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Articles publicats en revistes (Ciències Clíniques)

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    Prenatal phenol exposure and child behaviour: insights into the hypothalamic-pituitary-adrenal axis from two prospective mother-child cohorts
    (2025-12-09) Rolland, Matthieu; Bustamante Pineda, Mariona; Jedynak, Paulina; Thomsen, Cathrine; Sakhi, Amrit K.; Foraster, Maria; Gascón, Mireia; Gómez Roig, Ma. Dolores; Llurba Olivé, Elisa; Rivas, Ioar; Ouellet-Morin, Isabelle; Ferrer, Muriel; Morillas, Alex; Carras, Sylvain; Bayat, Sam; Lyon-Caen, Sarah; Pozo, Oscar J.; Vrijheid, Martine; Sunyer, Jordi; Slama, Rémy; Dadvand, Payam; Philippat, Claire
    Background: Synthetic phenols are widely used chemicals with potential neurodevelopmental toxicity. Human studies are often limited by small sample sizes and exposure misclassification. Identifying the biological pathways affected by these substances is crucial for understanding key drivers of toxicity. We aimed to study associations between prenatal exposure to synthetic phenols and child behaviour, exploring the potential mediating role of maternal steroid hormones. Methods: We pooled data from two European cohorts: the Barcelona Life Study Cohort (BiSC; Barcelona, Spain, 2018-21, N=1080) and Suivi de l'Exposition à la Pollution Atmosphérique durant la Grossesse et Effets sur la Santé (SEPAGES; Grenoble, France, 2014-17, N=484). Mothers older than 18 years having a singleton pregnancy of less than 19 weeks gestational age were eligible for inclusion in the cohorts; those having multiple pregnancies were excluded. Repeated urine samples (up to 24 in BiSC; up to 42 in SEPAGES) collected in the second and third trimesters were pooled and analysed for 12 synthetic phenols. Child behavioural outcomes were assessed at 18 months in BiSC and 24 months in SEPAGES using the Child Behavior Checklist for Ages 1·5-5 (CBCL). Concentrations of total cortisol, total cortisone, and 11-dehydrocorticosterone-steroid hormones involved in the hypothalamic-pituitary-adrenal axis-were measured from maternal hair samples. Associations between phenol exposure and behavioural outcomes were estimated by adjusted linear regression analysis, and mediation by steroid hormones was assessed with regression-based causal mediation analysis within the counterfactual framework. Findings: 1024 mother-child pairs were included in the study: 607 from BiSC and 417 from SEPAGES. Maternal exposure to methylparaben in the third trimester of pregnancy was associated with higher internalising scores (change in score of 0·44 [95% CI 0·10-0·79] points) and externalising scores (0·67 [0·12-1·24]) in the CBCL. In boys, maternal exposure to bisphenol S in the third trimester was linked to increased internalising scores (0·92 [0·15 to 1·75]; p=0·019) and could be linked to increased externalising scores (1·14 [-0·09 to 2·44]; p=0·070). In girls, second-trimester butylparaben and propylparaben exposure were associated with lower internalising (-1·03 [-1·84 to -0·09], p=0·033) and externalising (-0·68 [-1·23 to -0·12]; p=0·019) scores. No mediation by steroid hormones was observed. Interpretation: Prenatal exposure to phenols might influence early behavioural development, with sex-specific patterns. There was no strong evidence of mediation by maternal steroid hormones, suggesting the involvement of alternative pathways in the biological effects of phenols. Together with previous findings, these results highlight the need for stricter regulation of these compounds to reduce prenatal exposure.
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    The use of lymphocyte-depleting antibodies in specific populations of kidney transplant recipients: A systematic review and meta-analysis
    (Elsevier, 2023-09-27) Montero Pérez, Núria; Rodrigo, Emilio; Crespo Barrio, Marta; Cruzado, Josep Ma.; Gutierrez Dalmau, Alex; Mazuecos Blanca, María Auxiliadora; Sancho Calabuig, Maria Asuncion; Belmar Vega, Lara; Calatayud Aristoy, Emma; Mora Lopez, Paula; Oliveras, Laia; Solà, Eulàlia; Villanego, Florentino; Pascual, Julio (Pascual Santos)
    Background: Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic review aims to reevaluate, based on actual studies, the effects of different antibody preparations when used in specific KTR subgroups. Methods: We searched MEDLINE and CENTRAL and selected randomized controlled trials (RCT) and observational studies looking at different antibody preparations used as induction in KTR. Comparisons were categorized into different KTR subgroups: standard, high risk of rejection, high risk of delayed graft function (DGF), living donor, and elderly KTR. Two authors independently assessed the risk of bias. Results: Thirty-seven RCT and 99 observational studies were finally included. Compared to anti-interleukin-2-receptor antibodies (IL2RA), anti-thymocyte globulin (ATG) reduced the risk of acute rejection at two years in standard KTR (RR 0.74, 95%CI 0.61-0.89) and high risk of rejection KTR (RR 0.55, 95%CI 0.43-0.72), but without decreasing the risk of graft loss. We did not find significant differences comparing ATG vs. alemtuzumab or different ATG dosages in any KTR group. Conclusions: Despite many studies carried out on induction treatment in KTR, their heterogeneity and short follow-up preclude definitive conclusions to determine the optimal induction therapy. Compared with IL2RA, ATG reduced rejection in standard-risk, highly sensitized, and living donor graft recipients, but not in high DGF risk or elderly recipients. More studies are needed to demonstrate beneficial effects in other KTR subgroups and overall patient and graft survival.
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    Impact on delay times and characteristics of patients undergoing primary percutaneous coronary intervention in the southern metropolitan area of Barcelona after implementation of the infarction code program
    (Elsevier España, 2012-10) Gómez Hospital, Joan Antoni; Cequier Fillat, Àngel R.; Dallaglio, Paolo D.; Sánchez Salado, Jose Carlos; Ariza Solé, Albert; Homs, Silvia; Lorente, Victòria; Ferreiro Gutiérrez, José Luis; Gómez Lara, Josep; Romaguera, Rafael; Salazar Mendiguchía, Joel; Teruel Gila, Luis Miguel
    [eng] A standardized protocol of emergent transfer for primary percutaneous coronary intervention for patients with ST elevation myocardial infarction, defined as the Infarction Code, was implemented in June 2009 in the Catalan regional health system. The objective of this study was to evaluate the impact of the new protocol on delay times, number of procedures and clinical characteristics compared with the previous period in the population of patients referred to our hospital. Methods All consecutive patients undergoing primary percutaneous coronary intervention in our hospital were prospectively registered. The clinical characteristics, delay times and mortality in the follow-up of the protocol implementation period (June 2009-May 2010) were analyzed and compared with the previous year (June 2008-May 2009). Results During the protocol period, 514 patients were included, compared with 241 in the previous year. Age, cardiovascular risk factors, anterior myocardial infarction and procedure characteristics were similar in the 2 groups. The first medical contact to balloon time was lower in the protocol period (median time 120 min vs 88 min; P<.001). Patients in the protocol period showed a trend toward less severe disease (Killip III, rescue angioplasty). The multivariate regression analysis showed a significant association between 1-year mortality and age, Killip class≥III at admission, anterior infarction and 3-vessel disease. Conclusions The introduction of the Infarction Code program increased the number of patients treated by primary percutaneous coronary intervention with a reduction in delay times and better clinical characteristics at presentation.
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    Participant selection for lung cancer screening using primary care electronic medical records: The Catalan scenario
    (Elsevier España, 2025-11-18) Marzo Castillejo, Mercè; Mascort Roca, Juanjo; Brau Tarrida, Albert; Carrasco Ribelles, Lucía A.; Monteagudo Zaragoza, Mònica; Guiriguet Capdevila, Carolina; Espinàs Piñol, Josep Alfons; Cabrera Godoy, Olivia; Borràs Andrés, Josep Maria
    Objective: To assess the feasibility of using primary care electronic health records (EHRs) and the PLCOm2012noRace lung cancer (LC) risk prediction model to identify high-risk individuals in the Catalan population. Design: Population-based cohort study. SITE: Catalonia, using data from the Information System for the Improvement of Research in Primary Care (SIDIAP), which covers approximately 80% of the population. Participants: A total of 1,998,282 individuals aged 55-79 years were initially considered, with data spanning from 2012 to 2023. After applying inclusion and exclusion criteria based on smoking status, 24,294 individuals with complete smoking history were included. Interventions: Estimation of LC risk using the PLCOm2012noRace model. Main measurements: Variables: age, smoking history, body mass index, educational level, chronic obstructive pulmonary disease, personal history of cancer, and family history of LC. A 6-year risk threshold of ≥2.6% was used to define eligibility for LC screening. Results: Overall, 18.6% of individuals exceeded the risk threshold, with higher prevalence in men (21.4%) and those aged 60-79 years (23.8%). Current smokers had the highest risk (25.7%), which decreased with time since quitting. On average, high-risk individuals could have been identified 4.29 years before. Conclusions: The use of EHRs and the PLCOm2012noRace model is a feasible approach to identify individuals at high risk of LC in the Catalan population. However, missing or outdated data, especially regarding smoking intensity, may limit the predictive performance. These findings highlight the need for systematic and timely data collection to support effective risk-based screening strategies.
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    Effect of a nutritional intervention based on an energy-reduced Mediterranean diet on environmental impact
    (Elsevier B.V., 2024-06-10) Cano Ibáñez, Naomi; Álvarez-Álvarez, Laura; Rubín García, María; Vitelli Storelli, Facundo; García, Sílvia; Bouzas, Cristina; Martínez González, Miguel Ángel, 1957-; Corella Piquer, Dolores; Salas Salvadó, Jordi; Malcampo, Mireia; Martínez, J. Alfredo; Alonso Gómez, Ángel M.; Wärnberg, Julia; Vioque, Jesús; Romaguera, Dora; López Miranda, José; Estruch Riba, Ramon; Tinahones, Francisco J.; Lapetra, José; Serra Majem, Lluís; Bueno Cavanillas, Aurora; García Fernández, Camino; Pintó Sala, Xavier; Delgado Rodríguez, Miguel; Matía Martín, Pilar; Vidal i Cortada, Josep; Vázquez, Clotilde; Daimiel, Lidia; Ros Rahola, Emilio; Garcia-Arellano, Ana; Martínez Rodríguez, María Ángeles; Sorlí, José V.; Zomeño Fajardo, María Dolores; García Rios, Antonio; González Palacios, Sandra; Monserrat Mesquida, Margalida; Abete, Itziar; Colom Fernández, Antoni; Casas Rodríguez, Rosa M.; Ugarriza, Lucía; Bernal López, M. Rosa; Bes Rastrollo, Maira; Paz Graniel, Indira; Asensio, Eva M.; Fitó Colomer, Montserrat; Arenas Larriva, Antonio P.; Oncina Cánovas, Alejandro; Vázquez Ruiz, Zenaida; Fernández de la Puente, María; Pérez Vega, Karla Alejandra; Tur Marí, Josep A. (Josep Antoni); Martín Sánchez, Vicente
    Objective: To estimate the environmental impact of a dietary intervention based on an energy-reduced Mediterranean diet (MedDiet) after one year of follow-up. Methods: Baseline and 1-year follow-up data were used for 5800 participants aged 55-75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT-Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate to what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact. Results: We observed a significant reduction in the intervention group compared to the control group in acidification levels (-13.3 vs. -9.9 g SO2-eq), eutrophication (-5.4 vs. -4.0 g PO4-eq) and land use (-2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %. Conclusions: A nutritional intervention based on consumption of an energy-reduced MedDiet for one year was associated with an improvement in different environmental quality parameters.
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    Ibrutinib followed by ofatumumab consolidation in previously untreated patients with chronic lymphocytic leukemia (CLL): GELLC-7 trial from the Spanish group of CLL (GELLC)
    (Elsevier, 2024-05-25) Abrisqueta Costa, Pau; González Barca, Eva; Ferrà, Christelle; Rios-Herranz, Eduardo; Fernández de la Mata, Margarita; Delgado, Julio (Delgado González); Andreu, Rafael; Hernandez Rivas, Jose Angel; Terol, María José; Navarro-Bailón, Almudena; Vidriales, Belén; Baltasar, Patricia; De la Serna, Javier; Ramírez, Ángel; Ballester, Carmen; Moreno, Carol; García-Marco, José Antonio; Córdoba, Raúl; Yáñez, Lucrecia; Casado, Luís Felipe; González, Marcos; Bosch Albareda, Francesc
    Background: BTK inhibitors have been concurrently administered with anti-CD20 monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL). However, the optimal regimen for combining these two drugs remains pending. Methods: This multi-center phase 2 study aimed to analyze whether consolidation with ofatumumab improved the response in patients with CLL receiving front-line treatment with ibrutinib. Patients received 12 cycles of ibrutinib monotherapy. Those who achieved CR after this induction were maintained on ibrutinib. Conversely, those who did not attain CR continued with ibrutinib in addition to a consolidation, which involved 7 doses of ofatumumab. The primary objective was the complete response (CR) rate at cycle 20. This study is registered within the EU Clinical Trials Register (EudraCT 2016-004937-26). Findings: Between September 8, 2017, and May 21, 2018, 84 patients (median age, 69 years) were included. After completion of 12 cycles of ibrutinib (n = 80), 4 patients (5%) were in CR, 67 (84%) in partial response (PR), and 6 patients (7%) had a PR with lymphocytosis (PRL). After consolidation with ofatumumab, 20 patients improved the response from PR to CR and 6 patients with PRL obtained a PR. Seventy-one patients (85%) completed 20 cycles of treatment, with a CR rate of 24/71 (34%). According to the intention-to-treat analysis at cycle 20, the ORR was 69/84 (82.2%), with a CRR of 24/84 (28.6%). Progression-free survival and overall survival at 48-months were 89.9% (CI: 82.4-95.5) and 92.2% (CI: 85.3-97.1), respectively. Interpretation: These findings underscore the potential for a consolidation strategy in CLL, wherein the addition of a mAb in patients with low tumor burden might enhance the quality of the response.
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    Insulin and disorders of behavioural flexibility
    (Elsevier, 2023-04-27) Scholtz, Samantha; Glennon, Jeffrey C.; Sullivan, Mairead; Fernández Aranda, Fernando; Camacho Barcia, Lucía; Harkin, Andrew; Macrì, Simone; Mora Maltas, Bernat; Jiménez-Murcia, Susana; O'Leary, Aet; Ottomana, Angela Maria; Presta, Martina; Slattery, David
    Behavioural inflexibility is a symptom of neuropsychiatric and neurodegenerative disorders such as Obsessive-Compulsive Disorder, Autism Spectrum Disorder and Alzheimer's Disease, encompassing the maintenance of a behaviour even when no longer appropriate. Recent evidence suggests that insulin signalling has roles apart from its regulation of peripheral metabolism and mediates behaviourally-relevant central nervous system (CNS) functions including behavioural flexibility. Indeed, insulin resistance is reported to generate anxious, perseverative phenotypes in animal models, with the Type 2 diabetes medication metformin proving to be beneficial for disorders including Alzheimer's Disease. Structural and functional neuroimaging studies of Type 2 diabetes patients have highlighted aberrant connectivity in regions governing salience detection, attention, inhibition and memory. As currently available therapeutic strategies feature high rates of resistance, there is an urgent need to better understand the complex aetiology of behaviour and develop improved therapeutics. In this review, we explore the circuitry underlying behavioural flexibility, changes in Type 2 diabetes, the role of insulin in CNS outcomes and mechanisms of insulin involvement across disorders of behavioural inflexibility.
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    Prognostic impact of chronic total occlusion in a nonculprit artery in patients with acute myocardial infarction undergoing primary angioplasty.
    (Elsevier España, 2014-05-01) Ariza Solé, Albert; Teruel Gila, Luis Miguel; Marco, Andrea di; Lorente, Victòria; Sánchez Salado, Jose Carlos; Sánchez Elvira, Guillermo; Romaguera, Rafael; Gómez Lara, Josep; Gómez Hospital, Joan Antoni; Cequier Fillat, Àngel R.
    [eng] Introduction and objectives: The prognostic value of chronic total occlusion in nonculprit coronary arteries in patients with myocardial infarction undergoing primary angioplasty remains controversial. Several publications have described different methodologies and conflicting findings. In addition, causes of death were not reported. Our aim is to analyze the prognostic impact of chronic total occlusion in nonculprit coronary arteries and the role of left ventricular ejection fraction in this analysis. Methods: Prospective inclusion of consecutive patients with ST-segment elevation myocardial infarction who underwent primary angioplasty. We recorded baseline characteristics, in-hospital clinical course, and mortality and its causes during follow-up. We assessed the impact of chronic total occlusion on mortality using Cox regression analysis. Results: Chronic total occlusion in nonculprit arteries was present in 125 of 1176 patients (10.6%); in 79 of these 125 patients, chronic total occlusion was present in the proximal segments. The mean follow-up was 339 days; 64 (5.8%) patients died during the first 6 months. Patients with chronic total occlusions had more comorbidities, poorer ventricular function, and higher mortality (hazard ratio=2.79; 95% confidence interval, 1.71-4.56). Chronic total occlusion was also associated with noncardiac death (hazard ratio=3.83; 95% confidence interval, 2.10-7.01). Chronic total occlusion in proximal segments was associated with both cardiac (hazard ratio=3.22; 95% confidence interval, 1.42-7.30) and noncardiac deaths (hazard ratio=3.43; 95% confidence interval, 1.67-7.06). The multivariate analysis performed without including left ventricular ejection fraction showed a significant association between chronic total occlusion and mortality. However, when left ventricular ejection fraction was included in the analysis, this association was nonsignificant (hazard ratio=1.76; 95% confidence interval, 0.85-3.65; P=.166). Conclusions: Chronic total occlusion in this clinical setting identified patients at higher risk with more comorbidities and higher mortality, but did not behave as an independent predictor of mortality when left ventricular ejection fraction was included in the analysis.
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    Is it possible to separate ischemic and bleeding risk in patients with non-ST segment elevation acute coronary syndromes?
    (Elsevier B.V., 2014-02-15) Ariza Solé, Albert; Sánchez Salado, Jose Carlos; Lorente, Victòria; Sánchez Elvira, Guillermo; Muntané, Guillem; Salazar Mendiguchía, Joel; Cequier Fillat, Àngel R.
    Both intensive antithrombotic therapy and an early invasive strategy reduce the incidence of ischemic events in patients with non-ST segment elevation acute coronary syndromes (NSTE-ACS), at the expense of increasing the rate of bleeding complications. Current recommendations [1] emphasize the use of an early invasive strategy in patients at higher risk. However, most registries show a more conservative management in these patients
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    Efficacy of Bleeding Risk Scores in Elderly Patients With Acute Coronary Syndromes
    (Elsevier España, 2014-06) Ariza Solé, Albert; Formiga Pérez, Francesc; Lorente, Victòria; Sánchez Salado, Jose Carlos; Sánchez Elvira, Guillermo; Roura Ferrer, Gerard; Sánchez Prieto, Remedios; Vila Sala, Maria; Moliner Borja, Pedro; Cequier Fillat, Àngel R.
    [eng] The incidence of acute coronary syndromes is high in the elderly population. Bleeding is associated with a poorer prognosis in this clinical setting. The available bleeding risk scores have not been validated specifically in the elderly. Our aim was to assess predictive ability of the most important bleeding risk scores in patients with acute coronary syndrome aged >= 75 years. Methods: We prospectively included consecutive acute coronary syndromes patients. Baseline characteristics, laboratory findings, and hemodynamic data were collected. In-hospital bleeding was defined according to CRUSADE, Mehran, ACTION, and BARC definitions. CRUSADE, Mehran, and ACTION bleeding risk scores were calculated for each patient. The ability of these scores to predict major bleeding was assessed by binary logistic regression, receiver operating characteristic curves, and area under the curves. Results: We included 2036 patients, with mean age of 62.1 years; 369 patients (18.1%) were >= 75 years. Older patients had higher bleeding risk (CRUSADE, 42 vs 22; Mehran, 25 vs 15; ACTION, 36 vs 28; P<.001) and a slightly higher incidence of major bleeding events (CRUSADE bleeding, 5.1% vs 3.8%; P=.250). The predictive ability of these 3 scores was lower in the elderly (area under the curve, CRUSADE: 0.63 in older patients, 0.81 in young patients; P = .027; Mehran: 0.67 in older patients, 0.73 in younger patients; P = .340; ACTION: 0.58 in older patients, 0.75 in younger patients; P = .041). Conclusions: Current bleeding risk scores showed poorer predictive performance in elderly patients with acute coronary syndromes than in younger patients.
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    CRUSADE bleeding risk score validation for ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention
    (Elsevier Ltd., 2013-10-10) Ariza Solé, Albert; Sánchez Elvira, Guillermo; Sánchez Salado, Jose Carlos; Lorente-Tordera, Victoria; Salazar Mendiguchía, Joel; Sánchez Prieto, Remedios; Romaguera-Torres, Rafael; Ferreiro Gutiérrez, José Luis; Gómez Hospital, Joan Antoni; Cequier Fillat, Àngel R.
    Introduction: The CRUSADE bleeding risk score (CBRS) accurately predicts major bleeding in non-ST segment elevation myocardial infarction NSTEMI patients. However, little information exists about its application in ST segment elevation myocardial infarction STEMI. We aimed to assess the ability of CBRS to predict in-hospital major bleeding in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Materials and methods: We prospectively analyzed consecutive STEMI patients undergoing PPCI. Baseline characteristics, in-hospital complications and mid term mortality were recorded. Major bleeding was defined by the CRUSADE definition. Predictive ability of the CBRS was assessed by logistic regression method and the area under the ROC curve (AUC). Results: We included 1064 patients (mean age 63years). Mean CBRS value was 24. Most of patients (740/1064 (69.6%)) were in the two lowest risk quintiles of CBRS. Incidence of in-hospital major bleeding was 33/1064 (3.1%). The rates of in-hospital bleeding across the quintiles of risk groups were 0.4% (very low risk), 2.6% (low), 4.6% (moderate), 7.2% (high), and 13.4% (very high) (p 0.001). AUC was 0.80 (95% CI 0.73-0.87 p 0.001). In patients with radial access angiography (n=621) AUC was 0.81 (95% CI: 0.65-0.97). Mean follow up was 344days. Patients with bleeding events had higher mortality during follow up (HR 6.91; 95% CI 3.72-12.82; p 0.001). Conclusions: Our patients had a significantly lower bleeding risk as compared to CRUSADE NSTEMI population. CBRS accurately predicted major in-hospital bleeding in this different clinical scenario, including patients with radial artery approach.
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    Early anticoagulation may improve preprocedural patency of the infarct-related artery in primary percutaneous coronary intervention.
    (Elsevier España, 2013-02-01) Ariza Solé, Albert; Ferreiro Gutiérrez, José Luis; Sánchez Salado, Jose Carlos; Lorente, Victòria; Gómez Hospital, Joan Antoni; Cequier Fillat, Àngel R.
    The aim of this study was to evaluate the impact of early administration of anticoagulation therapy (at diagnosis) compared with its application in the cardiac catheterization laboratory at the start of the procedure on the initial patency of the infarct-related artery (IRA) in patients undergoing pPCI as a reperfusion strategy.
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    Geriatric assessment for predicting outcomes among patients with aortic stenosis undergoing transcatheter aortic valve implantation
    (Tsinghua University Press, 2025-12-01) Calvo, Elena; Castillo, P.; Romaguera, Rafael; Llaó, Isaac; Zafrilla Nieto, Raquel; Domene, Gerard; Alegre Canals, Oriol; Lorente, Victòria; Muntané Carol, Guillem; Formiga Pérez, Francesc; Cuerda Llorente, Francisco Javier de la; Gómez Hospital, Joan Antoni; Ariza Solé, Albert
    Background There is scarce data about comparisons between geriatric assessment tools in patients with aortic stenosis (AS). We aimed to describe the geriatric profile of patients with AS undergoing transcatheter aortic valve implantation (TAVI) and to analyze the ability of different tools for predicting clinical outcomes in this context. Methods This was a single center retrospective registry including patients with AS undergoing TAVI and surviving to hospital discharge. The primary endpoint was all-cause mortality or need for urgent readmission one year after TAVI. Results A total of 377 patients were included (mean age of 80.4 years). Most patients were independent or mildly dependent, with an optimal cognitive status. The proportion of frailty ranged from 17.6% to 49.8%. A total of 20 patients (5.3%) died and 110/377 patients (29.2%) died or were readmitted during follow up. Overall, most components of the geriatric assessment showed an association with clinical outcomes. Disability for instrumental activities showed a significant association with mortality and a strong association with the rate of mortality or readmission. The association between frailty and clinical outcomes was higher for short physical performance battery (SPPB), essential frailty toolset (EFT) and the frailty index based on comprehensive geriatric assessment (IF-VIG) and lower for Fried criteria and FRAIL scale. Conclusions AS patients from this series presented a good physical performance, optimal cognitive status and a reasonably low prevalence of frailty. The best predictive ability was observed for disability for instrumental activities and frailty as measured by the EFT, SPPB and the IF-VIG.
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    Time from symptoms onset to remdesivir is associated with the risk of ICU admission: a multicentric analyses
    (BioMed Central, 2023-05-04) Alonso Navarro, Rodrigo; Ramírez, Margarita; Masiá, Mar; Paredes, Roger; Montejano, Rocío; Povar Echeverria, Marina; Carratalà, Jordi; Salavert, Miguel; Bernal, Enrique; Dueñas, Carlos; Flores, Juan; Fanjul, Francisco; Gutiérrez, Isabel; Rico, Verónica; Mateu, Lourdes; Cadiñanos, Julen; Berenguer Berenguer, Juan; Soriano, Alex
    Background Shorter duration of symptoms before remdesivir has been associated with better outcomes. Our goal was to evaluate variables associated with the need of ICU admission in a cohort of hospitalized patients for COVID-19 under remdesivir including the period from symptoms onset to remdesivir. Methods We conducted a retrospective multicentric study analysing all patients admitted with COVID-19 in 9 Spanish hospitals who received treatment with remdesivir in October 2020. The main outcome was the need of ICU admission after 24 h of the first dose of remdesivir. Results In our cohort of 497 patients, the median of days from symptom onset to remdesivir was 5 days, and 70 of them (14.1%) were later admitted into ICU. The clinical outcomes associated with ICU admission were days from symptoms onset (5 vs. 6; p = 0.023), clinical signs of severe disease (respiratory rate, neutrophil count, ferritin levels and very-high mortality rate in SEIMC-Score) and the use of corticosteroids and anti-inflammatory drugs before ICU. The only variable significatively associated with risk reduction in the Cox-regression analyses was ≤ 5 days from symptoms onset to RDV (HR: 0.54, CI95%: 0.31–0.92; p = 0.024). Conclusion For patients admitted to the hospital with COVID-19, the prescription of remdesivir within 5 days from symptoms onset diminishes the need of ICU admission.
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    Association of monetary diet cost of foods and diet quality in Spanish older adults
    (Frontiers Media, 2023-07-25) García-Ríos, Antonio; Bouzas, Cristina; Pastor, Rosario; García, Silvia; Monserrat Mesquida, Margalida; Martínez-González, Miguel Ángel; Salas Salvadó, Jordi; Corella Piquer, Dolores; Schröder, Helmut; Martínez, J. Alfredo; Alonso-Gómez, Ángel M.; Wärnberg, Julia; Vioque, Jesús; Romaguera, Dora; Lopez-Miranda, José; Estruch Riba, Ramon; Tinahones, Francisco J.; Lapetra, José; Serra Majem, Lluís; Riquelme Gallego, Blanca; Romero-Secin, Anny; Pintó Sala, Xavier; Gaforio, José J.; Matía Martín, Pilar; Vidal i Cortada, Josep; Zapatero, Miriam; Daimiel, Lidia; Ros Rahola, Emilio; García-Arellano, Ana; Babio, Nancy; González Monje, Inmaculada; Castañer Niño, Olga; Abete, Itziar; Tojal Sierra, Lucas; Benavente Marín, Juan Carlos; Signes Pastor, Antonio J.; Konieczna, Jadwiga; Castro-Barquero, Sara; Fernández-García, José C.; Santos Lozano, Jose Manuel; Bes Rastrollo, Maira; Mestres, Cristina; Guillem Saiz, Patricia; Goday Arnó, Albert; Goicolea Güemez, Leire; Puig-Aguiló, Estanislao; Ruiz-Canela, Miguel; Palau Galindo, Antoni; Fitó, Montse; Tur, Josep A.
    Background: A major barrier to a healthy diet may be the higher price of healthy foods compared to low-quality foods. Objectives: This study aimed to assess the association between the monetary cost of food and diet quality in Spanish older adults at high risk of cardiovascular disease. Methods: Cross-sectional analysis was carried out in Spanish older adults (n = 6,838; 48.6% female). A validated food frequency questionnaire was used to assess dietary intake. Metabolic syndrome severity, adherence to the Mediterranean diet (MedDiet), adherence to a provegetarian dietary pattern, and dietary inflammatory index were assessed. The economic cost of the foods was obtained from the Spanish Ministry of Agriculture Fisheries and Food database (2015-2017, the period of time when the participants were recruited). The total cost of diet adjusted per 1,000 kcal was computed. Results: The healthier dietary pattern was associated with a higher cost of the diet. Higher adherence to the MedDiet, anti-inflammatory diet, and the healthy version of the provegetarian dietary pattern were related to higher costs of the diet. Conclusion: Higher diet quality was associated with a higher dietary cost of the diet per 1,000 kcal/day. Food prices can be an important component of interventions and policies aimed at improving people's diets and preventing diet-related chronic diseases.
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    Cigarettes vs. e-cigarettes: Passive exposure at home measured by means of airborne marker and biomarkers
    (Elsevier, 2014-09-27) Ballbè i Gibernau, Montse; Martínez Sánchez, José M.; Sureda, Xisca; Fu Balboa, Marcela; Pérez Ortuño, Raúl; Pascual, José A.; Saltó, Esteve; Fernández Muñoz, Esteve
    Background: There is scarce evidence about passive exposure to the vapour released or exhaled from electronic cigarettes (e-cigarettes) under real conditions. The aim of this study is to characterise passive exposure to nicotine from e-cigarettes' vapour and conventional cigarettes' smoke at home among non-smokers under real-use conditions. Methods: We conducted an observational study with 54 non-smoker volunteers from different homes: 25 living at home with conventional smokers, 5 living with nicotine e-cigarette users, and 24 from control homes (not using conventional cigarettes neither e-cigarettes). We measured airborne nicotine at home and biomarkers (cotinine in saliva and urine). We calculated geometric mean (GM) and geometric standard deviations (GSD). We also performed ANOVA and Student's t tests for the log-transformed data. We used Bonferroni-corrected t-tests to control the family error rate for multiple comparisons at 5%. Results: The GMs of airborne nicotine were 0.74 μg/m(3) (GSD=4.05) in the smokers' homes, 0.13 μg/m(3) (GSD=2.4) in the e-cigarettes users' homes, and 0.02 μg/m(3) (GSD=3.51) in the control homes. The GMs of salivary cotinine were 0.38 ng/ml (GSD=2.34) in the smokers' homes, 0.19 ng/ml (GSD=2.17) in the e-cigarettes users' homes, and 0.07 ng/ml (GSD=1.79) in the control homes. Salivary cotinine concentrations of the non-smokers exposed to e-cigarette's vapour at home (all exposed ≥ 2 h/day) were statistically significant different that those found in non-smokers exposed to second-hand smoke ≥ 2 h/day and in non-smokers from control homes. Conclusions: The airborne markers were statistically higher in conventional cigarette homes than in e-cigarettes homes (5.7 times higher). However, concentrations of both biomarkers among non-smokers exposed to conventional cigarettes and e-cigarettes' vapour were statistically similar (only 2 and 1.4 times higher, respectively). The levels of airborne nicotine and cotinine concentrations in the homes with e-cigarette users were higher than control homes (differences statistically significant). Our results show that non-smokers passively exposed to e-cigarettes absorb nicotine.
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    Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of- opportunity SOLTI TOT-HER3 pre-operative study
    (Oxford University Press, 2023-05-19) Santhanagopal, Anu; Sellami, Dalila; Villacampa, Guillermo; Ferrero Cafiero, Juan Manuel; Pascual, Tomás; Prat Aparicio, Aleix; Vidal Espinar, Miquel; Martínez Sáez, Olga; Paré Brunet, Laia; González Farré, Blanca; Sanfeliu, Esther; Ciruelos, Eva; Espinosa Bravo, Martin; Pernas, Sònia; Izarzugaza, Y.; Esker, Stephen; Oliveira, Mafalda; Falato, Claudette; Cejalvo Andújar, Juan Miguel; Margelí Vila, Mireia; Tolosa, Pablo; Salvador Bofill, Francisco Javier; Cruz Jurado, Josefina; Arumi de Dios, Miriam; Luna Barrera, Ana María; Guerra, Juan Antonio; Fan, Pang-dian; Parul, Patel
    Background: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %) + 1.3 × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. Patients and methods: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. Results: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. Conclusions: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.
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    Holistic evaluation of the impact of pregnancy urban exposome on infant wheezing and chest infections: an outcome-wide approach
    (Elsevier Ltd., 2025-11-08) Gómez Roig, Ma. Dolores; Sunyer, Jordi; Marcon, Alessandro; Johannessen, Ane; Dadvand, Payam; Sinsamala, Robin M.; Anguita-Ruiz, Augusto; Basagaña, Xavier; Foraster, Maria; Gascón, Mireia; Llurba Olivé, Elisa; Luo, Chongliang; Nieuwenhuijsen, Mark J.; Persavento, Cecilia; Rivas, Ioar; Zhao, Yu
    Background: Few studies have considered the complex interplay of the urban exposome in association with multiple respiratory outcomes during infancy. Aim: Utilizing an outcome-wide exposome approach, we aimed to assess associations of pregnancy urban exposome with offspring wheezing and chest infections at different time points within the first 18 months of life. Methods: The analysis included data from 1032 mother-child pairs from the Barcelona Life Study Cohort (BiSC) (2018-2021). In total, 44 urban exposome factors were assessed during pregnancy, including air pollution, noise, temperature, humidity, green and blue spaces, and socioeconomic and lifestyle factors. Wheezing and chest infection were evaluated simultaneously at 2, 6, 12, and 18 months. We applied mixed-response sparse reduced-rank regression (MsRRR), with resampling procedures, adjusting for potential confounders. This many-to-many modelling approach identifies exposures concurrently associated with multiple interrelated outcomes. Results: We found 13 exposures consistently associated with wheezing and chest infection across four time-points. Maternal education was the most consistent protective factor with odds ratios (OR) ranging from 0.65 to 0.81 for university and 0.88 to 0.96 for secondary education (vs. primary education) (all p < 0.05). Other important protective factors were size of nearest green space and maternal light-intensity physical activity. NO2 (OR 1.02-1.08), outdoor temperature (OR 1.02-1.04), and noise annoyance (OR 1.01-1.03) were consistently associated with increased risk. Area-level socioeconomic status indicators showed inverse associations. Conclusion: Pregnancy urban exposome may influence both wheezing and chest infections in infancy. Identifying key determinants through an outcome-wide exposome approach can inform targeted public health interventions towards more holistic urban planning strategies.
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    Functional recovery of islet β cells in human type 2 diabetes: Transcriptome signatures unveil therapeutic approaches
    (American Association for the Advancement of Science, 2025-10-10) Kerr-Conte, Julie; Pattou, François; Nacher, Montserrat; Montanya Mias, Eduard; Mourad, Nizar; Buemi, Antoine; Citi, Valentina; Martelli, Alma; Benedetti, Giada; Calderone, Vicenzo; De Luca, Carmela; Rossi, Leonardo; Sebastiani, Guido; Paolicchi, Aldo; Saponaro, Chiara; Cardarelli, Francesco; Pugliese, Licia Anna; Dotta, Francesco; Del Guerra, Silvia; Eizirik, Décio L.; Pocai, Alessandro; Ibberson, Mark; Simone, Paolo De; Marchetti, Piero; Ghinolfi, Davide; Cnop, Miriam; Boggi, Ugo; Kessler, Camille; Suleiman, Mara; Sawatani, Toshiaki; Tesi, Marta; Yi, Xiaoyan; Papadopoulou, Theodora; Rufer, Chantal; Lytrivi, Maria; Bosi, Emanuele; Burdet, Frederic; Fantuzzi, Federica; Marselli, Lorella; Grieco, Giuseppina Emanuela; Fignani, Daniela
    Remission of type 2 diabetes (T2D) can occur after hypocaloric diet, bariatric surgery, or pharmacological treatments and associates with improved β cell function. Here, we studied islets from nondiabetic (n = 15) and T2D (n = 21) donors. We examined whether T2D β cell dysfunction can be rescued, charted the underlying molecular mechanisms by RNA sequencing, and mined transcriptomes for drug targets. Glucose responsiveness of T2D β cells improved in 60% of preparations after 3-day culture in euglycemic conditions. This was accompanied by changes in expression of >400 genes involved in functional or inflammatory pathways. Drug repurposing and target identification analyses predicted chemical and genetic hits, including JAK inhibitors, which were validated in a β cell line, human islets, and db/db mice. Therefore, defective β cell glucose responsiveness in T2D can recover, demonstrating β cell functional plasticity. The recovery associates with transcriptomic traits, pointing to targetable defects to induce T2D remission.
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    Indirect comparison of epcoritamab vs chemoimmunotherapy, mosunetuzumab, or odronextamab in follicular lymphoma
    (American Society of Hematology, 2025-08-12) Ding, Zhijie; Alshreef, Abualbishr; Favaro, Elena; Hoehn, Daniela; Sureda, Anna; Danilov, Alexey V.; Thiruvengadam, Swetha Kambhampati; Linton, Kim; Cumings, Karen; Chirikov, Viktor; Mutebi, Alex; Chawla, Savreet Bains; Chhibber, Anindit; Rivas Navarro, Fernando; Gonçalves, Felipe Marques; Wang, Anthony
    This matching-adjusted indirect comparison evaluated the efficacy of epcoritamab vs standard of care (SOC), mosunetuzumab, or odronextamab, and assessed safety vs mosunetuzumab and odronextamab. Individual patient-level data from the EPCORE NHL-1 follicular lymphoma (FL) cohort for epcoritamab were used with pooled data from SCHOLAR-5 for SOC (mostly chemoimmunotherapy [CIT]), and aggregate data from GO29781 for mosunetuzumab and ELM-2 for odronextamab. Trial populations were match-adjusted using propensity score weights for key baseline characteristics. Compared with SOC/CIT, epcoritamab provided significantly higher response rates (overall response rate [ORR], 90.9% vs 56.8%; P < .001; complete response [CR] rate, 73.7% vs 32.0%; P < .001). Epcoritamab showed numerically higher ORR (90.9% vs 80.0%; P = .067) and CR rate (72.8% vs 60.0%; P = .159) vs mosunetuzumab. Epcoritamab provided significantly higher ORR (91.5% vs 80.5%; P = .026) and numerically lower CR rate (67.5% vs 73.4%; P = .428) vs odronextamab. Epcoritamab did not have any grade ≥3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS; any grade) events compared with CRS (grade ≥3) in 2.2% and 3.9% and ICANS in 4.4% and 0.8% of patients treated with mosunetuzumab and odronextamab, respectively (P < .001). In addition to being a convenient subcutaneous option, epcoritamab showed significantly superior response rates and survival outcomes vs SOC/CIT among patients with relapsed or refractory FL after ≥2 systemic therapies. Epcoritamab also exhibited clinically relevant, numerically higher ORRs and demonstrated improved safety for CRS (grade ≥3) and ICANS vs mosunetuzumab or odronextamab.