Marcos-Jubilar, M. (María)
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- Immunothrombosis: molecular aspects and new therapeutic perspectives(2023) Paramo, J.A. (José Antonio); Marcos-Jubilar, M. (María); Lecumberri, R. (Ramón)Thromboinflammation or immunothrombosis is a concept that explains the existing link between coagulation and inflammatory response present in many situations, such as sepsis, venous thromboembolism, or COVID-19 associated coagulopathy. The purpose of this review is to provide an overview of the current data regarding the mechanisms involved in immunothrombosis in order to understand the new therapeutic strategies focused in reducing thrombotic risk by controlling the inflammation.
- 11C-methionine PET/CT in assessment of multiple myeloma patients: comparison to 18F-FDG PET/CT and prognostic value evaluation(2022) Guillén-Valderrama, E.F. (Edgar Fernando); Marcos-Jubilar, M. (María); Sancho-Rodriguez, L. (Lidia); Prieto-Azcárate, E. (Elena); Alfonso-Piérola, A. (Ana); Garcia-Velloso, M. J. (María José); Rodriguez-Otero, P. (Paula); Rosales, J.J. (Juan José); Nuñez-Cordoba, J.M. (Jorge M.); San-Miguel, J.F. (Jesús F.); Morales-Lozano, M. I. (Mª Isabel)Multiple myeloma (MM) is the second most common haematological malignancy and remains incurable despite therapeutic advances. 18F-FDG (FDG) PET/CT is a relevant tool MM for staging and it is the reference imaging technique for treatment evaluation. However, it has limitations, and investigation of other PET tracers is required. Preliminary results with L-methyl-[11C]- methionine (MET), suggest higher sensitivity than 18F-FDG. This study aimed to compare the diagnostic accuracy and prognostic value of 1FDG and MET in MM patients. We prospectively compared FDG and MET PET/CT for assessment of bone disease and extramedullary disease (EMD) in a series of 52 consecutive patients (8 smoldering MM, 18 newly diagnosed MM and 26 relapsed MM patients). Bone marrow (BM) uptake patterns and the detection of focal lesions (FLs) and EMD were compared. Furthermore, FDG PET parameters with known MM prognostic value were explored for both tracers, as well as total lesion MET uptake (TLMU). Median patient age was 61 years (range, 37-83 years), 54% were male, 13% of them were in stage ISS (International Staging System) III, and 31% had high-risk cytogenetics. FDG PET/CT did not detect active disease in 6 patients, while they were shown to be positive by MET PET/CT. Additionally, MET PET/CT identified a higher number of FLs than FDG in more than half of the patients (63%). For prognostication we focussed on the relapsed cohort, due to the low number of progressions in the two other cohorts. Upon using FDG PET/CT in relapsed patients, the presence of more than 3 FLs (HR 4.61, p = 0.056), more than 10 FLs (HR 5.65, p = 0.013), total metabolic tumor volume (TMTV) p50 (HR 4.91, p = 0.049) or TMTV p75 (HR 5.32, p = 0.016) were associated with adverse prognosis. In MET PET/CT analysis, TMTV p50 (HR 4.71, p = 0.056), TMTV p75 (HR 6.27, p = 0.007), TLMU p50 (HR 8.8, p = 0.04) and TLMU p75 (HR 6.3, p = 0.007) adversely affected PFS. This study confirmed the diagnostic and prognostic value of FDG in MM. In addition, it highlights that MET has higher sensitivity than FDG PET/CT for detection of myeloma lesions, including FLs. Moreover, we show, for the first time, the prognostic value of TMTV and TLMU MET PET/CT in the imaging evaluation of MM patients.
- Association of SDF1 and MMP12 with atherosclerosis and inflammation: clinical and experimental study(MDPI, 2021) Paramo, J.A. (José Antonio); Colina, I. (Inmaculada); Machado, F. J. D. (Florencio J.D.); Marcos-Jubilar, M. (María); Orbe, J. (Josune); Rodriguez, J.A. (José Antonio); Rodil-Fraile, R. (Raquel); Fernandez-Montero, A. (Alejandro); Roncal, C. (Carmen); Pastrana-Delgado, J. (Juan)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.
- Seguridad y eficacia de un concentrado de complejo protrombínico en pacientes con coagulopatía y hemorragia(Gobierno de Navarra, 2014) Paramo, J.A. (José Antonio); Marcos-Jubilar, M. (María); Martinez-Calle, N. (Nicolas); Hidalgo, F. (Francisco); Alfonso, A. (A.); Hernandez, M. (Milagros); Lecumberri, R. (Ramón)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
- Análisis de subpoblaciones monocitarias y su asociación con el riesgo cardiovascular. Hallazgo de nuevos biomarcadores séricos: SDF1 y MMP-12(Universidad de Navarra, 2021-12-15) Marcos-Jubilar, M. (María); Paramo, J.A. (José Antonio); Pastrana-Delgado, J. (Juan)En la actualidad, la prevalencia de las enfermedades cardiovasculares (ECV) es de 108,7 millones de personas, presentando una incidencia anual de 19,9 millones de casos nuevos en la Unión Europea (UE), siendo mayor en mujeres. A día de hoy las ECV siguen siendo la principal causa de muerte en los países miembros de la UE, sumando un total de 2,2 millones en mujeres y 1,9 millones en hombres, lo que representa un 47% y 39% de las muertes totales respectivamente (1). En nuestro país, las ECV también representan la principal causa de mortalidad con aproximadamente 120.000 muertes al año, siendo la razón de una de cada 4 muertes en varones y una de cada 3 en mujeres. Si bien, en varones la enfermedad coronaria aguda encabeza la lista, en mujeres lo presenta el accidente cerebrovascular (2).
- 18F-FDG and 11C-Methionine PET/CT in Newly Diagnosed Multiple Myeloma Patients: Comparison of Volume-Based PET Biomarkers(2020) Prieto, E. (Elena); Samnick, S. (Samuel); Marcos-Jubilar, M. (María); Buck, A.K. (Andreas K.); Kortüm, K.M. (K. Martin); Viering, O. (Oliver); Garcia-Velloso, M. J. (María José); Rasche, L. (Leo); Rodriguez-Otero, P. (Paula); Lapa, C. (Constantin); San-Miguel, J.F. (Jesús F.); Morales-Lozano, M. I. (Mª Isabel)11C-methionine (11C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than 18F-fluorodeoxyglucose (18F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of 11C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to 18F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone 11C-MET and 18F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion 11C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), 11C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in 11C-MET than in 18F-FDG (p < 0.05, respectively). 11C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that 11C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than 18F-FDG. Its implications for prognosis evaluation need further investigation.
- 11C-Methionine PET/CT in Assessment of Multiple Myeloma Patients: Comparison to 18F-FDG PET/CT and Prognostic Value(MDPI, 2022) Sin Autoridad; Rodriguez-Otero, P. (Paula); Sancho-Rodriguez, L. (Lidia); Nuñez-Cordoba, J.M. (Jorge M.); Prieto, E. (Elena); Marcos-Jubilar, M. (María); Rosales, J.J. (Juan José); Alfonso-Piérola, A. (Ana); Guillén-Valderrama, E.F. (Edgar Fernando); San-Miguel, J.F. (Jesús F.); Garcia-Velloso, M. J. (María José)Multiple myeloma (MM) is the second most common haematological malignancy and remains incurable despite therapeutic advances. 18F-FDG (FDG) PET/CT is a relevant tool MM for staging and it is the reference imaging technique for treatment evaluation. However, it has limitations, and investigation of other PET tracers is required. Preliminary results with L-methyl-[11C]- methionine (MET), suggest higher sensitivity than 18F-FDG. This study aimed to compare the diagnostic accuracy and prognostic value of 1FDG and MET in MM patients. We prospectively compared FDG and MET PET/CT for assessment of bone disease and extramedullary disease (EMD) in a series of 52 consecutive patients (8 smoldering MM, 18 newly diagnosed MM and 26 relapsed MM patients). Bone marrow (BM) uptake patterns and the detection of focal lesions (FLs) and EMD were compared. Furthermore, FDG PET parameters with known MM prognostic value were explored for both tracers, as well as total lesion MET uptake (TLMU). Median patient age was 61 years (range, 37–83 years), 54% were male, 13% of them were in stage ISS (International Staging System) III, and 31% had high-risk cytogenetics. FDG PET/CT did not detect active disease in 6 patients, while they were shown to be positive by MET PET/CT. Additionally, MET PET/CT identified a higher number of FLs than FDG in more than half of the patients (63%). For prognostication we focussed on the relapsed cohort, due to the low number of progressions in the two other cohorts. Upon using FDG PET/CT in relapsed patients, the presence of more than 3 FLs (HR 4.61, p = 0.056), more than 10 FLs (HR 5.65, p = 0.013), total metabolic tumor volume (TMTV) p50 (HR 4.91, p = 0.049) or TMTV p75 (HR 5.32, p = 0.016) were associated with adverse prognosis. In MET PET/CT analysis, TMTV p50 (HR 4.71, p = 0.056), TMTV p75 (HR 6.27, p = 0.007), TLMU p50 (HR 8.8, p = 0.04) and TLMU p75 (HR 6.3, p = 0.007) adversely affected PFS. This study confirmed the diagnostic and prognostic value of FDG in MM. In addition, it highlights that MET has higher sensitivity than FDG PET/CT for detection of myeloma lesions, including FLs. Moreover, we show, for the first time, the prognostic value of TMTV and TLMU MET PET/CT in the imaging evaluation of MM patients.