Jose A Páramo

Jose A Páramo
Universidad de Navarra | UNAV · Department of Hematology

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388
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Introduction

Publications

Publications (388)
Article
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Article
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Article
Haemophilia A and B are congenital bleeding disorders characterized by missing or defective factor VIII or factor IX, respectively. Factor replacement therapy has been the gold standard for prophylaxis and treatment of bleeding complications. However, the inconvenience of regular intravenous administration, along with progression of arthropathy and...
Article
Full-text available
In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematolo...
Article
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 administ...
Article
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 thromb...
Article
Resumen Los pacientes con cáncer presentan un riesgo elevado de trombosis, que condiciona una elevada morbimortalidad. Se han desarrollado diversas escalas predictivas para la identificación de aquellos con alto riesgo trombótico, incorporando datos clínicos y biológicos, pero, en general, no permiten una selección óptima de los sujetos candidatos...
Article
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. Further, microvascular thrombosis has recently been demonstrated in patients with COVID-19, and has been proposed to mediate the pathogenesis of...
Article
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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 re...
Article
Resumen La trombosis en la microcirculación está presente en numerosas situaciones clínicas, como coagulación intravascular diseminada, microangiopatía trombótica o anemia falciforme, entre otras. Asimismo, se ha demostrado trombosis microvascular en pacientes con COVID-19 como un mecanismo patogénico implicado en la lesión tisular pulmonar y de ot...
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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 paramete...
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Full-text available
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 inf...
Article
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...
Article
Resumen La terapia anticoagulante conlleva un riesgo aumentado de complicaciones hemorrágicas. Las escalas predictivas son un componente importante en la estratificación del riesgo de sangrado en pacientes anticoagulados con fibrilación auricular y tromboembolismo venoso. La combinación de diversos marcadores clínicos, biológicos y genéticos permit...
Article
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...
Article
When activated, neutrophils release structures (NETs) composed of DNA, histones and granular proteins that provide an ideal matrix for platelet activation and coagulation mechanisms, thereby contributing to the pathogenesis of thrombosis in venous and arterial territories, as well as cancer-associated thrombosis. NETs play a key role in immunothrom...
Article
Full-text available
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 characteristi...
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Full-text available
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 =...
Preprint
Full-text available
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 in...
Article
Resumen El sistema hemostático actúa en concierto con la inflamación, de forma que tras la respuesta inflamatoria diversos mediadores activan el sistema hemostático a través de disfunción endotelial, activación plaquetar y de coagulación, promoviendo la trombosis, lo que se ha denominado tromboinflamación. En este proceso adquiere especial relevanc...
Article
When activated, neutrophils release structures (NETs) composed of DNA, histones and granular proteins that provide an ideal matrix for platelet activation and coagulation mechanisms, thereby contributing to the pathogenesis of thrombosis in venous and arterial territories, as well as cancer-associated thrombosis. NETs play a key role in immunothrom...
Article
Full-text available
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...
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Full-text available
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 dia...
Article
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 characterise these subpopulations and their association with cardiovascular risk factors. Methods Transversal study including 102 se...
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Full-text available
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 lev...
Article
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 10...
Article
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 bleedi...
Article
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 sever...
Article
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...
Article
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...
Article
Introduction: Wound healing after myocardial infarction (MI) is mediated by different cell types, secreted proteins, components of the extracellular matrix (ECM) and, as increasing evidences suggest, extracellular vesicles (EVs). We aim to determine the dynamics of release and origin of EVs after MI, as well as their biological activity on endothe...
Article
Objective The prognosis of patients with peripheral arterial disease (PAD) is characterized by an exceptionally high risk for myocardial infarction, ischemic stroke, and death; however, studies in search of new prognostic biomarkers in PAD are scarce. Even though low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with h...
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Background Chemotherapy is considered the most appropriate treatment for metastatic uterine sarcoma, despite its limited efficacy. No other treatment has been conclusively proved to be a real alternative, but some reports suggest that anti-hormonal therapy could be active in a small subset of patients. We report the case of a patient with metastati...
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Purpose: To investigate whether arterial spin labeling (ASL) MRI could detect renal hemodynamic impairment in diabetes mellitus (DM) along different stages of chronic kidney disease (CKD). Materials and methods: Three Tesla (3T) ASL-MRI was performed to evaluate renal blood flow (RBF) in 91 subjects (46 healthy volunteers and 45 type 2 diabetic...
Article
Aim: Considering that MMP-10 improves stroke injury, we have examined the therapeutic and protective effect of MMP10 and tPA/MMP10 as clot-dissolving and neuroprotective agent in an experimental model of ischemic stroke and studied in vitro the molecular pathways involved in MMP10-mediated effects. Methods and results: Cerebral ischemia was indu...
Article
Full-text available
Fundamento. Las placas ateroscleróticas que producen la mayoría de los síndromes coronarios agudos al romperse son los fibroateromas de cápsula fina, denominados placas vulnerables. Éstas pueden ser detectadas únicamente con técnicas invasivas de imagen intracoronaria. Es preciso encontrar un biomarcador no invasivo que permita identificar a los pa...
Article
As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilisation via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The conc...
Article
Resumen La patogenia de los síndromes coronarios agudos está relacionada con la rotura o erosión de una placa aterosclerótica vulnerable. La estabilización de dicha placa, por reducción del núcleo lipídico y/o aumento de la capa fibrosa, sería uno de los mecanismos potencialmente beneficiosos observados con agentes antiateroscleróticos. El concepto...
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Objective: To audit the impact upon mortality of a massive bleeding management protocol (MBP) implemented in our center since 2007. Design: A retrospective, single-center study was carried out. Patients transfused after MBP implementation (2007-2012, Group 2) were compared with a historical cohort (2005-2006, Group 1). Background: Massive blee...
Article
Background and purpose: The debate over the fact that experimental drugs proposed for the treatment of stroke fail in the translation to the clinical situation has attracted considerable attention in the literature. In this context, we present a retrospective pooled analysis of a large data set from preclinical studies, to examine the effects of e...
Article
La hemorragia masiva es una entidad frecuente que se asocia a una elevada morbimortalidad. Ante la necesidad de la implementación y estandarización de su manejo, se realizó una revisión sistemática de la literatura, con extracción de recomendaciones en base a las evidencias existentes. A partir de las mismas se redactó un documento de consenso mult...
Article
Objective: To assess differences in the gene expression profile of peripheral blood cells between patients with early recurrent thrombosis versus patients without recurrent events after withdrawal of anticoagulant therapy for a first episode of unprovoked deep vein thrombosis (uDVT), in order to identify novel predictors of recurrence. Methods:...
Article
Introduction: Current clinical practice guidelines do not recommend routine pharmacological thromboprophylaxis in cancer outpatients receiving chemotherapy. However, a high proportion of cancer-associated venous thromboembolism (VTE) events occur in this setting. There are scarce data on the use of thromboprophylaxis in ambulatory cancer patients...
Article
Massive haemorrhage is common and often associated with high morbidity and mortality. We perform a systematic review of the literature, with extraction of the recommendations from the existing evidences because of the need for its improvement and the management standardization. From the results we found, we wrote a multidisciplinary consensus docum...
Article
Full-text available
In the last years, circulating matrix metalloproteinases (MMP)-9 levels have been associated with functional outcome in ischemic stroke patients. However the prognostic value of circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 and MMP-10 in functional outcome of ischemic stroke patients has been scarcely studied. In addi...
Article
Matrix metalloproteinases (MMPs) participate in tissue repair after acute injury, but are also major players in cancer by promoting a pro-tumorigenic microenvironment. Previously we reported a key role for MMP10 in mouse liver regeneration. Herein we investigated MMP10 expression and function in human hepatocellular carcinoma (HCC) and diethylnitro...
Article
Discovery of potent and safe therapeutics that improve upon currently available antifibrinolytics; e.g., tranexamic acid (TXA, 1) and aprotinin, has been challenging. Matrix metalloproteinases (MMP) participate in thrombus dissolution; then, we designed a novel series of optimized MMP inhibitors that went through phenotypic screening consisting of...
Article
Growing evidence suggests that matrix metalloproteinases (MMP) are involved in thrombus dissolution; then, considering that new therapeutic strategies are required for controlling hemorrhage, we hypothesized that MMP inhibition may reduce bleeding by delaying fibrinolysis. Thus, we designed and synthesized a novel series of MMP inhibitors to identi...
Article
Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Until recently, treatment of VTE was based on parenteral or low-molecular-weight heparin for initial therapy (5-10 days) and oral vitamin K antagonists for long-term therapy. Those treat...
Article
Fundamento: Los concentrados de factores del complejo protrombínico (CCP) están indicados para reversión del efecto de antagonistas de vitamina K (AVK). Recientemente se han utilizado en el manejo de la coagulopatía de la hemorragia masiva. El objetivo del presente trabajo es evaluar la seguridad y eficacia del CCP en dos situaciones clínicas, para...
Article
Peripheral arterial disease (PAD) is associated with poor prognosis in terms of cardiovascular (CV) morbidity and mortality. Matrix metalloproteinases (MMPs) contribute to vascular remodeling by degrading extracellular matrix components and play a role in atherosclerosis as demonstrated for MMP-10 (stromelysin-2). This study analyzed MMP-10 levels...
Article
The standard treatment of venous thromboembolism has been the use of parenteral unfractionated or low molecular weight heparin, followed by oral vitamin K antagonists. New oral anticoagulants that selectively inhibit coagulation proteins such as thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban, edoxaban) have shown to be effective alterna...
Article
Background & AimsRadioembolization may rarely induce liver disease resulting in a syndrome that is similar to veno-occlusive disease complicating bone marrow transplantation where inflammation, endothelial cell activation and thrombosis are likely involved. We hypothesized that similar mechanisms could be implicated in radioembolization-induced liv...
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Higher plasma plasminogen activator inhibitor-1 (PAI-1) levels have been reported in septic patients. However, some questions remain unanswered, such as whether there is an association between plasma PAI-1 levels and sepsis severity and mortality, and inflammation state during the first week. Multicenter, observational and prospective study carried...
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Full-text available
Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-survivin...
Article
Full-text available
Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play a role in neuroinflammation after brain trauma injury (TBI). Previous studies with small sample size have reported higher circulating MMP-2 and MMP-9 levels in patients with TBI, but no association between those levels and mortality. Thus, the aim of th...
Article
Peripheral arterial disease is a relevant public health problem associated with increased risk of morbimortality. Most of the patients with this condition are asymptomatic. Therefore, the development of accessible biochemical markers seems to be necessary to anticipate diagnosis. Our hypothesis is that asymptomatic subjects with objectively confirm...