Grupos Investigadores

Líneas de Investigación

  • Nuevos mecanismos fisiopatológicos asociados al envejecimiento, los trastornos metabólicos y la inflamación en la enfermedad vascular y trombosis.
  • Nuevos biomarcadores en la estratificación y predicción del riesgo cardiovascular y trombótico.
  • Nuevos abordajes para el diagnóstico y el tratamiento de la patología trombótica arterial y venosa.
  • Estudio de los factores clínicos y biológicos asociados a la enfermedad tromboembólica venosa y su recurrencia.

Palabras Clave

  • Trombosis
  • Inflamación
  • Hemostasia
  • Estrés oxidativo
  • Aterosclerosis

Publicaciones Científicas desde 2018

  • Autores: Páramo Fernández, José Antonio (Autor de correspondencia); Marcos Jubilar, María; Lecumberri Villamediana, Ramón
    Revista: REVISTA CLINICA ESPAÑOLA
    ISSN 0014-2565 Vol.222 N° 2 2022 págs. 93 - 99
    Resumen
    Patients with cancer present with an elevated risk of thrombosis, which entails high morbidity and mortality. Various predictive scales that incorporate clinical and biological data have been developed to identify those at high risk of thrombosis, but, in general, they do not allow for the optimal selection of subjects who are candidates for thromboprophylaxis. Recent studies have demonstrated that the mutation profile has a high impact on the risk of thrombosis; this will facilitate developing new predictive models of thrombosis in patients with cancer. (C) 2021 Elsevier Espana, S.L.U. and Sociedad Espanola de Medicina Interna (SEMI). All rights reserved.
  • Autores: Santos-Lasaosa, S. (Autor de correspondencia); Belvis, R.; Cuadradodo, M. L.; et al.
    Revista: NEUROLOGIA
    ISSN 0213-4853 Vol.37 N° 5 2022 págs. 390 - 402
    Resumen
    Introduction: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity.Development: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics.Conclusions: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.
  • Autores: Martín-Ventura, J. L. (Autor de correspondencia); Roncal Mancho, Carmen (Autor de correspondencia); Orbe Lopategui, Josune; et al.
    Revista: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
    ISSN 2296-634X Vol.10 2022 págs. 813885
    Resumen
    Cardiovascular diseases (CVDs) are the first cause of death worldwide. In recent years, there has been great interest in the analysis of extracellular vesicles (EVs), including exosomes and microparticles, as potential mediators of biological communication between circulating cells/plasma and cells of the vasculature. Besides their activity as biological effectors, EVs have been also investigated as circulating/systemic biomarkers in different acute and chronic CVDs. In this review, the role of EVs as potential diagnostic and prognostic biomarkers in chronic cardiovascular diseases, including atherosclerosis (mainly, peripheral arterial disease, PAD), aortic stenosis (AS) and aortic aneurysms (AAs), will be described. Mechanistically, we will analyze the implication of EVs in pathological processes associated to cardiovascular remodeling, with special emphasis in their role in vascular and valvular calcification. Specifically, we will focus on the participation of EVs in calcium accumulation in the pathological vascular wall and aortic valves, involving the phenotypic change of vascular smooth muscle cells (SMCs) or valvular interstitial cells (IC) to osteoblast-like cells. The knowledge of the implication of EVs in the pathogenic mechanisms of cardiovascular remodeling is still to be completely deciphered but there are promising results supporting their potential translational application to the diagnosis and therapy of different CVDs.
  • Autores: Piñana, J. L. (Autor de correspondencia); Vázquez, L.; Martino, R. ; et al.
    Revista: LEUKEMIA AND LYMPHOMA
    ISSN 1042-8194 Vol.63 N° 3 2022 págs. 538 - 550
    Resumen
    In the midst of the COVID-19 pandemic, different vaccines in front of SARS-CoV-2 have been approved and administered in different vulnerable populations. As patients with cancer were excluded from pivotal trials of vaccination, little is known on their immunogenic response to these vaccines, particularly in patients with severely impaired immune system. In response to that uncertainty, the Spanish Society of Hematology and Hemotherapy launched an initiative aimed to provide recommendations for vaccination of the main hematological conditions. This document is based on the available information on COVID-19 outcomes, prior knowledge on vaccination in hematological patients, recent published data on serological response in oncohematological patients and expert opinions. New information about SARS-CoV-2 vaccination will be gathered in the near future, providing new scientific grounds to delineate the most adequate management of vaccination in patients with hematological diseases. The current limited data on SARS-CoV-2 vaccines in hematological patients represents a major limitation of this expert consensus opinion. In fact, the speed in which this field evolves may reduce their validity in the near future.
  • Autores: González-Porras, J. R. (Autor de correspondencia); Mateo, J.; González-Calle, V.; et al.
    Revista: CLINICAL AND TRANSLATIONAL ONCOLOGY
    ISSN 1699-048X Vol.24 N° 5 2022 págs. 770 - 783
    Resumen
    Venous thromboembolism (VTE) is a serious complication in hematologic neoplasms, so finding adequate prevention strategies is an urgent requirement. However, prospective studies with large enough cohorts are scarce, limiting the development of evidence-based thromboprophylaxis guidelines. The present position paper is addressed to all hematologists treating patients affected by hematologic neoplasms with the aim to provide clinicians with a useful tool for the prevention of VTE.
  • Autores: Marcos Jubilar, María; Carmona de la Torre, Francisco de Asís; Vidal, R.; et al.
    Revista: THROMBOSIS AND HAEMOSTASIS
    ISSN 0340-6245 Vol.122 N° 2 2022 págs. 295 - 299
    Resumen
    Thromboprophylaxis with low molecular weight heparin in hospitalized patients with COVID-19 is mandatory, unless contraindicated. Given the links between inflammation and thrombosis, the use of higher doses of anticoagulants could improve outcomes. We conducted an open-label, multicenter, randomized, controlled trial in adult patients hospitalized with nonsevere COVID-19 pneumonia and elevated D-dimer. Patients were randomized to therapeutic-dose bemiparin (115 IU/kg daily) versus standard prophylaxis (bemiparin 3,500 IU daily), for 10 days. The primary efficacy outcome was a composite of death, intensive care unit admission, need of mechanical ventilation support, development of moderate/severe acute respiratory distress, and venous or arterial thrombosis within 10 days of enrollment. The primary safety outcome was major bleeding (International Society on Thrombosis and Haemostasis criteria). A prespecified interim analysis was performed when 40% of the planned study population was reached. From October 2020 to May 2021, 70 patients were randomized at 5 sites and 65 were included in the primary analysis; 32 patients allocated to therapeutic dose and 33 to standard prophylactic dose. The primary efficacy outcome occurred in 7 patients (22%) in the therapeutic-dose group and 6 patients (18%) in the prophylactic-dose (absolute risk difference 3.6% [95% confidence interval [CI], -16% -24%]; odds ratio 1.26 [95% CI, 0.37-4.26]; p = 0.95). Discharge in the first 10 days was possible in 66 and 79% of patients, respectively. No major bleeding event was registered. Therefore, in patients with COVID-19 hospitalized with nonsevere pneumonia but elevated D-dimer, the use of a short course of therapeutic-dose bemiparin does not appear to improve clinical outcomes compared with standard prophylactic doses. Trial Registration: ClinicalTrials.gov NCT04604327.
  • Autores: Páramo Fernández, José Antonio
    Revista: REUMATOLOGIA CLINICA
    ISSN 1699-258X Vol.18 N° 1 2022 págs. 1 - 4
    Resumen
    The haemostatic system acts in concert with inflammation, so that after inflammatory response various mediators activate the haemostatic system through endothelial dysfunction, platelet activation and coagulation promoting thrombosis, which is termed thromboinflammation. In this process, the inflammasome acquires special relevance; its stimulation promotes innate and adaptive immune responses. Inflamma some activation plays an important physiopathological role in several disorders with inflammatory and thrombotic phenomena. The role of thromboinflammation has become relevant in the COVID-19 pandemic, in which a cytokine storm has been described as one of the mechanisms responsible.
  • Autores: Lobo, J. L.; Alonso, S.; Arenas, J.; et al.
    Revista: ARCHIVOS DE BRONCONEUMOLOGIA
    ISSN 0300-2896 Vol.58 N° 3 2022 págs. 246 - 254
    Resumen
    El objetivo del presente documento es actualizar el consenso previo publicado en 2013, en relación con 12 áreas controvertidas en el manejo de la tromboembolia de pulmón (TEP). Para cada área se realizó una exhaustiva revisión bibliográfica y una propuesta de recomendación, sometida a un proceso de debate interno en dos teleconferencias sucesivas. En relación con el diagnóstico, recomendamos no utilizar la escala Pulmonary Embolism Rule Out Criteria (PERC) de forma aislada para descartar la TEP y, cuando haya indicación de dímero D, recomendamos emplear un punto de corte ajustado a la edad. Sugerimos utilizar la angiotomografía computerizada de tórax como prueba de imagen para el diagnóstico de la mayoría de los pacientes con sospecha de la enfermedad. Se recomienda utilizar anticoagulantes de acción directa (en vez de antagonistas de la vitamina K) para el tratamiento de la mayoría de los pacientes con TEP, y se sugiere utilizar anticoagulación para la mayoría de los pacientes con TEP subsegmentaria. Se recomienda no colocar un filtro de vena cava inferior en la mayoría de los pacientes. Si se indica tratamiento de reperfusión, el panel recomienda utilizar fibrinolisis sistémica a dosis completas. La duración de la anticoagulación está condicionada principalmente por la presencia (o ausencia) y el tipo de factor de riesgo para enfermedad tromboembólica venosa, y recomendamos no realizar estudios de trombofilia para decidir la duración de la anticoagulación a la mayoría de los pacientes con TEP. Finalmente, sugerimos no realizar cribado extendido de cáncer oculto en pacientes con TEP.
  • Autores: Páramo Fernández, José Antonio (Autor de correspondencia); Lozano, M. L.; González-Porras, J. R.; et al.
    Revista: MEDICINA CLINICA
    ISSN 0025-7753 Vol.158 N° 2 2022 págs. 82 - 89
  • Autores: Bikdeli, B. (Autor de correspondencia); Jiménez, D.; Demelo-Rodríguez, P.; et al.
    Revista: VIRUSES-BASEL
    ISSN 1999-4915 Vol.14 N° 2 2022 págs. 178
    Resumen
    Background: Venous thromboembolism (VTE)-including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)-may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2. Methods: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbolica (RIETE) platform, patients with VTE 4-30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018-2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes. Results: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7-94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07-47.13). ...
  • Autores: Irimia Sieira, Pablo; García-Azorín, D.; García De Polavieja, P.; et al.
    Revista: VALUE IN HEALTH
    ISSN 1098-3015 Vol.25 N° 1 2022 págs. S269
  • Autores: Páramo Fernández, José Antonio (Autor de correspondencia)
    Revista: MEDICINA CLINICA
    ISSN 0025-7753 Vol.156 N° 12 2021 págs. 609 - 614
    Resumen
    Thrombosis is often present in the microcirculation in a variety of significant human diseases, such as disseminated intravascular coagulation, thrombotic microangiopathy, sickle cell disease, and others. Microvascular thrombosis has also recently been demonstrated in patients with COVID-19 and has been proposed to mediate the pathogenesis of organ injury in the lung and other organs. In many of these conditions, microvascular thrombosis is accompanied by inflammation, an association referred to as thromboinflammation or immunothrombosis. A greater understanding of the links between inflammation and thrombosis in the microcirculation will provide new therapeutic options for human diseases accompanied by microvascular thrombosis.
  • Autores: Páramo Fernández, José Antonio (Autor de correspondencia)
    Revista: MEDICINA CLINICA
    ISSN 0025-7753 Vol.157 N° 12 2021 págs. 583 - 587
    Resumen
    La hemofilia A y B son trastornos hemorrágicos congénitos causados por deficiencia de los factores VIII y IX de la coagulación, respectivamente. La terapia sustitutiva del factor deficitario ha sido clásicamente la base de la profilaxis y del tratamiento de las complicaciones hemorrágicas, pero presenta varias limitaciones, como la administración frecuente por vía intravenosa, el desarrollo progresivo de artropatía y la presencia de inhibidores. Ello ha motivado la búsqueda de alternativas terapéuticas para un control más efectivo de la hemorragia y mayor facilidad de administración, tales como los factores de vida media extendida, fármacos procoagulantes como emicizumab de administración subcutánea, bloqueo de las vías anticoagulantes naturales (hemostasia rebalanceada) y la terapia génica, con las que se ha conseguido un control efectivo de la hemorragia o se encuentran en fase avanzada de investigación clínica.
  • Autores: Sáenz de Pipaon Echarren, Goren; Echeverría Andueza, Saioa; Orbe Lopategui, Josune; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN 2077-0383 Vol.10 N° 10 2021 págs. 2046
    Resumen
    Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in developed countries, affecting more than 40% of diabetes mellitus (DM) patients. DKD pathogenesis is multifactorial leading to a clinical presentation characterized by proteinuria, hypertension, and a gradual reduction in kidney function, accompanied by a high incidence of cardiovascular (CV) events and mortality. Unlike other diabetes-related complications, DKD prevalence has failed to decline over the past 30 years, becoming a growing socioeconomic burden. Treatments controlling glucose levels, albuminuria and blood pressure may slow down DKD evolution and reduce CV events, but are not able to completely halt its progression. Moreover, one in five patients with diabetes develop DKD in the absence of albuminuria, and in others nephropathy goes unrecognized at the time of diagnosis, urging to find novel noninvasive and more precise early diagnosis and prognosis biomarkers and therapeutic targets for these patient subgroups. Extracellular vesicles (EVs), especially urinary (u)EVs, have emerged as an alternative for this purpose, as changes in their numbers and composition have been reported in clinical conditions involving DM and renal diseases. In this review, we will summarize the current knowledge on the role of (u)EVs in DKD.
  • Autores: Sáenz de Pipaon Echarren, Goren; Martínez-Aguilar, E.; Orbe Lopategui, Josune; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN 1422-0067 Vol.22 N° 7 2021 págs. 3601
    Resumen
    Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. In this review, we will discuss the usefulness of inflammatory molecules, matrix metalloproteinases (MMPs), and cardiac damage markers, as well as novel components of the liquid biopsy, extracellular vesicles (EVs), and non-coding RNAs for lower limb PAD identification, stratification, and outcome assessment. We will also explore the potential of machine learning methods to build prediction models to refine PAD assessment. In this line, the usefulness of multimarker approaches to evaluate this complex multifactorial disease will be also discussed.
  • Autores: Láinez, J. M.; Ashina, M.; Belvís, R.; et al.
    Revista: REVISTA DE NEUROLOGIA
    ISSN 0210-0010 Vol.72 N° Suppl. 2 2021 págs. S1 - S19
    Resumen
    Introduction. After the European Headache Federation (EHF) Congress, renowned Spanish neurologists specialised in migraine presented the most significant latest developments in research in this field at the Post-EHF Meeting. Development. The main data presented concerning the treatment of chronic and episodic migraine were addressed, with attention paid more specifically to those related to preventive treatments and real-life experience in the management of the disease. An important review was carried out of the new therapeutic targets and the possibilities they offer in terms of understanding the pathophysiology of migraine and its treatment. An update was also presented of the latest developments in the treatment of migraine with fremanezumab, a monoclonal antibody recently authorised by the European Medicines Agency. Participants were also given an update on the latest developments in basic research on the pathology, as well as an overview of the symptoms of migraine and COVID-19. Finally, the repercussions of migraine in terms of its burden on the care and economic resources of the health system were addressed, along with its impact on society. Conclusions. The meeting summarised the content presented at the 10 EHF Congress, which took place in late June/early July 2020.
  • Autores: Gonzalez-Oria, C.; Belvis, R.; Cuadrado, M. L.; et al.
    Revista: NEUROLOGIA
    ISSN 0213-4853 Vol.36 N° 3 2021 págs. 229 - 240
    Resumen
    Introduction: Medication overuse headache is a secondary headache in which the regular or frequent use of analgesics can increase the frequency of the episodes, causing the transition from episodic to chronic headache. The prevalence of medication overuse headache is approximately 1-2%, with higher rates among women aged 30-50 years and with comorbid psychiatric disorders such as depression or anxiety, or other chronic pain disorders. It is important to be familiar with the management of this disease. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a consensus document addressing this disorder. Development: These guidelines were prepared by a group of neurologists specialising in headache after a systematic literature review and provides consensus recommendations on the proper management and treatment of medication overuse headache. The treatment of medication overuse headache is often complex, and is based on 4 fundamental pillars: education and information about the condition, preventive treatment, discontinuation of the drug being overused, and treatment for withdrawal symptoms. Follow-up of patients at risk of recurrence is important. Conclusions: We hope that this document will be useful in daily clinical practice and that it will update and improve understanding of medication overuse headache management. (C) 2020 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U.
  • Autores: Perdomo Zelaya, Carolina María; García Fernández, Nuria (Autor de correspondencia); Escalada San Martín, Francisco Javier
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN 2077-0383 Vol.10 N° 9 2021 págs. 2040
    Resumen
    Non-alcoholic fatty liver disease is a highly prevalent disease worldwide with a renowned relation to cardiovascular disease and chronic kidney disease. These diseases share a common pathophysiology including insulin resistance, oxidative stress, chronic inflammation, dysbiosis and genetic susceptibilities. Non-alcoholic fatty liver disease is especially prevalent and more severe in type 2 diabetes. Patients with non-alcoholic fatty liver disease should have liver fibrosis assessment in order to identify those at the highest risk of adverse outcomes so that appropriate management strategies can be implemented. Early diagnosis and treatment of non-alcoholic fatty liver disease could ameliorate the burden of cardiovascular disease and chronic kidney disease.
  • Autores: Páramo Fernández, José Antonio (Autor de correspondencia)
    Revista: MEDICINA CLINICA
    ISSN 0025-7753 Vol.156 N° 1 2021 págs. 20 - 25
    Resumen
    Major bleeding is a common complication of anticoagulant treatment. Risk assessment tools are relevant in the management of patients with atrial fibrillation and venous thromboembolism. The combination of clinical, biological and genetic markers is incorporated to build predictive scores to help in the decision process about intensity and duration of treatment. The optimal management of bleeding involves the application of predictive scores in combination with anticoagulant reversal strategies.
  • Autores: Marcos Jubilar, María (Autor de correspondencia); Orbe Lopategui, Josune; Roncal Mancho, Carmen; et al.
    Revista: LIFE
    ISSN 2075-1729 Vol.11 N° 5 2021 págs. 414
    Resumen
    BACKGROUND: Atherosclerosis is the main etiology of cardiovascular diseases (CVD), associated to systemic inflammation. Matrix metalloproteinases (MMPs) are related to atherosclerosis progression through the SDF1/CXCR4 axis promoting macrophages recruitment within the vascular wall. The goal was to assess new circulatory inflammatory markers in relation to atherosclerosis. METHODS: Measurement of SDF1, MMP12 and CRP in blood samples of 298 prospective patients with cardiovascular risk. To explore atherosclerosis progression, CXCR4/SDF1 axis and MMP12 expression were determined by RT-qPCR and by immunohistochemistry in the aorta of accelerated and delayed atherosclerosis mice models (Apoe-/- and Apoe-/-Mmp10-/-). RESULTS: SDF1, MMP12 and CRP were elevated in patients with clinical atherosclerosis, but after controlling by confounding factors, only SDF1 and CRP remained increased. Having high levels of both biomarkers showed 2.8-fold increased risk of presenting clinical atherosclerosis (p = 0.022). Patients with elevated SDF1, MMP12 and CRP showed increased risk of death in follow-up (HR = 3.2, 95%CI: 1.5-7.0, p = 0.004). Gene and protein expression of CXCR4 and MMP12 were increased in aortas from Apoe-/- mice. CONCLUSIONS: The combination of high circulating SDF1, MMP12 and CRP identified patients with particular inflammatory cardiovascular risk and increased mortality. SDF1/CXCR4 axis and MMP12 involvement in atherosclerosis development suggests that they could be possible atherosclerotic targets.
  • Autores: Marta Enguita, J.; Navarro Oviedo, Manuel; Muñoz, R.; et al.
    Revista: FRONTIERS IN NEUROLOGY
    ISSN 1664-2295 Vol.12 2021 págs. 599498
    Resumen
    Background: Actual clinical management of ischemic stroke (IS) is based on restoring cerebral blood flow using tissue plasminogen activator (tPA) and/or endovascular treatment (EVT). Mechanical thrombectomy has permitted the analysis of thrombus structural and cellular classic components. Nevertheless, histological assessment of hemostatic parameters such as thrombin-activatable fibrinolysis inhibitor (TAFI) and matrix metalloproteinase 10 (MMP-10) remains unknown, although their presence could determine thrombus stability and its response to thrombolytic treatment, improving patient's outcome. Methods: We collected thrombi (n = 45) from large vessel occlusion (LVO) stroke patients (n = 53) and performed a histological analysis of different hemostatic parameters [TAFI, MMP-10, von Willebrand factor (VWF), and fibrin] and cellular components (erythrocytes, leukocytes, macrophages, lymphocytes, and platelets). Additionally, we evaluated the association of these parameters with plasma levels of MMP-10, TAFI and VWF activity and recorded clinical variables. Results: In this study, we report for the first time the presence of MMP-10 and TAFI in all thrombi collected from LVO patients. Both proteins were localized in regions of inflammatory cells, surrounded by erythrocyte and platelet-rich areas, and their content was significantly associated (r = 0.41, p < 0.01). Thrombus TAFI was lower in patients who died during the first 3 months after stroke onset [odds ratio (OR) (95%CI); 0.59 (0.36-0.98), p = 0.043]. Likewise, we observed that thrombus MMP-10 was inversely correlated with the amount of VWF (r = -0.30, p < 0.05). Besides, VWF was associated with the presence of leukocytes (r = 0.37, p < 0.05), platelets (r = 0.32, p < 0.05), and 3 months mortality [OR (95%CI); 4.5 (1.2-17.1), p = 0.029]. Finally, plasma levels of TAFI correlated with circulating and thrombus platelets, while plasma MMP-10 was associated with cardiovascular risk factors and functional dependence at 3 months. Conclusions: The present study suggests that the composition and distribution of thrombus hemostatic components might have clinical impact by influencing the response to pharmacological and mechanical therapies as well as guiding the development of new therapeutic strategies.
  • Autores: Avendaño-Sola, C.; de la Cámara, R.; Castellanos, M.; et al.
    Revista: NEUROLOGIA
    ISSN 0213-4853 Vol.36 N° 6 2021 págs. 451 - 461
    Resumen
    Introduction: Cases of cerebral venous sinus thrombosis have been reported in individuals vaccinated against COVID-19 with non-replicating adenoviral vector vaccines. We issue our recommendations on the diagnosis and management of patients presenting this complication. Method: The multidisciplinary working group, led by the Spanish Federation of Medical and Scientific Associations and including representatives of several scientific societies, reviewed the available evidence from the literature and reports of the European Medicines Agency. We establish a definition for suspected cases and issue diagnostic and treatment recommendations regarding vaccine-induced immune thrombotic thrombocytopaenia. Results: We define suspected cases as those cases of cerebral venous sinus thrombosis occurring between 3 and 21 days after the administration of non-replicating adenoviral vector vaccines, in patients with a platelet count below 150,000/4 or presenting a decrease of 50% with respect to the previous value. Findings suggestive of vaccine-induced immune thrombotic thrombocytopaenia include the presence of antibodies to platelet factor 4, D-dimer levels 4 times greater than the upper limit of normal, and unexplained thrombosis. The recommended treatment includes intravenous administration of non-specific human immunoglobulin or alternatively plasmapheresis, avoiding the use of heparin, instead employing argatroban, bivalirudin, fondaparinux, rivaroxaban, or apixaban for anticoagulation, and avoiding platelet transfusion. Conclusions: Non-replicating adenoviral vector vaccines may be associated with cerebral venous sinus thrombosis with thrombocytopaenia; it is important to treat the dysimmune phenomenon and the cerebral venous sinus thrombosis. (C) 2021 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U.
  • Autores: Bornstein, R. (Autor de correspondencia); Páramo Fernández, José Antonio
    Revista: JOURNAL OF THROMBOSIS AND THROMBOLYSIS
    ISSN 0929-5305 Vol.51 N° 3 2021 págs. 633 - 636
  • Autores: Lecumberri Villamediana, Ramón (Autor de correspondencia); Jiménez, L.; Ruiz Artacho, Pedro Celso; et al.
    Revista: TH OPEN
    ISSN 2567-3459 Vol.5 N° 3 2021 págs. e319 - e328
    Resumen
    The performance of validated bleeding risk scores in patients with venous thromboembolism (VTE) could be different depending on the time after index event or the site of bleeding. In this study we compared the "classic" Registro Informatizado de Enfermedad TromboEmbólica (RIETE) score and the more recently developed VTE-BLEED score for the prediction of major bleeding in patients under anticoagulant therapy in different time intervals after VTE diagnosis. Out of 82,239 patients with acute VTE, the proportion of high-risk patients according to the RIETE and VTE-BLEED scores was 7.1 and 62.3%, respectively. The performance of both scores across the different study periods (first 30 days after VTE diagnosis, days 31-90, days 91-180, and days 181-360) was similar, with areas under the receiving operating characteristics (ROC) curve (AUC) ranging between 0.69 and 0.72. However, the positive predictive values were low, ranging between 0.6 and 3.9 (better for early major bleeding than for later periods). A sensitivity analysis limited to patients with unprovoked VTE showed comparable results. Both scores showed a trend toward a better prediction of extracranial than intracranial major bleeding, the RIETE score resulting more useful for early extracranial bleeding and the VTE-BLEED for late intracranial hemorrhages. Our study reveals that the usefulness of available bleeding scores may vary depending on the characteristics of the patient population and the time frame evaluated. ...
  • Autores: Irimia Sieira, Pablo (Autor de correspondencia); Martínez Valbuena, Iván; Mínguez Olaondo, Ane; et al.
    Revista: CEPHALALGIA
    ISSN 0333-1024 Vol.41 N° 5 2021 págs. 604 - 612
    Resumen
    Background Recently, amylin and its receptors were found in different structures involved in migraine pathophysiology. Here, we evaluate interictal concentrations of amylin and calcitonin gene-related peptide in peripheral blood as biomarkers for chronic migraine. Methods We prospectively recruited patients with episodic migraine, chronic migraine and healthy controls. Interictal amylin and calcitonin gene-related peptide levels were assessed in blood samples using enzyme linked immunosorbent assay. Results We assessed plasma samples from 58 patients with episodic migraine (mean age 37.71 +/- 10.47, 87.9% female), 191 with chronic migraine (mean age 46.03 +/- 11.93, 95% female), and on 68 healthy controls (mean age 43.58 +/- 11.08 years, 86% female). Body mass index was 25.94 +/- 4.53 kg/m(2) for migraine patients and 25.13 +/- 4.92 kg/m(2) for healthy controls (p = 0.0683). Interictal plasma amylin levels were higher in chronic migraine patients (47.1 pg/mL) than in the episodic migraine patients (28.84 pg/mL, p < 0.0001) and healthy controls (24.74 pg/mL, p < 0.0001). Plasma calcitonin gene-related peptide levels were increased (20.01 pg/mL) in chronic migraine patients when compared to healthy controls (11.37 pg/mL, p = 0.0016), but not to episodic migraine patients (18.89 pg/mL, p = 0.4369). Applying a cut-off concentration of 39.68 pg/mL plasma amylin, the sensitivity to differentiate chronic migraine from healthy controls was 57.6% and the specificity was 88.2%. Variables such as age, analgesic overuse, depression, allodynia, use of preventive medication or a history of aura did not influence the plasma concentrations of amylin or calcitonin gene-related peptide. Conclusion Interictal plasma amylin levels are higher in patients with chronic migraine and may serve as a diagnostic biomarker for chronic migraine.
  • Autores: Riera-Mestre, A. (Autor de correspondencia); Jara-Palomares, L.; Lecumberri Villamediana, Ramón; et al.
    Revista: VIRUSES-BASEL
    ISSN 1999-4915 Vol.13 N° 11 2021 págs. 2128
    Resumen
    Patients with coronavirus disease 2019 (COVID-19) have a higher risk of venous thromboembolic disease (VTE) than patients with other infectious or inflammatory diseases, both as macrothrombosis (pulmonar embolism and deep vein thrombosis) or microthrombosis. However, the use of anticoagulation in this scenario remains controversial. This is a project that used DELPHI methodology to answer PICO questions related to anticoagulation in patients with COVID-19. The objective was to reach a consensus among multidisciplinary VTE experts providing answers to those PICO questions. Seven PICO questions regarding patients with COVID-19 responded with a broad consensus: 1. It is recommended to avoid pharmacological thromboprophylaxis in most COVID-19 patients not requiring hospital admission; 2. In most hospitalized patients for COVID-19 who are receiving oral anticoagulants before admission, it is recommended to replace them by low molecular weight heparin (LMWH) at therapeutic doses; 3. Thromboprophylaxis with LMWH at standard doses is suggested for COVID-19 patients admitted to a conventional hospital ward; 4. Standard-doses thromboprophylaxis with LMWH is recommended for COVID-19 patients requiring admission to Intensive Care Unit; 5. It is recommended not to determine D-Dimer levels routinely in COVID-19 hospitalized patients to select those in whom VTE should be suspected, or as a part of the diagnostic algorithm to rule out or confirm a VTE event; 6. It is recommended to discontinue pharmacological thromboprophylaxis at discharge in most patients hospitalized for COVID-19; 7. It is recommended to withdraw anticoagulant treatment after 3 months in most patients with a VTE event associated with COVID-19. The combination of PICO questions and DELPHI methodology provides a consensus on different recommendations for anticoagulation management in patients with COVID-19.
  • Autores: García-García, P.; Reyes, R.; Rodríguez García, José Antonio; et al.
    Revista: PHARMACEUTICS
    ISSN 1999-4923 Vol.13 N° 7 2021 págs. 979
    Resumen
    Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold's slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.
  • Autores: Panizo Morgado, Elena; Páramo Fernández, José Antonio
    Revista: PEDIATRIA INTEGRAL
    ISSN 1135-4542 Vol.25 N° 5 2021 págs. 265.e1 - 265.e11
    Resumen
    La hemostasia comprende un complejo sistema de reacciones en cadena, sinérgicas y coordinadas, cuya finalidad última es mantener la sangre fluida en el interior de los vasos sanguíneos. Para ello, existe un delicado equilibrio entre los factores procoagulantes y anticoagulantes. Disponemos de una amplia variedad de pruebas analíticas que exploran el sistema hemostático en sus distintas fases (hemostasia primaria, hemostasia secundaria y fibrinólisis). Para poder solicitarlas con criterio y saber interpretarlas, es preciso tener unas nociones básicas de la fisiología de la hemostasia. En el presente artículo, se explican las bases fisiológicas de la coagulación, haciendo hincapié en las peculiaridades de la ¿hemostasia del desarrollo¿ del niño y se exponen las pruebas de estudio disponibles, sus indicaciones y su interpretación.
  • Autores: Gómez-Outes, A. (Autor de correspondencia); Alcubilla, P.; Calvo-Rojas, G.; et al.
    Revista: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
    ISSN 0735-1097 Vol.77 N° 24 2021 págs. 2987 - 3001
    Resumen
    BACKGROUND Direct oral anticoagulants (DOACs) have shown a positive benefit-risk balance in both clinical trials and real-world data, but approximately 2% to 3.5% of patients experience major bleeding annually. Many of these patients require hospitalization, and the administration of reversal agents may be required to control bleeding. OBJECTIVES The aim of this study was to investigate clinical outcomes associated with the use of 4-factor pro thrombin complex concentrates, idarucizumab, or andexanet for reversal of severe DOAC-associated bleeding. METHODS The investigators systematically searched for studies of reversal agents for the treatment of severe bleeding associated with DOAC. Mortality rates, thromboembolic events, and hemostatic efficacy were meta-analyzed using a random effects model. RESULTS The investigators evaluated 60 studies in 4,735 patients with severe DOAC-related bleeding who were treated with 4-factor prothrombin complex concentrates (n = 2,688), idarucizumab (n = 1,111), or andexanet (n = 936). The mortality rate was 17.7% (95% confidence interval [CI]: 15.1% to 20.4%), and it was higher in patients with intracranial bleedings (20.2%) than in patients with extracranial hemorrhages (15.4%). The thromboembolism rate was 4.6% (95% CI: 3.3% to 6.0%), being particularly high with andexanet (10.7%; 95% CI: 6.5% to 15.7%). The effective hemostasis rate was 78.5% (95% CI: 75.1% to 81.8%) and was similar regardless of the reversal agent considered. The rebleed
  • Autores: Belvis, R.; Irimia Sieira, Pablo (Autor de correspondencia); Seijo-Fernandez, F.; et al.
    Revista: NEUROLOGIA
    ISSN 0213-4853 Vol.36 N° 1 2021 págs. 61 - 79
    Resumen
    Introduction: Numerous invasive and non-invasive neuromodulation devices have been developed and applied to patients with headache and neuralgia in recent years. However, no updated review addresses their safety and efficacy, and no healthcare institution has issued specific recommendations on their use for these 2 conditions. Methods: Neurologists from the Spanish Society of Neurology's (SEN) Headache Study Group and neurosurgeons specialising in functional neurosurgery, selected by the Spanish Society of Neurosurgery (SENEC), performed a comprehensive review of articles on the MEDLI NE database addressing the use of the technique in patients with headache and neuralgia. Results: We present an updated review and establish the first set of consensus recommendations of the SEN and SENC on the use of neuromodulation to treat headache and neuralgia, analysing the current levels of evidence on its effectiveness for each specific condition. Conclusions: Current evidence supports the indication of neuromodulation techniques for patients with refractory headache and neuralgia (especially migraine, cluster headache, and trigeminal neuralgia) selected by neurologists and headache specialists, after pharmacological treatment options are exhausted. Furthermore, we recommend that invasive neuromodulation be debated by multidisciplinary committees, and that the procedure be performed by teams of neurosurgeons specialising in functional neurosurgery, with acceptable rates of morbidity and mortality. (C) 2020 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U.
  • Autores: Cortés Jiménez, Adriana; Pejenaute Martínez de Lizarrondo, Álvaro; Marques Cantero, Javier; et al.
    Revista: ANTIOXIDANTS
    ISSN 2076-3921 Vol.10 N° 2 2021 págs. 194
    Resumen
    Oxidative stress constitutes a key molecular mechanism in the development of cardiovascular diseases. A potential relationship between reactive oxygen species (ROS) driven by the NADPH oxidase family (NOX) and the unfolded protein response (UPR) has been postulated. Nevertheless, there is a lack of information about the crosstalk between NOX5 homologue and the UPR in a cardiovascular context. The main aim was to analyze NOX5-mediated ROS effects in the UPR and its importance in cardiovascular diseases. To this effect, we used an adenoviral NOX5-beta overexpression model in human aortic endothelial cells (HAEC) and a conditional endothelial NOX5 knock-in mouse. Using expression arrays, we investigated NOX5-induced genomic changes in HAEC. Compared with the control HAEC, 298 genes were differentially expressed. Gene ontology analysis revealed the activation of numerous cellular routes, the most relevant being the UPR pathway. Using real-time PCR and Western Blot experiments, we confirmed that NOX5 overexpression induced changes in the expression of the UPR components, which were associated with increased apoptosis. Moreover, in endothelial-specific NOX5 knock-in mice, we found changes in the expression of the UPR components genes. In these mice, myocardial infarction was performed by permanent coronary artery ligation; however, NOX5 expression was not associated with differences in the UPR components mRNA levels. In these animals, we found significant associations between the U
  • Autores: Caronna, E.; Gallardo, V. J.; Alpuente, A.; et al.
    Revista: NEUROLOGIA
    ISSN 0213-4853 Vol.36 N° 8 2021 págs. 611 - 617
    Resumen
    Background and objective: CGRP, a neuropeptide involved in migraine pathophysiology, is also known to play a role in the respiratory system and in immunological conditions such as sepsis. We analyzed the impact of the use of CGRP antagonists in patients with migraine during the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus. Methods: This is a multicentre cross-sectional study. From May to November 2020, through a national survey distributed by the Spanish Society of Neurology, we collected data about the presence of COVID-19 symptoms including headache and their characteristics and severity in patients with migraine treated with anti-CGRP monoclonal antibodies (mAb), and compared them with patients with migraine not receiving this treatment. We also conducted a subanalysis of patients with COVID-19 symptoms. Results: We recruited 300 patients with migraine: 51.7% (155/300) were taking anti-CGRP mAbs; 87.3% were women (262/300). Mean age (standard deviation) was 47.1 years (11.6). Forty-one patients (13.7%) met diagnostic criteria for COVID-19, with no statistically significant difference between patients with and without anti-CGRP mAb treatment (16.1% vs 11.0%, respectively; P = .320). Of the patients with COVID-19, 48.8% (20/41) visited the emergency department and 12.2% (5/41) were hospitalised. Likewise, no clinical differences were found between the groups of patients with and without anti-CGRP mAb treatment. Conclusion: Anti-CGRP mAbs may be safe in clinical practice, presenting no association with increased risk of COVID-19.
  • Autores: Marta-Enguita, J.; Navarro Oviedo, Manuel; Rubio-Baines, I.; et al.
    Revista: JOURNAL OF NEUROINFLAMMATION
    ISSN 1742-2094 Vol.18 N° 1 2021 págs. 3
    Resumen
    Background Inflammatory response plays an important role in many processes related to acute ischemic stroke (AIS). Calprotectin (S100A8/S100A9), released by monocytes and neutrophils, is a key protein in the regulation of inflammation and thrombosis. The purpose of this study is to evaluate the association of circulating calprotectin with other inflammatory biomarkers and AIS prognosis, as well as the calprotectin content in stroke thrombi. Methods Among the 748 patients treated at a comprehensive stroke center between 2015 and 2017, 413 patients with confirmed acute ischemic injury were prospectively evaluated. Patients with systemic inflammation or infection at onset were excluded. Plasma calprotectin was measured by ELISA in blood samples of AIS patients within the first 24 h. Univariate and multivariate logistic regression models were performed to evaluate its association with mortality and functional independence (FI) at 3 months (defined as modified Rankin Scale < 3) and hemorrhagic transformation (HT) after ischemic stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n = 44). Results Higher calprotectin levels were associated with 3-month mortality, HT, and lower 3-month FI. After adjusting for potential confounders, plasma calprotectin remained associated with 3-month mortality [OR (95% CI) 2.31 (1.13-4.73)]. Patients with calprotectin >= 2.26 mu g/mL were 4 times more likely to die [OR 4.34 (1.95-9.67)]. Addition of calprotectin to clinical variables led to significant improvement in the discrimination capacity of the model [0.91 (0.87-0.95) vs 0.89 (0.85-0.93); p < 0.05]. A multimarker approach demonstrated that patients with increased calprotectin, CRP, and NLR had the poorest outcome with a mortality rate of 42.3% during follow-up. S100A9 protein, as part of the heterodimer calprotectin, was present in all thrombi retrieved from AIS patients. Mean S100A9 content was 3.5% and tended to be higher in patients who died (p = 0.09). Moreover, it positively correlated with platelets (Pearson r 0.46, p < 0.002), leukocytes (0.45, p < 0.01), and neutrophil elastase (0.70, p < 0.001) thrombus content. Conclusions Plasma calprotectin is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with poor outcome after AIS. The presence of S100A9 in stroke thrombi suggests a possible inflammatory mechanism in clot formation, and further studies are needed to determine its influence in resistance to reperfusion.
  • Autores: Figueroa, R. E.; Marcos Jubilar, María; García-Mouriz, A.; et al.
    Revista: THROMBOSIS RESEARCH
    ISSN 0049-3848 Vol.200 N° Supl. 1 2021 págs. S77 - S78
  • Autores: Figueroa, R. E.; Marcos Jubilar, María; García-Mouriz, A.; et al.
    Revista: THROMBOSIS RESEARCH
    ISSN 0049-3848 Vol.200 N° Supl. 1 2021 págs. S7 - S7
  • Autores: Irimia Sieira, Pablo; García-Azorín, D.; Núñez, M.; et al.
    Revista: JOURNAL OF THE NEUROLOGICAL SCIENCES
    ISSN 0022-510X Vol.429 N° Supl. S 2021 págs. 232
  • Autores: Sáenz de Pipaon Echarren, Goren; Van Der Bent, M. L.; Martínez-Aguilar, E.; et al.
    Revista: ATHEROSCLEROSIS
    ISSN 0021-9150 Vol.331 2021 págs. E221 - E221
  • Autores: García Fernández, Nuria (Autor de correspondencia); Jacobs-Cacha, C.; Mora Gutiérrez, Jose María; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN 2077-0383 Vol.9 N° 2 2020 págs. 472
    Resumen
    Abstract: Around the world diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD), which is characterized by mesangial expansion, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. The hallmark of the pathogenesis of DKD is an increased extracellular matrix (ECM) accumulation causing thickening of the glomerular and tubular basement membranes, mesangial expansion, sclerosis, and tubulointerstitial fibrosis. The matrix metalloproteases (MMPs) family are composed of zinc-dependent enzymes involved in the degradation and hydrolysis of ECM components. Several MMPs are expressed in the kidney; nephron compartments, vasculature and connective tissue. Given their important role in DKD, several studies have been performed in patients with DKD proposing that the measurement of their activity in serum or in urine may become in the future markers of early DKD. Studies from diabetic nephropathy experimental models suggest that a balance between MMPs levels and their inhibitors is needed to maintain renal homeostasis. This review focuses in the importance of the MMPs within the kidney and their modifications at the circulation, kidney and urine in patients with DKD. We also cover the most important studies performed in experimental models of diabetes in terms of MMPs levels, renal expression and its down-regulation effect.
  • Autores: Santos-Lasaosa, S. (Autor de correspondencia); Cuadrado, M. L.; Gago-Veiga, A. B.; et al.
    Revista: NEUROLOGIA
    ISSN 0213-4853 Vol.35 N° 8 2020 págs. 568 - 578
    Resumen
    Introduction: In the field of headaches, onabotulinumtoxinA (onabotA) is well established as a treatment for chronic migraine (CM). In recent years, it has been used increasingly to treat other primary headaches (high-frequency episodic migraine, trigeminal-autonomic cephatalgias, nummular headache) and trigeminal neuralgia. As this treatment will progressively be incorporated in the management of these patients, we consider it necessary to reflect, with a fundamentally practical approach, on the possible indications of onabotA, beyond CM, as well as its administration protocol, which will differ according to the type of headache and/or neuralgia. Development: This consensus document was drafted based on a thorough review and analysis of the existing literature and our own clinical experience. The aim of the document is to serve as guidelines for professionals administering onabotA treatment. The first part will address onabotA's mechanism of action, and reasons for its use in other types of headache, from a physiopathological and clinical perspective. In the second part, we will review the available evidence and studies published in recent years. We will add an "expert recommendation" based on our own clinical experience, showing the best patient profile for this treatment and the most adequate dose and administration protocol. Conclusion: Treatment with onabotA should always be individualised and considered in selected patients who have not responded to conventional therapy. (C) 2017 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U.
  • Autores: Schunemann, H. J. (Autor de correspondencia); Ventresca, M.; Crowther, M.; et al.
    Revista: THE LANCET. HAEMATOLOGY
    ISSN 2352-3026 Vol.7 N° 10 2020 págs. e746 - e755
    Resumen
    Background Study-level meta-analyses provide high-certainty evidence that heparin reduces the risk of symptomatic venous thromboembolism for patients with cancer; however, whether the benefits and harms associated with heparin differ by cancer type is unclear. This individual participant data meta-analysis of randomised controlled trials examines the effect of heparin on survival, venous thromboembolism, and bleeding in patients with cancer in general and by type. Methods In this systematic review and meta-analysis we searched MEDLINE, Embase, and The Cochrane Library for randomised controlled trials comparing parenteral anticoagulants with placebo or standard care in ambulatory patients with solid tumours and no indication for anticoagulation published from the inception of each database to January 14, 2017, and updated it on May 14, 2020, without language restrictions. We calculated the effect of parenteral anticoagulant administration on all-cause mortality, venous thromboembolism occurrence, and bleeding related outcomes through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect, adjusting for age, cancer type, and metastatic status. Interaction terms were tested to investigate effects in predefined subgroups. This study is registered with PROSPERO, CRD42013003526. Findings We obtained individual participant data from 14 of 20 eligible randomised controlled trials (8278 [79%] of 10 431 participants; 4139 included in the low-molecular-weight heparin group and 4139 in the control group). Meta-analysis showed an adjusted relative risk (RR) of mortality at 1 year of 0.99 (95% CI 0.93-1.06) and a hazard ratio of 1.01 (95% CI 0.96-1.07). The number of patients with venous thromboembolic events was 158 (4.0%) of 3958 with available data in the low-molecular-weight heparin group compared with 279 (7.1%) of 3957 in the control group. Major bleeding events occurred in 71 (1.7%) of 4139 patients in the control population and 88 (2.1%) in the low-molecular-weight heparin group, and minor bleeding events in 478 (12.1%) of 3945 patients with available data in the control group and 652 (16.6%) of 3937 patients in the low-molecular-weight heparin group. The adjusted RR was 0.58 (95% CI 0.47-0.71) for venous thromboembolism, 1.27 (0.92-1.74) for major bleeding, and 1.34 (1.19-1.51) for minor bleeding. Prespecified subgroup analysis of venous thromboembolism occurrence by cancer type identified the most certain benefit from heparin treatment in patients with lung cancer (RR 0.59 [95% CI 0.42-0.81]), which dominated the overall reduction in venous thromboembolism. Certainty of the evidence for the outcomes ranged from moderate to high. Interpretation Low-molecular-weight heparin reduces risk of venous thromboembolism without increasing risk of major bleeding compared with placebo or standard care in patients with solid tumours, but it does not improve survival. Copyright (C) 2020 Elsevier Ltd. All rights reserved.
  • Autores: Lou-Mercade, A. C.; Gavin, O.; Oros, D.; et al.
    Revista: ULTRASOUND IN OBSTETRICS AND GYNECOLOGY
    ISSN 0960-7692 Vol.56 N° 1 2020 págs. 111 - 112
  • Autores: Mora Gutiérrez, Jose María; Rodríguez García, José Antonio; Fernández Seara, María Asunción; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN 2045-2322 Vol.10 N° 1 2020
    Resumen
    Matrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473¿±¿274¿pg/ml vs. 332¿±¿151; p¿=¿0.02) and TIMP-1 (573¿±¿296¿ng/ml vs. 375¿±¿317; p¿<¿0.001) levels were significantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to end-stage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and significant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.
  • Autores: Navarro Oviedo, Manuel; Munoz-Arrondo, R.; Zandio, B.; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN 2045-2322 Vol.10 N° 1 2020 págs. 10329
    Resumen
    Matrix metalloproteinases (MMPs) are proteolytic zinc-endopeptidases regulated by tissue Inhibitors of matrix metalloproteinases (TIMPs). We evaluated the potential of MMPs and TIMPs as clinical tools for Intracranial Haemorrhage (ICH). Spontaneous non-traumatic ICH patients were recruited from two hospitals: Complejo Hospitalario de Navarra (CHN=29) and Vall d ' Hebron (VdH=76). Plasmatic levels of MMP-1, -2, -7, -9, -10 and TIMP-1 and their relationship with clinical, radiological and functional variables were evaluated. We further studied the effect of TIMP-1 (0.05-0.2mg/Kg) in an experimental tail-bleeding model. In CHN, TIMP-1 was associated with admission-hematoma volume and MMP-7 was elevated in patients with deep when compared to lobar hematoma. In VdH, admission-hematoma volume was associated with TIMP-1 and MMP-7. When data from both hospitals were combined, we observed that an increase in 1ng/ml in TIMP-1 was associated with an increase of 0.14ml in haemorrhage (combined beta =0.14, 95% CI=0.08-0.21). Likewise, mice receiving TIMP-1 (0.2mg/Kg) showed a shorter bleeding time (p<0.01). Therefore, the association of TIMP-1 with hematoma volume in two independent ICH cohorts suggests its potential as ICH biomarker. Moreover, increased TIMP-1 might not be sufficient to counterbalance MMPs upregulation indicating that TIMP-1 administration might be a beneficial strategy for ICH.
  • Autores: Alpuente, A. ; Gallardo, V. J.; Torres-Ferrus, M.; et al.
    Revista: EUROPEAN JOURNAL OF NEUROLOGY
    ISSN 1351-5101 Vol.27 N° 10 2020 págs. 2102 - 2108
    Resumen
    Background and purpose OnabotulinumtoxinA is an effective preventive treatment for chronic migraine (CM). In CM, in addition to a reduction in headache frequency, a decreased reliance on oral prophylactics is also indicative of treatment effectiveness. This study aimed to quantify the change in the use of oral prophylactics after treatment with onabotulinumtoxinA in patients with CM. Methods This was a retrospective, multicentric, cross-sectional study. Patients with CM (International Classification of Headache Disorders-3beta) that had been treated with onabotulinumtoxinA were enrolled consecutively. We collected parameters related to each patient's pre-treatment situation, as well as their current situation, focusing on frequency and intensity of migraine, number of oral prophylactics and the respective cycle of onabotulinumtoxinA. Univariate and logistic regression analyses were performed. Results We included 542 patients, 90.0% of whom were taking oral preventive treatments. During treatment with onabotulinumtoxinA, 47.8% withdrew at least one prophylactic and 41.6% stopped using oral prophylactics altogether. Factors associated with a reduction or cessation of oral prophylactics were >50% improvement in frequency and intensity, remission to episodic migraine, use of topiramate as an initial treatment, increased number of infiltrations and shorter chronification period (P < 0.05). The multivariate analysis showed that a chronification period <20 months, more than five cycles of onabotulinumtoxinA, >50% improvement in pain intensity and topiramate as an initial treatment were predictors of a reduction in oral prophylactics (area under the curve, 70.3%;P < 0.001). Conclusions Our study demonstrated the efficacy and safety of onabotulinumtoxinA. This treatment reduced the use of oral prophylactics. Withdrawal of oral prophylactics was most likely to occur after five cycles of treatment.
  • Autores: Marques Cantero, Javier; Cortés Jiménez, Adriana; Pejenaute Martínez de Lizarrondo, Álvaro; et al.
    Revista: INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELL BIOLOGY
    ISSN 1357-2725 Vol.128 2020 págs. 105851
    Resumen
    Oxidative stress is one of the main mechanisms involved in the pathophysiology of vascular diseases. Among others, oxidative stress promotes endothelial dysfunction, and accelerated ageing and remodelling of vasculature. Lately, NADPH oxidases have been demonstrated to be involved in cardiovascular diseases. NADPH oxidase 5 has emerged as a new player in oxidative stress-mediated endothelial alterations, involved in the pathophysiology of hypertension, diabetes, atherosclerosis, myocardial infarction and stroke. This oxidase seems to mediate its detrimental effects by promoting inflammation. NADPH oxidase 5 has been studied in a lesser extent compared with the other members of the NADPH oxidase family due to its loss in the rodent genome, the main experimental research model. In addition, its potential as a therapeutic target remains unexplored given the lack of specific inhibitors. In this review the latest findings on NADPH oxidase 5 regulation, implications in vascular pathophysiology and therapeutic approaches will be updated.Oxidative stress is one of the main mechanisms involved in the pathophysiology of vascular diseases. Among others, oxidative stress promotes endothelial dysfunction, and accelerated ageing and remodelling of vasculature. Lately, NADPH oxidases have been demonstrated to be involved in cardiovascular diseases. NADPH oxidase 5 has emerged as a new player in oxidative stress-mediated endothelial alterations, involved in the pathophysiology of hypertension, diabetes, atherosclerosis, myocardial infarction and stroke. This oxidase seems to mediate its detrimental effects by promoting inflammation. NADPH oxidase 5 has been studied in a lesser extent compared with the other members of the NADPH oxidase family due to its loss in the rodent genome, the main experimental research model. In addition, its potential as a therapeutic target remains unexplored given the lack of specific inhibitors. In this review the latest findings on NADPH oxidase 5 regulation, implications in vascular pathophysiology and therapeutic approaches will be updated.
  • Autores: Moreno Ajona, David; Irimia Sieira, Pablo (Autor de correspondencia); Rodríguez García, José Antonio; et al.
    Revista: BMC CARDIOVASCULAR DISORDERS
    ISSN 1471-2261 Vol.20 N° 1 2020 págs. 93
    Resumen
    Background Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by F-18-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. Methods This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. F-18-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. Results The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with F-18-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by F-18-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by F-18-FDG-PET was not significant. Conclusions Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.
  • Autores: Matilla, L.; Roncal Mancho, Carmen; Ibarrola, J.; et al.
    Revista: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
    ISSN 1079-5642 Vol.40 N° 5 2020 págs. 1370 - 1382
    Resumen
    Objective: Aortic valve (AV) calcification plays an important role in the progression of aortic stenosis (AS). MMP-10 (matrix metalloproteinase-10 or stromelysin-2) is involved in vascular calcification in atherosclerosis. We hypothesize that MMP-10 may play a pathophysiological role in calcific AS. Approach and Results: Blood samples (n=112 AS and n=349 controls) and AVs (n=88) from patients undergoing valve replacement were analyzed. Circulating MMP-10 was higher in patients with AS compared with controls (P<0.001) and correlated with TNF alpha (tumor necrosis factor alpha; r(S)=0.451; P<0.0001). MMP-10 was detected by immunochemistry in AVs from patients with AS colocalized with aortic valve interstitial cells markers alpha-SMA (alpha-smooth muscle actin) and vimentin and with calcification markers Runx2 (Runt-related transcription factor 2) and SRY (sex-determining region Y)-box 9. MMP-10 expression in AVs was further confirmed by RT-qPCR and western blot. Ex vivo, MMP-10 was elevated in the conditioned media of AVs from patients with AS and associated with interleukin-1 beta (r(S)=0.5045, P<0.001) and BMP (bone morphogenetic protein)-2 (r(S)=0.5003, P<0.01). In vitro, recombinant human MMP-10 induced the overexpression of inflammatory, fibrotic, and osteogenic markers (interleukin-1 beta, alpha-SMA, vimentin, collagen, BMP-4, Sox9, OPN [osteopontin], BMP-9, and Smad 1/5/8; P<0.05) and cell mineralization in aortic valve interstitial cells isolated from human AVs, in a mechanism involving Akt (protein kinase B) phosphorylation. These effects were prevented by TIMP-1 (tissue inhibitor of metalloproteinases type 1), a physiological MMP inhibitor, or specifically by an anti-MMP-10 antibody. Conclusions: MMP-10, which is overexpressed in aortic valve from patients with AS, seems to play a central role in calcification in AS through Akt phosphorylation. MMP-10 could be a new therapeutic target for delaying the progression of aortic valve calcification in AS.
  • Autores: Irimia Sieira, Pablo (Autor de correspondencia); Garrido-Cumbrera, M.; Santos-Lasaosa, S.; et al.
    Revista: EUROPEAN JOURNAL OF NEUROLOGY
    ISSN 1351-5101 Vol.27 N° 12 2020 págs. 2616 - 2624
    Resumen
    Background and purpose Migraine is a common and costly neurological disorder. The aims of this study were to quantify the costs of chronic (CM) and episodic migraine (EM) in Spain, evaluating the impact of psychiatric comorbidities and disability, and to estimate the economic savings associated with reducing the number of migraine-days by 50%. Methods This was an observational, cross-sectional analysis of data from migraine patients who participated in the Spanish Migraine Atlas. The participants were invited to complete a structured questionnaire including the following scales: the Headache Needs Assessment, the Hospital Anxiety and Depression Scale, and the Migraine Disability Assessment Scale (MIDAS). Results A total of 475 patients were included, of whom 187 had CM (39.4%). Total costs per patient/year were: euro16 578.2 +/- euro34 568.1 for CM and euro6227.8 +/- euro6515.7 for EM. A higher degree of disability, according to MIDAS, significantly increased the total cost of migraine, while the presence of psychiatric comorbidity increased costs for EM patients only. A reduction of 1 migraine-day per month decreased average total costs by euro744.14 per patient/year for EM and euro663.20 per patient/year for CM, while a reduction in the number of migraine-days by 50% would result in economic savings of euro2232.44 per patient/year (R-2 = 0.927) for EM and euro6631.99 per patient/year (R-2 = 0.886) for CM. Conclusions The costs associated with migraine were driven by migraine frequency and the degree of disability, whereas psychiatric comorbidity only influenced the cost of EM. These results highlight the need to optimize migraine management to reduce the economic migraine burden. Future studies are needed to confirm our results.
  • Autores: Robin, P. (Autor de correspondencia); van Es, N. ; Le Roux, P. Y.; et al.
    Revista: THROMBOSIS RESEARCH
    ISSN 0049-3848 Vol.194 2020 págs. 153 - 157
    Resumen
    Introduction: Venous thromboembolism (VTE) may be the first manifestation of cancer. We aimed at evaluating the performance of F-18-Fluorodesoxyglucose Positron-Emission Tomography/Computed Tomography (FDG PET/CT) for occult cancer screening in patients with unprovoked VTE. Methods: This was a pre-specified analysis of a systematic review and individual patient data meta-analysis including prospective studies assessing cancer screening in patients with unprovoked VTE. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FDG PET/CT were calculated based on cancer diagnosis during a 1-year follow-up period. Results: Four studies were identified as using FDG PET/CT as part of their extensive screening strategy. Out of the 332 patients who underwent FDG PET/CT, the scan was interpreted as positive in 67 (20.2%), as equivocal in 27 (8.1%), and as negative in 238 (71.7%). Seventeen (5.1%) patients were diagnosed with cancer at inclusion or during the 12-month follow up period. All cancers were diagnosed at initial screening. Pooled sensitivity, specificity, NPV, and PPV were 87.3% (95% CI, 55.3 to 97.4), 70.2% (95% CI, 48.2 to 85.6), 98.9% (95% CI, 94.3 to 99.7), and 17.9% (95% CI, 8.5 to 33.6), respectively. Conclusion: FDG PET/CT appears to have satisfactory accuracy indices for cancer diagnosis in patients with unprovoked VTE. In particular, it exhibits a very high negative predictive value and could be used to rule out the presence of an underlying occult malignancy in this setting.
  • Autores: Lecumberri Villamediana, Ramón (Autor de correspondencia); Ruiz Artacho, Pedro Celso; Trujillo-Santos, J.; et al.
    Revista: THROMBOSIS RESEARCH
    ISSN 0049-3848 Vol.195 2020 págs. 139 - 145
    Resumen
    Introduction: Treatment of venous thromboembolism (VTE) in cancer patients with thrombocytopenia is challenging due to perceived higher risk of bleeding. Material and methods: We used the RIETE registry to compare the 10- and 30-day outcomes in cancer patients with acute VTE, according to platelet count at baseline. Results: As of December 2018, 15,337 cancer patients with VTE were included: 166 (1.1%) had < 50 x 10(9) platelets/L (severe thrombocytopenia), 711 (4.6%) had 50-99 x 10(9)/L (mild thrombocytopenia) and 14,460 (94.3%) had >= 100 x 10(9)/L (normal count). Most patients in all subgroups received initial therapy with low-molecular-weight heparin (LMWH), but 62% of those with severe thrombocytopenia received < 150 IU/kg/day LMWH, 42% received < 100 IU/kg/day. The mortality rate progressively decreased with increasing platelet counts (12%, 9.4% and 3.3% respectively at 10 days, 27%, 18% and 9.4% at 30 days), but the major bleeding rates did not (1.2%, 2.5% and 1.3% respectively at 10 days, 2.4%, 4.4% and 2.2% at 30 days). On multivariable analysis, patients with severe thrombocytopenia had a similar risk for major bleeding at 10 days (OR 0.84; 95%CI 0.20-3.49) and at 30 days (OR 0.90; 95%CI 0.32-2.49), but those with mild thrombocytopenia were at increased risk both at 10 days (OR 2.11; 95%CI 1.27-3.49) and at 30 days (OR 1.91; 95%CI 1.29-2.84). Conclusions: Cancer patients with acute VTE and baseline thrombocytopenia often receive initial lower-than recommended doses of LMWH. Although caution is required, this practice seems to be safe in patients with severe thrombocytopenia. Nonetheless, there was an inverse correlation between baseline platelet count and mortality.
  • Autores: van-Es, N.; Ventresca, M.; Di-Nisio, M.; et al.
    Revista: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
    ISSN 1538-7933 Vol.18 N° 8 2020 págs. 1940 - 1951
    Resumen
    Background Oncology guidelines suggest using the Khorana score to select ambulatory cancer patients receiving chemotherapy for primary venous thromboembolism (VTE) prevention, but its performance in different cancers remains uncertain. Objective To examine the performance of the Khorana score in assessing 6-month VTE risk, and the efficacy and safety of low-molecular-weight heparin (LMWH) among high-risk Khorana score patients. Methods This individual patient data meta-analysis evaluated (ultra)-LMWH in patients with solid cancer using data from seven randomized controlled trials. Results A total of 3293 patients from the control groups with an available Khorana score had lung (n = 1913; 58%), colorectal (n = 452; 14%), pancreatic (n = 264; 8%), gastric (n = 201; 6%), ovarian (n = 184; 56%), breast (n = 164; 5%), brain (n = 84; 3%), or bladder cancer (n = 31; 1%). The 6-month VTE incidence was 9.8% among high-risk Khorana score patients and 6.4% among low-to-intermediate-risk patients (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). The dichotomous Khorana score performed differently in lung cancer patients (OR 1.1; 95% CI, 0.72-1.7) than in the group with other cancer types (OR 3.2; 95% CI, 1.8-5.6;P-interaction = .002). Among high-risk patients, LMWH decreased the risk of VTE by 64% compared with controls (OR 0.36; 95% CI, 0.22-0.58), without increasing the risk of major bleeding (OR 1.1; 95% CI, 0.59-2.1). Conclusion The Khorana score was unable to stratify patients with lung cancer based on their VTE risk. Among those with other cancer types, a high-risk score was associated with a three-fold increased risk of VTE compared with a low-to-intermediate risk score. Thromboprophylaxis was effective and safe in patients with a high-risk Khorana score.
  • Autores: Mínguez Olaondo, Ane; Martínez Valbuena, Iván; Romero, S.; et al.
    Revista: JOURNAL OF HEADACHE AND PAIN
    ISSN 1129-2369 Vol.21 N° 1 2020 págs. 9
    Resumen
    Objective To investigate the specific relationship between cutaneous allodynia (CA) and the percentages of body fat (BF) and abdominal fat in migraineurs. Additionally, we compared serum levels of inflammatory biomarkers in patients with and without CA. Background Excess abdominal fat might facilitate progressive changes in nociceptive thresholds causing central sensitization, clinically reflected as CA, which could drive migraine progression. Methods This prospective cohort study included 80 patients with migraine (mean age 39 years, 81.2% female) and 39 non-migraine controls. We analysed each participant's height, body weight, and body mass index (BMI). The amount and distribution of BF was also assessed by air displacement plethysmography (ADP) and ViScan, respectively. We analysed serum levels of markers of inflammation, during interictal periods. Results We studied 52 patients with episodic migraine (EM) and 28 with chronic migraine (CM). Of the 80 patients, 53 (53.8%) had CA. Migraineurs with CA had a higher proportion of abdominal fat values than patients without CA (p = 0.04). The independent risk factors for CA were the use of migraine prophylaxis (OR 3.26, 95% CI [1.14 to 9.32]; p = 0.03), proportion of abdominal fat (OR 1.13, 95% CI [1.01 to 1.27]; p = 0.04), and presence of sleep disorders (OR 1.13, 95% CI [00.01 to 1.27]; p = 0.04). The concordance correlation coefficient between the ADP and BMI measurements was 0.51 (0.3681 to 0.6247). CA was not correlated with the mean plasma levels of inflammatory biomarkers. Conclusions There is a relation between excess abdominal fat and CA. Abdominal obesity might contribute to the development of central sensitization in migraineurs, leading to migraine chronification.
  • Autores: Lecumberri Villamediana, Ramón (Autor de correspondencia); Krsnik, I. ; Askari, E.; et al.
    Revista: AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
    ISSN 1350-6129 Vol.27 N° 3 2020 págs. 163 - 167
    Resumen
    Management of patients with relapsed or refractory (R/R) AL amyloidosis is complex. Some initial reports have shown positive results with daratumumab in heavily pre-treated AL amyloidosis patients. In this retrospective multicentric study, 38 patients (mean age 64 +/- 9 years) with R/R AL amyloidosis treated with daratumumab were included. Cardiac and renal involvement was present in 76 and 74% of patients, and 42% had >= 3 organs involved. Median number of previous lines of therapy was 2 (range 1-8). Overall hematological response was 72%, including 28% complete responses. The median time to first hematological response was 2 weeks. A high-quality response (>= very good partial response) was obtained in 65% of patients who had never achieved such depth of response previously. Hematological responses were more frequent among patients receiving daratumumab as second-line therapy compared to subsequent therapies (92 vs. 61%). Cardiac and renal organ response rates were 37 and 59%. At 12 months, overall and progression-free survival were 59% (95%CI: 0.36-0.77) and 52% (95%CI: 0.29-0.70), respectively. Daratumumab is a safe and effective drug in the treatment of R/R AL amyloidosis and should be considered early in the course of the disease.
  • Autores: Bermejo, S.; Gonzalez, E.; Lopez-Revuelta, K.; et al.
    Revista: CLINICAL KIDNEY JOURNAL
    ISSN 2048-8505 Vol.13 N° 3 2020 págs. 380 - 388
    Resumen
    Background. Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. Methods. Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. Results. In total, 832 patients were included: 621 men (74.6%), mean age of 61.7612.8 years, creatinine was 2.862.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2-5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02-1.05, P< 0.001], microhaematuria (OR = 1.51, 95% CI: 1.03-2.21, P = 0.033) and absence of diabetic retinopathy (DR) (OR = 0.28, 95% CI: 0.19-0.42, P< 0.001) were independently associated with NDRD. Kaplan-Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P< 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P< 0.001), higher serum creatinine (P< 0.001), higher proteinuria (P< 0.001), DR (P = 0.007) and DN (P< 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P< 0.001), peripheral vascular disease (P = 0.002), higher creatinine (P = 0.01) and DN (P = 0.015) were independent risk factors for mortality. Conclusions. The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.
  • Autores: Páramo Fernández, José Antonio (Autor de correspondencia)
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN 1137-6627 Vol.43 N° 2 2020 págs. 245 - 249
    Resumen
    One of the most significant negative prognostic factors in patients suffering from the disease caused by SARS-CoV-2 (COVID-19) is the development of coagulopathy, associated with abnormal laboratory findings, such as increased D-dimer, and venous thromboembolic complications, requiring thromboprophylactic strategies. The main clinical characteristics of COVID-19 patients are revised here as compared to other coronavirus infections, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), emphasizing clinical, diagnostic and therapeutic aspects.
  • Autores: Barril, G.; Nogueira, A.; García Fernández, Nuria; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.35 N° Supl. 3 2020 págs. 1270
  • Autores: Irimia Sieira, Pablo; Minguez-Olaondo, A. ; Martínez Valbuena, Iván; et al.
    Revista: CEPHALALGIA
    ISSN 0333-1024 Vol.40 N° 1_SUPPL 2020 págs. 34 - 35
  • Autores: Janssens, R. ; Morgan, K. ; Silvennoinen, R. ; et al.
    Revista: VALUE IN HEALTH
    ISSN 1098-3015 Vol.23 2020 págs. S474 - S475
  • Autores: Irimia Sieira, Pablo; Benhaddi, H. ; Morand, F.; et al.
    Revista: VALUE IN HEALTH
    ISSN 1098-3015 Vol.23 2020 págs. S632 - S632
  • Autores: Mínguez-Olaondo, A.; García-Azorín, D.; Sánchez-Mateos, N. M.; et al.
    Revista: EUROPEAN JOURNAL OF NEUROLOGY
    ISSN 1351-5101 Vol.27 N° Supl. 1 2020 págs. 864
  • Autores: Marta Enguita, J. ; Navarro Oviedo, Manuel; Rubio Baines, Íñigo; et al.
    Revista: INTERNATIONAL JOURNAL OF STROKE
    ISSN 1747-4930 Vol.15 N° 1_SUPPL 2020 págs. 491 - 491
  • Autores: Marta Enguita, J. ; Rubio Baines, I. ; Blanco Luquin, I.; et al.
    Revista: INTERNATIONAL JOURNAL OF STROKE
    ISSN 1747-4930 Vol.15 N° 1_SUPPL 2020 págs. 422 - 422
  • Autores: Gago-Veiga, A. B.; Santos-Lasaosa, S.; Cuadrado, M. L.; et al.
    Revista: NEUROLOGÍA (BARCELONA. ED. IMPRESA)
    ISSN 0213-4853 Vol.34 N° 6 2019 págs. 408 - 417
    Resumen
    OnabotulinumtoxinA has been demonstrated to be effective as a preventive treatment in patients with chronic migraine (CM). Five years after the approval of onabotulinumtoxinA in Spain, the Headache Study Group of the Spanish Society of Neurology considered it worthwhile to gather a group of experts in treating patients with CM in order to draw up, based on current evidence and our own experience, a series of guidelines aimed at facilitating the use of the drug in daily clinical practice. For this purpose, we posed 12 questions that we ask ourselves as doctors, and which we are also asked by our patients. Each author responded to one question, and the document was then reviewed by everyone. We hope that this review will constitute a practical tool to help neurologists treating patients with CM.
  • Autores: Arrieta, V.; Sadaba, J. R.; Alvarez, V. ; et al.
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN 1137-6627 Vol.42 N° 2 2019 págs. 199 - 208
    Resumen
    Aortic stenosis is one of the most common heart valve diseases, as well as one of the most common causes of heart failure in the elderly. Currently, there are no medical therapies to prevent or slow the progression of the disease. When symptoms develop alongside severe aortic stenosis, there is a poor prognosis unless aortic valve replacement is performed. Aortic stenosis is a heterogeneous disease with a complex pathophysiology involving structural and biological changes of the valve, as well as adaptive and maladaptive compensatory changes in the myocardium and vasculature in response to chronic pressure overload. Galectin-3 serves important functions in numerous biological activities including cell growth, apoptosis, differentiation, inflammation and fibrosis. With evidence emerging to support the function of Galectin-3, the current review aims to summarize the latest literature regarding the potential of Galectin-3 as therapeutic target in aortic valve and cardiovascular alterations associated with aortic stenosis.
  • Autores: Doménech López, Pablo (Autor de correspondencia); Robles García, José Enrique; Gutiérrez Castañé, Cristina; et al.
    Revista: ACTAS UROLOGICAS ESPAÑOLAS
    ISSN 0210-4806 Vol.43 N° 43747 2019 págs. 455 - 466
    Resumen
    Introduction: With the advanced laparoscopic and robotic surgery, thromboembolic prophylaxis in urologic procedures has traditionally been based on the experience of other surgical specialties. This paper aims to analyze the current recommendations, through a detailed study of the European clinical guidelines and bibliography, applying the recommendations of thromboprophylaxis to the daily urological practice. Objectives: To elaborate general recommendations to surgical patients in Urology, avoiding the risk of perioperative thromboembolic events. Optimize medication in chronic patients and accurately classify who are eligible for bridge therapy. Material and methods: A review of the available literature and the European clinical guidelines was carried out. We analyzed the most recent consensus articles by studying the available bibliography, trials and reviews on which the European guidelines for thromboprophytaxis in urology are based. Results: Thromboembolic prophylaxis should be targeted towards surgeries that require abdominal approaches, prolonged bed rest or oncologicat pathologies. Bridge therapies with low molecular weight heparins should be limited. Patients undergoing treatment for chronic conditions can benefit from bridge therapies in specific cases. Conclusions: According to the current guidelines, there might be an overuse of heparins in the daily clinical practice. The development of -direct oral- anticoagulants have shown to reduce the time to reintroduction of medication for chronic conditions as well as a more effective bleeding management. (C) 2019 AEU. Published by Elsevier Espana, S.L.U. All rights reserved.
  • Autores: Figueroa Mora, María del Rocío; Alfonso Piérola, Ana; Marcos, M.; et al.
    Revista: TH OPEN
    ISSN 2512-9465 Vol.3 N° 2 2019 págs. e153 - e156
  • Autores: Lasaosa, S. S. ; Irimia Sieira, Pablo (Autor de correspondencia)
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN 1137-6627 Vol.42 N° 2 2019 págs. 235 - 238
  • Autores: Irimia Sieira, Pablo (Autor de correspondencia); Martínez Vila, Eduardo Antonio
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN 1137-6627 Vol.42 N° 1 2019 págs. 119 - 120
  • Autores: Arias Pou, Paloma María; Aquerreta González, Irene; Idoate García, Antonio Joaquín; et al.
    Revista: EUROPEAN JOURNAL OF HOSPITAL PHARMACY - SCIENCE AND PRACTICE
    ISSN 2047-9956 Vol.26 N° 1 2019 págs. 33 - 38
    Resumen
    Objective Electronic alert systems have shown their capacity for improving the detection of acute kidney injury (AKI). The aim of this study was to design and implement a clinical decision support system (CDSS) for improving drug selection and reducing nephrotoxic drug use in patients with AKI. Methods The study was designed as an intervention study comparing a pre and post cohort of patients admitted during April 2014 and April 2015, respectively (phase I and phase II). The intervention was a CDSS which provided kidney function and nephrotoxic drug information. Furthermore, an interruptive alert was designed to detect patients suffering an AKI event while taking a nephrotoxic drug and to see if the dose was then reduced or the drug was discontinued by the physicians. Results One-third of the inpatients were included in the analysis because they met the inclusion criteria (1004 and 1002 patients in phases I and II, respectively). 735 and 761 of them received at least one nephrotoxic alert (73% vs 76%; p=0.763). 65 and 88 patients suffered AKI during admission (6.5% vs 8.8%; p=0.051). In phase I, patients received 384 nephrotoxic alerts (55%) with 78 (20%) of them provoking a change or discontinuation of the nephrotoxic drug. In phase II this value increased to 154 out of 526 (29%) after implementation of the CDSS (p<0.01). Conclusions A CDSS with interruptive alerts that inform of the development of AKI in real time in patients with nephrotoxic drug prescription has a positive impact on the judicious use of these drugs.
  • Autores: Lorente, L. (Autor de correspondencia); Martin, M. M.; Ramos, L.; et al.
    Revista: JOURNAL OF CRITICAL CARE
    ISSN 0883-9441 Vol.51 2019 págs. 117 - 121
    Resumen
    Purpose: Previously, higher circulating levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor matrix metalloproteinases (TIMP)-1 were reported in the first hours after TBI in blood samples from patients with poor prognosis. Thus, the objectives of this study were to determine whether MMP-9 and TIMP-1 levels during the first week of a severe TBI could be used as biomarker predictive of mortality. Methods: We included patients with severe TBI (defined as Glasgow Coma Scale lower than 9), and with Injury Severity Score in non-cranial aspects lower than 9. We determined serum concentrations of MMP-9 and TIMP-1 at days 1, 4 and 8 of TBI. Results: TIMP-1 concentrations at days 1 (p < .001), 4 (p = .001), and 8 (p = .01) of TBI were higher in nonsurviving (n = 34) than in surviving (n = 90) patients. ROC curve analyses showed an area under curve of TIMP-1 concentrations at days 1, 4, and 8 of TBI to predict 30-day mortality of 78% (p < .001), 76% (p <.001) and 71% (p= .02) respectively. Conclusions: The most relevant new findings of our study were that TIMP-1 levels during the first week of a severe TBI were higher in non-surviving than in surviving patients and that could be used as biomarker predictive of mortality. (C) 2019 Elsevier Inc. All rights reserved.
  • Autores: Reyes, L. ; Herrero Santos, José Ignacio; Rotellar Sastre, Fernando; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN 1130-0108 Vol.111 N° 6 2019 págs. 437 - 444
    Resumen
    Introduction: portal vein thrombosis is a relatively common complication of advanced cirrhosis that increases perioperative risk in liver transplant recipients. This condition was characterized in a cohort of patients, including risk factors and their influence on survival. Material and methods: a retrospective study of liver transplant recipients at the Clinica Universidad de Navarra was performed between 2000 and 2015. Differences in clinical and biological characteristics and survival were analyzed in subjects with and without portal vein thrombosis. A predictive index was also developed. Results: a total of 288 patients were included in the study, portal vein thrombosis was recorded in 46 (16%) cases and seven (15.2%) had stage 3/4 disease according to Yerdel's classification. Factors associated with the presence of esophageal/gastric varices (OR = 3.7; p = 0.03) included variceal ligation or sclerotherapy (OR = 2.3; p = 0.01), being overweight/obesity (OR = 2.1; p = 0.04) and thrombocytopenia (OR = 3.6; p = 0.04). There were no significant differences between the groups with and without portal vein thrombosis in terms of survival according to Kaplan-Meier curve analysis (p = 0.7). However, the mortality rate was higher for Yerdel stages 3-4 (p < 0.01). A predictive index was developed that included varices, body mass index (BMI), thrombocytopenia and activated partial thromboplastin time (APTT). This index had a sensitivity of 76.1% and a specificity of 53.7% for the development of portal thrombosis. Conclusions: the presence of esophageal/gastric varices, variceal ligation/sclerotherapy, thrombocytopenia and being overweight/obesity was associated with a higher rate of portal vein thrombosis. Advanced stages had an impact on survival.
  • Autores: Arrieta Pey, María; Molero Santos, Patricio
    Revista: MEDICINE (ELSEVIER)
    ISSN 0304-5412 Vol.12 N° 86 2019 págs. 5081 - 5087
    Resumen
    ipolar disorder (BD) is a serious mental disorder of chronic and recurrent course, characterized by episodes of mania, hypomania, depressive or mixed. Detailed clinical history, in order to identify the symptoms of each episode, is required for a proper diagnosis. Diagnostic criteria for each episode, as well as the different BD subtypes, are well described in the main psychiatric diagnostic manuals of mental illnesses (CIE and DSM). Taking into account the episode showed by the patient, pharmacological approach varies. Early clinical and functional recovery is the main goal of therapeutic approach to acute episode; the safety of the patient and relatives or close persons has to be taking into account. Long term overall stabilization of the patient, prevention of relapses or additional episodes, together with preservation of functionality are the main therapeutic goals.
  • Autores: Moreno Ajona, David; Moreno Artero, Ester; García de Eulate Ruiz, María Reyes; et al.
    Revista: CEPHALALGIA
    ISSN 0333-1024 Vol.39 N° 4 2019 págs. 564 - 568
    Resumen
    Background Localized facial scleroderma usually presents as frontal linear morphea or progressive hemifacial atrophy. Only isolated cases of trigeminal painful neuropathy have been described. Case report A 43-year-old woman developed an oval lesion on the right cheek. After 1 year, she noticed constant "pulling" pain and episodes of lancinating pain, both spontaneous and triggered by chewing and cold drinks. She was diagnosed with solitary morphea profunda and CT scan, ultrasonography, cranial MRI and biopsy were completed. Methylprednisolone (1¿gr/day for 3 days) was prescribed. For pain, gabapentin, oxcarbazepine, amitryptiline, pregabalin and eslicarbacepine were all ineffective. A capsaicin patch was placed with prolonged benefit. Later on, the pain slightly worsened; occipital blockade was effective and methotrexate was recommended. Conclusion This is the first case of solitary morphea profunda associated with painful trigeminal neuropathy. Treatment should include immunosuppressants and treatment of neuropathic pain, in which local therapies seem particularly beneficial.
  • Autores: Martínez Vila, Eduardo Antonio; Domínguez Echávarri, Pablo Daniel; Toledano Illán, Carlos; et al.
    Revista: MEDICINE (ELSEVIER)
    ISSN 0304-5412 Vol.12 N° 70 2019 págs. 4108 - 4119
    Resumen
    El ictus isquémico de causa inhabitual representa el 8% de los infartos y el 30% en los adultos jóvenes. Se caracteriza por su heterogeneidad etiológica y puede ser la primera manifestación de la enfermedad de base o una complicación evolutiva más. Los síntomas/signos asociados a la enfermedad subyacente suelen orientar el diagnóstico. El tratamiento es el de la enfermedad de base, si resulta posible, y los fármacos antitrombóticos. La oclusión trombótica de las venas encefálicas y senos durales es más frecuente en adultos jóvenes y predomina en las mujeres (3:1). Las trombofilias hereditarias, embarazo y puerperio, anticonceptivos orales, neoplasias, arteriopatías inflamatorias e infecciones son los principales factores de riesgo. El síntoma más frecuente es la cefalea. Los principales síndromes de presentación son: hipertensión intracraneal aislada, encefalopatía subaguda y cuadro focal. Se trata con anticoagulantes y su pronóstico es generalmente bueno.
  • Autores: Diener, H. C. (Autor de correspondencia); Goadsby, P. J.; Ashina, M. ; et al.
    Revista: CEPHALALGIA
    ISSN 0333-1024 Vol.39 N° 12 2019 págs. 1475 - 1487
    Resumen
    Introduction Non-invasive vagus nerve stimulation (nVNS; gammaCore (R)) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data. Methods This multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-week open-label period of nVNS. Patients were to administer two 120-second stimulations bilaterally to the neck three times daily (6-8 hours apart). Results Of 477 enrolled patients, 332 comprised the intent-to-treat (ITT) population. Mean reductions in migraine days per month (primary outcome) were 2.26 for nVNS (n = 165; baseline, 7.9 days) and 1.80 for sham (n = 167; baseline, 8.1 days) (p = 0.15). Results were similar across other outcomes. Upon observation of suboptimal adherence rates, post hoc analysis of patients with >= 67% adherence per month demonstrated significant differences between nVNS (n = 138) and sham (n = 140) for outcomes including reduction in migraine days (2.27 vs. 1.53; p = 0.043); therapeutic gains were greater in patients with aura than in those without aura. Most nVNS device-related adverse events were mild and transient, with application site discomfort being the most common. Conclusions Preventive nVNS treatment in episodic migraine was not superior to sham stimulation in the ITT population. The "sham" device inadvertently provided a level of active vagus nerve stimulation. Post hoc analysis showed significant effects of nVNS in treatment-adherent patients. Study identification and registration: PREMIUM; NCT02378844;
  • Autores: Pereira Sánchez, Víctor; Molero Santos, Patricio
    Revista: MEDICINE (ELSEVIER)
    ISSN 0304-5412 Vol.12 N° 86 2019 págs. 5070 - 5074
    Resumen
    When adequate therapeutic measures are implemented, the response rates of depressive disorders, despite being a major cause of discomfort, disability and suicide, are acceptable. Diagnosis is based on anamnesis, detailed psychopathological exploration and data collection from third persons, if possible. In order to rule out general medical conditions, complementary tests can be requested. It is mandatory to determine the severity of the condition by assessing the impact of the symptoms and the risk of harm to oneself or third parties. Treatment has to be consistent with the severity of symptoms, personalized to each patient and based on scientific evidence. Hygienic-dietetic guides, psychotherapy, pharmacological treatments, neuromodulation therapies and functional rehabilitation, are included in the therapeutic measures. Two algorithms for clinical decision making are included in the present protocol.
  • Autores: Calsina Juscafresa, Laura (Autor de correspondencia); Páramo Alfaro, María; Grochowicz, Lukasz Karol; et al.
    Revista: DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY
    ISSN 1305-3825 Vol.25 N° 2 2019 págs. 166 - 168
    Resumen
    Aneurysms of the portal vein and its branches have been rarely described. Their natural history is unknown although large ones (>3 cm in diameter) have been reported to cause rupture, thrombosis, duodenal or biliary obstruction, inferior vena cava compression and/or portal hypertension. We report the case of an incidentally diagnosed 4.5 cm splenic vein aneurysm repaired by endovascular treatment through a transhepatic route. The aneurysm was successfully excluded using a covered stent (Viabahn, Gore). The transhepatic route opens the possibility of offering a minimally invasive approach to vascular lesions of the portal vein system.
  • Autores: Navarro Oviedo, Manuel; Roncal Mancho, Carmen; Salicio Castillo, Agustina; et al.
    Revista: TRANSLATIONAL STROKE RESEARCH
    ISSN 1868-4483 Vol.10 N° 4 2019 págs. 389 - 401
    Resumen
    Diabetes is an important risk factor for ischemic stroke (IS). Tissue-type plasminogen activator (tPA) has been associated with less successful revascularization and poor functional outcome in diabetes. We assessed whether a new thrombolytic strategy based on MMP10 was more effective than tPA in a murine IS model of streptozotocin (STZ)-induced diabetes. Wild-type mice were administered a single dose of streptozotocin (STZ) (180mg/kg) to develop STZ-induced diabetes mellitus. Two weeks later, IS was induced by thrombin injection into the middle cerebral artery and the effect of recombinant MMP10 (6.5 mu g/kg), tPA (10mg/kg) or tPA/MMP10 on brain damage and functional outcome were analysed. Motor activity was assessed using the open field test. Additionally, we studied plasminogen activator inhibitor-1 (PAI-1) and thrombin-antithrombin complex levels (TAT) by ELISA and oxidative stress and blood-brain barrier (BBB) integrity by immunohistochemistry and western blot. MMP10 treatment was more effective at reducing infarct size and neurodegeneration than tPA 24h and 3days after IS in diabetic mice. Locomotor activity was impaired by hyperglycemia and ischemic injury, but not by the thrombolytic treatments. Additionally, TAT, oxidative stress and BBB permeability were reduced by MMP10 treatment, whereas brain bleeding or PAI-1 expression did not differ between treatments. Thrombolytic treatment with MMP10 was more effective than tPA at reducing stroke and neurodegeneration in a diabetic murine model of IS, without increasing haemorrhage. Thus, we propose MMP10 as a potential candidate for the clinical treatment of IS in diabetic patients.
  • Autores: Rabadan, I. R.; de Lecinana, M. A.; Martin, R. B.; et al.
    Revista: CLINICA E INVESTIGACION EN ARTERIOSCLEROSIS
    ISSN 0214-9168 Vol.31 N° 6 2019 págs. 263 - 270
    Resumen
    A multidisciplinary panel of cardiologists, neurologists, internal medicine and specialists in hemostasis and thrombosis has elaborated this document showing recent scientific evidences supporting a better profile of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKA), as well as the indications of specific antidotes and hemostatic agents to reverse the anticoagulant effects of DOACs. The analysis reinforces the best profile of DOACs and its special benefit in patients with basal high hemorrhagic risk.
  • Autores: Marcos Jubilar, María (Autor de correspondencia); García-Erce, J. A.; Martinez-Calle, N.; et al.
    Revista: TRANSFUSION MEDICINE
    ISSN 0958-7578 Vol.29 N° 4 2019 págs. 268 - 274
    Resumen
    Objective To evaluate the effectiveness and safety of prothrombin complex concentrates (PCCs) in approved and off-label indications. Background PCCs are approved for the urgent reversal of vitamin K antagonists (VKAs). Data concerning the efficacy, safety and dosing for off-label indications are limited, but they are included in massive bleeding protocols. Methods This was a retrospective review of cases treated with four-factor PCCs (4F-PCCs) between January 2009 and 2016. Efficacy end-points include: (i) VKA reversal efficacy assessed by international normalised ratio (INR) normalisation (<1 center dot 5) and (ii) clinical efficacy as bleeding cessation and/or decreased number of transfused blood components and 24-h mortality in bleeding coagulopathy. The safety end-point is the incidence of thromboembolic events. Results A total of 328 patients were included (51 center dot 8% male, median age 78 years old). Indications were as follows: VKA reversal (66 center dot 6%), bleeding coagulopathy (30 center dot 5%) and direct anticoagulant (DOAC) reversal due to bleeding (2 center dot 5%). VKA reversal was effective in 97 center dot 1% of patients, and 76 center dot 5% demonstrated complete reversal (INR < 1 center dot 5); only 34 center dot 3% patients needed hemoderivatives. Prior to emergency procedures, PCCs achieved global responses in 83% of patients, with no bleeding complication during intervention. DOAC reversal was effective in 88 center dot 9% of patients. Bleeding cessation was associated with the dose administered (P = 0 center dot 002). In coagulopathy bleeding, haemorrhage cessation, established by the International Society of Thrombosis and Haemostais (ISTH) definition, occurred in 56 center dot 7% of massive bleeding events and in 42 center dot 5% of other coagulopathies; 24-h mortality was 30%, mainly related to active bleeding. Ten thrombotic episodes were observed (3 center dot 1%). Conclusion 4F-PCC was effective as adjuvant treatment with an acceptable safety profile, not only for the emergent reversal of VKAs but also for refractory coagulopathy associated with major bleeding.
  • Autores: Marcos Jubilar, María; Orbe Lopategui, Josune; Roncal Mancho, Carmen; et al.
    Revista: CLINICA E INVESTIGACION EN ARTERIOSCLEROSIS
    ISSN 0214-9168 Vol.31 N° 4 2019 págs. 152 - 159
    Resumen
    Introduction: Monocytes play an important role in atherosclerotic progression having both pro and anti-inflammatory effects depending on different circulating monocyte subpopulations. The objective of this study is to characterize these subpopulations and their association with cardiovascular risk factors. Methods: Transversal study including 102 selected patients, mean age: 65 years-old (range 41-86), 69% males. A set of specific antibodies against classical monocytes (Mont, CD14+CD16- CD300e+HLADR+), intermediate (Mon2, CD14+CD16+CD300e+HLADR+) and nonclassical (Mon3, CD14 CD16+CD300e+HLADR+) was assayed. Three groups of patients were included: 17 asymptomatic with more than one cardiovascular risk factor (group 1), 56 subjects asymptomatic but with vascular pathology assessed by ultrasound or microalbuminuria (group 2) and 19 patients with a previous atherothrombotic event (group 3). The cardiovascular risk was determined by Framingham and REGICOR scores. Results: An association between study groups and the percentage of Mon1 and Mon2 was observed (ANOVA, p <.05), being independent of age and sex for Mon2. Likewise Mont and Mon2 subpopulations were associated with cardiovascular adverse events (beta=0.86, p=.02 beta-0.1 p=.002, respectively), independently of age and sex in the case of Mon2. Moreover the percentage of Mon3 was associated with the presence of several cardiovascular risk factors ((3 = 0.21, p =.04) in the univariate analysis. In addition, there was a correlation between the levels of Mon1 and Mon2 and leukocytes (r =0.7, p <.001 and r =0.26, p =.01, respectively). Conclusions: The analysis of monocyte subpopulations may be clinically useful to stratify the inflammatory profile related to the different cardiovascular risk groups.
  • Autores: Lorente, L. (Autor de correspondencia); Martin, M. M. ; Ramos, L.; et al.
    Revista: BMC NEUROLOGY
    ISSN 1471-2377 Vol.19 2019 págs. 167
    Resumen
    Background: Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 early after ischemic stroke have been associated with lower survival. The objectives of this study were to determine serum TIMP-1 levels during the first week of a severe cerebral infarction in surviving and non-surviving patients, and whether those levels during the first week could be used as a mortality biomarker for these patients. Methods: We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as computer tomography showing ischaemic changes in more than 50% of the middle cerebral artery territory and Glasgow Coma Scale (GCS) <= 8. We measured serum levels of matrix metalloproteinases (MMP)-9 and TIMP-1. End-point study was 30-day mortality. Results: We found higher TIMP-1 concentrations at days 1 (p < 0.001), 4 (p = 0.001), and 8 (p = 0.03) of MMCAI in non-urviving (n = 34) than in surviving (n = 34) patients. We found lower serum MMP-9 concentrations at day 1 (p = 0.03) of MMCAI and no significant differences at days 4 and 8. ROC curve analysis of TIMP-1 concentrations performed at days 1, 4, and 8 of MMCAI showed an area under curve to predict 30-day mortality of 81% (p < 0.001), 80% (p < 0.001) and 72% (p = 0.07) respectively. Conclusions: The new findings of our study were that non-surviving MMCAI patients showed higher serum TIMP-1 levels during the first week of MMCAI that surviving patients, and those levels during the first week of MMCAI could be used as mortality biomarkers.
  • Autores: Páramo Fernández, José Antonio (Autor de correspondencia); Lecumberri Villamediana, Ramón
    Revista: MEDICINA CLINICA
    ISSN 0025-7753 Vol.153 N° 2 2019 págs. 78 - 81
  • Autores: Jara-Palomares, L. (Autor de correspondencia); van Es, N.; Praena-Fernandez, J. M.; et al.
    Revista: THROMBOSIS RESEARCH
    ISSN 0049-3848 Vol.176 2019 págs. 79 - 84
    Resumen
    Background: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to assess the period prevalence of occult cancer detection stratified by VTE location (deep vein thrombosis [DVT], pulmonary embolism [PE] or both) and the anatomical relationship between occult cancer and VTE. Methods: Post-hoc analysis of a systematic review and individual patient data meta-analysis of adults with unprovoked VTE with at least 12 months of follow-up. Cancer types were grouped according to thoracic, abdomino-pelvic, or other locations. Results: A total of 2300 patients were eligible including 1218 with DVT only (53%), 719 with PE only (31%), and 363 with both PE and DVT (16%). The pooled 12-month period prevalence of cancer in DVT only, PE only, and DVT + PE was 5.6% (95% CI, 4.4 to 7.2), 4.3% (95% CI, 2.7 to 6.9), and 5.6% (95% CI, 1.7 to 15.5), respectively. Most occult cancers were located in the abdomen (68.4%). The proportion of patients with an abdomino-pelvic cancer was not different in patients with DVT + PE (81%; 95% CI, 54 to 96) than in those with DVT (68%; 95% CI, 57 to 78) or PE alone (65%; 95% CI, 48 to 79). Conclusion: The 12-month prevalence of occult cancer was similar in patients with DVT only, PE only, or both. Most cancers were located in the abdomen, and there was no relationship between VTE type and cancer location.
  • Autores: Martos, L. ; Fernandez-Pardo, A. ; Lopez-Fernandez, M. F.; et al.
    Revista: THROMBOSIS AND HAEMOSTASIS
    ISSN 0340-6245 Vol.119 N° 9 2019 págs. 1409 - 1418
    Resumen
    Presently, no data on the molecular basis of hereditary protein C (PC) deficiency in Spain is available. We analyzed the PC gene ( PROC ) in 109 patients with symptomatic PC deficiency and in 342 relatives by sequencing the 9 PROC exons and their flanking intron regions. In 93 probands, we found 58 different mutations (26 novel). Thirty-seven consisted of a nucleotide change, mainly missense mutations, 1 was a 6-nucleotide insertion causing the duplication of 2 amino acids, and 4 were deletions of 1, 3, 4, and 16 nucleotides. Nine mutations caused type II deficiencies, with the presence of normal antigen levels but reduced anticoagulant activity. Using a PC level of 70% as lowest normal limit, we found no mutations in 16 probands and 25 relatives with PC levels <= 70%. On the contrary, 4 probands and 12 relatives with PC levels > 70% carried the mutation identified in the proband. The spectrum of recurrent mutations in Spain is different from that found in the Netherlands, where the most frequent mutations were p.Gln174* and p.Arg272Cys, and is more similar to that found in France, where the most frequent were p.Arg220Gln and p.Pro210Leu. In our study, p.Val339Met (9 families), p.Tyr166Cys (7), p.Arg220Gln (6), and p.Glu58Lys (5) were the most prevalent. This study confirms the considerable heterogeneity of the genetic abnormality in PC deficiencies, and allowed genetic counseling to those individuals whose PC levels were close to the lower limit of the normal reference range.
  • Autores: Roncal Mancho, Carmen; Martinez-Aguilar, E.; Orbe Lopategui, Josune; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN 2045-2322 Vol.9 2019 págs. 15580
    Resumen
    Peripheral artery disease (PAD) is a major cause of acute and chronic illness, with extremely poor prognosis that remains underdiagnosed and undertreated. Trimethylamine-N-Oxide (TMAO), a gut derived metabolite, has been associated with atherosclerotic burden. We determined plasma levels of TMAO by mass spectrometry and evaluated their association with PAD severity and prognosis. 262 symptomatic PAD patients (mean age 70 years, 87% men) categorized in intermittent claudication (IC, n = 147) and critical limb ischemia (CLI, n = 115) were followed-up for a mean average of 4 years (min 1-max 102 months). TMAO levels were increased in CLI compared to IC (P < 0.001). Receiver operating characteristic (ROC) curves for severity (CLI) rendered a cutoff of 2.26 mu mol/L for TMAO (62% sensitivity, 76% specificity). Patients with TMAO > 2.26 mu mol/L exhibited higher risk of cardiovascular death (sub-hazard ratios >= 2, P < 0.05) that remained significant after adjustment for confounding factors. TMAO levels were associated to disease severity and CV-mortality in our cohort, suggesting an improvement of PAD prognosis with the measurement of TMAO. Overall, our results indicate that the intestinal bacterial function, together with the activity of key hepatic enzymes for TMA oxidation (FMO3) and renal function, should be considered when designing therapeutic strategies to control gut-derived metabolites in vascular patients.
  • Autores: Irimia Sieira, Pablo; Esparragosa Vázquez, Inés; Valentí Azcárate, Rafael; et al.
    Revista: MEDICINE (ELSEVIER)
    ISSN 0304-5412 Vol.12 N° 70 2019 págs. 4075 - 4084
    Resumen
    Intracerebral hemorrhage (ICH) accounts for 20% of all strokes; caused by the collection of blood within the cerebral parenchyma as the result of vascular rupture. Taking into account its etiology, primary hemorrhages are the most common and are caused by the vascular wall weakness as a result of chronic arterial hypertension or due to degenerative processes as amyloid angiopathy. Secondary causes include arteriovenous malformations, tumors, hemorrhages induced by drugs and substance abuse. The most important risk factors for developing ICH are arterial hypertension, smoking, substance abuse (alcohol and drugs). Hemorrhage location and bleeding volume determine clinical manifestations. In order to distinguish between ICH and other ischemic or structural lesions, both computed tomography (CT) and magnetic resonance imaging (MRI) may be used for the diagnosis. To determine the most likely bleed cause, bleed location and microbleed detection (only detected by MRI) are necessary. Treatment for patients with ICH is fundamentally medical, and they must be cared for in a hospital with stroke unit. Surgical treatment is only recommended for a reduced number of carefully selected cases.
  • Autores: Irimia Sieira, Pablo; Moreno Ajona, David; Sanchez del Río González, Margarita; et al.
    Revista: MEDICINE (ELSEVIER)
    ISSN 0304-5412 Vol.12 N° 71 2019 págs. 4194 - 4198
    Resumen
    Chronic headaches encompass different types of headaches (primary and secondary). Proper clinical history and detailed physical and neurological exam are required in order to perform additional diagnostic tests. Most of the patients suffer primary headache syndromes. Sometimes, pain becomes chronic by the abuse of analgesic drugs. In patients older than 50 years of age, erythrocyte sedimentation rate has to be performed in order to rule out temporal arteritis diagnostic. When warning signs or suspicious of atypical headaches are present, brain imaging tests are required. Underlying cause determines the treatment. Sympthomatic pain treatment is required, but analgesic drugs must be limited. In order to reduce the intensity and frequency of bouts, prophylactic treatment is indicated for chronic primary headaches.
  • Autores: Figueroa Mora, María del Rocío; Alfonso Piérola, Ana; López-Picazo González, José María; et al.
    Revista: CLINICAL AND TRANSLATIONAL ONCOLOGY
    ISSN 1699-048X Vol.21 N° 6 2019 págs. 805 - 809
    Resumen
    PURPOSE: Thromboprophylaxis use among medical inpatients, including cancer patients, is suboptimal. We aimed to evaluate the impact of a novel multiscreen version (v2.0) of an e-alert system for VTE prevention in hospitalised cancer medical patients compared to the original software. METHODS: Prospective study including 989 consecutive adult cancer patients with high-risk of VTE. Patients were followed-up 30 days post-discharge. Two periods were defined, according to the operative software. RESULTS: E-alert v2.0 was associated with an increase in the use of LMWH prophylaxis (65.5% vs. 72.0%); risk difference (95% CI) 0.064 (0.0043-0.12). Only 16% of patients in whom LMWH prophylaxis was not prescribed lacked a contraindication. No significant differences in the rates of VTE (2.9% vs. 3.2%) and major bleeding (2.7% vs. 4.0%) were observed. CONCLUSIONS: E-alert v2.0 further increased the use of appropriate thromboprophylaxis in hospitalised cancer patients, although was not associated with a reduction in VTE incidence.
  • Autores: Lecumberri Villamediana, Ramón; Krsnik, I. ; Askari, E.; et al.
    Revista: HAEMATOLOGICA
    ISSN 0390-6078 Vol.104 N° Supl. 3 2019 págs. 16 - 16
  • Autores: Navarro Oviedo, Manuel; Enguita, J. M.; Saldise, M. B.; et al.
    Revista: HAEMATOLOGICA
    ISSN 0390-6078 Vol.104 2019 págs. 135 - 136
  • Autores: Domper, L. F. ; Roncal Mancho, Carmen; Martinez-Aguilar, E. ; et al.
    Revista: HAEMATOLOGICA
    ISSN 0390-6078 Vol.104 2019 págs. 137 - 137
  • Autores: Marcos Jubilar, María; Pastrana Delgado, Juan Carlos; Orbe Lopategui, Josune; et al.
    Revista: HAEMATOLOGICA
    ISSN 0390-6078 Vol.104 2019 págs. 144 - 144
  • Autores: Sáenz de Pipaon Echarren, Goren; Orbe Lopategui, Josune; Aguilar, E. M.; et al.
    Revista: ATHEROSCLEROSIS
    ISSN 0021-9150 Vol.287 2019 págs. E141 - E141
  • Autores: Irimia Sieira, Pablo; Garrido-Cumbrera, M. ; Blanch, C.; et al.
    Revista: CEPHALALGIA
    ISSN 0333-1024 Vol.39 2019 págs. 130 - 130
  • Autores: Roncal Mancho, Carmen; Martinez-Aguilar, E.; Orbe Lopategui, Josune; et al.
    Revista: ATHEROSCLEROSIS
    ISSN 0021-9150 Vol.287 2019 págs. E233 - E233
  • Autores: Lavilla Royo, Francisco Javier; Alfaro Sanchez, Christian Israel; González Arostegui, Omar Jose; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.34 2019 págs. 152 - 152
  • Autores: Figueroa Mora, María del Rocío; Alfonso Piérola, Ana; Garcia-Mouriz, A. ; et al.
    Revista: HAEMATOLOGICA
    ISSN 0390-6078 Vol.104 2019 págs. 136 - 136
  • Autores: Mora Gutiérrez, Jose María; Romeo, M. J. S.; Fernández Seara, María Asunción; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.34 2019
  • Autores: Fernandez-Pardo, A. ; Oto, J.; Martos, L.; et al.
    Revista: HAEMATOLOGICA
    ISSN 0390-6078 Vol.104 N° Supl. 3 2019 págs. 136 - 137
  • Autores: Bermejo, S.; Gonzalez, E. ; Martin, N.; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.34 2019
  • Autores: Echarri González, Gemma; Duque Sosa, Paula Andrea; García Fernández, Nuria; et al.
    Revista: EUROPEAN JOURNAL OF ANAESTHESIOLOGY
    ISSN 0265-0215 Vol.35 N° 1 2018 págs. 65 - 66
    Resumen
    BACKGROUND Four predictive models for acute kidney injury associated with cardiac surgery were developed by Demirjian in the United States in 2012. However, the usefulness of these models in clinical practice needs to be established in different populations independent of that used to develop the models. OBJECTIVES Our aim was to evaluate the predictive performance of these models in a Spanish population. DESIGN A multicentre, prospective observational study. DATA SOURCES Twenty-three Spanish hospitals in 2012 and 2013. ELIGIBILITY CRITERIA Of 1067 consecutive cardiac patients recruited for the study, 1014 patients remained suitable for the final analysis. MAIN OUTCOME MEASURES Dialysis therapy, and a composite outcome of either a doubling of the serum creatinine level or dialysis therapy, in the 2 weeks (or until discharge, if sooner) after cardiac surgery. RESULTS Of the 1014 patients analysed, 34 (3.4%) required dialysis and 95 (9.4%) had either dialysis or doubled their serum creatinine level. The areas under the receiver operating characteristic curves of the two predictive models for dialysis therapy, which include either presurgical variables only, or combined presurgical and intrasurgical variables, were 0.79 and 0.80, respectively. The model for the composite endpoint that combined presurgical and intrasurgical variables showed better discriminatory ability than the model that included only presurgical variables: the areas under the receiver operating characteristic
  • Autores: Sanz Ganuza, María (Autor de correspondencia); Hidalgo Martínez, Francisco Nicesio; García Fernández, Nuria
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN 1137-6627 Vol.41 N° 1 2018 págs. 135 - 136
  • Autores: Maduell, F.; García Fernández, Nuria; Manrique, J.; et al.
    Revista: HYPERTENSION
    ISSN 0194-911X Vol.72 N° 2 2018 págs. 277 - 278
  • Autores: Ibarrola, J.; Arrieta, V.; Sadaba, R.; et al.
    Revista: CLINICAL SCIENCE
    ISSN 0143-5221 Vol.132 N° 13 2018 págs. 1471 - 1485
    Resumen
    Galectin-3 (Gal-3) is increased in heart failure (HF) and promotes cardiac fibrosis and inflammation. We investigated whether Gal-3 modulates oxidative stress in human cardiac fibroblasts, in experimental animal models and in human aortic stenosis (AS). Using proteomics and immunodetection approaches, we have identified that Gal-3 down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. In parallel, Gal-3 increased peroxide, nitrotyrosine, malondialdehyde, and N-carboxymethyl-lysine levels and decreased total antioxidant capacity. Gal-3 decreased prohibitin-2 expression without modifying other mitochondrial proteins. Prx-4 silencing increased oxidative stress markers. In Gal-3-silenced cells and in heart fromGal-3 knockout mice, Prx-4 was increased and oxidative stress markers were decreased. Pharmacological inhibition of Gal-3 with modified citrus pectin restored cardiac Prx-4 as well as prohibitin-2 levels and improved oxidative status in spontaneously hypertensive rats. In serum from 87 patients with AS, Gal-3 negatively correlated with total antioxidant capacity and positively correlated with peroxide. In myocardial biopsies from 26 AS patients, Gal-3 up-regulation paralleled a decrease in Prx-4 and in prohibitin-2. Cardiac Gal-3 inversely correlated with Prx-4 levels in myocardial biopsies. These data suggest that Gal-3 decreased Prx-4 antioxidant system in cardiac fibroblasts, increasing oxidative stress. In pathological models presenting enhanced cardiac Gal-3, the decrease in Prx-4 expression paralleled increased oxidative stress. Gal-3 blockade restored Prx-4 expression and improved oxidative stress status. In AS, circulating levels of Gal-3 could reflect oxidative stress. The alteration of the balance between antioxidant systems and reactive oxygen species production could be a new pathogenic mechanism by which Gal-3 induces cardiac damage in HF.
  • Autores: de Miguel, I.; Orbe Lopategui, Josune; Sanchez-Arias, J. A. ; et al.
    Revista: ACS MEDICINAL CHEMISTRY LETTERS
    ISSN 1948-5875 Vol.9 N° 5 2018 págs. 428 - 433
    Resumen
    In an effort to find novel chemical series as antifibrinolytic agents, we explore alpha-phenylsulfonyl-alpha-spiropiperidines bearing different zinc-binding groups (ZBGs) to target those metalloproteinases involved in the fibrinolytic process: MMP3 and MMP10. Surprisingly, all these new chemical series were inactive against these metalloproteinases; however, several new molecules retained the antifibrinolytic activity in a phenotypic functional assay using thromboelastometry and human whole blood. Further optimization led to compound 38 as a potent antifibrinolytic agent in vivo, three times more efficacious than the current standard-of-care (tranexamic acid, TXA) at 300 times lower dose. Finally, in order to decipher the underlying mode-of action leading to this phenotypic response, an affinity-based probe 39 was successfully designed to identify the target involved in this response: a potentially unknown mechanism-of-action in the fibrinolytic process.
  • Autores: Iñurrieta, A.; Pedrajas, J. M.; Núñez, M. J.; et al.
    Revista: TH OPEN
    ISSN 2567-3459 Vol.2 N° 4 2018 págs. e428 - e436
    Resumen
    Background The ideal duration of anticoagulant therapy in elderly patients with unprovoked venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE ( R egistro I nformatizado E nfermedad T rombo E mbólica) registry to compare the rate and severity of pulmonary embolism (PE) recurrences versus major bleeding beyond the third month of anticoagulation in patients >75 years with a first episode of unprovoked VTE. Results As of September 2017, 7,830 patients were recruited: 5,058 (65%) presented with PE and 2,772 with proximal deep vein thrombosis (DVT). During anticoagulant therapy beyond the third month (median, 113 days), 44 patients developed PE recurrences, 36 developed DVT recurrences, 101 had major bleeding, and 241 died (3 died of recurrent PE and 19 of bleeding). The rate of major bleeding was twofold higher than the rate of PE recurrences (2.05 [95% confidence interval, CI: 1.68-2.48] vs. 0.90 [95% CI: 0.66-1.19] events per 100 patient-years) and the rate of fatal bleeding exceeded the rate of fatal PE events (0.38 [95% CI: 0.24-0.58] vs. 0.06 [95% CI: 0.02-0.16] deaths per 100 patient-years). On multivariable analysis, patients who had bled during the first 3 months (hazard ratio [HR]: 4.32; 95% CI: 1.58-11.8) or with anemia at baseline (HR: 1.87; 95% CI: 1.24-2.81) were at increased risk for bleeding beyond the third month. Patients initially presenting with PE were at increased risk for PE recurrences (HR: 3.60; 95% CI: 1.28-10.1)...
  • Autores: Páramo Fernández, José Antonio (Autor de correspondencia)
    Revista: MEDICINA CLINICA
    ISSN 0025-7753 Vol.151 N° 5 2018 págs. 207 - 209
  • Autores: Avendano, M. S.; Garcia-Redondo, A. B.; Zalba Goñi, Guillermo; et al.
    Revista: HYPERTENSION
    ISSN 0194-911X Vol.72 N° 2 2018 págs. 492 - 502
    Resumen
    mPGES-1 (microsomal prostaglandin E synthase-1), the downstream enzyme responsible for PGE(2) (prostaglandin E-2) synthesis in inflammatory conditions and oxidative stress are increased in vessels from hypertensive animals. We evaluated the role of mPGES-1-derived PGE(2) in the vascular dysfunction and remodeling in hypertension and the possible contribution of oxidative stress. We used human peripheral blood mononuclear cells from asymptomatic patients, arteries from untreated and Ang II (angiotensin II)-infused mPGES-1(-/-) and mPGES-1(+/+) mice, and vascular smooth muscle cells exposed to PGE(2). In human cells, we found a positive correlation between mPGES-1 mRNA and carotid intima-media thickness (r=0.637; P<0.001) and with NADPH oxidase-dependent superoxide production (r=0.417; P<0.001). In Ang II-infused mice, mPGES-1 deletion prevented all of the following: (1) the augmented wall:lumen ratio, vascular stiffness, and altered elastin structure; (2) the increased gene expression of profibrotic and proinflammatory markers; (3) the increased vasoconstrictor responses and endothelial dysfunction; (4) the increased NADPH oxidase activity and the diminished mitochondrial membrane potential; and (5) the increased reactive oxygen species generation and reduced NO bioavailability. In vascular smooth muscle cells or aortic segments, PGE(2) increased NADPH oxidase expression and activity and reduced mitochondrial membrane potential, effects that were abolished by antagonists of the PGE(2) receptors (EP), EP1 and EP3, and by JNK (c-Jun N-terminal kinase) and ERK1/2 (extracellular-signal-regulated kinases 1/2) inhibition. Deletion of mPGES-1 augmented vascular production of PGI(2) suggesting rediversion of the accumulated PGH(2) substrate. In conclusion, mPGES-1-derived PGE(2) is involved in vascular remodeling, stiffness, and endothelial dysfunction in hypertension likely through an increase of oxidative stress produced by NADPH oxidase and mitochondria.
  • Autores: Figueroa Mora, María del Rocío; Alfonso Piérola, Ana; López-Picazo González, José María; et al.
    Revista: PLOS ONE
    ISSN 1932-6203 Vol.13 N° 8 2018 págs. e0200220
    Resumen
    Hospitalized cancer patients are at high risk of venous thromboembolism (VTE). Despite current recommendations in clinical guidelines, thromboprophylaxis with low molecular weight heparin (LMWH) is underused. We performed an observational prospective study to analyse factors influencing prophylaxis use, VTE events and mortality in cancer-hospitalized patients. 1072 consecutive adult cancer patients were included in an University Hospital from April 2014 to February 2017, and followed-up for 30 days after discharge. The rate of LMWH prophylaxis was 67.6% (95% confidence interval [CI]64.7% to 70.4%), with a 2.8% rate of VTE events (95% CI 1.9% to 3.9%) and 3.5% rate of major bleeding events (95% CI 2.5% to 4.8%). 80% of VTE events occurred despite appropriate thromboprophylaxis. Overall, 30-day mortality rate was 13.2% (95% C111.2% to 15.3%). Active chemotherapy treatment, hospital stay >= 4 days, and metastatic disease were associated with a higher use of LMWH. On the contrary, patients with hematologic malignancies,anemia or thrombocytopenia were less prone to receive thromboprophylaxis. The main reasons for not prescribing LMWH prophylaxis were thrombocytopenia (23.9%) and active/recent bleeding (21.8%). The PRETEMED score, used for VTE risk stratification, correlated with 30-day mortality. There is room for improvement in thromboprophylaxis use among hospitalized-cancer patients, especially among those with hematologic malignancies. A relevant number of VTE events occurred despite prophylaxis with LMWH. Therefore, identification of risk factors for thromboprophylaxis failure is needed.
  • Autores: Pachón, V.; Trujillo-Santos, J.; Domenech, P.; et al.
    Revista: TH OPEN
    ISSN 2567-3459 Vol.2 N° 4 2018 págs. e373 - e386
    Resumen
    Despite the growing interest and improved knowledge about venous thromboembolism in cancer patients in the last years, there are still many unsolved issues. Due to the limitations of the available literature, evidence-based clinical practice guidelines are not able to give solid recommendations for challenging scenarios often present in the setting of cancer-associated thrombosis (CAT). A multidisciplinary expert panel from three scientific societies-Spanish Society of Internal Medicine (SEMI), Spanish Society of Medical Oncology (SEOM), and Spanish Society Thrombosis and Haemostasis (SETH)-agreed on 12 controversial questions regarding prevention and management of CAT, which were thoroughly reviewed to provide further guidance. The suggestions presented herein may facilitate clinical decisions in specific complex circumstances, until these can be made leaning on reliable scientific evidence.
  • Autores: Reyes, R.; Rodríguez García, José Antonio; Orbe Lopategui, Josune; et al.
    Revista: DRUG DELIVERY
    ISSN 1071-7544 Vol.25 N° 1 2018 págs. 750 - 756
    Resumen
    The effect of dual delivery of bone morphogenetic protein-2 (BMP-2) and matrix metalloproteinase 10 (MMP10) on bone regeneration was investigated in a murine model of calvarial critical-size defect, hypothesizing that it would result in an enhanced bone formation. Critical-size calvarial defects (4 mm diameter) were created in mice and PLGA microspheres preloaded with either BMP-2, MMP10 or a microsphere combination of both were transplanted into defect sites at different doses. Empty microspheres were used as the negative control. Encapsulation efficiency was assessed and in vivo release kinetics of BMP-2 and MMP10 were examined over 14 days. Histological analyses were used to analyze bone formation after four and eightweeks. Combination with MMP10 (30 ng) significantly enhanced BMP-2 (600ng)-mediated osteogenesis, as confirmed by the increase in percentage of bone fill (p < .05) at four weeks. Moreover, it also increased mineral apposition rate (p < .05), measured by double labeling with tetracycline and calceine. MMP10 accelerates bone repair by enhancing BMP-2-promoted bone healing and improving the mineralization rate. In conclusion combination of MMP10 and BMP-2 may become a promising strategy for repair and regeneration of bone defects.
  • Autores: Páramo Fernández, José Antonio (Autor de correspondencia)
    Revista: CLINICA E INVESTIGACION EN ARTERIOSCLEROSIS
    ISSN 0214-9168 Vol.30 N° 3 2018 págs. 133 - 136
    Resumen
    Recent research has revealed that clonal hematopoyesis of indeterminate potential (CHIP) characterized by the acquisition of somatic mutations in hematopoietic stem cells, is not only a common age-related disorder and a premalignant condition, but it is also associated with the development of atherosclerotic vascular diseases. Mutations in DNMT3A, TET2 and ASXL1 were each individually associated with coronary heart disease, stroke and coronary calcification. Therefore, CHIP emerges as a new risk factor for atherosclerotic vascular pathologies and its detection may be relevant as a new therapeutic target in order to modify the natural course of the disease. (C) 2018 Sociedad Espanola de Arteriosclerosis. Published by Elsevier Espana, S.L.U. All rights reserved.
  • Autores: Calsina Juscafresa, Laura (Autor de correspondencia); Grochowicz, Lukasz Karol
    Revista: HANDCHIRURGIE MIKROCHIRURGIE PLASTISCHE CHIRURGIE
    ISSN 0722-1819 Vol.50 N° 1 2018 págs. 52 - 56
    Resumen
    Introduction In 1934 von Rosen first described a posttraumatic thrombosis of the distal ulnar artery resulting from blunt a trauma to the hypothenar region. But it was Conn in 1970 who named it the hypothenar hammer syndrome (HHS) 1-2 .
  • Autores: Purroy López, Ana Isabel; Roncal Mancho, Carmen; Orbe Lopategui, Josune; et al.
    Revista: ATHEROSCLEROSIS
    ISSN 0021-9150 Vol.278 2018 págs. 124 - 134
    Resumen
    Background and aims: Matrix metalloproteinases (MMPs) have been implicated in atherosclerosis and vascular calcification. Among them, we reported that MMP10 is present in human atheroma, associated with atherosclerosis. However, it remains unclear whether MMP10 is involved in atherogenesis and vascular calcification. Methods: MMP10 was measured in serum from patients with subclinical atherosclerosis and analyzed in carotid endarterectomies by immunostaining. ApoE-deficient mice (Apoe(-/-)) were crossed to MMP10-deficient (Mmp10(-/-)) mice and followed up to 20 months. Plaque area and composition were assessed by histology and immunohistochemistry. Inflammatory markers were measured in atherosclerotic plaques by RT-qPCR, and leukocyte subpopulations were analyzed by flow cytometry. In vitro calcification assays were performed in aortic vascular smooth muscle cells (VSMC). Results: MMP10 serum levels were associated with coronary calcification in subjects with subclinical atherosclerosis. Immunostaining revealed MMP10 expression in human atheromas, spatially associated with calcification areas, and complicated plaques released higher amounts of MMP10 than non-diseased segments. Interestingly, vascular MMP10 expression was confined to the atherosclerotic lesion in Apoe(-/-) mice, and Apoe(-/-) Mmp10(-/-) showed a substantial reduction in atherosclerotic lesion size, macrophage content and plaque calcification. Reduced local and systemic inflammatory markers could be demonstrated in Apoe(-/-) Mmp10(-/-) by gene expression and flow cytometry analysis. Calcium phosphate deposition and vascular calcification markers were downregulated in VSMC from Apoe(-/-) Mmp10(-/-) mice. Conclusions: Delayed plaque progression and altered cellular composition in the absence of MMP10 suggests that MMP10 plays a role in atherosclerosis, favoring inflammation, development and complication of the plaque.
  • Autores: Gómez-Outes, A. (Autor de correspondencia); Terleira-Fernández, A. I.; Lecumberri Villamediana, Ramón; et al.
    Revista: SEMINARS IN THROMBOSIS AND HEMOSTASIS
    ISSN 0094-6176 Vol.44 N° 4 2018 págs. 377 - 387
    Resumen
    Death is more frequent than nonfatal recurrent venous thromboembolism (VTE) and major bleeding after acute VTE. The analysis of the causes of death is fundamental to explore new strategies to reduce mortality rates in these patients. The authors performed a meta-analysis to analyze mortality and independently adjudicated causes of death in anticoagulated patients due to VTE, and to evaluate potential differences between different anticoagulant schemes. They searched MEDLINE and CENTRAL, from January 1, 2000, to January 31, 2017, and performed additional searches in Web sites of regulatory agencies, clinical trial registers, and conference proceedings. Two investigators independently selected studies and extracted the data. Study quality was assessed with the Cochrane Collaboration's tool for assessing the risk of bias in randomized studies. Seven prospective randomized trials in 29,844 patients (22,025 patient-year follow-up) were included, comparing dabigatran, rivaroxaban, apixaban, and edoxaban with the standard anticoagulant treatment of VTE. A total of 718 patients died during the follow-up (3.4% per year; 95% confidence interval [CI]: 2.3-4.8). The most frequent causes of death were cancer (42%), followed by VTE (20%), infections (13%), hemorrhage (6%), heart disease (4%), and stroke (2%). There were no differences in the overall survival and causes of death according to the anticoagulant type. Concomitant active cancer during the study was significantly associated with death (odds ratio: 15.2; 95% CI: 9.2-25.1). Cancer is the leading cause of death in contemporary VTE trials. Interventions beyond anticoagulation, particularly in patients with active cancer, are needed.
  • Autores: Selby, N. M. (Autor de correspondencia); Blankestijn, P. J.; Boor, P. ; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.33 N° Supl.2 2018 págs. II4 - II14
    Resumen
    Functional renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. Such biomarkers are sensitive to changes in renal blood flow, tissue perfusion, oxygenation and microstructure (including inflammation and fibrosis), processes that are important in a range of renal diseases including chronic kidney disease. However, several challenges remain to move these techniques towards clinical adoption, from technical validation through biological and clinical validation, to demonstration of cost-effectiveness and regulatory qualification. To address these challenges, the European Cooperation in Science and Technology Action PARENCHIMA was initiated in early 2017. PARENCHIMA is a multidisciplinary pan-European network with an overarching aim of eliminating the main barriers to the broader evaluation, commercial exploitation and clinical use of renal MRI biomarkers. This position paper lays out PARENCHIMA's vision on key clinical questions that MRI must address to become more widely used in patients with kidney disease, first within research settings and ultimately in clinical practice. We then present a series of practical recommendations to accelerate the study and translation of these techniques.
  • Autores: Mora Gutiérrez, Jose María; Fernández Seara, María Asunción; Slon Roblero, María Fernanda; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.33 N° Supl. 1 2018 págs. SP453
  • Autores: Alfaro Sanchez, Christian Israel; Echarri González, Gemma; Moirón Fernández-Felechosa, José Pelayo; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.33 N° Supl. 1 2018 págs. i425 - i426
  • Autores: Roncal Mancho, Carmen; Martinez-Aguilar, E. ; Orbe Lopategui, Josune; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 121 - 122
  • Autores: Garcia-Redondo, A. B.; Avendano, M. S.; Aguado, A.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 122 - 122
  • Autores: Navarro Oviedo, Manuel; Salicio, M.; Rabal Gracia, María Obdulia; et al.
    Revista: HAEMATOLOGICA
    ISSN 0390-6078 Vol.103 N° Supl. 2 2018 págs. 2 - 2
  • Autores: Lavilla Royo, Francisco Javier; Moirón Fernández-Felechosa, José Pelayo; Alfaro Sanchez, Christian Israel; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.33 N° Supl. 1 2018 págs. i412
  • Autores: Irimia Sieira, Pablo; Garrido-Cumbrera, M. ; Santos-Lasaosa, S.; et al.
    Revista: JOURNAL OF HEADACHE AND PAIN
    ISSN 1129-2369 Vol.19 N° Supl. 1 2018 págs. P170
  • Autores: Mínguez Olaondo, Ane; Romero, S.; Fruhbeck Martínez, Gema; et al.
    Revista: JOURNAL OF HEADACHE AND PAIN
    ISSN 1129-2369 Vol.19 N° Supl. 1 2018 págs. P161
  • Autores: Lavilla Royo, Francisco Javier; Moirón Fernández-Felechosa, José Pelayo; Alfaro Sanchez, Christian Israel; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.33 N° Supl. 1 2018 págs. i419
  • Autores: Lainez, M. J. A.; Santos, S. ; Pozo-Rosich, P.; et al.
    Revista: HEADACHE
    ISSN 0017-8748 Vol.58 N° 8 2018 págs. 1309 - 1309
  • Autores: Torres-Ferrus, M.; Lasaosa, S. S.; Peral, A. G.; et al.
    Revista: JOURNAL OF HEADACHE AND PAIN
    ISSN 1129-2369 Vol.19 N° Supl. 1 2018 págs. P114
  • Autores: Diener, H. C.; Goadsby, P. J.; Ashina, M. ; et al.
    Revista: JOURNAL OF HEADACHE AND PAIN
    ISSN 1129-2369 Vol.19 N° Supl. 1 2018
  • Autores: Bermejo, S.; González, E.; Lopez, K. ; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.33 N° Supl.1 2018 págs. SP416
  • Autores: Diener, H. C.; Goadsby, P. J.; Ashina, M.; et al.
    Revista: CEPHALALGIA
    ISSN 0333-1024 Vol.38 N° Supl. 1 2018 págs. 58 - 59
  • Autores: Bermejo, S. ; Gonzalez, E. ; Lopez, K.; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.33 N° Supl.1 2018 págs. 491
  • Autores: Lavilla Royo, Francisco Javier; Moirón Fernández-Felechosa, José Pelayo; Alfaro Sanchez, Christian Israel; et al.
    Revista: NEPHROLOGY DIALYSIS TRANSPLANTATION
    ISSN 0931-0509 Vol.33 N° Supl. 1 2018 págs. i418
  • Autores: Romero, S.; Mínguez Olaondo, Ane; Lainez, J. M.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl 1 2018 págs. 206 - 207
  • Autores: Martínez Espartosa, Débora; Landecho Acha, Manuel Fortún; Alegre Garrido, Félix; et al.
    Libro: Balcells. La clínica y el laboratorio: Interpretación de análisis y pruebas funcionales. Exploración de los síndromes. Cuadro biológico de las enfermedades
    ISSN 978-84-9113-301-8 2019 págs. 35 - 109
  • Autores: Pejenaute Martínez de Lizarrondo, Álvaro; Zalba Goñi, Guillermo
    Libro: Telomeres, diet and human disease: advances and therapeutic opportunities
    ISSN 9781498750912 2018 págs. 39 - 54
  • Autores: Pejenaute Martínez de Lizarrondo, Álvaro; Zalba Goñi, Guillermo
    Libro: Obesity: oxidative stress and dietary antioxidants
    ISSN 978-0-12-812504-5 2018 págs. 93 - 110
    Resumen
    Oxidative stress, a pathological situation created by an imbalance between reactive oxygen species production and antioxidant capacity, is a critical mechanism that underlies the pathophysiology of cardiovascular diseases and is involved in obesity, metabolic syndrome, and diabetes. The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme family is the main source of reactive oxygen species and its expression and activity is enhanced and plays a critical role in the onset and/or development of cardiovascular diseases. The phagocytic NADPH oxidase, a member of the NADPH oxidase family present in lymphocytes, monocytes, and neutrophils, has been implicated in the pathophysiology of these vascular and metabolic disorders, by promoting detrimental prooxidant processes that could increase the morbidity and mortality in these diseases. A present challenge consists of the development of novel NADPH oxidase-selective drugs that could prevent and/or treat cardiovascular and metabolic diseases.

Proyectos desde 2018

  • Título: RICORS2040
    Código de expediente: RD21/0005/0024
    Investigador principal: NURIA GARCIA FERNANDEZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2021 AES Redes de Investigación cooperativa orientadas a resultados (RICORS)
    Fecha de inicio: 01-01-2022
    Fecha fin: 31-12-2024
    Importe concedido: 105.765,00 €
    Fondos FEDER: SI
  • Título: Caracterización del estrés oxidativo vascular en la fisiopatología de la diabetes: NADPH oxidasa 5 como potencial diana terapéutica
    Código de expediente: 40/2021
    Investigador principal: GUILLERMO ZALBA GOÑI.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2021 GN Proyectos de Investigación en salud
    Fecha de inicio: 23-12-2021
    Fecha fin: 22-12-2024
    Importe concedido: 78.200,00 €
    Fondos FEDER: NO
  • Título: Estudio genómico para la personalización del diagnóstico y el tratamiento de los pacientes con insuficiencia Cardíaca crónica y enfermedad renal crónica (Medicina cardIoreNal pERsonalizada en NaVArra)-II (MINERVA-II)
    Código de expediente: 0011-1411-2021-000094
    Investigador principal: JUAN JOSE GAVIRA GOMEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2021 GN PROYECTOS ESTRATEGICOS DE I+D 2021-2024
    Fecha de inicio: 01-05-2021
    Fecha fin: 31-12-2023
    Importe concedido: 100.748,76 €
    Fondos FEDER: NO
  • Título: Papel de la MMP-10 y la perfusión tisular en el diagnóstico y seguimiento de la nefropatía y patología cardiovascular de pacientes con diabetes mellitus tipo 2.
    Código de expediente: PI20/01678
    Investigador principal: NURIA GARCIA FERNANDEZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2020 AES Proyectos de investigación
    Fecha de inicio: 01-01-2021
    Fecha fin: 31-12-2023
    Importe concedido: 102.608,00 €
    Fondos FEDER: SI
  • Título: Factores genéticos responsables de la concentración plasmática de metaloproteinasa 10 y riesgo de enfermedad cardiovascular
    Código de expediente: PI19/01631
    Investigador principal: JOSE MARIA HERMIDA SANTOS.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2019 AES Proyectos de investigación
    Fecha de inicio: 01-01-2021
    Fecha fin: 31-12-2022
    Importe concedido: 40.938,70 €
    Fondos FEDER: SI
  • Título: Alianza en Genómica Avanzada para el desarrollo de Terapias Personalizadas en Navarra
    Código de expediente: 0011-1411-2020-000010
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2020 GN PROYECTOS ESTRATEGICOS DE I+D 2020-2022
    Fecha de inicio: 17-06-2020
    Fecha fin: 30-11-2022
    Importe concedido: 725.480,08 €
    Fondos FEDER: NO
  • Título: Papel del RNU6 aislado de exosomas circulantes como marcador diagnóstico y de seguimiento en pacientes con glioblastoma
    Código de expediente: PI19/01440
    Investigador principal: JAIME GALLEGO PEREZ DE LARRAYA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2019 AES Proyectos de investigación
    Fecha de inicio: 01-01-2020
    Fecha fin: 31-12-2022
    Importe concedido: 96.800,00 €
    Fondos FEDER: SI
  • Título: CARACTERIZACIÓN DE LA NADPH OXIDASA 5 COMO DIANA TERAPÉUTICA EN EL ICTUS. NOXICTUS
    Código de expediente: 0011-1383-2020-000010 PC159 UNAV NOXICTUS
    Investigador principal: GUILLERMO ZALBA GOÑI.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2020 GN Proyectos Colaborativos
    Fecha de inicio: 01-01-2020
    Fecha fin: 30-11-2022
    Importe concedido: 139.351,50 €
    Fondos FEDER: NO
  • Título: Creación de una plataforma para el desarrollo de vectores de terapia génica con tropismo renal (DRONES GÉNICOS)
    Código de expediente: 0011-1411-2019-000048
    Investigador principal: NURIA GARCIA FERNANDEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2019 GN PROYECTOS ESTRATEGICOS DE I+D 2019-2021
    Fecha de inicio: 01-04-2019
    Fecha fin: 30-11-2021
    Importe concedido: 64.625,00 €
    Fondos FEDER: NO
  • Título: MINERVA. Estudio genómico para la personalización del diagnóstico y el tratamiento de los pacientes con insuficiencia Cardíaca crónica y enfermedad renal crónica (Medicina cardIoreNal pERsonalizada en NaVArra)
    Código de expediente: 0011-1411-2018-000043
    Investigador principal: DOMINGO FRANCISCO JAVIER DIEZ MARTINEZ, DOMINGO FRANCISCO JAVIER DIEZ MARTINEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2018- GN PROY. ESTRATEGICOS DE I+D 2018-2020
    Fecha de inicio: 01-04-2018
    Fecha fin: 30-11-2020
    Importe concedido: 1.001.241,69 €
    Fondos FEDER: NO
  • Título: Implantación del diagnóstico de la epilepsia y la migraña en Navarra (Geneurona)
    Código de expediente: 0011-1411-2018-000053
    Investigador principal: MARIA CRUZ RODRIGUEZ OROZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2018 GN PROYECTOS ESTRATEGICOS DE I+D 2018-2020
    Fecha de inicio: 01-04-2018
    Fecha fin: 30-11-2020
    Importe concedido: 18.481,69 €
    Fondos FEDER: NO
  • Título: Estudio genómico para la personalización del diagnóstico y el tratamiento de los pacientes con insuficiencia cardiaca crónica y enfermedad renal crónica (Medicina cardIoreNal pERsonalizada en NaVArra) (MINERVA)
    Código de expediente: 0011-1411-2018-000036
    Investigador principal: JUAN JOSE GAVIRA GOMEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2018 GN PROYECTOS ESTRATEGICOS DE I+D 2018-2020
    Fecha de inicio: 01-04-2018
    Fecha fin: 30-11-2020
    Importe concedido: 97.237,60 €
    Fondos FEDER: NO
  • Título: Enfermedades Vasculares Cerebrales (INVICTUS)
    Código de expediente: RD16/0019/0016
    Investigador principal: EDUARDO ANTONIO MARTINEZ VILA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2016 AES REDES
    Fecha de inicio: 01-01-2017
    Fecha fin: 31-12-2021
    Importe concedido: 23.897,50 €
    Fondos FEDER: SI
  • Título: Caracterización fisiopatológica de la isoforma 5 de la NADPH oxidasa (Nox5) en la obsisdad y su repercusión en la enfermedad cardiovascular
    Código de expediente: SAF2016-79151-R
    Investigador principal: GUILLERMO ZALBA GOÑI.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2016 MINECO RETOS INVESTIGACION. PROYECTOS I+D+i
    Fecha de inicio: 30-12-2016
    Fecha fin: 29-12-2020
    Importe concedido: 181.500,00 €
    Fondos FEDER: SI
  • Título: Estudio clínico y experimental del papel de la MMP-10 en la nefropatía diabética tipo 2
    Código de expediente: PI15/02111
    Investigador principal: NURIA GARCIA FERNANDEZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2015 AES PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2016
    Fecha fin: 30-11-2020
    Importe concedido: 116.765,00 €
    Fondos FEDER: SI
  • Título: Interacción metaloproteinasas-hemostasia, un nuevo mecanismo en la hemorragia intracraneal: estrategias terapéuticas basadas en la modulación de la actividad MMPs
    Código de expediente: 2/2015
    Investigador principal: JOSUNE ORBE LOPATEGUI.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2015 PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 06-12-2015
    Fecha fin: 05-12-2018
    Importe concedido: 46.377,00 €
    Fondos FEDER: SI
  • Título: Utilidad de un perfil de ARN pequeño no codificante aislado en exosomas circulantes como marcador diagnóstico y de seguimiento en pacientes con glioblastoma multiforme
    Código de expediente: 42/2015
    Investigador principal: JAIME GALLEGO PEREZ DE LARRAYA.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2015 GN SALUD
    Fecha de inicio: 06-12-2015
    Fecha fin: 05-12-2018
    Importe concedido: 50.682,00 €
    Fondos FEDER: NO