Artículos (Instituto de Biomedicina de Sevilla (IBIS))

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Prospective validation of imaging and serum diagnostic biomarkers of steatohepatitis and fibrosis in MASLD: the LITMUS Imaging Study
(Springer Nature, 2026-07-24) Pavlides, Michael; Vali, Yasaman; Mózes, Ferenc E.; Wonders, Kristy; Akhtar, Salma; Hockings, Paul D.; Romero Gómez, Manuel; Anstee, Quentin M.; Medicina; Instituto de Biomedicina de Sevilla (IBIS); Cancer Research UK (CR-UK); National Institute for Health Research (NIHR); Oxford Biomedical Research Centre; Oxford Centre for Early Cancer Detection; Cancer Research UK Oxford Centre; Siemens Healthineers; Newcastle NIHR Biomedical Research Centre; Horizon Europe, IMI-2; European Union (UE); NIHR Nottingham Biomedical Research Centre; PNRR M4C2I1.3 Heal Italia; LITMUS central laboratory; UK Department of Health; LITMUS Histopathology Group (LHG)
There is a need for robust evaluations of noninvasive biomarkers for metabolic dysfunction-associated steatotic liver disease. This prospective multicenter study assessed the diagnostic accuracy of imaging (including liver stiffness measurement (LSM) using magnetic resonance elastography (MRE) and FibroScan (vibration-controlled transient elastography (VCTE)), serum biomarkers (including NIS2+) and composite scores (including Agile 3+ and Agile 4) for centrally read steatohepatitis and fibrosis. For cirrhosis, several biomarkers exceeded the minimum acceptable performance criterion (MAC), including MRE (area under the receiver operating curve (AUC) 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Among 357 participants, fibrosis stages F0–F4 were present in 12%, 16%, 25%, 32% and 15%, respectively. NIS2+ had the highest diagnostic accuracy among serum biomarkers for metabolic dysfunction-associated steatohepatitis (MASH; AUC 0.83) and at-risk MASH (MASH with at least stage 2 fibrosis; AUC 0.82), although neither significantly exceeded the MAC (P = 0.15 and P = 0.19). Among imaging biomarkers, MRE showed the highest performance for MASH (AUC 0.71) and at-risk MASH (AUC 0.75), but these remained below the MAC. For fibrosis staging, performance was stronger: MRE met the MAC for advanced fibrosis (AUC 0.91; P < 0.01), as did Agile 3+ (AUC 0.84; P = 0.03). For cirrhosis, several biomarkers exceeded the MAC, including MRE (AUC 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Serum biomarkers tended to outperform imaging for identifying at-risk MASH, whereas elastography and composite scores showed excellent accuracy for staging advanced fibrosis and cirrhosis.
No Differences of Immune Activation and Microbial Translocation Among HIV-infected Children Receiving Combined Antiretroviral Therapy or Protease Inhibitor Monotherapy
(Wolters Kluwer Health, Inc., 2015-03) Falcon-Neyra, Lola; Benmarzouk-Hidalgo, Omar J.; Madrid, Lola; Noguera-Julián, Antoni; Fortuny, Claudia; Neth, Olaf; López Cortés, Luis Fernando; Medicina; Farmacología, Pediatría y Radiología; Instituto de Biomedicina de Sevilla (IBIS)
This is a cross-sectional study of 15 aviremic chronic HIV-infected children revealing no differences in immune activation (IA; HLA-DR+CD38+ CD4+ and CD8+ T cells, and sCD14) and microbial translocation (MT; lipopolysaccharides (LPS) and 16S rDNA) among HIV-infected patients under combined antiretroviral treatment (cART; n = 10) or ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv; n = 5). In both cases, IA and MT were lower in healthy control children (n = 32). This observational study suggests that ritonavir boosted protease inhibitor monotherapy (mtPI/rtv) is not associated with an increased state of IA or MT as compared with children receiving cART.
Productivity loss due to premature mortality caused by blood cancer: a study based on patients undergoing stem cell transplantation
(Elsevier, 2015-06) Ortega-Ortega, Marta; Oliva-Moreno, Juan; Jiménez Aguilera, Juan de Dios; Romero-Aguilar, Antonio; Espigado Tocino, Ildefonso; Medicina; Instituto de Biomedicina de Sevilla (IBIS)
Introduction: Stem cell transplantation has been used for many years to treat haematological malignancies that could not be cured by other treatments. Despite this medical breakthrough, mortality rates remain high. Our purpose was to evaluate labour productivity losses associated with premature mortality due to blood cancer in recipients of stem cell transplantations. Methods: We collected primary data from the clinical histories of blood cancer patients who had undergone stem cell transplantation between 2006 and 2011 in two Spanish hospitals. We carried out a descriptive analysis and calculated the years of potential life lost and years of potential productive life lost. Labour productivity losses due to premature mortality were estimated using the Human Capital method. An alternative approach, the Friction Cost method, was used as part of the sensitivity analysis. ResultsOur findings suggest that, in a population of 179 transplanted and deceased patients, males and people who die between the ages of 30 and 49 years generate higher labour productivity losses. The estimated loss amounts to over €31.4 million using the Human Capital method (€480,152 using the Friction Cost method), which means an average of €185,855 per death. The highest labour productivity losses are produced by leukaemia. However, lymphoma generates the highest loss per death. Conclusions: Further efforts are needed to reduce premature mortality in blood cancer patients undergoing transplantations and reduce economic losses.
Can We Safely Decrease Early-Term Delivery and Cesarean Section Rate in Pregnancies Complicated by Fetal Transposition of Great Arteries?
(MDPI, 2023-09-14) Chimenea-Toscano, Ángel; García Díaz, Lutgardo; Méndez, Ana; Antiñolo Gil, Guillermo; Cirugía; Instituto de Biomedicina de Sevilla (IBIS)
Background: Transposition of the great arteries (TGA) is a common critical neonatal congenital heart defect. After birth, physiological shunts close rapidly, necessitating early treatment with prostaglandin infusion and balloon-atrial septostomy. Timing of delivery is challenging, balancing the risks and advantages of early-term delivery and specialized care. The aim of this study is to assess the safety of a full-term delivery policy in fetuses diagnosed with TGA. Methods: A retrospective chart review was conducted of 17 women with a prenatal diagnosis of fetal TGA at Virgen del Rocío University Hospital between 2015 and 2021. Primary outcomes included: incidence of preterm, early-term, full-term, and late-term delivery, and rate of cesarean section. Secondary outcomes included: Saturday to Sunday admission and birth, and delivery between 0:00 a.m. and 8:00 a.m. Results: Full-term birth was achieved in 94.1%, reaching a low cesarean delivery rate (17.6%). A total of 82.4% of infants were born on weekdays, and only in three of the cases (17.6%) did delivery occur between 0 a.m. and 8 a.m. The median birth weight was 3300 g. Intravenous prostaglandins were administered in all cases, and 94.1% required balloon-atrial septostomy. Conclusions: In our study favoring full-term delivery, we reduce early-term deliveries and the cesarean section rate in prenatally diagnosed TGA.
Hirschsprung's disease as a model of complex genetic etiology
(F Hernandez, 2013-04-19) Borrego, Salud; Ruiz-Ferrer, Macarena; Fernández, Raquel M.; Antiñolo Gil, Guillermo; Cirugía; Instituto de Biomedicina de Sevilla (IBIS); Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad de España; Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía
Hirschsprung disease (HSCR), or aganglionic megacolon, is a developmental disorder characterised by the absence of ganglion cells along variable length of the distal gastrointestinal tract, leading to the most common form of functional intestinal obstruction in neonates and children. Aganglionosis is attributed to a failure of neural crest cells to migrate, proliferate, differentiate or survive during enteric nervous system (ENS) development in the embryonic stage. The incidence of HSCR is estimated at 1/5000 live births and most commonly presents sporadically with reduced penetrance and male predominance, although it can be familial and may be inherited as autosomal dominant or autosomal recessive. In 70% of cases, HSCR occurs as an isolated trait and in the other 30% HSCR is associated with other congenital malformation syndromes. HSCR has a complex genetic etiology with several genes and loci being described as associated with either isolated or syndromic forms. These genes encode for receptors, ligands (especially those participating in the RET and EDNRB signaling transduction pathways), transcriptional factors or other cell elements that are usually involved in the neural crest cell development and migration that give rise to ENS. Nevertheless, the RET proto-oncogene is considered the major disease causing gene in HSCR. A common RET variant within the conserved transcriptional enhancer sequence in intron 1 has been shown to be associated with a great proportion of sporadic cases and could act as a modifier by modulating the penetrance of mutations in other genes and possibly of those mutations in the RET proto-oncogene itself.
Menopause age and hypercholesterolemia comorbidities: a region-wide retrospective cohort study in Andalusia, Spain (2016–2022)
(BMJ Group, 2026) Esteban Medina, Alberto; Fernández del Valle, Patricia; Fernández del Valle, Patricia; Sánchez, Ana; Susin, M. Belén; Loucera Muñecas, Carlos; Antiñolo Gil, Guillermo; Dopazo, Joaquín; Cirugía; Instituto de Biomedicina de Sevilla (IBIS); Ciencias de la Computación e Inteligencia Artificial; Junta de Andalucía; Ministerio de Ciencia y Tecnología (MCYT). España
Objectives: To quantify sex- and age-related differences in hypercholesterolaemia diagnosis and associated comorbidities around the menopausal transition, using a population-based real-world dataset. Design: Retrospective, multicentre, non-interventional observational cohort study. Setting: Region-wide public healthcare system data (primary and secondary care) from Andalusia (Spain), 2016–2022. Participants: All adult patients meeting inclusion criteria with a recorded diagnosis of hypercholesterolaemia between 1 January 2016 and 31 December 2022 (n=557 034; 227 834 men and 329 200 women). Interventions: None. Primary and secondary outcome measures: Primary outcomes were age- and sex-stratified patterns of hypercholesterolaemia diagnosis and comorbidity burden before and after age 50 years (proxy for post-menopausal age). Secondary outcomes included comorbidity-specific comparisons between sexes across age strata and trajectory-based analyses (OR trajectories and incidence-ratio summaries). Results: Women were diagnosed later than men (mean age 59.1 vs 56.0 years; mean difference 3.1 years, 95% CI 3.03 to 3.17). Hypercholesterolaemia diagnoses in women rose sharply around ages 50–55 and remained higher than in men at older ages. Comorbidity patterns differed by sex across age strata: compared with men, women aged ≥50 years had higher frequencies of osteoporosis (42 255 vs 2623), anxiety disorder (94 916 vs 31 374) and hypertension (147 538 vs 91 532), with statistically significant differences for these comparisons (p<0.001). Conclusions: Menopause age is a pivotal period associated with a shift towards higher hypercholesterolaemia diagnosis rates and a greater burden of specific comorbidities in women. These findings support sex-specific prevention and management strategies, particularly targeting the menopausal transition and early post-menopause.
Reducción del cuadro clínico asociado con la metatarsalgia en mujeres con un elemento tridimensional de descarga en calcetines biomecánicos: un informe preliminar de un ensayo clínico aleatorio
(Inspira Network Group S.L, 2024-12-26) Martínez Nova, Alfonso; Sánchez Rodríguez, Raquel; Munuera Martínez, Pedro Vicente; Podología
Objetivo: Aunque se conoce que calcetines con elementos biomecánicos reducen las presiones plantares, se desconoce si esto tiene un efecto beneficioso en pacientes con metatarsalgia. Por ello, el objetivo de este estudio fue valorar la escala clínica en pacientes mujeres con metatarsalgia tras un mes de uso de calcetines de alivio metatarsal. Pacientes y métodos: La muestra se compuso de 32 mujeres mayores de 55 años con metatarsalgia. Se realizaron dos grupos al azar, uno de 16 participantes (grupo experimental), que llevaría el calcetín Podoks Metatarsal® con descarga integrada durante un mes y otro de 16 participantes (grupo control), que llevaría un calcetín de iguales fibras y características, pero sin descarga integrada. Se realizó a todos los participantes el cuestionario Foot Function Index previo, y tras 30 días de uso. Resultados: Tras el mes de uso de los calcetines, las pacientes que usaron el calcetín experimental presentaron una mejor puntuación en la escala de dolor del Foot Function Index, presentando el grupo Podoks® una media de 29.8 ± 15.16 y el grupo control 38.3 ± 19.77 (p = 0.032). Las diferencias en la escala global se identifican en los apartados de dolor y discapacidad donde las pacientes que llevaron los calcetines experimentales presentaron valores más bajos en dichas subescalas (p = 0.023 y p = 0.042, respectivamente). Conclusiones: El uso de calcetines con elementos de descarga muestra una reducción del dolor asociada a la metatarsalgia, y también una mejora en la discapacidad percibida por la paciente. Así, los calcetines con elementos biomecánicos podrían formar parte del arsenal terapéutico del podólogo, como un elemento de tratamiento en estadios iniciales o bien como coadyuvante en deformidades más severas
Ceftaroline and ceftobiprole monotherapy for the treatment of Staphylococcus aureus infections: a systematic review and Bayesian meta-analysis
(Oxford University Press, 2026-07-14) Rando, Emanuele; Magrini, Eugenia; Sangiorgi, Flavio; Salvati, Federica; Catania, Francesca; Chiuchiarelli, Marta; López Cortés, Luis Fernando; Rodríguez-Baño, Jesús; Murri, Rita; Medicina; Instituto de Biomedicina de Sevilla (IBIS)
Background: The comparative efficacy of ceftaroline and ceftobiprole against standard of care for Staphylococcus aureus infections, including methicillin-resistant S. aureus remains uncertain. Thus, we conducted a systematic review and Bayesian meta-analysis to assess the efficacy and safety of ceftaroline and ceftobiprole monotherapy for non-urinary S. aureus infections. Methods: We registered the protocol in PROSPERO. We searched PubMed, Embase, Scopus, and Web of Science. We included randomized controlled trials and comparative non-randomized studies reporting adjusted estimates, enrolling patients with non-urinary S. aureus infections. The primary analysis assessed clinical cure in randomized trials using a Bayesian random-effects model with a vague prior. For ceftaroline, we additionally conducted an exploratory analysis using an observationally informed prior derived from non-randomized studies with variance inflation. Risk of bias was assessed with RoB 2 and ROBINS-I and certainty of evidence with GRADE. Results: Sixteen studies met inclusion criteria [11 ceftaroline (1030 subjects); 5 ceftobiprole (1265 subjects)]. In the primary analysis, the pooled odds ratio for clinical cure was 1.38 (95% CrI 0.81–2.44) for ceftaroline and 0.99 (95% CrI 0.59–1.62) for ceftobiprole. The exploratory ceftaroline analysis using an observationally informed prior yielded an odds ratio of 1.45 (95% CrI 0.91–2.38). Adverse events and serious adverse events were similar between groups. Certainty of evidence was low for ceftaroline and moderate for ceftobiprole. Conclusions: Current evidence does not demonstrate superiority of ceftaroline or ceftobiprole over standard-of-care therapy for clinical cure in non-urinary S. aureus infections. Estimates remain imprecise and are largely driven by registrational trials and subgroup data. These findings support cautious, indication-specific interpretation rather than routine preference of these agents over established therapies.
Bystander Effect Induced by Electrical Stimulation Promotes N2a Differentiation Through Interleukin-6
(MDPI, 2026-08-18) Martín Fernández, Daniel; Orta, Luis; Dorronsoro, Akaitz; Ruano Caballero, Diego; Yúfera García, Alberto; Daza Navarro, María Paula; Tecnología Electrónica; Biología Celular; Bioquímica y Biología Molecular; Ministerio para la Transformación Digital y de la Función Pública. España; European Union (UE); Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Ministerio de Hacienda. España; Junta de Andalucía
The bystander effect describes the induction of responses in non-targeted cells through cell signaling by directly stimulated cells. While this phenomenon has been extensively studied in the context of ionizing radiation, its occurrence following electrical stimulation (ES) remains poorly understood. Conditioned medium from N2a neuroblastoma cells exposed to voltage-controlled biphasic pulses at 500 mV/mm and 100 Hz induced neuronal differentiation in non-stimulated cells through an ES bystander effect. Bystander medium promoted morphological changes associated with neuronal differentiation, including increased neurite outgrowth and a reduction in the proliferation marker KI-67, indicating that the effects of ES extend to neighboring non-targeted cells. Molecular analysis revealed increased expression and secretion of interleukin-6 (IL-6) following ES, while neutralization of the IL-6 receptor inhibited the effects of ES, highlighting the role of IL-6 as a key mediator of this effect. We provide the first evidence that ES promotes a differentiation-associated bystander effect mediated by IL-6.
Integrated analysis of hematopoietic changes following heterochronic bone marrow transplantation between young and aged mice
(Elsevier, 2026-09-11) Bejarano García, José Antonio; Nufer, Melanie; Caracuel, Rocío; Caballero Velázquez, Teresa; Rodríguez Gil, Alfonso; Jordano, Alicia; Muñoz, Raquel; Piruat, José Ignacio; Pérez Simón, José Antonio; Medicina; Fisiología Médica y Biofísica; Instituto de Biomedicina de Sevilla (IBIS); BIO271: Expresión Génica en Eucariontes
Background Aging is a multifactorial process characterized by progressive loss of tissue homeostasis and regenerative capacity, with haematopoiesis being profoundly affected. Age-associated changes in hematopoietic stem cells (HSCs) include increased frequency but reduced function, impaired self-renewal, and myeloid bias, driven by both intrinsic defects and extrinsic cues from the bone marrow (BM) niche. While heterochronic BM transplantation (hBMT) has been used to distinguish donor- versus niche-driven mechanisms, most studies have focused on isolated readouts under simplified conditions. Objective to perform a systematic and descriptive analysis of hematopoietic reconstitution following hBMT in mice. Study design Young and aged CD45.1 mouse BM cells were transplanted into lethally irradiated young or aged CD45.2 recipients mice, and hematopoietic output was evaluated six months later. Age-matched non-transplanted controls were included to contextualize aging trajectories. Results The study confirm canonical features of hematopoietic aging, such as HSC accumulation, impaired lymphopoiesis, T cell memory skewing, and erythroid decline, but reveal that their expression after transplantation depends on the interplay of donor age, recipient environment, and procedural stress. Donor-intrinsic programs dominated the T cell compartment, driving naïve-to-memory conversion, PD1 upregulation, and Helios expression in regulatory T cells. By contrast, myeloid skewing and erythroid decline were dictated by recipient age, underscoring environmental influence. Importantly, the transplantation process itself imposed selective lineage stress, disproportionately affecting B cell development and conventional T cells, while sparing regulatory T cells and most myeloid compartment. Conclusions Together, this study provides a descriptive phenotypic atlas of post-transplant haematopoiesis, highlighting detrimental effects of the transplantation process itself and lineage- and tissue-specific vulnerabilities.
IL-6 family cytokines behind acute COVID-19 and Long COVID syndrome: Mechanisms, biomarkers, and intervention strategies
(Elsevier, 2026-10) Bustos, Matilde; Rodríguez Hernández, María A.; Biología Celular; Instituto de Salud Carlos III; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; European Union (UE); Consejo Superior de Investigaciones Científicas (CSIC)
IL-6 family of cytokines is increasingly recognized as a potential contributor to the immune alterations observed in COVID-19 and its long-term sequelae. Beyond the well-established pro-inflammatory actions of IL-6 itself, members of this family collectively orchestrate a complex network integrating antiviral defence, tissue repair, and maladaptive inflammation. Evidence accumulated over the past five years suggests altered regulation and signalling of those cytokines may help explain the heterogeneity of clinical outcomes, ranging from acute respiratory failure to persistent post-COVID symptoms. Recent advances -including the development of multispecific fusion proteins capable of simultaneously blocking viral entry and selectively modulating IL-6–related inflammatory pathways- highlight the expanding therapeutic potential of targeting this cytokine axis. Effective intervention requires precise knowledge of the cytokines temporal expression patterns to avoid interfering with beneficial immune responses. This review examines the molecular mechanisms involving IL-6 family cytokines, their promise as biomarkers of disease progression, and the current or emerging therapeutic strategies aimed at modulating their signalling pathways.
Progression of liver stiffness predicts clinical events in HIV/HCV-coinfected patients with compensated cirrhosis
(Springer Nature, 2015-12-07) Merchante Gutiérrez, Nicolás; Téllez, Francisco; Rivero-Juárez, Antonio; Ríos-Villegas, María José; Merino, Dolores; Márquez-Solero, Manuel; Macías Sánchez, Juan; Pineda Vergara, Juan Antonio; Medicina; Instituto de Biomedicina de Sevilla (IBIS); Junta de Andalucía; Fundación para la Investigación y la Prevención del SIDA en España (FIPSE); Ministerio de Sanidad. España; Instituto de Salud Carlos III; Fondo de Investigaciones Sanitarias; Plan Nacional R + D + I
Background: Our objective was to assess the predictive value of the changes of liver stiffness (LS) for clinical outcome in HIV/HCV-coinfected patients with compensated liver cirrhosis and a LS value < 40 kPa. Methods: Prospective cohort of 275 HIV/HCV-coinfected patients with cirrhosis, no previous liver decompensation (LD) and LS < 40 kPa. The time from diagnosis to LD and/or hepatocellular carcinoma (HCC) and the predictors of this outcome were evaluated. Significant progression of LS was defined as an increase ≥ 30 % over the baseline value at any time during the follow-up. Results: After a median (Q1-Q3) follow-up of 32 (20–48) months, 19 (6.9 %, 95 % CI: 3.8 %–9.9 %) patients developed a first LD and/or HCC. At the end of the follow-up, 247 (90 %) patients had undergone a further LS examination. Of them, 77 (31 %) patients had a significant progression of LS. The mean (SD) survival time free of LD and/or HCC was 67 (3) and 77 (1) months in patients with or without significant progression of LS (p = 0.01). Significant progression of LS was an independent predictor of LD and/or HCC (Adjusted Hazard Ratio 4.63; 95 % confidence interval: 1.34–16.02; p = 0.015). Conclusions: Significant progression of LS is associated with a higher risk of clinical events in HIV/HCV-coinfected patients with compensated cirrhosis and LS < 40 kPa.
The Effect of Incidental Consolidation on Management and Outcomes in COPD Exacerbations: Data from the European COPD Audit
(PLOS, 2015-07-27) Saleh, Aarash; López-Campos Bodineau, José Luis; Hartl, Sylvia; Pozo Rodríguez, Francisco; Roberts, C. Michael; Medicina; Instituto de Biomedicina de Sevilla (IBIS); European Respiratory Society
Objective: There is controversy regarding the significance of radiological consolidation in the context of COPD exacerbation (eCOPD). While some studies into eCOPD exclude these cases, consolidation is a common feature of eCOPD admissions in real practice. This study aims to address the question of whether consolidation in eCOPD is a distinct clinical phenotype with implications for management decisions and outcomes. Patients and Methods: The European COPD Audit was carried out in 384 hospitals from 13 European countries between 2010 and 2011 to analyze guideline adherence in eCOPD. In this analysis, admissions were split according to the presence or not of consolidation on the admission chest radiograph. Groups were compared in terms of clinical and epidemiological features, existing treatment, clinical care utilized and mortality. Results: 14,111 cases were included comprising 2,714 (19.2%) with consolidation and 11,397 (80.8%) without. The risk of radiographic consolidation increased with age, female gender, cardiovascular diseases, having had two or more admissions in the previous year, and sputum color change. Previous treatment with inhaled steroids was not associated. Patients with radiographic consolidation were significantly more likely to receive antibiotics, oxygen and non-invasive ventilation during the admission and had a lower survival from admission to 90-day follow-up. Conclusions: Patients admitted for COPD exacerbation who have radiological consolidation have a more severe illness course, are treated more intensively by clinicians and have a poorer prognosis. We recommend that these patients be considered a distinct subset in COPD exacerbation.
Polyphenol-rich Salicornia extract in lacunar stroke: a pilot randomised trial of safety and exploratory clinical outcomes
(Oxford University Press, 2026-05-20) Pérez Sánchez, Soledad; Río Mercado, Carmen del; Núñez Jurado, David; Najar, Ana María; Ocete, Rafael F.; López Azcárate, Cristina; Domínguez Ruiz, Carmen; Magni, Eleonora; León Justel, Antonio; Montaner, Joan; Biología Celular; Enfermería; Instituto de Salud Carlos III; European Union (UE)
Introduction: Cerebral small vessel disease is a major cause of lacunar stroke and vascular cognitive impairment, for which effective disease-modifying treatments are lacking. Polyphenols have shown neurovascular and neuroprotective effects in experimental models. We conducted a randomised pilot trial primarily to evluate the safety and tolerability of a polyphenol-rich Salicornia extract in patients with lacunar stroke. Patients and methods: In this randomised, double-blind, placebo-controlled, parallel-group pilot trial, patients with recent lacunar stroke received either 1 g/day of a polyphenol-rich Salicornia extractor placebo for 12 months (Clinical Trials. gov NCT06076122). The primary endpoint was safety and tolerability. Secondary exploratory outcomes included cognitive performance (Montreal Cognitive Assessment), physical function (6-min walk test and gait speed), biochemical parameters, ambulatory blood pressure and neuroimaging markers, assessed at baseline, 6 months and study completion. Results: Seventy-one participants were randomised (40 to placebo and 31 to Salicornia extract). No treatment-related serious adverse events were observed. Exploratory analyses of secondary outcomes suggested possible between-group differences in some cognitive and physical measures. At 12 months, adjusted MoCA scores were higher in the Salicornia group than in the placebo group (adjusted mean difference 2.22 points; 95% CI, 0.08–4.36;P = .042), although cognitive data were available for only 22/40 placebo-treated and 19/31 Salicornia-treated participants. Apparent differences were also observed in some physical function measures during follow-up. In biochemical parameters, a reduction in homocysteine levels was observed in both groups. No relevant between-group differences were detected in neuroimaging markers during follow-up. These secondary findings should be interpreted as exploratory only and not as evidence of efficacy. Discussion: Any apparent differences in secondary exploratory cognitive, functional and biochemical outcomes should be interpreted cautiously because of baseline imbalances, small sample size and substantial missing follow-up data. These findings should be considered hypothesis-generating only and not as evidence of efficacy. Conclusions: Long-term supplementation with a polyphenol-rich S ramosissima extract showed an acceptable safety profile in patients with lacunar stroke, although tolerability should be interpreted cautiously given the withdrawal rate. Larger, adequately powered trials are needed to determine whether these preliminary findings represent true treatment effects.
Muribaculum as a microbial contributor of rifaximin-induced mucosal protection during chemotherapy
(Taylor and Francis, 2026-06-12) Correale, Carmen; Morandi, Martina; Gil Gómez, Antonio; Silvestri, Alessandra; Gatti, Andrea; Braga, Daniele; Maroli, Annalisa; Foppa, Caterina; Zanet, Stefano de; Rescigno, Maria; Fisiología
Chemotherapy-induced intestinal mucositis is a frequent and dose-limiting toxicity that compromises cancer treatment outcomes and lacks effective targeted interventions. Here, we investigate the mechanisms by which the nonabsorbable antibiotic rifaximin mitigates chemotherapy-induced intestinal injury, focusing on microbiota-mediated preservation of epithelial barrier integrity. In a murine model of 5-fluorouracil (5-FU)- induced intestinal injury, rifaximin pretreatment reduced mucosal inflammation and tissue damage, preserved epithelial and mucus barrier integrity, and limited systemic endotoxemia. Importantly, rifaximin did not impair the antitumor efficacy of 5-FU in ApcMin/+C3arKO mice. To assess translational relevance, we employed a human intestinal ex vivo organ culture system (EVOC) and found that rifaximin preserved mucosal architecture, mucus balance, and tight junction integrity following inflammatory challenge. Microbiome profiling revealed that rifaximin reshaped the intestinal microbial community, preventing the depletion of health-associated taxa, including Muribaculum and Parasutterella. Functional experiments demonstrated that Muribaculum intestinale supplementation alone attenuated 5-FU–induced injury, reproducing key protective features of rifaximin treatment. Together, these findings identify Muribaculum as a microbial contributor to rifaximin's protective effects, supporting its potential role as a safe adjunctive strategy to improve gastrointestinal tolerability of cancer treatment.
Prevalence of Obstructive Sleep Apnea Among Patients With Venous Thromboembolism: A Systematic Review and Meta-Analysis
(Elsevier, 2026-07-24) Carrera-Cueva, Carlos; Vallejo Vaz, Antonio Javier; Sánchez López, Verónica; Mendoza Zambrano, Elva María; Brown Arreola, Adela Berenice; López-Ríos, Mª del Carmen; Medrano Ortega, Francisco Javier; Calderón Sandubete, Enrique José; Medicina; Instituto de Biomedicina de Sevilla (IBIS); Beca SEPAR (Sociedad espanola de enfermedades respiratorias) para proyectos de investigacion: Estudio clinico-traslacional del impacto de la Apnea obstructiva del sue no en la persistencia de los defectos de perfusion tras una Embolia de pulmon
Introduction Obstructive sleep apnea (OSA) and venous thromboembolism (VTE) share multiple risk factors and comorbidities, and several studies have reported a frequent coexistence of both conditions. However, the prevalence and clinical relevance of OSA among patients with acute VTE remain incompletely characterized. Methods Systematic review and meta-analysis including studies reporting OSA prevalence in patients with acute VTE. PRISMA recommendations were followed. Each step was performed by ≥2 investigators. We searched Pubmed/Cochrane/Embase until September 2024 using free/MeSH/Emtree terms related to VTE/PE/DVT and OSA. Quality of evidence was evaluated. A meta-analysis was conducted to estimate the pooled prevalence across the studies according to different criteria. Heterogeneity was assessed (I2 statistics) and subgroup, sensitivity and meta-regression analysis were conducted. Results From 5066 articles retrieved, 25 studies were eligible. Quality assessment of studies suggested low risk of bias for internal validity but frequent high risk of bias regarding external validity. Meta-analyses revealed an OSA prevalence defined by an apnea–hypopnea index (AHI) ≥ 5, ≥15 and ≥30 of 70% (95%CI 63–76%), 41% (95%CI 32–50%) and 21% (95%CI 16–26%), respectively. Prevalence was 8% (95%CI 4–13%) in studies assessing a known diagnosis of OSA through screening of health records. Heterogeneity was high (I2 > 70%). Conclusions Systematic sleep assessment in patients with VTE identifies a substantial burden of sleep-disordered breathing, with wide variability across studies. Mild AHI elevations should be interpreted cautiously, whereas moderate-to-severe OSA and hypoxemia-related phenotypes appear more clinically relevant. These findings support a targeted clinical evaluation and the need for prospective studies in this population.
What pulmonologists think about the asthma– COPD overlap syndrome
(Taylor & Francis Group, 2015-07) Miravitlles, Marc; Alcázar, Bernardino; Álvarez, Francisco Javier; Bazús, Teresa; Calle, Myriam; Casanova, Ciro; López-Campos Bodineau, José Luis; Plaza, Vicente; Medicina; Instituto de Biomedicina de Sevilla (IBIS)
Background: Some patients with COPD may share characteristics of asthma; this is the so-called asthma–COPD overlap syndrome (ACOS). There are no universally accepted criteria for ACOS, and most treatments for asthma and COPD have not been adequately tested in this population. Materials and methods: We performed a survey among pulmonology specialists in asthma and COPD aimed at collecting their opinions about ACOS and their attitudes in regard to some case scenarios of ACOS patients. The participants answered a structured questionnaire and attended a face-to-face meeting with the Metaplan methodology to discuss different aspects of ACOS. Results: A total of 26 pulmonologists with a mean age of 49.7 years participated in the survey (13 specialists in asthma and 13 in COPD). Among these, 84.6% recognized the existence of ACOS and stated that a mean of 12.6% of their patients might have this syndrome. In addition, 80.8% agreed that the diagnostic criteria for ACOS are not yet well defined. The most frequently mentioned characteristics of ACOS were a history of asthma (88.5%), significant smoking exposure (73.1%), and postbronchodilator forced expiratory volume in 1 second/forced vital capacity <0.7 (69.2%). The most accepted diagnostic criteria were eosinophilia in sputum (80.8%), a very positive bronchodilator test (69.2%), and a history of asthma before 40 years of age (65.4%). Up to 96.2% agreed that first-line treatment for ACOS was the combination of a long-acting β2-agonist and inhaled steroid, with a long-acting antimuscarinic agent (triple therapy) for severe ACOS. Conclusion: Most Spanish specialists in asthma and COPD agree that ACOS exists, but the diagnostic criteria are not yet well defined. A previous history of asthma, smoking, and not fully reversible airflow limitation are considered the main characteristics of ACOS, with the most accepted first-line treatment being long-acting β2-agonist/inhaled corticosteroids.
Metabolic and functional analysis including repetitive antigen stimulation provides a more accurate assessment for CAR-T cell product quality and long-term functionality
(Biomed central LTD; BMC; Springer Science and Business Media LLC; Springer Nature, 2026-07-11) Beatriz Guijarro-Albaladejo; Belén Sierro-Martínez; Inmaculada Carrasco-Brocal; Paola Hernández-Díaz; María de la Rosa-Garrido; Raquel Muñoz-García; Rodríguez Gil, Alfonso; Pérez Simón, José Antonio; Estefanía García-Guerrero; Fisiología Médica y Biofísica; Medicina; Instituto de Biomedicina de Sevilla (IBIS); Instituto de Salud Carlos III; BIO271: Expresión Génica en Eucariontes
Background: BCMA-directed CAR-T cell therapy has demonstrated remarkable clinical efficacy in multiple myeloma, but robust methods to evaluate product quality and predict long-term functionality remain underdeveloped. While immunophenotypic features of leukapheresis products correlate with clinical outcomes, the characterization of infused CAR-T cell products remains challenging and inconsistent across studies. METHODS: We compared two versions of our academic BCMA-CAR product, CARTemis-1, differing only in their costimulatory domains (4-1BB vs. CD28), and performed a detailed functional and molecular characterization before and after antigen stimulation to identify which analytical approaches best capture functionally relevant differences between CAR-T cell products. Analyses included conventional flow cytometry, short-term cytotoxicity assays, repetitive antigen stimulation, metabolic profiling, and transcriptomic evaluation. Finally, metabolic profile of patient derived CAR-T cells products (n = 15) was also analyzed. RESULTS: Although previous studies have reported functional differences between CAR-T cell products incorporating distinct costimulatory domains, conventional assays in our system revealed no significant differences in viability, expansion dynamics, immunophenotype, or activation/exhaustion marker expression. In contrast, more functionally demanding assays revealed clear differences between constructs. Repetitive antigen stimulation revealed superior long-term cytotoxicity in CARTemis-1-BB, while metabolic profiling demonstrated enhanced spare respiratory capacity and maximal respiration after antigen exposure. Transcriptomic analysis further showed distinct pathway regulation, with enrichment of T cell activation signatures in CARTemis-1-BB and Wnt/TGFβ-related responses in CARTemis-1-28. Importantly, metabolic profiling of infused CAR-T cell products also identified distinct signatures associated with clinical outcome, distinguishing products administered to long-term responders from those infused into short-term or non-responding patients. CONCLUSIONS: Persistence and metabolic analyses represent key tools for optimizing CAR-T cell construct selection during preclinical development, providing a more accurate assessment of CAR-T cell product quality than standard immunophenotyping and enabling the identification of constructs with superior therapeutic potential
Family quality of life in early intervention: systematic review and meta-analysis
(Frontiers media SA, 2026-06-24) Pérez-Granado, Sara; Palomo-Carrión, Rocío; Piñero Pinto, Elena; Fisioterapia; Instituto de Biomedicina de Sevilla (IBIS); CTS1174: Human Function Research Group - FunctionLab
Background: Family Quality of Life (FQOL) in Early Intervention (EI) has become a key factor for the evaluation of its results, since, in early ages, the family plays a fundamental role. The main objective of this review was to examine the scientific evidence on FQOL of families with children who attend EI services. Methods: This systematic review was conducted in the Pubmed, Scopus, Web of Science and CINAHL databases. Two meta-analyses were carried out using Cronbach's α of the measurement instruments and the means and standard deviations of FQOL. Results: The search produced 7,249 records, of which 10 were included. The statistical result of Cronbach's α was high, and that of FQOL was medium-high. Conclusions: Families participating in EI programs tend to report medium-to-high levels of FQOL. The factors that contribute to improving FQOL include: the supports provided by the professional, identification of strengths, satisfaction with the service, and transdisciplinary interventions focused on the family.
Genetically Engineered Mouse Models of Pituitary Tumors
(Frontiers Media SA., 2014-08-01) Cano, David A.; Soto Moreno, Alfonso Manuel; Leal Cerro, Alfonso; Medicina; Instituto de Biomedicina de Sevilla (IBIS); Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía; Ministerio de Sanidad. España; Instituto de Salud Carlos III
Animal models constitute valuable tools for investigating the pathogenesis of cancer as well as for preclinical testing of novel therapeutics approaches. However, the pathogenic mechanisms of pituitary-tumor formation remain poorly understood, particularly in sporadic adenomas, thus, making it a challenge to model pituitary tumors in mice. Nevertheless, genetically engineered mouse models (GEMMs) of pituitary tumors have provided important insight into pituitary tumor biology. In this paper, we review various GEMMs of pituitary tumors, highlighting their contributions and limitations, and discuss opportunities for research in the field.

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