The Department of Health has awarded three grants under the PERIS 2025 program to intensify research activity to professionals from the Sant Pau Research Institute (IR Sant Pau). Each initiative will receive €149,760, representing a total investment of €449,280 aimed at promoting research lines that may transform the diagnosis, monitoring, and management of various neurological diseases.

PERIS strengthens research carried out within the healthcare system and enables professionals who combine clinical practice and research to have protected time to advance priority projects. In this call, the three proposals from IR Sant Pau focus on strategic areas for public health: the early detection of neurodegenerative diseases, improved diagnosis of rare disorders, and the management of a particularly relevant complication in Down syndrome.

Characterization of the Early Phases of the Alzheimer–Lewy Spectrum

One of the supported research lines focuses on understanding what happens in the brain long before symptoms of diseases such as Alzheimer’s disease or dementia with Lewy bodies become evident. The work led by Dr. Daniel Alcolea is based on an ambitious goal: to accurately describe the earliest phases of neurodegeneration and to understand how the pathological process begins. The study places particular emphasis on this initial phase—known as the prodromal stage—in which the brain already begins to undergo changes even though the individual has not yet developed symptoms.

To characterize this stage, the team combines multiple complementary sources of information, including cerebrospinal fluid and plasma biomarkers, recordings of brain activity, sleep studies, and high-resolution magnetic resonance imaging. This multimodal approach provides a comprehensive view of the process that precedes cognitive decline and makes it possible to identify patterns that would not be detectable using a single technique.

The project is structured in three successive phases that include the validation of cerebrospinal fluid and plasma biomarkers, the study of cohorts with differentiated biochemical profiles, and the integration of functional and imaging data. The ultimate goal is to build a reliable map of this silent yet decisive period, with the capacity to improve diagnostic stratification and lay the groundwork for future preventive or therapeutic interventions.

Plasma and Imaging Biomarkers for the Diagnosis of 4R Tauopathies

Another funded proposal addresses a key challenge in neurodegeneration: advancing early molecular diagnosis of the two main 4R tauopathies, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Although they are often considered “rare” diseases, together they represent a frequent cause among patients who seek care for cognitive, behavioral, and motor impairment once Alzheimer’s disease has been ruled out.

At present, these diseases are frequently diagnosed when they are already in advanced, palliative stages, with a high degree of disability, and when clinical differentiation between PSP and CBD is particularly challenging due to symptom overlap and variability in presentation. The research led by Dr. Ignacio Illán-Gala proposes an innovative strategy based on the combination of novel imaging markers and plasma biomarkers, with the aim of shifting diagnosis toward minimally symptomatic stages. This shift is critical because it is precisely during these early phases that disease-modifying treatments are expected to be most effective.

The project will assess the performance of this multimodal approach both to increase diagnostic accuracy and to more reliably distinguish PSP from CBD in early stages. It will also examine the longitudinal evolution of these markers and their relationship with clinical progression. This knowledge may improve patient stratification, optimize the design of clinical trials, and ultimately move diagnosis toward a scenario in which care is earlier, more specific, and potentially more disease-modifying.

Epilepsy in Alzheimer’s Disease Associated With Down Syndrome

The third line of research addresses a particularly relevant challenge: the development of epilepsy in individuals with Down syndrome who develop Alzheimer’s disease, a phenomenon that accelerates cognitive decline and increases dependency. In the early stages, these seizures can be difficult to detect because they present in subtle ways.

The research coordinated by Dr. María Carmona-Iragui combines EEG, sleep studies, plasma biomarkers, and magnetic resonance imaging to identify early signs of cerebral hyperexcitability and to understand how this epileptic activity influences disease progression. This integrated approach makes it possible to describe phenomena that often go unnoticed in routine clinical practice.

This analysis is complemented by a phase III clinical trial designed to determine whether levetiracetam can prevent or delay the onset of seizures. This is a pioneering approach that could establish, for the first time, a preventive strategy for this population, with the potential to significantly improve quality of life.

With these three PERIS grants, IR Sant Pau strengthens its leadership in neurodegenerative research and consolidates its commitment to projects that combine scientific rigor, clinical utility, and direct impact on people’s health. Although they address different challenges, these initiatives share a common orientation: translating scientific knowledge into clinical practice to improve early detection, anticipate disease progression, and open new therapeutic opportunities.

Therapy-related myeloid neoplasms represent one of the most significant current challenges in hematologic oncology due to their biological complexity, their aggressive clinical course, and the limited effectiveness of conventional treatments. In this context, biomedical research is seeking new strategies that make it possible to move toward more precise approaches tailored to the characteristics of each patient.

Along these lines, an international research project is being carried out with the participation of the Sant Pau Research Institute (IR Sant Pau), focused on the development of precision medicine strategies to improve the management of this type of hematologic cancer. The study is led by Dr. Manel Esteller, head of the Cancer Epigenetics group at IR Sant Pau, and has received a competitive grant from the Instituto de Salud Carlos III (ISCIII). This is within the framework of the 2025 International Collaboration Projects call of the Strategic Action in Health.

The project will have a total budget of €300,000 and will be carried out over three years (2026–2028), within the context of the European program EP PerMed (European Partnership for Personalised Medicine), which promotes innovative approaches based on pharmacogenomics and the personalization of treatments.

A Molecular Approach to a Highly Complex Hematologic Cancer

Therapy-related myeloid neoplasms arise because of previous oncologic treatments and are characterized by marked molecular heterogeneity, which complicates their clinical management and limits responses to standard therapies. This biological diversity makes it particularly necessary to gain more in-depth insight into the mechanisms underlying the disease and their relationship with treatment response.

In this regard, the project proposes an advanced molecular characterization of the disease with the aim of identifying biological profiles that enable improved patient stratification and optimized therapy selection. “Gaining an in-depth understanding of the molecular alterations that characterize these neoplasms is key to moving toward more effective treatments tailored to each patient, especially in a clinical context as complex as that of therapy-related myeloid neoplasms,” explains Dr. Esteller.

To this end, the study will integrate state-of-the-art genomic and transcriptomic technologies, including single-cell analyses, advanced sequencing, and multi-omics analysis strategies, which will provide a detailed view of the biological processes involved in the disease.

Advanced Analysis and International Collaboration

The work will be carried out in collaboration with other national and international research groups within the framework of the networks promoted by EP PerMed. It will make extensive use of scientific infrastructures specialized in genomics, data analysis, and sequencing platforms. This approach will make it possible to obtain an integrated view of the molecular mechanisms involved in the disease and their impact on therapeutic response.

The funding awarded will be used primarily to cover costs associated with advanced scientific services, such as specialized sequencing, the processing, and analysis of large data volumes, international project coordination, and the dissemination of results at scientific conferences. It also covers open-access publications.

Advancing Research in Precision Medicine

The participation of IR Sant Pau in this project reinforces its commitment to translational research and precision medicine. It also involves international initiatives aimed at improving the diagnosis, prognosis, and treatment of complex oncologic diseases through personalised approaches based on molecular knowledge of the disease.

The Sant Pau Research Institute (IR Sant Pau) has obtained two Sara Borrell contracts in the 2025 call of the Instituto de Salud Carlos III (ISCIII), within the framework of the Strategic Action in Health. These grants, aimed at postdoctoral researchers, are designed to support the continuity and consolidation of scientific careers in the field of biomedical research within the National Health System.

The grants have been awarded to Dr. Víctor de la Peña Arteaga and Dr. Iñigo Rodríguez Baz, who will carry out their research activities at IR Sant Pau. Here they will be able to deepen their scientific specialization and advance their research careers in an accredited healthcare research environment.

In the case of Dr. Víctor de la Peña Arteaga, the contract will make it possible to consolidate his research in the field of mental health, with a neurobiological and translational approach focused on treatment-resistant depression. This is within a line of work coordinated by Dr. Narcís Cardoner. His research activity focuses on studying the brain mechanisms involved in therapeutic response, with particular attention to the factors associated with the lack of response to conventional antidepressant treatments.

In this context, Dr. de la Peña’s research includes the identification and validation of biomarkers of functional neuroimaging linked to the clinical evolution of patients with treatment-resistant depression. Integrating this strategy into a clinical setting helps deepen the biological and functional characterization of the disorder and contributes to a more profound understanding of its underlying mechanisms, an area of significant clinical and social impact.

For his part, Dr. Iñigo Rodríguez Baz will conduct his research in the field of dementia, with a specific focus on Lewy body dementia, within a research line coordinated by Dr. Daniel Alcolea. His research centers on the clinical and biological phenotyping of the disease, including its prodromal phases, with the goal of describing its clinical and evolutionary heterogeneity with greater precision.

His work integrates the analysis of biomarkers in different biological fluids—plasma, serum, and cerebrospinal fluid—with neuroimaging and neurophysiological biomarkers, such as magnetic resonance imaging, nuclear medicine techniques, and polysomnography. This multimodal approach enables progress in early diagnosis, patient stratification, and the prediction of clinical progression in Lewy body dementia, a pathology that is notably complex from a diagnostic standpoint.

In both cases, Institut de Recerca Sant Pau serves as the host institution for the grants, providing the institutional and scientific framework necessary for the development of the research activity. The incorporation of Dr. Víctor de la Peña Arteaga and Dr. Iñigo Rodríguez Baz strengthens IR Sant Pau’s commitment to the recruitment and consolidation of postdoctoral research talent. It also aims to advance research lines aligned with priority areas such as mental health and neurodegenerative diseases.

The awarding of these two Sara Borrell contracts adds to the set of competitive grants obtained by IR Sant Pau in the 2025 call. It reinforces its role as a reference environment for postdoctoral training and the development of high-quality biomedical research. This has the potential to advance scientific knowledge and improve patient care.

The Sant Pau Research Institute (IR Sant Pau) has been awarded three highly competitive grants from the Spanish State Research Agency (AEI), corresponding to two Ramón y Cajal contracts and one Juan de la Cierva contract. This recognition reflects the quality of the research carried out at the center and its ability to attract, foster, and project scientific talent. It also promotes the participation and leadership of women in science, a strategic priority that IR Sant Pau actively advances to move toward more diverse and inclusive research.

The Ramón y Cajal grants are aimed at researchers with an outstanding scientific track record. They make it possible both to recruit new profiles and to advance the careers of those already working at centers of excellence, fostering the development of independent lines of research. For their part, the Juan de la Cierva grants support postdoctoral specialization and strengthen the progression of early-career researchers within groups with strong training capacity.

In this context, IR Sant Pau welcomes Dr. Dora Koller through a Ramón y Cajal grant. Dr. Koller is an interdisciplinary researcher whose profile combines genomics, pharmacogenetics, precision medicine, and computational analysis. Her international career, which includes an extended period at Yale University (United States), has focused on identifying complex genetic relationships between physical conditions—such as endometriosis or chronic pain—and psychiatric disorders. She has an extensive national and international collaboration network and plays a prominent role as a lead analyst in major reference consortia, such as the Women’s Health Initiative and the Chronic Pain Genomics Consortium.

Dr. Koller has led pioneering studies that provide an integrated view of mental and physical health. Her expertise in pharmacogenetics platforms and advanced analytical methods represents a strategic boost for the development of new personalized medicine approaches at IR Sant Pau. Dr. Koller will join the Perinatal and Women’s Medicine Group, led by Dr. Elisa Llurba.

The second Ramón y Cajal grant has been awarded to Dr. Marta Cano Català, who was already conducting her scientific work at IR Sant Pau and who, through this grant, strengthens her career trajectory at the center. Dr. Cano is a recognized expert in neuroimaging applied to affective disorders, with a particular interest in the mechanisms of action of rapid-acting antidepressant treatments, such as electroconvulsive therapy (ECT).

Her research has made it possible to identify structural and functional biomarkers that improve understanding of therapeutic response, opening new avenues toward precision psychiatry. Her participation in international consortia such as GEMRIC and ENIGMA helps position IR Sant Pau as a reference center in the field of clinical neuroimaging. Dr. Cano will join the Mental Health Group, led by Dr. Maria J. Portella.

Meanwhile, the Juan de la Cierva grant has been awarded to Dr. Estela Rosell Mases, a new addition to the research group in Endocrinology, Diabetes, and Nutrition, led by Dr. Dídac Mauricio. This contract allows her to strengthen her scientific profile and contribute to a line of work with a strong translational component. Dr. Rosell’s research will focus on evaluating the role of molecules derived from the gut microbiota in metabolic-associated fatty liver disease in in vitro and in vivo experimental models and in human cohorts.

The awarding of these three grants underscores IR Sant Pau’s commitment to scientific excellence, personalized medicine, mental health, translational research, and the promotion of female talent in science. All the beneficiaries are early-career researchers who help strengthen the presence of women in traditionally underrepresented fields, a priority aspect of the center’s strategy to foster equal opportunities and ensure more competitive and equitable research. Through competitive programs such as those of the AEI, IR Sant Pau continues to reinforce its role within the biomedical ecosystem and to generate impactful knowledge to improve people’s health.

The Sant Pau Research Institute (IR Sant Pau) has been awarded a Juan Rodés contract from the Carlos III Health Institute (ISCIII). This is a national program aimed at consolidating the research careers of clinical professionals within the National Health System and facilitating the stable integration of research into the hospital setting.

The beneficiary of the contract is Dr. Carla Abdelnour Ruiz, a specialist in neurology, who will carry out her activity in the neurology department of Sant Pau Hospital. The contract, with a duration of four years, allows clinical care to be combined with sustained dedication to research, strengthening the hospital’s role as an environment for generating biomedical knowledge closely linked to patient care.

Dr. Abdelnour Ruiz carries out her clinical and scientific activity in the field of cognitive impairment and neurodegenerative diseases, with a specific focus on dementias and, in particular, dementia with Lewy bodies. Her research trajectory is framed within consolidated lines of the Neurology Department and IR Sant Pau, with participation in clinical and translational research projects focused on these conditions. She also participates in studies aimed at improving their clinical characterization and diagnostic approach.

The Juan Rodés program is specifically designed to promote the stabilization of attending physicians with a scientific vocation, allowing continuity in clinical careers that structurally integrate research into professional practice. Through this model, talent retention within the public system is promoted, and links between hospitals and health research institutes are strengthened.

In this case, IR Sant Pau acts as the applicant institution and Sant Pau Hospital as the host institution, ensuring a stable framework for the joint development of clinical care and clinical research activity in neurology. This structure facilitates the continuity of existing lines of research and their translation into the clinical setting.

The awarding of this Juan Rodés contract represents a new boost to IR Sant Pau’s strategy to promote stable clinician-researcher career paths. It reinforces the center’s commitment to research aimed at improving knowledge, diagnosis, and care in dementias and other neurodegenerative diseases.

The Sant Pau Research Institute (IR Sant Pau) has secured six Río Hortega 2025 contracts from the Instituto de Salud Carlos III (ISCIII), a program designed to consolidate the careers of healthcare professionals who combine clinical practice with biomedical research.

These two-year grants will allow specialists with healthcare training and research experience to devote a significant portion of their time to research in hospital settings, integrating clinical practice with the generation of new knowledge. They aim to promote continuity in scientific careers at post-training stages and to strengthen translational clinical research within the National Health System.

This achievement consolidates the role of IR Sant Pau as an environment of excellence for training clinically oriented professionals with a strong research vocation. It underscores its commitment to the promotion of talent and the transfer of knowledge into clinical practice.

The new grants cover a wide range of areas, from cardiovascular diseases to neurosciences and genomics, and will be carried out in collaboration with established researchers at IR Sant Pau who lead competitive projects in their respective fields.

In the cardiovascular area, Dr. Jesús Díaz Gutiérrez, who will collaborate with the team led by Dr. Gemma Vilahur, will focus his work on studying the inflammatory and metabolic mechanisms involved in myocardial injury and in the progression of atherothrombosis. His research aims to understand how inflammation and lipid metabolism contribute to the development of cardiovascular disease and to identify new strategies to anticipate complications in patients with coronary artery disease. By applying molecular biology techniques and analyzing different cardiac imaging modalities, the project seeks to contribute to the development of more precise and personalized prevention strategies.

In the field of neurology, Dr. Joan Miquel Fernández Vidal, who will collaborate with Dr. Sònia Benítez, will direct his research toward cerebrovascular disorders. Dr. Fernández Vidal will study the role of lipid and inflammatory biomarkers associated with the progression of carotid atherosclerotic plaque. The aim is to identify factors that determine the risk of ischemic stroke and its recurrence, as well as the occurrence of other cardiovascular events. His project will combine clinical studies and laboratory analyses in patient cohorts to improve prognostic prediction. His work seeks to optimize stroke risk stratification and to guide therapeutic decision-making in a common condition with a major public health impact.

Also within the field of neurology, Dr. Júlia Peris Subiza, who will collaborate with Dr. Olivia Belbin, and Dr. Sara Rubio Guerra, affiliated with the team led by Dr. Ignacio Illán-Gala, will promote projects focused on neurodegenerative diseases. Dr. Peris Subiza will orient her research toward the development of biomarkers to improve the diagnosis of mental disorders and neurodegenerative diseases and to assess treatment efficacy. Dr. Rubio Guerra, for her part, will focus her project on the clinical and biological characterization of frontotemporal dementia and amyotrophic lateral sclerosis (ALS), integrating neuroimaging techniques, analysis of proteins associated with neuronal damage, and longitudinal patient follow-up. Her research will help define biological subtypes of these conditions and improve diagnostic precision.

Also in the area of neurology, but with a stronger focus on omics tools, Dr. Franco Emanuel Appiani, in collaboration with Dr. Israel Fernández, will participate in projects exploring gene regulation mechanisms in neurological and metabolic diseases. Using large-scale genomic and proteomic techniques, his research will seek to identify key biological pathways and biomarkers with diagnostic or prognostic value. These studies will contribute to a more in-depth understanding of the molecular bases of various complex diseases and to building bridges between molecular biology and clinical practice.

Finally, in the field of neurosciences, Dr. Helena Codes Méndez will develop a project in collaboration among the neuromuscular, rheumatology, and multiple sclerosis units, under the coordination of Dr. Luis Querol. Trained as a rheumatologist, Dr. Codes will focus her research on the early detection and biomarker-based monitoring of neurological complications associated with systemic autoimmune diseases. The study aims to identify biological indicators that enable early recognition of nervous system involvement and monitoring of its progression, with the goal of improving diagnosis and clinical management of these patients. This is a cross-cutting project that integrates clinical and experimental knowledge and strengthens collaboration across different specialties in a field of growing clinical and research relevance.

Securing these Río Hortega contracts reinforces the role of IR Sant Pau as a reference environment for training and incorporating new generations of clinical professionals into research. The projects to be carried out under these grants reflect the center’s commitment to research aimed at improving the diagnosis, treatment, and prevention of diseases with a high public health impact.

The Sant Pau Research Institute (IR Sant Pau) has been awarded five Predoctoral Training Contracts in Health Research (PFIS) from the Carlos III Health Institute (ISCIII) under the 2025 call. These four-year contracts are among Spain’s main national instruments for promoting early-stage training of researchers in biomedical sciences and represent a key pathway for entry into the health research system.

The award of these four grants will enable new PhD candidates to pursue their doctoral theses in competitive projects led at IR Sant Pau. They will integrate into well-established research teams and contribute to advances in knowledge in areas of high clinical relevance. The PFIS program combines advanced methodological training, participation in ongoing studies, and mentoring during the early stages of a scientific career, reinforcing the institute’s commitment to emerging talent.

One of the new PhD candidates is Ainel Iskakova, who will carry out her research under the supervision of Dr. María José Martínez-Zapata. Her thesis is part of projects aimed at improving postoperative care through the use of innovative digital tools. Specifically, her work will focus on evaluating interventions that facilitate remote monitoring of patients after major cardiac surgery, with the goal of optimizing clinical management and helping to reduce complications and hospital readmissions. The analysis of different digital systems will make it possible to assess their impact on postoperative recovery and on the early detection of adverse events, ultimately supporting clinical decision-making and improving patient safety.

Also joining the institute is Montserrat Moncunill, who will develop her doctoral thesis under the supervision of Dr. Luis Prats Sánchez, with the collaboration of Dr. Sònia Benítez and Dr. Núria Puig, within a line of research focused on intracerebral hemorrhage. This type of stroke, one of the most severe, with a mortality rate of 40%, still lacks tools that allow accurate prediction of its clinical course. Her research will be integrated into projects that combine clinical, neuroimaging, and biomarker data to identify factors that may help anticipate hematoma progression and the risk of complications. The findings could contribute to improving early management of these patients and to fostering more personalized care based on noninvasive biomarkers.

In the field of mental health, Ariana Murillo will begin her predoctoral training under the supervision of Dr. Narcís Cardoner, Dr. Romina Miranda-Olivos, and Dr. Marta Cano, participating in research focused on the identification of potential biomarkers of response to rapid-acting antidepressants. Her thesis will explore the mechanisms of action of these therapeutic strategies through the integration of magnetic resonance imaging with syndromic and dimensional clinical assessments, with the aim of identifying individualized brain biomarkers that may optimize treatment personalization and advance toward precision psychiatry. This line of work is particularly relevant at a time when mental health research is moving toward more integrative models that combine clinical, neurobiological, and behavioral data to improve understanding and management of affective disorders.

For her part, Judit Selma González will carry out her doctoral thesis under the supervision of Dr. Ignacio Illán-Gala, within projects devoted to the study of neurodegenerative diseases. Her research will focus on evaluating the role of cognitive measures, together with emerging biomarkers, to gain a more in-depth understanding of the changes that occur in conditions such as Alzheimer’s disease and frontotemporal dementia. The use of advanced analytical techniques and the integration of clinical, cognitive, and biological information will make it possible to explore the evolution of these processes at early stages, contributing to improved early detection and to the identification of profiles with potential relevance for more targeted therapeutic strategies.

The fifth predoctoral grant has been awarded to Aya El Allam Kanice, who will carry out her doctoral thesis under the supervision of Dr. Mireia Tondo Colomer. Her research will focus on studying the role of high-density lipoprotein–mediated cholesterol transport (HDL) in the progression of Alzheimer’s disease in adults with Down syndrome. The project, which is part of the DOWNLIP study, combines analyses of plasma and cerebrospinal fluid biomarkers with longitudinal clinical and cognitive assessment, with the aim of identifying early indicators of cognitive decline and gaining a more profound understanding of the biological mechanisms linking lipid metabolism and neurodegeneration. The results could help improve early detection and open new opportunities for personalized medicine in a particularly vulnerable population.

The award of these five PFIS contracts reinforces IR Sant Pau’s commitment to the training of new scientific talent and the attraction of competitive funding. The PhD candidates will join an environment of excellence, where they will be able to build a solid research career and contribute to advances in biomedical research and improvements in patient health.

The choice of the drug used to induce sedation during emergency intubation in critically ill patients may have a meaningful impact on in-hospital survival. This is suggested by a recent study analyzing clinical outcomes associated with the use of etomidate and ketamine, two of the most commonly used agents for rapid sequence intubation in emergency departments.

The study, published in JAMA Network Open, is a multicenter investigation based on data from 18 hospitals in Brazil and was led by an international team of specialists in emergency medicine and critical care. The research included participation from the Sant Pau Research Institute (IR Sant Pau), through Dr. Otavio Ranzani, head of the DataHealth Lab at IR Sant Pau and senior coauthor of the article.

Differences in Mortality Associated With the Induction Agent

The study evaluated 1,810 critically ill adult patients who required emergency intubation and received either etomidate or ketamine as the sole induction agent. Using an advanced observational design that emulates a clinical trial, the investigators compared in-hospital mortality at 7 and 28 days after the procedure, adjusting results for multiple clinical and demographic variables.

The results show that patients who received etomidate had higher in-hospital mortality compared with those treated with ketamine. In the primary analysis, 28-day mortality was higher in the etomidate group, with a clinically meaningful absolute risk difference. This association remained consistent across multiple sensitivity analyses, reinforcing the robustness of the findings.

Regarding secondary outcomes, no significant differences were observed between the two groups in first-attempt intubation success or in most of the adverse events assessed. A higher frequency of early hemodynamic instability was observed in patients who received ketamine, a finding previously described and potentially related to the pharmacological properties of the drug and to patients’ clinical profiles.

Implications for Clinical Practice

Dr. Otavio Ranzani highlights the clinical relevance of the results: “Our data suggest that the choice of induction agent during emergency intubation is not a neutral decision and may influence outcomes as relevant as in-hospital survival. Although this is an observational study, the magnitude and consistency of the observed association justify further investigation into the impact of induction agents on clinical outcomes across different settings.” Dr. Ranzani adds, “This month, one of the largest clinical trials on this topic, the long-anticipated RSI trial, was published in The New England Journal of Medicine, showing neutral results regarding mortality but also raising questions about whether it had sufficient power to assess this outcome or whether its findings are applicable to settings beyond U.S. emergency departments and ICUs, where the trial was conducted.”

The authors emphasize that the study does not allow a definitive causal relationship to be established, but it does provide solid evidence to question the routine use of etomidate in critically ill patients. Particularly in a context in which widely available alternatives such as ketamine exist. In this regard, the work reinforces the need for continued research into how pharmacological decisions made in emergencies can have meaningful consequences for patient outcomes.

The participation of IR Sant Pau in this study reflects its commitment to clinical research aimed at improving the safety and outcomes of critically ill patients, as well as to generating high-impact scientific evidence that helps optimize clinical practice.

Reference Article:

Maia IWA, Decker SRR, Oliveira J E Silva L, von Hellmann R, Alencar JCG, Hajjar LA, de Carvalho JMD, Pedrollo DF, Nogueira CG, Figueiredo NMP, Miranda CH, Martins D, Baumgratz TD, Bergesch B, Colleoni O, Zanettini J, Freitas AP, Tambelli R, Costa MC, Correia W, de Maria RG, Filho UAV, Weber AP, da Silva Castro V, Dornelles CFD, Tabach BS, Moreira NP, Gaspar PL, Guimarães HP, Stanzani G, Gava TF, Mullan A, Brown CS, Bellolio F, Jeffery MM, Ranzani OT, Besen BAMP, Brazilian Airway Registry Cooperation (BARCO) group. Ketamine, etomidate, and mortality in emergency department intubations. JAMA Netw Open 2025;8:e2548060. https://doi.org/10.1001/jamanetworkopen.2025.48060

The Sant Pau Research Institute (IR Sant Pau) has led a multicenter project that redefines what is considered normal cognitive performance. The work, carried out in collaboration with Hospital Clínic de Barcelona, Hospital Universitario Marqués de Valdecilla in Santander, and the CITA-Alzheimer Foundation in San Sebastián, has resulted in two complementary scientific articles published in the journal Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM), which establish new cognitive reference standards based exclusively on individuals without amyloid pathology and demonstrate their ability to improve early diagnosis.

This initiative emerges at a pivotal moment for clinical practice. The arrival of disease-modifying therapies requires increasingly precise identification of patients who are in very early stages, when intervention is most effective and safest. However, traditional neuropsychology faces a fundamental challenge: determining what “normal performance” truly means in older adults, given that part of age-related decline can be confused with changes inherent to the preclinical phase of Alzheimer’s disease. The project addresses this need by redefining cognitive reference standards using advanced tools and data from rigorously selected populations, allowing for a more accurate delineation of the threshold between healthy aging and true cognitive decline.

New Reference Standards Based on Amyloid-Negative Individuals

In the first part of the project, neuropsychological reference standards based exclusively on individuals without Alzheimer’s disease biomarkers were developed for the first time, using advanced statistical models that take age, educational level, and sex into account. This combination, which until now had only been applied partially in certain specific tests, is used for the first time simultaneously and across such a broad battery of neuropsychological assessments, representing a significant methodological advance at the international level. This approach allows for a more precise definition of what can be considered truly normal cognitive performance in aging. By excluding individuals who already show amyloid pathology in the preclinical phase—still without symptoms—it prevents the mild decline associated with the disease from being mistaken for healthy aging.

The development of these new reference standards was based on a cohort of nearly 800 cognitively healthy adults and on advanced statistical models capable of describing in detail how age, education, and biological sex influence each cognitive domain. This approach made it possible to identify subtle but relevant differences between men and women, as well as nonlinear effects of age and education that previous methods could not detect, substantially increasing the precision of cognitive assessments.

In parallel, the team developed a clinical calculator that allows for rapid and accurate calculation of adjusted scores, facilitating individualized interpretation of each case in memory clinics. Although it is not intended for the public, the tool is designed so that all professionals who assess patients with suspected cognitive impairment can use it as diagnostic support, promoting consistent application of the new reference values in clinical practice.

As explained by Dr. Sara Rubio-Guerra, researcher in the Neurobiology of Dementias group, neurologist at the Sant Pau Memory Unit, and first author of the study, “a key part of diagnosis is clearly defining what we mean by cognitive normality. If this reference point is not accurate, we may overlook very early alterations or, conversely, raise concerns in completely healthy individuals. These new norms allow us to interpret performance more precisely and better distinguish between healthy aging and the earliest changes associated with the disease.”

The New Norms Enable Earlier Detection of the Earliest Cognitive Decline

In the second part of the study, an analysis was conducted in a sample of more than 2,400 individuals without dementia, demonstrating that application of these new reference standards substantially improves the ability to identify very mild cognitive alterations. The new standards make it possible to detect earlier one in five cases of incipient cognitive impairment that previously went unnoticed.

The data confirm that this group does not represent cognitive variability inherent to aging. These individuals show high rates of Alzheimer’s disease biomarkers and a faster cognitive decline in longitudinal analyses, indicating that they are indeed in an early stage of the disease. Earlier detection allows for more precise guidance of the diagnostic workup and helps determine when further evaluation with biomarkers is warranted.

By contrast, the number of individuals whom the new norms would classify as impaired in the absence of biological evidence of disease is small, around 3%, and in most of these cases biomarkers are negative. This minimizes the risk of overdiagnosis and avoids subjecting healthy individuals to unnecessary testing.

Earlier Diagnosis in the Era of Disease-Modifying Therapies

According to Dr. Ignacio Illán-Gala, researcher in the Neurobiology of Dementias group at IR Sant Pau, neurologist at the Sant Pau Memory Unit, and senior author of the study, “early diagnosis is key in the era of new disease-modifying therapies. Detecting these incipient cases earlier means being able to offer therapies at the time when they are most effective and safest.” The neurologist emphasizes that neuropsychology acts as “a gateway to the diagnostic workup,” especially when memory complaints are very subtle and the decision to request biomarkers requires knowing with precision whether true cognitive decline is present. “With more accurate reference values, we can better determine who needs further evaluation and who can be reassured, avoiding both overdiagnosis and missed therapeutic opportunities,” he adds.

Overall, the project consolidates IR Sant Pau’s leadership in the development of biomarkers and precision tools and lays the groundwork for future improvements as markers for other neurodegenerative diseases in preclinical stages are identified.

Reference Articles:

1. Rubio-Guerra S, Sánchez-Saudinós MB, Sala I, Videla L, Bejanin A, Estanga A, Ecay-Torres M, de Luis CL, Rami L, Tort-Merino A, Castellví M, Pozueta A, García-Martínez M, Gómez-Andrés D, Lage C, López-García S, Sánchez-Juan P, Balasa M, Lladó A, Altuna M, Tainta M, Arranz J, Zhu N, Alcolea D, Lleó A, Fortea J, Rodríguez ER, Sánchez-Valle R, Martínez-Lage P, Illán-Gala I. Development of amyloid-negative neuropsychological norms using GAMLSS. Alzheimers Dement (Amst) 2025;17. https://doi.org/10.1002/dad2.70224.
2. Rubio-Guerra S, Sala I, Sánchez-Saudinós MB, Videla L, Bejanin A, Estanga A, Ecay-Torres M, de Luis CL, Rami L, Tort-Merino A, Castellví M, Pozueta A, García-Martínez M, Gómez-Andrés D, Lage C, López-García S, Sánchez-Juan P, Balasa M, Lladó A, Altuna M, Tainta M, Arranz J, Zhu N, Alcolea D, Lleó A, Fortea J, Rodríguez ER, Sánchez-Valle R, Martínez-Lage P, Illán-Gala I. Amyloid-negative neuropsychological norms: Added value in the era of biomarkers and disease-modifying therapies. Alzheimers Dement (Amst) 2025;17. https://doi.org/10.1002/dad2.70223.

The Sant Pau Research Institute (IR Sant Pau) has been selected to participate in three high-impact scientific and technological projects funded through the 2024 Public-Private Collaboration Projects call from the Spanish State Research Agency (AEI), under the Ministry of Science, Innovation, and Universities. These grants, aimed at fostering the transfer of knowledge from research to the productive sector, represent a total funding of over €650,000 for the institute to develop new digital health tools. Innovative strategies for women’s health, and targeted cancer therapies based on nanotechnology.

The simultaneous award of these three projects places IR Sant Pau in a strategic position within translational research in Spain. This reinforces its role as a key scientific partner in public-private consortia that seek to transform laboratory advances into clinically applicable solutions.

ASISTE: Artificial Intelligence to Transform the Patient Experience in the Healthcare System

The project ASISTE – “Advancing Interactive and Technological Solutions for the User Experience,” coordinated by Digimevo in collaboration with Eurecat and IR Sant Pau, aims to make a qualitative leap in the relationship between patients and healthcare services. The consortium will develop an advanced virtual assistant based on artificial intelligence technologies, capable of providing personalized information, supporting decision-making, and integrating recommendations to improve therapeutic adherence and self-care.

Unlike conventional systems, ASISTE will explore multimodal and adaptive models that anticipate patients’ needs, reduce uncertainty, and optimize the flow of clinical information before, during, and after healthcare delivery. The project aligns with current trends in digital health, which emphasize patient empowerment and care efficiency.

The participation of IR Sant Pau, led by Dr. Elisa Llurba, will be essential to bring the technology into a real clinical environment. The institute will coordinate the pilot validation of the virtual assistant at Sant Pau Hospital, including methodological design, usability assessment, impact measurement in clinical practice, and evaluation of health outcomes. This work will draw on the experience and capabilities of the Clinical Research and Clinical Trials Unit (UICEC) Sant Pau and the Drug Research Center (CIM), essential infrastructures to ensure a safe and effective deployment in patients. The project has been granted €153,643.99 for IR Sant Pau.

OXO-001: A New Path to Modulate the Vaginal Microbiota and Improve Reproductive Health

The second funded project, Study and Development of a Strategy to Modulate the Vaginal Microbiota with the Compound OXO-001, led by the biotech company Oxolife, focuses on the compound OXO-001 and its ability to modulate the vaginal microbiota and correct dysbiosis. The conditions that can affect gynecological and reproductive health. The initiative, involving the University of Barcelona and IR Sant Pau, addresses an emerging and relevant clinical field in which the vaginal microbiota is increasingly recognized as a key determinant of fertility and reproductive success.

IR Sant Pau plays a central role in the project’s clinical phase, in which the safety and biological effects of OXO-001 will be studied in healthy female volunteers, analyzing how it modulates microbial balance and assessing its potential to open new therapeutic strategies in fertility and women’s health, with Dr. Rosa Antonijoan as principal investigator. A leading expert in clinical pharmacology and first-in-human trials, Dr. Antonijoan will head the planning, execution, and supervision of the clinical study, which will be conducted at the CIM Sant Pau facilities, a platform renowned for its expertise in early-phase studies, safety assessment, and rigorous data monitoring. The grant awarded to IR Sant Pau for this project amounts to €147,129.81.

NNL1524: A Next-Generation Nanodrug for Tumors Overexpressing CXCR4

The third project, Innovative Nanodrug Targeted to CXCR4+ Tumor Cells: Toward the First-in-Human Clinical Trials of a Revolutionary Therapy for Aggressive Cancers, coordinated by the company Nanoligent—a spin-off linked to the UAB and IR Sant Pau—represents an innovative approach in precision oncology. The Institute of Nanoscience and Materials of Aragon and the Margarita Salas Center for Biological Research, both part of the Spanish National Research Council (CSIC), will also participate in its development.

The goal is to advance the preclinical development of the nanodrug NNL1524, based on a disruptive protein-drug nanoconjugate technology capable of specifically targeting tumor cells that overexpress the CXCR4 receptor. This receptor is a pan-cancer biomarker associated with tumor aggressiveness, poor prognosis, metastasis, and therapeutic resistance.

NNL1524 combines a modular protein design, a high-affinity ligand, and a potent cytotoxic agent, resulting in small-sized, highly selective nanomedicines that maximize targeted drug delivery to enhance antitumor efficacy while minimizing toxicity in healthy tissues. The project includes producing the first non-GMP batch of the nanodrug, extended pharmacokinetic and metabolism studies, and consolidating the preclinical evidence required for a first-in-human clinical trial application.

IR Sant Pau’s role in this consortium is pivotal. Under the direction of Dr. Ramon Mangues, the institute will conduct an extensive series of animal model studies to evaluate the nanodrug’s efficacy compared with standard treatments, characterize CXCR4 expression levels predictive of therapeutic response, and assess whether combining it with immunotherapies—such as immune checkpoint inhibitors—enhances antitumor effects. These studies are essential to define the clinical positioning of NNL1524 and support the design of future human trials. The project has received over €2.5 million in total funding, of which €360,720.89 corresponds to IR Sant Pau.

Three Projects Driving IR Sant Pau’s Research Strategy

IR Sant Pau’s participation in these three AEI-funded projects strengthens its role as a center of excellence in translational biomedical research, capable of integrating fundamental science, technological innovation, clinical validation, and collaboration with the business sector. The institution provides consortia with a cutting-edge scientific ecosystem that includes the UICEC Sant Pau, CIM, Biobank, omics platforms, advanced imaging services, cytometry, microscopy, proteomics, and an animal experimentation service that enables complex in vivo studies.

Overall, the CPP2024 grants provide IR Sant Pau with €661,494.64 in competitive funding, supporting the development of innovative solutions with a direct impact on three priority areas for public health: digitalization of healthcare, women’s health promotion, and advancement of targeted cancer therapies.

The Sant Pau Research Institute (IR Sant Pau) has secured two competitive grants from the Strategic Plan for Health Research and Innovation (PERIS) 2022–2027, a program of the Department of Health of the Government of Catalonia designed to strengthen applied research within the Catalan healthcare system. This funding will enable progress in developing artificial intelligence tools aimed at improving diagnosis and clinical decision-making in two highly time-dependent medical emergencies: acute myocardial infarction and stroke. In total, IR Sant Pau has received 129,735 euros under the medical technology and digital health category.

The first funded project is RAPID-AIM, co-led by Dr. Matías E. Calandrelli, cardiologist at the Cardiology Department of Hospital de Sant Pau, specialized in cardiac imaging and the application of digital technologies to clinical practice, together with Dr. Martín Descalzo, coordinator of Cardiac MRI in the Cardiac Imaging and Function Unit. They will develop an autonomous clinical agent capable of interpreting electrocardiograms from a simple photograph taken with a mobile phone. This approach makes it possible to identify different types of heart attacks without requiring digitized ECGs or advanced IT systems, making it a particularly valuable solution for regional hospitals, resource-limited emergency departments, or situations in which no cardiologist is available. The project plans the progressive integration of this tool into the clinical workflows of Hospital de Sant Pau and the execution of a prospective study to assess its real-world clinical impact, with a view to future certification as medical software.

According to Dr. Calandrelli, the project’s transformative potential is clear. “Our goal is for any professional, in any setting, to have immediate access to a second opinion powered by artificial intelligence. Every minute gained during a heart attack means saving heart muscle and saving lives.” The researcher also highlights RAPID-AIM’s innovative element, noting that it “works directly with ECG images, making it universally applicable even in settings without advanced digital systems.”

The second funded project, RACE+BIO, is led by Dr. Natalia Pérez de la Ossa, a vascular neurologist at Hospital de Sant Pau and an international reference in prehospital stroke care, author of the RACE scale, and principal investigator of the RACECAT study. The project builds upon the development and refinement of the RACE+ tool, a predictive algorithm powered by artificial intelligence that can accurately predict the main stroke subtypes, particularly large-vessel occlusion, and guide early decisions on the patient’s hospital destination. This can reduce critical delays and increase access to advanced therapies. The development includes, on the one hand, validating the RACE+ tool across diverse international healthcare ecosystems and, on the other, combining it with point-of-care blood biomarkers—rapid, portable tests that can be performed directly in the ambulance and deliver results within minutes without requiring a laboratory.

For Dr. Pérez de la Ossa, this technology represents a significant advancement in urgent stroke care. “RACE+BIO will allow us to know, from the ambulance and in under ten minutes, what type of stroke the patient has—information that is essential to deciding which hospital they should be taken to based on therapeutic needs. This information is critical because a two-hour delay can reduce the chances of recovery by 10%,” she explains. The researcher also stresses the project’s broader potential: “If we succeed in integrating artificial intelligence and biomarkers into prehospital triage, we will transform how emergency systems make decisions, particularly in rural areas or locations far from tertiary centers.”

Both projects share common goals, such as reducing inequity, optimizing healthcare system resources, and improving clinical outcomes in time-dependent conditions. The integration of digital tools powered by artificial intelligence will shorten critical delays, avoid unnecessary transfers, strengthen coordination between the Medical Emergency System (SEM) and hospitals, and support professionals acting during the first minutes of cardiovascular or neurological emergencies.

The awarding of these PERIS grants by the Department of Health reinforces IR Sant Pau’s leadership in digital health and reaffirms its commitment to translational research focused on solving real-world clinical challenges. RAPID-AIM and RACE+BIO represent a step forward in incorporating artificial intelligence into the Catalan healthcare system and pave the way for new diagnostic tools that could be integrated into emergency services in the near future, contributing to more equitable, efficient, and evidence-based care.

A research team led by Dr. Àlex Bayés, Head of the Molecular Physiology of the Synapse Group at the Institut de Recerca Sant Pau (IR Sant Pau), has achieved what for decades had been an elusive goal: obtaining a precise, differentiated molecular portrait of individual synaptic types in the hippocampus, the brain structure that serves as the core of learning and memory.

The study, published in Nature Communications and conducted almost entirely at IR Sant Pau, details with unprecedented resolution which proteins are present in each type of synapse and in what quantities. This reveals patterns that help explain how connections that appear similar can perform different functions and display specific characteristics. Understanding how these connections are altered is critical because synaptic dysfunction is implicated in most neurological and psychiatric diseases, from Alzheimer’s and Parkinson’s to epilepsy and schizophrenia.

Synapses, the contact points between neurons, are extremely numerous and diverse: the human brain is estimated to contain between 100 and 1,000 trillion of them. Each one transmits information with slight variations in structure and function, allowing neural circuits to process signals flexibly and precisely. However, until now it was unknown how this diversity was reflected at the molecular level. “For years, scientists have known that each type of synapse has unique electrical properties, but they had not been able to map their protein composition accurately due to technical limitations,” explains Dr. Bayés. “Available methods required analyzing large tissue fragments that mixed different classes of connections, producing an average profile that blurred subtle yet critical differences for their function.”

A Technical Challenge Solved Through Methodological Innovation

Studying synapses individually has been an almost impossible challenge for decades. They are tiny structures—barely one micron—distributed densely and interwoven throughout the brain, making physical isolation difficult. Moreover, their number is so colossal that, if each synapse were a grain of sand, there would be enough to fill half a stadium like Camp Nou, an image that illustrates the magnitude of the challenge facing neuroscience.

The IR Sant Pau team has overcome this obstacle through a combination of tools that take synaptic analysis to a new level. Laser-capture microdissection makes it possible to precisely isolate microscopic hippocampal layers, selecting only those regions containing the synapse type of interest. Then, an optimized protocol for extracting synaptic proteins preserves the integrity of these molecules and prevents losses, which is crucial when working with minuscule amounts of material.

Thanks to this approach, the researchers were able to characterize individually the proteome of the three synapse types that make up the trisynaptic hippocampal circuit, perhaps the most extensively studied circuit in the brain. It is a characteristic network that transmits information in three steps: first from the entorhinal cortex to the dentate gyrus, then from the dentate gyrus to the CA3 region, and finally from CA3 to CA1. This circuit is essential for memory processing and the integration of sensory and contextual information.

The importance of this achievement is not only technical. “Because we can examine specific synapses without requiring genetic manipulation, the methodology can also be applied to human samples, opening a range of possibilities for precisely studying how these connections are altered in neurological diseases,” notes Dr. Bayés.

The Same Menu, Served Differently

The study revealed a surprising pattern: the three synapses analyzed share the vast majority of their proteins but vary significantly in the relative quantities of each. The comparison can be understood as if all of them used the same basic ingredients for cooking but modified the proportions to create different recipes with their nuances in flavor, texture, and properties.

In this “synaptic menu,” there is one ingredient always present that defines the character of the dish: glutamate receptors and the proteins that regulate them. Glutamate is the main excitatory neurotransmitter in the brain, and its receptors are essential for signal transmission and synaptic plasticity—the mechanism that allows connections to strengthen or weaken depending on experience.

“We observed that the functional identity of each synapse is not built on an exclusive set of proteins, but rather on how it adjusts the proportion of shared components to meet its needs,” says Dr. Àlex Bayés, “and what is most surprising is that, in all cases, glutamate receptors and their regulators form the core of that specialization.”

Three Molecular Profiles With Specific Functions

Quantitative differences in protein composition translate into specialized functional profiles. CA3–CA1 synapses display very precise control of a specific AMPA receptor subtype (GluA2), a high capacity to remodel their structure, and elevated energy consumption, all of which are associated with their role in memory consolidation and long-term plasticity.

DG–CA3 synapses stand out for their high abundance of metabotropic glutamate receptors (mGluR1) and for possessing especially active machinery for local protein synthesis in their presynaptic terminals. This feature allows them to adapt rapidly to changes in neuronal activity.

Meanwhile, EC–DG synapses present a distinct extracellular matrix, rich in proteoglycans, which may influence the mobility and stability of receptors, as well as specialized metabolic pathways to obtain energy from specific amino acids. These traits may relate to their role in the first stage of processing the information reaching the hippocampus.

The Role of Genetic Regulation

The study also identified a genetic component in this specialization: each neuron type activates or silences specific synaptic genes to adjust the molecular composition of its connections. This differential regulation was observed especially in genes related to glutamate receptors and the proteins that modulate their function, confirming that their central role in synaptic specialization is also encoded in the neuron’s genetic program.

“This is the first time we can link the molecular specialization of a synapse so directly to gene expression programs unique to each neuron. This brings us closer to understanding how synaptic diversity translates into unique functions for each brain circuit,” adds Dr. Bayés.

Implications and Next Steps

The ability to analyze the molecular identity of specific synapses with such precision not only in animal models but also in human tissue opens a range of applications in biomedical research. The hippocampus is one of the first structures affected in neurodegenerative diseases such as Alzheimer’s, so understanding how these “molecular recipes” are altered could help identify early biomarkers and develop more specific therapeutic strategies.

Reference Article:

Reig-Viader R, Del Castillo-Berges D, Burgas-Pau A, Arco-Alonso D, Zerpa-Rios O, Ramos-Vicente D, Picañol J, Castellanos A, Soto D, Roher N, Sindreu C, Bayés À. Synaptic proteome diversity is shaped by the levels of glutamate receptors and their regulatory proteins. Nat Commun 2025;16:10487. https://doi.org/10.1038/s41467-025-65490-9

The Sant Pau Research Institute (IR Sant Pau) has appointed David González Gil as its new general manager, a nomination approved by the Foundation’s Board of Trustees at its extraordinary session on October 6. David González officially took office on December 9, with the aim of driving a new phase of growth and consolidation for the center.

With more than twenty years of experience in managing research institutions, universities, and internationally oriented foundations, the new general manager joins IR Sant Pau with a strong profile in strategic leadership, resource mobilization, and organizational sustainability. Over the course of his career, he has led multidisciplinary teams and contributed to strengthening the competitiveness and visibility of a range of scientific and academic institutions.

Before joining IR Sant Pau, he served as general manager of the National Center for Genomic Analysis (CNAG), where he oversaw the establishment and consolidation of this scientific infrastructure of reference in genome research. This infrastructure was created through the partial spin-off of the Center for Genomic Regulation (CRG). Previously, he held the general manager position at the Pontifical University of Salamanca as a member of the rector’s office and chief executive of the leadership team, promoting the new strategic plan and the institution’s repositioning. He also held senior leadership roles at La Salle–Ramon Llull University, contributing to its global growth.

David González holds a Bachelor’s Degree in Economics from the University of Barcelona and has completed executive education programs at IESE, Harvard Business School, EADA, Aston University, and La Salle. He is currently a doctoral candidate in Economics and Law at the International University of Catalonia.

Upon his appointment, the new general manager expressed his satisfaction with joining the IR Sant Pau project, noting that “it is an honor to join an institute distinguished by its talent, commitment, and scientific contribution. My goal is to strengthen the conditions that will allow us to continue generating excellent research and maximize its impact on health and society.”

Regarding his appointment, IR Sant Pau highlights that the new general manager brings a combination of strategic vision, management experience, and driving capacity that will be key to advancing the institute’s objectives for growth, competitiveness, and scientific impact.

With this new chapter, IR Sant Pau also expresses its gratitude for the work and dedication of Jaume Bacardit, who has served as the institution’s general manager for the past three years.

The new XWHIN (Women’s Health Innovation Network), coordinated by the Institut de Recerca Sant Pau (IR Sant Pau), has been established with the support of the Agency for the Management of University and Research Grants (AGAUR), which has awarded funding of 1 million euros under the Xarxes d’R+D+I 2025 call. This initiative represents a recognition of IR Sant Pau’s leadership in responsible research with a gender perspective and strengthens its role as a key player in Catalonia’s health R&D&I ecosystem.

XWHIN is the first network in Catalonia and Spain to integrate R&D&I, gender equity, technology transfer, and social participation in women’s health. Its pioneering nature lies in the systematic incorporation of the biological and social dimensions of sex and gender across all innovation processes, generating ethical, efficient, and equitable solutions. At the European level, no other network exists with such an integral approach, placing Catalonia in a leadership position in this emerging field.

The initiative was created with the aim of promoting a new way of doing science, one that is more collaborative, open, and sensitive to the biological and social differences that affect women’s health. “With XWHIN, we aim to foster a change in perspective that integrates sex and gender into every stage of health innovation, from basic research to clinical and social application,” explains Dr. Maria Rosa Ballester, head of the Responsible Research and Innovation Unit (URRI) at IR Sant Pau and director of the network. “The project seeks to position Catalonia as a European benchmark in gender-sensitive health innovation, leveraging the country’s scientific and technological strengths and its tradition of excellence in biomedical research.”

A Network to Reduce Health Inequalities

Despite scientific and social progress lately, women continue to experience structural health inequalities at multiple levels, from research and diagnosis to access to treatment or participation in clinical trials. Cardiovascular, neurological, or autoimmune diseases, for example, impact women and men differently, yet medical protocols and available studies often fail to reflect these differences.

On top of these biological gaps, social and cultural factors shape women’s health and well-being, including gender roles, caregiving burdens, and the invisibility of pain and conditions that predominantly affect them. The lack of sex- and gender-disaggregated evidence directly impacts the quality and equity of healthcare and limits the system’s ability to provide personalized and effective responses.

In this context, XWHIN was created to address and reverse these inequalities by promoting a global and interdisciplinary vision of women’s health. The network will promote high-impact scientific, technological, and social projects to identify unmet needs, generate new knowledge, and transfer it to clinical practice and public policies. The network’s director notes that “the sex and gender perspective is essential for better understanding diseases, how drugs work, and for offering responses that are more just, safe, effective, and equitable.” She adds, “With XWHIN, we want to transform the way we think about research and care, and how we approach health—placing women at the center of innovation and promoting research that reflects the true diversity of society.”

A Collaborative and Cross-Cutting Initiative

The XWHIN network is the result of an unprecedented alliance between public institutions, universities, research centers, companies, and social organizations. Altogether, it comprises 47 research groups and 8 collaborating organizations working in areas related to women’s health and health innovation. This open and cross-cutting structure will make it possible to address women’s health challenges from multiple perspectives—biomedical, technological, social, and economic—yielding more integrated and effective responses.

The network is coordinated by IR Sant Pau and includes participation from leading research centers and universities across the region, as well as companies and foundations in the health and technology sectors and patient organizations. “The value of XWHIN lies in its ability to connect disciplines and institutions that traditionally worked in isolation,” explains Dr. Maria Rosa Ballester. “This network seeks to create real synergies between research, industry, and society, transforming knowledge into tangible solutions that improve women’s health and well-being.”

A Firm Commitment to Research on Health and Gender

IR Sant Pau had already taken a major step in this area in 2023 with the creation of the Transversal Program for Research in Women’s and Gender Health. This pioneering initiative in Catalonia aimed at incorporating sex and gender perspectives into all its research areas. The program, developed within the framework of the Responsible Research and Innovation (RRI) Plan, provides the methodological framework and tools needed to integrate this perspective into all projects—from basic research to clinical and public health research.

Coordinated by Dr. Elisa Llurba, head of the Women’s and Perinatal Medicine Research Group at IR Sant Pau and director of the Obstetrics and Gynecology Department at Hospital Sant Pau, together with Dr. Maria Rosa Ballester. The program channels research initiatives on women’s health. It promotes collaboration between groups and supports the attraction of talent and funding in this field.

According to Dr. Elisa Llurba, “prioritizing the sex and gender perspective in biomedical research not only makes science more ethical and responsible, it also makes it more reproducible and increases its quality and its ability to generate useful results for the entire population.”

This trajectory strengthens IR Sant Pau’s leadership in gender-perspective research and lays the foundation for collaborative projects such as XWHIN, which represent a further step toward building more just, inclusive, and socially impactful biomedical research.

Four Pillars for Transforming Health Innovation

The development of XWHIN is structured around four areas of action that translate its vision into concrete and measurable objectives. The first is responsible research and innovation, which integrates sex and gender perspectives into all project phases, from experimental design to clinical application. With this approach, XWHIN seeks to ensure that research results reflect the biological and social diversity of the population, contributing to more equitable and personalized care.

The second area focuses on training and capacity building, aiming to prepare professionals to incorporate gender perspectives into their work. The network will promote specialized training programs, awareness-raising initiatives, and spaces for exchange among researchers, clinicians, and policymakers, fostering a more inclusive scientific culture committed to equality.

The third area centers on knowledge transfer and valorization, promoting collaboration between research groups, companies, and public institutions to translate science into applicable solutions. XWHIN will encourage the creation of entrepreneurial projects and spin-offs with the potential to improve women’s health and reduce inequalities, thereby strengthening an innovation ecosystem that delivers social and economic impact.

Finally, the fourth area is communication and awareness, aimed at highlighting the importance of integrating gender perspectives in health and engaging the public in transforming the healthcare system. The network will work to bring scientific knowledge closer to society and foster public debate on the specific challenges of women’s health.

According to Dr. Ballester, “These four areas define a very practical, results-oriented way of working, with a clear commitment to transforming research into tangible improvements. We want to show that integrating the gender perspective is not only a matter of equity but also of efficiency and scientific quality.”

A National Project with an International Outlook

With the creation of XWHIN, Catalonia takes a major step toward becoming a European benchmark in health innovation with a sex and gender perspective. The network is born with a clear ambition for international collaboration and plans to establish partnerships with European programs such as Horizon Europe or EU4Health, as well as with other leading women’s health networks and centers worldwide.

This global approach will enable knowledge exchange, promotion of best practices, and joint projects that will position Catalonia on the map of gender-sensitive biomedical innovation. In addition, the network seeks to actively contribute to European equality and public health strategies by providing a reproducible model of responsible, transversal, and sustainable R&D&I.

From IR Sant Pau, as the coordinating entity, scientific coherence and social impact will be ensured so that the network’s results extend beyond the academic sphere and generate real benefits for society. Through this collective effort, XWHIN aims not only to generate scientific, economic, and social impact but also to inspire new public policies and consolidate Catalonia as a European leader in gender-perspective innovation.

XWHIN Network Members

Coordinating Entity

• Institut de Recerca Sant Pau (IR Sant Pau)

Participating Institutions

• Universitat Ramon Llull
• Institute for Bioengineering of Catalonia (IBEC)
• Primary Care Research Institute Jordi Gol i Gurina (IDIAPJGol)
• August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
• Bellvitge Biomedical Research Institute (IDIBELL)
• Josep Trueta Biomedical Research Institute of Girona (IDIBGI)
• Josep Carreras Leukemia Research Institute (IJC)
• Barcelona Institute for Global Health (ISGlobal)
• Parc Taulí Research and Innovation Institute (I3PT)
• Autonomous University of Barcelona (UAB)
• Open University of Catalonia (UOC)
• Vall d’Hebron Research Institute (VHIR)
• Barcelona Supercomputing Center (BSC)
• Acondicionamiento Tarrasense – LEITAT
• Sant Joan de Déu Private Foundation for Research and Teaching (FSJD)

Collaborating Entities

• Iolanda Marchueta (self-employed, trainer)
• Barcelona Mobile World Capital Foundation (MWC)
• Catalan Fragile X Syndrome Association (ACSXF)
• Osteoarthritis Foundation International (OAFI)
• Pfizer, SLU
• Organon Salud, SL
• Cotton High Tech, SL

The 2025 update of Stanford University’s bibliometric database has identified fourteen researchers affiliated with the Sant Pau Research Institute (IR Sant Pau) among the top 2% of the world’s most influential scientists corresponding to the most recent year analyzed. This classification, based on Scopus data, evaluates nearly one hundred thousand authors across 22 academic fields and annually recognizes those with the greatest global impact on the scientific community.

This is the seventh edition of this compilation, launched in 2019, which has become an international reference tool for measuring scientific influence across disciplines. The ranking is based on normalized indicators that consider essential aspects such as publication volume, citation quality and impact, each researcher’s career trajectory, and their actual weight in each article through metrics such as the C-Score. This approach helps overcome common biases—such as self-citations or the high variability between scientific fields—and provides a more rigorous picture of each author’s true impact on knowledge generation.

The presence of fourteen IR Sant Pau authors in this edition reflects the diversity and strength of the institute’s research areas. Among the recognized researchers, the Clinical Epidemiology and Health Services Group stands out, led by Dr. Pablo Alonso-Coello, together with Dr. Xavier Bonfill Cosp, Dr. Ivan Solà, and Dr. Maria Ximena Rojas. Their contributions to evidence-based medicine, the critical evaluation of scientific literature, and the development of clinical guidelines have had a direct influence on medical decision-making worldwide and have strengthened IR Sant Pau’s international prestige in this field.

Also included is the Neurobiology of Dementias Group, led by Dr. Alberto Lleó with Dr. Daniel Alcolea as a prominent researcher. Both are international leaders in the development of diagnostic and prognostic biomarkers for Alzheimer’s disease and other neurodegenerative disorders, an area in which Sant Pau has achieved globally recognized standing. Their research has helped redefine the early stages of the disease and promote new diagnostic criteria that are now used worldwide.

In addition, Stanford’s database includes other Sant Pau researchers with impactful careers across multiple specialties. Dr. Cándid Villanueva has excelled in the field of liver disease and gastrointestinal bleeding; Dr. Carol Moreno in hematology and translational research in oncohematologic disorders; Dr. Margarita Majem in thoracic oncology; Dr. Teresa Padró in vascular research and atherosclerotic disease; Dr. Pere Domingo in infectious diseases and HIV; Dr. Lluís Puig in dermatology and immune-mediated diseases; and Dr. Carlos Brotons in primary care, prevention, and community health research. Among these names, Dr. Antonio J. Bayés-De-Luna, a retired cardiologist, also stands out, as his influence remains exceptional thanks to a decades-long scientific career that has decisively contributed to the understanding of cardiac rhythm disorders.

This collective recognition highlights Sant Pau’s role as a generator of high-impact biomedical knowledge and as an institution that integrates clinical, translational, and epidemiological research with a multidisciplinary vision oriented toward the common good. The inclusion of fourteen researchers among the top 2% most influential in the world confirms the strength of their contributions and reinforces the international projection of the IR Sant Pau. This includes fields as diverse as neuroscience, epidemiology, cardiovascular diseases, oncology, infectious diseases, and primary care research.

Researchers from the Biomarkers of Cardiovascular Disease Progression group at the Institut de Recerca Sant Pau (IR Sant Pau) have identified a new mechanism by which complement C3, a key immune system protein, can directly influence the progression of atherosclerosis. The study, published in the journal Cells, shows that activation of this molecule alters the structure and behavior of the cells that form the arterial wall, contributing to lesions becoming more unstable and more prone to rupture.

Atherosclerosis is a chronic disease characterized by the accumulation of cholesterol and other substances in the arteries, which triggers an inflammatory response that disrupts the balance of vascular tissues. Among the different types of cells involved in this process, vascular smooth muscle cells play a crucial role: under normal conditions, they maintain vessel elasticity, but when activated by inflammatory or lipid signals, they can change their shape and function, participate in plaque formation, and contribute to plaque fragility.

“Understanding how lipids, inflammation, and arterial wall cells interact is essential to prevent cardiovascular complications,” explains Dr. Teresa Padró, head of the Biomarkers of Cardiovascular Disease Progression group at IR Sant Pau and researcher at CIBERCV. “In this work, we have identified a new role of complement C3 that links the immune response with the cellular processes that remodel the arteries.”

The finding provides a new insight into how inflammation and lipids combine to modify the structure of the arterial wall. It highlights the role of complement C3 as a mediator between the body’s defenses and the cellular mechanisms that determine arterial stability.

Cellular Remodeling in the Arterial Wall

The study shows that activation of complement C3 triggers a series of changes in the smooth muscle cells of the arterial vascular wall, which stop behaving like contractile cells—responsible for maintaining vessel tone and structure—to adopt a more mobile profile with greater remodeling capacity. Although this phenomenon is part of natural repair mechanisms, when sustained over time, it can promote disease progression.

The researchers identified that the activated complement fragment known as iC3b acts as a signal that reorganizes the cell interior. Specifically, they observed that it modifies the distribution of paxillin (PXN), a protein essential for cell adhesion and communication with the environment. This change directly affects the cytoskeleton, the internal structure that supports the cell, regulates its shape, and enables movement.

Using advanced microscopy techniques, the team found that when smooth muscle cells of the arterial wall are exposed to aggregated low-density lipoproteins (agLDL)—a modified form of “bad” cholesterol that accumulates in arteries—the amount of paxillin decreases and its location within the cell is altered. In contrast, when these lipid-loaded cells are exposed to the iC3b fragment of the complement system, paxillin redistributes. Its relationship with F-actin, a key component of the internal cytoskeletal fibers, changes in a pattern that reflects greater migratory and remodeling activity. In the context of atherosclerosis, this behavior may facilitate the movement of lipid-laden smooth muscle cells within the arterial intima layer and contribute to changes that make plaques more vulnerable.

“We knew from previous work by our group that C3 complement products are present in atherosclerotic lesions, affecting the structure and function of smooth muscle cells,” notes Dr. Teresa Padró, adding that “the current results help us better understand the mechanisms involved, showing that iC3b-mediated signaling directly affects paxillin organization and thus cytoskeletal dynamics, a key aspect of arterial wall stability.”

Paxillin, the Axis of a Gene Network Linked to Cell Migration

To understand the mechanisms behind these changes, the researchers analyzed which genes are activated when smooth muscle cells begin to migrate. They identified 30 genes with altered expression, six of which—PXN, AKT1, RHOA, VCL, CTNNB1, and FN1—are directly related to cytoskeletal organization and cell motility.

Among them, PXN, the gene encoding paxillin, emerged as the central node of the molecular network that coordinates the cellular response to inflammatory and lipid stimuli. This protein acts as a bridge between the outside and the inside of the cell, regulating how the cell adheres, changes shape, and moves.

“The discovery of PXN as the central axis of the gene network suggests that cytoskeletal remodeling is not an isolated phenomenon but a coordinated response involving multiple signaling pathways,” highlights Dr. Teresa Padró. “The connection between these cellular pathways helps us understand how inflammation and lipids can remodel the arterial wall from within.”

A New Link Between Inflammation and Arterial Plaque Fragility

The study’s results suggest that the complement system, in addition to its classical role in immune defense, also influences the processes that determine the shape and stability of arteries. The iC3b fragment not only participates in the inflammatory response but can directly modify the behavior of smooth muscle cells, contributing to arterial plaque fragility.

Until now, research on atherosclerosis had focused mainly on macrophages and endothelial cells. However, this work shows that smooth muscle cells also interpret inflammatory signals and respond by transforming, making them active agents in the progression of the disease.

“This dialogue between complement C3 and paxillin reveals a little-explored connection between immune mechanisms and the cellular biology of the arterial wall,” notes Dr. Teresa Padró. “Understanding how inflammation and lipid load modulate smooth muscle cell migration may help identify new therapeutic targets to prevent the progression of atherosclerosis and stabilize plaques.”

The researchers suggest that this interaction may facilitate the movement of smooth muscle cells from the deeper layers of the artery toward the area where plaques form, weakening their structure and making them more prone to rupture. In addition, prolonged exposure to iC3b may encourage these cells to change function and stop behaving like contractile cells, adopting a more inflammatory and reparative profile.

Understanding this new iC3b–paxillin molecular axis may help design therapeutic strategies that reduce inflammation or cholesterol and reinforce the mechanical stability of arteries. In the future, this line of research may contribute to identifying biomarkers that help detect, at an early stage, the most vulnerable plaques with the highest risk of rupture.

The study was funded by the Instituto de Salud Carlos III (ISCIII), the Next Generation EU program of the Recovery and Resilience Mechanism, the Agencia Estatal de Investigación (AEI), and the Generalitat de Catalunya.

Article References:

1. Garcia-Arguinzonis M, Escate R, Lugano R, Peña E, Borrell-Pages M, Badimon L, Padro T. Gene expression pattern associated with cytoskeletal remodeling in lipid-loaded human vascular smooth muscle cells: Crosstalk between C3 complement and the focal adhesion protein paxillin. Cells 2025;14. https://doi.org/10.3390/cells14161245
2. Garcia-Arguinzonis M, Diaz-Riera E, Peña E, Escate R, Juan-Babot O, Mata P, Badimon L, Padro T. Alternative C3 complement system: Lipids and atherosclerosis. Int J Mol Sci 2021;22:5122. https://doi.org/10.3390/ijms22105122

The Sant Pau Research Institute (IR Sant Pau) has received a donation of 2,500 euros from the Viladecans Cancer Coordinator Association, aimed at boosting the research conducted by the centre on CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a hereditary disease that affects the small blood vessels of the brain and can cause migraine, psychiatric disorders, recurrent strokes, and dementia. Despite recent progress, there is still no curative treatment.

The contribution from the Viladecans Cancer Coordinator Association will support the drug repositioning project led by the Pharmacogenomics and Neurovascular Genetics Research Group at IR Sant Pau, headed by Dr. Israel Fernández-Cadenas. The team investigates medicines already approved for other conditions that may have beneficial effects on CADASIL—an approach that can accelerate the development of potential therapies.

The support of organizations committed to research is essential to keeping active the study of rare diseases. Contributions like this one help facilitate the acquisition of materials, specialized analyses, and the development of new studies that enhance understanding of the disease and explore new therapeutic avenues.

IR Sant Pau expresses its deep gratitude to the Viladecans Cancer Coordinator Association for its trust and support. Their contribution is vital to continue advancing scientific knowledge and improving the quality of life of people affected by CADASIL and their families.

The Sant Pau Research Institute (IR Sant Pau) has received new national funding from the Spanish State Research Agency (AEI), an agency under the Ministry of Science, Innovation, and Universities. This is through the 2025 Call for Grants for the Preparation and Management of European Projects and for Facilitating the Attraction of International Talent. This support will help consolidate and expand the structure of the European Projects Office (OPE) and is aligned with the institute’s strategy to strengthen its presence in the Horizon Europe program, articulated through the plan “Horizon Sant Pau: Enhancing Excellence and Innovation in Horizon Europe”, which guides the center’s main lines of international growth.

According to Noemí Carranza, head of the OPE, “this grant represents a decisive step toward further professionalizing our internationalization structure and better supporting research groups in preparing competitive proposals. Recently we have made great progress, but the demand for support continues to grow. Having a more robust structure allows IR Sant Pau to consolidate its leadership in Horizon Europe and open new opportunities for our research talent to participate in high-impact projects.”

The awarded grant amounts to €145,889.00, which will be used to promote advanced training in European programs, improve digital tools for analyzing funding opportunities, and strengthen technical support in preparing competitive proposals.

Sustained Growth in International Activity

Lately, IR Sant Pau has experienced sustained growth in its international activity. The creation of the OPE in 2021 marked a turning point: the number of proposals submitted to European programs has increased significantly, financial returns have risen substantially. In 2024, the institute obtained, for the first time, a coordinated Horizon Europe project with €7 million in funding, of which more than €1 million is allocated to the institute. In addition, researchers at the center have secured eight projects funded by the U.S. National Institutes of Health (NIH) in just three years, strengthening the diversification of its international portfolio and providing essential structural resources to support scientific management.

This progress has been consolidated thanks to a clear institutional commitment to internationalization, reflected in IR Sant Pau’s 2025–2030 strategy. This roadmap sets as priority objectives the strengthening of scientific leadership in Europe, the attraction of international talent, and the reinforcement of alliances with institutions, companies, and strategic networks. The new funding will deepen this direction by enabling intensive training programs, specialized workshops, coordinated proposal-preparation activities, and new semantic analysis tools that will facilitate the reading and interpretation of European work programs.

Strengthening the OPE will also improve internal coordination among the units involved in international projects, from innovation to clinical trials. It will also expand support for the clinical groups of Hospital de Sant Pau, from which a large portion of the institute’s research staff originates. This integration is essential to increase the quality, maturity, and robustness of proposals submitted to Horizon Europe, particularly in strategic areas such as neurosciences, cardiovascular research, hematology, oncology, and advanced therapies.

A Consolidated Track Record of Funding to Boost Internationalization

This new national grant adds to a solid trajectory of funding that has allowed IR Sant Pau to build and consolidate its international structure. In 2022, the institute received a national grant of €174,986.30 through the call for Preparation and Management of European Projects, allocated for the 2023–2024 period and extended until September 2025. This funding enabled staff expansion, stronger internal training, and improvements in analytical and research-support tools.

Additionally, the regional program Go Europe awarded IR Sant Pau €299,940, extended until June 2026. This support funds specialized human resources, technological platforms, partner-search tools, and networking and training activities—key elements for consolidating a professional and stable model of European project management.

Thanks to this trajectory, IR Sant Pau now has a mature structure that combines specialized technical staff, solid work procedures, advanced digital platforms, and an expanding network of national and international collaborations. The new funding allows the institute to take another step forward, strengthening its capacity to lead high-impact projects, attract competitive funding, and transfer knowledge for of the healthcare system and society.

Hospital de Sant Pau recently hosted the First National Meeting of the GEICEN Group (Stable Research Group in Gynecologic Cancer), a gathering that brought together researchers and specialists from across Spain dedicated to the study of gynecologic cancer from a basic, translational, and clinical perspective. GEICEN is made up of 10 research groups from different academic and hospital institutions, and its objective is to promote collaborative projects that advance the understanding of these tumors and the clinical management of patients.

The event featured the participation of the Gynecological and Breast Pathology Group of the Sant Pau Research Institute (IR Sant Pau), which served as host of this first edition. Dr. Silvia Cabrera, head of the group, highlighted that “this meeting is an essential step toward consolidating a national research network in gynecologic cancer. Sharing results, challenges, and methodologies allows us to move forward faster and offer more efficient responses to patients, and for our group, hosting this first meeting is an honor and a boost to continue growing in this field.”

The program included short presentations from each of the groups that make up GEICEN, with participation from IR Sant Pau, IRYCIS, IRBLleida, IDIBELL, UB, IDIS, FMDA, and VHIR, among others. The presentations made it possible to share strategic projects and research lines in areas such as biomarkers, preclinical models, emerging therapies, biobanks, omics technologies, and new diagnostic approaches in gynecologic oncology. Representing IR Sant Pau, in addition to Dr. Silvia Cabrera, Dr. Alba Farrés also participated, presenting a new project being launched on endometrial cancer.

Following the morning scientific sessions, the event continued with internal meetings focused on the strategy of principal investigators and the coordination of early-career researchers, aimed at defining new collaborative lines and preparing future competitive proposals. The holding of this first national meeting marks an important step for GEICEN, which aims to become a stable reference space for coordinated research on gynecologic tumors, which affect thousands of women every year.

Researchers from the Sant Pau Research Institute (IR Sant Pau) have conducted a clinical trial demonstrating that the combination of two widely available drugs, carvedilol and simvastatin, significantly improves the control of portal hypertension in patients with hepatic cirrhosis.

The study, published in the scientific journal Hepatology, lists Dr. Edilmar Alvarado and Dr. Anna Brujats as first authors and Dr. Cándido Villanueva as senior author. All of them are investigators of the Digestive Pathology group at IR Sant Pau and hepatologists at Hospital de Sant Pau. The collaborating team also includes researchers from the hepatology group at Hospital Sant Pau—Dr. Berta Cuyás, Dr. María Poca, Dr. Xavier Torras, and Dr. Angels Escorsell, among others—researchers in experimental immunology—Dr. E. Cantó—pharmacy—Ainhoa Rodríguez Arias—and biochemistry—Álvaro García-Osuna.

The research stems from a clear clinical need: to find new strategies capable of effectively reducing portal pressure in people with advanced cirrhosis. According to Dr. Alvarado, “These patients continue to have a very high risk of gastrointestinal bleeding, among other complications of portal hypertension, even with standard treatment, and we needed to explore simple options that could improve their prognosis.”

What Is Portal Hypertension and Why Is It Important?

Cirrhosis is a disease in which the liver gradually becomes hardened and scarred, hindering the flow of blood through it. As a result, the blood arriving from the digestive tract via the portal vein encounters more resistance as it passes through the liver, and pressure in this major vessel rises abnormally. This phenomenon, known as portal hypertension, is one of the main drivers of complications in advanced liver disease.

When portal pressure becomes too high, dilated veins form in the esophagus and stomach—the so-called varices—which are extremely fragile and can rupture, causing potentially life-threatening gastrointestinal bleeding. Portal hypertension also contributes to the accumulation of fluid in the abdomen (ascites) and to kidney problems. Reducing it significantly has proven crucial for improving survival and quality of life in these patients.

In clinical practice, this pressure is measured through the hepatic venous pressure gradient (HVPG), a procedure that reliably quantifies the severity of portal hypertension and helps determine whether a pharmacologic treatment is effective.

Available Treatments and Their Limitations

To prevent gastrointestinal bleeding, nonselective beta-blockers such as propranolol or nadolol have been used for decades, as they reduce the amount of blood reaching the liver. However, in many patients these drugs do not sufficiently lower portal pressure.

Recently, carvedilol has proved more effective because, in addition to blocking beta-receptors, it also acts on alpha-1 receptors in blood vessels. This dual action causes greater relaxation of intrahepatic vessels, more effectively reducing resistance to blood flow.

Still, in a substantial proportion of patients treated only with carvedilol, the goal of lowering portal pressure is not achieved. Dr. Alvarado explains the team’s reasoning: “We knew that statins could improve blood vessel function and reduce inflammation in the liver. We thought that administering a statin alongside carvedilol could create a complementary effect and increase treatment efficacy by further reducing portal pressure.”

Although several statins are available, simvastatin was chosen because it has the most prior research in cirrhosis, where it had shown the ability to improve liver blood vessel function safely.

A Clinical Trial Designed to Address an Unmet Need

With this hypothesis, the Sant Pau team launched a randomized, double-blind, placebo-controlled clinical trial. A total of 82 patients with advanced cirrhosis and high-risk varices were recruited, all of whom had shown an insufficient response to traditional beta-blockers.

First, the researchers confirmed that portal pressure had not decreased adequately with standard treatments. From that point on, all patients started taking carvedilol, and were then randomly assigned to receive either simvastatin or a placebo for 4 to 6 weeks, without doctors or patients knowing who received which treatment.

The impact of treatment was measured through HVPG. In addition, the researchers took measurements after a nutritional supplement, a moment when portal pressure typically increases and bleeding risk intensifies, to determine whether the combination could better blunt this effect. Blood samples were also collected to analyze inflammatory cytokines and oxidative stress markers, to assess whether the benefits extended beyond portal pressure reduction.

“We designed the study with real-life patient situations in mind—from the impact of meals to the inflammatory processes that accompany cirrhosis,” Dr. Alvarado explains.

A Step Forward in Preventing Gastrointestinal Bleeding

The results confirmed the initial hypothesis. Carvedilol alone and in combination with simvastatin both reduced portal pressure, but the decrease was significantly greater in the group receiving the two drugs. In absolute terms, HVPG fell from 18.6 to 15.7 mmHg with the combination (versus a reduction from 18.9 to 16.9 mmHg with placebo).

Additionally, 37% of patients treated with carvedilol plus simvastatin achieved a clinically meaningful pressure reduction (≥ 20%), compared with only 15% in the control group. The combination also blunted the increase in portal pressure after the nutritional supplement (12% versus 23%) and more strongly reduced several inflammatory blood markers. All of this occurred with good tolerance and a similar incidence of adverse events in both groups.

For Dr. Alvarado, these findings are promising: “This is a simple strategy using inexpensive, widely available drugs that could have a real impact on preventing decompensations associated with portal hypertension.”

This study opens the door to new therapeutic strategies in cirrhosis. Larger trials will be needed to confirm these results and to assess long-term effects on bleeding prevention and patient survival. But, as Dr. Alvarado concludes, “We have shown that even with well-known treatments, if we combine them effectively, we can take a meaningful step forward in caring for patients with cirrhosis.”

Reference Article:

Alvarado-Tapias E, Brujats A, Puente A, Ardevol A, Rodriguez-Arias A, Fajardo J, Pavel O, Garcia-Guix M, Aracil C, Poca M, Cuyàs B, Cantó E, Montañés R, Garcia-Osuna A, Escorsell À, Torras X, Villanueva C. Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized trial. Hepatology 2025;82:140–54. <a href=”https://doi.org/10.1097/HEP.0000000000001148″>https://doi.org/10.1097/HEP.0000000000001148