expression of TRAF1 and C5. Conclusion: Variants in IL-6, IL-10 and FCRL3 were not associated with radiographic progression. Rs2900180 in C5-TRAF1 and linked variants in a 66Kb region were associated with radiographic progression in ACPA-negative RA. © 2014 van Steenbergen et al.


Falcon B.S.,Complutense University of Madrid | Sanchez A.A.,Complutense University of Madrid | Diaz-Rubio M.,San Carlos Clinical Hospital | Rey E.,Complutense University of Madrid
Age and Ageing | Year: 2017

Background: faecal impaction (FI) is a common problem in old people living in nursing home. Its prevalence and associated factors remain unknown in the general population. Aim: to evaluate FI prevalence in the Spanish population older than 65 years and to assess the factors associated with it. Methods: a telephone survey was carried out of a Spanish population older than 65 years random sample (N = 1000). FI was assessed using a previously validated questionnaire. Results: a total of 28,128 calls were made; 1,431 subjects were eligible and 1,000 subjects were enrollled, mean aged 74.6 ± 7.3 (65-97); 57.5% were women. At least 53 people reported FI within the past year (5.3% (CI 95%: 3.9-6.7%)). Only 0.03% met criteria for chronic constipation and faecal incontinence. FI-associated factors were constipation, female gender, reduced physical activity, and chronic renal failure (CRF). Conclusion: FI is a prevalent problem in old Spanish population. Constipation and female gender are the main associated factors; low physical activity and CRF appear to play also a significant role. Further studies are required to confirm this association. © The Author 2016. All rights reserved.


Vicario-de-la-Torre M.,Complutense University of Madrid | Vicario-de-la-Torre M.,National Health Research Institute | Benitez-del-Castillo J.M.,National Health Research Institute | Benitez-del-Castillo J.M.,San Carlos Clinical Hospital | And 7 more authors.
Investigative Ophthalmology and Visual Science | Year: 2014

RESULTS. The mean liposome size was less than 1 lm and surface tension < 30 mN/m for all formulations. The final liposomal formulation (PC–cholesterol–vit E in a ratio of 8:1:0.8) had physiological values of pH (6.45 ± 0.09), osmolarity (289.43 ± 3.28 mOsm), and viscosity (1.82 ± 0.02 mPa×s). Cell viability was greater than 80% in the corneal and conjunctival cells. This formulation was well tolerated by experimental animals.CONCLUSIONS. The unpreserved liposomal formulation has suitable properties to be administered by a topical ophthalmic route. The liposome-based artificial tear had good in vitro and in vivo tolerance responses. This formulation, composed of a combination of liposomes and bioadhesive polymers, may be used successfully as a tear film substitute in DE therapy.PURPOSE. Dry eye (DE) includes a group of diseases related to tear film disorders. Current trends for DE therapy focus on providing lipid components to replace the damaged lipid layer. Formulations that contain aqueous and mucin-like compounds may have additional therapeutic benefits for DE patients. The aim of this work was to design and evaluate novel formulations having the potential to become topical treatment for DE.METHODS. Unpreserved liposomal formulations composed of phosphatidylcholine (PC), cholesterol, and α-tocopherol (vit E) were prepared by the thin-film hydration technique. Formulations were characterized in terms of liposome size, pH, surface tension, osmolarity, and viscosity. In vitro tolerance assays were performed on macrophage, human corneal, and conjunctival cell lines at short- and long-term exposures. In vivo ocular tolerance was studied after instillation of the formulation. © 2014 The Association for Research in Vision and Ophthalmology, Inc.


Van Steenbergen H.W.,Leiden University | Raychaudhuri S.,Harvard University | Raychaudhuri S.,University of Manchester | Raychaudhuri S.,The Broad Institute of MIT and Harvard | And 8 more authors.
Arthritis and Rheumatology | Year: 2015

Objective For decades it has been known that the HLA-DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide-binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe at HLA-DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti-citrullinated protein antibody (ACPA) status. Methods A total of 4,911 radiograph sets from 1,878 RA patients included in the Leiden Early Arthritis Clinic (The Netherlands), Umeå (Sweden), Hospital Clinico San Carlos-Rheumatoid Arthritis (Spain), and National Data Bank for Rheumatic Diseases (US) cohorts were studied. HLA was imputed using single-nucleotide polymorphism data from an Immunochip, and the amino acids listed above were tested in relation to radiographic progression per cohort using an additive model. Results from the 4 cohorts were combined in inverse-variance weighted meta-analyses using a fixed-effects model. Analyses were conditioned on SE and ACPA status. Results Val and Leu at HLA-DRB1 position 11 were associated with more radiographic progression (meta-analysis P = 5.11 × 10-7); this effect was independent of SE status (meta-analysis P = 0.022) but not independent of ACPA status. Phe at HLA-DPB1 position 9 was associated with more severe radiographic progression (meta-analysis P = 0.024), though not independent of SE status. Asp at HLA-B position 9 was not associated with radiographic progression. Conclusion Val and Leu at HLA-DRB1 position 11 conferred a risk of a higher rate of radiographic progression independent of SE status but not independent of ACPA status. These findings support the relevance of these amino acids at position 11. Copyright © 2015 by the American College of Rheumatology.


Perez de Diego R.,University Institute of La Paz | Sanchez-Ramon S.,San Carlos Clinical Hospital | Lopez-Collazo E.,University Institute of La Paz | Martinez-Barricarte R.,Rockefeller University | And 7 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of eachof the components of the CBM complex to human immunity. © 2015 American Academy of Allergy, Asthma & Immunology.


Ramos-Levi A.M.,La Princesa University Hospital | Duran Rodriguez-Hervada A.,San Carlos Clinical Hospital | Mendez-Bailon M.,San Carlos Clinical Hospital | Marco-Martinez J.,San Carlos Clinical Hospital
Minerva Endocrinologica | Year: 2014

Hyponatremia, defined as serum sodium concentrations <135 mmol/L, is the most frequent electrolyte disturbance observed in both hospitalized and ambulatory patients, and has been associated to relevant negative consequences regarding morbidity and mortality. Drug-induced hyponatremia has been widely observed. However, since it may be clinically symptomatic or asymptomatic, it is frequently an underdiagnosed condition. This review aims to highlight the main drugs involved in the pathophysiology of hyponatremia, which should be considered in the differential diagnosis when approaching a patient with hyponatremia. We discuss their impact and relative importance. In order to prevent undesirable negative consequences we also emphasize the need for awareness of this clinically-relevant adverse effect, and we suggest how clinical management of patients may be approached.


Garcia Garcia-Esquinas M.,San Carlos Clinical Hospital | Garcia-Saenz J.A.,San Carlos Clinical Hospital | Rrazola Garcia J.A.,San Carlos Clinical Hospital | Fuentes Ferrer M.E.,San Carlos Clinical Hospital | And 4 more authors.
Quarterly Journal of Nuclear Medicine and Molecular Imaging | Year: 2014

Aim. Classical prognostic and predictive factors serve to predict outcome and response to neoadjuvant treatment in stage II and III breast cancer. The purpose is to determine the relation between the SUVmax of the locoregional disease with these classical prognostic factors. Methods. A prospective study including 43 stage II and III breast cancer patients was performed. In all the patients, two 18F-FDG PET-CT studies were performed before and after neoadjuvant chemotherapy. After this treatment, surgery and adjuvant treatment were carried out. To combine the information of the locoregional disease, the SUVmax of the lesion (tumor or abnormal lymphnodes) with the highest uptake was used. SUVmax and prognostic factors were studied with the Kruskal-Wallis non-parametric test and with the Mann-Whitney U. Results. A statistically significant association between elevated SUVmax value and absence of estrogen receptors (ER) expression (16 vs.. 10; P<0.019) was found. Locorregional disease with positive HER2 phenotype had a statistically significant SUVmax value greater than Luminal A (estrogen and/or progesterone positive receptors with Ki67<15%) and B (estrogen and/or progesterone positive receptors with Ki67≥to 15%) (13.4 vs. 7.9 and 8.9; P<0.022 and P<0.024, respectively). Triple negative phenotype disease had higher SUVmax than Luminal A and B (15.4; P<0.030 and P<0.038). Positive correlation between the percentage of the Ki67 Proliferation Index and SUVmax (P<0.007) was demonstrated. High grade disease had a higher SUVmax than low grade (P<0.004). Conclusion. Locorregional SUVmax is associated to prognostic and predictive factors and reaffirms the utility of PET-CT as a tool in the common clinical practice.


Fernandez Lopez M.,Fuenlabrada University Hospital | Fernandez Lopez M.,Rey Juan Carlos University | Ruiz Giardin J.M.,Fuenlabrada University Hospital | San Martin Lopez J.V.,Fuenlabrada University Hospital | And 4 more authors.
Malaria Journal | Year: 2015

Background: Arrival of inmigrants from malaria endemic areas has led to a emergence of cases of this parasitic disease in Spain. The objective of this study was to analyse the high incidence rate of imported malaria in Fuenlabrada, a city in the south of Madrid, together with the frequent the lack of chemoprophylaxis, for the period between 2004 and 2014. Both pregnant women and HIV risk groups have been considered. Methods: Retrospective descriptive study of laboratory-confirmed malaria at the Fuenlabrada University Hospital, in Madrid, during a 10-year period (2004-2014). These data were obtained reviewing medical histories of the cases. Relevant epidemiological, clinical and laboratory results were analysed, with focus on the following risk groups: pregnant women and individuals with HIV. Results: A total of 185 cases were diagnosed (90.3 % Plasmodium falciparum). The annual incidence rate was 11.9/100,000 inhabitants/year. The average age was 30.8 years (SD: 14.3). Infections originating in sub-Saharan Africa comprised the 97.6 % of the cases. A total of 85.9 % were Visiting Friends and Relatives. Only a 4.3 % completed adequate prophylaxis. A total of 14.28 % of the fertile women were pregnant, and 8 cases (4.3 %) had HIV. None of them in these special groups completed prophylaxis. Conclusions: The incidence rate in Fuenlabrada is higher than in the rest of Spain, due to the large number of immigrants from endemic areas living in the municipality. However, the results are not representative of all the country. It seems to be reasonable to implement prevention and pre-travel assessment programs to increase chemoprophylaxis. Pregnancy tests and HIV serology should be completed for all patients to improve prophylactic methods. © 2015 Fernández López et al.

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