IDIBELL - Instituto de Investigación Biomédica de Bellvitge (Cataluña)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/16962

El Instituto de Investigación Biomédica de Bellvitge (IDIBELL) es un centro de investigación en biomedicina participado por el Hospital Universitario de Bellvitge y el Hospital de Viladecans del Instituto Catalán de la Salud, el Instituto Catalán de Oncología, la Universidad de Barcelona y el Ayuntamiento de l’Hospitalet de Llobregat. En 2017, el Centro de Medicina Regenerativa de Barcelona (CMR[B]), ahora parte del IDIBELL, inicia el despliegue del Programa de Traslación Clínica de Medicina Regenerativa de Cataluña (P-CMR[C]) con el IDIBELL. Los focos de investigación del IDIBELL son el cáncer, las neurociencias, la medicina traslacional y la medicina regenerativa. La investigación, la innovación y la sociedad son los pivotes sobre los que los investigadores trabajan cada día para mejorar la calidad de vida de los ciudadanos y ciudadanas. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2009, 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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Mammographic density and breast cancer pathological subtypes by menopausal status and body mass index.
(BioMed Central (BMC), 2025-10-24) Fernández-Morata, Julia; Pollan-Santamaria, Marina; Fernandez de Larrea-Baz, Nerea; Pachón-Olmos, Vanessa; García-Pérez, Javier; Castelló Pastor, Adela; Sierra, Maria Angeles; de Lucas, Maria Pilar; Llobet, Rafael; Stradella, Agostina; Cantos, Blanca; Ramón Y Cajal, Teresa; Santisteban, Marta; Seguí, Miguel Ángel; Santaballa Bertrán, Ana; Granja, Mónica; Camps-Herrero, Julia; Recalde, Sabela; Núñez-García, Beatriz; Calvo Verges, Nuria; Perez-Gomez, Beatriz; Pastor-Barriuso, Roberto; Lope Carvajal, Virginia; Instituto de Salud Carlos III
Background: Mammographic density (MD) is an established biomarker of breast cancer (BC) risk. However, its relationship to BC pathological subtypes remains unclear. This study aimed to investigate this association and assess whether it differs by body mass index (BMI) and menopausal status. Methods: MD percentage was assessed in the diagnostic mammograms of the contralateral breast of 714 BC patients recruited from eight Spanish hospitals. Participants completed an epidemiological questionnaire, and hospital researchers collected clinical and pathological data. Standardized prevalences (SPs) and standardized prevalence ratios (SPRs) for each BC pathological subtype across MD categories were estimated based on multinomial logistic regression models, both overall and stratified by BMI and menopausal status. Results: Mean MD was 26.1% (SD = 17.3). Although no statistically significant differences were detected, women with MD ≥ 50% had a 13% lower SP of hormone receptor positive tumors (SPR = 0.87; 95% CI 0.67-1.13), a 36% higher SP of human epidermal growth factor receptor 2 positive (HER2+) tumors (SPR = 1.36; 95% CI 0.72-2.58), and a 23% higher SP of triple negative (TN) tumors (SPR = 1.23; 95% CI 0.47-3.22), compared to those with MD < 10%. These patterns were mainly observed in pre/perimenopausal women and in those with BMI ≥ 25 kg/m. Conclusions: High MD might be mainly associated with the development of more aggressive and non-hormone-dependent cancers, such as HER2+ and TN BC, especially among pre/perimenopausal an overweight women.
Determinants of Adherence to World Cancer Research Fund/American Institute for Cancer Research Recommendations in Women with Breast Cancer
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-02-19) Pachón Olmos, Vanessa; Pollan-Santamaria, Marina; Fernandez de Larrea-Baz, Nerea; Fernández-Morata, Julia; Ruiz Moreno, Emma; García-Pérez, Javier; Castelló Pastor, Adela; Sierra, Maria Angeles; de Lucas, Maria Pilar; Alonso Ledesma, Isabel; Stradella, Agostina; Cantos, Blanca; Ramón Y Cajal, Teresa; Santisteban, Marta; Seguí, Miguel Ángel; Santaballa Bertrán, Ana; Granja, Mónica; Camps-Herrero, Julia; Recalde, Sabela; Mendez, Miriam; Calvo Verges, Nuria; Perez-Gomez, Beatriz; Pastor-Barriuso, Roberto; Lope Carvajal, Virginia; Instituto de Salud Carlos III
Background/objectives: The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations benefit primary prevention and survivor outcomes. This study evaluated the adherence to these recommendations during the year prior to breast cancer diagnosis and identified related clinical and sociodemographic factors. Methods: A total of 915 patients with breast cancer were recruited from eight hospitals in four regions of Spain. The participants completed an epidemiologic questionnaire and a food frequency questionnaire. The compliance with the WCRF/AICR recommendations was assessed using a standardized score based on seven recommendations. Standardized prevalences and standardized prevalence ratios (SPRs) for moderate and high adherence were calculated based on participant characteristics using binary and multinomial logistic regression models. Results: The mean adherence was 3.5 points out of 7. The recommendations with the best and worst adherence were avoiding sugar-sweetened drinks (54.4% adherence) and maintaining a fiber-rich diet (4.4% consumed ≥30 g/day). The overall adherence was better in women aged ≥60 years (SPR = 1.55; 95% CI = 1.09-2.22), and worse in those with a caloric intake ≥2000 kcal/day (SPR = 0.48; 95% CI = 0.37-0.62) or ≥2 comorbidities (SPR = 0.66; 95% CI = 0.49-0.89). The adherence to maintaining a healthy weight was worse in those with ≥2 comorbidities and stage III-IV tumors. The physical activity adherence was worse in working women and those with ≥2 comorbidities. The alcohol restriction adherence was worse in smokers. Younger women, smokers and those with a low calorie intake were less adherent to the fruit/vegetable recommendation. The consumption of fiber and limited consumption of red/processed meat adherence was poor in all the subgroups. The adherence to a limited consumption of fast food and sugary drinks was worse in younger women and high-calorie-diet consumers. Conclusions: The differences in the adherence to recommendations according to patient characteristics justify the design of personalized interventions for breast cancer patients.
Calibration of Toenail Metal Concentrations for Sample Mass Heterogeneity and Between-Batch Variability: The COMET Approach
(National Institute of Environmental Health Sciences (NIEHS), 2025-04) Pastor-Barriuso, Roberto; Gutiérrez-González, Enrique; Varea-Jiménez, Elena; Gómez-Ariza, José Luis; Castaño-Vinyals, Gemma; Aragonés, Nuria; Molina, Antonio José; Dierssen-Sotos, Trinidad; Fernández-Tardón, Guillermo; Amiano, Pilar; Ederra-Sanz, María; Moreno, Victor; Jiménez-Moleón, José Juan; Molina-Barceló, Ana; Marcos-Gragera, Rafael; Casabonne, Delphine; Alguacil, Juan; Gómez-Gómez, Jesús Humberto; García-Barrera, Tamara; Kogevinas, Manolis; Pollan-Santamaria, Marina; Perez-Gomez, Beatriz; Instituto de Salud Carlos III; Asociación Española Contra el Cáncer; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Scientific Foundation
Background: Toenails are promising biomarkers of long-term metal exposure in epidemiological studies, but their accuracy may be compromised by systematic and random errors associated with heterogeneous toenail sample masses, as well as by substantial variability across laboratory batches. Objectives: We propose a novel modeling approach to calibrate toenail metal concentrations for the heterogeneity in sample masses and the variability between batches. Methods: We developed a heteroscedastic spline mixed model relating sample mass and laboratory batch with measured concentrations, allowing for an average bias in measurements over all batches as a smooth function of sample mass, random variation in mass-related biases across batches, and mass-related heterogeneity in within-batch error variance. The model allowed partitioning the total variance of measured concentrations into the extraneous variances (due to different sample masses and laboratory batches) and the intrinsic variance (resulting from distinct metal exposures). We derived calibrated metal concentrations from the model by removing both sources of extraneous variation and estimating the predicted concentrations had all toenail samples been analyzed in a single batch and of the same mass. We provide the R script COMET (COrrected METals) to fit the proposed model, extract variance components, and calibrate metal concentrations. Results: In a multicase-control study in Spain (MCC-Spain) with toenail determinations for 16 metals in 4,473 incident cases of five common cancers and 3,450 population controls, sample mass and batch accounted for 26%-60% of the total variance of measured concentrations for most metals. In comparison with calibrated concentrations, odds ratios for measured concentrations were biased by > 10% toward or away from the null in one-quarter of the estimated metal-cancer associations. Discussion: The proposed model allows correcting toenail metal concentrations for sample mass heterogeneity and between-batch variability and could be applied to other biological specimens of heterogeneous size, distinct laboratory techniques, and different study designs.
Novel risk loci for COVID-19 hospitalization among admixed American populations
(eLife Sciences Publications, 2024-10-03) Diz-de Almeida, Silvia; Cruz, Raquel; Luchessi, Andre D; Lorenzo-Salazar, José M; López de Heredia, Miguel; Quintela, Inés; González-Montelongo, Rafaela; Nogueira Silbiger, Vivian; Porras, Marta Sevilla; Tenorio Castaño, Jair Antonio; Nevado, Julián; Aguado, José María; Aguilar, Carlos; Aguilera-Albesa, Sergio; Almadana, Virginia; Almoguera, Berta; Alvarez, Nuria; Andreu-Bernabeu, Álvaro; Arana-Arri, Eunate; Arango, Celso; Arranz, María J; Artiga, Maria-Jesus; Baptista-Rosas, Raúl C; Barreda-Sánchez, María; Belhassen-García, Moncef; Bezerra, Joao F; Bezerra, Marcos A C; Boix-Palop, Lucía; Brion, María; Brugada, Ramón; Bustos, Matilde; Calderón, Enrique J; Carbonell, Cristina; Castano, Luis; Castelao, Jose E; Conde-Vicente, Rosa; Cordero-Lorenzana, M Lourdes; Cortes-Sanchez, Jose L; Corton, Marta; Darnaude, M Teresa; De Martino-Rodríguez, Alba; Del Campo-Pérez, Victor; Diaz de Bustamante, Aranzazu; Domínguez-Garrido, Elena; Eirós, Rocío; Fariñas, María Carmen; Fernandez-Nestosa, María J; Fernández-Robelo, Uxía; Fernandez-Rodriguez, Amanda; Fernández-Villa, Tania; Gago-Dominguez, Manuela; Gil-Fournier, Belén; Gómez-Arrue, Javier; González Álvarez, Beatriz; González Bernaldo de Quirós, Fernan; González-Neira, Anna; González-Peñas, Javier; Gutiérrez-Bautista, Juan F; Herrero, María José; Herrero-Gonzalez, Antonio; Jimenez-Sousa, Maria Angeles; Lattig, María Claudia; Liger Borja, Anabel; Lopez-Rodriguez, Rosario; Mancebo, Esther; Martín-López, Caridad; Martín, Vicente; Martinez-Nieto, Oscar; Martinez-Lopez, Iciar; Martinez-Resendez, Michel F; Martinez-Perez, Angel; Mazzeu, Juliana F; Merayo Macías, Eleuterio; Minguez, Pablo; Moreno Cuerda, Victor; Oliveira, Silviene F; Ortega-Paino, Eva; Pompa-Mera, Ericka N; Parellada, Mara; Paz-Artal, Estela; Santos, Ney PC; Pérez-Matute, Patricia; Perez, Patricia; Pérez-Tomás, M Elena; Perucho, Teresa; Pinsach-Abuin, Mel·lina; Pita, Guillermo; Porras-Hurtado, Gloria L; Pujol, Aurora; Ramiro León, Soraya; Resino, Salvador; Fernandes, Marianne R; Rodríguez-Ruiz, Emilio; Rodríguez-Artalejo, Fernando; Rodriguez-Garcia, José A; Ruiz-Cabello, Francisco; Ruiz-Hornillos, Javier; Ryan, Pablo; Soria, José Manuel; Souto, Juan Carlos; Tamayo, Eduardo; Tamayo-Velasco, Álvaro; Taracido-Fernandez, Juan Carlos; Teper, Alejandro; Torres-Tobar, Lilian; Urioste, Miguel; Valencia-Ramos, Juan; Yáñez, Zuleima; Zarate, Ruth; de Rojas, Itziar; Ruiz, Agustín; Sánchez, Pascual; Real, Luis Miguel; SCOURGE Cohort Group; Guillén-Navarro, Encarna; Ayuso, Carmen; Parra, Esteban; Riancho, José A; Rojas-Martinez, Augusto; Flores, Carlos; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Banco Santander; Fundación La Caixa; Agencia Estatal de Investigación (España); Gobierno de Canarias (España); Fundación Canaria de Investigación Sanitaria; Xunta de Galicia (España); Fundación Amancio Ortega; Estrella de Levante; Colabora Mujer
The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations ( and ). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in . Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.
Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study
(Elsevier, 2024-06) Calvo-Silveria, Sara; González-Díaz, Aida; Grau, Inmaculada; Marimón, José María; Cercenado, Emilia; Quesada, M Dolores; Casabella, Antonio; Larrosa, Nieves; Yuste, Jose Enrique; Berbel, Dàmaris; Alonso, Marta; Tubau, Fe; Belman, Sophie; Cadenas-Jiménez, Irene; Martin-Galiano, Antonio Javier; Domínguez, María Ángeles; Martí, Sara; Liñares, Josefina; Pallarés, Román; Càmara, Jordi; Ardanuy, Carmen; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERES (Enfermedades Respiratorias); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Background: Invasive pneumococcal disease due to serotype 3 (S3-IPD) is associated with high mortality rates and long-term adverse effects. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the Spanish paediatric immunisation programme has not led to a decrease in the adult S3-IPD. We aimed to analyse the incidence, clinical characteristics and genomics of S3-IPD in adults in Spain. Methods: Adult IPD episodes hospitalized in a Southern Barcelona hospital were prospectively collected (1994-2020). For genomic comparison, S3-IPD isolates from six Spanish hospitals (2008-2020) and historical isolates (1989-1993) were analysed by WGS (Illumina and/or MinION). Findings: From 1994 to 2020, 270 S3-IPD episodes were detected. When comparing pre-PCV (1994-2001) and late-PCV13 (2016-2020) periods, only modest changes in S3-IPD were observed (from 1.58 to 1.28 episodes per 100,000 inhabitants year). In this period, the incidence of the two main lineages shifted from 0.38 to 0.67 (CC180-GPSC12) and from 1.18 to 0.55 (CC260-GPSC83). The overall 30-day mortality remained high (24.1%), though a decrease was observed between the pre-PCV (32.4%; 95.0% CI, 22.0-45.0) and the late-PCV13 period (16.7%; 95.0% CI, 7.5-32.0) (p = 0.06). At the same time, comorbidities increased from 77.3% (95.0% CI, 65.0-86.0) to 85.7% (95.0% CI, 71.0-94.0) (p = 0.69). There were no differences in clinical characteristics or 30-day mortality between the two S3 lineages. Although both lineages were genetically homogeneous, the CC180-GPSC12 lineage presented a higher SNP density, a more open pan-genome, and a major presence of prophages and mobile genetic elements carrying resistance genes. Interpretation: Adult S3-IPD remained stable in our area over the study period despite PCV13 introduction in children. However, a clonal shift was observed. The decrease in mortality rates and the increase in comorbidities suggest a change in clinical management and overall population characteristics. The low genetic variability and absence of clinical differences between lineages highlight the role of the S3 capsule in the disease severity.
Impact of the COVID-19 pandemic on the self-care and health condition of the older adults. CUIDAMOS+75. A mixed methods study protocol
(Frontiers Media, 2024) Rico-Blazquez, Milagros; Esteban-Sepúlveda, Silvia; Sánchez-Ruano, Raquel; Aritztegui-Echenique, Ana María; Artigues-Barbera, Eva María; Brito-Brito, Pedro-Ruymán; Casado-Ramirez, Elvira; Cidoncha-Moreno, María Ángeles; Fabregat-Julve, María Inmaculada; Feria-Raposo, Isabel; Hernandez-Pascual, Montserrat; Lozano-Hernández, Cristina; Moreno-Casbas, Teresa; Otones-Reyes, Pedro; Palmar-Santos, Ana María; Pedraz-Marcos, Azucena; Romero-Rodriguez, Esperanza María; Solé-Agustí, María Cristina; Taltavull-Aparicio, Joana María; Vidal-Thomàs, María Clara; González-Chordá, Víctor M; Cuidamos+75 Group; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Aims: To assess the impact of the COVID-19 pandemic on the health condition of people ≥75 years of age and on their family caregivers in Spain. Design: Multicentric, mixed method concurrent study. Methods: This work, which will be conducted within the primary care setting in 11 administrative regions of Spain, will include three coordinated studies with different methodologies. The first is a population-based cohort study that will use real-life data to analyze the rates and evolution of health needs, care provision, and services utilization before, during, and after the pandemic. The second is a prospective cohort study with 18 months of follow-up that will evaluate the impact of COVID-19 disease on mortality, frailty, functional and cognitive capacity, and quality of life of the participants. Finally, the third will be a qualitative study with a critical social approach to understand and interpret the social, political, and economic dimensions associated with the use of health services during the pandemic. We have followed the SPIRIT Checklist to address trial protocol and related documents. This research is being funded by the Instituto de Salud Carlos III since 2021 and was approved by its ethics committee (June 2022). Discussion: The study findings will reveal the long-term impact of the COVID-19 pandemic on the older adults and their caregivers. This information will serve policymakers to adapt health policies to the needs of this population in situations of maximum stress, such as that produced by the COVID-19 pandemic. Trial registration: Identifier: NCT05249868 [ClinicalTrials.gov].
Health-Related Quality of Life in Long-Term Colorectal Cancer Survivors
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-09-25) Marcos-Delgado, Alba; Martín-Sánchez, Vicente; Molina-Barceló, Ana; Alonso-Molero, Jéssica; Perez-Gomez, Beatriz; Pollán, Marina; Aragones, Nuria; Ederra-Sanz, María; Fernández-Tardón, Guillermo; Binefa, Gemma; Moreno, Victor; Barrios-Rodríguez, Rocío; Amiano, Pilar; Huerta, José María; Teso, Enrique Pastor; Alguacil, Juan; Castaño-Vinyals, Gemma; Kogevinas, Manolis; Molina de la Torre, Antonio José; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Junta de Castilla y León (España); Regional Government of Andalusia (España)
The aim of our study is to evaluate the relationship between sociodemographic and clinical characteristics of individuals with Colorectal Cancer (CRC), tumour-intrinsic characteristics and treatment received with health-related quality of life (HRQoL). Methods: Cross-sectional analysis of data from 805 survivors from the MCC study was conducted. HRQoL was assessed through a general and specific questionnaire, SF-12 and FCSI (Colorectal Symptom Index). Statistical analyses were performed with linear regression with adjustment for sociodemographic variables, stage at diagnosis and histological grade. Results: Participants had survived a median of 7.9 years from diagnosis (IQR 7.1-8.5 years). Age at diagnosis, sex and area showed a clear association with HRQoL in both physical and mental dimensions of the SF-12 questionnaire. A direct association between CRC recurrence was also found in the PCS-12 and MCS-12 dimensions and radical surgery in the PCS-12. Regarding the scores in FCSI questionnaire, statistically significant differences were observed by sex, age and area, with older women being the most impaired (p < 0.001). Conclusions: Age, sex and area was associated with lower scores of HRQoL among CRC survivors. Knowing the determinants related to HRQoL would allow us to lay the groundwork to develop strategies that help reduce morbidity and mortality, relapses and increase HRQoL.
Burden of postmenopausal breast cancer attributable to excess body weight: comparative study of body mass index and CUN-BAE in MCC-Spain study
(BMJ Publishing Group, 2024-12-10) Cubelos-Fernández, Naiara; Dávila-Batista, Verónica; Fernández-Villa, Tania; Castaño-Vinyals, Gemma; Perez-Gomez, Beatriz; Amiano, Pilar; Ardanaz, Eva; Delgado Sillero, Irene; Llorca, Javier; Tardón, Guillermo Fernández; Alguacil, Juan; Vanaclocha-Espi, Mercedes; Marcos-Gragera, Rafael; Moreno, Victor; Aragones, Nuria; Dorronsoro, Ane; Guevara, Marcela; Reguero Celada, Sofía; Pollan-Santamaria, Marina; Kogevinas, Manolis; Martín, Vicente; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Ministerio de Ciencia e Innovación (España); Fundación Marqués de Valdecilla; International Cancer Genome Consortium; Ministerio de Economía y Competitividad (España); Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España); Junta de Castilla y León (España); Regional Government of Andalusia (España); Generalitat Valenciana (España); Fundación La Caixa; Basque Government (España); Gobierno de la Región de Murcia (España); Unión Europea. Comisión Europea; Asociación Española Contra el Cáncer; Agència de Gestió d´Ajuts Universitaris i de Recerca (AGAUR); Government of Catalonia (España); Fundación Caja de Ahorros de Asturias; University of Oviedo (España); Unión Europea. Fondo Social Europeo (ESF/FSE)
Background: 10% of postmenopausal breast cancer cases are attributed to a high body mass index (BMI). BMI underestimates body fat, particularly in older women, and therefore the cancer burden attributable to obesity may be even higher. However, this is not clear. CUN-BAE (Clínica Universidad de Navarra-Body Adiposity Estimator) is an accurate validated estimator of body fat, taking into account sex and age. The objective of this study was to compare the burden of postmenopausal breast cancer attributable to excess body fat calculated using BMI and CUN-BAE. Methods: This case-control study included 1033 cases of breast cancer and 1143 postmenopausal population controls from the multicase-control MCC-Spain study. Logistic regression models were used to calculate odds ratios (ORs). The population attributable fraction (PAF) of excess weight related to breast cancer was estimated with both anthropometric measures. Stratified analyses were carried out for hormone receptor type. Results: Excess body weight attributable to the risk of breast cancer was 23.0% when assessed using a BMI value ≥30 kg/m2 and 38.0% when assessed using a CUN-BAE value of ≥40% body fat. Hormone receptor stratification showed that these differences in PAFs were only observed in hormone receptor positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE. Conclusion: These findings suggest that the significance of excess body fat in postmenopausal hormone receptor positive breast cancer could be underestimated when assessed using only BMI. Accurate estimation of the cancer burden attributable to obesity is crucial for planning effective prevention initiatives.
Olfactory Receptor OR2K2 Expression in Human Choroid Plexus as a Potential Marker in Early Sporadic Alzheimer's Disease
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-03-21) Alves, Victoria Cunha; Figueiro-Silva, Joana; Trullas, Ramon; Ferrer, Isidre; Carro, Eva; Instituto de Salud Carlos III; Comunidad de Madrid (España); Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)
Epithelial cells comprising the choroid plexus (CP) form a crucial barrier between the blood and the cerebrospinal fluid, thereby assuming a central position in brain homeostasis and signaling. Mounting evidence suggests that the impairment of CP function may be a significant contributor to Alzheimer's disease (AD) pathogenesis. CP function relies on the expression of specific receptors, and the potential involvement of olfactory receptors (ORs) and taste receptors (TASRs) in chemical surveillance within the CP is being investigated. Previous studies have implicated ORs and TASRs in neurodegenerative disorders like AD, although the direct evidence of their expression in the human CP remains to be established. In this study, we conducted a transcriptomic analysis encompassing eleven and in the CP, comparing samples from healthy age-matched controls to those from patients with AD spanning Braak stages I to VI. Among these receptors, a striking finding emerged- exhibited robust expression, with a statistically significant upregulation noted at Braak stage I. Surprisingly, at the protein level, OR2K2 showed a significant decrease in both Braak stage I and VI. Additionally, we identified CP epithelial cells as the source of OR2K2 expression, where it colocalized with autophagy markers LC3 and p62. We postulate that OR2K2 could be subjected to degradation by autophagy in the early stages of AD, triggering a compensatory mechanism that leads to increased mRNA transcription. This study uncovers a potential role for OR2K2 in AD pathogenesis, offering a novel perspective on the intricate dynamics at play in this neurodegenerative disorder.
Clinical performance evaluation of the Idylla™ EGFR Mutation Test on formalin-fixed paraffin-embedded tissue of non-small cell lung cancer
(2020-04-03) Delgado-García, Mercedes; Weynand, Birgit; Gómez-Izquierdo, Lourdes; Hernández, María José; Blanco, Ángela María; Varela, Mar; Matias-Guiu, Xavier; Nadal, Ernest; Márquez-Lobo, Bélgica; Alarcão, Ana; de Álava, Enrique; Biscuola, Michele
Background: Detection of epidermal growth factor receptor (EGFR) mutations in exons 18-21 is recommended in all patients with advanced Non-small-cell lung carcinoma due to the demonstrated efficiency of the standard therapy with tyrosine kinase inhibitors in EGFR-mutated patients. Therefore, choosing a suitable technique to test EGFR mutational status is crucial to warrant a valid result in a short turnaround time using the lowest possible amount of tissue material. The Idylla™ EGFR Mutation Test is a simple, fast and reliable method designed for the detection of EGFR mutations from formalin-fixed paraffin-embedded samples. The aim of this study was the Clinical Performace Evaluation of the Idylla™ EGFR Mutation Test on the Idylla™ System. Methods: EGFR mutational status was determined on 132 archived formalin-fixed paraffin-embedded tissue sections with Idylla™ technology. Results were compared with the results previously obtained by routine method in the reference lab (Therascreen® EGFR RGQ PCR v2, Qiagen in Molecular Pathology lab, Hospital Universitario Virgen del Rocío de Sevilla). Results: The overall agreement between results obtained with the Idylla™ EGFR Mutation Test and the Comparator test method was 95.38% (with 1-sided 95% lower limit of 91.7%) showing Positive Diagnostic Agreement of 93.22% and Negative Diagnostic Agreement of 97.18%, with a Limit Of Detection ≤5%. Conclusions: The Idylla™ EGFR Mutation Test passed its clinical validity performance characteristics for accuracy.
Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain.
(2020-05-11) Gonzalez-Quereda, Lidia; Rodriguez, Maria Jose; Diaz-Manera, Jordi; Alonso-Perez, Jorge; Gallardo, Eduard; Nascimento, Andres; Ortez, Carlos; Natera-de Benito, Daniel; Olive, Montse; Gonzalez-Mera, Laura; Munain, Adolfo Lopez de; Zulaica, Miren; Poza, Juan Jose; Jerico, Ivonne; Torne, Laura; Riera, Pau; Milisenda, Jose; Sanchez, Aurora; Garrabou, Gloria; Llano, Isabel; Madruga-Garrido, Marcos; Gallano, Pia
The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients' clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.
RING1B contributes to Ewing sarcoma development by repressing the NaV1.6 sodium channel and the NF-κB pathway, independently of the fusion oncoprotein
(2016) Hernandez-Muñoz, Inmaculada; Figuerola, Elisabeth; Sanchez-Molina, Sara; Rodriguez, Eva; Fernández-Mariño, Ana Isabel; Pardo-Pastor, Carlos; Bahamonde, María Isabel; Fernández-Fernández, José M; García-Domínguez, Daniel J; Hontecillas-Prieto, Lourdes; Lavarino, Cinzia; Carcaboso, Angel M; de Torres, Carmen; Tirado, Oscar M; de Álava, Enrique; Mora, Jaume
Ewing sarcoma (ES) is an aggressive tumor defined by EWSR1 gene fusions that behave as an oncogene. Here we demonstrate that RING1B is highly expressed in primary ES tumors, and its expression is independent of the fusion oncogene. RING1B-depleted ES cells display an expression profile enriched in genes functionally involved in hematological development but RING1B depletion does not induce cellular differentiation. In ES cells, RING1B directly binds the SCN8A sodium channel promoter and its depletion results in enhanced Nav1.6 expression and function. The signaling pathway most significantly modulated by RING1B is NF-κB. RING1B depletion results in enhanced p105/p50 expression, which sensitizes ES cells to apoptosis by FGFR/SHP2/STAT3 blockade. Reduced NaV1.6 function protects ES cells from apoptotic cell death by maintaining low NF-κB levels. Our findings identify RING1B as a trait of the cell-of-origin and provide a potential targetable vulnerability.
SEOM clinical guidelines for the management of germ cell testicular cancer (2016)
(2016-11-04) Aparicio, J; Terrasa, J; Durán, I; Germà-Lluch, J R; Gironés, R; González-Billalabeitia, E; Gumà, J; Maroto, P; Pinto, A; García-Del-Muro, X
Testicular cancer represents the most common malignancy in males aged 15-34 years and is considered a model of curable neoplasm. Maintaining success, reducing treatment burden, and focusing on survivorship are then key objectives. Inguinal orchiectomy is the first recommended maneuver that has both diagnostic and therapeutic aims. Most patients are diagnosed with stage I disease (confined to the testicle). Close surveillance and selective, short-course adjuvant chemotherapy are accepted alternatives for these cases. In patients with more advanced disease (stages II and III), 3-4 courses of cisplatin-based chemotherapy (according to IGCCCG risk classification) followed by the judicious surgical removal of residual masses represent the cornerstone of therapy. Poor-risk patients and those failing a first-line therapy should be referred to specialized tertiary centers. Paclitaxel-based conventional chemotherapy and high-dose chemotherapy plus autologous hematopoietic support can cure a proportion of patients with relapsing or refractory disease.
Deletion of the RGD motif from the penton base in oncolytic adenoviruses enhances antitumor efficacy of combined CAR T cell therapy
(Elsevier, 2024-09-19) Morales-Molina, Alvaro; Rodriguez-Milla, Miguel A; García-Rodriguez, Patricia; Hidalgo, Laura; Alemany, Ramon; Garcia-Castro, Javier; National Institutes of Health Sciences (Japón); Instituto de Salud Carlos III; Unión Europea. Comisión Europea. NextGenerationEU; Plan de Recuperación, Transformación y Resiliencia (España); Plan Estatal de Investigación Científica y Técnica y de Innovación; Comunidad de Madrid (España); Fundación Oncohematología Infantil; Asociación de Familias de Niños con Cáncer de Castilla-La Mancha; Asociación Pablo Ugarte contra el cáncer infantil
Oncolytic viruses often face challenges in achieving optimal antitumor immunity as standalone therapies. The penton base RGD-integrin interactions play a significant role in wild-type adenovirus-induced innate immune responses. To modify these responses, we present ISC301, a novel oncolytic adenovirus engineered by deleting the natural RGD motifs in the penton base while incorporating artificial RGD motifs in the fiber knobs. ISC301 demonstrated comparable infectivity, cytotoxic effects, and signaling profiles across various cell types to its parental ICOVIR-5, which retains the penton base RGD motif. In immunodeficient and immunocompetent mouse models, ISC301 exhibited similar antitumor efficacy to ICOVIR-5. However, ISC301 induced higher intratumoral inflammation through NF-κB activation, leading to increased levels of tumor-infiltrating leukocytes and higher proportion of cytotoxic CD8 T cells. In addition, ISC301 elicits a heightened pro-inflammatory response in peripheral blood. Importantly, when combined with CAR T cell therapy, ISC301 exhibited superior antitumor efficacy, surpassing monotherapy outcomes. These findings emphasize the impact of adenoviral modifications on antitumor immune responses. The deletion of penton base RGD motifs enhances ISC301's pro-inflammatory profile and boosts CAR T cell therapy efficacy. This study enhances understanding of oncolytic virus engineering strategies, positioning ISC301 as a promising candidate for combined immunotherapeutic approaches in cancer treatment.
Microbial Phenolic Metabolites Are Associated with Improved Cognitive Health
(Wiley, 2024-01) Domínguez-López, Inés; Galkina, Polina; Parilli-Moser, Isabella; Arancibia-Riveros, Camila; Martínez-González, Miguel Ángel; Salas-Salvado, Jordi; Corella, Dolores; Malcampo, Mireia; Martínez, J Alfredo; Tojal-Sierra, Lucas; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, José; Estruch, Ramon; Tinahones, Francisco J; Santos-Lozano, José Manuel; Serra-Majem, Lluis; Bueno-Cavanillas, Aurora; Tur, Josep A; Rubín-García, María; Pintó, Xavier; Fernández-Aranda, Fernando; Delgado-Rodríguez, Miguel; Barabash-Bustelo, Ana; Vidal, Josep; Vazquez, Clotilde; Daimiel, Lidia; Ros, Emilio; Toledo, Estefanía; Atzeni, Alessandro; Asensio, Eva M; Vera, Natàlia; Garcia-Rios, Antonio; Torres-Collado, Laura; Pérez-Farinós, Napoleón; Zulet, Marian; Chaplin, Alice; Casas, Rosa; Martín-Peláez, Sandra; Vaquero-Luna, Jessica; Gómez-Pérez, Ana Maria; Vazquez-Ruiz, Zenaida; Shyam, Sangeetha; Ortega-Azorín, Carolina; Talens, Natàlia; Peña-Orihuela, Patricia J; Oncina-Canovas, Alejandro; Diez-Espino, Javier; Babio, Nancy; Fitó, Montserrat; Lamuela-Raventós, Rosa M
Scope: Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk. Methods and results: A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores. Conclusions: These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population.
Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population
(Springer, 2024-01-13) Baenas, I; Camacho-Barcia, L; Granero, R; Razquin, C; Corella, D; Gómez-Martínez, Carlos; Castañer-Niño, O; Martínez, JA; Alonso-Gómez, ÁM; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, J; Estruch, R; Tinahones, Francisco J; Lapetra, J; Serra-Majem, Lluis; Cano-Ibáñez, N; Tur, Josep A; Martín-Sánchez, V; Pintó, X; Gaforio, J J; Matía-Martín, P; Vidal, Josep; Vazquez, Clotilde; Daimiel, L; Ros, Emilio; Jiménez-Murcia, S; Dalsgaard, S; Garcia-Arellano, A; Babio, N; Sorli, Jose V; Lassale, C; García-de-la-Hera, M; Gómez-García, E; Zulet, MA; Konieczna, Jadwiga; Martín-Peláez, S; Tojal-Sierra, Lucas; Basterra-Gortari, FJ; de Las Heras-Delgado, S; Portoles, O; Muñoz-Pérez, MÁ; Arenas-Larriva, AP; Compañ-Gabucio, L; Eguaras, S; Shyam, Sangeetha; Fitó, M; Baños, RM; Salas-Salvado, Jordi; Fernández-Aranda, F
Objectives: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. Methods: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. Results: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. Conclusions: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.
In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-01-16) Escarrer-Garau, Gabriel; Martín-Medina, Aina; Truyols-Vives, Joan; Gómez-Bellvert, Cristina; Elowsson, Linda; Westergren-Thorsson, Gunilla; Molina-Molina, Maria; Mercader-Barceló, Josep; Sala Llinàs, Ernest
Lung-resident mesenchymal stem cells (LR-MSC) are thought to participate in idiopathic pulmonary fibrosis (IPF) by differentiating into myofibroblasts. On the other hand, LR-MSC in IPF patients present senescence-related features. It is unclear how they respond to a profibrotic environment. Here, we investigated the profibrotic response of LR-MSC isolated from IPF and control (CON) patients. LR-MSC were inoculated in mice 48 h after bleomycin (BLM) instillation to analyze their contribution to lung damage. In vitro, LR-MSC were exposed to TGFβ. Mice inoculated with IPF LR-MSC exhibited worse maintenance of their body weight. The instillation of either IPF or CON LR-MSC sustained BLM-induced histological lung damage, bronchoalveolar lavage fluid cell count, and the expression of the myofibroblast marker, extracellular matrix (ECM) proteins, and proinflammatory cytokines in the lungs. In vitro, IPF LR-MSC displayed higher basal protein levels of aSMA and fibronectin than CON LR-MSC. However, the TGFβ response in the expression of TGFβ, aSMA, and ECM genes was attenuated in IPF LR-MSC. In conclusion, IPF LR-MSC have acquired myofibroblastic features, but their capacity to further respond to profibrotic stimuli seems to be attenuated. In an advanced stage of the disease, LR-MSC may participate in disease progression owing to their limited ability to repair epithelial damage.
Ultra-processed foods consumption as a promoting factor of greenhouse gas emissions, water, energy, and land use: A longitudinal assessment
(Elsevier, 2023-05-24) Garcia, Silvia; Pastor, Rosario; Monserrat-Mesquida, Margalida; Álvarez-Álvarez, Laura; Rubín-García, María; Martínez-González, Miguel Ángel; Salas-Salvado, Jordi; Corella, Dolores; Fito, Montserrat; Martínez, J Alfredo; Tojal-Sierra, Lucas; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, José; Estruch, Ramon; Tinahones, Francisco J; Santos-Lozano, José Manuel; Serra-Majem, Lluis; Cano-Ibañez, Naomi; Pintó, Xavier; Delgado-Rodriguez, Miguel; Matía-Martín, Pilar; Vidal, Josep; Vazquez, Clotilde; Daimiel, Lidia; Ros, Emilio; Buil-Cosiales, Pilar; Martínez-Rodríguez, María Ángeles; Coltell, Oscar; Castañer, Olga; Garcia-Rios, Antonio; Barceló Cañellas, María de la Concepión; Gómez-Gracia, Enrique; Zulet, Maria Ángeles; Konieczna, Jadwiga; Casas, Rosa; Massó-Guijarro, Paloma; Goicolea-Güemez, Leire; Rosa Bernal-Lopez, Maria; Bes-Rastrollo, Maira; Shyam, Sangeetha; González, José I; Zomeño-Fajardo, María Dolores; Peña-Orihuela, Patricia J; González-Palacios, Sandra; Toledo, Estefanía; Khoury, Nadine; Perez, Karla Alejandra; Martín-Sánchez, Vicente; Tur, Josep A; Bouzas, Cristina
Background: Dietary patterns can produce an environmental impact. Changes in people's diet, such as the increased consumption of ultra-processed food (UPF) can not only influence human health but also environment sustainability. Objectives: Assessment of the impact of 2-year changes in UPF consumption on greenhouse gas emissions and water, energy and land use. Design: A 2-year longitudinal study after a dietary intervention including 5879 participants from a Southern European population between the ages of 55-75 years with metabolic syndrome. Methods: Food intake was assessed using a validated 143-item food frequency questionnaire, which allowed classifying foods according to the NOVA system. In addition, sociodemographic data, Mediterranean diet adherence, and physical activity were obtained from validated questionnaires. Greenhouse gas emissions, water, energy and land use were calculated by means of the Agribalyse® 3.0.1 database of environmental impact indicators for food items. Changes in UPF consumption during a 2-year period were analyzed. Statistical analyses were conducted using computed General Linear Models. Results: Participants with major reductions in their UPF consumption reduced their impact by -0.6 kg of CO2eq and -5.3 MJ of energy. Water use was the only factor that increased as the percentage of UPF was reduced. Conclusions: Low consumption of ultra-processed foods may contribute to environmental sustainability. The processing level of the consumed food should be considered not only for nutritional advice on health but also for environmental protection. Trial registration: ISRCTN, ISRCTN89898870. Registered 05 September 2013, http://www.isrctn.com/ISRCTN89898870.
The CARBA-MAP study: national mapping of carbapenemases in Spain (2014-2018)
(Frontiers Media, 2023) Gracia-Ahufinger, Irene; López-González, Laura; Vasallo, Francisco José; Galar, Alicia; Siller, María; Pitart, Cristina; Bloise, Iván; Torrecillas, Miriam; Gijón-Cordero, Desirée; Viñado, Belén; Castillo-García, Javier; Campo, Rainer; Mulet, Xavier; Madueño-Alonso, Ana; Chamizo-López, Francisco Javier; Arrastia-Erviti, Maitane; Galán-Sánchez, Fátima; Fernández-Quejo, Melisa; Rodríguez-Díaz, Juan Carlos; Gutiérrez-Zufiaurre, María Nieves; Rodríguez-Maresca, Manuel Angel; Ortega-Lafont, María Del Pilar; Yague-Guirao, Genoveva; Chaves-Blanco, Lucía; Colomina-Rodríguez, Javier; Vidal-Acuña, María Reyes; Portillo, María Eugenia; Franco-Álvarez de Luna, Francisco; Centelles-Serrano, María José; Azcona-Gutiérrez, José Manuel; Delgado-Iribarren García Campero, Alberto; Rey-Cao, Sonia; Muñoz, Patricia; Calvo-Montes, Jorge; Zboromyrska, Yuliya; Grandioso, David; Càmara, Jordi; Cantón, Rafael; Larrosa-Escartín, Nieves; Díaz-Regañón, Jazmín; Martínez-Martínez, Luis
Introduction: Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018. Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0. Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017-2018 compared to 2014-2016. Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms.
Sex differences in the comorbidity of patients seeking a first treatment for Alcohol Use Disorder
(Springer, 2023) García-Marchena, Nuria; Sanvisens, Arantza; Abellí-Deulofeu, Enric; Blanes, Rafael; Torrens, Marta; Miquel, Laia; Rubio, Gabriel; Bolao, Ferran; Muga, Robert; Zuluaga, Paola; Fuster, Daniel; Hernández-Rubio, Anna; Farre, Magi; Papasseit, Esther; Pérez-Mañá, Clara; Poyatos, Lourdes; Moranta, Catalina; Sion, Ana; Ortega, Lluisa; Bruguera, Pol; Caballeria, Elsa; Messeguer, Ana; Fonseca, Francina; Mestre-Pinto, Joan-Ignasi; Alías, María; Dinamarca, Fernando; Rodríguez-Fonseca, Fernando; Pavón-Morón, Francisco Javier; Marcos, Miguel; Martín, Candelaria; Pérez-Hernández, Onán; Manzanares, Jorge; Navarrete, Francisco; Gasparyan, Ani
Background: The CohRTA multicenter study aims to characterize patients undergoing a first treatment for alcohol use disorder (AUD). The objective is to analyze sex-specific differences in the comorbidity of AUD when starting the first treatment for the disorder. Methods: A multicenter study was carried out between 2014 and 2021 in 6 public centers in Spain. Sociodemographic characteristics were collected, variables related to alcohol consumption, medical comorbidity according to Cumulative Illness Rating Scale-Substance Abuse (CIRS-SA), antecedent of psychiatric comorbidity, general blood test and screening for drugs in urine. Logistic regression models were used to establish associations. Results: A total of 896 patients (634 M, 262 W) were included. Median age at admission was 48 years [IQR:41ﾖ56 years]. Men reported beginning regular alcohol consumption at an earlier age and drank more alcohol. The most frequent medical comorbidities were hepatic, respiratory, vascular and neurological. The median number of affected systems was three, with no differences between men and women. However, depressive disorder was more frequent in women. In the multivariate analysis, women were up to 4 times more likely to have a major depressive disorder, elevated ESR and elevated total cholesterol than men. Men started alcohol consumption earlier, had a higher body mass index (BMI), a higher probability of using cocaine and a higher frequency of GGT and bilirubin alteration than women. Conclusion: Differences by sex were found among individuals beginning first treatment for AUD. These differences must be taken into account when designing specific therapeutic strategies for men and women.

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