What connection could there possibly be between thrombosis, a severe disease that causes one death every minute in Europe, and high-altitude mountains? Much more than we might imagine. At high altitudes, environmental conditions such as hypoxia and extreme physical effort can trigger physiological responses that increase the risk of blood clot formation, a situation similar to what people affected by thrombosis experience. This connection not only offers an opportunity to raise awareness about the disease but also draws parallels between the challenges of climbing mountains and the fight against a complex and often deadly condition.

In the charity book Life Flows Through Your Veins, the elite of global Himalayan climbing has joined forces with the Sant Pau Research Institute (IR Sant Pau) and the Activa’TT association to raise awareness about the importance of this disease and to collect funds for its research at IR Sant Pau. This pioneering project combines the majesty of mountaineering with the scientific challenge of combating thrombosis, a disease that causes 10 million deaths worldwide each year.

This initiative, led by Dr. José Manuel Soria, head of the Complex Disease Genomics Group at IR Sant Pau, and journalist Jordi Viader, gathers the experiences of fourteen renowned mountaineers who have conquered some of the world’s highest peaks. In the book, each recounts not only their battle against the adversities of high-altitude climbing but also how these experiences resemble the resilience needed to overcome serious illnesses like thrombosis.

The Modernist Site of Sant Pau served as the venue for the book’s presentation, where, alongside Dr. Soria and Jordi Viader, ten of the fourteen participating mountaineers were present: Núria Balagué, Javier Camacho, Rosa Fernández, Ferran Latorre, Jesús Morales, Juanito Oiarzabal, Jordi Pons, Lina Quesada, Ester Sabadell, and Carlos Soria.

Additionally, Núria Balagué, Juanito Oiarzabal, and Lina Quesada shared their personal experiences with thrombosis, a disease all three suffered from, specifically in high-altitude environments. “I had always adapted very well to high altitudes until I had my first pulmonary embolism, which took me to the hospital in Kathmandu,” explained Oiarzabal, adding that it was there that two small clots were detected. “During my first ascent of an eight-thousand-meter peak, I made many mistakes, which forced me to endure significant strain,” commented Lina Quesada. As a result of this extreme effort, she developed a hemorrhoidal crisis that caused a clot. “When I used to go to the mountains, I didn’t really know what to put in my medical kit, and thanks to this book, I’ve learned a lot about thrombosis,” added Núria Balagué.

Thrombosis and High Mountains

The link between thrombosis and extreme mountaineering is stronger than it appears. At high altitudes, oxygen pressure decreases, forcing the body to adapt. This process, while necessary for survival, can increase blood viscosity and promote clot formation.

This mirrors the situation faced by thrombosis patients, where factors like immobility or pre-existing conditions generate similar risks. Moreover, the personal and physical struggle of climbing a mountain becomes a powerful metaphor for the fight that patients and researchers face to overcome a disease like thrombosis.

Just as mountaineers need training, preparation, and proper equipment to reach the summit, doctors and researchers rely on innovative tools and resources to advance the understanding and treatment of this disease. “Each ascent is a test of physical and mental endurance. That same strength is what we need to overcome such a complex condition as thrombosis,” said Dr. Soria during the presentation.

What Is Thrombosis, and Why Is It Important to Discuss?

Venous Thromboembolic Disease (VTE), commonly known as thrombosis, occurs when a blood clot fully or partially blocks a blood vessel, hindering normal blood flow. This disease is one of the leading causes of serious events such as pulmonary embolisms, heart attacks, and strokes. Additionally, it is the primary cause of death in cancer patients.

Risk factors for thrombosis include family history, prolonged immobilization, recent surgeries, certain chronic illnesses, and sedentary lifestyles. However, this condition can often be prevented with proper knowledge and action. “The lack of information about thrombosis means that many people are unaware of their risk until it’s too late. This project aims to change that by raising awareness beyond medical circles and reaching society at large,” Dr. Soria emphasized.

The Charity Project Behind the Book

Life Flows Through Your Veins is not just a book; it is a call to action. Its goal is to raise funds for thrombosis research at IR Sant Pau, a leading institution in scientific innovation. Each copy sold will directly contribute to financing projects aimed at developing new diagnostic and treatment tools.

The book is available for purchase here.

The Sant Pau Research Institute (IR Sant Pau) has been honored with two awards for its research at the recent National Congress of the Spanish Society of Hematology and Hemotherapy (SEHH), held in Palma, reaffirming its leadership in innovative research to improve hematology treatments.

The presentation titled “Phase I/II clinical trial with academic CAR-T30 (HSP-CAR30) for the treatment of Hodgkin lymphoma or CD30+ T-cell non-Hodgkin lymphoma in relapsed or refractory cases: efficacy and safety results”, presented by Dr. Ana Caballero, a researcher from the Cellular Immunotherapy and Gene Therapy Group, was awarded as the Best oral communication in chronic lymphoproliferative syndromes. This academic study on HSP-CAR30, the only anti-CD30 CAR-T product in Europe, demonstrates high antitumor efficacy in patients with relapsed or refractory Hodgkin lymphoma and CD30+ T-cell non-Hodgkin lymphoma. The data show it is possible to achieve durable complete responses in patients with multi-refractory disease, with an adequate safety profile.

The other award went to the presentation titled “Efficacy and safety of reduced-dose cyclophosphamide post-transplantation outside the setting of haploidentical hematopoietic progenitor cell transplantation”, by Drs. Irene García Cadenas and Sara Redondo from the Hematologic Oncology and Transplantation Research Group. This work was recognized as the Best work in the Hematopoietic Progenitor Transplantation section. The study, which initially presented preliminary data from 31 patients, updated its results during the congress to include more than 50 patients who received this therapeutic platform. The research proposes reducing the dose of cyclophosphamide to decrease the drug’s associated toxicity in the context of bone marrow transplantation while maintaining its effectiveness in preventing graft-versus-host disease, one of the most severe complications of the procedure. The results have been so positive that this strategy is now routinely used for most transplanted patients at Sant Pau Hospital, paving the way to improve outcomes, not only in terms of efficacy but also in quality of life.

In addition, researchers from IR Sant Pau presented another study as an oral communication titled “Towards dose individualization of ruxolitinib in patients with corticosteroid-refractory graft-versus-host disease: development and validation of tandem mass spectrometry liquid chromatography”, which stood out for its innovative proposal to personalize treatment in patients with graft-versus-host disease unresponsive to conventional treatments. This multidisciplinary work, in collaboration with the Pharmacy and Biochemistry Departments at Sant Pau Hospital, introduces a new system to measure ruxolitinib levels, the current second-line treatment, and adjust the dose for each patient to minimize risks and improve therapeutic responses. Given the remarkable results of the pilot study, the research will continue with the launch of a multicenter study within the Spanish Group for Transplantation and Cellular Therapy (GETH-TC) in early 2025, led by the Hematologic Oncology and Transplantation Research Group at IR Sant Pau.

The Memory Unit of the Neurology Service at Hospital Sant Pau expresses great satisfaction with the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommendation of lecanemab for treating early-stage Alzheimer’s. This decision follows the reconsideration of the initial evaluation during the appeals process.

Hospital Sant Pau, together with other Spanish centers, participated in the Phase 3 study of lecanemab, a pivotal investigation that enabled this recommendation. Following the model established in the United Kingdom, the drug’s use is limited to a subgroup of patients based on safety and efficacy data. Patients on anticoagulants and those carrying two copies of the APOE4 allele are excluded from treatment.

Despite these restrictions, this recommendation represents a historic milestone in the fight against Alzheimer’s, as lecanemab is the first drug capable of slowing the disease’s progression. Furthermore, its introduction into clinical practice marks a new paradigm in treating this fatal condition, which has until now been diagnosed in its early stages only in certain specialized centers. This approval will not only facilitate access to new diagnostic techniques but also drive the development of treatments for Alzheimer’s and other neurodegenerative diseases, as seen with fibrinolysis and the creation of stroke units or advancements in managing multiple sclerosis.

“The EMA’s recommendation marks the beginning of a new care model for people with Alzheimer’s,” highlights Juan Fortea, head of the Neurobiology of Dementias research group at the Sant Pau Research Institute (IR Sant Pau) and director of the Memory Unit at Hospital Sant Pau. “This new phase will require the implementation of biomarkers, training for specialized professionals, and increased resource allocation to ensure comprehensive and innovative care that can, for the first time, change the clinical course of the disease.”

The EMA’s decision also corrects an initial stance that left Europe at risk of lagging in global Alzheimer’s research. With this resolution, the European Commission will need to determine marketing authorization for the entire European Union. Once approved, each member state must define the treatment’s pricing and implementation based on their healthcare system’s characteristics, a process that may take 1 to 2 years.

While this approval is not the end goal, it represents a crucial first step toward improving the quality of life and future of individuals affected by this disease.

According to a new study conducted on participants in the El Bus de la Salut (ILERVAS) project cohort, adherence to the Mediterranean diet could play a key role in preventing subclinical atherosclerotic disease, a condition that develops silently before leading to serious cardiovascular diseases. The research, led by investigators from CERCA centers, the Sant Pau Research Institute, and the Biomedical Research Institute of Lleida (IRBLleida), has been published in the journal *Nutrients*.

The study, which included 3,097 participants, demonstrated that a healthy Mediterranean diet, rich in nuts, vegetables, fish, and olive oil, was associated with a significant reduction in atherosclerotic plaques in the arteries. Specifically, researchers observed a 3% decrease in the number of territories affected by plaques in participants with higher adherence to the Mediterranean dietary pattern, as assessed by the MEDAS (Mediterranean Diet Adherence Screener) scale.

“We designed a healthy lifestyle index based on the Mediterranean diet and physical exercise to evaluate its relationship with the progression of atherosclerotic plaques. Although the overall score did not show an association with progression, when analyzing the components separately, we found that exercise did not offer significant protection, while adherence to the Mediterranean diet was indeed associated with less progression of atherosclerotic plaques,” explained Marina Rojo, a researcher in the Endocrinology, Diabetes, and Nutrition group at IR-Sant Pau.

“This research highlights the cardiovascular benefits of the Mediterranean diet, demonstrating that it not only helps prevent disease but also reduces the progression of atherosclerosis, one of the main risk factors for heart disease,” commented Marcelino Bermúdez, professor at the University of Lleida and researcher in the vascular and renal translational research group at IRBLleida. “These findings underscore that promoting adherence to the Mediterranean diet, along with managing traditional risk factors such as hypertension and smoking, could be an effective public health intervention to prevent atherosclerosis and reduce the burden of cardiovascular diseases on society,” added the researcher.

Although physical activity did not show a significant association with the progression of atherosclerotic disease in this study, the results suggest that the Mediterranean diet might play a more prominent role in protecting against atherosclerosis. This finding reinforces the importance of healthy eating as a fundamental part of an integrated cardiovascular prevention strategy.

The study also identified other risk factors for the future development of fatty plaques in the arteries, such as advanced age, hypertension, smoking, and dyslipidemia. Additionally, the researchers found that being female might have a protective effect against the progression of the disease.

This research was funded by the CIBER-Consortium for Research in Biomedicine in Network-(CB15/00071) of the Carlos III Health Institute, the Ministry of Science, Innovation and Universities, the Strategic Health Research and Innovation Plan (PERIS) 2021–2024 of the Generalitat of Catalonia, the State Research Agency, the European Union “NextGeneration EU,” the Agency for the Management of University and Research Grants, the Lleida Provincial Council, the European Regional Development Fund “A Way to Make Europe,” the Biomedical Research Networking Center in the area of Biomedical Engineering, Biomaterials and Nanomedicine (CIBER-BBN), and the CERCA Program/Generalitat of Catalonia.

Reference Article:
Rojo-López MI, Bermúdez-López M, Castro E, Farràs C, Torres G, Pamplona R, Lecube A, Valdivieso JM, Fernández E, Julve J, et al. *Mediterranean Diet Is a Predictor of Progression of Subclinical Atherosclerosis in a Mediterranean Population: The ILERVAS Prospective Cohort Study.* Nutrients. 2024; 16(21):3607. [https://doi.org/10.3390/nu16213607](https://doi.org/10.3390/nu16213607)

The Aut-CARE project (Autism Cognitive-Afective REmediation for adults), created by the Sant Pau Research Institute (IR Sant Pau) and the Friends Foundation, has been selected by Fundación “la Caixa” in its Connecta Call: from Research to Social Practice. The goal of this initiative is to improve the cognitive and emotional functioning of young adults on the autism spectrum and to support their social and workplace integration.

Autism is a lifelong neurodevelopmental condition. Diagnosis and interventions generally focus on childhood and adolescence, which makes it challenging—or even impossible—for individuals to meet environmental demands, such as employment and social integration, often leading to additional mental health issues in autistic adults.

According to data from Autism Europe, between 76% and 90% of adults with autism spectrum disorder (ASD) are unemployed, making them the disability group with the highest unemployment rate. Although the Autism Spain Confederation and other associations prioritize the inclusion of people with ASD in the workforce, significant employment barriers remain. There is a lack of evidence-based interventions tailored to meet the specific needs of individuals with autism, and existing programs tend to be generalist and do not fully address the cognitive and emotional characteristics of autism.

The goal of Aut-CARE is to co-design an intervention to address the inherent challenges of autism, providing strategies for accessing the job market that, in turn, will help improve participants’ emotional well-being and overall psychosocial adaptation. Led by Dr. Maria J. Portella, head of the Mental Health Research Group at IR Sant Pau, and Susanna Díaz, director of the Friends Foundation, this project aligns with the Connecta Call’s goals, conceptualizing and co-designing Aut-CARE to complement the efforts and interventions currently underway in the nonprofit sector to increase the social inclusion of these young adults and support their mental health.

The Connecta Call by Fundación “la Caixa” aims to support research projects focused on emotional well-being and mental health in Spain, carried out collaboratively between research entities and organizations within the social sector. The evaluation process of the proposals was conducted by academic and social sector experts, resulting in the selection of 12 projects from a total of 106 submissions.

Turning an innovative idea into a concrete solution is not always easy; in fact, the real challenge lies in transforming these ideas into tangible realities. For this reason, the Sant Pau Research Institute (IR Sant Pau) has been promoting the INNOPAU initiative – Sant Pau Ideas Incubator – for the past two years. Its goal is to capture innovative ideas in their early stages and define a roadmap that enables their transfer to the market and clinical practice, thereby benefiting society.

This Friday, November 8th, the second edition of INNOPAU kicked off with an event where the seven projects participating this year were presented. During the event, the program and its first work module were explained, providing an opportunity for the teams to meet each other.

The seven projects participating in this edition are:

• MARPRESSING: a medical device designed to prevent endoscope loops that form during colonoscopies, thereby reducing clinician injuries by lowering the continuous pressure needed to avoid loop formation. The team includes Jessica Marin, Ana Marin, and Oliva Ros from Hospital Sant Pau.
• CUMADE: a methodology that uses medical imaging and 3D reconstructions to reduce leaks in current cardiac prostheses, enabling the creation of customized devices for each patient. This project is led by Dabit Arzamendi and Abdel Hakim from Hospital Sant Pau, together with Oscar Camara from Pompeu Fabra University (UPF).
• AQUAFLOW: an innovative swimsuit for patients undergoing peritoneal dialysis that prevents infections at the catheter exit site and allows them to enjoy the benefits of water safely. Sandra Peña, Mireia Plans, Piedad Arias, and Esther Franquet from the Puigvert Foundation are responsible for this proposal.
• RADAR: a digital tool that enables the automatic recognition of adverse drug reactions in real-time, aimed at primary care. The team comprises Carlen Reyes, Helena Serrano, Ana Isabel Posa, Elisabet Rayó, and Jara González from EAP Sardenya.
• DAMMPIS: multimodal detection devices for abnormal movements and removal of medical equipment for ICU patients, aimed at improving patient safety and reducing potential complications. This project is led by Jaume Baldira, Ariadna Bellès, Matias Flores, Rosa Maria Oms, and Carles Subirà from Hospital Sant Pau.
• CHYMERA: a digital solution that uses Machine Learning and Deep Learning to quickly and automatically assess the quality of X-rays, aligned with European and American criteria and standards. This team consists of Josep Munuera, Lucia Borrego, Daniel Caballero, and Lydia Canales from Hospital Sant Pau.
• PADAC: a hybrid model that combines in-person and home care to reduce the number of hospital visits for patients in oncology clinical trials. Romina Ribas, Mireia Llobet, Diana Castells, Laia Lavernia, Silvia Molina, Laia Ribas, and Judith Reyes from Hospital Sant Pau lead this proposal.

Throughout the program, teams will go through various training modules where they will receive advice in key areas such as intellectual property management, funding search, applicable regulations, business model development, and project structuring.

The edition will culminate with INNOVATION DAY, an event to be held on June 17, 2025, where the teams will present their progress before the innovation ecosystem of Barcelona and Spain, connecting with strategic actors such as pharmaceutical leaders, investment funds, and other key professionals. Moreover, on that day, several financial grants will be awarded, thanks to the contribution from the Private Foundation Hospital de la Santa Creu i Sant Pau. One for the winning project of 50,000 euros and another for the second project of 15,000.

With this new edition, IR Sant Pau reaffirms its commitment to innovation, supporting professionals in the development of projects that can positively impact society.

Stay tuned for INNOPAU’s progress!

The Sant Pau Research Institute (IR) will launch a new Phase I/IIB clinical trial for patients with Fanconi anemia diagnosed with head and neck cancer. The study, known as the AFAN trial (EU CT No.: 2024-511477-29-00), is led by Dr. Jordi Surrallés, head of the Cancer Predisposition Syndromes Group, scientific director of the IR Sant Pau, and professor in the Department of Genetics and Microbiology at the UAB. The trial will evaluate the safety and efficacy of the drug afatinib in patients with Fanconi anemia and locally advanced, unresectable, or metastatic squamous cell carcinoma located in the oral cavity, oropharynx, hypopharynx, or larynx, making it the first clinical trial worldwide for this indication. The study, approved by the Spanish Agency for Medicines and Medical Devices (AEMPS) last August, began recruiting patients this October, with a process expected to last approximately four years.

This project is the result of joint research by the Sant Pau Research Institute (IR), the Autonomous University of Barcelona (UAB), and the Biomedical Research Networking Center (CIBER), which led to the discovery of a new therapeutic use for afatinib, a drug currently administered to treat certain types of lung cancer in the general population. This project is, therefore, a drug repurposing initiative, transferring a treatment from a common disease to a rare disease with no therapeutic alternatives.

Fanconi anemia is a rare genetic disorder caused by a defect in DNA repair. It leads to bone marrow malfunction, and patients are particularly prone to developing head and neck tumors at a very young age. Due to their genetic defect, cancer patients cannot undergo chemotherapy and therefore have no effective treatments beyond surgery, making this the leading cause of mortality among the adult population affected by this disease.

The new use of afatinib developed by researchers from these institutions has led to a patent recently granted in Europe and pending in the United States. Additionally, as a rare disease, the project has received afatinib’s designation as an Orphan Drug by the EMA, expediting the development timeline for this new drug use.

To carry out this clinical trial, the crucial collaboration of Boehringer Ingelheim, the current owner and distributor of afatinib, has been secured, and they will provide the drug to be administered to patients during the study. This advancement marks a significant step forward in the treatment of patients with Fanconi anemia, who have developed this type of cancer and currently lack therapeutic alternatives. To ensure the success of the trial, patients will be treated not only at Sant Pau Hospital but also at Hannover University Hospital in Germany, where EMA approval is also expected soon.

The AFAN research team, led by Dr. Jordi Surrallés, includes Dr. Georgia Anguera, AFAN’s principal investigator, and Dr. Oscar Gallego (oncologists from the Medical Oncology Service at Sant Pau Hospital), Drs. Núria Berga and Maria Estela Moreno from the hospital’s Pharmacy Service, with the collaboration of Dr. Javier León from the Otolaryngology Service and Dr. Ramón García-Escudero from the Research Institute at Hospital 12 de Octubre, who will perform genomic analyses associated with the trial.

The institutions wish to thank all the entities that have made possible all the preclinical research and the current AFAN clinical trial, including industry partners like Boehringer Ingelheim, who support cutting-edge R&D, as well as the various institutions and patient associations that have provided financial support for the clinical research project, such as the Carlos III Health Institute (ICI22/00076, funded by the European Union – NextGenerationEU) and the Fanconi Anemia Research Fund (https://fanconi.org/).

The Sant Pau Research Institute (IR Sant Pau) held its 1st Primary Care Research Conference this Monday, October 28, aimed at emphasizing the significance of research in this field. The event brought together researchers from the institution and professionals from various Primary Care centers to foster debate on the current state of this research and the opportunities it may offer.

“With this conference, within the framework of IR Sant Pau, we aimed to promote collaboration among Primary Care professionals, both doctors and nurses, and those from the hospital. We also sought to establish connections with public health professionals, as research in Primary Care is deeply linked to community care and public health,” explained Dr. Carlos Brotons, head of the Primary Care research group at IR Sant Pau and director of the EAP Sardenya Research Unit, one of the organizers of the event along with Dr. Pablo Alonso-Coello, director of the Epidemiology, Public Health, and Primary Care area at IR Sant Pau.

Brotons added: “Additionally, we organized a roundtable on clinical trials in Primary Care, a field with great development potential. For this, we invited experts with successful experiences in this area to share their knowledge.”

Throughout the day, clinical research experiences were presented in areas such as musculoskeletal diseases, with projects focused on osteoporosis and gout; non-oncologic chronic pain, highlighting the importance of preventing and reducing the use of pharmacological treatments as the sole therapeutic option; diabetes; and heart failure. Community research topics were also addressed, including health surveys in Barcelona, used to monitor Primary Care from the population’s perspective and analyze inequalities; colorectal cancer screening as a collaborative research opportunity; and the “Barcelona Salut als Barris” program.

The event featured Pilar Gayoso, Deputy Director of Research Evaluation and Promotion at the Carlos III Health Institute in Madrid, who delivered a lecture on the present and future of Primary Care research and its integration into health research institutes. “Institutes must incorporate Primary Care researchers, but not forcibly; the goal is to encourage their proactive integration,” Gayoso emphasized during her presentation. She also added, “It’s essential that these professionals do not abandon clinical care but rather have spaces to reflect on the results they obtain in consultations.”

To carry out this event, IR Sant Pau collaborated with EAP Sardenya, Dreta de l’Eixample, and Disset de Setembre; ABS Sagrada Familia; the Primary Care Consortium of Barcelona Esquerra (CAPSBE), the Catalan Institute of Health (ICS); IDIAP Jordi Gol; the Barcelona Public Health Agency (ASPB); professionals from various departments of the Hospital de la Santa Creu i Sant Pau, and the Carlos III Health Institute.

Two recent studies, led by researchers from the Sant Pau Research Institute (IR Sant Pau) and conducted in collaboration with hospitals across Spain, have identified significant genetic loci, or DNA regions, associated with lacunar stroke and spontaneous intracerebral hemorrhage. These discoveries open new possibilities for the development of personalized therapies and underscore the importance of genetics in risk stratification for these severe cerebrovascular diseases.

CTNND2 Gene and Lacunar Stroke

The first study, published in Stroke and led by Dr. Jara Cárcel Márquez and Dr. Israel Fernández-Cadenas from the Pharmacogenomics and Neurovascular Genetics Group at IR Sant Pau, focused on lacunar stroke, a subtype of ischemic stroke caused by the occlusion of small cerebral vessels. This study, the first comprehensive genomic analysis conducted on the Spanish population, highlighted the importance of the CTNND2 gene in the risk of lacunar stroke, particularly in men.

Researchers analyzed data from 9,081 individuals, including 3,493 ischemic stroke cases and 5,588 healthy controls, and validated their findings with international consortia such as MEGASTROKE, GIGASTROKE, and the UK Biobank. One of the most noteworthy discoveries was the identification of locus 5p15.2, with the rs59970332-T variant being the main one associated with lacunar stroke. The CTNND2 gene, located near this locus, may play a crucial role in vascular health and the formation of new blood vessels. Additionally, associations were found with other stroke-related genes, such as F2 and FGG.

This genetic study on the Spanish population has confirmed risk variants in 12 known genes associated with stroke in other international populations, which is essential for the application of precision medicine in Spain. Dr. Cárcel emphasizes that these findings “can help us identify individuals at higher risk of stroke, enabling the implementation of targeted preventive measures in the future.” According to the researchers, this study represents a significant advance in understanding the genetic basis of ischemic stroke and highlights the need to consider sex differences in genetic research.

Newly Discovered Loci in Spontaneous Intracerebral Hemorrhage

The second study, published in Neurology and also from the IR Sant Pau group, led by Dr. Elena Muiño and Dr. Israel Fernández-Cadenas, investigated spontaneous intracerebral hemorrhage (ICH), a serious condition affecting 30 out of every 100,000 people globally each year. Using an innovative approach, the study uncovered genetic variants associated with this disease that had previously gone undetected in traditional studies.

The key innovation was a meta-analysis integrating genetic data from various diseases associated with intracerebral hemorrhage, such as vascular conditions, rather than limiting the scope to genetic variants exclusively tied to cerebral hemorrhage. This approach increased statistical power, leading to the detection of four genetic loci associated with ICH that had not been identified before.

Until now, GWAS studies had identified only two main loci associated with ICH: APOE for lobar hemorrhage and locus 1q22 for non-lobar hemorrhage. However, by analyzing data from 1,543 patients with ICH, alongside five related phenotypes and a replication cohort of 399,717 individuals from the UK Biobank, the research team identified several new genetic loci, including OBFC1 (10q24.33), NECTIN2 and APOC1 (19q13.32), and the SH3PXD2A gene, now linked to ICH risk. Additionally, loci ICA1L (2q33.2) and COL4A2 (13q34), previously described, were replicated for the first time.

“This approach allowed us to identify several new genetic loci, including those associated with biological processes like amyloid protein deposition or lipid metabolism, which could be promising therapeutic targets to reduce intracerebral hemorrhage risk in genetically predisposed individuals,” explains Dr. Muiño.

The study employed bioinformatics tools like TWAS (Transcriptome-Wide Association Studies) and PWAS (Protein-Wide Association Studies), enabling a deeper understanding of the underlying biology of ICH by examining the relationship between genetic variants and protein or transcript expression.

“This is a significant step forward in understanding the genetic basis of intracerebral hemorrhage,” notes Dr. Muiño. “The identification of these loci not only provides critical insight into the underlying biological mechanisms but could also point to new therapeutic targets to reduce the risk of ICH in the future and aid decision-making in complex patients.”

The study lays the groundwork for future research, including the use of methods like Mendelian randomization to explore whether the proteins associated with the discovered loci, beyond being associated with hemorrhage, are causal factors in this condition.

Funding and Collaboration

The lacunar stroke study was funded by the Instituto de Salud Carlos III, ERA-NET NEURON, the Cooperative Health Research Network on Vascular Diseases, the Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), European Union Next Generation funds, the CERCA program from the Generalitat de Catalunya, the Marató de 3cat, and the National Institutes of Health (NIH).

The intracerebral hemorrhage study received funding from the Instituto de Salud Carlos III, the Generación Project, the Maestro Project, the INVICTUS+ network, and European Union Next Generation funds. Both studies were made possible through collaboration with multiple hospitals in Spain and international consortia.

Reference Articles

Cárcel-Márquez, J. et al. (2024) “Sex-stratified genome-wide association study in the Spanish population identifies a novel locus for lacunar stroke”, Stroke; a journal of cerebral circulation, 55(10), pp. 2462–2471. Disponible en: https://doi.org/10.1161/STROKEAHA.124.047833

Muiño, E. et al. (2024) “Identification of genetic loci associated with intracerebral hemorrhage using a multitrait analysis approach”, Neurology, 103(8), p. e209666. Disponible en: https://doi.org/10.1212/WNL.0000000000209666

With the collaboration of:

Dr. Antoni Betbesé-Roig, a researcher from the Intensive Care Medicine Group at the Sant Pau Research Institute (IR) and a professional from the Intensive Care Medicine Service at Hospital Sant Pau, and Dr. Mercedes Camacho, from the Complex Disease Genomics Group at IR, have participated in a study led by Hospital Universitari de Bellvitge and IDIBELL, which has just been published in the Journal of the American Medical Association (JAMA). The results show that the use of a new extracorporeal blood purification membrane significantly reduces acute kidney injury after high-complexity cardiac surgery.

Acute kidney injury is a condition in which the kidneys suddenly stop functioning and cannot remove toxins from the blood, a common issue in critically ill patients or those undergoing high-complexity cardiac surgeries. This has driven research into procedures that may help address this problem, leading to the SIRAKI02 study. Researchers from Hospital Universitari Germans Trias i Pujol also participated in this study.

The aim of the study was to assess whether using an enhanced adsorption membrane, known as oXiris®, during cardiac surgery could reduce the incidence of kidney injury in patients requiring extracorporeal circulation. This membrane is already used in intensive care units for sepsis treatment and continuous renal replacement, but this is the first time it has been associated with positive clinical outcomes in the context of cardiac surgery.

The trial included 343 patients from Bellvitge and Germans Trias i Pujol hospitals who underwent surgeries between 2016 and 2022, requiring extracorporeal circulation for more than 90 minutes. The inflammatory response of the patients was measured through indicators obtained before and after the procedure, in collaboration with the Biochemistry Laboratory at Hospital Sant Pau.

The results show that, in the control group (169 patients), 40% developed acute kidney injury in the week following surgery, while in the group treated with the new membrane (174 patients), this percentage dropped to 28%. Furthermore, no additional complications were detected from using the device, and perfusionists reported that it was simple and efficient to operate.

If these results are confirmed in larger studies, this device could become a routine part of treatment for high-risk patients undergoing cardiac surgery with extracorporeal circulation, with the potential to reduce ICU stay time and offer other clinical benefits.

Reference Study:

Pérez-Fernández, X. et al. (2024) “Extracorporeal blood purification and acute kidney injury in cardiac surgery: The SIRAKI02 randomized clinical trial”, JAMA: the journal of the American Medical Association [Preprint]. Available at: https://doi.org/10.1001/jama.2024.20630

Researchers at the Sant Pau Research Institute (IR Sant Pau) have published a study showing that “brain alterations related to the more aggressive forms of cognitive decline in Parkinson’s disease can be detected years before cognitive impairment manifests.” The research is part of a project funded by the Fundación la Marató de TV3 and led by Dr. Javier Pagonabarraga, researcher of the Parkinson’s Disease Group at IR Sant Pau and neurologist at the Movement Disorders Unit of the Neurology Department at Hospital de Sant Pau. The results open new avenues to anticipate, understand, and intervene in cognitive disorders related to this disease.

Unlike what occurs in other neurodegenerative diseases like Alzheimer’s, not all people with Parkinson’s develop cognitive impairment or dementia. Unfortunately, a significant proportion does, and in some cases, cognitive decline is very aggressive during the early years of the disease.

Currently, it is very difficult to predict which recently diagnosed Parkinson’s patients or those without cognitive problems will develop dementia, but researchers have a clear understanding of the brain and cognitive anomalies that are commonly present in people with Parkinson’s who experience severe cognitive disorders.

“In many cases, when the brain is becoming diseased, neuropsychological evaluation tests and brain imaging techniques do not allow us to see phenomena that are already present. When we detect problems clinically, we know that significant brain damage has already occurred. Therefore, to intervene before the brain damage becomes too extensive, we need to develop techniques that allow us to observe phenomena that are already present in those who will experience a more aggressive form of the disease, but which we cannot yet detect,” explains Dr. Saül Martínez-Horta, researcher of the Parkinson’s Disease Group at IR Sant Pau and neuropsychologist at the Movement Disorders Unit of the Neurology Department at Hospital de Sant Pau.

In this study, researchers focused on newly diagnosed Parkinson’s patients without cognitive problems and followed them for four years. Initially, they measured brain activity using an electroencephalogram (EEG), took brain images using magnetic resonance imaging (MRI), and measured the levels of a blood marker related to neuronal damage known as neurofilament light chain (NfL); in addition, every year they underwent an extensive neuropsychological examination to assess their cognitive state.

The follow-up showed that there are two large groups of patients: one group did not show significant cognitive decline during the first four years, while the other group dramatically worsened after the second year. Interestingly, MRI measures, NfL levels, or cognitive performance during the first visit did not detect differences between these two groups. In other words, these commonly used measures did not anticipate how the patients would progress. However, EEG analyses showed that those who would experience clear cognitive decline two years later already exhibited significant slowing of brain activity in the temporal, parietal, and frontal lobes during the first visit.

According to Dr. Arnau Puig-Davi, researcher of the Parkinson’s Disease Group at IR Sant Pau and neuropsychologist at the Movement Disorders Unit of the Neurology Department at Hospital de Sant Pau, “thanks to resting EEG, we can detect brain anomalies related to changes that already affect patients who will later present clear cognitive decline and dementia, even in the early stages before mild cognitive impairment.”

This study opens new horizons for the early detection of cases that will develop dementia associated with Parkinson’s disease. The results obtained will help researchers better study and understand the mechanisms underlying the cognitive evolution differences observed in Parkinson’s patients. The researchers believe that this discovery could be very useful for early evaluation of treatments aimed at minimizing the risk of developing Parkinson’s-related cognitive impairment.

Reference article

Arnau Puig-Davi, Saül Martínez-Horta, L., et al. (2024). Prediction of Cognitive Heterogeneity in Parkinson’s Disease: A 4-Year Longitudinal Study Using Clinical, Neuroimaging, Biological and Electrophysiological Biomarkers. Annals of Neurology 2024 Aug 5; 00:1-13 DOI: 10.1002/ana.27035

Project funded by the Fundación la Marató de TV3: “Blood and Neurophysiological Markers of Cognitive Decline Progression in Parkinson’s Disease” (Expedient: 20142910; PI: Dr. Javier Pagonabarraga).

Every minute, a person dies in Europe due to thrombosis. This October 13 is World Thrombosis Day, and for that reason, we want to give a voice to this disease, which is often invisible but has serious consequences. Thrombosis occurs when blood clots form in veins or arteries, partially or completely blocking blood circulation. This condition can trigger complications such as heart attacks, strokes, or pulmonary embolisms, and it is the leading global cause of mortality related to cardiovascular diseases.

Dr. José Manuel Soria, head of the Genomics of Complex Diseases group at the Sant Pau Research Institute, highlights the importance of understanding the risk factors of this disease, which range from genetics to environmental causes. “It is a complex combination of genetic and environmental factors,” explains Dr. Soria. These factors can include prolonged immobilization, major surgeries, pregnancy, use of contraceptives, or other illnesses such as cancer or severe infections like COVID-19. It is essential to understand these risk factors to prevent this disease.

Research Is Key

At Sant Pau, thrombosis research is a priority. Our researchers are working to develop new biomarkers that can help predict which patients are at higher risk of thrombosis, enabling the application of personalized treatments that reduce mortality.

A Charitable Book: “La vida corre per les teves venes”

To mark World Thrombosis Day, the Activa’TT Association and the Sant Pau Research Institute are organizing an event to launch one of their fundraising projects: the presentation of the book La vida corre per les teves venes, a work that shares the experiences of renowned mountaineers and their connection to thrombosis. Some of them have experienced this disease, showing how it can affect anyone.

The book will be available in the coming weeks and can be purchased through this link. The proceeds will be directed to thrombosis research, particularly in cancer patients, one of the most vulnerable groups.

Join the Fight Against Thrombosis

You can support this cause by purchasing the book or making a direct donation through this link. We encourage you to become aware of this disease and collaborate in the research that will allow us to advance its prevention and treatment.

The Vall d’Hebron University Hospital has developed, in collaboration with the Hospital de Sant Pau and the Hospital del Mar, a predictive model, published in The Lancet, which helps oncologists identify which patients with metastatic cancer and systemic treatment who are admitted to emergency care, primarily for pain, fever, or difficulty breathing, are at greater risk of dying in the next 90 days.

This tool, called “PROMISE Score” stands for “Prognostic Score for Hospitalized Cancer Patients” It is a simple web application for healthcare professionals to use. Based on clinical and laboratory information readily available at the time of admission, it accurately predicts the 90-day mortality risk in patients with advanced cancer receiving active treatment. The main goal of this application is to assist the medical team in identifying patients who are more likely to survive without the need for further testing and to help them make decisions.

Identifying risk parameters at the time of admission helps the medical team guide their care, improve the quality of assistance, and avoid unnecessary procedures in situations where there will be no clear benefit from treatment, beyond cost reduction. “The model we have developed has strong predictive power for patients with a favorable prognosis, with whom we can more confidently opt for aggressive therapeutic interventions,” explains Dr. Oriol Mirallas, an attending physician in the Medical Oncology Department at Vall d’Hebron Hospital and a researcher at the Molecular Therapy Research Unit UITM-CaixaResearch at the Vall d’Hebron Institute of Oncology (VHIO). Dr. Oriol Mirallas is the lead author of this study, which involved the collaboration of 41 professionals, along with Dr. Joan Carles, head of the hospital’s section and head of the Genitourinary, Central Nervous System, Sarcoma, and Unknown Primary Tumor Unit, as well as the Genitourinary, Central Nervous System, and Sarcoma Tumor Group at VHIO, and Dr. Rodrigo Dienstmann, head of the Oncology Data Science (ODysSey) Group at VHIO, who helped develop the model and the web tool.

Thanks to this new tool, patients at high risk of mortality can be spared invasive treatments that will not improve their prognosis, reducing unnecessary suffering. “It is proven that nutritional support and community-based palliative care improve the quality of life and survival of patients in this advanced stage of the disease” emphasizes Dr. Joan Carles.

First Tool Filling a Gap in Clinical Practice

Survival estimates are a key element when making decisions about cancer patient care. “Until now, professionals used clinical data validated in outpatient patients, such as tumor stage, treatment response, or the patient’s functional level according to the ECOG scale (designed by the Eastern Cooperative Oncology Group and validated by the World Health Organization), which assesses the quality of life of cancer patients, combined with clinical experience to determine the best medical management” explains Dr. Oriol Mirallas. “But with this prognostic model, we have an objective and quantifiable measure that will help us understand the patient’s evolution upon admission. The PROMISE tool will provide more precise data to improve and facilitate decision-making” he adds.

Dr. Berta Martín Cullell, from the Medical Oncology Department at the Hospital de Sant Pau and a researcher in the study, comments that “with the validation of the PROMISE Score tool at our center, we have confirmed that this model allows us to accurately predict the prognosis of oncology patients admitted with acute complications” “This helps us identify which patients may benefit from more aggressive interventions and improves the quality of medical decisions. This tool, based on accessible clinical data, is a valuable resource for optimizing personalized treatment and preserving the quality of life of patients” she specifies.

Dr. Sònia Servitja, head of the Breast Section of the Medical Oncology Department at the Hospital del Mar and a researcher in the study, adds that “it was essential to develop a tool to individualize the therapeutic intensity for admitted patients, beyond parameters like ECOG and treatment response” “Currently, we are able to individualize treatment thanks to molecular studies; we have toxicity prediction scales for cancer treatments, especially in older and/or frail patients, which allow us to decide whom and how to treat, but we lacked more objective data to decide when to stop treatment, avoiding doing more harm than good. Now, with the PROMISE Score, we can identify hospitalized patients with a better prognosis, and it will help us make decisions” she emphasizes.

This new prognostic model fills a gap in the knowledge and clinical practice for hospitalized oncology patients. The available studies to date have focused on geriatric patients or studies conducted in a single center, with few patients primarily treated with chemotherapy, which does not reflect the current therapeutic landscape. “The current availability of personalized oncology treatments, with combinations of immunotherapy and other targeted therapies applied to thousands of patients, has forced us to seek new tools to assess prognosis and impact in this population, in order to optimize and adapt our daily clinical practice” points out Dr. Sònia Serradell, head of the Medical Oncology ward at Vall d’Hebron.

A Personalized Algorithm

To create this application and obtain an objective measure, a sample of 1,009 patients was analyzed: 749 admitted to Vall d’Hebron and 260 from the Hospital de Sant Pau and the Hospital del Mar, who have been the validation group. At the time of admission, the patients were over 18 years old, had a confirmed advanced or metastatic solid tumor (primarily lung, gastrointestinal, or gynecological, the most prevalent), had received anticancer systemic treatment at least six months before hospitalization, and were admitted to emergency care or the ward for a minimum of 24 hours. The patients in the Vall d’Hebron model creation group were admitted between March 2020 and February 2022, and those in the external validation group between January 2021 and February 2022. The average age was 65 years, 51% were women, with an average time since diagnosis of 22 months, and the average hospitalization lasted 9 days.

The web application https://promise.vhio.net/ allows for the calculation of an individualized value to predict 90-day mortality in patients hospitalized for emergency care with advanced cancer and active treatment. It analyzes a series of clinical and laboratory factors readily available at the time of admission. A high level of LDH (tumor burden), neutrophils (inflammation), and albumin (a protein that indicates the nutritional status of the patient) in the blood analysis at emergency admission are associated with a worse prognosis. The ECOG functional status, the latest CT reports estimating treatment response and disease progression, the tumor stage, and the patient’s emotional state are also evaluated. With these values, the PROMISE Score calculates an algorithm that helps identify those patients who would have a survival exceeding 90 days without the need for additional testing. “The survival percentage is an objective measure that helps the medical team make clinical decisions, but the final strategy planning will always be done in consensus with the patients, their families, and the treating physician” specifies Dr. Oriol Mirallas.

Care Adapted to Each Patient

“Unscheduled hospitalizations are common in cancer patients and are usually related to complications arising from cancer, infections, or treatment-related toxicity problems” states Dr. Joan Carles. This tool can help expedite decisions and optimize hospitalizations, as well as reduce prolonged and repeated admissions that can be avoided in terminal patients. Cancer treatment is a delicate balance between prolonging survival and maximizing quality of life. Hospitalization does not always provide benefits and can even be a stressful experience for both patients and caregivers, as well as impose a greater financial burden compared to outpatient care. “We are fully committed to the well-being and care of our patients, and this tool will help us tailor therapeutic efforts to each patient, achieving maximum benefit” emphasizes Dr. Sònia Serradell.

The web application is available for professionals treating oncology patients through the link https://promise.vhio.net/. “We will continue working to refine and validate the PROMISE Score in other populations and contexts to help as many patients and professionals as possible” concludes Dr. Oriol Mirallas. This tool, which will now be implemented in other centers to conduct an international study with more patients, was designed during Dr. Oriol Mirallas‘s second year of residency and also involved the collaboration of physicians from the Medical Oncology Department, the supervisor of the Medical Oncology ward, Ada Alonso, nursing auxiliary care technicians, and the nutrition team.

Going to a concert by a favourite performer or to the theatre to see a moving play often cause feelings of pleasure, well-being and satisfaction that transcend the moment and spill over into our lives, lifting our mood. For this reason, the arts are considered by the World Health Organization to be an effective tool for improving the emotional well-being of the population. But are they beneficial for everyone? What about people with neurodegenerative diseases? Can they serve as non-medical therapy to influence their mental health?

These are some of the questions that will be tackled by the research project Dramatizing health: the role of theatre in emotional, social and cognitive well-being, promoted by Universitat Oberta de Catalunya (UOC) researchers in association with the Teatre Lliure and the Hospital de la Santa Creu i Sant Pau. The aim is to evaluate the emotional and cognitive benefits of a theatrical arts programme in patients with Parkinson’s disease.

“It’s not art therapy, because we’re not going to treat the symptoms of the disease directly, but Arts in Health is an indirect way of providing benefits to people through participatory activities, such as going to the theatre, and participatory workshops that will be given by experts in coaching actors,” said Marco Calabria, researcher at the eHealth Center’s NeuroAdas Lab and member of the Faculty of Health Sciences at the UOC.

Arts in Health

The project, which has been selected in the “la Caixa” Foundation Social Observatory’s Connecta funding call, is based on a previous pilot study carried out last year by UOC researchers, also in association with the Teatre Lliure and the Hospital de la Santa Creu i Sant Pau, in which they studied the effects of therapeutic intervention based on the performing arts. These new tools, called “arts in health”, use forms of art, such as theatre, dance or the visual arts, to generate emotional and cognitive benefits.

The new project will seek to establish a theoretical framework that explains the relationship between the enjoyment of the moment and an improvement in the spectator’s emotional state and how this is transferred to mental health.

“We want to see if this well-being produced by the arts has a domino effect that has an impact on the real lives of patients,” said Calabria, the principal investigator. He pointed out that, unlike other experiences, this project “was created with a clear research focus. Many interventions involving the arts are intended to have an impact on health, but their effectiveness hasn’t been studied.”

“We’re delighted to continue working with the UOC and the Hospital de Sant Pau on this project, which links the arts and health; the pilot test enabled us to obtain some initial positive results and see the development of the participants,” explained Alícia Gorina, head of the Teatre Lliure’s Educational Programme. Violeta Sugranyes, the theatre’s project coordinator, added: “We want to continue working to develop a method that can be applied in other social contexts and strengthen the argument for prescribing the arts as part of the health system in the future.”

Parkinson’s, the second most prevalent neurodegenerative disease

The project focuses on patients with Parkinson’s because it is the second most prevalent neurodegenerative disease in society and its incidence is expected to increase considerably over the next 20 years. In addition to problems with movement, sufferers have cognitive difficulties, especially in terms of attention and working memory; they also tend to suffer from apathy, anxiety and even depression. Moreover, there is still a stigma attached to the condition, which leads to a reduction in social relationships.

Participants will be recruited with the assistance of the Movement Disorder Unit at the Hospital de la Santa Creu i Sant Pau. For its part, the Teatre Lliure will be in charge of designing activities together with the UOC researchers, selecting the plays that the participants will see and organizing the workshops.

According to Carmen García, neuropsychologist with the Neurology Service at the Hospital de la Santa Creu i Sant Pau, “the therapeutic approach to Parkinson’s disease is complex and requires a combination of pharmacological and non-pharmacological treatments. We’re very happy to be participating in this project, which offers an opportunity to contribute to our knowledge of the efficacy of non-pharmacological therapeutic options applying the necessary scientific rigour. The project combines performance activities and has the therapeutic advantage of being carried out in the context of a group of people with the same disease, which is very beneficial psychologically”.

A total of 50 volunteers will participate, divided into two groups: 25 will participate in theatre activities and another 25 will be limited to doing cognitive stimulation, attention and memory activities from home with materials that will be supplied to them. In both groups, the emotional and cognitive state of the participants will be evaluated before and after the intervention.

In a second phase, they will repeat the theatre activity but online, with the aim of breaking down barriers for people who do not live near cultural facilities. “We’ll try to determine whether remote participation brings the same benefits as face-to-face participation. Here, the key element will be the role played by the group factor”, Calabria commented.

The emotional and cognitive alterations of neurodegenerative diseases have a negative impact on the quality of life of those affected and their environment, with a progressive worsening throughout the disease. We therefore need to investigate new approaches to treating these alterations in combination with pharmacological therapy. Arts in Health could be an innovative methodology to meet this need to improve well-being.

With the collaboration of:

Dr. Noemí Rotllan Vila, principal investigator of the Pathophysiology of Lipid-Related Diseases Group at the Sant Pau Research Institute (IR Sant Pau), has been consulted as an expert by the Science Media Centre platform to provide her assessment of the awarding of the Nobel Prize in Physiology or Medicine to scientists Victor Ambros and Gary Ruvkun. This award recognizes their significant contributions to the discovery of microRNAs, small non-coding RNA molecules that play a fundamental role in regulating gene expression.

“I cannot hide my joy in seeing how the pioneering work of two great scientists, who began their research in the 1980s, is recognized worldwide,” Dr. Rotllan stated. According to the expert, the studies of Ambros and Ruvkun have not only expanded the understanding of cellular development but also opened the door to new therapeutic avenues for various diseases, including cancer and cardiovascular diseases.

Dr. Rotllan highlighted that her own research also focuses on the fascinating world of microRNAs. “These small sequences of only 19-22 nucleotides are capable of regulating gene expression at the post-transcriptional level, either by inhibiting translation or promoting messenger RNA degradation. It is astonishing how a single microRNA can control more than 100 mRNAs and, at the same time, how a single mRNA can be regulated by several microRNAs,” she explained.

Additionally, the researcher emphasized the potential of microRNAs as therapeutic targets and biomarkers in various pathologies. “Although clinical trials are in their early stages, as is the case with Miravirsen, the first drug specifically targeting a microRNA, it is a promising step towards personalized medicine,” she noted. Nonetheless, Dr. Rotllan wanted to remind that much research remains to be done before these therapies can be widely applied.

Finally, she underscored the importance of basic research conducted with model organisms, such as the small worm Caenorhabditis elegans. “Studies with these organisms are key to understanding fundamental biology and should not be underestimated,” she concluded.

This recognition of the discovery of microRNAs not only celebrates their scientific relevance but also highlights the path that remains to be traveled in the field of biomedicine, a path that researchers like Dr. Noemí Rotllan Vila continue to pave.

Biomarkers have revolutionized the understanding of Alzheimer’s disease (AD), enabling early detection and opening the door to personalized treatments. A series of six papers published in The Lancet Healthy Longevity and eBioMedicine, coordinated by researchers from the Sant Pau Research Institute (IR Sant Pau)—who led two of the six studies—highlight the main technical, clinical, and regulatory challenges currently faced when integrating these biomarkers into daily clinical practice and adapting them to different healthcare settings. The goal is to make them truly useful, accelerate Alzheimer’s diagnosis, and improve global access to preventive and therapeutic treatments.

In this series, experts emphasize the transformative potential of biomarkers in advancing the diagnosis and treatment of Alzheimer’s disease, while also underscoring the complex challenges of integrating these tools into clinical practice and trials. Research on biomarkers—or biological indicators—for Alzheimer’s disease has traditionally focused on their sensitivity and specificity in diagnosing the pathology. However, in clinical practice, their utility will greatly depend on their positive and negative predictive value, which is significantly influenced by different healthcare settings.

One of the two papers led by IR Sant Pau, “Challenges in the practical implementation of blood biomarkers for Alzheimer’s disease,” highlights the challenges in implementing newly developed plasma biomarkers to detect this neurodegenerative disease and discusses the main limitations for their use in different settings, stressing the need for standardization to ensure accuracy and reliability of results.

“For example, in specialized or primary care, or in potential implementation in screening programs, among others. Some of these challenges are as basic as understanding the influence of preanalytical effects, such as how the sample is extracted and processed before the biomarker analysis itself,” explains Dr. Daniel Alcolea, researcher at the Memory Unit of IR Sant Pau and member of the Neurology Department at Hospital de Sant Pau. “Another challenge is understanding the influence of other diseases that may alter the interpretation of these markers’ results.”

A special case: Biomarkers in Genetic Forms of Alzheimer’s Disease

The series of papers highlight two clinical practice scenarios where the importance of context in their use stands out. The first, addressed in the study led by Dr. Maria Carmona, researcher at the Memory Unit of IR Sant Pau and member of the Neurology Department at Hospital de Sant Pau, “Clinical and research application of fluid biomarkers in autosomal dominant Alzheimer’s disease and Down syndrome,” is the use of biomarkers in genetically determined forms of Alzheimer’s, such as early-onset autosomal dominant or Down syndrome. “Here, they are not so useful for diagnosing the disease, but rather help us understand what stage it’s in and monitor its progression.”

The second is the diagnosis of Alzheimer’s disease in populations with intellectual disabilities, one of the greatest challenges. In these individuals, symptoms may be masked by the underlying disability, and the use of reliable biomarkers can significantly improve diagnostic accuracy and facilitate access to disease-modifying therapies. This is especially important at a time when current diagnostic frameworks often exclude these populations.

Beyond the diagnostic realm, the six studies also emphasize the growing and crucial role of biomarkers in clinical trials, using them for appropriate participant selection, monitoring disease progression, and evaluating treatment efficacy. Biomarkers are essential tools that can significantly accelerate the development of effective treatments for Alzheimer’s and related dementias.

Reference Articles

1. Schöll M, Verberk I, del Campo M, et al. Challenges in the practical implementation of blood biomarkers for Alzheimer’s disease. THELANCETHEALTHLONGEVITY-D-23-00585R2.
2. Carmona-Iragui M, O’Connor A, Llibre-Guerra J, et al. Clinical and research application of fluid biomarkers in autosomal dominant Alzheimer’s disease and Down syndrome. EBIOM-D24-01284R2.
3. McFeely A, O’Connor A, P Kenelly S. The use of biomarkers in the diagnosis of Alzheimer’s disease in adults with intellectual disability. THELANCETHEALTHLONGEVITY-D- 2300442R1.
4. McGlinchey E. Duran-Aniotz C, Akinyemi R, et al. Biomarkers of neurodegeneration across the Global South. THELANCETHEALTHLONGEVITY-D-23-004551R3.
5. Pascoal T, Aguzzoli C, Lussier F, et al. Insights into the use of biomarkers in clinical trials in Alzheimer’s disease. EBIOM-D-24-01017R1.
6. Karlawish J, Grill J. Alzheimer’s disease biomarkers and the tyranny of treatment. EBIOM-D-23-04741R3.

Yang Song, postdoctoral researcher at the Iberoamerican Cochrane Centre, has been awarded the 2024 Najoua Mlika-Cabanne Prize by the Guidelines International Network (GIN) during the recent Global Evidence Summit (GES) held in Prague from September 10 to 13. Yang is the third researcher to receive this award for projects conducted at the Iberoamerican Cochrane Centre, following Robin Vernooji and Héctor Pardo, in the 12 editions of these awards.

Song, who also works as an assistant professor at the Chinese University of Hong Kong (Shenzhen), has been focused for the past six years on improving methodology and implementing guideline adaptation. Notably, she has led the RIGHT-Ad@pt checklist, participated in guideline adaptation, and contributed as vice-chair of GIN’s Adaptation Working Group.

“I am deeply honored to have been selected to receive the prestigious GIN Award in 2024, named after the esteemed Dr. Najoua Mlika-Cabanne. I am grateful for this recognition from the GIN community and am committed to continuing to promote innovation and collaboration in her legacy,” Yang Song stated.

She was nominated for this award by her doctoral thesis supervisor, Pablo Alonso Coello, a researcher at the Sant Pau Research Institute and collaborator at the Iberoamerican Cochrane Centre, for her contribution to advancing methodology for guideline adaptation, including living guidelines. Her role as vice-chair of GIN’s Adaptation Working Group also demonstrates her potential leadership in the methodological community.

On September 4th, Dr. M. Rosa Ballester i Verneda, Head of Responsible Research and Innovation (RRI) at the Sant Pau Research Institute, was inducted as a Corresponding Academic at the Royal Academy of Pharmacy of Catalonia. During the Extraordinary Public Session, held in the Academy’s auditorium, she delivered her speech titled “Gender and Sex Perspective in Biomedical Research: An Ethical Issue.”

This induction recognizes her outstanding career and reinforces the commitment of the Sant Pau Research Institute to integrating gender and sex perspectives into science, and to promoting research that upholds equality and ethics across all fields.

A study led by the Pharmacy and Neurology Services, with the collaboration of Impuls Digital, has evaluated the persistence, effectiveness, and tolerability of monoclonal antibodies targeting the calcitonin gene-related peptide (anti-CGRP) in patients with chronic migraine (CM) under real-world clinical conditions. Anti-CGRPs are drugs that work to prevent migraines, helping to reduce the pain burden on patients. The drugs studied include erenumab, fremanezumab, and galcanezumab.

If a patient is treated with one drug and does not improve, switching to another is possible, as even in a third of cases, the patient may respond to the change.
The retrospective and observational study included 281 patients treated with anti-CGRP between January 2019 and December 2022 at the Hospital de Sant Pau. Treatment persistence was measured, as well as the percentage of patients who maintained the treatment at 3, 6, and 12 months. Effectiveness was defined as a ≥50% reduction in the number of monthly migraine days (MMD), and tolerability was measured by the number and type of adverse events reported.

The results, published in the journal Headache, showed that treatment persistence at 12 months was higher with the first anti-CGRP treatment (66.7%) compared to the second (49.8%) and third (37.2%). Regarding effectiveness, a ≥50% reduction in MMD was achieved in 57.6% of patients with the first treatment at 3 months, while only 25.0% and 11.8% of patients achieved this response with the second and third treatments, respectively. In terms of tolerability, 55 adverse events were reported in 43 patients (15.3%), mostly mild, and only 14 patients (5.0%) discontinued treatment due to these effects.

The study concludes that persistence with anti-CGRP treatment is higher with the first anti-CGRP treatment and decreases with subsequent treatments, especially when the change is due to lack of effectiveness or severe adverse effects. Additionally, it confirms that the tolerability profile of anti-CGRP monoclonal antibodies is favorable, with a relatively low number of treatment discontinuations due to side effects.

The researchers emphasize the need for further studies to identify predictors of response after changes in anti-CGRP treatment in patients with chronic migraine.

Reference Article:

De Dios A, Pagès-Puigdemont N, Ojeda S, Riera P, Pelegrín R, Morollon N, Belvís R, Real J, Masip M. Persistence, effectiveness, and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies in patients with chronic migraine. Headache. 2024 Sep 13. doi: 10.1111/head.14827. Epub ahead of print. PMID: 39268992.

A new study reveals a therapeutic pathway that could improve the cardioprotective potential of “good” cholesterol (carried by HDL) in people with familial hypercholesterolemia, a genetic disorder that leads to very high levels of “bad” cholesterol (LDL). The study was conducted by researchers from the CIBER Diabetes and Associated Metabolic Diseases (CIBERDEM) and Cardiovascular Diseases (CIBERCV) areas of the Sant Pau Research Institute and the Hospital de Sant Pau in Barcelona.

Heterozygous familial hypercholesterolemia is a disorder primarily inherited due to mutations in the LDL receptor gene and is characterized by high levels of LDL cholesterol, often associated with low HDL cholesterol levels. Familial hypercholesterolemia is quite common, with an estimated prevalence of at least 1 in 250 people, and carries a high cardiovascular risk.

The study, led by Joan Carles Escolà Gil and Francisco Blanco Vaca, researchers from CIBERDEM at the Sant Pau Research Institute and Hospital de Sant Pau in Barcelona, has been published in the journal JACC: Basic to Translational Science.

New Pathway to Eliminate “Bad” Cholesterol

PCSK9 protein inhibitors are among the most advanced and effective treatments for reducing LDL cholesterol levels and, consequently, cardiovascular risk. This new study has now identified a new metabolic pathway through which these PCSK9 protein inhibitors promote HDL’s ability to transport cholesterol from macrophages in the arterial wall and transfer it to LDL, allowing its subsequent elimination from the body through the liver, bile, and feces.

The study’s results show that functional alterations in the LDL receptor reduce cholesterol transport from macrophages and its elimination from the body, which can be reversed with PCSK9 inhibitors. Carla Borràs, the first author of the study and a researcher at CIBERDEM in the Sant Pau Research Institute, indicates that “the findings of this new study could open up new therapeutic possibilities to prevent cardiovascular risk in patients by increasing this metabolic pathway.”

Additionally, Marina Canyelles, co-first author of the study, from the same research group, states that “future research should analyze the effects of PCSK9 inhibitors on this pathway in other forms of hypercholesterolemia and their association with the reduction of cardiovascular events.”

Researchers from the Sant Joan University Hospital in Reus, the Institute for Biomedical Research of Barcelona/CSIC, the Ramón y Cajal University Hospital, and Finnish institutions such as the Wihuri Research Institute and the Minerva Foundation Institute for Medical Research also participated in the study.

Reference Article

Carla Borràs, Marina Canyelles, Josefa Girona, Daiana Ibarretxe, David Santos, Giovanna Revilla, Vicenta Llorente-Cortes, Noemí Rotllan, Petri T. Kovanen, Matti Jauhiainen, Miriam Lee-Rueckert, Luis Masana, Francisco Arrieta, Javier Martínez-Botas, Diego Gómez-Coronado, Josep Ribalta, Mireia Tondo, Francisco Blanco-Vaca, Joan Carles Escolà-Gil, PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia, JACC: Basic to Translational Science, 2024, ISSN 2452-302X, https://doi.org/10.1016/j.jacbts.2024.06.008. (https://www.sciencedirect.com/science/article/pii/S2452302X24002535)