INCLIVA - Instituto de Investigación Sanitaria Fundación para la Investigación del Hospital Clínico de Valencia (C. Valenciana)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/16984

Forman parte de INCLIVA el Hospital Clínico Universitario de Valencia y su Departamento de Salud, así como los grupos de excelencia científica de la Facultad de Medicina y Odontología de la Universidad de Valencia y de la Fundación IGENOMIX. El INCLIVA cuenta con personal investigador reconocido prestigio en la comunidad científica internacional y dispone de tecnología de primer nivel para el desarrollo de una investigación de calidad certificada por diferentes certificaciones. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2011, y renovando esta acreditación cada 5 años, forma parte así del total de 34 Institutos de Investigación Sanitaria acreditados existentes en la actualidad.

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Multicohort Epigenome-Wide Association Study of All-Cause Cardiovascular Disease and Cancer Incidence: A Cardio-Oncology Approach
(Elsevier, 2024-10) Domingo-Relloso, Arce; Riffo-Campos, Angela L; Zhao, Naisi; Ayala, Guillermo; Haack, Karin; Manterola, Carlos; Rhoades, Dorothy A; Umans, Jason G; Fallin, M Daniele; Herreros-Martinez, Miguel; Pollan-Santamaria, Marina; Boerwinkle, Eric; Platz, Elizabeth A; Jones, Miranda R; Bressler, Jan; Joehanes, Roby; Ryan, Calen P; Gonzalez, Juan R; Levy, Daniel; Belsky, Daniel W; Cole, Shelley A; Michaud, Dominique S; Tellez-Plaza, Maria; Navas-Acien, Ana; NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos); NIH - National Institute of Environmental Health Sciences (NIEHS) (Estados Unidos); Instituto de Salud Carlos III; Agencia Estatal de Investigación (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Ministerio de Ciencia e Innovación (España); Ministerio de Universidades (España); Unión Europea. Comisión Europea. NextGenerationEU; Fundación La Caixa; United States Department of Health and Human Services; NIH - National Cancer Institute (NCI) (Estados Unidos); Centers for Disease Control and Prevention (Estado Unidos); University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
Background: Emerging evidence reveals a complex relationship between cardiovascular disease (CVD) and cancer, which share common risk factors and biological pathways. Objectives: The aim of this study was to evaluate common epigenetic signatures for CVD and cancer incidence in 3 ethnically diverse cohorts: Native Americans from the SHS (Strong Heart Study), European Americans from the FHS (Framingham Heart Study), and European Americans and African Americans from the ARIC (Atherosclerosis Risk In Communities) study. Methods: A 2-stage strategy was used that included first conducting untargeted epigenome-wide association studies for each cohort and then running targeted models in the union set of identified differentially methylated positions (DMPs). We also explored potential molecular pathways by conducting a bioinformatics analysis. Results: Common DMPs were identified across all populations. In a subsequent meta-analysis, 3 and 1 of those DMPs were statistically significant for CVD only and both cancer and CVD, respectively. No meta-analyzed DMPs were statistically significant for cancer only. The enrichment analysis pointed to interconnected biological pathways involved in cancer and CVD. In the DrugBank database, elements related to 1-carbon metabolism and cancer and CVD medications were identified as potential drugs for target gene products. In an additional analysis restricted to the 950 SHS participants who developed incident CVD, the C index for incident cancer increased from 0.618 (95% CI: 0.570-0.672) to 0.971 (95% CI: 0.963-0.978) when adjusting the models for the combined cancer and CVD DMPs identified in the other cohorts. Conclusions: These results point to molecular pathways and potential treatments for precision prevention of CVD and cancer. Screening based on common epigenetic signatures of incident CVD and cancer may help identify patients with newly diagnosed CVD at increased cancer risk.
Gestational breast cancer: distinctive molecular and clinico-epidemiological features
(Springer, 2024-11-08) de la Haba-Rodríguez, J R; Mínguez, P; Rojo, F; Martín, M; Alba, E; Servitja, S; Prat, A; Pérez-Fidalgo, Jose Alejandro; Gavilá, J; Morales, C; Rodriguez-Lescure, A; Herrero, C; Peña-Enriquez, R; Herranz, J; Hernando, C; Hernández-Blanquisett, A; Guil-Luna, S; Martinez, M T; Blanch, S; Caballero, R; Martín, N; Pollan-Santamaria, Marina; Guerrero-Zotano, Ángel; Bermejo, B; Instituto de Salud Carlos III; University of Córdoba (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Gestational breast cancer (GBC), defined as breast cancer (BC) diagnosed during pregnancy or the first-year post-partum, accounts for 6-15% of BC cases in women aged 20-44 years. GBC has worse prognosis than non-GBC, but reasons behind are not clear. The GEICAM/2012-03 Study (Molecular Characterization of Gestational Breast Cancer) is a multicenter prospective/retrospective observational registry of patients diagnosed with GBC. From November 2014 to June 2015 seventy patients diagnosed with GBC were included in the study, 30 diagnosed during pregnancy and 40 after delivery. Our current study was aimed to explore differences in epidemiological, clinico-pathological and gene expression features of GBC tumors, from the GEICAM/2012-03 Study, compared to non-GBC tumors from patients of similar age (< 43 years) from six different GEICAM studies, used as non- GBC control population. As per the main objective, the study found multiple differences showing GBC tumors as a different biological entity. GBC showed a more aggressive biology, with higher Ki67 levels, higher incidence of breast and/or ovarian cancer family history, and germline deleterious BRCA1/2 mutations, and are enriched in basal-like intrinsic subtype. GBC patients showed a lower number of tumor infiltrating lymphocytes, while specific genetic signatures highlight differences in GBC´s distinctive transcriptome. Our study shows that GBC is potentially a clinically and molecularly different entity, with specific epidemiological, clinical, and histological features, as well as a distinctive altered immune state and genetic signature. Nevertheless, further studies are needed to better understand the biology of GBC and to identify new targets against which develop new, more effective, targeted therapies.
Cross-sectional and longitudinal associations of adherence to WCRF/AICR cancer prevention recommendations with health-related quality of life in breast cancer survivors. Health-EpiGEICAM study
(Elsevier, 2024-08) Lope Carvajal, Virginia; Guerrero-Zotano, Ángel; Fernandez de Larrea-Baz, Nerea; Antolín, Silvia; Benavent Viñuales, Marta; Bermejo, Begoña; Ruiz Moreno, Emma; Baena-Cañada, José Manuel; París, Lorena; Antón, Antonio; Chacón, José Ignacio; Muñoz, Montserrat; García-Sáenz, José Ángel; Olier, Clara; Sánchez Rovira, Pedro; Arcusa Lanza, Angels; González, Sonia; Brunet, Joan; Oltra, Amparo; Bezares, Susana; Rosell, Libertad; Perez-Gomez, Beatriz; Pastor-Barriuso, Roberto; Martín, Miguel; Pollan-Santamaria, Marina; Asociación Española Contra el Cáncer; Instituto de Salud Carlos III
Objectives: Adherence to healthy lifestyle recommendations has been reported to improve health-related quality of life (HRQL) in breast cancer (BC) patients, but the influence of long-term behavioral changes remains unknown. We evaluated the association between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and HRQL both, at BC diagnosis and the change 7-12 years later. Design: Prospective cohort study. Settings and participants: A total of 406 breast cancer survivors, from the EpiGEICAM study, were recruited in 16 Spanish hospitals. Measurements: Epidemiological, clinical, dietary, physical activity and HRQL information was collected both at recruitment and 7-12 years later. A 7-item score to measure compliance with recommendations was assessed according to the 2018 WCRF/AICR scoring criteria. HRQL was evaluated using SF-36 questionnaire. Linear mixed models for longitudinal data were used to assess the cross-sectional and longitudinal association between adherence score and the physical and mental component summary scores. Results: At diagnosis, for each unit increase in WCRF/AICR score adherence, the HRQL physical domain increased 0.78 points (95%CI: -0.04 to 1.60; P trend:0.06). The mean change in physical HRQL from diagnosis to follow-up per unit increase in within-subject adherence score was 0.73 points (95%CI: -0.18 to 1.65; P trend: 0.12). For the mental domain, no association was observed with compliance with the recommendations at diagnosis, nor with changes in adherence over time. Conclusions: Our results suggest that Increased adherence to WCRF/AICR cancer prevention recommendations over time could contribute to slightly improved long-term physical HRQoL in BC survivors.
Diagnosis and treatment of disorders of intracranial pressure: consensus statement of the Spanish Society of Neurology's Headache Study Group
(Elsevier, 2024-02-29) García-Ull, J; González-García, N; Torres-Ferrus, Marta; García-Azorín, D; Molina-Martinez, Francisco José; Beltrán-Blasco, I; Santos-Lasaosa, Sonia; Latorre, G; Gago-Veiga, A B; Láinez, J M; Porta-Etessam, J; Nieves-Castellanos, C; Mínguez-Olaondo, A; López-Bravo, A; Quintas, S; Morollón, N; Díaz-Insa, S; Belvís, R; Irimia, P
[EN] Primary intracranial pressure disorders include idiopathic intracranial hypertension and spontaneous intracranial hypotension. These two entities have presented a remarkable advance in diagnostic and therapeutic techniques in recent years. Therefore, the Spanish Society of Neurology's Headache Study Group (GECSEN) considered it necessary to prepare this consensus document with the inclusion of diagnostic and therapeutic algorithms to facilitate and improve their management in clinical practice. This document was created by a committee of experts of the GECSEN based on a systematic review of the literature, incorporating the experience of the participants, and establishing practical recommendations with levels of evidence and grades of recommendation. [ES] Los trastornos primarios de la presión intracraneal incluyen la hipertensión intracraneal idiopática y la hipotensión intracraneal espontánea. El diagnóstico y tratamiento de ambas entidades ha presentado un avance destacable en los últimos años; por lo que desde el Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología (GECSEN) consideramos necesaria la elaboración de este documento de consenso con la inclusión de algoritmos diagnósticos y terapéuticos para mejorar su manejo en la práctica diaria. Este documento ha sido redactado por un comité de expertos del GECSEN tras realizar una revisión sistemática de la bibliografía, incorporando la experiencia de los participantes y estableciendo unas recomendaciones prácticas con niveles de evidencia y grados de recomendación.
SEOM-GEICO clinical guidelines on endometrial cancer (2021)
(Springer, 2022-04) Barretina-Ginesta, Maria Pilar; Quindós, María; Alarcón Company, Jesús; Esteban, Carmen; Gaba Garcia, Lydia; Gomez, Cesar; Perez Fidalgo, Jose Alejandro; Romero, Ignacio; Santaballa, Ana; Rubio-Perez, Maria Jesús
Endometrial cancer (EC) is the second most common gynecological malignancy worldwide, the first in developed countries [Sung et al. in CA Cancer J Clin 71:209-249, 2021]. Although a majority is diagnosed at an early stage with a low risk of relapse, an important proportion of patients will relapse. Better knowledge of molecular abnormalities is crucial to identify high-risk groups in early stages as well as for recurrent or metastatic disease for whom adjuvant treatment must be personalized. The objective of this guide is to summarize the current evidence for the diagnosis, treatment, and follow-up of EC, and to provide evidence-based recommendations for clinical practice.
Amphilimus- vs. zotarolimus-eluting stents in patients with diabetes mellitus and coronary artery disease: the SUGAR trial
(Oxford University Press, 2022-03-31) Romaguera, Rafael; Salinas, Pablo; Gomez-Lara, Josep; Brugaletta, Salvatore; Gomez-Menchero, Antonio; Romero, Miguel A; Garcia-Blas, Sergio; Ocaranza, Raymundo; Bordes, Pascual; Kockar, Marcelo Jimenez; Salvatella, Neus; Jimenez-Diaz, Victor A; Alameda, Maria del Mar; Trillo, Ramiro; Lee, Dae Hyun; Martin, Pedro; Lopez-Benito, Maria; Freites, Alfonso; Pascual-Tejerina, Virginia; Hernandez-Hernandez, Felipe; Del Blanco, Bruno Garcia; Mohandes, Mohsen; Bosa, Francisco; Pinar, Eduardo; Roura, Gerard; Comin-Colet, Josep; Fernandez-Ortiz, Antonio; Macaya, Carlos; Rosselló, Xavier; Sabate, Manel; Pocock, Stuart J; Gomez-Hospital, Joan A; SUGAR Trial Investigators; Romaguera, Rafael; Salinas, Pablo; Gomez-Lara, Josep; Brugaletta, Salvatore; Gomez-Menchero, Antonio; Romero, Miguel A; Garcia-Blas, Sergio; Ocaranza, Raymundo; Bordes, Pascual; Kockar, Marcelo Jimenez; Salvatella, Neus; Jimenez-Diaz, Victor A; Alameda, Maria del Mar; Trillo, Ramiro; Lee, Dae Hyun; Martin, Pedro; Lopez-Benito, Maria; Freites, Alfonso; Pascual-Tejerina, Virginia; Hernandez-Hernandez, Felipe; Del Blanco, Bruno Garcia; Mohandes, Mohsen; Bosa, Francisco; Pinar, Eduardo; Roura, Gerard; Comin-Colet, Josep; Fernandez-Ortiz, Antonio; Macaya, Carlos; Rosselló, Xavier; Sabate, Manel; Pocock, Stuart J; Gomez-Hospital, Joan A; SUGAR Trial Investigators
Aim: Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes. Methods and results: We did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.44-0.96; Pnon-inferiority < 0.001; P-superiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs. 11.1%, HR: 0.67, 95% CI: 0.46-0.99; P = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups. Conclusion: In patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome.
Impact of COVID-19 Confinement on Physical Activity and Sedentary Behaviour in Spanish University Students: Role of Gender
(Multidisciplinary Digital Publishing Institute (MDPI), 2021-01) Rodriguez-Larrad, Ana; Manas, Asier; Labayen, Idoia; Gonzalez-Gross, Marcela; Espin, Ander; Aznar, Susana; Serrano-Sanchez, Jose Antonio; Vera-Garcia, Francisco J; Gonzalez-Lamuno, Domingo; Ara, Ignacio; Carrasco-Paez, Luis; Castro-Pinero, Jose; Gomez-Cabrera, Mari Carmen; Marquez, Sara; Tur, Josep A; Gusi, Narcis; Benito, Pedro J; Moliner-Urdiales, Diego; Ruiz, Jonatan R; Ortega, Francisco B; Jimenez-Pavon, David; Casajus, Jose Antonio; Irazusta, Jon
During the COVID-19 pandemic, entire populations were instructed to live in home-confinement to prevent the expansion of the disease. Spain was one of the countries with the strictest conditions, as outdoor physical activity was banned for nearly two months. This study aimed to analyse the changes in physical activity and sedentary behaviours in Spanish university students before and during the confinement by COVID-19 with special focus on gender. We also analysed enjoyment, the tools used and motivation and impediments for doing physical activity. An online questionnaire, which included the International Physical Activity Questionnaire Short Form and certain ad hoc questions, was designed. Students were recruited by distributing an invitation through the administrative channels of 16 universities and a total of 13,754 valid surveys were collected. Overall, university students reduced moderate (-29.5%) and vigorous (-18.3%) physical activity during the confinement and increased sedentary time (+52.7%). However, they spent more time on high intensity interval training (HIIT) (+18.2%) and mind-body activities (e.g., yoga) (+80.0%). Adaptation to the confinement, in terms of physical activity, was handled better by women than by men. These results will help design strategies for each gender to promote physical activity and reduce sedentary behaviour during confinement periods.
HOPE (SOLTI-1903) breast cancer study: real-world, patient-centric, clinical practice study to assess the impact of genomic data on next treatment decision-choice in patients with locally advanced or metastatic breast cancer
(Nature Publishing Group, 2023) Olivera-Salguero, Rubén; Seguí, Elia; Cejalvo, Juan Miguel; Oliveira, Mafalda; Tolosa, Pablo; Vidal, Maria; Malumbres Martinez, Marcos; Gavilá, Joaquín; Saura, Cristina; Pernas, Sonia; López, Rafael; Margelí, Mireia; Balmaña, Judith; Muñoz, Montserrat; Blancas, Isabel; Boni, Valentina; Ciruelos, Eva; Galve, Elena; Perelló, Antonia; Sánchez-Bayona, Rodrigo; de la Cruz, Susana; de la Hoya, Miguel; Galván, Patricia; Sanfeliu, Esther; Gonzalez-Farre, Blanca; Sirenko, Valeria; Blanch-Torras, Aura; Canes, Jordi; Masanas, Helena; Olmos, Rosa; Forns, Margarita; Prat, Aleix; Casas, Ana; Pascual, Tomás; Ministerio de Economía y Competitividad (España); Instituto de Salud Carlos III
BACKGROUND: Metastatic breast cancer (mBC) causes nearly all BC-related deaths. Next-generation sequencing (NGS) technologies allow for the application of personalized medicine using targeted therapies that could improve patients' outcomes. However, NGS is not routinely used in the clinical practice and its cost induces access-inequity among patients. We hypothesized that promoting active patient participation in the management of their disease offering access to NGS testing and to the subsequent medical interpretation and recommendations provided by a multidisciplinary molecular advisory board (MAB) could contribute to progressively overcome this challenge. We designed HOPE (SOLTI-1903) breast cancer trial, a study where patients voluntarily lead their inclusion through a digital tool (DT). The main objectives of HOPE study are to empower mBC patients, gather real-world data on the use of molecular information in the management of mBC and to generate evidence to assess the clinical utility for healthcare systems. TRIAL DESIGN: After self-registration through the DT, the study team validates eligibility criteria and assists patients with mBC in the subsequent steps. Patients get access to the information sheet and sign the informed consent form through an advanced digital signature. Afterwards, they provide the most recent (preferably) metastatic archival tumor sample for DNA-sequencing and a blood sample obtained at the time of disease progression for ctDNA analysis. Paired results are reviewed by the MAB, considering patient's medical history. The MAB provides a further interpretation of molecular results and potential treatment recommendations, including ongoing clinical trials and further (germline) genetic testing. Participants self-document their treatment and disease evolution for the next 2 years. Patients are encouraged to involve their physicians in the study. HOPE also includes a patient empowerment program with educational workshops and videos about mBC and precision medicine in oncology. The primary endpoint of the study was to describe the feasibility of a patient-centric precision oncology program in mBC patients when a comprehensive genomic profile is available to decide on a subsequent line of treatment. CLINICAL TRIAL REGISTRATION: www.soltihope.com, identifier NCT04497285.
Comparison of the 2022 and 2017 European LeukemiaNet risk classifications in a real-life cohort of the PETHEMA group
(Nature Publishing Group, 2023-05-12) Sargas, Claudia; Ayala, Rosa; Larráyoz, María J; Chillón, María C; Rodriguez-Arboli, Eduardo; Bilbao, Cristina; Prados de la Torre, Esther; Martínez-Cuadrón, David; Rodríguez-Veiga, Rebeca; Boluda, Blanca; Gil, Cristina; Bernal, Teresa; Bergua, Juan; Algarra, Lorenzo; Tormo, Mar; Martínez-Sánchez, Pilar; Soria, Elena; Serrano, Josefina; Alonso-Dominguez, Juan M; García, Raimundo; Amigo, María Luz; Herrera-Puente, Pilar; Sayas, María J; Lavilla-Rubira, Esperanza; Martinez-Lopez, Joaquin; Calasanz, María J; García-Sanz, Ramón; Pérez-Simón, José A; Gómez Casares, María T; Sánchez-García, Joaquín; Barragán, Eva; Montesinos, Pau; PETHEMA cooperative study group; Ministerio de Ciencia, Innovación y Universidades (España); Instituto de Salud Carlos III
Next-Generation Sequencing is needed for the accurate genetic risk stratification of acute myeloid leukemia according to European LeukemiaNet (ELN) guidelines. We validated and compared the 2022 ELN risk classification in a real-life cohort of 546 intensively and 379 non-intensively treated patients. Among fit patients, those aged ?65 years old showed worse OS than younger regardless risk classification. Compared with the 2017 classification, 14.5% of fit patients changed the risk with the 2022 classification, increasing the high-risk group from 44.3% to 51.8%. 3.7% and 0.9% FLT3-ITD mutated patients were removed from the favorable and adverse 2017 categories respectively to 2022 intermediate risk group. We suggest that midostaurin therapy could be a predictor for 3 years OS (85.2% with vs. 54.8% without midostaurin, P = 0.04). Forty-seven (8.6%) patients from the 2017 intermediate group were assigned to the 2022 adverse-risk group as they harbored myelodysplasia (MDS)-related mutations. Patients with one MDS-related mutation did not reach median OS, while patients with ?2 mutations had 13.6 months median OS (P = 0.002). Patients with TP53 � complex karyotype or inv(3) had a dismal prognosis (7.1 months median OS). We validate the prognostic utility of the 2022 ELN classification in a real-life setting providing supportive evidences to improve risk stratification guidelines.
Development of a genetic risk score to predict the risk of hypertension in European adolescents from the HELENA study
(Frontiers Media, 2023-06-01) Pérez-Gimeno, Gloria; Seral-Cortes, Miguel; Sabroso-Lasa, Sergio; Esteban, Luis Mariano; Lurbe, Empar; Béghin, Laurent; Gottrand, Frederic; Meirhaeghe, Aline; Muntaner, Manon; Kafatos, Anthony; Molnár, Dénes; Leclercq, Catherine; Widhalm, Kurt; Kersting, Mathilde; Nova, Esther; Salazar-Tortosa, Diego F; Gonzalez-Gross, Marcela; Breidenassel, Christina; Sinningen, Kathrin; De Ruyter, Thaïs; Labayen, Idoia; Rupérez, Azahara I; Bueno-Lozano, Gloria; Moreno, Luis A; HELENA study group; Pérez-Gimeno, Gloria; Seral-Cortes, Miguel; Sabroso-Lasa, Sergio; Esteban, Luis Mariano; Lurbe, Empar; Béghin, Laurent; Gottrand, Frederic; Meirhaeghe, Aline; Muntaner, Manon; Kafatos, Anthony; Molnár, Dénes; Leclercq, Catherine; Widhalm, Kurt; Kersting, Mathilde; Nova, Esther; Salazar-Tortosa, Diego F; Gonzalez-Gross, Marcela; Breidenassel, Christina; Sinningen, Kathrin; De Ruyter, Thaïs; Labayen, Idoia; Rupérez, Azahara I; Bueno-Lozano, Gloria; Moreno, Luis A; HELENA study group
INTRODUCTION: From genome wide association study (GWAS) a large number of single nucleotide polymorphisms (SNPs) have previously been associated with blood pressure (BP) levels. A combination of SNPs, forming a genetic risk score (GRS) could be considered as a useful genetic tool to identify individuals at risk of developing hypertension from early stages in life. Therefore, the aim of our study was to build a GRS being able to predict the genetic predisposition to hypertension (HTN) in European adolescents. METHODS: Data were extracted from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study. A total of 869 adolescents (53% female), aged 12.5-17.5, with complete genetic and BP information were included. The sample was divided into altered (?130 mmHg for systolic and/or ?80 mmHg for diastolic) or normal BP. Based on the literature, a total of 1.534 SNPs from 57 candidate genes related with BP were selected from the HELENA GWAS database. RESULTS: From 1,534 SNPs available, An initial screening of SNPs univariately associated with HTN (p < 0.10) was established, to finally obtain a number of 16 SNPs significantly associated with HTN (p < 0.05) in the multivariate model. The unweighted GRS (uGRS) and weighted GRS (wGRS) were estimated. To validate the GRSs, the area under the curve (AUC) was explored using ten-fold internal cross-validation for uGRS (0.802) and wGRS (0.777). Further covariates of interest were added to the analyses, obtaining a higher predictive ability (AUC values of uGRS: 0.879; wGRS: 0.881 for BMI z-score). Furthermore, the differences between AUCs obtained with and without the addition of covariates were statistically significant (p < 0.05). CONCLUSIONS: Both GRSs, the uGRS and wGRS, could be useful to evaluate the predisposition to hypertension in European adolescents.
Janus kinase inhibitor ruxolitinib in combination with nilotinib and prednisone in patients with myelofibrosis (RuNiC study): A phase Ib, multicenter study
(Wiley, 2023-04-16) Ayala, Rosa; Fernández, Rafael Alonso; García-Gutiérrez, Valentín; Alvarez-Larrán, Alberto; Osorio, Santiago; Sánchez-Pina, Jose M; Carreño-Tarragona, Gonzalo; Álvarez, Noemi; Gómez-Casares, María Teresa; Duran, Antonia; Gorrochategi, Julian; Hernández-Boluda, Juan Carlos; Martinez-Lopez, Joaquin; Instituto de Salud Carlos III; CRIS contra el Cáncer; Novartis Foundation
This phase Ib, non-randomized, open-label study evaluates the safety and tolerability of ruxolitinib in combination with nilotinib and prednisone in patients with naïve or ruxolitinib-resistant myelofibrosis (MF). A total of 15 patients with primary or secondary MF received the study treatment; 13 patients had received prior ruxolitinib treatment (86.7%). Eight patients completed seven cycles (53.3%) and six patients completed twelve cycles of treatment (40%). All the patients experienced at least one adverse event (AE) during the study (the most common AEs were hyperglycemia, asthenia, and thrombocytopenia), and 14 patients registered at least one treatment-related AE (the most common treatment-related AEs were hyperglycemia (22.2%; three grade 3 cases). Five treatment-related serious AEs (SAEs) were reported in two patients (13.3%). No deaths were registered throughout the study. No dose-limiting toxicity was observed. Four out of fifteen (27%) patients experienced a 100% spleen size reduction at Cycle 7, and two additional patients achieved a >50% spleen size reduction, representing an overall response rate of 40% at Cycle 7. In conclusion, the tolerability of this combination was acceptable, and hyperglycemia was the most frequent treatment-related AE. Ruxolitinib in combination with nilotinib and prednisone showed relevant clinical activity in patients with MF. This trial was registered with EudraCT Number 2016-005214-21.
Palbociclib and ribociclib in breast cancer: consensus workshop on the management of concomitant medication
(SAGE Publishing, 2019-05) Bellet, Meritxell; Ahmad, Faten; Villanueva, Rafael; Valdivia, Carolina; Palomino-Doza, Julian; Ruiz, Ada; Gonzalez, Xavier; Adrover, Encarna; Azaro, Analia; Valls-Margarit, Maria; Parra, Josep Lluis; Aguilar, Juan; Vidal, Maria; Martin, Anastasi; Gavila, Joaquin; Escriva-de-Romani, Santiago; Perello Martorell, Antonia; Hernando, Cristina; Lahuerta, Ainhara; Zamora, Pilar; Reyes, Victoria; Alcalde, Maria; Masanas, Helena; Celiz, Pamela; Ruiz, Isabel; Gil, Miguel; Segui, Miguel Angel; de la Pena, Lorena
Drug-drug interactions are of significant concern in clinical practice in oncology, particularly in patients receiving Cyclin-dependent kinase (CDK) 4/6 inhibitors, which are typically exposed to long-term regimens. This article presents the highlights from the 'First Workshop on Pharmacology and Management of CDK4/6 Inhibitors: Consensus about Concomitant Medications'. The article is structured into two modules. The educational module includes background information regarding drug metabolism, corrected QT (QTc) interval abnormalities, management of psychotropic drugs and a comprehensive review of selected adverse effects of palbociclib and ribociclib. The collaborative module presents the conclusions of the five working groups, each of which comprised five experts from different fields. From these conclusions positive lists of drugs for treating common comorbid conditions that can be safely administered concomitantly with palbociclib and/or ribociclib were developed.
Blood cell transcript levels in 5-year-old children as potential markers of breastfeeding effects in those small for gestational age at birth
(BioMed Central (BMC), 2019-05-07) Alvarez-Pitti, Julio; Amparo Ros-Fores, Maria; Bayo-Perez, Ana; Palou, Mariona; Lurbe, Empar; Palou, Andreu; Picó, Catalina
Background: Nutrition of the newborn during the early postnatal period seems to be of capital importance and there is clinical evidence showing the protective effect of breastfeeding compared with formula feeding on childhood obesity and its comorbidities. Infants born small for gestation age may be more sensitive to the type of feeding during lactation. Here, we aimed to analyze the impact of birth weight and the type of infant feeding on the expression levels in peripheral blood cells of selected candidate genes involved in energy homeostasis in 5-year-old children, to find out potential early biomarkers of metabolic programming effects during this period of metabolic plasticity. Methods: Forty subjects were recruited at birth and divided in four groups according to birth weight (adequate or small for gestational age) and type of infant feeding (breastfeeding or formula feeding). They were followed from birth to the age of 5years. Results: At 5years, no significant differences regarding anthropometric parameters were found between groups, and all children had normal biochemical values. Expression levels of UCP2 and MC4R in peripheral blood cells were lower and higher, respectively, in formula feeding children compared with breastfeeding ones (P=0.002 and P=0.064, two-way ANOVA). Differences were more marked and significant by Student's t test in small for gestation age children (P<0.001 and P=0.017, respectively). Transcript levels of FASN and FTO in peripheral blood cells were also different according to the type of infant feeding, but only in small for gestation age children. Conclusions: Altogether, these results suggest that small for gestation age infants are more sensitive to the type of feeding during lactation, and transcript levels of particular genes in peripheral blood cells, especially the MC4R/UCP2 mRNA ratio, may precisely reflect these effects in the absence of clear differences in phenotypic traits.
A proposal for the withdrawal of inhaled corticosteroids in the clinical practice of chronic obstructive pulmonary disease
(BioMed Central (BMC), 2017-11-28) Miravitlles, Marc; García-Cosío, Borja; Arnedillo, Aurelio; Calle, Myriam; Alcazar-Navarrete, Bernardino; Gonzalez, Cruz; Esteban, Cristobal; Antonio Trigueros, Juan; Rodriguez Gonzalez-Moro, Jose Miguel; Quintano Jimenez, Jose Antonio; Baloira, Adolfo
According to the current clinical practice guidelines for chronic obstructive pulmonary disease (COPD), the addition of inhaled corticosteroids (ICS) to long-acting beta(2) agonist therapy is recommended in patients with moderate-to-severe disease and an increased risk of exacerbations. However, ICS are largely overprescribed in clinical practice, and most patients are unlikely to benefit from long-term ICS therapy. Evidence from recent randomized-controlled trials supports the hypothesis that ICS can be safely and effectively discontinued in patients with stable COPD and in whom ICS therapy may not be indicated, without detrimental effects on lung function, health status, or risk of exacerbations. This article summarizes the evidence supporting the discontinuation of ICS therapy, and proposes an algorithm for the implementation of ICS withdrawal in patients with COPD in clinical practice. Given the increased risk of potentially serious adverse effects and complications with ICS therapy (including pneumonia), the use of ICS should be limited to the minority of patients in whom the treatment effects outweigh the risks.
Noninvasive ventilation during the weaning process in chronically critically ill patients.
(2016) Sancho, Jesus; Servera, Emilio; Jara-Palomares, Luis; Barrot, Emilia; Sanchez-Oro-Gomez, Raque; Gomez de Terreros, F Javier; Martin-Vicente, M Jesus; Utrabo, Isabel; Núñez, Belén; Binimelis Varella, Alicia; Sala, Ernest; Zamora, Enrique; Segrelles, Gonzalo; Ortega-Gonzalez, Angel; Masa, Fernando
Chronically critically ill patients often undergo prolonged mechanical ventilation. The role of noninvasive ventilation (NIV) during weaning of these patients remains unclear. The aim of this study was to determine the value of NIV and whether a parameter can predict the need for NIV in chronically critically ill patients during the weaning process. We conducted a prospective study that included chronically critically ill patients admitted to Spanish respiratory care units. The weaning method used consisted of progressive periods of spontaneous breathing trials. Patients were transferred to NIV when it proved impossible to increase the duration of spontaneous breathing trials beyond 18 h. 231 chronically critically ill patients were included in the study. 198 (85.71%) patients achieved weaning success (mean weaning time 25.45�16.71 days), of whom 40 (21.4%) needed NIV during the weaning process. The variable which predicted the need for NIV was arterial carbon dioxide tension at respiratory care unit admission (OR 1.08 (95% CI 1.01-1.15), p=0.013), with a cut-off point of 45.5 mmHg (sensitivity 0.76, specificity 0.67, positive predictive value 0.76, negative predictive value 0.97). NIV is a useful tool during weaning in chronically critically ill patients. Hypercapnia despite mechanical ventilation at respiratory care unit admission is the main predictor of the need for NIV during weaning.
The Genotype of the Donor for the (GT)(n) Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation
(Public Library of Science (PLOS), 2015-10-16) Noriega, Victor; Martinez-Laperche, Carolina; Buces, Elena; Sanchez-Hernandez, Noemi; Martin-Antonio, Beatriz; Guillem, Vicent; Bosch-Vizcaya, Anna; Bento, Leyre; Gonzalez-Rivera, Milagros; Balsalobre, Pascual; Kwon, Mi; Serrano, David; Gayoso, Jorge; de la Cámara, Rafael; Brunet, Salut; Rojas-Contreras, Rafael; Nieto, Jose B.; Martinez, Carmen; Gonzalez, Marcos; Espigado, Ildefonso; Vallejo, Juan C.; Sampol Mayol, Antonia; Jimenez-Velasco, Antonio; Urbano-Ispizua, Alvaro; Solano, Carlos; Gallardo, David; Diez-Martin, Jose L; Buno, Ismael; Spanish Hematopoietic Stem Cell Tr
The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (<=(GT)(15)) for the (GT)(n) polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto-or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients.
Adherencia a las recomendaciones internacionales para la prevención del cáncer en supervivientes de cáncer de mama. Estudio health-epigeicam
(Elsevier, 2023) Lope Carvajal, Virginia; Guerrero-Zotano, Ángel; Ruiz Moreno, Emma; Bermejo, B; Antolín, Silvia; Montaño, A; Fernandez de Larrea-Baz, Nerea; Martín, M; Pollan-Santamaria, Marina
Antecedentes/Objetivos: El Fondo Internacional para la Investigación del Cáncer (WCRF) aconseja a las supervivientes de cáncer seguir sus recomendaciones generales sobre estilos de vida para la prevención de esta neoplasia. Nuestro objetivo fue explorar el cumplimiento de estas recomendaciones en mujeres con historia de cáncer de mama (CM) e identificar factores clínicos y sociodemográficos potencialmente asociados. Métodos: Un total de 420 supervivientes de CM, de 31 a 80 años, participantes en el estudio previo EpiGeicam, fueron recontactadas 7-12 años después del diagnóstico en 16 hospitales españoles. A partir de información sobre dieta y actividad física se calculó la adherencia a las recomendaciones del WCRF de 2018 en una escala de 0-7, de acuerdo a criterios de puntuación estandarizados. Se estimaron prevalencias estandarizadas y razones de prevalencias estandarizadas de adherencia moderada y alta a las recomendaciones, por características de las participantes, mediante modelos de regresión logística multinomial. También se calcularon prevalencias estandarizadas de alta adherencia a cada recomendación individual con modelos de regresión logística binaria. Resultados: La adherencia media fue de 3,9 (DE: 1,0) sobre 7 puntos. Las recomendaciones con peor adherencia fueron las de limitar el consumo de carne roja/procesada (12% de cumplimiento, IC95%: 8,2-15,0) y tomar ≥ 30 g/día de fibra (22%, IC95%: 17,6-27,0). En general, la adherencia fue peor en mujeres con formación universitaria y en aquellas con familiares de primer grado con CM. La prevalencia de normopeso fue mayor en mujeres con mayor nivel educativo y en las que no tenían historia familiar de CM. Aquellas que no trabajaban cumplieron mejor la recomendación de actividad física. La prevalencia de abstemias fue mayor en las más jóvenes. El seguimiento de la recomendación sobre ingesta de fibra fue menor en las que estaban bajo tratamiento. Finalmente, muy pocas participantes con estudios universitarios cumplieron la recomendación de limitar el consumo de carne. Conclusiones/Recomendaciones: Esta información puede ser de interés para diseñar e implementar medidas preventivas personalizadas y adaptadas a las características de estas pacientes.
Monkeypox virus genomic accordion strategies
(Nature Publishing Group, 2024-04-18) Monzon-Fernandez, Sara; Varona Fernandez, Sarai; Negredo, Anabel; Vidal-Freire, Santiago; Patiño-Galindo, Juan Angel; Ferressini-Gerpe, Natalia; Zaballos, Ángel; Orviz, Eva; Ayerdi, Oskar; Muñoz-Gómez, Ana; Delgado-Iribarren, Alberto; Estrada, Vicente; Garcia-Amil, Cristina; Molero-Sanz, Francisca; Sánchez-Mora, Patricia; Torres, Montserrat; Vazquez, Ana; Galán, Juan Carlos; Torres, Ignacio; Causse Del Río, Manuel; Merino-Diaz, Laura; López, Marcos; Galar, Alicia; Cardeñoso, Laura; Gutiérrez, Almudena; Loras, Cristina; Escribano, Isabel; Alvarez-Argüelles, Marta E; Del Río, Leticia; Simón, María; Meléndez, María Angeles; Camacho, Juan; Herrero, Laura; Jimenez Sancho, Maria Pilar; Navarro-Rico, María Luisa; Jado, Isabel; Giannetti, Elaina; Kuhn, Jens H; Sanchez-Lockhart, Mariano; Di Paola, Nicholas; Kugelman, Jeffrey R; Guerra, Susana; García-Sastre, Adolfo; Cuesta de la Plaza, Isabel; Sánchez-Seco, María Paz; Palacios, Gustavo; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Icahn School of Medicine at Mount Sinai; NIH - National Institute of Allergy and Infectious Diseases (NIAID) (Estados Unidos)
The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.
Serum vascular endothelial growth factor b and metabolic syndrome incidence in the population based cohort Di@bet.es study.
(2022-08-20) Lago-Sampedro, Ana; Lhamyani, Said; Valdés, Sergio; Colomo, Natalia; Maldonado-Araque, Cristina; González-Molero, Inmaculada; Doulatram-Gamgaram, Viyey; Delgado, Elias; Chaves, Felipe J; Castaño, Luis; Calle-Pascual, Alfonso; Franch-Nadal, Josep; Rojo-Martínez, Gemma; García-Serrano, Sara; García-Escobar, Eva
Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up. A total of 908 subjects from the Di@bet.es cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physical activity. A fasting blood extraction and an oral glucose tolerance test were performed. Serum determinations of glucose, lipids, hsCRP and insulin were made. VEGFb levels were determined and categorized according to the 75th percentile of the variable. New cases of MS and its components were defined according to ATPIII and IDF criteria. A total of 181 or 146 people developed MS defined by IDF or ATP-III criteria respectively. Serum triglyceride levels, hs-CRP and systolic blood pressure at the baseline study were significantly different according to the VEGFb categories. Adjusted logistic regression analysis showed that the likelihood of developing MS and abdominal obesity was statistically reduced in subjects included in the higher VEGFb category. Low serum levels of VEGFb may be considered as early indicators of incident MS and abdominal obesity in the Spanish adult population free of MS, independently of other important predictor variables.
Ambient air pollution and thyroid function in Spanish adults. A nationwide population-based study (Di@bet.es study).
(2022-08-17) Valdés, Sergio; Doulatram-Gamgaram, Viyey; Maldonado-Araque, Cristina; Lago-Sampedro, Ana; García-Escobar, Eva; García-Serrano, Sara; García-Vivanco, Marta; Garrido Juan, Luis; Theobald, Mark Richard; Gil, Victoria; Martín-Llorente, Fernando; Ocon, Pilar; Calle-Pascual, Alfonso; Castaño, Luis; Delgado, Elías; Menendez, Edelmiro; Franch-Nadal, Josep; Gaztambide, Sonia; Girbés, Joan; Chaves, F Javier; Galán-García, José L; Aguilera-Venegas, Gabriel; Gutierrez-Repiso, Carolina; Fernández-García, José Carlos; Colomo, Natalia; Soriguer, Federico; García-Fuentes, Eduardo; Rojo-Martínez, Gemma
Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain. The Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter In multivariate linear regression models, there was a highly significant negative correlation between PM2.5 concentrations and both FT4 (p Exposures to PM2.5 in the general population were associated with mild alterations in thyroid function.

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