The Sant Pau Research Institute has published its 2024 Annual Report, a yearly overview of a full year of research, collective effort, and meaningful results.
The document outlines the activity carried out throughout 2024 and highlights the scientific impact of the Institute, which continues to strengthen its role as a national and international benchmark. It also serves as a recognition of the daily work of all the professionals involved.
The Sant Pau Research Institute (IR Sant Pau) is leading the new multicenter clinical trial FTAA (Fast Track in Acute Appendicitis), aimed at improving the postoperative management of complicated appendicitis in children. The study proposes an innovative antibiotic treatment strategy that could reduce hospitalization time without compromising the safety or efficacy of the therapeutic approach.
The trial was recently presented at the European Association for Clinical Pharmacology and Therapeutics Congress (EACPT 2025), held in Helsinki, Finland, from June 28 to July 1. This is the first randomized clinical trial in a pediatric population comparing two antibiotic treatment duration strategies following surgery for complicated appendicitis, one of the most common surgical emergencies in childhood.
The project is coordinated by Dr. María José Martínez Zapata from the Clinical Epidemiology and Healthcare Services Research Group at IR Sant Pau, together with Dr. Carlos Leganés, a pediatric surgeon at Hospital Sant Pau. Also participating are Drs. Rosa María Antonijoan and Claudia Erika Delgado-Espinoza from the Clinical Pharmacology Department and Dr. José María Valle from the Pediatrics Department of the same hospital.
In addition to Hospital Sant Pau, the trial involves collaboration with six other leading hospitals: Hospital Sant Joan de Déu and Hospital del Mar in Barcelona, Hospital Germans Trias i Pujol in Badalona, Hospital Joan XXIII in Tarragona, Hospital Clínico Universitario in Santiago de Compostela, and Hospital Universitario Dr. Josep Trueta in Girona. This broad participation will provide representative and nationally applicable results.
The study has received funding from the 2023 Independent Clinical Research call by the Instituto de Salud Carlos III (ICI23/00070) and is supported by the Spanish Clinical Research Network (SCReN), aimed at facilitating clinical trials of interest to the National Health System.
The primary objective of the FTAA trial is to evaluate whether a shorter antibiotic regimen—three days of intravenous antibiotics in the hospital followed by two days of oral outpatient treatment with amoxicillin-clavulanate—is as effective as the standard five-day in-hospital antibiotic treatment in preventing complications within 30 days of surgery. A total of 772 pediatric patients are planned for recruitment.
If the outpatient strategy proves non-inferior, the study could represent a significant change in clinical practice, reducing children’s hospital stays and promoting quicker recovery in the home environment. This optimization of treatment would not only benefit the quality of life for patients and their families but also contribute to greater efficiency in healthcare resource utilization and decreased exposure to risks associated with prolonged hospitalization.
IR Sant Pau thus reaffirms its commitment to clinical research aimed at improving healthcare, especially in high-impact areas such as pediatric surgery and the rational use of antibiotics.
The CIBEREHD group from the Digestive Diseases Department at Hospital de Sant Pau has participated in an international clinical trial recently published in JAMA (Journal of the American Medical Association), one of the most prestigious medical journals worldwide. The study, conducted within the framework of the LIVERHOPE Consortium and led by Dr. Elisa Pose and Dr. Pere Ginès from Hospital Clínic de Barcelona, evaluated whether the combined administration of simvastatin and rifaximin, added to standard treatment, could reduce clinical complications and mortality in patients with decompensated cirrhosis—one of the most severe and complex stages of liver disease. The study was funded through a Horizon 2020 grant with European funds.
The study was conducted between January 2019 and December 2022 and included a total of 237 patients with decompensated cirrhosis recruited from 14 European centers, including Hospital de Sant Pau. It was a double-blind, randomized, placebo-controlled trial in which participants received either the combination of simvastatin (20 mg/day) and rifaximin (1,200 mg/day) or a placebo for one year, in addition to standard medical therapy.
The scientific rationale behind this combination lies in their complementary mechanisms of action. Simvastatin not only lowers blood cholesterol levels but is also known for its anti-inflammatory and antifibrotic properties, as well as its ability to reduce hepatic portal pressure—effects that, in a previous clinical study, appeared to reduce mortality. Rifaximin, on the other hand, is an antibiotic with very low systemic absorption that modulates the gut microbiome and likely inhibits bacterial translocation, endotoxemia, and inflammation, helping to reduce hepatic encephalopathy. Based on this, the project set out to determine whether this combined strategy could prevent the development of the severe condition known as acute-on-chronic liver failure (ACLF), other cirrhosis-related complications, and mortality.
However, the results were unexpected. The study showed no significant differences between the treated group and the placebo group in terms of ACLF incidence, liver transplant rates, or mortality. There were also no differences in the occurrence of typical cirrhosis complications such as ascites, hepatic encephalopathy, esophageal variceal bleeding, acute kidney injury, or infections.
As for safety, the therapeutic combination was generally well tolerated, although a few cases of rhabdomyolysis—a muscle-related complication—were reported in the treatment group. This underscores the need for caution when using statins in this patient population. This trial was based on previous phase II studies that had shown a good safety profile with low doses of simvastatin, like those used in the current study, although higher doses had occasionally been linked to liver and muscle toxicity.
Although the results were not positive, the researchers emphasized the importance of publishing this kind of evidence. In the words of Dr. Germán Soriano, physician in the Digestive Diseases Department at Hospital de Sant Pau and one of the authors of the article, “This study is a clear example that in clinical research, negative results are also valuable. They help us rule out approaches that seemed promising and better focus our efforts on strategies that are truly effective for our patients.” Dr. Soriano also highlighted the significance of participating in a multicenter study of this caliber: “It is important for Sant Pau to be part of international alliances that allow us to tackle global clinical challenges with a collaborative and rigorous approach.”
Reference article:
Pose E, Jiménez C, Zaccherini G, Campion D, Piano S, Uschner FE, de Wit K, Roux O, Gananandan K, Laleman W, Solé C, Alonso S, Cuyàs B, Ariza X, Juanola A, Ma AT, Napoleone L, Gratacós-Ginès J, Tonon M, Pompili E, Sánchez-Delgado J, Allegretti AS, Morales-Ruiz M, Carol M, Pérez-Guasch M, Fabrellas N, Pich J, Martell C, Joyera M, Domenech G, Ríos J, Torres F, Serra-Burriel M, Hernáez R, Solà E, Graupera I, Watson H, Soriano G, Bañares R, Mookerjee RP, Francoz C, Beuers U, Trebicka J, Angeli P, Alessandria C, Caraceni P, Vargas VM, Abraldes JG, Kamath PS, Ginès P, LIVERHOPE Consortium. Simvastatin and rifaximin in decompensated cirrhosis: A randomized clinical trial. JAMA 2025;333:864–74. https://doi.org/10.1001/jama.2024.27441
The Neuromodulation in Movement Disorders Group at Hospital de Sant Pau has received the Best Oral Presentation Award at the 2025 Congress of the Spanish Society of Neurosurgery (SENEC), recently held in Zaragoza. The award recognizes a pioneering study focused on deep brain stimulation (DBS) in Parkinson’s disease, one of the most advanced therapies for managing this neurodegenerative condition.
The winning study developed a functional three-dimensional map of the subthalamic nucleus (STN)—a key brain structure involved in movement control—based on the analysis of local field potentials (LFPs) recorded during surgery in patients with advanced Parkinson’s. These LFPs reflect the brain’s electrical activity and enable a more precise understanding of how its internal networks function in real time.
One of the study’s most relevant findings is that brain oscillations—especially those in the beta band, which are associated with the rigidity and slowness of movement characteristic of Parkinson’s—are not always confined within the classical anatomical boundaries of the STN. This suggests that traditional targeting based solely on anatomical criteria may not be sufficient to achieve optimal therapeutic outcomes.
Thanks to advanced neuroimaging tools, spectral analysis, and computational modeling, the team has shown that the closer the electrode is placed to areas of high beta activity, the better the motor outcomes after surgery. This approach strengthens the case for “functional targeting,” a surgical strategy that considers both the anatomy and the brain physiology of each patient.
“Every brain is different, and in a complex disease like Parkinson’s, knowing the precise location of pathological activity allows us to personalize the therapy more effectively,” explains Dr. Juan Aibar, one of the researchers behind the study, together with Dr. Ignacio Aracil, Dr. Rodrigo Rodríguez, Dr. Berta Pascual, Dr. Alex Gironell, and Antonia Campolongo. “Our goal is to move toward precision neuromodulation, based on brain biomarkers that can guide us before, during, and after the procedure.”
Deep brain stimulation is a surgical technique that has transformed the treatment of advanced Parkinson’s disease. It involves implanting electrodes in specific brain regions to modulate their activity through electrical impulses. When applied correctly, DBS can significantly improve motor symptoms and quality of life, while reducing the need for medication.
This new study from Sant Pau not only enhances the scientific understanding of brain function in Parkinson’s disease but also provides concrete tools to improve surgical planning and maximize the benefits of deep brain stimulation.
Sant Pau’s Neuromodulation in Movement Disorders Group has a long-standing track record in translational DBS research, combining neurosurgery, neurology, biomedical engineering, and data analysis. This award provides renewed momentum for the team’s commitment to translating scientific knowledge into tangible benefits for people affected by neurological disorders.
A team of researchers at the Sant Pau Research Institute (IR Sant Pau) has demonstrated that the plasma biomarker p-tau217, obtained through a simple blood test, can predict the clinical progression of Alzheimer’s disease even in its earliest stages. This is when symptoms are not yet evident. The study, published in the journal Neurology, reinforces the role of blood tests in the future of diagnosing and monitoring dementias.
The study, conducted within the framework of the SPIN cohort (Sant Pau Initiative on Neurodegeneration), included 731 individuals with and without cognitive impairment who were followed for an average of up to 10 years. The researchers analyzed levels of p-tau217—a specific form of the tau protein associated with neurodegeneration—and observed that this marker not only correlates with the presence of Alzheimer’s disease but also enables prediction of the rate of cognitive decline and progression to more advanced stages of the disease. This includes dementia.
“This marker has enormous potential as a clinical tool. It not only accurately identifies Alzheimer’s disease, but also allows us to estimate how fast it will progress—an essential factor in making therapeutic decisions,” says Dr. Ignacio Illán, researcher in the Neurobiology of Dementia group and neurologist at Sant Pau Hospital, who led the study.
For her part, Judit Selma-González, first author and research neuropsychologist, also from the Neurobiology of Dementia group, highlights that “one of the most relevant findings is that p-tau217 allows us to identify people who do not yet have cognitive symptoms but are at higher risk of developing the disease in the short or medium term. This can help us better select patients eligible to participate in clinical trials of disease-modifying treatments.”
Until now, the most reliable biomarkers for detecting and monitoring Alzheimer’s disease have required invasive techniques such as lumbar puncture (to analyze cerebrospinal fluid) or costly procedures such as positron emission tomography (PET). The use of plasma p-tau217 offers a non-invasive, more accessible, and affordable alternative with both clinical and research applications.
The study indicated that p-tau217 levels increased progressively from the preclinical stages to the advanced stages of dementia, and were independently associated with a higher risk of cognitive decline (measured, among other tools, with the Mini-Mental State Examination) and conversion to dementia. In fact, the marker showed better prognostic ability than its cerebrospinal fluid equivalent, p-tau181, which is widely used today.
This advance is particularly relevant in the current context, where disease-modifying treatments—such as anti-amyloid antibodies—are already being approved, and their use depends on the stage of Alzheimer’s disease progression. The possibility of using a blood test to determine this clinical stage and monitor its progression represents a major step toward more personalized and precise medicine. “In a memory clinic, having access to this information through a blood test opens up possibilities that were previously limited to highly specialized centers,” notes Dr. Ignacio Illán.
This study was funded by the Instituto de Salud Carlos III (ISCIII) through projects PI14/01126, PI17/01019, PI18/00335, PI19/00882, PI18/00435, PI22/00611, INT19/00016, INT23/00048, PI17/01896, PI22/00307, PI20/01473, PI23/01786, PI21/00791, and PI24/00598, and co-funded by the European Union. It was also supported by research programs of the Spanish Biomedical Research Network Center on Neurodegenerative Diseases (CIBERNED) and the La Marató de 3cat Foundation (projects 20141210, 044412, and 20142610), as well as by the “la Caixa” Foundation (DABNI project), the Catalan Down Syndrome Foundation, the Víctor Grífols i Lucas Foundation, and the Government of Catalonia (2017-SGR-547, SLT006/17/125, SLT006/17/119, SLT002/16/408).
Several researchers were supported by competitive contracts, including Río Hortega and Sara Borrell fellowships from ISCIII in collaboration with the European Social Fund Plus. In addition, various authors are affiliated with the Global Brain Health Institute (GBHI) as fellows of the Atlantic Fellow for Equity in Brain Health program, with additional funding from the Alzheimer’s Association, the Alzheimer Society, and the Jérôme Lejeune Foundation. International collaboration was strengthened through the participation of the Institute of Neuroscience and Physiology at the University of Gothenburg (Sweden), the Banner Alzheimer’s Institute (United States), and the Barcelona Down Medical Center.
Selma-Gonzalez J, Rubio-Guerra S, García-Castro J, Vera-Campuzano E, Sala I, Sánchez-Saudinós MB, Zhu N, Arranz J, Arriola-Infante JE, Rodríguez-Baz Í, Maure-Blesa L, Dols-Icardo O, Videla L, Valldeneu S, Barroeta I, Santos-Santos M, Carmona-Iragui M, Vaqué-Alcázar L, Alvarez-Sanchez E, Lorente O, Carreras M, Belbin O, Arslan B, Ashton NJ, Zetterberg H, Blennow K, Montoliu-Gaya L, Bejanin A, Lleó A, Fortea J, Alcolea D, Illan-Gala I. Association of plasma phosphorylated tau 217 with clinical deterioration across Alzheimer disease stages. Neurology. 2025;105:e213769. https://doi.org/10.1212/WNL.0000000000213769.
The prestigious journal Trends in Neurosciences recently published a scientific commentary authored by Dr. Oriol Dols-Icardo, a researcher with the Neurobiology of Dementias group at the Sant Pau Research Institute (IR Sant Pau) and the Memory Unit at Hospital de Sant Pau. The article provides a critical and contextualized analysis of recent advances in the genetics of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), a neurodegenerative disease that ranks among the most common causes of dementia after Alzheimer’s disease.
The commentary focuses on a study by Pottier and colleagues published in Nature Communications, which represents the most extensive whole-genome sequencing analysis conducted to date in patients with FTLD-TDP. The study included nearly 1,000 patients diagnosed with FTLD-TDP and its pathological subtypes A, B, and C, as well as more than 3,000 control individuals, and identified multiple genetic variants—both common and rare—specifically associated with each subtype. Some of these risk factors have also been linked to other diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and hippocampal sclerosis, all of which are associated to varying degrees with the presence of TDP-43 inclusions.
As corresponding author, Dr. Dols-Icardo led the writing of the commentary and invited two prominent international researchers to contribute: Dr. Lianne M. Reus from Vrije Universiteit Amsterdam in the Netherlands, and Dr. Alfredo Ramírez from the University of Cologne and the German Center for Neurodegenerative Diseases – DZNE. All three experts emphasize the importance of these findings for advancing the understanding of the biological and clinical heterogeneity of FTLD-TDP.
“Our commentary highlights that the different subtypes of FTLD-TDP may be driven by distinct genetic mechanisms, which supports the notion that they represent separate biological entities,” explains Dr. Oriol Dols-Icardo. Furthermore, TDP-43 is the primary aggregated protein in FTLD-TDP, ALS, and hippocampal sclerosis, but it is also present in 60% of individuals with Alzheimer’s disease. Dr. Dols-Icardo points out that “some of the identified genetic factors also play a key role in these diseases. This approach brings us closer to earlier and more accurate diagnosis and more personalized risk stratification, with clear implications for the development of targeted therapies.”
The article also underscores the need to replicate the findings in independent cohorts, as well as the importance of having in vivo biomarkers capable of distinguishing between the pathological subtypes of FTLD-TDP. In addition, it highlights how next-generation sequencing technologies—particularly long-read techniques—can reveal structural variants, alternative isoforms, and complex splicing variations associated with TDP-43 dysfunction, a key protein not only in FTLD but also in other neurodegenerative disorders.
This commentary is a significant contribution to the current scientific discussion on neurodegenerative diseases associated with TDP-43 protein inclusions and reinforces Sant Pau’s leadership—and that of its research team—in the field of neurodegenerative diseases.
Dols-Icardo O, Reus LM, Ramirez A. Genetic architecture of FTLD-TDP pathological subtypes. Trends Neurosci 2025. https://doi.org/10.1016/j.tins.2025.06.005
The Technology Transfer and Innovation Unit (UTI) at the Sant Pau Research Institute (IR Sant Pau) has obtained ISO 56001 certification, an international standard that sets out the requirements for implementing, maintaining, and continuously improving an innovation management system. This accreditation recognizes organizations that integrate innovation as a strategic and cross-cutting component of their activity, promoting an innovation-driven culture aligned with their goals and expected social impact.
ISO 56001 provides a framework that helps systematize the processes of ideation, development, and transfer of innovative solutions. In this regard, the certification marks a step forward in consolidating an ecosystem that fosters the generation of new ideas, interdisciplinary collaboration, and the practical application of research results.
The UTI at IR Sant Pau plays a key role in promoting a culture of innovation, protecting and leveraging research outcomes, and encouraging collaboration with the business sector and other stakeholders in the surrounding ecosystem. With the attainment of ISO 56001, the institution strengthens its commitment to excellence and reinforces a path focused on creating added value through knowledge.
This new milestone adds to the UNE 166002 certification obtained in 2022, which certifies a solid and effective R&D&I management system. Together, these certifications position IR Sant Pau as one of the pioneering centers in Catalonia in the implementation of advanced innovation management mechanisms. In fact, it becomes the third research institute in Catalonia to receive ISO 56001 accreditation.
IR Sant Pau will continue working to transform scientific knowledge into real-world solutions that improve people’s health and quality of life, through high-quality research committed to innovation, knowledge transfer, and social progress.
The Sant Pau Research Institute (IR Sant Pau) is actively participating in the CADASIMUS project, a collaborative initiative recently selected in the “Dr. Miguel Blanco” seed funding call of the RICORS-ICTUS thematic network (Research Network on Outcomes and Quality of Stroke Care), funded by the Carlos III Health Institute as part of the new program of Cooperative Health-Oriented Research Networks (RICORS)).
The project was one of those selected in this competitive call, which aims to support the development of innovative preclinical studies to test a new drug for CADASIL. Thanks to this grant, CADASIMUS will receive €15,000 in funding, intended to cover the study’s key experimental costs. This funding will allow the launch of planned activities during the first year, such as drug treatment in a CADASIL cell model, as well as the study of the proteomic profile of the cell model and patient plasma and will serve as a basis for future applications for larger national or international projects.
The project is coordinated by the Translational Stroke Group at the Health Research Institute of Santiago de Compostela (IDIS) and involves the participation of IR Sant Pau, the Institute of Biomedicine of Seville (IBiS), and Donostia University Hospital. The co–principal investigators are Ana Bugallo Casal, Paula Villatoro González (IR Sant Pau), Ana Domínguez, and Patricia de la Riva.
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a rare disease caused by genetic variants in the NOTCH3 gene and is considered the genetic model more than all others of cerebral small vessel disease. Currently, no specific treatment exists for this condition. The CADASIMUS project will explore the potential of a drug already approved for other indications to modulate altered cellular mechanisms in CADASIL, such as autophagy, using an approach based on patient-derived cell models and biomarker analysis in human samples.
According to Paula Villatoro, “This project has a significant social and economic impact by addressing CADASIL, a rare disease with no specific treatment that causes progressive disability, recurrent subcortical strokes, and early vascular dementia. Identifying an already approved drug as a potential treatment would accelerate its clinical application and reduce costs associated with developing new therapies. Moreover, implementing biomarkers would optimize clinical trials by reducing the need for large cohorts and shortening study durations.”
The use of advanced omics technologies (such as proteomics via Olink technology) will enable the identification of potential therapeutic targets and biomarkers that can be validated in future clinical trials. One of the project’s innovative elements is the stratified analysis by biological sex, aiming to advance toward more equitable precision medicine.
IR Sant Pau’s involvement also includes the CADAGENIA biobank, which houses samples from patients with CADASIL, and collaboration with the CADASIL Spain Association, which actively contributes to the dissemination and alignment of the project with real patient needs.
Paula Villatoro also highlights the importance of network collaboration: “Collaboration among centers like IDIS, Sant Pau, IBiS, and Donostia is essential to combine capabilities, share resources, and accelerate knowledge. The RICORS-ICTUS structure precisely facilitates this cooperation, with a shared goal: to improve the clinical and therapeutic management of cerebrovascular diseases.”
With this recognition, IR Sant Pau reinforces its commitment to research in rare neurological diseases and to network-based collaboration within RICORS-ICTUS—a key collaborative structure for advancing the quality of care and outcomes in stroke and related diseases.
Early detection of Alzheimer’s disease has undergone a shift recently with the incorporation of biomarkers that allow for the identification of brain changes even before the first symptoms appear. However, the application of these new diagnostic frameworks—focused exclusively on biological parameters—raises clinical, ethical, and social questions that remain unanswered.
In this context, the article “On the complexity of biomarker-driven diagnoses of Alzheimer’s disease”, recently published in the Journal of Neuropsychology, reflects on the challenges and risks of diagnosing the disease based solely on the presence of -amyloid or phosphorylated tau in the brain. This is especially true for individuals who show no cognitive impairment. The paper is authored by Dr. Miguel Ángel Santos-Santos, a researcher in the Neurobiology of Dementias group at the Sant Pau Research Institute (IR Sant Pau) and neurologist at the Memory Unit of Hospital de Sant Pau. Together with Dr. Stephanie Grasso and Dr. Alexandra Leigh Clark, both from the University of Texas at Austin.
“Biomarkers are a promising tool, but we cannot yet consider a positive result as a diagnosis in itself. In cognitively healthy individuals, it’s more responsible to interpret them as indicators of elevated risk,” says Dr. Santos-Santos. The article highlights that a significant portion of people with abnormal biomarkers never go on to develop dementia, likely thanks to mechanisms of cognitive reserve and brain resilience. This concept, influenced by factors such as educational level, life experiences, and sociocultural context, is key to understanding the progression of the disease.
However, as the authors warn, current diagnostic models are based on studies involving homogeneous populations, which limits their applicability to minority groups or people with different life trajectories. “Diagnostic models must take racial, cultural, and structural diversity into account if we want to move toward truly equitable precision medicine,” explains Dr. Santos-Santos.
The researchers propose an alternative approach based on multifactorial risk prediction models that integrate biological data, neuropsychological testing, and social determinants of health. These models would better identify those individuals who would truly benefit from monitoring or early intervention strategies, avoiding unnecessary diagnostic labeling.
In addition, the commentary emphasizes the importance of clearly and responsibly communicating biomarker findings to patients, to avoid misunderstandings and negative impacts on their psychological well-being. In this regard, the authors advocate for an interdisciplinary approach that combines scientific evidence with each individual’s personal context.
This work reinforces the commitment of IR Sant Pau and the Memory Unit at Hospital de Sant Pau to cutting-edge international research in brain aging and dementias. Their contribution to the global debate on how to ethically, equitably, and effectively use the diagnostic tools of the future.
Reference article:
Grasso SM, Santos-Santos MÁ, Clark AL. On the complexity of biomarker-driven diagnoses of Alzheimer’s disease. J Neuropsychol 2025. https://doi.org/10.1111/jnp.12428
On Thursday the 26th, the documentary A Journey to the Limits of Human Adaptation was presented at Girona Cinemas. Produced by Tarannà Viatges and the Sant Pau Research Institute (IR Sant Pau), this production blends science, adventure, and public outreach to explore how the human body responds to the most extreme conditions of altitude and oxygen deprivation. The film is based on the scientific project Sherpa Project 2017: Effects of Exposure to Extreme Environmental Hypoxia on the Human Body, led by Dr. José Manuel Soria, head of the Complex Disease Genomics Research Group at IR Sant Pau.
This groundbreaking project had a highly ambitious goal: to move the lab into the most extreme natural environment to study, in real time, how the human body reacts to severe environmental hypoxia, such as that found in the Himalayas above 5,000 meters of altitude. Hypoxia—a decrease in oxygen availability in body tissues—is a condition that can occur not only at high altitudes, but also in various respiratory and cardiovascular diseases. Understanding how the body adapts to it can provide valuable insights for medicine.
The documentary follows the expedition of mountaineer Ferran Latorre along the southern face of Everest in Nepal, and showcases the scientific logistics involved in such a hostile environment. Biological samples were collected from 52 participants—15 trekkers (individuals hiking to base camp without summiting), 15 elite climbers, and 22 Sherpas—at three different altitude points: at sea level (Barcelona), at 5,400 meters (Everest base camp, after the acclimatization trek), and beyond 8,000 meters, in the so-called “death zone,” where only Sherpas and elite climbers were able to reach. In addition to blood samples, physiological data such as oxygen saturation, heart rate, and respiratory response were recorded, allowing for in-depth analysis of adaptation mechanisms to extreme environments.
The study also aimed to compare adaptation among individuals with different levels of training and acclimatization: from occasional trekkers, to professional climbers, to Sherpas—an indigenous Himalayan population with a genetically inherited ability to adapt to high altitudes that makes them unique in the world. This comparison helps identify differences between adaptation gained through training and adaptation passed down genetically over generations.
The documentary offers a human and intimate look at the challenges of conducting science in extreme conditions, and highlights the collaborative effort between scientists, athletes, and the local population. It also reflects on the limits of the human body and how far we can adapt to seemingly impossible environmental conditions.
All proceeds from the documentary screening will go entirely to thrombosis research conducted by IR Sant Pau, through the Activa’TT Foundation for Health, thereby helping to advance knowledge and treatment of this vascular disease.
Physicians from the Intensive Care Medicine Department at Hospital Sant Pau, members of the Sant Pau Research Institute (IR Sant Pau), have participated in the international PROMIZING study. This is one of the most ambitious clinical trials to date aimed at optimizing the discontinuation of mechanical ventilation in patients with severe respiratory failure. Recently published in The New England Journal of Medicine, the study compares proportional-assist ventilation (PAV+) with pressure-support ventilation (PSV), with the goal of determining whether the former method could facilitate faster and less complicated weaning from the ventilator.
Sant Pau’s participation in the trial was significant thanks to the contribution of a team of intensivists with a strong track record in clinical research. The trial was designed and directly led by Dr. Jordi Mancebo, a leading figure in the field of mechanical ventilation and one of the driving forces behind the study from the beginning. Furthermore, by Dr. Juan Carlos Suárez, a close collaborator and also a physician in the Intensive Care Department. Sadly, both passed away before the final publication of the study and were honored by their colleagues with a special dedication at the end of the article. Also listed as coauthors of the paper are Dr. Indalecio Morán and Dr. Núria Rodríguez, active members of the hospital’s care and research team.
PROMIZING (short for Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation) was a prospective, multicenter, randomized study conducted across 23 hospitals in 7 countries (Canada, France, Italy, Greece, Argentina, Saudi Arabia, and Spain). The study enrolled 722 patients admitted after an episode of severe acute respiratory failure, of whom 573 were randomized. All participants were adults who had been under invasive mechanical ventilation for at least 24 hours and had failed an initial spontaneous breathing trial. They were randomized to receive spontaneous mechanical ventilation in either PAV+ or PSV mode. The primary endpoint was the time to successful liberation from the ventilator, defined as definitive discontinuation of ventilation without the need for reintubation for at least seven days.
Using the method proposed in the study to compare both modes during the weaning phase, the authors found no significant differences between PAV+ and PSV regarding the time to successful ventilator liberation. Specifically, the average time to permanent disconnection was nearly identical in the PAV+ group (7.3 days) compared to the PSV group (6.8 days), with the small difference not being statistically significant. The probability of successful liberation at 28 days was also very similar between the two groups (83.3% with PAV+ and 85.2% with PSV). Likewise, the average number of ventilator-free days during this period was 20.4 for PAV+ and 21.3 for PSV.
Regarding 90-day mortality, the results showed a rate of 29.6% in the PAV+ group and 26.6% in the PSV group, with no statistically relevant differences.
In addition to findings on ventilation duration and mortality, the study also explored factors relevant to quality of care and patient safety, such as the incidence of delirium, the cumulative use of sedatives and opioids, tolerance to the assigned ventilatory mode, and complications associated with the weaning process.
The incidence of delirium was similar between the two groups, suggesting that the ventilatory mode alone is not a determining factor in patients’ acute cognitive state. However, the study did note that patients in the PAV+ group tended to require lower cumulative doses of sedatives during the early observation period, which could suggest better synchrony between the patient and the ventilator. Despite this trend, the difference was not statistically significant. Opioid use was also tracked and compared, with no substantial differences between groups.
On the other hand, patients in the PAV+ group were switched to controlled ventilation modes more frequently than those in the PSV group. According to the authors, this may reflect both the clinical management complexity and a lower level of familiarity among staff with this strategy. Specifically regarding tolerance to the assigned mode, most patients were able to complete the intervention period in their assigned mode. However, there was a slight increase in mode changes within the PAV+ group, often due to clinical decisions related to respiratory stability or patient adaptation to the ventilator.
There were also no differences between groups in terms of complications related to the weaning process or the ventilatory mode itself, reaffirming the safety of PAV+ use in centers experienced in mechanical ventilation. While the study did not show statistically significant differences between PAV+ and PSV, it provides valuable information for better understanding the practical implications and clinical acceptability of proportional-assist ventilation.
According to Dr. Indalecio Morán, “PROMIZING provides very robust knowledge to guide decision-making during mechanical ventilation withdrawal and to further study spontaneous ventilation modes during the weaning phases, while validating the safety of proportional ventilation in centers with excellence in mechanical ventilation management.” For her part, Dr. Núria Rodríguez noted, “This study shows us that what can truly make a difference is an individualized weaning strategy applied with rigor. The ventilatory mode is a tool, but the key is how we use it within a coherent, patient-centered clinical framework.”
Bosma KJ, Burns KEA, Martin CM, Skrobik Y, Mancebo Cortés J, Mulligan S, Lafreniere-Roula M, Thorpe KE, Suárez Montero JC, Morán Chorro I, Rodríguez-Farré N, Butler R, Bentall T, Beduneau G, Enguerrand P, Santos M, Piraino T, Spadaro S, Montanaro F, Basmaji J, Campbell E, Mercat A, Beloncle FM, Carteaux G, Maraffi T, Charbonney E, Lecronier M, Dres M, Arabi YM, Amaral ACK, Marinoff N, Adhikari NKJ, Geagea A, Shin P, Vaporidi K, Kondili E, Shahin J, Campisi J, Rodriguez PO, Setten M, Goligher EC, Ferguson ND, Fanelli V, Ferreyra G, Lellouche F, Sibley S, Brochard L, PROMIZING Study Investigators, the Canadian Critical Care Trials Group, and the REVA Network. Proportional-assist ventilation for minimizing the duration of mechanical ventilation. N Engl J Med. 2025. https://doi.org/10.1056/NEJMoa2505708
A recent international multicenter study published in JAMA Otolaryngology–Head & Neck Surgery has shown that adding chemotherapy to adjuvant radiotherapy after surgery improves survival outcomes in patients with oral cavity squamous cell carcinoma. This is when there is major extranodal extension (ENE) of the disease. In contrast, in patients with minor ENE, chemotherapy does not appear to significantly improve clinical outcomes, which could prompt a reconsideration of current therapeutic recommendations.
The study, led by the Princess Margaret Cancer Centre in Toronto, included 755 patients treated between 2005 and 2018 at leading centers in Canada, the United States, and Australia. Among the authors is Dr. Cristina Valero, a researcher at the Sant Pau Research Institute (IR Sant Pau) and Memorial Sloan Kettering Cancer Center in New York, who was the only contributor affiliated with a Spanish institution.
Extranodal extension (ENE) is a pathological feature indicating that the tumor has spread to lymph nodes and breached their capsule, infiltrating surrounding tissues. This extension can be classified as minor (≤2 mm) or major (>2 mm), and its presence is generally associated with a poorer prognosis, including higher risk of recurrence and reduced survival.
ENE has long been considered a high-risk criterion justifying the use of concurrent chemotherapy with adjuvant radiotherapy following surgery. However, the findings of this new study challenge the need to add chemotherapy in all ENE cases, particularly those with minor extension.
“Currently, any degree of ENE is an indication for chemotherapy in combination with adjuvant radiotherapy, regardless of the extent of extranodal spread,” explains Dr. Valero. “The results of this study suggest that this approach may not be necessary for patients with minor ENE, thus avoiding treatments that do not provide clinical benefit and may lead to significant toxicities. More studies are needed to validate our findings before clinical protocols can be reconsidered.”
The findings of this study have important translational value. In patients with major ENE, chemoradiotherapy significantly improved both disease-free survival and overall survival. However, in patients with minor ENE, these improvements were not statistically significant, even after adjusting for age, tumor stage, surgical margins, or radiotherapy.
This evidence supports the need for a more refined risk stratification approach in the treatment of advanced oral cancer, aiming to personalize therapeutic decisions and reduce exposure to unnecessary aggressive treatments.
“Collaborative research of this kind is essential for advancing personalized medicine and for generalizing findings,” adds Dr. Valero. “It allows us to critically evaluate our clinical practices and make decisions based on the best available evidence.”
Leadership and Excellence in International Research
The study involved a large multidisciplinary team of oncologists, pathologists, surgeons, epidemiologists, and biostatisticians from top-tier institutions, including Memorial Sloan Kettering Cancer Center (U.S.), University Health Network in Toronto (Canada), Chris O’Brien Lifehouse (Australia), and the Medical University of South Carolina (U.S.). Dr. Valero is among the co-authors who contributed to data acquisition, analysis, and interpretation.
Her involvement highlights IR Sant Pau’s commitment to high-quality international clinical research and its active role in studies that have the potential to change clinical practice for the benefit of patients.
Manojlovic-Kolarski M, Su S, Weinreb I, Calvisi R, Perez-Ordonez B, Smith S, Patel S, Valero C, Xu B, Ghossein R, Katabi N, Clark J, Low T-HH, Gupta R, Graboyes E, Davies J, Richardson M, Goldstein D, Huang SH, O’Sullivan B, Xu W, Hansen A, de Almeida JR. Adjuvant chemoradiotherapy for oral cavity SCC with minor and major extranodal extension. JAMA Otolaryngol Head Neck Surg 2025. https://doi.org/10.1001/jamaoto.2025.1721.
The Sant Pau Research Institute (IR Sant Pau) held its annual Innovation Day 2025 this Tuesday, a flagship event that showcases the talent, creativity, and commitment of the center’s professionals to health innovation. During the event, and as part of the second edition of the INNOPAU program, this year’s winners were announced.
The project CUMADE received the first prize and will be awarded €50,000 to continue its development. The second prize, endowed with €15,000, went to project CHYMERA. Both awards were made possible through the support of the Private Foundation of the Hospital de la Santa Creu i Sant Pau. Projects CUMADE and CHYMERA also received special mentions as the most disruptive initiatives, with €8,000 each in funding provided by the ITEMAS platform of the Carlos III Health Institute (ISCIII). Finally, project RADAR was selected by Padcelona for the development of a Minimum Viable Product (MVP) in Digital Health.
During the event, the six finalist projects were presented, selected for their capacity to innovate from clinical knowledge and practice. All of them address real challenges identified within the hospital and propose concrete, applicable solutions with the potential to significantly impact patient quality of life and the efficiency of the healthcare system.
The projects were developed throughout the INNOPAU program, an incubator driven by IR Sant Pau that supports teams in transforming innovative care ideas into viable projects. During the program, participants take part in various training modules and receive specialized guidance in key areas such as intellectual property management, fundraising, healthcare regulations, business modeling, and strategic project development.
The culmination of the program is Innovation Day, held on June 17, where teams present their progress to the broader innovation ecosystem. The event also serves to connect professionals with strategic players such as representatives from the pharmaceutical industry, investment funds, technology centers, and other key stakeholders in the health sector.
The day also featured a roundtable discussion on “New Technologies and Transformation in Health,” with participation from professionals across clinical, research, tech, and business domains, as well as dedicated networking spaces to foster collaboration among ecosystem players.
With strong support from the Foundation and IR Sant Pau, the institution is positioning innovation as a strategic pillar for transforming the healthcare system. Beyond research, innovation is a key tool for anticipating emerging social challenges, adopting new technologies, and improving the quality of care in tangible ways.
For Sant Pau, innovation means listening to professionals, identifying opportunities from clinical practice, and providing the support and tools to help their ideas grow. It means investing in a more efficient, personalized, and sustainable healthcare model. Ultimately, it means transforming knowledge into impact.
With events like Innovation Day, Sant Pau reaffirms its leadership as a pioneering institution in translational research and health innovation, positioning itself as a hub of excellence in the development of solutions that put people at the center.
Fetuses more exposed to certain air pollutants show changes in the size of specific brain structures, particularly during the second and third trimesters of pregnancy. This is the main finding of a new study led by the Barcelona Institute for Global Health (ISGlobal), a center supported by the “la Caixa” Foundation, in collaboration with the BCNatal center (Hospital Sant Joan de Déu, Hospital Clínic, and University of Barcelona) and the Hospital de Sant Pau. It is the first study to specifically examine the association of air pollution on fetal brain development during pregnancy.
The study, published in The Lancet Planetary Health, analyzed data collected between 2018 and 2021 from 754 mother-fetus pairs participating in the BiSC (Barcelona Life Study Cohort) project in Barcelona. This study aimed to understand the association of air pollution on child health and brain development, and is considered one of the most comprehensive studies in this field.
During the third trimester of pregnancy, participants underwent transvaginal neurosonography, a specialized ultrasound that allows the analysis of fetal brain shape and structures. Exposure to nitrogen dioxide (NO₂), particulate matter (PM2.5), and black carbon was estimated with hybrid models that combine data from real measurements with advanced statistical methods. The research considered three “microenvironments”: the participants’ homes, workplaces, and commuting routes. Data on activity patterns were collected via a geolocation app installed on the participants’ mobile phones.
The research team observed that prenatal exposure to NO₂, PM2.5, and black carbon in all aforementioned microenvironments combined was associated with an increase in the volume of various brain cavities that contain cerebrospinal fluid. Specifically, direct associations were identified between exposure to these pollutants and increased volume of the lateral ventricles, located in each brain hemisphere. There was also an enlargement of the cisterna magna, a cavity located in the lower part of the brain. An increase in the width of the cerebellar vermis —the central part of the cerebellum, essential for balance and motor coordination— was also detected.
The study results also showed an association between higher exposure to black carbon and a reduction in the depth of the lateral sulcus (also known as the Sylvian fissure), a deep groove that runs through the brain, which might suggest less maturation of the brain.
The associations between exposure to air pollution and changes in the morphology of these brain structures were stronger during the second and third trimesters of pregnancy. “During mid to late gestation, the fetal brain enters a key phase of its development, making it particularly vulnerable to external factors such as pollution,” explains Payam Dadvand, ISGlobal researcher and a senior author of the study.
“As clinicians, we are now seeing compelling evidence that even in pregnancies that appear healthy by all conventional measures, factors such as air pollution can subtly affect fetal brain development. These findings underline the importance of increased awareness and education, both within the health community and across society,” say Elisa Llurba and Lola Gómez-Roig, clinicians at the Hospital de Sant Pau and BCNatal-Hospital Sant Joan de Déu, respectively, and co-authors of the study.
The observed effects do not imply that the children participating in the BiSC project have pathological brain alterations. In fact, all measurements of the participants’ brain structures are within the range considered normal. “The point is that these differences, although small at the individual level, are indeed relevant from a population perspective, as they inform us about how pollution impacts the fetal brain and its vulnerability to environmental exposures,” says Laura Gómez-Herrera, ISGlobal researcher and co-lead author of the study.
The research team emphasizes the need for further studies to confirm these findings and track their potential consequences over time. “At this stage, we can only report having observed differences in the brains of fetuses with higher exposure to pollution compared to those with lower exposure. Additional research is needed to determine whether these effects are reversible after birth or if they persist, and whether they have any implications for neurodevelopmental outcomes in later stages,” emphasizes Jordi Sunyer, a senior author of the study.
Despite the uncertainties that remain, this study could have significant implications for public health policy. “Our findings strengthen the evidence supporting the need to reduce pregnant women’s exposure to air pollution, particularly in urban settings,” says Yu Zhao, ISGlobal researcher and co-lead author of the study.
Laura Gómez-Herrera, Yu Zhao, Ioar Rivas, Elisenda Eixarch, Carla Domínguez-Gallardo, Toni Galmes, Marta Muniesa, Maria Julia Zanini, Alan Domínguez, Marta Cirach, Mark Nieuwenhuijsen, Xavier Basagaña, Xavier Querol, Maria Foraster, Mariona Bustamante, Jesus Pujol, Mireia Gascon, Elisa Llurba, María Dolores Gómez-Roig, Payam Dadvand, Jordi Sunyer. Air pollution and foetal brain morphological development: a prospective study. The Lancet Planetary Health, Vol 9, June 2025. https://doi.org/10.1016/S2542-5196(25)00093-2
A study led by the Sant Pau Research Institute (IR Sant Pau) has succeeded in describing, for the first time in detail, the structural evolution of the medial temporal lobe (MTL) regions across the clinical stages of Alzheimer’s disease in people with Down syndrome. The results, published in the journal Brain, reveal that volume and cortical thickness loss in these regions can begin 13 to 15 years before the onset of symptoms, marking a significant advance in early diagnosis and the design of preventive clinical trials.
The study is based on a large cohort of 259 adults with Down syndrome and 138 euploid controls (individuals without Down syndrome), all of whom underwent high-resolution magnetic resonance imaging (MRI), cerebrospinal fluid biomarker analysis, and detailed clinical and neuropsychological characterization. It is the first study to systematically map the trajectory of MTL subregions—including the anterior and posterior hippocampus, entorhinal cortex, parahippocampus, and Brodmann areas 35 and 36—in relation to cognitive decline and biological markers of the disease.
“We chose to focus on the medial temporal lobe because it is one of the first regions affected by the accumulation of tau neurofibrillary tangles, one of the two key pathologies of Alzheimer’s disease,” explains Dr. Alexandre Bejanin, from the Neurobiology of Dementias group at IR Sant Pau and coordinator of the study. “These regions are also involved in functions such as episodic memory and spatial orientation, which are altered early in the disease.”
People with Down syndrome have a unique genetic predisposition: overexpression of the APP gene due to trisomy of chromosome 21 leads to overproduction of beta-amyloid (Aβ) protein, making them a natural genetic model of Alzheimer’s. It is estimated that over 90% of this population will develop the disease during their lifetime.
This genetic singularity allowed the researchers to use participants’ age as an estimate of the time to symptom onset (Estimated Years to Onset, EYO), providing an objective temporal framework to study brain changes before dementia. According to their calculations, the inflection point in structural degeneration occurs between 15 and 9 years before the average age of symptom onset.
“This approach allowed us to observe that the entorhinal cortex and posterior hippocampus are the first regions to show structural loss, even before symptoms appear,” notes Alejandra Morcillo-Nieto, also a researcher in the Neurobiology of Dementias group and first co-author of the study. “Moreover, some regions like the parahippocampus initially show cortical thickening, possibly reflecting inflammatory or compensatory processes, before entering a phase of atrophy—although this is a hypothesis that should be confirmed in future studies.”
The work is part of the Down-Alzheimer Barcelona Neuroimaging Initiative (DABNI) and used MRI images acquired at two hospitals in Barcelona: Hospital de Sant Pau and Hospital Clínic. For automated segmentation of MTL subregions, the study used ASHS-T1 software, previously validated in Alzheimer’s populations. This system enables segmentation not only of the anterior and posterior hippocampus, but also key cortical structures such as the entorhinal cortex, Brodmann areas 35 and 36 (including the transentorhinal cortex), and the parahippocampus. In addition, a complementary algorithm (CRASHS) was used to model cortical thickness with greater surface precision.
“We didn’t use novel images per se, but advanced analytical techniques applied to standard images typically obtained in clinical practice,” emphasizes Dr. Alexandre Bejanin. “What we did was apply a specific segmentation software that allows very precise quantification of these medial temporal lobe regions—something that had not been done before in the context of Down syndrome.”
The researchers normalized volumes and thicknesses using scores adjusted for age, sex, and intracranial volume, and harmonized data from different scanners using the ComBat method. Image quality was verified through automatic analysis (CAT12) and visual evaluation by experts.
In parallel, cerebrospinal fluid samples from 243 participants with Down syndrome were analyzed to determine levels of Aβ42/40, phosphorylated tau at position 181 (pTau181), and neurofilament light chain (NfL). The researchers correlated these biomarkers with the structural measures obtained through imaging.
The analysis revealed an orderly anatomical progression of atrophy, consistent with the classical pattern of tau propagation. The entorhinal cortex was the first region to show a cortical thickness inflection point (EYO = -15.7 years), followed by the posterior hippocampus (EYO = -13.5), Brodmann 35 (-13), the anterior hippocampus (-11.5), the parahippocampus (-9.8), and Brodmann 36 (-9).
Posterior hippocampal volume showed particularly strong correlations with all cerebrospinal fluid biomarkers: positive with Aβ42/40 and negative with pTau181 and NfL. Among all structures studied, this region was also the most effective in distinguishing asymptomatic individuals from those with clinical symptoms, with an accuracy of 86.3%. When included in a multivariate model with age, pTau181, and parahippocampal thickness, diagnostic accuracy rose to 96.4%.
“Our data indicate that structural MRI not only enables early detection of changes, but can effectively complement fluid biomarkers in predicting clinical status,” says Benjamin Buehner, first co-author of the study. “This is especially relevant in Down syndrome, where cognitive testing may be limited by baseline intellectual disability.”
This study provides, for the first time, a detailed map of how the medial temporal lobe is affected by Alzheimer’s disease in Down syndrome and places the onset of structural changes more than a decade before clinical symptoms appear. This information is critical for designing future therapeutic trials aimed at intervening during preclinical stages to prevent neurodegeneration.
The authors emphasize that while the cross-sectional design limits the establishment of a causal temporal sequence, the genetic homogeneity of Down syndrome and the reliability of the EYO model provide exceptional robustness to the findings.
The study involved collaboration from more than twenty national and international centers and institutions, including Hospital Clínic de Barcelona, the University of Barcelona, the Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), the University of Pennsylvania, and the French INSERM.
Buehner BJ, Morcillo-Nieto AO, Zsadanyi SE, Rozalem Aranha M, Arriola-Infante JE, Vaqué-Alcázar L, Arranz J, Rodríguez-Baz Í, Maure Blesa L, Videla L, Barroeta I, Del Hoyo Soriano L, Benejam B, Fernández S, Sanjuan Hernandez A, Bargalló N, González-Ortiz S, Giménez S, de Flores R, Yushkevich PA, Alcolea D, Belbin O, Lleó A, Carmona-Iragui M, Fortea J, Bejanin A. Medial Temporal Lobe Atrophy in Down Syndrome Along the Alzheimer’s Disease Continuum. Brain. 2025. https://doi.org/10.1093/brain/awaf133
A scientific review by Dr. Anna Aulinas, coordinator of the Functional Unit for Pituitary Diseases at Hospital de Sant Pau and researcher with the Pituitary Diseases group at the Sant Pau Research Institute (IR Sant Pau), together with Dr. Elizabeth Lawson, professor at Harvard Medical School, offers a new perspective on hypopituitarism. The review focuses on an aspect that has so far received little attention: the potential oxytocin deficiency in these patients.
The review, titled “The Oxytocin System and Implications for Oxytocin Deficiency in Hypothalamic-Pituitary Disease”, was published in Endocrine Reviews, one of the most prestigious international journals in the field of endocrinology. In addition to being pioneering in its subject, the review was highlighted by the journal itself as the “Featured Article of the Week,” a distinction reserved for the most relevant and potentially impactful contributions within the scientific community.
Oxytocin is a hormone produced in the hypothalamus and secreted by the posterior pituitary gland, traditionally known for its role in childbirth and lactation. However, recent studies have proved that it also plays a central role in regulating food intake, body composition, bone health, cardiovascular activity, emotions, and social bonding.
The review compiles, for the first time in a comprehensive way, data pointing to a potential oxytocin deficiency in individuals with hypothalamic and/or pituitary damage—caused by tumors, surgery, radiotherapy, or inflammatory diseases. This could contribute to some persistent symptoms these patients experience, despite conventional hormone replacement therapy.
The concept of oxytocin deficiency in hypopituitarism is not yet fully recognized but is emerging as a clinical entity with its own distinct features. Through analysis of existing literature, the review identifies evidence linking this deficiency to poorer quality of life, psychosocial disturbances, a tendency toward obesity, and bone fragility, among other issues.
Although some patients have begun to receive oxytocin as an experimental therapy in highly controlled clinical settings, the authors emphasize that further research is needed before it can be recommended for widespread use. In particular, there is an urgent need to develop specific diagnostic tests to detect oxytocin deficiency, as well as to assess the safety and efficacy of treatments in well-designed clinical trials.
The review concludes that incorporating oxytocin into the set of hormones considered in the management of hypopituitarism could represent a paradigm shift in patient care. The proposal is clear: when symptoms persist despite standard hormone replacement therapy, it may be necessary to look beyond and also consider the function of the neurohypophysis.
According to Dr. Aulinas, “Oxytocin deficiency could explain part of the invisible suffering experienced by these patients. Recognizing it opens the door to a new research path and, in the future, to a more comprehensive and humane approach to their medical care.” This work marks a turning point in the understanding of “non-classical” hormonal deficits associated with hypopituitarism and invites a reevaluation of how these complex disorders are diagnosed and treated.
Aulinas A, Lawson EA. The oxytocin system and implications for oxytocin deficiency in hypothalamic-pituitary disease. Endocr Rev 2025. https://doi.org/10.1210/endrev/bnaf008
This past weekend, the Born Centre for Culture and Memory was the venue for the 18th Science Festival, a large gathering for all audiences to engage with science and knowledge. The Sant Pau Research Institute was one of the participating entities, offering three workshops that captivated numerous families.
On Saturday afternoon, visitors were able to enjoy a dynamic and educational activity to find out what the brain, heart and blood look like and how they work through life-size 3D models and interactive posters. Children had to connect the parts of the organs and identify their functions in order to better understand these three fundamental pillars of the human body. The activity, led by Jorge Clusa, outreach coordinator at the Sant Pau Research Institute, was very popular among children.
On Sunday morning, Marta Cano and Romina Miranda, researchers from the mental health group at the Sant Pau Research Institute, also invited the youngsters to explore the structures of the brain and its functions by assembling a 3D paper puzzle of this organ. The attendees also had a lot of fun participating in an original brain bingo game in which each move revealed a curiosity about the human brain.
To close the Festival, on Sunday afternoon, Dr. Robert Belvís, Dr. Noemí Morollón, Dr. Juan Aibar, professionals of the Headache and Neuralgia Unit of the Hospital de Sant Pau, with the support of Iago Andreu, a clinical engineer from the hospital’s Dimension Lab, explored the complexity of neurosurgery. The attendees who joined us discovered how technology helps to plan operations with more precision and safety, and were able to live an immersive experience by trying on virtual reality glasses.
The Sant Pau Research Institute thanks everyone who made this success possible, both the organizers and the participants, who contributed to making this Science Festival a memorable edition.
Researchers at the Sant Pau Research Institute (IR Sant Pau) have published a study in Epilepsy & Behavior documenting a high frequency of neuropsychiatric symptoms in adults with tuberous sclerosis complex (TSC), a rare, multisystem genetic disorder with highly variable clinical expression. While the condition primarily affects the nervous system, it can also impact other organs such as the kidneys, heart, skin, and lungs.
The study provides an in-depth analysis of the cognitive and emotional profiles of 28 adult patients with confirmed TSC and no severe intellectual disability, highlighting an unmet clinical need. Although most participants exhibited significant emotional, cognitive, or behavioral alterations, only a minority had received specialized mental health care.
The most common symptoms included mood swings (reported in 80% of cases), excessive shyness (70%), and sleep and attention disorders (60%). Additionally, half of the patients reported low self-esteem. Despite this symptom burden, only four individuals—14% of the sample—had received psychiatric or psychological care. “Our patients have many problems in these neuropsychiatric domains, but they don’t seek help for them. And unfortunately, we don’t have the resources to monitor them more closely either because there are so many gaps in mental health care that this ends up being an unmet need,” explains Dr. Alba Sierra, researcher in the Epilepsy Group at IR Sant Pau, neurologist at Hospital Sant Pau, and corresponding author of the study.
TSC is caused by mutations in the TSC1 or TSC2 genes, which lead to abnormal activation of the mTOR pathway and the formation of hamartomas—benign masses made up of normal but disorganized cells. These can develop in different organs. When they affect the central nervous system, they may cause epilepsy, intellectual disability, and neuropsychiatric disorders.
While the impact of epilepsy in TSC has been widely studied, emotional and cognitive symptoms—collectively known as TAND (TSC-Associated Neuropsychiatric Disorders)—have received less attention, especially in adults. “Disease severity is highly variable: some people have mild symptoms and are diagnosed by chance in adulthood, while others experience severe epilepsy, intellectual disability, and multi-organ involvement. That’s why we included a wide age range, from 18 to 65 years. This disease can manifest at any point in life,” notes Dr. Sierra.
The study combined a clinical evaluation with an extensive neuropsychological battery. All patients underwent standardized intelligence testing (WAIS-IV) and cognitive screening (MoCA), along with specific scales to assess anxiety, depression, quality of life, and subjective health perception. The researchers also used the TAND-L checklist to detect symptoms across different domains, from behavior to academic skills. Clinically, the study considered epilepsy history, infantile spasms, findings from MRI and EEG, and genetic profile when available.
Results showed a clear link between epilepsy severity and duration and poorer cognitive performance. Significant associations were also observed with other clinical factors. For example, patients with a history of infantile spasms or mutations in the TSC2 gene had more impaired cognitive profiles and greater emotional and academic difficulties. Additionally, the presence of hamartomas in the frontal and parietal lobes was associated with behavioral, learning, and other specific cognitive impairments.
“We found that epilepsy isn’t the only factor driving these symptoms. Genetics and the location of brain hamartomas also play a role. The impact is multifactorial,” emphasizes Dr. Sierra.
Beyond the clinical findings, the study encourages reflection on the current care model for TSC patients. Traditionally, neurology appointments have focused on controlling epileptic seizures, without systematically addressing neuropsychiatric symptoms. “We tend to focus heavily on purely neurological symptoms, and perhaps haven’t explored these other issues—ones that directly affect quality of life—as much. This study draws attention to the need to look beyond the seizures,” adds Dr. Sierra.
In line with this more holistic perspective, the team underscores the need for multidisciplinary care. TSC doesn’t just impact the brain—it can lead to serious complications in vital organs, including kidney failure, cardiac issues, or lung disease. “Follow-up has to be comprehensive. A systemically involved disease like this requires joint work among specialists. It’s the only way to ensure high-quality care,” concludes Dr. Sierra.
The study opens the door to future research aimed at tracking the progression of these symptoms over time. Longitudinal studies could provide more in-depth insight into how neuropsychiatric alterations evolve with age and help develop more effective, personalized intervention strategies.
Toscano-Prat C, García-Sánchez C, Ros-Castelló V, Barguilla-Arribas A, Saladich IG, Rodríguez-Clifford K, Torra-Balcells R, Boronat S, Sierra-Marcos A. Cognitive and neuro-psychiatric profile in adult patients with epilepsy secondary to Tuberous Sclerosis Complex. Epilepsy Behav. 2025;166:110380. https://doi.org/10.1016/j.yebeh.2025.110380
The Sant Pau Research Institute and The Hospital de Sant Pau, who have once again participated together in the BCN Salut Games— the solidarity olympics of the health and research sector— have been crowned champions of this year’s edition, which gathered a total of 5,435 participants from 51 different centers.
More than 400 professionals from Hospital de Sant Pau took part in this sports event, where Sant Pau finished in first place, followed by Hospital Clínic and Sant Joan de Déu, in second and third place respectively.
The aim of this solidarity olympics is to encourage physical activity and healthy habits in the healthcare field, while also fostering cohesion, togetherness, and motivation within institutions and among participating organizations.
In addition, Sant Pau raised a total of €2,597 this year in solidarity donations from participating professionals. These funds will go to the Kàlida Foundation, a support center for people affected by cancer, offering care and guidance to individuals going through or having gone through cancer, as well as to their close circle of family, caregivers, and friends.
Soon, the BCN Salut Games organization will present Sant Pau’s management team with the trophy recognizing them as champions of the 2025 edition. The Kàlida Foundation will also receive the solidarity check with the funds raised, handed over by Sant Pau’s management.
An international study involving researchers from the Sant Pau Research Institute (IR Sant Pau) has demonstrated that women who are carriers of genetic mutations causing frontotemporal dementia (FTD) show a greater capacity to compensate for brain damage than men, at least in the early stages of the disease. The discovery suggests that sex is a key biological factor in the evolution of this hereditary form of dementia and opens the door to more gender-sensitive precision medicine.
The article was published in the journal Alzheimer’s & Dementia, the official publication of the Alzheimer’s Association, and is part of a series of three scientific papers on sex differences in the clinical and biological manifestations of genetic FTD. The research is part of the North American ALLFTD consortium and included collaboration from leading neuroscience and neuroimaging centers in San Francisco (UCSF) and Toronto (University of Toronto).
“What we observed is that, for the same degree of brain damage, women with FTD performed better than men in executive function and social cognition tests. This indicates they have greater cognitive and behavioral reserve,” explains Dr. Jesús García Castro, neurologist and researcher in the team led by Dr. Ignacio Illán-Gala at the Sant Pau Memory Unit and Sant Pau Research Institute (IR Sant Pau), and first author of the study.
FTD is a neurodegenerative disease still not well known to the general public, but which has gained recent attention following the diagnosis of actor Bruce Willis. Unlike Alzheimer’s, which primarily affects memory, FTD presents as personality changes, social behavior disturbances, and language or speech difficulties. It typically begins at an earlier age—between 45 and 65 years—and may lead to a progressive loss of executive functions such as judgment, empathy, or impulse control. For this reason, the study of behavioral changes is key to early detection.
Frontotemporal dementia is a rare neurodegenerative disease that usually appears between 45 and 65 years of age and severely affects personality, social behavior, and language. In about 30% of cases, it is caused by mutations in genes such as C9orf72, GRN, or MAPT, which lead to abnormal protein accumulation and progressive loss of brain tissue, especially in the frontal and temporal lobes.
Thanks to the systematic follow-up of the ALLFTD consortium, the researchers were able to analyze over 670 brain MRIs and clinical data from 394 carriers of pathogenic mutations and 279 non-carrier relatives over several years. They studied both asymptomatic individuals (presymptomatic phase) and those already diagnosed with mild cognitive impairment or dementia.
“This longitudinal design allowed us to observe how the disease evolves even before the first symptoms appear. And this is where we saw the female advantage: women showed better cognitive performance despite having greater degrees of frontal brain atrophy,” highlights Dr. García Castro.
The team used an innovative methodology known as the residual approach, which quantifies cognitive reserve: the discrepancy between a person’s actual performance and what would be expected based on their degree of neurodegeneration. This approach revealed that women, especially those carrying the C9orf72 expansion, maintained better executive and social functioning despite cortical thinning.
Statistical models also showed that this female advantage is not permanent. As the disease progresses and brain damage extends, compensatory capacity decreases, and deterioration trajectories equalize between men and women in advanced stages.
“It’s as if the female brain has more capacity to resist the disease for a time, but once a certain threshold is reached, the decline accelerates,” summarizes Dr. García Castro. “This matches what has been observed in Alzheimer’s: greater initial resilience in women, followed by faster deterioration when symptoms emerge.”
Indeed, the study observed a trend towards later symptom onset in women (up to 6.5 years on average), although this result did not reach statistical significance due to sample size.
The work has important implications for the design of clinical trials and progression prediction models in hereditary dementias. Until now, most studies had not considered sex as a differentiating variable, which may have obscured important patterns in treatment response or clinical evolution.
“Our findings reinforce the need to integrate sex and gender perspectives into precision medicine, especially in diseases like FTD, where variability is enormous even within the same genetic mutation,” notes Dr. García Castro.
The Sant Pau group, in collaboration with international partners of the ALLFTD consortium, continues to analyze other modulators of progression in genetic FTD, including immunological, hormonal, and structural markers.
The research was conducted as part of the North American ALLFTD (Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects) consortium, funded by the U.S. National Institute on Aging (NIA) and the U.S. National Institute of Neurological Disorders and Stroke (NINDS).
In addition, the work was supported by the Carlos III Health Institute through multiple projects (PI20/01473, PI23/01786, PI18/00435, PI20/01330, PI21/01395, PI21/00791, CP20/00038, PI22/00307, INT21/00073, CM21/00243 and CM23/00176), co-financed by the European Union. It also received funding from the Biomedical Research Network Centre on Neurodegenerative Diseases (CIBERNED) and the European Regional Development Fund (ERDF) under the slogan “A way to make Europe”.
At the international level, the study was supported by the Alzheimer’s Association (grants AARG-22-923680, AARF-22-924456 and GBHI ALZ UK-21-720973), the Alzheimer Society (UK), and the Global Brain Health Institute (GBHI). It also received support from the Tatiana Pérez de Guzmán el Bueno Foundation, and from the Horizon 2020 programme of the European Union.
In Catalonia, the research was promoted by the Department of Health of the Generalitat through the Strategic Plan for Health Research and Innovation (PERIS), and was supported by clinical talent contracts such as Juan Rodés and Río Hortega.
This institutional support has made it possible to carry out a large-scale multicenter study with participation from 18 centers in the United States and Canada, and consolidates Sant Pau’s leadership in advancing precision medicine in the field of neurodegenerative diseases.
Garcia Castro J, Rubio-Guerra S, Casaletto KB, Selma González J, Memel M, Vaqué-Alcázar L, Morcillo-Nieto A, Arriola-Infante J, Dols-Icardo O, Bejanin A, Belbin O, Fortea J, Alcolea D, Carmona-Iragui M, Barroeta I, Santos-Santos M, Sánchez Saudinós MB, Sala Matavera I, Heuer HW, Forsberg LK, Kantarci K, Staffaroni AM, Tartaglia C, Rankin KP, Boeve B, Boxer A, Rosen HJ, Lleó A, Illán-Gala I, ALLFTD Consortium. Sex differences in the executive and behavioral reserve of autosomal dominant frontotemporal dementia. Alzheimers Dement 2025;21:e70070. https://doi.org/10.1002/alz.70070
