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Articles publicats en revistes (Medicina)

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    Trends in revascularization therapies for patients with acute stroke with large infarcts: A population-based study
    (BMJ Publishing Group, 2025-10-01) Doncel Moriano, Antonio; Rodríguez Vázquez, Alejandro; Rosa, Irene; Rudilosso, Salvatore; Serrano Clerencia, Mònica; Renú, Arturo; Cabero Arnold, Andrea; Blasco, Jordi; Amaro, Sergio; Llull, Laura; Molina, Carlos A.; Cardona Portela, Pere; Camps Renom, Pol; Millán, Mónica; Figueras Aguirre, Georgina; Rodríguez Campello, Ana; Silva, Yolanda; Purroy, Francisco; Salvat, Mercè; Vargas, Martha; Urra, Xabier; Chamorro Sánchez, Ángel
    Background Evidence from randomized clinical trials shows that mechanical thrombectomy (MT) enhances functional outcomes in patients with large core ischemic stroke. Objective To evaluate trends in the use of revascularization therapies, particularly MT, and their impact on functional outcomes in patients with large core ischemic stroke in routine clinical settings. Methods Observational data from the Stroke Code Registry of Catalonia (CICAT, 2016–2024) were analyzed. Patients with anterior circulation ischemic stroke and Alberta Stroke Program Early CT Score (ASPECTS) <6, whether treated with reperfusion therapies or not, were included. Statistical analyses included trend analysis and multivariable logistic regression to identify predictors of favorable outcomes (modified Rankin Scale score 0–3 at 90 days) and mortality. Results Among 599 patients, MT use increased significantly from 22% pre-2022 to 36% post-2022. This increase was associated with improved functional outcomes, with favorable outcomes rising from 29% to 43% post-2022. MT was a significant independent predictor of favorable outcomes (OR 3.4, 95% CI 2.1 to 5.5) and reduced mortality (OR 0.46, 95% CI 0.32 to 0.68). Intravenous thrombolysis also improved outcomes (OR 2.1, 95% CI 1.3 to 3.5). The benefit of MT was consistent across ASPECTS subgroups (0–2 and 3–5). Mediation analysis indicated that 88% of improvement could be attributed to increased MT use. Conclusions Increased MT use significantly improved outcomes for patients with large core ischemic stroke, particularly after 2022. Benefits were observed across subgroups, including those with very low ASPECTS. These findings support broadening MT access and suggest the need to update treatment guidelines to consider patients with large ischemic cores, aiming to optimize outcomes in routine clinical practice.
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    Mind the gap: The impact of discrepancy between current cognitive function and premorbid intelligence on psychosocial functioning in older age bipolar disorder
    (Elsevier B.V., 2025-08-21) Montejo Egido, Laura; Mariegaard Schandorff, Johanna; Zarp, Jeff; Lie Kjærstad, Hanne; Elleby Jespersen, Andreas; Bort, Marta; Ruiz Muñoz, Andrea; Solé Cabezuelo, Brisa; Torrent Font, Carla; Martínez-Arán, Anabel, 1971-; Vieta i Pascual, Eduard, 1963-; Miskowiak, Kamilla W.
    Introduction: A discrepancy between current cognitive performance and premorbid IQ may indicate cognitive decline and relate to poorer psychosocial functioning in bipolar disorder, even when cognition appears unimpaired by standard norms. This study examined how objective cognition and IQ-cognition discrepancy relate to psychosocial functioning in older age bipolar disorder (OABD). Methods: OABD underwent neurocognitive assessment, intelligence quotient (IQ) estimation (using vocabulary subtest of WAIS-III), and psychosocial functioning assessment via the Functioning Assessment Short Test (FAST). IQ-cognition discrepancy scores were calculated as the difference between current cognitive performance and estimated premorbid IQ (range: -10 to +10; negative values indicating possible cognitive decline). Linear regressions examined associations between cognition, discrepancy score, and psychosocial functioning. Discriminant analyses evaluated the ability of these scores to predict functional impairment. Results: The sample included 165 participants (116 OABD and 49 healthy controls). Poorer cognitive performance was significantly associated with worse psychosocial functioning (β = -3.38, p = .002). Greater IQ-cognition discrepancy also predicted worse functioning (β = -0.92, p = .04), though cognitive performance showed a stronger association (β = -2.93, p = .017) and better discriminative ability for functional impairment (AUC = 0.75; cut-off = -0.4 SD; sensitivity = 0.69; specificity = 0.72) compared to discrepancy score (AUC = 0.64; sensitivity = 0.39; specificity = 0.87). Conclusions: IQ-cognition discrepancy may serve as a useful idiographic marker of functional impairment in OABD, particularly for individuals with high premorbid IQ. Its use could enhance clinical decision-making and broaden inclusion in pro-cognitive intervention trials.
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    Influence of Persistent Inflammation in Follow-Up Biopsies After Antibody-Mediated Rejection in Kidney Transplantation.
    (Frontiers Media, 2021-11-12) Piñeiro, Gastón Julio; Montagud Marrahi, Enrique; Ríos, José; Ventura Aguiar, Pedro; Cucchiari, David; Revuelta, Ignacio; Lozano, Miquel; Cid Vidal, Joan; Cofán Pujol, Frederico; Esforzado Armengol, Nuria; Palou Ribera, Eduard; Oppenheimer Salinas, Federico; Campistol Plana, Josep M.; Bayés Genís, Beatriu; Rovira Juárez, Jordi; Diekmann, Fritz
    Background: Despite recent advances in immunosuppression treatment, antibody-mediated rejection (ABMR) remains the leading cause of kidney graft loss. Information about prognostic markers and the efficacy of treatment is scarce. Methods: Retrospective study with kidney recipients diagnosed an active ABMR from January 1, 2004 to December 31, 2019 to explore the influence of persistent inflammation in follow-up biopsies on graft survival after ABMR treatment. Results: About 116 patients were included. Active ABMR were treated with a combination of plasma exchange (PE), intravenous immunoglobulin (IVIg), rituximab, and steroids. At 6 months of treatment, 63 (54.3%) patients presented a stabilization or improvement in kidney-graft function. The effectiveness varied depending on the timepoint of the presentation between transplantation and rejection, which is lower for those with late ABMR (63 vs. 21% for early vs. late ABMR, respectively). Ninety patients (77%) underwent a control biopsy after ABMR treatment, from which 46 (51%) responded to the treatment. Microvascular inflammation (MVI) persisted in 64 (71%) biopsies, whereas tubulitis persisted in 17 (19%) biopsies. Death-censored graft survival at 1 year was significantly lower in patients with persistent MVI (86% vs. 95% without persistent MVI, P = 0.002), or with persistent tubulitis (44% vs. 66% without tubulitis, P = 0.02). In the Cox Regression analysis, the persistence of MVI [hazard ratio (HR), 4.50 (95%CI, 1.35-14.96), P = 0.01] and tubulitis [HR 2.88 95%CI (1.24-6.69), P = 0.01) in follow-up biopsies significantly increased the risk of graft failure. Conclusion: Persistent inflammation in follow-up biopsies after ABMR treatment was associated with an increased risk of graft loss, even without meeting Banff rejection criteria. Study Registration: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTRINM-2017-01
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    Experiences during Switching from Two-Stage to One-Stage Revision Arthroplasty for Chronic Total Knee Arthroplasty Infection
    (MDPI, 2021-11-24) Navarro, Guillem; Lozano, Luis; Sastre, Sergi; Bori, Rosa; Bosch Mestres, Jordi; Bori Tuneu, Guillem
    The objective of this study was to evaluate our preliminary results after changing our surgical strategy from 2-stage revision arthroplasty to 1-stage revision arthroplasty for patients with chronic knee periprosthetic joint infection. We conducted a prospective study of knee arthroplasty patients that had been diagnosed with chronic infection and treated using a 1-stage revision regardless of the traditional criteria applied for indication thereof. We evaluated two main variables: infection control and economic costs. The definitive diagnosis of infection of the revision was determined by using the criteria proposed by the Musculoskeletal Infection Society. The costs were calculated as average costs in USD, as described by Srivastava (2019), for 1-stage or 2-stage revisions. Eighteen patients were included in the study, and infection was controlled in 17 patients. The total economic savings for our hospital from these 18 patients amounted to USD 291,152. This clinical success has led to major changes in how our hospital approaches the treatment of chronically infected knee replacements, in addition to substantial economic advantages for the hospital.
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    Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort
    (BioMed Central, 2023-10-13) Matía-Martín, Pilar; Shyam, Sangeetha; García Gavilán, Jesús; Paz-Graniel, Indira; Gaforio, José J.; Martínez-González, Miguel Ángel, 1957-; Corella Piquer, Dolores; Martínez Hernández, José Alfredo; Alonso Gómez, Ángel M.; Wärnberg, Julia; Vioque, Jesús; Romaguera, Dora; López-Miranda, José; Estruch Riba, Ramon; Tinahones, Francisco José; Lapetra, José; Serra-Majem, J. Luis; Bueno-Cavanillas, Aurora; Tur, Josep Antoni; Martín-Sánchez, V.; Pintó Sala, Xavier; Vidal i Cortada, Josep; Vázquez, Clotilde; Daimiel, Lidia; Ros Rahola, Emilio; Fernández Aranda, Fernando; Nishi, Stephanie K; Garcia-Regata, Oscar; Toledo, Estefanía; Asensio, Eva M; Castañer Niño, Olga; Garcia-Rios, Antonio; Torres-Collado, Laura; Gómez Gracia, Enrique; Zulet, M. Angeles; Goñi Ruiz, Nuria; Casas Rodríguez, Rosa M.; Cano Ibáñez, Naomi; Tojal-Sierra, Lucas; Gómez-Perez, AM; Sorlí, José V; Cinza-Sanjurjo, Sergio; Martín-Peláez, Sandra; Peña-Orihuela, Patricia J; Oncina-Canovas, Alejandro; Perez-Araluce, Rafael; Zomeño, Maria Dolores; Chaplin, Alice; Delgado Rodriguez, Miguel; Babio, Nancy; Fitó Colomer, Montserrat; Salas-Salvadó, Jordi
    Background: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. Methods: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. Results: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. Conclusions: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19.
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    Clinical, imaging, and serum biomarker predictors of malignant cerebral infarction
    (MDPI, 2025-10-04) Rodríguez Vázquez, Alejandro; Rudilosso, Salvatore; Doncel Moriano, Antonio; Cabero Arnold, Andrea; Laredo, Carlos; Ramis, Darío; Moraleja, David; Serrano Clerencia, Mònica; Gonzalez Romero, Yolanda; Renú, Arturo; Bartolomé Arenas, Inés; Rosa Batlle, Irene; Dolz Alvarez de la Ballina, Guillem; Torné, Ramón; Vargas, Martha; Urra, Xabier; Chamorro, Ángel
    Malignant cerebral infarction (MCI) is rare but often fatal. Early identification helps guide monitoring and decompressive surgery. This study evaluated whether serum biomarkers add predictive value beyond clinical and imaging data in severe stroke patients with anterior circulation large vessel occlusion (LVO). In this prospective study, 73 acute severe LVO stroke patients underwent whole-brain CT perfusion (CTP) with rCBV-based core measurement at admission and follow-up MRI at 24 ± 12 h for infarct and edema volume assessment. Serum biomarkers (s100b, NSE, VEGF, ICAM1) were sampled a median of 20.5 h after baseline imaging. Logistic regression models predicted MCI using baseline variables (NIHSS, ASPECTS, rCBV < 30%), adding treatment data (rtPA, mTICI, NIHSS posttreatment), and adding serum biomarkers. Performance was assessed by AUC, accuracy, F1, and cross-validated R2. MCI occurred in 18/73 (24%) patients. Baseline models showed an AUC of 0.72; adding treatment improved the AUC to 0.88. Biomarkers slightly increased the AUC (0.90) but did not improve F1. Higher s100b was associated with more severe injury but did not enhance the prediction of MCI. Models with baseline imaging and treatment best explained infarct (R2 ≈ 0.27) and edema (R2 ≈ 0.58). In conclusion, admission severity, CTP, and early treatment response are the main predictors of MCI and aid early risk stratification of patients. Despite their pathophysiologic relevance, serum biomarkers do not add substantial predictive value.
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    Clinical Variables Related to Functional Capacity and Exertional Desaturation in Patients with COVID-19
    (MDPI, 2023-07-20) Larrateguy, Santiago; Vinagre, Julian; Londero, Federico; Dabin, Johana; Ricciardi, Evangelina; Jeanpaul, Santiago; Torres Castro, Rodrigo; Núñez Cortés, Rodrigo; Sánchez Ramírez, Diana; Gimeno Santos, Elena, 1980-; Blanco Vich, Isabel
    Impaired functional capacity is one of the most commonly reported consequences among post-COVID-19 patients. This study aimed to analyse the clinical variables related to functional capacity and exertional desaturation in post-COVID-19 patients at the time of hospital discharge. A cross-sectional study was conducted on patients recovering from COVID-19 pneumonia. The main outcomes measures were functional capacity, assessed using the 1 min sit-to-stand test (1 min STST), and exertional desaturation, defined as a drop of ≥4% in the arterial oxygen saturation. Factors used to characterise the participant outcomes included the use of a high-flow nasal cannula (HFNC), prolonged hospitalisation, occurrence of pulmonary embolism during hospitalisation, and underlying comorbidities. A total of 381 participants (mean age = 53.7 ± 13.2 years, 65.6% men) were included. Participants completed a mean of 16.9 ± 6.2 repetitions in the 1 min STST. Exertional desaturation was observed in 51% of the patients. Higher odds of exertional desaturation were found in the participants who used a HFNC (OR = 3.6; 95%CI: 1.6 to 7.8), were admitted in the hospital >10 days (OR = 4.2; 95%CI: 2.6 to 6.8), and had a pulmonary embolism (OR = 3.5; 95%CI: 2.2. to 5.3). Use of a HFNC (β = -3.4; 95%CI: -5.3 to -1.44), a hospital stay >10 days (β = -2.2; 95%CI: -3.4 to -0.9), and a history of pulmonary embolism (β = -1.4; 95%CI: -2.6 to -0.2) were also negatively associated with the 1 min STST. Most post-COVID-19 patients exhibited reduced functional capacity at the time of hospital discharge, and approximately half had exertional desaturation after the 1 min STST. The use of a HFNC, prolonged hospitalisation and pulmonary embolism were the main clinical variables associated with worse a 1 min STST performance and a higher likelihood of exertional desaturation.
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    Effectiveness of inspiratory muscle training in patients with a chronic respiratory disease: an overview of systematic reviews
    (Frontiers Media, 2025-05-21) Torres Castro, Rodrigo; Caicedo Trujillo, Saul; Gimeno Santos, Elena, 1980-; Gutiérrez Arias, Ruvistay; Alsina Restoy, Xavier; Vasconcello Castillo, Laura; Seron, Pamela; Spruit, Martijn A.; Blanco Vich, Isabel; Vilaró, Jordi
    Introduction: There has been inconclusive findings regarding the effectiveness of inspiratory muscle training (IMT) in chronic respiratory diseases (CRDs). Our objective was to determine the effectiveness of IMT on exercise tolerance, maximum respiratory pressure, lung function, symptoms and quality of life in different CRDs. Methods: We conducted an overview of systematic reviews (SRs) in adults with CRDs who underwent IMT. We reviewed five databases in March 2025. We chose the most comprehensive SRs to report on the analysed outcomes. Results: Twenty-three SRs were included. In chronic obstructive pulmonary disease (COPD), IMT increased the six-minute walk distance (6MWD) by 35.7 m (95% CI 25.7, 45.7), maximum inspiratory pressure (MIP) by 10.9 cmH2O (95% CI 8.0, 13.9). In asthma, IMT increased the forced expiratory volume in the first second (FEV1) by 3.3%pred (95% CI 1.4, 5.1), forced vital capacity (FVC) by 4.1%pred (95% CI 1.0, 7.3), MIP by 21.9 cmH2O (95% CI 15.0, 28.8), and dyspnoea was reduced (standard mean difference -0.8, 95% CI -1.3,-0.2). In obstructive sleep apnoea (OSA), IMT increased MIP by 29.6 cmH2O (95% CI 6.0, 53.1). In pulmonary hypertension (PH), IMT increased 6MWD by 39.0 m (95% CI 20.7, 57.4), MIP in 21.2 cmH2O (95% CI 11.3, 31.1), maximum expiratory pressure by 14.4 cmH2O (95% CI 6.9, 21.9), and dyspnoea was reduced by 0.5 (95% CI 0.1, 0.9) in modified Medical Research Council scale. In lung resection (LR), IMT increased MIP by 8.1 cmH2O (95% CI 1.3, 14.9). In bronchiectasis, IMT increased MIP by 6.1 cmH2O (95% CI 1.4, 10.8). Overall, the most consistent effect of IMT across different CRDs was an increase in MIP. Conclusion: IMT improved several clinically relevant outcomes, including MIP, exercise capacity, and dyspnoea in different CRDs. However, the limited evidence for certain outcomes and populations highlights the need for further high-quality studies.
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    Leveraging Genetics to Support Forensic Toxicology Analysis: Demonstrating  Concordance Among Marijuana Samples
    (Elsevier, 2024-12) Di Nunzio, Michele; Pieri, Maria; Gangitano, David; Di Nunzio, Ciro; Tinto, Nadia; Niola, Massimo; Barrot i Feixat, Carme
    Cannabis sativa is an important plant for industrial purposes. Indeed, it is legal to cultivate and supply authorized low level Δ9-tetrahydrocannabinol (THC) cannabis plants for fiber and seeds (i.e., 0.2 % according to the European Union regulation on drugs). Today, chromatography/mass spectrometry-based procedures are successfully applied to determine THC concentration. Unfortunately, when cannabis samples have been degraded because wrongfully stored, toxicological results were affected, altering the final status of legal sample or illegal sample. Rather, genetic identification could give more information about the identity of these plants. For this reason, a degradation study was run to support how can help to detect concordance in cannabis highly-degraded samples. Forty cannabis sub-samples were stored (for one week, two weeks, one month and two months) in auto-sealing bag to assess the effects of a wrong cannabis storage on weight reduction, genomic DNA changes, and corresponding profiles. Once respective time-period elapsed, each sub-sample’s weight was measured, the percentage weight loss calculated, and the genomic DNA was extracted and quantified, obtaining a complete STR profile for all samples. Furthermore, the aim of this study was to assess the same 13-loci short tandem repeat (STR) multiplex system used for the degradation experiment and evaluate the power of such markers in the identification and discrimination of highly degraded cannabis samples coming from real cases. The results of this study demonstrated that the 13-loci STR multiplex system successfully achieved the objective both for industry and forensic purposes. For each sample, all 13 loci were amplified, and degraded samples were correctly identified, suggesting that genetic typification could be a useful tool. The proposed procedure could be parallelly applied to toxicology analysis to detect if vegetable sample become from authorized plant, to help courts track back illegal samples or to achieve illegal cannabis genetic profiles for further comparison.
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    Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis
    (Elsevier, 2025-08-21) Gascón-Bayarri, Jordi; Mosquera Mayo, José Luís; Blanch Lozano, Marta; Martí Benaiges, Pau; Fontal Aina, Beatriz; Trapero Candela, Carla; Rojo Fité, Nuria; Rico, Inma; Campdelacreu i Fumadó, Jaume; Fowler, Cristopher; Laws, Simon M.; Tort Merino, Adrià; Sánchez del Valle Díaz, Raquel; Bello, Joan; Fortea Ormaechea, Juan; Lleó Bisa, Alberto; Mehanian, Courosh; Swerdlow, Russell H.; Reñé Ramírez, Ramon; Barrachina, Marta
    Alzheimer's Disease Dementia (ADD) prognosis is an unmet medical need. Mitochondrial dysfunction is an early AD etiopathogenic factor. The present study analyzed mitochondrial DNA (mtDNA) methylation patterns in blood samples from patients with mild cognitive impairment (MCI) who progressed to ADD (P), MCI remained stable (NP), and Cognitively Normal (CN) individuals. Differentially methylated sites were identified in the D-loop region in both CN vs. NP and NP vs. P comparisons, even before β-amyloid positivity. A Random Forest model was developed using mtDNA methylation data combined with cognitive and risk factor features. Model's performance was assessed by cross-validation and tested on an independent set, achieving 84.4% accuracy in training and 83.2% (95% CI: 75.2%-89.4%) in testing. For identifying P patients, sensitivity and specificity were 95.1% and 70.7%, respectively. The AUC-ROC was 90.3%. The developed model demonstrates predictive capacity in distinguishing cognitive decline and stability in MCI individuals, independently of their β-amyloid status.
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    Ex vivo normothermic preservation of a kidney graft from uncontrolled donation after circulatory death over 73 hours
    (Frontiers Media, 2023-01-12) Montagud Marrahi, Enrique; Luque, Yosu; Rabadán Ros, Rubén; Ajami, Tarek; Estrella, Héctor; Arancibia, Andrés; Sánchez-Etayo, Gerard; Bohils-Valle, Marc; Marrero, Ramsés; Fundora, Yilian; Cuadrado Payán, Elena; Ramírez Bajo, María José; Bañón Maneus, Elisenda; Rovira, Jordi; Larque, Ana-Belén; Campistol Plana, Josep M.; Diekmann, Fritz; Musquera i Felip, Mireia
    The transplant community is focused on prolonging the ex vivo preservation time of kidney grafts to allow for long-distance kidney graft transportation, assess the viability of marginal grafts, and optimize a platform for the translation of innovative therapeutics to clinical practice, especially those focused on cell and vector delivery to organ conditioning and reprogramming. We describe the first case of feasible preservation of a kidney from a donor after uncontrolled circulatory death over a 73-h period using normothermic perfusion and analyze hemodynamic, biochemical, histological, and transcriptomic parameters for inflammation and kidney injury. The mean pressure and flow values were 71.24 ± 9.62 mmHg and 99.65 ± 18.54 mL/min, respectively. The temperature range was 36.7°C-37.2°C. The renal resistance index was 0.75 ± 0.15 mmHg/mL/min. The mean pH was 7.29 ± 0.15. The lactate concentration peak increased until 213 mg/dL at 6 h, reaching normal values after 34 h of perfusion (8.92 mg/dL). The total urine output at the end of perfusion was 1.185 mL. Histological analysis revealed no significant increase in acute tubular necrosis (ATN) severity as perfusion progressed. The expression of KIM-1, VEGF, and TGFβ decreased after 6-18 h of perfusion until 60 h in which the expression of these genes increased again together with the expression of β-catenin, Ki67, and TIMP1. We show that normothermic perfusion can maintain a kidney graft viable ex vivo for 3 days, thus allowing a rapid translation of pre-clinical therapeutics to clinical practice.
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    Enhanced i-Motif Stability through Consecutive 2,2-Difluorocytidine Incorporation
    (Wiley-VCH, 2025-11-19) Domínguez, Arnau; Cabrero, Cristina; Gómez-Pinto, Irene; Fàbrega, Carmen ; Gargallo Gómez, Raimundo; Eritja i Casadellà, Ramon; González, Carlos; Aviñó Andrés, Anna
    Chemical modifications of nucleic acids are widely used to tune stability and functionality in therapeutic and nanotechnological applications. Among these, fluorinated cytidine derivatives such as 2-fluoro-arabinocytidine (2F-araC) and 2-fluoro-ribocytidine (2F-riboC) have been shown to influence i-motif structures differently, with 2F-araC strongly stabilizing and 2F-riboC exerting a mildly deleterious effect. In this study, we investigate the impact of gemcitabine (2-deoxy-2,2-difluorocytidine, dFdC) on i-motif stability. dFdC exhibits small effects in single or double substituted sequences, but a pronounced stabilization when multiple consecutive residues are incorporated. Thermal and pH-dependent analyses demonstrate that sequences containing fully substituted dFdC maintain i-motif folding at neutral pH and show enhanced thermal stability. Structural insights suggest that this stabilization arises from a combination of factors, such as hyperconjugative interactions, hydrogen bonding, and dipole alignment, while the adaptable sugar conformation mitigates destabilizing minor groove contacts observed in other more rigid modifications, such as 2-F-riboC. Cooperative interactions among adjacent dFdC residues and potential changes in hydration may play a key factor in reinforcing stability. These results highlight the unique capacity of dFdC to enhance i-motif robustness and suggest that strategically placed difluoro substitutions can be exploited to design i-motifs with improved stability, expanding their potential in biotechnology and therapeutic applications.
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    Por una bioética en acción: Recursos formativos en abierto desarrollados por la UNESCO
    (Ministerio de Salud de la Provincia de Neuquén (Argentina), 2015-05) Lecuona Ramírez, Itziar de
    El artículo tiene como objetivo contribuir al debate sobre los retos que afronta la bioética en el siglo XXI y, en especial, los comités de ética, mecanismos que han de permitir el paso de la teoría a la acción en base a una bioética práctica, vinculada a los derechos humanos internacionalmente reconocidos. Una bioética que evoluciona hacia la responsabilidad social, especialmente en salud, con el referente que supone, desde 2005, la Declaración Universal sobre Bioética y Derechos Humanos de la UNESCO. Se revisa el origen, funciones y características de los Comités de ética nacionales, asistenciales y de investigación, destacando la labor de promoción del debate y sensibilización que se les encomienda, y por tanto, la importancia de la formación y la adquisición de capacidades en bioética de los miembros de comités. Al mismo tiempo, se plantea una visión crítica de estas instancias desde la biopolítica. Finalmente, se sistematizan los recursos en abierto desarrollados por el Programa de Bioética de la UNESCO para la formación y capacitación en bioética y que son de utilidad para los miembros de comités de ética. También para los diversos agentes que intervienen en los procesos asistenciales y de investigación, que han de tomar decisiones a diario y que requieren un análisis interdisciplinario y una preparación que excede la formación técnica y específica. Los conflictos y situaciones de aspecto bioético obligan a integrar otros conocimientos y a desarrollar habilidades que exigen el uso de herramientas que permitan detectar las cuestiones relevantes, cuáles son los problemas y de qué tipo, y cómo se puede llegar a propuestas argumentadas, válidas y razonables.
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    Gene-Specific Detection Rate of Adenomas and Advanced Adenomas in Lynch Syndrome
    (Elsevier, 2025-09-01) Sánchez Brualla, Alicia; Castillo Iturra, Joaquín; Balmaña, Judith; Brunet, Joan; Castells Sánchez, Alba; Capellá, G. (Gabriel); Ladabaum, Uri; Dekker, Evelien; Moreira, Luciana; Pellisé, M.; Balaguer Prunés, Francesc; López Fernández, Adrià; Salces, Inmaculada; Picó, María Dolores; Rivas, Laura; Bujanda, Luis; Garzon, Marta; Pizarro, Angeles; Martinez de Castro, Eva; Roos, V.H.; Dueñas, Nuria; Pineda Riu, Marta; Moreno Calle, Lorena; Rodríguez Alonso, Lorena; Ramon y Cajal, Teresa; Llort, Gemma; Piñol, Virginia; López Arias, María .Jesús; Poves, Carmen; Garau, Catalina; Rodríguez Alcalde, Daniel; Herraiz, Maite; Álvarez Urrutia, Cristina; Dacal, Andrés; Carrillo Palau, Marta; Cid, Lucía; Ponce, Marta; Barreiro Alonso, Eva; Saperas, Esteban; Aguirre, Elena; Bastiaansen, B.; Ocaña, Teresa; Carballal, Sabela; Rivero Sánchez, Liseth; Ortiz, Oswaldo; Daca Álvarez, María; Prat Galito, Ricard; Bessa, Xavier; Cubiella, Joaquin; Jover, Rodrigo; Rodríguez Moranta, Francisco
    Background & Aims Colonoscopy is expected to reduce colorectal cancer (CRC) incidence in Lynch syndrome (LS) by detecting and removing adenomas. The existence of gene-specific differences in adenoma detection has been proposed yet remains insufficiently explored. This study aims to elucidate gene-specific adenoma detection rates and their association with post-colonoscopy CRC (PCCRC), which stands as an important issue in LS surveillance. Methods In this multicenter study, we analyzed 1072 LS carriers without prior CRC undergoing surveillance colonoscopy, evaluating adenoma and advanced adenoma (AA) detection rates by gene. The primary outcome was to compare adenoma detection rates in individuals without prior CRC carrying pathogenic variants in MLH1/MSH2 vs MSH6/PMS2. Subgroup analysis was performed to assess the intermediate risk profile in MSH6 carriers relative to MLH1/MSH2 and PMS2 carriers. We compared overall adenoma detection rates, adenoma burden, age at first adenoma occurrence, and 10-year cumulative detection rates. Risk factors for AA and PCCRC were also identified. Multiple testing and multivariate analyses were performed. Results The adenoma detection rates were similar across the 4 genes. However, MLH1/MSH2 carriers had a higher overall AA detection rate compared with MSH6/PMS2 carriers (14.5% vs 11.9%; P = .04) and showed higher cumulative AA detection rates over 10 years (21.6% vs 19.7%; P = .04). Subgroup analysis indicated that MSH6 carriers had an intermediate AA detection rate positioned between MLH1/MSH2 carriers and PMS2 carriers. Multivariate analysis indicated that AAs (odds ratio, 2.12; 95% confidence interval, 1.08–4.17; P=.03) and repeated AA detection (odds ratio, 4.62; 95% confidence interval, 1.70–12.57; P < .01) were independent risk factors for PCCRC. Conclusions Carriers of MLH1/MSH2 pathogenic variants are at a higher risk of developing AAs compared with those with MSH6/PMS2 mutations, with MSH6 carriers exhibiting an intermediate risk profile. AAs are an independent risk factor for PCCRC. LS patients with AAs should be identified as high risk and undergo enhanced colonoscopy surveillance.
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    Highest correlations between emotion regulation strategies and mood symptoms in bipolar disorder: A systematic review and Bayesian network meta-analysis
    (Elsevier, 2025-02-01) Oliva, Vincenzo; De Prisco, Michele; Fico, Giovanna; Possidente, Chiara; Bort, Marta; Fortea, Lydia; Montejo Egido, Laura; Anmella, Gerard; Hidalgo Mazzei, Diego; Murru, Andrea; Fornaro, Michele; Vieta i Pascual, Eduard, 1963-; Radua, Joaquim
    Bipolar disorder (BD) is associated with alterations in emotion regulation (ER) strategies, with both depressive and (hypo)manic symptoms correlated with utilization of maladaptive instead of adaptive strategies. However, which ER strategies are the most affected during the most severe mood symptoms remains unclear despite the potentially relevant treatment implications. To this end, we conducted a systematic review and Bayesian network meta-analysis (NMA) of studies documenting correlations between ER and depressive and (hypo)manic symptoms of BD, from inception until November 9th, 2023. We included 15 studies in the review, 14 of which provided data to conduct a Bayesian NMA. Rumination emerged as the ER strategy most strongly associated with both depressive (ES=0.43, 95%CrI=0.27,0.59) and (hypo)manic symptoms (ES=0.26, 95%CrI=0.05,0.46) of BD. Other ER strategies showed associations primarily with depressive symptoms. There was no significant heterogeneity or network inconsistency. These findings emphasize the importance of rumination in BD and suggest that altered ER strategies are more evident in depressive symptoms rather than (hypo)manic ones. While promising for targeted interventions, these results are based on crosssectional data, limiting causal interpretation. Future longitudinal studies are necessary to clarify the temporal dynamics of the relationship between affective symptoms and ER in BD. 
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    Circulating extracellular vesicles and neutrophil extracellular traps contribute to endothelial dysfunction in preeclampsia
    (Frontiers Media, 2024-12-13) Ramos, Alex; Youssef, Lina; Molina, Patricia; Torramade Moix, Sergi; Martínez Sánchez, Julia; Moreno Castaño, Ana Belen; Blasco, Miquel; Guillén Olmos, Elena; Moner Rafel, Blanca de; Pino, Marc; Tortajada, Marta; Camacho, Marta; Borrell, Maria; Crovetto, Francesca; Ramírez Bajo, María José; Ventura Aguiar, Pedro; Bañón Maneus, Elisenda; Rovira, Jordi; Escolar Albaladejo, Ginés; Carreras, Enric; Gratacós Solsona, Eduard; Diaz Ricart, M. Isabel; Crispi Brillas, Fàtima; Palomo, Marta
    Background: Preeclampsia (PE) is a pregnancy complication characterized by hypertension, proteinuria, endothelial dysfunction, and complement dysregulation. Placenta-derived extracellular vesicles (EVs), necessary in maternal-fetal communication, might contribute to PE pathogenesis. Moreover, neutrophil extracellular traps (NETs) play a pathogenic role in other complement-mediated pathologies, and their contribution in PE remains unexplored. Materials and methods: EVs were isolated from PE (peEVs) and normotensive pregnant women sera. NETs were obtained incubating donor-pre-activated neutrophils with PE or control sera. Microvascular (HMEC) endothelial cells (ECs) were incubated with PE or control sera with or without (depleted sera) EVs or NETs, to assess changes in VCAM-1, ICAM-1, VE-cadherin, eNOS, VWF, ROS, and C5b-9 deposits. Results were expressed as fold increase vs. control. Results: VWF, VCAM-1, and ROS expression was significantly higher in cells exposed to PE sera vs. control (12.3 ± 8.1, 3.6 ± 2.3, and 1.8 ± 0.2, respectively, p < 0.05), though significantly lower in cells exposed to depleted PE (dPE) sera (6.1 ± 2.7, 0.7 ± 0.6, and 1.2 ± 0.1, respectively, vs. control, p < 0.05). EC exposure to depleted control sera supplemented with peEVs (dC+peEVs) significantly increased VWF, VCAM-1, and ROS compared to non-supplemented sera (4.5 ± 0.3, 2.8 ± 2.0, and 1.4 ± 0.2, respectively, p < 0.05). ICAM-1, VE-cadherin, and C5b-9 did not differ among groups. ECs incubated with PE-NETs increased VWF and VCAM-1 and decreased VE-cadherin expression vs. control (4 ± 1.6, 5.9 ± 1.2, and 0.5 ± 0.1, respectively, p < 0.05), and notably increased C5b-9 deposit (7.5 ± 2.9, p < 0.05). ICAM-1 and ROS did not differ. Conclusions: Both circulating EVs and NETs from PE pregnant women exhibit a deleterious effect on ECs. Whereas EVs trigger a pro-oxidant and proinflammatory state, NETs potentiate the activation of the complement system, as already described in PE.
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    The portal vein in patients with cirrhosis is not an excessively inflammatory or hypercoagulable vascular bed a prospective cohort study
    (Wiley, 2022-07-11) Driever, Ellen G.; Magaz Martínez, Marta; Adelmeijer, Jelle; Turon, Fanny; Baiges Aznar, Anna; Olivas, Pol; Pérez Campuzano, Valeria; Hernández Gea, Virginia; Blasi Ibánez, Annabel; García Pagán, Juan-Carlos; Lisman, Ton
    Background: A hypercoagulable state is not associated with development of portal vein thrombosis in cirrhosis, as we previously demonstrated. However, some groups demonstrated elevated levels of inflammatory markers and activation of hemostasis in the portal vein (PV) compared to posthepatic veins, but because the liver is involved in clearance of these markers, we hypothesize that interpretation of these data is not straightforward. Aim: To determine whether the PV has particular proinflammatory/hypercoagulable characteristics by comparing plasma sampled in the PV, hepatic vein (HV), and the systemic circulation. Methods: Plasma samples from 51 cirrhotic patients with portal hypertension undergoing transjugular intrahepatic portosystemic shunt placement, were taken from the PV, HV, and jugular vein (JV). Markers of inflammation (lipopolysaccharide, tumor necrosis factor-α, interleukin-6, thiobarbituric acid-reactive substances), neutrophil-extracellular-traps (cfDNA, MPO-DNA), endothelial damage (von Willebrand factor [VWF]), and hemostasis were determined and compared among the three vascular beds. Results: Markers of inflammation were slightly, but significantly higher in the PV than in the HV and systemic circulation. VWF and markers of hemostasis were modestly elevated in the PV. Levels of multiple markers were lower in the HV compared with the PV and systemic circulation. Higher model for end-stage liver disease score was associated with a more prothrombotic state in all three sample sites. Conclusion: In contrast to published studies, we did not detect a clear proinflammatory or prothrombotic environment in the PV of cirrhotic patients. Many markers are lowest in the HV, indicating that the low levels of these markers in the HV, at least in part, reflect clearance of those markers in the liver.
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    Effect of immunosuppression in miRNAs from extracellular vesicles of colorectal cancer and their influence on the pre-metastatic niche
    (Nature Publishing Group, 2019-08-01) Ramírez Bajo, María José; Revuelta, Ignacio; Tubita, Valeria; Seguí Barber, Joan; Lozano, Juan José; Bañón Maneus, Elisenda; Rovira, Jordi; Cucchiari, David; Moya Rull, Daniel; Oppenheimer Salinas, Federico; Del Portillo, Hernando A.; Campistol Plana, Josep M.; Diekmann, Fritz
    Colorectal cancer (CRC) occurs with more aggressiveness in kidney transplant recipients compared to the general population. Immunosuppressive therapy plays a crucial role in the development of post-transplant malignancy. Concretely, cyclosporine A (CsA) has intrinsic pro-oncologic properties, while several studies report a regression of cancer after the introduction of rapamycin (RAPA). However, their effect on the extracellular vesicle (EV) content from CRC cell lines and their relevance in the pre-metastatic niche have not yet been studied. Here, we investigated the effect of RAPA and CsA in EV-miRNAs from metastatic and non-metastatic CRC cell lines and the role of relevant miRNAs transferred into a pre-metastatic niche model. EV-miRNA profiles showed a significant upregulation of miR-6127, miR-6746-5p, and miR-6787-5p under RAPA treatment compared to CsA and untreated conditions in metastatic cell lines that were not observed in non-metastatic cells. From gene expression analysis of transfected lung fibroblasts, we identified 22 shared downregulated genes mostly represented by the histone family involved in chromatin organization, DNA packaging, and cell cycle. These results suggest that EV-miR-6127, miR-6746-5p and miR-6787-5p could be a potential epigenetic mechanism induced by RAPA therapy in the regulation of the pre-metastatic niche of post-transplant colorectal cancer.
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    Assessing the role of endothelium-protective drugs: Functional and molecular insights into chronic thromboembolic pulmonary hypertension derived endothelial cells
    (Elsevier Masson SAS, 2025-07-31) Poyatos Dorado, Paula; Tura Ceide, Olga; Peinado Cabré, Víctor Ivo; Blanco Vich, Isabel; Osorio, Jeisson; Yuan, Shuai; Ramírez, Ana M.; Castellà Pericàs, Manuel; Rigol Muxart, Montserrat; Solanes, Núria; Straub, Adam C; Barberà i Mir, Joan Albert
    Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by the presence of organized clots obstructing the pulmonary arteries. Pulmonary endarterectomy (PEA) is the standard treatment, but in cases of inoperability, Riociguat, a soluble guanylate cyclase (sGC) stimulator, is the only approved pharmacological option. Endothelial dysfunction (ED) plays a central role, with the NO/sGC/cGMP pathway being critically involved. The aim of this study is to identify the molecular pathways contributing to ED and assess the therapeutic potential of Riociguat, BAY 60-2770, and Sildenafil in reinstating vascular homeostasis. Materials and methods: Endothelial cells (ECs) were isolated from PEA specimens of individuals diagnosed with CTEPH (CTEPH-EC). ECs derived from healthy pulmonary arteries (HPAECs) were used as controls. Cells were treated with different concentrations of Riociguat, BAY-60-2770 and Sildenafil, followed by functional assays, transcriptomic, and molecular analyses. Results: The drugs used induced significant effects on endothelial cell dynamics, including decreased proliferation, increased apoptosis, and enhanced angiogenesis both in vitro and in vivo. Transcriptomic analysis followed by validation studies identified significant alterations in genes related to angiogenesis, with marked changes observed following BAY 60-2770 treatment. Dysregulation in the ERK/eNOS/PKG signaling pathway was demonstrated in CTEPH-EC compared to HPAEC at both the gene and protein level. Treatment with Riociguat and Sildenafil restored ERK/eNOS, but not PKG signaling. Conclusion: Therapeutic approaches targeting endothelial dysfunction and the NO/sGC pathway in CTEPH partially restore endothelial function, highlighting the dual action of Riociguat and Sildenafil, stimulating sGC while exerting upstream effects by enhancing eNOS signaling. These findings underscore the importance of targeted pharmacological approaches to improve patient outcomes.
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    Functional impairment in adult bipolar disorder with ADHD
    (Elsevier B.V., 2018-02) Torres, Imma; Garriga, Marina; Solé Cabezuelo, Brisa; Bonnín Roig, Caterina del Mar; Corrales, Montserrat; Jiménez Martínez, Esther; Solé, Eva; Ramos-Quiroga, Josep Antoni; Vieta i Pascual, Eduard, 1963-; Goikolea, José Manuel; Martínez-Arán, Anabel, 1971-
    Background: It is well established that patients with either bipolar disorder (BD) or attention-deficit/hyperactivity disorder (ADHD) present functional impairment even when in remission. Nevertheless, research on functional impairment with adult patients with bipolar disorder comorbid to ADHD (BD+ADHD) is very scarce. The main objective of the current report was to evaluate the overall and specific domains of functioning, in patients with BD+ADHD compared to patients with pure bipolar disorder (pBD) and healthy controls (HCs). Method: 162 subjects from 3 groups were compared: 63 pBD, 23 BD+ADHD and 76 HCs. All the patients with BD had been euthymic for at least 6 months and they were recruited at the Hospital Clinic of Barcelona. All the participants were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS) and the Functioning Assessment Short Test (FAST). Clinical, and sociodemographic data were also recorded. Results: Clinical groups, pBD and BD+ADHD, showed lower overall functioning (p < 0.001) in each domain of the FAST scale compared to the HCs. Moreover, the Tukey post hoc test revealed that the BD+ADHD group showed a worse score than pBD in the cognitive domain of the FAST. However, after controlling for potential confounding variables, only the HDRS scores (p < 0.026) remained significant for the cognitive domain of the FAST. Limitations: The small sample size of the comorbid BD+ADHD group. Conclusions: Adult patients with BD+ADHD showed the worst scores in functioning compared with the HCs, but did not show more severe functional impairment than the pBD group except for the cognitive domain. Therefore our findings suggest that depressive symptoms in adults with BD+ADHD may negatively influence cognitive functioning. Further studies are needed to confirm our findings for the management of BD+ADHD.