Dr. Carmen García-Sánchez, neuropsychologist at the Neurology Service of Sant Pau Hospital and researcher at the Sant Pau Research Institute (IR Sant Pau), has presented the findings of a study on persistent COVID-19 and the potential relationship between body mass index and cognitive performance at the 52nd Annual Congress of the International Neuropsychological Society, recently held in New York (United States).

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The study, titled “Body Mass Index (BMI) and Psychological Health in Long-COVID-19 Patients: An Exploration of Cognitive Function, Anxiety, Depression, Apathy, Fatigue, and General Health Status,” was conducted on a total of 118 patients with persistent COVID-19, aiming to analyze the potential association between body mass index (BMI) and cognitive performance, anxiety, depression, apathy, and fatigue among these individuals. The study also explored whether BMI influences the overall health perception of these patients. The results obtained by the research team have shown that BMI may not be a direct determinant of these psychological aspects in the context of prolonged COVID-19.

According to Dr. Carmen García-Sánchez, fatigue has been associated “with medical conditions such as post-viral infections or neurological diseases. But there is no universally accepted definition of this clinical condition, and our knowledge of its underlying pathogenic mechanism is limited, which is why it represents a clinical challenge for experts.”For this reason, “it is necessary to thoroughly assess the sequelae in post-COVID-19 patients and continue studying their evolution to reduce cognitive deterioration and promote recovery.”

This new study presented at the Congress of the International Neuropsychological Society represents another step in the research line developed by IR Sant Pau, which has already published other studies revealing a connection between fatigue, depression, anxiety, and other cognitive deficits in patients with post-COVID syndrome. One of them, published in the journal Brain and Behavior, showed that the disease had a widespread impact on attention skills, executive functions, learning, and long-term memory. And another, published in the Journal of Neurology, revealed that fatigue in post-COVID patients was associated with anxiety, depression, and apathy.

The Sant Pau Research Institute has stabilized two researchers from the Miguel Servet program of the Carlos III Institute of Health (ISCIII): Dr. Mª Virtudes Céspedes and Dr. Mª José Martínez Zapata. This stabilization responds to the Miguel Servet evaluation policy carried out by the Institute and which both researchers have successfully passed, standing out for their excellence in research, leadership and innovation.

Dr. Céspedes, a graduate in Biology from the Complutense University of Madrid, a doctor in Neurosciences from the Institute of Neurosciences of the CSIC-Universidad Miguel Hernández (2001), and a master’s degree in Analysis and Quality Control from the Technological Institute of the Chemical and Pharmaceutical Industry, has been a pioneer in identifying new therapeutic targets in peritoneal cancers, mainly in the most aggressive endometrial and ovarian cancers.

Her dedication to studying the influence of the nervous system on tumor progression and the application of high-throughput screening platforms and artificial intelligence aims to open new avenues for improving diagnostic and therapeutic strategies in oncology, consolidating her role as principal investigator of the emerging Gynecological and Peritoneal Oncology Group.

Since joining the IR Sant Pau in 2001, in the Oncogenesis and Antitumor Drugs group led by Dr. Ramon Mangues, Dr. Céspedes has evolved from a postdoctoral student to the leader of an innovative research group, obtaining a Miguel Servet researcher position in 2016. Her research line, which crosses the boundaries between neuroscience and oncology, seeks to develop advanced therapies that can transform the care of patients with these devastating cancers.

Her research lines focus on modeling highly metastatic gynecological cancers, using 2D and 3D systems, and xenotransplants derived from patient mice, to better understand the tumor’s pathophysiology and for use in preclinical evaluation of antimetastatic therapies based on nanoparticles, and tumor neuromodulation, both aimed at eliminating cancer stem cells.

On the other hand, and jointly with clinical researchers from the gynecology and obstetrics department of the Hospital de Sant Pau, she is working on identifying new prognostic markers and therapeutic targets using high-throughput screening platforms, big data, and artificial intelligence to improve the prognostic and therapeutic stratification of patients with endometrial cancer.

Over the past 5 years, she has obtained 7 competitive projects as PI and human resources from ISCIII and private institutions, actively contributed to drug development through contracts with the pharmaceutical industry. Among her most outstanding achievements, she is also a co-inventor of 3 patents covering the use of T22-targeted nanoparticle vehicles to deliver drugs and diagnostic agents into CXCR4+ cells (cancer stem cells).

On the other hand, Dr. Martínez Zapata, a medical graduate from the University of Barcelona (1988), specialized in Clinical Pharmacology trained at the Vall d’Hebron Hospital (HVH, 1993-96), and obtained her doctorate from the Autonomous University of Barcelona (UAB, 2006). Since 2016, as a senior associate researcher Miguel Servet, she has developed a line of clinical research on patient safety during surgery. She has conducted studies as PI, funded by competitive public grants, and has obtained human resources from ISCIII. She is also a researcher in group 43 of the CIBER of Epidemiology and Public Health (CIBERESP), and the Consolidated Catalan Group of Clinical Research and Applied Health. She is a member of the Ibero-American Cochrane Network, Cochrane Collaboration, and the Spanish Society of Clinical Pharmacology.

With an exceptional academic and professional background, she has focused her research on evaluating the safety and efficacy of clinical interventions, including the use of tranexamic acid to reduce bleeding in orthopedic surgery, platelet-rich plasma for wound healing, and the treatment of chronic venous insufficiency. Throughout her career, she has led several independent randomized clinical trials and has collaborated on international research projects, consolidating herself as a key figure within group 43 of the CIBER of Epidemiology and Public Health and the Consolidated Catalan Group of Clinical Research and Applied Health.

On the other hand,

The consolidation of Drs. Martínez Zapata and Céspedes symbolizes not only the recognition of their excellence and commitment to quality research, but also the commitment of the Sant Pau Research Institute to retaining talent and promoting scientific advancement in the field of health. Their stabilization will allow the continuation and expansion of initiated research projects, with the hope of reaching new discoveries that can transform the treatment and care of patients in the coming years.

The Pharmacogenomics and Neurovascular Genetics Group of the Sant Pau Research Institute (IR Sant Pau) has conducted a pioneering study that reveals significant differences in gut microbiota between men and women who have suffered an ischemic stroke. This research highlights the importance of biological sex in studies related to cerebrovascular disorders and gut microbiota.

The study, published in the European Journal of Neurology, was carried out within the framework of the Maestro project, granted to Dr. Israel Fernández-Cadenas, head of this research group, by the Carlos III Health Institute.

Ischemic stroke, a cerebrovascular disease affecting blood flow to the brain, maintains a well-established connection with gut microbiota through the bidirectional gut-brain axis. Until now, no data were available relating the intestinal microbiota to the sex of ischemic stroke patients. According to Dr. Miquel Lledós, from the Pharmacogenomics and Neurovascular Genetics Group of IR Sant Pau and principal investigator of the study, “the vast majority of microbiota research related to stroke does not delve into specific microbial species. We wanted to work with more specific techniques that allow us to study these species, which are ultimately the most important.“

The study involved a cohort of 89 patients who had suffered an ischemic stroke and included 12 healthy individuals as a control group. Researchers analyzed taxonomic differences in gut microbiota between men and women with ischemic stroke using complete metagenomic sequencing.

Analysis results revealed that men who have suffered an ischemic stroke exhibit greater species diversity compared to affected women. Additionally, sex differences were found in ischemic stroke patients regarding the Fusobacteriaceaefamily. It was also observed that these bacteria were not a consequence of the stroke but were already present before experiencing it, thus constituting a risk factor for the manifestation of this disease.

Dr. Fernández-Cadenas comments that the bacteria found in the group of women who had suffered an ischemic stroke “were different from the controls, and we don’t see this in men. In the group of men, there were no differences between stroke patients and controls; therefore, these bacteria were specific to stroke risk in women. Additionally, we validated this with bioinformatics studies, where we saw that these bacteria were not a consequence of having had a stroke but were present before it, and therefore, were a risk factor.”

This study is the first to indicate that there are differences in gut microbiota between men and women who have suffered an ischemic stroke, identifying high levels of Fusobacteriaceae in women as a specific risk factor for the disease. This finding underscores the importance of including biological sex in the design, analysis, and interpretation of studies on stroke and gut microbiota.

Reference article

• Miquel Lledós, Luís Prats-Sánchez, Laia Llucià-Carol, Jara Cárcel-Márquez, Elena Muiño, Natalia Cullell, Cristina Gallego-Fabrega, Jesús M. Martín-Campos, Ana Aguilera-Simón, Marina Guasch-Jiménez, Daniel Guisado-Alonso, Anna Ramos-Pachón, Alejandro Martínez-Domeño, Artur Izquierdo, Rebeca Marín, Pol Camps-Renom, Joan Martí-Fàbregas, Israel Fernández-Cadenas. Ischaemic stroke patients present sex differences in gut microbiota. European Journal of Neurology. Volume30, Issue11. November 2023. Pages 3497-3506 https://doi.org/10.1111/ene.15931

The so-called deferred prescription of antibiotics is a strategy to reduce the inappropriate use of these medications, which can be helpful in addressing the serious global problem of bacterial resistance. This strategy has been shown to be slightly more efficient than immediate prescription and non-prescription of antibiotics and is perceived as a useful tool by professionals in situations of uncertainty, according to two new studies published by researchers from the Sant Pau Research Institute and the Ibero-American Cochrane Center.

In the first study, researchers conducted a cost-effectiveness analysis, comparing deferred prescription to immediate prescription and non-prescription of antibiotics. The analysis included data from a clinical trial conducted by the research group, showing that deferred prescription was slightly more efficient than immediate prescription and non-prescription of antibiotics.

Dr. Pablo Alonso, Director of the Epidemiology and Public Health and Primary Care Area at IR Sant Pau, researcher at the Ibero-American Cochrane Center, and principal investigator of this line of work, states that “deferred treatment in the pediatric population showed slightly superior results than other strategies, even when considering the costs of bacterial resistance”.

In the second study, researchers explored the perceptions and attitudes of primary care professionals regarding antibiotics and deferred prescription as a treatment for adult patients with respiratory infections. The study showed that this prescription strategy was useful for professionals in situations of diagnostic uncertainty, providing patients with a safety net in managing their health problem and representing an opportunity to educate patients about the proper use of antibiotics, giving them greater autonomy.

Researcher Gemma Mas, professor at the Sant Pau Nursing School, coordinator of the Nursing Care Research Group, and first author of both studies, points out that “deferred prescription is used by professionals in cases of doubt and, in very specific situations, such as before the weekend when the patient cannot consult their primary care center again in case of deterioration.” She adds, “deferred prescription is an opportunity to educate the population about these types of infections, antibiotics, and when they are necessary“.

Patients more involved in their treatment

These Sant Pau experts explain that deferred prescription implies that, in cases where the pediatrician or family doctor is unsure whether the infection is bacterial or viral and, therefore, uncertain about the need to prescribe antibiotics to a patient based on their clinical condition at that time, a prescription is given, and the patient or responsible person is also informed about the natural history of the disease and when they should consider using the prescription. “The days during which the child may have these symptoms and what the warning signs would be. Thus, parents or the affected person can assess whether, after a few days, they need to use this prescription or not. In other words, they are given structured advice and guidelines based on the progression of the disease“,emphasizes Dr. Gemma Mas, who highlights that this strategy provides a safety net, empowers patients, and educates them about the proper use of antibiotics.

“For example, in the case of an ear infection, we can explain that if the patient does not improve after 3 days, or if they are much worse after 24 hours, it is necessary to consider using the prescription we have given them“. In this example, if the child improves, unnecessary use of an antibiotic is avoided – with its associated adverse effects and the risk of resistance – or the need to return to the doctor to seek a prescription in case of worsening, as explained by Dr. Gemma Mas.

Dr. Pablo Alonso comments that, although deferred prescription is only relatively implemented in primary care centers in Catalonia, there is still room for improvement. Lack of specificity in clinical guidelines and the need for more detailed tools were identified as areas for improvement for a more effective implementation of this strategy.

In summary, deferred prescription of antibiotics emerges as a valuable tool, not only to reduce costs and bacterial resistance but also to empower patients and educate about the real need for antibiotics in specific cases.

These experts emphasize that this deferred prescription strategy “is a patient-centered approach, providing us with a great opportunity to educate and empower them for decision-making“.

Patient satisfaction, resistance, and system sustainability

Dr. Joaquín López-Contreras, director of the Infectious Diseases Unit and responsible for the Nosocomial Infections and Antibiotic Policy Program at Sant Pau Hospital, indicates that “the use of deferred prescription in primary care is a strategy that has shown savings in the use of unnecessary antibiotics and, therefore, should have an impact on the progression of bacterial resistance in the community“.

From his point of view, these studies provide scientific evidence, “now it is necessary to analyze why this strategy, which has already demonstrated its effectiveness, is not implemented one hundred percent, and we must try to generalize it since, in addition to being positive in terms of patient satisfaction and resistance evolution, it is efficient in an economic sense, and this is also important to contribute to the sustainability of the health system“.

Dr. López-Contreras has emphasized that there is a correlation between the use of antibiotics and the percentage of resistance in different geographical areas of the world. “Southern European countries and countries in South Asia are very important consumers of antibiotics. Performing these types of interventions in Primary Care that educate citizens about the importance of the proper use of antibiotics and also help reduce their use seems to me a good strategy, with a global approach, to reduce the significant health problem posed by bacterial resistance”.

Trust and a good doctor-patient relationship are key factors in implementing this strategy, explains Dr. María Quinteiro, a pediatrician at the Sardenya Primary Care Center, who regularly uses deferred prescription in her practice. “I think it is very important that as a professional, you know the patient to whom you are explaining this, that you are able to trust them and provide adequate support, and that they also trust you to carry out what you are explaining correctly. Education is key“.

This pediatrician explains that the more active patients are and the more they are involved in their disease, the better clinical outcomes are usually achieved. “But that’s why previous education and support are needed; otherwise, it is impossible“.

Especially useful tool in primary care

Dr. Albert Boada Valmaseda, a reference in Primary Care in the Care Area of Catsalut, recalls that antibiotic resistance is a global problem, considered one of the main threats to health and humanity by the WHO. “Primary Care is the main prescriber of antibiotics in the community, and respiratory infections are the main etiology for which they are prescribed. Often, this prescription is inappropriate, given the main viral origin of these infections. That is why it is necessary to provide strategies to reduce the inappropriate prescription of antibiotics“.

From the perspective of this expert, “deferred prescription of antibiotics should be a strategy to promote in primary care for respiratory infections, as it is the area of ​​ highest prescription and is well accepted by professionals and patients. These studies increase knowledge about professionals’ perception of its use and cost-effectiveness”.

Reference Articles

• Mas-Dalmau G, Pérez-Lacasta MJ, Alonso-Coello P, Gorrotxategi-Gorrotxategi P, Argüelles-Prendes E, Espinazo-Ramos O, Valls-Duran T, Gonzalo-Alonso ME, Cortés-Viana MP, Menéndez-Bada T, Vázquez-Fernández ME, Pérez-Hernández AI, Muñoz-Ortiz L, Villanueva-López C, Little P, de la Poza-Abad M, Carles-Lavila M; DAP Paediatrics Group. A trial-based cost-effectiveness analysis of antibiotic prescription strategies for non-complicated respiratory tract infections in children. BMC Pediatr. 2023 Oct 2;23(1):497. doi:1186/s12887-023-04235-3. PMID: 37784098; PMCID: PMC10544479.
• Mas-Dalmau G, Pequeño-Saco S, de la Poza-Abad M, Borrell-Thió E, Besa-Castellà M, Alsina-Casalduero M, Cuixart-Costa L, Liroz-Navarro M, Calderón-Gómez C, Martí J, Cruz-Gómez I, Alonso-Coello P. Perceptions and attitudes regarding delayed antibiotic prescription for respiratory tract infections: a qualitative study. BMC Prim Care. 2023 Oct 4;24(1):204. doi: 10.1186/s12875-023-02123-4. PMID: 37794330; PMCID: PMC10548630.

A group of scientists from various hospitals and research centers in Catalonia, led by Drs. Álvaro Carbayo and Ricard Rojas, researchers from the Neuromuscular Diseases Group at the Sant Pau Research Institute, in collaboration with Dr. Sergi Borrego-Écija and Dr. Ellen Gelpi from the Alzheimer’s Disease and other Cognitive Disorders Group and the Neurological Tissue Bank of IDIBAPS, have published a study in the journal Brain that reveals connections between two devastating brain diseases: Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia.

The study examines the relationship and the full spectrum of these two neurodegenerative diseases, which share more similarities than initially thought. ALS, a disease affecting motor neurons, and frontotemporal dementia, characterized by cognitive and behavioral problems, exhibit a common but highly heterogeneous clinical, genetic, and pathological spectrum, as explained by Dr. Ricard Rojas, researcher at IR Sant Pau and head of the Neurodegenerative Diseases Unit at the Neurology Service of Sant Pau Hospital.

Clinical studies revealed that up to 50% of ALS patients may develop cognitive and behavioral symptoms, with 10 to 15% specifically meeting diagnostic criteria for frontotemporal dementia. Now, through neuropathological examination of a large series of ALS cases, it has been discovered that the actual figure may be much higher: 35.5% of cases also presented pathological features of frontotemporal dementia. Findings show that the pathological aggregation of the TDP-43 protein was present in 93.6% of ALS cases and was more extensive in those with the coexistence of frontotemporal dementia pathology.

While it is known that most cases share the presence of TDP-43 protein aggregates, the study highlights the marked heterogeneity of neuropathological characteristics, suggesting possible different pathophysiological mechanisms. It’s important to note that, currently, the identification of these proteins is done post-mortem, in the absence of a precise biomarker.

“Neuropathological studies and correlation with clinical characteristics help us expand our knowledge of the basis of diseases such as ALS and frontotemporal dementia, opening doors to future studies on biomarkers and specific therapies,” says Dr. Carbayo, the study’s lead author.

The research included all cases that met the neuropathological criteria for frontotemporal dementia from the Neurological Tissue Bank of the FRCB-IDIBAPS-Clinic Hospital of Barcelona between 1994 and 2022, regardless of their final clinical diagnosis. Clinical and neuropathological data were retrospectively reviewed, allowing analysis of the main clinical, genetic, and pathogenic characteristics, comparing patient groups with and without pathological changes of frontotemporal dementia, attempting to define specific subgroups.

“We have observed astonishing heterogeneity in the clinical presentation and pathological and genetic characteristics of patients, with a higher frequency of frontotemporal dementia than described in other series,” says Dr. Carbayo.

From his perspective, these results emphasize the importance of interdisciplinary collaboration between ALS and frontotemporal dementia professionals and units. “It is crucial that we work together to better understand this spectrum of neurodegenerative diseases and to better care for our patients. In fact, at Sant Pau, we have been working with this structure for 6 or 7 years,” concludes Dr. Carbayo.

Reference article:

– Álvaro Carbayo, Sergi Borrego-Écija, Janina Turon-Sans, Elena Cortés-Vicente, Laura Molina-Porcel, Jordi Gascón-Bayarri, Miguel Ángel Rubio, Mónica Povedano, Josep Gámez, Javier Sotoca, Raúl Juntas-Morales, Miriam Almendrote, Marta Marquié, Raquel Sánchez-Valle, Ignacio Illán-Gala, Oriol Dols-Icardo, Sara Rubio-Guerra, Sara Bernal, Marta Caballero-Ávila, Ana Vesperinas, Ellen Gelpi, Ricard Rojas-García, Clinicopathological correlates in frontotemporal lobar degeneration: motor neuron disease spectrum, Brain, 2024;, awae011, https://doi.org/10.1093/brain/awae011

Ms. Gemma Valeta, manager of Personalized and Precision Medicine of the Catalan Health Service, visited the Sant Pau Research Institute this morning. She was received by the director of this institution, Dr. Jordi Surrallés.

Ms. Valeta wanted to learn more about the work carried out in Sant Pau to look for synergies that contribute to promoting research, which is a fundamental pillar to achieve a more precise and individualized approach to the treatment of various diseases.

Without a doubt, research institutes are the epicenter of scientific innovation and the discovery of new therapies. Their ability to explore new scientific frontiers and develop new technologies is essential to advancing the field of personalized medicine.

The synergistic union between research institutes and government authorities can generate an environment conducive to the development and effective implementation of personalized medicine. The creation of spaces for collaboration between researchers and policy makers can facilitate the definition of policies that reflect the needs and opportunities offered by this new scientific frontier.

The detection of phosphorylated TAU 217 protein (p-tau217) in plasma has shown high precision in identifying pathological accumulations of beta-amyloid and TAU proteins. This precision is comparable to traditional biomarker detection in cerebrospinal fluid, as revealed by a recent study published in JAMA Neurology. Researchers from the Research Area in Neurological Diseases, Neuroscience, and Mental Health at the Sant Pau Research Institute, led by Dr. Juan Fortea, Director Sof the Memory Unit at the Neurology Department of the same hospital, participated in the study. These results pave the way for diagnosing Alzheimer’s disease through a blood test.

A few years ago, the only way to diagnose this neurodegenerative disease was through post-mortem brain samples. Subsequently, effective biomarkers were found for identification in cerebrospinal fluid. Now, research is focused on discovering blood biomarkers for less invasive diagnostic methods, as explained by Dr. Daniel Alcolea, researcher at the Dementia Neurobiology Group at the Sant Pau Research Institute and head of the biomarkers platform at the Memory Unit of the same hospital.

The researchers analyzed data from three observational cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) in Canada, the Wisconsin Registry for Alzheimer’s Prevention (WRAP) in the United States, and the Sant Pau Initiative on Neurodegeneration (SPIN) in Barcelona. The study involved samples from a total of 786 participants with an average age of 66.3 years, analyzed in Sweden, revealing an excellent accuracy of around 95% for detecting the presence of Alzheimer’s disease.

The results show that the p-tau217 biomarker offers precision comparable to cerebrospinal fluid biomarkers and proves to be particularly effective in detecting longitudinal changes, even in preclinical stages of the disease. An outstanding aspect of this technique is its ability to significantly reduce the need for additional confirmations, decreasing the number of tests required to confirm the diagnosis of the disease by 80%.

Dr. Alcolea explains that “this biomarker has shown very high performance in detecting Alzheimer’s in blood, with an accuracy between 90 and 95%. Of all the biomarkers currently being studied for diagnosing Alzheimer’s disease, this one has shown the best results.”

This discovery may open new avenues in the research and treatment of Alzheimer’s disease, offering an accessible and reliable tool for the medical community and patients. Dr. Alberto Lleó, researcher at the Dementia Neurobiology Group at the Sant Pau Research Institute and Director of the Neurology Department at the same hospital, explains that “this advance is particularly significant, as blood biomarkers could provide a more accessible and less invasive alternative for early diagnosis and monitoring of Alzheimer’s disease. Additionally, implementing this type of test could significantly improve clinical assessment and recruitment for clinical trials, as well as facilitate patient management and provide timely access to disease-modifying therapies.”

Reference article:

• Ashton NJ, Brum WS, Di Molfetta G, et al. Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology. JAMA Neurol. Published online January 22, 2024. doi:10.1001/jamaneurol.2023.5319

This week, the research support platforms of the Sant Pau Research Institute opened their doors to researchers and management staff in an initiative aimed at fostering collaboration and promoting the dissemination of the services they offer.

The main objectives of the platforms include facilitating access to high-level techniques and technologies that may not be accessible to individual groups and providing services at a reduced cost for the optimization of both human and equipment resources, as well as providing support to researchers with optimized workflows and methods.

During the visiting sessions, participants had the opportunity to familiarize themselves with the facilities and address questions with the expert and specialized staff of each platform.

Furthermore, technical and methodological advice was provided to the professionals who attended the visits, allowing them to closely explore the various resources offered by the platforms to successfully carry out their projects.

This initiative not only enabled direct interaction with the research infrastructure but also fostered the creation of an environment conducive to collaboration among members of the scientific community and closer engagement with all management staff at the Research Institute.

Sant Pau currently has eleven research support platforms:

• Genomics and Transcriptomics Platform
• Bioinformatics Platform
• Cytometry Platform
• Microscopy Platform
• Biobank and Immunohistochemistry Platform
• Cell culture service
• White Room Platform
• Proteomics Platform
• Radioactive Facility
• Common equipment
• Animal Experimentation Service

Sant Pau continues to lead in the treatment of pharmacoresistant schizophrenia with deep brain stimulation (DBS) worldwide. After performing the first intervention of this kind in 2014 and publishing a pioneering study in 2020, the hospital is now launching a second scientific study with a group of 6 new patients to analyze the long-term effects of DBS and expand therapeutic targets in the brain. This will further personalize the surgery, which is minimally invasive but extremely complex. Thus, Sant Pau is the hospital with the highest number of pharmacoresistant schizophrenia patients treated with DBS and monitored for an extended period.

“In 30% of cases, schizophrenia is resistant, and of this percentage, 60% do not respond to the last line of treatment. These patients still experience delusions and hallucinations… they are very isolated individuals with many health problems, at a higher risk of drug or alcohol consumption, and suicide… often precisely to alleviate these symptoms,” explains the principal investigator of the study, Dr. Iluminada Corripio, from the Neurological Diseases, Neuroscience, and Mental Health Group at the Sant Pau Research Institute and director of the Psychiatry and Mental Health Service at the Vic Hospital Consortium.

She adds, “Having reached the end of the road in terms of pharmacological treatment, we have decided to apply DBS in these patients, where we have all the experience of the Neurosurgery team, which has already successfully applied it in Parkinson’s, major depression, Huntington’s disease, and also in schizophrenia, publishing in 2020 the results of the first study carried out in the world in this field.”

The first pilot study was conducted on 8 patients with pharmacoresistant schizophrenia to evaluate the clinical response of DBS. According to the results, clinical improvement occurred in half of the patients, and in 2 of them, delusions and auditory hallucinations practically disappeared. According to Dr. Corripio, “the new study is a natural continuation of this first project but incorporates all the scientific improvements in terms of technique, knowledge of the pathology… and also in personalization, carefully choosing the location of the electrodes.”

More brain targets in each patient in a very complex and minimally invasive intervention

A key innovation in this new study is the increase in the number of therapeutic targets in each patient. Dr. Rodrigo Rodríguez, coordinator of the Functional Neurosurgery Unit and deputy of the Neurosurgery Service at Sant Pau, explains that “we have tried to further personalize the treatment, using longer electrodes than usual with the ability to include two different therapeutic targets in their trajectory, meaning they can act on two different brain networks of the limbic system, which controls the behavior of these patients. If one therapeutic target is not sufficiently effective, we can use the other and improve the results for the patient. We can stimulate each target independently or stimulate both simultaneously depending on each patient’s case.”

The intervention is very minimally invasive but involves highly complex surgery from a technological perspective. “The precision in placing the electrodes must be millimetric,” says Dr. Rodríguez, “and requires a detailed and precise preoperative neuroimaging study to determine the cerebral coordinates, the area of the brain network that the electrodes will stimulate, where the multidisciplinary work between psychiatrists and neurosurgeons is fundamental.”

During the intervention, data from the preoperative neuroimaging study, from the magnetic resonance imaging, is transferred to the neuronavigator and merged with an intraoperative CT scan that allows for this millimetric precision in placing the electrodes “using very sophisticated and advanced software.” The surgery, very minimally invasive, involves “making two perforations in the skull to place DBS electrodes that will regulate and neuromodulate the disorder caused by the patient’s motor dysfunction.” Subsequently, the electrodes are connected to small cables that run under the skin and reach a neurostimulator—similar to a small pacemaker—placed in the patient’s chest or abdomen.

This neurostimulator generates electrical impulses or stimulation waves that can be adjusted with an external remote control to observe the desired response. “We can control the intensity of the electrical current—i.e., the amperage—the waveform—which is like the beat produced by the electrode—and the stimulation frequency. This allows us to produce a change in neuronal response in the area that then interacts with the rest of the limbic system circuit.” Dr. Rodríguez notes that “we typically use high frequencies that produce an electrical block of the area, meaning the neuronal transmission in the area.”

Long-term results complemented with an individual recovery plan

Neuromodulation of brain networks with DBS is not immediate. Dr. Rodríguez explains that “the brain operates with electrical discharges, and interaction with the electrodes—with specific frequencies and intensities—can produce stimulation or inhibition of neuronal activity.” DBS in schizophrenia works as an inhibitor, “reducing the activity of that specific brain network, and this interacts with the rest of the brain circuits. As a result, neuromodulation normalizes the structures of the limbic system, and over time, regulates the disease.”

Dr. Alexandra Roldán, from the Psychiatry Service at Sant Pau, who conducted her doctoral thesis with the results of the first project, emphasizes that “based on our previous experience, a minimum of 6 months is needed to see if there is any type of response in patients. We have even seen how patients from the first pilot study who initially did not respond to DBS did so after a year, a year and a half, or even two years because the restructuring of brain circuits is not automatic, does not happen overnight, and requires time.”

Especially during the initial post-intervention stage, close monitoring of patients undergoing DBS is necessary, requiring a comprehensive intervention plan: pharmacological, psychotherapeutic, and rehabilitative in response to the improvement of schizophrenia symptoms.

“These patients need to readjust to daily life, family, and social environment. We provide psychological therapy focused on their social recovery,” explains Dr. Roldán. “They are individuals who have often been isolated at home because they are afraid to go out, feel threatened, and have no social interaction. Sometimes, they even have such severe symptoms that they are institutionalized. And we must carry out individual recovery because despite the significant improvement obtained with DBS, they cannot automatically return to normal life.”

Sant Pau, a global leader in Deep Brain Stimulation

Sant Pau Hospital has been using DBS for 25 years. Initially, in patients with Parkinson’s disease, but currently also in other pathologies such as cluster headache or suicide headache, Huntington’s disease, and major depression.

In October 2022, it applied DBS for the first time in Huntington’s disease, a hereditary, rare, and neurodegenerative neurological disorder where one of the main symptoms is chorea, continuous and uncontrolled movements in various parts of the body (St. Vitus dance). Worldwide, fewer than a hundred patients with this disease have undergone this technique, consolidating the leadership of the Movement Disorders Unit of the Neurology Service at Sant Pau and the Neurosurgery Service in this field.

In 2023, the Mental Health Research Group of the Sant Pau Research Institute published a study in The Journal of Clinical Psychiatry that included the longest follow-up of patients carried out in Europe (for 11 years, from January 2008 to June 2019) in 16 patients with major depression resistant to conventional treatments. The results concluded that DBS of the subcallosal cingulate gyrus can offer significant and lasting benefits to the majority of the studied patients: 75% responded to treatment, and 50% achieved remission, meaning a reduction of symptoms below the threshold considered pathological.

Reference articles

• Iluminada Corripio, Alexandra Roldán, Salvador Sarró, Peter J McKenna, Anna Alonso-Solís, Mireia Rabella, Anna Díaz, Dolors Puigdemont, Víctor Pérez-Solà, Enric Álvarez, Antonio Arévalo, Pedro P Padilla, Jesús M Ruiz-Idiago, Rodrigo Rodríguez, Joan Molet, Edith Pomarol-Clotet, Maria J Portella. Deep brain stimulation in treatment resistant schizophrenia: A pilot randomized cross-over clinical trial. eBioMedicine 2020 Jan: 51: 102568. DOI: 10.1016/j.ebiom.2019.11.029
• Carlo Alemany, Dolors Puigdemont, Ana Martín-Blanco, Rodrigo Rodríguez-Rodríguez, Juan A. Aibar-Durán, Muriel Vicent-Gil, Enric Álvarez, Víctor Pérez, Maria J. Portella, Javier de Diego-Adeliño. Response and Safety Outcomes in Treatment-Resistant Depression After Subcallosal Cingulate Gyrus Deep Brain Stimulation: Long-term Follow-up Study. J Clin Psychiatry 2023;84(0):22m14622 DOI: 10.4088/JCP.22m14622

Once again, the Scientific-Technical Service Platforms (PSCT) of the Sant Pau Research Institute and Sant Pau Hospital have successfully passed the ISO 9001 Quality Management System audit, demonstrating excellence in the provision of their services. The platforms currently included within the scope of certification are:

• Animal Experimentation Service
• Cellular Cultures Service
• Radioactive Installation
• Genomics and Transcriptomics Platform
• Cytometry Platform
• Confocal Microscopy Platform
• Biobank and Immunohistochemistry Platform

One of the objectives for 2024 is to expand the scope of certification to include the Proteomics Platform. Once achieved, IR-HSCSP will have all PSCT certified. In the case of the cleanroom, it holds the certification for Good Manufacturing Practices for Advanced Therapy Medicinal Products (NCF-MTA).

The PSCTs are structures that offer high-value-added services to researchers, both within the IR itself and from other institutions. The main goal of the PSCTs is to facilitate access to high-level techniques and technologies that may not be accessible to individual groups, as well as to provide services at a reduced cost for resource optimization (human resources and equipment). Additionally, the PSCTs provide support to researchers with optimized workflows and methods, advising them on technical and methodological aspects.

The PSCTs have a multidisciplinary team with many years of experience in their fields and possess technology knowledge to ensure the quality of services. They are characterized by their customer orientation and commitment to delivering results in short timelines.

They also facilitate direct contact between the client and the expert to address any doubts or issues that may arise during the experimentation process. The PSCTs can manage the entire process, from the initial sample to the acquisition of final results.

Today, we celebrated the Sant Pau Research Day with genomics and rare diseases taking center stage. The day began with an introduction by Dr. Xavier Prats Monné, president of the board of the Sant Pau Research Institute (IR Sant Pau), who highlighted the talent and excellent work carried out by professionals in this field at Sant Pau.

The overarching theme of this day revolved around the Transversal Program of Genomics and Rare Diseases, emphasizing significant technological and bioinformatic advancements in genomics. These advances have not only positively impacted the diagnosis of rare genetic diseases but have also contributed to identifying risk factors, prognosis, and treatment of more common pathologies.

Dr. Jordi Surrallés, director of IR Sant Pau, took the floor to explain the ongoing actions within the framework of the 2019-2024 strategic plan. In this context, he dedicated heartfelt words to Dr. Josep Torrent Farnell, recently departed, highlighting his contribution as an attending physician at Sant Pau Hospital and as an international reference in the field of rare diseases.

Various experts participated with presentations on relevant topics. Dr. Roser Torra, from the Nephrology research group at IR Sant Pau – Puigvert Foundation, highlighted the use of artificial intelligence for diagnosing hereditary kidney diseases. Also, Dr. Elena Muiño, a “Joan Rodes” researcher in the Pharmacogenomics and Neurovascular Genetics group, spoke about CADASIL, a rare cerebral vascular disease.

Dr. Montse Campmany, head of the Knowledge Management Unit at IR Sant Pau, explained that one of the main objectives of this unit is to enhance excellence in the management of institutional scientific information, complying with established regulations, to contribute to the development of biomedical research and the improvement of health and society’s well-being.

Dr. Leif Hove-Madsen, head of the Rhythm Regulation and Cardiac Contraction group at IR, discussed single nucleotide polymorphisms for personalized treatment of atrial fibrillation. Pharmacogenetics was the focus of Dr. Pau Riera’s intervention, a “Joan Rodes” researcher in the Genetic Diseases group.

On the other hand, Dr. Eduard Gallardo, a researcher in the neuromuscular diseases group and head of the CIBERER group, explained translational research applied to neuromuscular disease, myasthenia gravis.

Dr. Sandra Camino, head of the Genomics and Transcriptomics Platform at IR Sant Pau, spoke about the support they offer to the scientific community, both with specific equipment and genomic techniques.

Dr. Surrallés, this time as head of the DNA Repair Syndromes and Predisposition to Cancer group, explained the importance of genes in the therapies for Fanconi Anemia, a cancer predisposition syndrome.

Dr. Maria Sabater, a “Miguel Servet” researcher in the Complex Diseases Genomics group, highlighted the role of genomic medicine in vascular diseases. Dr. Anna Aulinas, a “Joan Rodés” researcher in the Pituitary Diseases research group, talked about the contribution to improving the diagnosis and treatment of patients with pituitary diseases.

Dr. Israel Fernández-Cadenas, head of the Pharmacogenomics group, explained how genetic studies can help find treatments for complex diseases.

The closing talk was given by Dr. Ángel Carracedo, director of the Galician Public Foundation of Genomic Medicine and President of the External Scientific Committee of IR Sant Pau, who emphasized the importance of personalized medicine and genomics. He also explained the need for biomarkers to stratify and thus achieve effectiveness in rare diseases.

The director of IR, Dr. Surrallés, and the director of Sant Pau Hospital, Dr. Adrià Comella, concluded the event by emphasizing the importance of joint work and coordination between the Research Institute and the Hospital to ensure quality healthcare for all.

During the Day, the exhibition “Research on Rare Diseases, in Photos” was also presented. It consists of a selection of photographs with which CIBERER researchers participated in the rare diseases photography contests in 2021 and 2022.

A study led by Dr. José Martínez-González, a researcher at Sant Pau Research Institute and the Biomedical Research Institute of Barcelona (IIBB-CSIC), and Dr. Cristina Rodríguez, head of the Cardiovascular Remodeling Regulatory Mechanisms group at IR Sant Pau, has identified lysyl oxidase (LOX) as a key component in cardiovascular calcification.

The study resulted from the collaboration of both researchers in the cardiovascular diseases field of the CIBER (CIBERCV) with researchers from CIBERCV at the Vall d’Hebron Hospital Research Institute (VHIR). Published in the Biomed Pharmacother journal, the research has demonstrated that the enzyme lysyl oxidase, which plays a fundamental role in determining the biomechanical properties of the extracellular matrix, has a significant role in the formation of mineral deposits in diseases such as aortic valve calcification and atherosclerosis.

“We have characterized how the alteration of the matrix induced by lysyl oxidase affects the development of valvular calcification, as well as the involvement of this enzyme in the development of atherosclerosis and calcification,” said Dr. Martínez-González.

The studies were conducted in two cohorts of patients with calcified aortic valve disease from Sant Pau Hospital and the University Hospital of Navarra. Analyses were performed on valve cells in culture and in an animal model that overexpresses human lysyl oxidase specifically in the vascular wall, inducing atherosclerosis and calcification. The research involved Dr. Antonio Rodríguez-Sinovas, a CIBERCV researcher at VHIR, and Dr. Natalia López-Andrés from NavarraBiomed.

“The results highlight the active contribution of lysyl oxidase in cardiovascular calcification and the importance of matrix remodeling, which acts as an anchor that promotes and guides the growth of calcium crystals in this disease,” explains Dr. Rodríguez.

“Cardiovascular calcification is a significant global health problem and an independent predictor of adverse cardiovascular events and mortality. Currently, there are no drugs available that can limit the development of this disease. This study suggests that treatment strategies targeting lysyl oxidase and matrix modification could be useful for its treatment,” concludes Dr. Carme Ballester, the first author of this work.

Reference article

Carme Ballester-Servera, Judith Alonso, Laia Cañes, Paula Vázquez-Sufuentes, Lídia Puertas-Umbert, Amaya Fernández-Celis, Manel Taurón, Antonio Rodríguez-Sinovas, Natalia López-Andrés, Cristina Rodríguez, José Martínez-González, Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease, Biomedicine & Pharmacotherapy, Volume 167, 2023, 115469, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2023.115469.

Dr. Silvia Vidal, head of the Inflammatory Diseases group at the Sant Pau Research Institute, participated in the “Immunotherapy & Hemopathies 2023” course, where she spoke about the immunological mechanisms at play when treating patients with multiple myeloma using anti-CD38 antibodies.

The researcher explained that anti-CD38 antibodies, such as daratumumab and isatuximab, can bind to the CD38 protein on cancer cells. This interaction triggers a cascade of responses, including the destruction of cancer cells, modulation of the immune system activity, induction of programmed cell death in myeloma cells, and inhibition of CD38 enzymatic functions that reduce the production of the immunosuppressive molecule adenosine. The synergy of these mechanisms, often used in combination with other therapies, represents a significant advancement in the treatment of multiple myeloma, providing a targeted and effective approach.

Dr. David Ramos Vicente has been awarded the Extraordinary Doctorate Prize granted by the Autonomous University of Barcelona (UAB), based on the proposal of the Academic Committee of the Doctoral Program in Neuroscience, for his thesis entitled “Glutamate as a neurotransmitter: revealing the complexity of its evolution and diversity in the nervous system.”

This research, supervised by Dr. Àlex Bayés, head of the Molecular Physiology of Synapses group at the Sant Pau Research Institute, focuses on glutamate, the main excitatory neurotransmitter in the nervous system of living beings, and its crucial role in the functioning of the nervous system and cognitive function. The research, conducted during his work at Sant Pau, explores in detail the proteins involved in glutamatergic neurotransmission, especially glutamate receptors and their auxiliary subunits, which play an essential role in regulating brain function.

One of the most noteworthy findings of Dr. Ramos’s thesis is the redefinition of the classification of glutamate receptors, currently divided into six classes. The work proposes a more precise classification into 4 subfamilies encompassing 10 classes, providing a new perspective on the complexity of these receptors in the evolution of metazoans. This redefinition has significant implications for understanding how the nervous system has evolved and shaped cognitive function.

This week, the Sant Pau Research Institute celebrated the Innovation Day, an event that marked the successful closure of the INNOPAU program. This program, designed to drive innovation at the Sant Pau Campus, has provided support and guidance to professionals in transforming innovative ideas into tangible projects with potential impact on society.

INNOPAU is an intensive six-month program that covers four fundamental modules. In the first module, the definition of the clinical need takes place, with the validation of key opinions from professionals (KOL) and the analysis of epidemiological data. Additionally, user profiling and the associated value proposition are developed. In the second module, resource identification is carried out through a planned route to scientifically validate the proposal, aligned with regulatory and budgetary requirements, as well as the identification of relevant stakeholders.

In the third module, the definition of intellectual property rights (IPR) and the development of a market strategy are carried out, updating the roadmap with strategies to secure IPR and business models. Finally, in the fourth module, the focus is on obtaining competitive funding, with the presentation of scientific results through Pitch Presentations and the use of grant application forms specific to INNOPAU.

This comprehensive program offers a unique opportunity for professionals at the Sant Pau Campus to transform their innovative ideas into projects with significant impact. Each module includes initial sessions, individual tutoring, training, and seminars with experts, culminating in deliverables. All participants had the opportunity to apply for the INNOPAU scholarship, awarded upon completion of the program, thanks to a €50,000 grant from the Private Foundation of the Hospital de la Santa Creu i Sant Pau.

INNOVATION AND NETWORKING

The Innovation Day brought together more than 130 people, with equal participation from private sector companies and professionals from the Sant Pau Campus. Prominent companies in the R&D&I ecosystem, such as CINFA and AMBIT-BST, sponsored the event.

The day’s program included presentations on the INNOPAU program, a roundtable on translational research and entering the healthcare system, as well as presentations and the awarding of grants to incubated projects.

In the roundtable, participants shared meaningful reflections on the importance of innovation in the health field. Gemma Vilahur, researcher in the Molecular Pathology and Therapeutics Research Group of Atherothrombotic and Ischemic Diseases at the Sant Pau Research Institute, emphasized the moral responsibility of creating a spin-off to improve human health and highlighted the benefits of establishing patents, emphasizing the creation of a multidisciplinary environment that provides support in areas such as marketing, legal advice, and business. She expressed gratitude for the support from the hospital’s Technology Transfer department to ensure that innovations reach patients.

Patricia Pesudo, Director of the Strategy and Transformation Area at Sant Pau, underscored the importance of sharing challenges and solutions, encouraging public-private collaboration and alliance to co-create positive solutions.

Antonio Herce, associated with Inveready, highlighted the need for calls that drive innovation, advocating for increased public funding for concept tests that help researchers advance to the next level.

During her intervention, Claudia Ben Dov, Head of Business Strategy for Medical Devices at AMBIT-BST, emphasized that it is not only necessary to generate funds but also crucial to streamline bureaucratic processes from the administration to accelerate the arrival of innovation to patients. Her statements highlight the importance of removing obstacles to facilitate the path of innovation for the benefit of the patient.

The event concluded with the intervention of Laia Arnal, General Director of Transfer and Knowledge Society of the Government of Catalonia, who presented the INNOPAU grant to the winning project team. Arnal highlighted the need for programs like INNOPAU to foster an innovative culture and generate competitive projects that address unmet medical needs. She emphasized the importance of working with a research center and a tertiary hospital like the Sant Pau Campus, ensuring robust clinical validation and scientific excellence.

With the success of the Innovation Day, the Sant Pau Research Institute continues to establish itself as a benchmark in promoting innovation in the field of health.

La Marató de TV3 Foundation will fund 8 cardiovascular health projects coordinated from the Sant Pau Research Institute, thanks to the funds raised in the last edition, which was specifically dedicated to these diseases. In total, Sant Pau will receive €2,296,961.25, which will be allocated to leading projects on diseases such as myocardial infarction, stroke, atherosclerosis, hypercholesterolemia, or arrhythmias, some of them in collaboration with other research centers. Additionally, researchers from Sant Pau are also involved in two selected projects coordinated from other centers.

Sant Pau is the leading center in the number of projects funded in the 2022 edition of La Marató de 3Cat. In total, 11.2 million euros were raised, which will be allocated to 71 research teams to carry out 37 projects in cardiovascular health to advance in the prevention, diagnosis, and treatment of diseases that are the leading cause of death in developed countries. Of the total selected projects, 15 are individual and 22 are coordinated between two or more research institutions.

Cardiology at Sant Pau

Sant Pau is a hospital that has made history in Medicine, particularly in Cardiology, which has always been at the center of its interest. In fact, research on cardiovascular diseases is one of the 5 strategic areas of the Research Institute and is one of the clearest examples of translational medicine, as it aims to address questions and needs that arise directly from the patient’s bedside. The goal is for findings, from preclinical genetic studies in cellular and animal models to advanced clinical research, to return in the form of answers to the patient’s bedside.

Sant Pau has witnessed the development of cardiology: it was the first hospital in Spain to perform a heart transplant and continues to be an advanced reference in research in this medical specialty, constantly developing new therapeutic procedures, advancing in the understanding of basic cardiology, and continually improving the care of cardiac patients.

“We are very pleased and grateful to La Marató,” says Dr. Jordi Surrallés, director of the Sant Pau Research Institute, highlighting the positive results of this year’s call and expressing his commitment to continue promoting research in this field. “In the coming years, we will work hard to invest these resources obtained thanks to La Marató to promote the pursuit of excellence and quality that characterizes us.”

One key to success is Sant Pau’s strategic commitment to promoting translational research: the incorporation of clinicians and basic researchers in strategic areas, such as cardiovascular, working together to provide the best solutions to patients as soon as possible.

• Impact of the molecular and functional composition of lipoproteins and inflammation on the clinical presentation of cardiovascular events in familial hypercholesterolemia (LipoComp).
  • Teresa Padró, head of the Biomarkers Research Group for the Evolution of Cardiovascular Disease at the Sant Pau Research Institute.

• Innovative Therapies based on HDL Nanoconstructions: the Power of Bioengineering to Protect the Infarcted Heart.
  

• Gemma Vilahur,  researcher in the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases Research Group at the Sant Pau Research Institute.

Acute myocardial infarction is a common cardiac pathology that often leads to heart failure and represents a significant burden on healthcare systems and associated costs. This project focuses on the use of high-density lipoproteins (HDL) modified through bioengineering to reduce cardiac damage and promote healing in cases of myocardial infarction. Through the identification of key constituents of HDL and the creation of HDL nanoconstructions, this innovative therapy aims to enhance cardiovascular protection.

• Early Repair of Endothelial Cell Damage to Promote Cardiovascular Health: Interaction between Endothelial Cells and Monocytes as a Key Strategy in Ischemic Diseases.
  • Gemma Arderiu, researcher in the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases Research Group at the Sant Pau Research Institute.

The project focuses on the body’s ability to detect and repair tissue damage, especially in endothelial cells of the cardiovascular system, which play a crucial role in detecting and correcting anomalies. The study concentrates on “patrolling” monocytes that, similar to immunotherapy in oncological research, could promote repair instead of eliminating damaged endothelial cells. This could improve endothelial health and prevent cardiovascular diseases such as peripheral arterial disease, myocardial infarction, and stroke.

• Electroporation in Cardiac Tissue: From Safe and Efficient Ablation of Cardiac Arrhythmias to New Therapeutic Indications. 
  • Jose Mª Guerra,  head of the Clinical and Translational Cardiology Research Group at the Sant Pau Research Institute and member of the Arrhythmia Unit in the Cardiology Department at Sant Pau Hospital.

The project focuses on the study of an innovative technique for the treatment of cardiac arrhythmias called pulsed field ablation (PFA), which uses high-intensity electrical pulses. This technique induces a local biological phenomenon in the tissue called electroporation, leading to the elimination of the arrhythmic substrate. The challenge lies in distinguishing between areas of irreversible electroporation and reversible electroporation around the treated area, as the latter may lead to an overestimation of properly treated areas. The project aims to understand these differences and develop precise detection methods. Additionally, the transient narrowing of coronary arteries during PFA application is addressed by exploring strategies to prevent it. Finally, the use of reversible electroporation in cardiac tissue is considered as a possible way to administer active compounds and personalized treatments. The research is based on a multidisciplinary approach and seeks to improve the effectiveness and safety of PFA in the treatment of arrhythmias.

• Stopped-Stroke. Reversible Epigenetic Therapies to HALT Biological Aging and Reduce the Risk of Stroke.
  • Israel Fernández Cadenas, cap del grup de Recerca en Farmacogenòmica i Genètica Neurovascular de l’Institut de Recerca Sant Pau.

In an effort to combat stroke, one of the leading causes of death and disability in adults, this innovative project focuses on epigenetics as a key element. With the aim of improving stroke prevention and treatment, the research team investigates how epigenetic changes can influence risk factors and the progression of the pathology. This opens the door to potential medications, including “Epidrugs” or epigenetic drugs, for the prevention and treatment of strokes. This approach could have a direct impact on patients and individuals with stroke risk factors.

• Gen-X: Genetic and Epigenetic Study of Ischemic Stroke and Its Sex Differences.
  • Jara Carcel, researcher in the Pharmacogenomics and Neurovascular Genetics Research Group at the Sant Pau Research Institute.

This project aims to investigate the genetic complexity of ischemic stroke in the Spanish population to identify differential genetic risk factors between men and women based on the etiology of the stroke they have experienced. Through various methods, such as genome-wide association studies and epigenomic association studies, the project aims to identify new drugs and pharmacological targets that could be useful for stroke prevention and risk stratification in patients.

• IDEA: Improvement of Diagnostic Efficiency in Patients with Abdominal Aortic Aneurysm.
  • Maria Sabater,  Miguel Servet researcher in the Genomics of Complex Diseases Research Group at the Sant Pau Research Institute.

Abdominal aortic aneurysm is a pathological dilation of the aorta, which is generally silent and can eventually rupture. The mortality rate in case of rupture is very high. This innovative project collects clinical, personal, genetic, and blood marker data from patients with this disease to develop a predictive tool capable of identifying patients at high risk of aneurysm rupture. Additionally, the project explores the effect of new drugs on aneurysm growth, impacting both prediction and disease prevention.

• Cerebral Lipid Homeostasis in Ischemic Stroke: Role of Lipoprotein Receptors and Pharmacological Interventions. 
  • Maria Borrell, researcher in the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases Research Group at the Sant Pau Research Institute.

A study published in Translational Research reveals that the nuclear receptor NOR-1 plays a key role in regulating the calcification of aortic valves and calcification associated with atherosclerosis. The work was led by José Martínez-González, a researcher at the Institute of Biomedical Research of Barcelona (IIBB-CSIC) and the Sant Pau Research Institute, and Cristina Rodríguez Sinovas, a researcher at the Sant Pau Research Institute, both affiliated with the cardiovascular diseases area of CIBER (CIBERCV). The CIBERCV team led by Francisco Marín from the Virgen de la Arrixaca University Clinical Hospital also collaborated.

“So far, we knew about NOR-1’s role in cardiac and blood vessel remodeling, but its connection to calcification in these tissues had not been established,” explains Dr. Martínez-González.

The study conducted analyses on human aortic valves and vascular cells, as well as on a genetically modified mouse model with elevated NOR-1 levels in the vascular wall. These mice showed a reduction in atherosclerosis development, lower vascular expression of osteogenic markers, and specifically, reduced vascular calcification.

“NOR-1 limits cardiovascular calcification, a complex, partially characterized process that poses a significant public health problem. Our analyses of human samples from aortic valves and calcified atherosclerotic lesions, studies on valve and vascular cells, and in vivo strategies demonstrate NOR-1’s involvement in regulating the complex network of genes contributing to cardiovascular calcification,” notes Dr. Rodríguez Sinovas.

The research team observed that cells responsible for calcium deposition in aortic valves and smooth muscle cells in arteries increase NOR-1 levels when calcification is induced. “When we increased or decreased NOR-1 levels in these cells, we saw significant changes in genes related to calcification.”

Until recently, vascular calcification was considered a passive and degenerative process associated with advanced age, atherosclerosis, various metabolic disorders like diabetes mellitus, or rare genetic diseases. However, in recent years, vascular calcification is viewed as an active and regulated process similar to bone mineralization and metabolism.

“Our data indicate that NOR-1 has a negative effect on the expression of genes related to calcification in both heart valve cells and arterial cells, and it prevents calcification in the cardiovascular system. This could have significant implications for the treatment of cardiovascular diseases,” adds Carme Ballester, the study’s lead author.

“The results enhance our understanding of the processes leading to ectopic mineralization and pave the way for future studies that will create new therapeutic opportunities in the fight against cardiovascular calcification,” concludes the team.

Reference Article

Carme Ballester-Servera, Laia Cañes, Judith Alonso, Lidia Puertas-Umbert, Paula Vázquez-Sufuentes, Manel Taurón, Elena Roselló-Díez, Francisco Marín, Cristina Rodríguez, José Martínez-González. Upregulation of NOR-1 in calcified human vascular tissues: impact on osteogenic differentiation and calcification. Translational Research (2023) – https://www.sciencedirect.com/science/article/pii/S1931524423001445?via%3Dihub

A study published in the journal Nature Communications, led by the National Center for Cardiovascular Research (CNIC) and involving researchers from the Cardiovascular Biochemistry Group at the Sant Pau Research Institute and the Biochemistry Service of the same hospital, has revealed essential information about atrial fibrillation and its impact on heart function.

The research, conducted in porcine models, showed that during the progression of atrial fibrillation, there is a disconnect between electrical and mechanical activity in the atrium of the heart. Furthermore, changes in cardiac cells and an increase in atrial fibrosis were observed, suggesting that this type of arrhythmia leads to profound remodeling of cardiac tissue. It was also found that electromechanical dissociation is an early indicator of atrial remodeling in atrial fibrillation, which could be crucial for clinical prognosis.

One of the authors of the study, Dr. Álvaro García Osuna, a physician in the Biochemistry Service and a researcher in the Cardiovascular Biochemistry Group, explains that “in the clinical part of the study, we measured cardiac troponin, which is the biomarker we normally use for the management of patients with suspected acute coronary syndrome. We were able to demonstrate a relationship between the progression of atrial fibrillation and an increase in cardiac troponin concentration.”

Another researcher in the study is Dr. Jordi Ordoñez-Llanos from the Biochemistry Service of the Hospital de Sant Pau, who played a prominent role in demonstrating that atrial fibrillation causes damage to myocardial cells in animal models. “This work is an example of the necessary collaboration between experimental and clinical research,” emphasize these experts.

Reference article

Enríquez-Vázquez, D., Quintanilla, J.G., García-Escolano, A. et al. Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value. Nat Commun 14, 4613 (2023). https://doi.org/10.1038/s41467-023-40196-y

El Congrés ESMO 2023, la trobada científica europea de referència en oncologia ha estat escenari d’una destacada participació dels experts de l’Institut de Recerca Sant Pau.

En aquesta important trobada científica, que s’ha celebrat aquest any a Madrid amb més de 33.000 participants de 144 països, s’han compartit els últims avenços en la recerca oncològica, oferint una formació de la més alta qualitat per als professionals de la salut i brindant oportunitats excepcionals per establir xarxes de contactes entre oncòlegs i altres implicats en aquest àmbit.

Els experts de l’Institut de Recerca Sant Pau han jugat un paper destacat en aquest esdeveniment, presentant diversos resultats i treballs científics, entre els quals destaquen tres estudis presentats a la sessió plenària del congrés i publicats simultàniament a la prestigiosa revista The New England Journal of Medicine. Un d’ells és l’estudi CodeBreak 300, en el qual va participar el Dr. David Paéz López Bravo, del Grup de Recerca en Oncologia Clínica.

En aquest estudi de fase 3, es va investigar l’eficàcia de l’inhibidor KRAS G12C sotorasib combinat amb el panitumumab, un inhibidor del receptor del factor de creixement epidermal (EGFR), en pacients amb càncer colorectal metastàsic quimiorrefractari amb KRAS G12C mutat. Els resultats van mostrar que ambdues dosis de sotorasib combinades amb panitumumab van aconseguir una supervivència lliure de progressió més llarga que el tractament estàndard.

També s’ha presentat en la sessió plenària l’estudi DeLLphi-301, el qual ha participat la Dra. Margarita Majem Tarruella, del Grup de Recerca en Oncologia Clínica, que va avaluar l’activitat antitumoral i la seguretat de tarlatamab, una immunoteràpia de cèl·lules T biespecífica que apunta al lligand delta-like 3 i CD3, en pacients amb càncer de pulmó de cèl.lula petita prèviament tractats. Els resultats mostren quetarlatamab presenta una notable activitat antitumoral amb respostes objectives duradores i resultats de supervivència prometedors en aquests pacients. També es va observar una seguretat manejable, essent la majoria dels efectes adversos de grau 1 o 2.

L’equip de la Dra. Majem també va participar l’estudi PAPILLON, presentat també en una sessió plenària del congrés. Aquest estudi  fase 3 mostra que l’ús d’amivantamab amb quimioteràpia millora significativament la supervivència lliure de progressió en els pacients amb càncer de pulmó no microcític avançat amb insercions en l’exó 20 del receptor del factor de creixement epidèrmic (EGFR), respecte a la quimioteràpia sola com a tractament de primera línia. Els efectes adversos principals d’aquesta teràpia estan relacionats amb problemes hematològics i cutanis i són reversibles.

Participació molt diversa

Per part del Servei d’Oncologia Mèdica de l’Hospital de Sant Pau, la Dra. Alejandra Romano Cardozo va presentar un estudi relatiu a la trombosis i les complicacions secundàries en pacients amb adenocarcinoma ductal de pàncrees i el Dr. Francisco José Pelegrín Mateo, un estudi de trombosi associada a catèter del registre TESEO.

La Dra. Maria Aguado Sorolla va compartir els resultats de l’aplicació de les escales de benefici clínic en fàrmacs aprovats pel tractament de Sarcomes. La Dra. Judit Sanz Beltran va presentar l’impacte del tractament de suport en la qualitat de vida dels pacients hospitalitzats, treball que forma part del projecte Plantology.

A més, el Dr José Antonio González, cirurgià de l’Hospital de la Santa Creu i Sant Pau, va presentar els resultats de l’estudi de fase 1 amb Ceb-01 per Sarcomes Retroperitoneals, un esforç multidisciplinari de tot l’equip de sarcomes.

La Dra. Aida Piedra Cascón va presentar els resultats d’un estudi retrospectiu multicèntric de pacients amb càncer de pulmó no cèl·lula petita avançat amb alta expressió de PD-L1 tractats amb Pembrolizumab en primera línia de tractament i el Dr. Sergio Martínez-Recio va presentar els resultats d’un estudi retrospectiu multicèntric que analitza l’impacte predictiu del temps transcorregut des de la resecció complerta del melanoma fins a l’inici de l’adjuvància amb anti-PD-1.

A més, en una interessant xerrada, la infermera gestora d’immunoteràpia, Jorgina Serra, va compartir coneixements sobre l’educació als pacients amb càncer d’endometri que comencen el tractament.

Finalment, la Dra. Ariadna Tibau Martorell va donar a conèixer els resultats de l’ús de les escales de benefici clínic en els fàrmacs dirigits a diana, realitzat gràcies a una beca de la Fundació Privada de Sant Pau.

Aquesta destacada participació de l’Institut de Recerca Sant Pau a l’ESMO 2023 demostra l’excel·lència de la recerca i la dedicació dels seus experts en la lluita contra el càncer.