Nuestros investigadores

Ramón Lecumberri Villamediana

Publicaciones científicas más recientes (desde 2010)

Autores: Puig, N. ; Lourenco, Bruno David, (Autor de correspondencia); Lasa, M.; et al.
Revista: LEUKEMIA
ISSN 0887-6924  Vol. 33  Nº 5  2019  págs. 1256 - 1267
Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 9 4) , MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N= 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: >= 2.9;P <= .03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFCbased automated risk classification ready for implementation in clinical practice.
Autores: Figueroa, Rocío; Alfonso, Ana; López-Picazo, José María; et al.
Revista: CLINICAL AND TRANSLATIONAL ONCOLOGY
ISSN 1699-048X  Vol. 21  Nº 6  2019  págs. 805 - 809
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: Martos, L. ; Fernandez-Pardo, A. ; Lopez-Fernandez, M. F.; et al.
Revista: THROMBOSIS AND HAEMOSTASIS
ISSN 0340-6245  Vol. 119  Nº 9  2019  págs. 1409 - 1418
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: 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
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: Páramo, José Antonio, (Autor de correspondencia); Lecumberri, Ramón;
Revista: MEDICINA CLINICA
ISSN 0025-7753  Vol. 153  Nº 2  2019  págs. 78 - 81
Autores: Figueroa, Rocío; Alfonso, Ana; López-Picazo, José María; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 13  Nº 8  2018  págs. e0200220
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: Puig, N.; Lourenco, Bruno David; Lasa, M.; et al.
Revista: BLOOD
ISSN 0006-4971  Vol. 132  Nº Supl. 1  2018 
Autores: Tamariz-Amador, L.E; Hernández-Santamaría, T. ; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 103  Nº Supl. 2  2018  págs. 118 - 118
Autores: Cuenca, I.; Sanchez-Vega, B. ; Lourenco, Bruno David; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 103  Nº Supl. 2  2018  págs. 91 - 91
Autores: Vicari, M. ; Lara-Astiaso, D.; et al.
Revista: BLOOD
ISSN 0006-4971  Vol. 132  Nº Supl. 1  2018  págs. 188
Autores: Delluc, A.; Antic, D.; Lecumberri, Ramón; et al.
Revista: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
ISSN 1538-7933  Vol. 15  Nº 10  2017  págs. 2076 - 2079
Autores: Allender, M.; Lecumberri, Ramón; et al.
Revista: THROMBOSIS AND HAEMOSTASIS
ISSN 0340-6245  Vol. 117  Nº 9  2017  págs. 1722 - 1729
Antithrombotic medications target coagulation factors. Their use is associated with an increased bleeding risk. Safer drugs are needed. The heat shock protein 70 (Hsp70) exhibits antithrombotic properties that do not influence bleeding. By using murine models, we aimed to test the hypothesis that overexpressing Hsp70 with CM-695, a first in class dual inhibitor of HDAC6 and phosphodiesterase 9, protects against thrombosis while leaves bleeding tendency unaltered. CM-695 was used to induce Hsp70 overexpression. Hsp70 overexpressing mice were submitted to three thrombosis-triggering procedures. The ferric chloride carotid artery model was used to compare the antithrombotic role of CM-695 and rivaroxaban, a direct oral anticoagulant. The mouse tail transection model was used to compare the bleeding tendency upon CM-695 or rivaroxaban administration. Intraperitoneal (i.p.) 20 mg/kg CM-695 increased Hsp70 expression markedly in the murine aortic tissue. This treatment delayed thrombosis in the collagen/epinephrine [p=0.04 (Log-Rank test), n=10], Rose Bengal/laser [median vessel occlusion time (OT): 58.6 vs 39.0 minutes (min) in the control group (CG), p=0.008, n >= 10] and ferric chloride (OT: 14.7 vs 9.2 min in the CG, p=0.032, n >= 10) models. I.p. 80 mg/kg CM-695 (n >= 9) and intravenous 3 mg/kg rivaroxaban (n >= 8) significantly delayed thrombosis. CM-695 did not induce bleeding [median bleeding time (BT): 8.5 vs 7.5 min in the CG, n >= 10]. However, BT was dramatically increased by rivaroxaban (30.0 vs 13.7 min in the CG, p=0.001, n=10). In conclusion, CM-695 is a new antithrombotic small molecule devoid of bleeding risk that may be envisioned as a useful clinical tool.
Autores: Vicente, V.; Martin, A. ; Lecumberri, Ramón; et al.
Revista: EMERGENCIAS
ISSN 1137-6821  Vol. 29  Nº 1  2017  págs. 18 - 26
Objective. To evaluate the level of agreement between hematologists and emergency medicine physicians regarding the best clinical practices for managing bleeding and anticoagulant reversal. Methods. Nationwide Spanish multicenter Delphi method study with a panel of experts on anticoagulation and the management of bleeding. Two survey rounds were carried out between April and September 2015. Consensus was reached when more than 75% of the panelists scored items in the same tertile. Results. Fifteen hematologists and 17 emergency medicine specialists from 14 Spanish autonomous communities participated. Consensus was reached on the use of both hemodialysis and an activated prothrombin complex concentrate (PCC) to antagonize significant/major bleeding in patients taking dabigatran. Use of an activated PCC was considered sufficient for patients on rivaroxaban or apixaban. The panel did not consider any PCC to be both effective and safe. Tests for activated partial thromboplastin, thrombin, diluted thrombin, and ecarin clotting times were considered useful in patients treated with dabigatran. A specific anti-Xa activity assay was suggested for patients who developed bleeds while treated with rivaroxaban or apixaban. Specific antidotes for direct-acting oral anticoagulants would be useful when severe bleeding occurs according to 97% of the panelists. Such antidotes would substantially change current treatment algorithms. Conclusion. The points of consensus were generally in line with clinical practice guidelines, but the Delphi process revealed that there are aspects of the clinical management of bleeding that require unified criteria. The need for specific antidotes for direct-acting oral anticoagulants was emphasized.
Autores: Martínez, Nicolás; Alfonso, Ana; Rifón, José Juan; et al.
Revista: EUROPEAN JOURNAL OF HAEMATOLOGY
ISSN 0902-4441  Vol. 98  Nº 1  2017  págs. 38 - 43
This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single-centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29-69), median time to diagnosis 50 months (range 0-100). PTLD type was predominantly late/monomorphic (79% and 75%), mostly diffuse large B-cell type. Overall response rate (ORR) was 62% (66% rituximab vs. 50% non-rituximab; P = 0.5). R-CHOP-like regimens were used most frequently (72% of patients treated with rituximab). Median overall survival was 64 months (CI 95% 31-96). OS was significantly increased in patients treated with rituximab (P = 0.01; CI 95% rituximab 58-79 months; non-rituximab 1-30 months). Post-transplant immunosuppression regimen had no effect on survival or time to PTLD, except for cyclosporine A (CyA), which associated with increased time to PTLD (P = 0.02). Rituximab was associated with increased survival in our single-centre series, and it should be considered as first-line therapy for PTLD patients. The possible protective effect of CyA for development of PTLD should be prospectively evaluated.
Autores: Figueroa, Rocío; Alfonso, Ana; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 102  Nº Supl. 2  2017  págs. 161 - 161
Autores: Lecumberri, Ramón;
Revista: ANGIOLOGIA
ISSN 0003-3170  Vol. 68  Nº 6  2016  págs. 456 - 458
Autores: Guruceaga, Elisabet; José R. González-Porras; Joan C. Reverter; et al.
Revista: EUROPEAN JOURNAL OF HAEMATOLOGY
ISSN 0902-4441  Vol. 97  Nº 2  2016  págs. 128-136
For the first time an association between ACSF2 expression and the risk of recurrent DVT is suggested. Should this association be confirmed in larger prospective studies, ACSF2 could become useful for the selection of patients requiring extended anticoagulant therapy.
Autores: Martínez, Nicolás; Hidalgo, Francisco Nicesio; Alfonso, Ana; et al.
Revista: MEDICINA INTENSIVA
ISSN 0210-5691  Vol. 40  Nº 9  2016  págs. 550 - 559
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 bleeding is associated to high mortality rates. Available MBPs are designed for trauma patients, whereas specific recommendations in the medical/surgical settings are scarce. Patients: After excluding patients who died shortly (<6 h) after MBP activation (n=20), a total of 304 were included in the data analysis (68% males, 87% surgical). Interventions: Our MBP featured goal-directed transfusion with early use of adjuvant hemostatic medications. Variables of interest: Primary endpoints were 24-h and 30-day mortality. Fresh frozen plasma to-red blood cells (FFP:RBC) and platelet-to-RBC (PLT:RBC) transfusion ratios, time to first FFP unit and the proactive MBP triggering rate were secondary endpoints. Results: After MBP implementation (Group 2; n=222), RBC use remained stable, whereas FFP and hemostatic agents increased, when compared with Group 1 (n=82). Increased FFP:RBC ratio (p = 0.053) and earlier administration of FFP (p = 0.001) were also observed, especially with proactive MBP triggering. Group 2 patients presented lower rates of 24-h (0.5% vs. 7.3%; p = 0.002) and 30-day mortality (15.9% vs. 30.2%; p = 0.018) - the greatest reduction corresponding to non-surgical patients. Logistic regression showed an independent protective effect of MBP implementation upon 30-day mortality (OR = 0.3; 95% CI 0.15-0.61). Conclusions: These data suggest that the implementation of a goal-directed MBP for prompt and aggressive management of non-trauma, massive bleeding patients is associated to reduced 24-h and 30-day mortality rates. (C) 2016 Elsevier Espana, S.L.U. y SEMICYUC. All rights reserved.
Autores: Allende, M.; Gonzalez-Porras, J. R. ; et al.
Revista: STROKE
ISSN 0039-2499  Vol. 47  Nº 3  2016  págs. 863 - 865
Background and Purpose- The risk of cardioembolic stroke in patients with atrial fibrillation (AF) cannot be accurately assessed and novel tools are needed to improve prediction. We hypothesize that telomere shortening constitutes a novel risk factor for cardioembolic stroke in patients with AF. Methods- The peripheral blood leukocyte telomere length (LTL) was determined by real-time polymerase chain reaction in 187 patients with AF, 93 of them without stroke history and 94 of them having suffered 1 cardioembolic stroke. Percentiles were calculated according to LTL values in the nonstroke group to estimate the cardioembolic stroke risk associated with LTL using logistic regression models. Results- Short LTL values were independently and dose-dependently associated with an increased risk of cardioembolic stroke, with an odds ratio (95% confidence interval) of 2.93 (1.24-6.94) and 6.26 (2.01-19.52), respectively, for sex, hypertension, diabetes mellitus, heart failure, and age-adjusted models using the LTL 10th and 5th percentile cut-offs, respectively. Conclusions- Telomere shortening is associated with cardioembolic stroke risk in patients with AF. Prospective studies are encouraged to establish the value of LTL to improve prediction tools to categorize cardioembolic stroke risk in AF.
Autores: Alfonso, Ana; García-Mouriz A; et al.
Revista: THROMBOSIS RESEARCH
ISSN 0049-3848  Vol. 136  Nº 6  2015  págs. 1145-1148
Although the type of malignancy appears as the most relevant variable for decision-making, additional efforts are required to identify patients at particular high thrombosis risk.
Autores: Ezponda, A; Alfonso, Ana; Iribarren, María Josefa; et al.
Revista: REVISTA ESPAÑOLA DE CARDIOLOGIA
ISSN 0300-8932  Vol. 68  Nº 7  2015  págs. 638-640
Nuestra experiencia indica que, para los pacientes con asistencia ventricular que sufran TIH sin trombosis asociada, en ausencia de test de activación plaquetaria disponible, la reexposición precoz a HNF exclusivamente durante el trasplante cardiaco podría ser una alternativa al uso de inhibidores directos de la trombina durante la CEC, siempre y cuando el recuento plaquetario se haya recuperado previamente y tras la intervención se reinicie un tratamiento anticoagulante alternativo a la heparina.
Autores: Ivars, Marta; Hashimoto, T; Ishii, N; et al.
Revista: JOURNAL OF DERMATOLOGY
ISSN 0385-2407  Vol. 42  Nº 11  2015  págs. 1128-9
Autores: Alfonso, Ana; Garcia-Mouriz, A.; et al.
Revista: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
ISSN 1538-7933  Vol. 13  Nº Supl 2  2015  págs. 551
Autores: Lecumberri, Ramón; Sola, I. ; Corrales, Fernando José; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 100  Nº Supl 4  2015  págs. 99
Autores: Lecumberri, Ramón; Montes, R.; Guruceaga, Elisabet; et al.
Revista: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
ISSN 1538-7933  Vol. 13  Nº Supl 2  2015  págs. 683
Autores: Martínez, Nicolás; Marcos-Jubilar, María; Alfonso, Ana; et al.
Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN 1137-6627  Vol. 37  Nº 3  2014  págs. 363 - 369
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 reversión de AVK y manejo integral de la hemorragia masiva. Material y métodos: Revisión retrospectiva de los casos tratados con CCP entre enero de 2010 y febrero de 2013 en un único centro universitario. El objetivo primario fue la seguridad de administración del CCP en cuanto a reacciones inmediatas y episodios trombóticos. El objetivo secundario fue la eficacia, en 2 grupos: 1) Reversión de AVK y 2) Corrección de coagulopatía en hemorragia masiva. Resultados: El análisis de seguridad incluyó 31 pacientes (22 varones), edad mediana 61 años (rango 30-86). No se registraron reacciones adversas durante la infusión y solo se observó un evento trombótico. La eficacia en la reversión de AVK fue del 100% (6/6 pacientes), alcanzando normalización del INR en todos los pacientes. En hemorragia masiva, la supervivencia a las 24 horas fue 64% (16/25). Se requirieron procedimientos invasivos adicionales en 28% de los pacientes (7/25). El uso de CCP se asoció a cese de hemorragia en 44% de los pacientes (11/25), que correlacionó positivamente con la supervivencia (p=0,01). Conclusión: El uso de CCP es una alternativa segura y eficaz, para la reversión urgente del efecto de AVK, así como para el control de sangrado en situación de hemorragia masiva.
Autores: Martos, L. ; Bonet, E.; Medina, P.; et al.
Revista: THROMBOSIS RESEARCH
ISSN 0049-3848  Vol. 133  Nº Supl 3  2014  págs. S78
Autores: Alfonso, Ana; Redondo M; Rubio T; et al.
Revista: INTERNATIONAL JOURNAL OF CANCER
ISSN 0020-7136  Vol. 133  Nº 9  2013  págs. 2157-2164
Extensive screening strategies to detect occult cancer in patients with unprovoked venous thromboembolism (VTE) are complex and no benefit in terms of survival has been reported. FDG-PET/CT (2-[F-18] fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography), a noninvasive technique for the diagnosis and staging of malignancies, could be useful in this setting. Consecutive patients with a first unprovoked VTE episode were prospectively included. Screening with FDG-PET/CT was performed 3-4 weeks after the index event. If positive, appropriate diagnostic work-up was programmed. Clinical follow-up continued for 2 years. FDG-PET/CT was negative in 68/99 patients (68.7%), while suspicious FDG uptake was detected in 31/99 patients (31.3%). Additional diagnostic work-up confirmed a malignancy in 7/31 patients (22.6%), with six of them at early stage. During follow-up, two patients with negative FDG-PET/CT were diagnosed with cancer. Sensitivity (S), positive (PPV) and negative predictive values (NPV) of FDG-PET/CT as single tool for the detection of occult malignancy were 77.8% (95% CI: 0.51-1), 22.6% (95% CI: 0.08-0.37) and 97.1% (95% CI: 0.93-1), respectively. Median tissue factor (TF) activity in patients with occult cancer was 5.38 pM vs. 2.40 pM in those without cancer (p = 0.03). FDG-PET/CT is feasible for the screening of occult cancer in patients with unprovoked VTE, showing high S and NPV.
Autores: Puchades Carrasco, L.; Lecumberri, Ramón; Martinez Lopez, J.; et al.
Revista: CLINICAL CANCER RESEARCH
ISSN 1078-0432  Vol. 19  Nº 17  2013  págs. 4770 - 4779
Purpose: Multiple myeloma remains an incurable disease. New approaches to develop better tools for improving patient prognostication and monitoring treatment efficacy are very much needed. In this study, we aimed to evaluate the potential of metabolomics by H-1-NMR to provide information on metabolic profiles that could be useful in the management of multiple myeloma. Experimental Design: Serum samples were collected from multiple myeloma patients at the time of diagnosis and after achieving complete remission. A matched control set of samples was also included in the study. The H-1-NMR measurements used to obtain the metabolic profile for each patient were followed by the application of univariate and multivariate statistical analyses to determine significant differences. Results: Metabolic profiles of multiple myeloma patients at diagnosis exhibited higher levels of isoleucine, arginine, acetate, phenylalanine, and tyrosine, and decreased levels of 3-hydroxybutyrate, lysine, glutamine, and some lipids compared with the control set. A similar analysis conducted in multiple myeloma patients after achieving complete remission indicated that some of the metabolic changes (i.e., glutamine, cholesterol, lysine) observed at diagnosis displayed a variation in the opposite direction upon responding to treatment, thus contributing to multiple myeloma patients having a closer metabolic profile to those of healthy individuals after the disappearance of major disease manifestations. Conclusions: The results highlight the potential of metabolic profiles obtained by H-1-NMR in identifying multiple myeloma biomarkers that may be useful to objectively discriminate individuals with and without multiple myeloma, and monitor response to treatment. (C)2013 AACR.
Autores: Lecumberri, Ramón; López-Vivanco, G.; Font, A.; et al.
Revista: THROMBOSIS RESEARCH
ISSN 0049-3848  Vol. 132  Nº 6  2013  págs. 666-70
The addition of bemiparin to first line therapy with chemoradiotherapy significantly increases survival in patients with newly-diagnosed, limited-stage small-cell lung cancer. (Funded by the Instituto Científico y Tecnológico, University of Navarra. ClinicalTrials.gov identifier: NCT00324558).
Autores: Lecumberri, Ramón; Marques, Margarita; et al.
Revista: THROMBOSIS AND HAEMOSTASIS
ISSN 0340-6245  Vol. 110  Nº 1  2013  págs. 184-190
Many cancer patients are at high risk of venous thromboembolism (VTE) during hospitalisation; nevertheless, thromboprophylaxis is frequently underused. Electronic alerts (e-alerts) have been associated with improvement in thromboprophylaxis use and a reduction of the incidence of VTE, both during hospitalisation and after discharge, particularly in the medical setting. However, there are no data regarding the benefit of this tool in cancer patients. Our aim was to evaluate the impact of a computer-alert system for VTE prevention in patients with cancer, particularly in those admitted to the Oncology/Haematology ward, comparing the results with the rest of inpatients at a university teaching hospital. The study included 32,167 adult patients hospitalised during the first semesters of years 2006 to 2010, 9,265 (28.8%) with an active malignancy. Appropriate prophylaxis in medical patients, significantly increased over time (from 40% in 2006 to 57% in 2010) and was maintained over 80% in surgical patients. However, while e-alerts were associated with a reduction of the incidence of VTE during hospitalisation in patients without cancer (odds ratio [OR] 0.31; 95% confidence interval [CI], 0.15-0.64), the impact was modest in cancer patients (OR 0.89; 95% CI, 0.42-1.86) and no benefit was observed in patients admitted to the Oncology/Haematology Departments (OR 1.11; 95% CI, 0.45-2.73). Interestingly, 60% of VTE episodes in cancer patients during recent years developed despite appro
Autores: Páramo, José Antonio; Lecumberri, Ramón;
Revista: HEMATOLOGIA
ISSN 2081-0768  Vol. 17  Nº 1  2013  págs. 1-7
Autores: Lecumberri, Ramón; Marques, Margarita; Alfonso, Ana; et al.
Revista: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
ISSN 1538-7933  Vol. 11  Nº Supl 2  2013  págs. 381
Many cancer patients are at high risk of venous thromboembolism (VTE) during hospitalisation; nevertheless, thromboprophylaxis is frequently underused. Electronic alerts (e-alerts) have been associated with improvement in thromboprophylaxis use and a reduction of the incidence of VIE, both during hospitalisation and after discharge, particularly in the medical setting. However, there are no data regarding the benefit of this tool in cancer patients. Our aim was to evaluate the impact of a computer-alert system for VTE prevention in patients with cancer, particularly in those admitted to the Oncology/Haematology ward, comparing the results with the rest of inpatients at a university teaching hospital. The study included 32,167 adult patients hospitalised during the first semesters of years 2006 to 2010, 9,265 (28.8%) with an active malignancy. Appropriate prophylaxis in medical pa, tents, significantly increased over time (from 40% in 2006 to 57% in 2010) and was maintained over 80% in surgical patients. However,; while e-alerts were associated with a reduction of the incidence of VTE during hospitalisation in patients without cancer (odds ratio [OR] 0.31; 95% confidence interval [CI], 0.15-0.64), the impact was modest in cancer patients (OR 0.89; 95% CI, 0.42-1.86) and no benefit was observed in patients admitted to the Oncology/Haematology Departments (OR 1.11; 95% CI, 0.45-2.73). Interestingly, 60% of VIE episodes in cancer patients during recent years developed despite app
Autores: Puchades-Carrasco, L. ; Lecumberri, Ramón; Martinez-Lopez, J; et al.
Revista: EUROPEAN JOURNAL OF CANCER
ISSN 0959-8049  Vol. 49  Nº Supl 4  2013  págs. S14
Autores: Páramo, José Antonio; Lecumberri, Ramón;
Revista: MEDICINE (ELSEVIER)
ISSN 0304-5412  Vol. 11  Nº 22  2012  págs. 1345-52
El tromboembolismo venoso (TEV) es una de las causas más importantes de morbilidad y mortalidad en nuestro medio. En su patogenia intervienen las alteraciones de la pared vascular, anomalías del flujo (estasis) y un estado de hipercoagulabilidad (o trombofilia) de la sangre. Los estados trombofílicos pueden ser congénitos, por pérdida de función, como en la deficiencia de anticoagulantes naturales (antitrombina y proteínas C y S), o ganancia de función, como el factor V Leiden o la mutación de la protrombina. El diagnóstico del TEV se realiza mediante la probabilidad clínica, pruebas de imagen no invasivas, como eco-doppler y angio-tomografía computadorizada (TC), y determinación del dímero D. El tratamiento consiste en la administración de heparina de bajo peso molecular por vía subcutánea, seguida de antivitaminas K (acenocumarol o warfarina) por vía oral durante 3¿6 meses o indefinidamente si existen factores de riesgo permanentes. En los últimos años se han desarrollado nuevos anticoagulantes orales, inhibidores directos de la trombina o del factor Xa (dabigatran, rivaroxaban, apixaban), que pueden reemplazar a corto plazo a las antivitaminas K.
Autores: Gomez-Outes, Antonio; Suarez-Gea, María Luisa; Calvo-Rojas, Gonzalo; et al.
Revista: CURRENT DRUG DISCOVERY TECHNOLOGIES
ISSN 1570-1638  Vol. 9 (2)  Nº Jun 1  2012  págs. 83 - 104
The history of the traditional anticoagulants is marked by both perseverance and serendipity. The anticoagulant effect of heparin was discovered by McLean in 1915, while he was searching for a procoagulant in dog liver. Link identified dicumarol from spoiled sweet clover hay in 1939 as the causal agent of the sweet clover disease, a hemorrhagic disorder in cattle. Hirudin extracts from the medicinal leech were first used for parenteral anticoagulation in the clinic in 1909, but their use was limited due to adverse effects and difficulties in achieving highly purified extracts. Heparins and coumarins (i.e.: warfarin, phenprocoumon, acenocoumarol) have been the mainstay of anticoagulant therapy for more than 60 years. Over the past decades, the drug discovery paradigm has shifted toward rational design following a target-based approach, in which specific proteins, or "targets", are chosen on current understandings of pathophysiology, small molecules that inhibit the target's activity may be identified by high-throughput screening and, in selected cases, these new molecules can be developed further as drugs. Despite the application of rational design, serendipity has still played a significant role in some of the new discoveries. This review will focus on the discovery of the main anticoagulant drugs in current clinical use, like unfractionated heparin, low-molecular-weight heparins, fondaparinux, coumarins (i.e.: warfarin, acenocoumarol, phenprocoumon), parenteral direct thrombin inhibitors (DTIs) (i.e.: argatroban, recombinant hirudins, bivalirudin), oral DTIs (i.e.: dabigatran) and oral direct factor Xa inhibitors (i.e.: rivaroxaban, apixaban).
Autores: Lecumberri, Ramón; SOLER, S; DEL TORO, J; et al.
Revista: Thrombosis and haemostasis
ISSN 0340-6245  Vol. 105  Nº 1  2011  págs. 45 - 51
Autores: Páramo, José Antonio; Varea, Sara; Lecumberri, Ramón;
Revista: Medicina clínica. (Ed. impresa)
ISSN 0025-7753  Vol. 137  Nº 10  2011  págs. 468 - 471
Autores: Lecumberri, Ramón; Pegenaute, Carlota María; Páramo, José Antonio;
Revista: Medicina clínica. (Ed. impresa)
ISSN 0025-7753  Vol. 137  Nº 10  2011  págs. 458 - 453
Autores: Gómez-Outes, A; Suarez-Gea, ML; Lecumberri, Ramón; et al.
Revista: THERAPEUTIC ADVANCES IN CARDIOVASCULAR DISEASE
ISSN 1753-9447  Vol. 5  Nº 1  2011  págs. 33 - 59
Autores: Lecumberri, Ramón; Gómez-Guiu, María de la Almudena; et al.
Revista: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
ISSN 1538-7933  Vol. 9  Nº 6  2011  págs. 1108-1115
Objectives: The prevention of venous thromboembolism (VTE) is a priority for improved safety in hospitalised patients. Worldwide, there is growing concern over the undersuse of appropriate thromboprophylaxis. Computerised decision support improves the implementation of thromboprophylaxis and reduces inpatient VTE. However, an economic assessment of this approach has not yet been performed. Objectives: To evaluate the economic impact of an electronic alert (e-alert) system to prevent VTE in hospitalised patients over a 4 year period. Patients/methods: All hospitalised patients at a single institution during the first semesters of 2005-2009 (n = 32 280) were included. All cases of VTE developed during hospitalisation were followed and direct costs of diagnosis and management collected. Results: E-alerts achieved a sustained reduction of the incidence of in-hospital VTE, OR 0.50 (95% CI, 0.29-0.84), the impact being especially significant in medical patients, OR 0.44 (95% CI, 0.22-0.86). No increase in prophylaxis-related bleeding was observed. In our setting, the mean direct cost (during hospitalisation and after discharge) of an in-hospital VTE episode is euro7058. Direct costs per single hospitalised patient were reduced after e-alerts from euro21.6 to euro11.8, while the increased use of thromboprophylaxis and the development of e-alerts meant euro3 and euro0.35 per patient, respectively. Thus, the implementation of e-alerts led to a net cost saving of euro6.5 per hospitalised patient. Should all hospitalised patients in Spain be considered, total yearly savings would approach euro30 million. Conclusions: E-alerts are useful and cost-effective tools for thromboprophylaxis strategy in hospitalised patients. Fewer thromboembolic complications and lower costs are achieved by its implementation
Autores: Gadelha, Telmla; Roldan, Vanessa; Lecumberri, Ramón; et al.
Revista: Thrombosis Research
ISSN 0049-3848  Vol. 126  Nº 4  2010  págs. 283 - 286
Autores: MONREAL, M; VIGNOLI, A; Lecumberri, Ramón; et al.
Revista: DRUGS
ISSN 0012-6667  Vol. 14  Nº 70 Suppl. 2  2010  págs. 35 - 42