Artículos (Medicina)

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Tratamiento de la bacteriemia por Staphylococcus aureus: evidencias y retos
(Elsevier, 2020-12) López-Cortés, Luis E.; Gálvez Acebal, Juan; Rodríguez-Baño, Jesús; Universidad de Sevilla. Departamento de Medicina; Gobierno de España; Instituto de Salud Carlos III
La bacteriemia por Staphylococcus aureus continúa siendo un reto diario para los clínicos. A pesar de todos los esfuerzos realizados, su mortalidad y morbilidad asociadas no han descendido de forma significativa en los últimos 20 años. Existe evidencia de que la adherencia a los indicadores de calidad para su manejo clínico es importante para mejorar el pronóstico de los pacientes, aunque su cumplimiento sigue siendo menor de lo deseado en muchos hospitales; en este sentido, la asistencia por especialistas en enfermedades infecciosas ha demostrado contribuir a reducir la mortalidad de estos pacientes. En este artículo se revisan los estudios clínicos más relevantes realizados en los últimos años con objeto de evaluar la eficacia y la seguridad de los fármacos alternativos a los clásicos. Sin embargo, estos siguen siendo utilizados en un alto porcentaje de pacientes, ya que los prometedores resultados obtenidos por esos fármacos alternativos y determinadas combinaciones en estudios in vitro y modelos animales no se han traducido en una evidente superioridad en los estudios clínicos con la frecuencia que se hubiera esperado. Dicho esto, existen datos que sugieren que determinadas alternativas pueden ofrecer ventajas en situaciones concretas. En general, es necesario un manejo individualizado y experto de los pacientes para decidir la mejor terapia en base al foco, la gravedad y las complicaciones, las características de los pacientes y los datos microbiológicos.
The challenge to improving and standardizing training in infectious diseases in Europe
(Elsevier, 2025-06) Rodríguez-Baño, Jesús; Skov, Robert L.; Friedland, Jon S.; Río, Carlos del; Akova, Murat; Zinkernagel, Annelies S.; Universidad de Sevilla. Departamento de Medicina
The recent COVID-19 pandemic once again demonstrates that infectious diseases pose a significant threat to humanity. Moreover, we are increasingly encountering emerging pathogens causing outbreaks, the growing problem of antimicrobial resistance threatens modern medicine, and the number of individuals at risk of serious infections is rising due to an ageing population and the more widespread use of immunosuppressive drugs and invasive procedures. Given these realities, it is no surprise that the medical specialty of infectious diseases (ID) has become a crucial component of modern clinical medicine, working in close collaboration with clinical microbiology and public health.
Individualised duration of treatment in febrile urinary tract infection: ready for prime time?
(Elsevier Science Ltd; Elsevier, 2025-04-02) Rodríguez-Baño, Jesús; Palacios-Baena, Zaira R.; Medicina
References The duration of antimicrobial treatment is currently a hot topic in the field of infectious diseases. For decades, the prevailing belief was that long treatments were essential to prevent relapses. This belief has been passed on to generations of trainees, even though there is little solid evidence to support it. However, ideas surrounding the duration of antibiotic treatment are evolving. Data from randomised trials have shown that shorter regimens (eg, 5–7 days) are non-inferior to longer regimens for pneumonia, soft tissue infections, intra-abdominal infections, urinary tract infections (UTIs), and bacteraemia.1 In this issue of The Lancet Infectious Diseases, Naqash Javaid Sethi and colleagues report the results of the INDI-UTI trial, which takes the concept of shorter antibiotic regimens a step further by testing an individualised duration of therapy.2
Effectiveness and tolerability of intravenous fosfomycin in treating complicated urinary tract infections caused by Escherichia coli: a prospective cohort study from the FOSFOMIC project
(Elsevier, 2025-05) Moreno Mellado, Elisa; Aslan, Abdullah Tarik; Akova, Murat; León, Eva; Merchante Gutiérrez, Nicolás; Vinuesa, David; Merino Bohórquez, Vicente; Rodríguez-Baño, Jesús; Docobo Pérez, Fernando; Gutiérrez Gutiérrez, Belén; Universidad de Sevilla. departamento de Medicina; Universidad de Sevilla. departamento de Farmacología; Universidad de Sevilla. departamento de Microbiología; CIBERINFEC; European Union (UE); Gobierno de España; Instituto de Salud Carlos III
Objectives: The FOSFOMIC study assessed the clinical and microbiological effectiveness, and safety of intravenous fosfomycin in treating complicated urinary tract infections (cUTIs) caused by Escherichia coli, in comparison with other intravenous antimicrobials. Methods: A prospective, multinational matched cohorts study involving adults with community-acquired cUTIs and receiving targeted therapy with intravenous fosfomycin or other first-line drugs (beta-lactams or fluoroquinolones) was conducted from November 2019 to May 2023 in ten centres from Spain, Italy, and Türkiye. Matching criteria included type of infection acquisition, Charlson and Pitt scores. Endpoints were clinical and microbiological cure, mortality, recurrence, and adverse effects. Analyses used conditional logistic regression and desirability of outcome ranking (DOOR). Results: Overall, 155 matched pairs were included. Clinical and microbiological cure rates were 65.2% (101/155; 95% CI, 57.4–72.2) and 63.2% (98/155; 95% CI, 55.4–70.4) with fosfomycin and comparators, respectively (adjusted OR, 1.09; 95% CI, 0.68–1.73; p 0.73). Mortality rates were 1.9% (3/155; 95% CI, 0.7–5.5) and 5.8% (9/155; 95% CI, 3.1–10.7), respectively (p 0.11). Recurrence rates were 14.2% (22/155; 95% CI, 9.6–20.6) in the fosfomycin group vs. 10.3% (16/155; 95% CI, 6.1–16.1) (p 0.39). Severe adverse effects occurred in 1.9% (3/155; 95% CI, 0.7–5.5) of patients treated with fosfomycin vs. 0.6% (1/155; 95% CI, 0.0–3.3) in the control group (p 0.62). Non-severe adverse effects were more frequent with fosfomycin, affecting 23.3% (36/155; 95% CI, 17.0–30.7) compared with 7.7% (12/155; 95% CI, 4.1–13.1) in the control group (adjusted OR, 5.36; 95% CI, 2.04–14.1; p < 0.001). In DOOR analysis, fosfomycin demonstrated comparable effectiveness in treating pyelonephritis (probability of better DOOR, 54.0%; 95% CI, 48.5–59.6) and in comparison with ceftriaxone (50.3%; 95% CI, 44.7–55.8), without evidence of inferiority in bacteraemic urinary tract infections (DOOR, 47.3%; 95% CI, 41.7–52.8). Discussion: Fosfomycin is a viable option for treating cUTIs caused by E. coli, allowing for diversification in the treatment of these high-incidence infections.
Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study)
(Elsevier Science Bv; Elsevier, 2021) Martínez Pérez-Crespo, Pedro María; Lanz-García, Joaquín Felipe; Bravo-Ferrer, José; Cantón Bulnes, María Luisa; Sousa Domínguez, Adrian; Goikoetxea Aguirre, Josune; Rodríguez-Baño, Jesús; López-Cortés, Luis E.; Medicina
The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60–81 years) and 3656 (58.3%; 95% confidence interval 57.1–59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients’ profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.
Mortality predictors and definition proposal for complicated coagulase-negative Staphylococcus bacteraemia: a multicentre prospective cohort study
(Wiley-Blackwell; Elsevier Sci Ltd, 2025) Varisco, Benedetta; Martínez Pérez-Crespo, Pedro María; Retamar Gentil, Pilar; López Hernández, Inmaculada; Fariñas Álvarez, Maria Carmen; Fernández-Natal, Isabel; Rodríguez-Baño, Jesús; López-Cortés, Luis E.; Medicina; Gobierno de España
Objectives The study aimed to explore a definition for complicated coagulase-negative staphylococci bloodstream infections (CoNS BSIs) and to identify predictors for mortality. Methods A prospective cohort study was conducted from October 2016 to March 2017 in 26 Spanish hospitals. Complicated CoNS BSI criteria included lack of early catheter removal in catheter-related cases, foreign indwelling implant, persistent bacteraemia, fever ≥72 hours on active therapy, metastatic infection or deep-seated focus, and infective endocarditis. Independent predictors for 30-day mortality were evaluated by Cox regression, and the impact of the definition of complicated bacteraemia was assessed. Results Overall, 445 CoNS BSI cases were included; catheter-related infections were predominant (336/445, 75.5%). Complicated bacteraemia was identified in 240 of 445 patients (53.9%); 30-day mortality in complicated and uncomplicated cases was 53 of 240 (22.1%) and 24/205 (11.7%), respectively (p 0.004). Predictors of 30-day mortality identified in the multivariate analysis included age (hazard ratio [HR]: 1.03, 95% CI: 1.01–1.05), cerebrovascular disease (HR: 2.58, 95% CI: 1.45–4.58), immunosuppressive therapy (HR: 2.16, 95% CI: 1.22–3.84), SOFA score (HR: 1.09, 95% CI: 1.03–1.16), and complicated bacteraemia (HR: 2.14, 95% CI: 1.29–3.53). A catheter-related source of bacteraemia was found to be protective (HR: 0.49, 95% CI: 0.30–0.80). When specific criteria to define complicated bacteraemia were included, fever ≥72 hours was associated with an increased risk of death (HR: 2.52, 95% CI: 1.52–4.17) and early catheter removal was protective (HR: 0.47, 95% CI: 0.26–0.83). Discussion A high proportion of patients presented complicated bacteraemia according to the proposed criteria; these patients had higher hazards for mortality. Other mortality predictors were identified. Further studies would be needed to validate the proposed criteria.
Baseline resistance-guided therapy does not enhance the response to interferon-free treatment of HCV infection in real life
(Nature Publishing Group; Nature Portfolio, 2018-10-08) Real Navarrete, Luis Miguel; Macías Sánchez, Juan; Pérez, Ana B.; Merino, Dolores; Granados, Rafael; Morano, Luis; Ríos-Villegas, María José; Merchante Gutiérrez, Nicolás; Pineda Vergara, Juan Antonio; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Universidad de Sevilla. TIC154: Departamento de Ingeniería Telemática
Hepatitis C virus (HCV) response to direct-acting antivirals (DAAs) may be influenced by the presence of resistance-associated substitutions (RASs). This study aimed to assess if NS5A baseline RAS-guided treatment enhances the rate of sustained viral response (SVR) in naïve HCV-infected patients in clinical practice. All HCV-infected patients who initiated treatment with interferon (IFN)-free DAA based regimens between March 2016 and May 2017 in 17 Spanish hospitals and who had evaluable SVR 12 weeks (SVR12) after the end of therapy were included. Patients had to be DAA naïve, with the exception of sofosbuvir with/without IFN. In one hospital, participants received therapy guided by the presence of NS5A-RASs (RGT population). Patients enrolled in the remaining hospitals, without baseline RASs testing, constituted the control population. A total of 120 and 512 patients were included in the RGT and control populations, respectively. Nine (7.5%) individuals in the RGT population showed baseline NS5A-RASs. All of them achieved SVR12. The SVR12 rate in the RGT population was 97.2% (three relapses) whereas it was 98.8% (six relapses) in the control population (p = 0.382). Our findings suggest that testing for baseline NS5A-RASs in naïve HCV-infected patients does not enhance the rate of SVR to DAA-based IFN-free therapy in clinical practice.
Shaping current European mitochondrial haplogroup frequency in response to infection: the case of SARS-CoV-2 severity
(Nature Briefing, 2025-01) Cabrera Alarcón, José Luis; Cruz, Raquel; Rosa-Moreno, Marina; Latorre-Pellicer, Ana; Diz de Almeida, Silvia; SCOURGE cohort group; Medrano Ortega, Francisco Javier; Rodríguez Hernández, María A.; Morilla Romero de la Osa, Rubén; Valido Morales, Agustín S.; Enríquez, José Antonio; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Enfermería; Instituto de Biomedicina de Sevilla (IBIS)
The frequency of mitochondrial DNA haplogroups (mtDNA-HG) in humans is known to be shaped by migration and repopulation. Mounting evidence indicates that mtDNA-HG are not phenotypically neutral, and selection may contribute to its distribution. Haplogroup H, the most abundant in Europe, improved survival in sepsis. Here we developed a random forest trained model for mitochondrial haplogroup calling using data procured from GWAS arrays. Our results reveal that in the context of the SARS-CoV-2 pandemic, HV branch were found to represent protective factors against the development of critical SARS-CoV-2 in an analysis of 14,349 patients. These results highlight the role of mtDNA in the response to infectious diseases and support the proposal that its expansion and population proportion has been influenced by selection through successive pandemics.
No association of a risk variant for severe COVID-19 with HIV protection in three cohorts of highly exposed individuals
(Oxford University Press, 2022-08-04) Sironi, Manuela; Cagliani, Rachele; Biasin, Mara; Lo Caputo, Sergio; Saulle, Irma; Forni, Diego; Real Navarrete, Luis Miguel; Pineda Vergara, Juan Antonio; Clerici, Mario; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Ministerio de Economia, Industria y Competitividad (MINECO). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
An extended haplotype on chromosome 3 is the major genetic risk factor for severe COVID-19. The risk haplotype, which was in herited from Neanderthals, decreases the expression of several cytokine receptors, including CCR5. Recently, a study based on three general population cohorts indicated that the minor allele of one of the variants in the haplotype (rs17713054) protects against HIV infection.We thus expectedthisallele to beover-represented in highly exposedindividuals whoremainuninfected(exposedseroneg ative individuals, ESN). To perform a meta-analysis, we genotyped rs17713054 in three ESN cohorts of European ancestry exposed to HIV through different routes. No evidence of association was detected in the single cohorts. The meta-analysis also failed to de tect any effect of the variant on protection from HIV-1. The same results were obtained in a Cox-regression analysis for the time to seroconversion. An in-vitro infection assay did not detect differences in viral replication as a function of rs17713054 genotype sta tus. We conclude that the rs17713054 minor allele is not associated with the ESN phenotype and does not modulate HIV infection in vitro.
Genetic associations between modifiable risk factors and Alzheimer disease
(Amer medical assoc, 2023-05-01) European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration; Mir Rivera, Pablo; Real Navarrete, Luis Miguel; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS)
IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]). CONCLUSIONS AND RELEVANCE This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.
Incidence of and factor sassociated with SARS-CoV-2 infection among people living with HIV in Southern Spain after one year of pandemic
(Wiley, 2021-08-17) Fernández-Fuertes, Marta; Corma-Gómez, Anaís;; Torres, Eva; Rodríguez-Pineda, Elena; Fuentes-López, Ana; Rincón, Pilar; Fernández, Nieves; García, Federico; Bernal, Samuel; Real Navarrete, Luis Miguel; Macías Sánchez, Juan; Pineda Vergara, Juan Antonio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Medicina; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Gobierno de España
Whether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of associated factors with and the clinical outcome of SARS-CoV-2 infection in PLWH in Southern Spain. This prospective cohort study included PLWH from a Tertiary University Hospital in Southern Spain. Patients were enrolled in the study if (1) they had attended as outpatients our Unit from 1 August 2019 to 8 February 2020 and (2) had two subsequent evaluations from 9 February 2020 to 4 March 2021. SARS-CoV-2 infections were diagnosed by PCR, antigen detection or serology. Seven hundred and nine PLWH were included in the study. Of them, 55 [7.8%, 95% confidence interval (95% CI) 5.9%–9.9%] patients developed SARS-CoV-2 infection. Between 18 May and 29 November 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%–9.0%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%–2.6%) for PLWH in this study (p = .001). After multivariable analysis, adjusted by age, sex, and risk factors for HIV infection, active tobacco use and CDC stage, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection [Incidence rate ratio: 0.29 (95% CI 0.16–0.55) p < .001]. In conclusion, the incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area.
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
(Natural Academy Sciences, 2023-08-29) Le Guen, Yann; Luo, Guo; Ambati, Aditya; Damotte, Vincent; Jansen, Iris E.; Yu, Eric; Mir Rivera, Pablo; Real Navarrete, Luis Miguel; Swieten, John Van; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
We report that specific HLA-DRB1*04 alleles are protective against Alzheimer’s dementia (AD), Parkinson’s disease (PD), and other neurodegenerative disorders. Further, we found that these HLA (Human Leukocyte Antigen) subtypes selectively bind a piece of Tau crucial to aggregation but only when it is acetylated (a-PHF6). This a-PHF6 piece is significant as it is a common posttranslational modification of Tau found in Alzheimer’s brains. Only when someone is HLA-DRB1*04:04 or HLA-DRB1*04:01 can PHF6 be presented as a T cell epitope to T cell receptors and mount a memory immune response against this pro-aggregation fragment. This immune response would protect against AD, PD, and neurodegeneration, explaining the HLA association. Vaccination with a-PHF6 in HLA-DRB1*04 individuals could have preventive effects.
Documento de consenso para la determinación e informe del perfil lipídico en laboratorios clínicos españoles: ¿Qué parámetros debe incluir un perfil lipídico básico?
(De Gruyter, 2023-05-18) Arrobas Velilla, Teresa; Guijarro, Carlos; Campuzano Ruiz, Raquel; Rodríguez Piñero, Manuel; Valderrama Marcos, José Francisco; Botana López, Antonio M.; Castilla Guerra, Luis; Salgueira Lazo, Mercedes; Pérez Pérez, Antonio; Grupo Multidisciplinar de Trabajo de Lípidos y Riesgo Vascular
Las enfermedades cardiovasculares (ECV) siguen siendo la principal causa de muerte en nuestro país. El control adecuado de las alteraciones del metabolismo lipídico es un reto clave en prevención cardiovascular que está lejos de alcanzarse en la práctica clínica real. Existe una gran heterogeneidad en los informes del metabolismo lipídico de los laboratorios clínicos españoles, lo que puede contribuir al mal control del mismo. Por ello, un grupo de trabajo de las principales sociedades científicas implicadas en la atención de los pacientes de riesgo vascular hemos elaborado este documento con una propuesta básica de consenso sobre la determinación del perfil lipídico básico en prevención cardiovascular, recomendaciones para su realización y unificación de criterios para incorporar los objetivos de control lipídico adecuados al riesgo vascular de los pacientes en los informes de laboratorio.
Development and Validation in Porcine and Human Models of a Bioimpedance Spectroscopy System for the Objective Assessment of Kidney Graft Viability
(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Naranjo Hernández, David; Reina Tosina, Luis Javier; Roa Romero, Laura María; Barbarov-Rostán, Gerardo; Calvillo Arbizu, Jorge; Talaminos Barroso, Alejandro; Pérez Valdivia, Miguel Ángel; Medina López, Rafael; Universidad de Sevilla. Departamento de Teoría de la Señal y Comunicaciones; Universidad de Sevilla. Departamento de Ingeniería Telemática; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Cirugía; Fundación Mutua Madrileña; Junta de Andalucía
This work presents an innovative bioimpedance spectroscopy device, developed as a support tool for decision-making during the evaluation of kidney viability for renal transplantation. Given the increasing demand for organs and the need to optimize donation criteria, the precise and objective assessment of renal graft functionality has become crucial. The device, based on a modular design and adapted to the surgical environment, uses a novel Cole model with a frequency-dependent membrane capacitance, which improves measurement accuracy and repeatability compared to conventional models. Adapting the device for operating room usege involved overcoming significant challenges, such as the need for sterilization and a visual, tactile and acoustic user interface that facilitates device usability. Optimizing the sensing stage has minimized the influence of measurement artifacts, which is crucial for obtaining accurate and representative measurements of renal tissue bioelectrical properties. In addition, a rigorous electrode sterilization protocol was designed, ensuring asepsis during the procedure. The results of tests on porcine renal models demonstrated the device’s ability to monitor pathophysiological changes associated with renal ischemia, with a notable improvement against measurement repeatability.
Cortical volumetry and longitudinal cognitive changes in Parkinson’s disease: insights from the COPPADIS cohort
(Springer, 2025) Álvarez-Avellón, Tania; Solares, Carmen; Álvarez‑Carriles, Juan; Franco-Rosado, Pablo; Diaz‑Galvan, Patricia; Santos-García, Diego; Mir Rivera, Pablo; Menéndez‑González, Manuel; Universidad de Sevilla. Departamento de Psicología Experimental; Universidad de Sevilla. Departamento de Medicina; Fundación Española de Ayuda a la Investigación en Enfermedades Neurodegenerativas y/o de Origen Genético; Alpha Bioresearch; Ministerio de Economía y Competitividad (MINECO). España; Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Fundación Alicia Koplowitz; European Union (UE)
Cognitive decline is a major non-motor symptom in Parkinson’s disease (PD), often linked to brain atrophy. This study examines the relationship between cortical atrophy and age groups in predicting cognitive decline in PD over five years. 188 PD patients from the COPPADIS cohort were stratified by age: young (30–55 years, N = 47), middle-aged (56–65 years, N = 59), and older adults (66–75 years, N = 82). Baseline cortical volume was assessed using T1-weighted MRI, and cognitive decline was evaluated using the annual rate of change of the Parkinson’s Disease-Cognitive Rating Scale (PD-CRS). Parametric or non-parametric tests were applied to evaluate group differences. Main analyses consist of several multiple regression analyses to examine associations between baseline brain atrophy and cognitive decline by age group. Older adults exhibited significantly greater cognitive decline in comparison to the younger age groups in the three compose scores of the PDCRS -Fronto-subcortical (H(2) = 41.08, p < 0.001), Posterior Cortical (H(2) = 22.03, p < 0.001), and Total(H(2) = 41.13, p < 0.001). Higher educational level has a significant positive effect on older adults, specifically for working memory performance, delayed verbal memory and the fronto-subcortical composed score. Multiple regression models underscored the predictive value of the bilateral hippocampus, bilateral medial orbitofrontal cortex, right precuneus, and right isthmus cingulate gyrus, together with being an older adult or having a higher education. MRI measures, age, and education predict cognitive decline in PD. Longitudinal assessments are essential for refining atrophy-cognition correlations and optimizing patient stratification.
X-chromosome-wide association study for Alzheimer's disease
(Nature publishing group; Springernature; Springer Science and Business Media LLC, 2024-12-04) Le Borgne, Julie; Heikkinen, Sami; Amin, Najaf; Ahmad, Shahzad; Choi, Seung Hoan; Bis, Joshua; Mir Rivera, Pablo; Real Navarrete, Luis Miguel; Rodriguez-Rodriguez, Eloy; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); NIA NIH HHS
Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10-6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.
The biochemical pattern defnes MASLD phenotypes linked to distinct histology and prognosis
(Springer, 2024-04-15) Ampuero Herrojo, Javier; Aller, Rocío; Gallego Durán, Rocío; Crespo, Javier; Calleja, Jose Luis; García-Monzón, Carmelo; Maya Miles, Douglas; Romero Gómez, Manuel; Universidad de Sevilla. Departamento de Medicina
Background,MASLD can manifest as hepatocellular damage, which can result in mild elevation of aminotransferases. However, in some patients, MASLD presents with cholestatic pattern.,Objective,To assess the impact of the biochemical pattern on the natural course of MASLD, including liver damage in histology, the accuracy of non-invasive tests(NITs), and prognosis.,Methods,Multicenter study enrolling 2156 patients with biopsy-proven MASLD, who were classified based on their[ALT/ULN)]/[(ALP/ULN)] levels at the time of biopsy: (a) hepatocellular pattern(H), > 5; (b) mixed pattern(M),2–5; (c) cholestatic pattern(C), < 2. Outcomes: (a) histological evaluation of the single components of NAS, MASH, and fibrosis; (b) NITs and transient elastography assessing advanced fibrosis; (c) prognosis determined by the appearance of decompensated cirrhosis and death.,Results,Out of the 2156 patients, 22.9% exhibited the H-pattern, whilst 31.7% exhibited the C-pattern. Severe steatosis, ballooning, lobular inflammation, and MASH (56.4% H vs. 41.9% M vs. 31.9% C) were more common in H-pattern (p = 0.0001),whilst C-pattern was linked to cirrhosis (5.8% H vs. 5.6% M vs. 10.9% C; p = 0.0001). FIB-4(0.74(95% CI 0.69–0.79) vs. 0.83 (95% CI 0.80–0.85); p = 0.005) and Hepamet Fibrosis Score(0.77 (95% CI 0.69–0.85) vs. 0.84 (95% CI 0.80–0.87); p = 0.044)exhibited lower AUROCs in the H-pattern. The C-pattern[HR 2.37 (95% CI 1.12–5.02); p = 0.024], along with age, diabetes, and cirrhosis were independently associated with mortality. Most patients maintained their initial biochemical pattern during the second evaluation.,Conclusions,The H-pattern exhibited greater necro-inflammation in the histology than the C-pattern, whereas the latter showed more cirrhosis. The accuracy of NITs in detecting fibrosis was decreased in H-pattern. The occurrence of decompensated events and mortality was predominant in C-pattern. Therefore, identifying MASLD phenotypes based on the biochemical presentation could be relevant for clinical practice.
Assessment of bleeding events in patients receiving DOACs with or without statins to treat venous thromboembolism: insights from the RIETE registry
(Bmj, 2024-10-22) Giorno, Rosaria del; Mazzolai, Lucía; Keller, Sanjiv; Siniscalchi, Carmine; López-Jiménez, Luciano; Ballaz, Aitor; Montenegro, Ana Cristina; Otero Candelera, Remedios; Rashidi, Farid; Monreal, Manuel; Autoría grupal: RIETE Investigators; Universidad de Sevilla. Departamento de Medicina
Objective To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE). Design Observational cohort analysis based on a multicentre international registry. Setting Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries. Participants A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low- molecular- weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins. Methods Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use. Results From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non- statin users on DOACs and 46 908 were non- statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient- years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non- users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76). Conclusions In patients with VTE receiving statins, long- term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.
A genome-wide association meta-analysis of all-cause and vascular dementia
(Elsevier Inc.; WILEY, 2024-07-24) Mega Vascular Cognitive Impairment and Dementia (MEGAVCID) consortium; Mir Rivera, Pablo; Real Navarrete, Luis Miguel; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS)
Introduction: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. Methods: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors. Results: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). Discussion: Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD. Highlights: We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease.
Uso de inteligencia artificial en la predisposición genética a enfermedad crítica por COVID-19: evaluación comparativa de modelos de aprendizaje automático
(De Gruyter, 2025-04-02) Martin Perez, Salomon; Sanchez Jimenez, Flora; Fuentes Cantero, Sandra; Jímenez Barragan, Marta; Sanchez Mora, Catalina; Borreguero Leon, Juan M.; Arrobas Velilla, Teresa; Valido-Morales, Agustín S.; León Justel, Antonio; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
Objetivos La predicción temprana de enfermedad crítica por COVID-19 es crucial para optimizar el manejo clínico. Este estudio tiene como objetivo optimizar la predicción de enfermedad crítica por COVID-19 mediante la integración de datos clínicos, de laboratorio y polimorfismos genéticos en modelos de inteligencia artificial, evaluando y comparando el rendimiento de distintos algoritmos de aprendizaje automático. Métodos Se analizaron 155 pacientes hospitalizados, 23 de los cuales desarrollaron enfermedad crítica. Se realizó un análisis univariante para evaluar la asociación entre siete SNPs y 9 variables clínicas y 10 parámetros de laboratorio en la analítica al ingreso. Resultados De los 7 SNPS, solo tres SNPs se asociaron significativamente con enfermedad crítica: rs77534576, rs10774671 y rs10490770. Los modelos de ensemble consiguieron el mejor rendimiento: Random Forest (AUC=0,989), XGBoost (AUC=0,954) y AdaBoost (AUC=0,927). La importancia de las variables varió entre los modelos, destacando la edad, proteína C reactiva, cardiopatías y los tres SNPs en la mayoría de ellos. La incorporación de los SNPs mejoró el poder predictivo en comparación con estudios previos sin datos genéticos. La validación interna confirmó la superioridad y estabilidad de los modelos de ensemble. Conclusiones Los modelos de aprendizaje automático pueden ayudar en la predicción por enfermedad crítica por Covid-19. La incorporación de SNPs asociados a gravedad a los datos clínicos y de laboratorio mejora el poder predictivo. Se requieren estudios adicionales con cohortes más grandes y diversas para validar y generalizar estos hallazgos antes de su aplicación clínica.

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