A study in which Dr. José Martínez-González, researcher at the Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC) and the IIB-Sant Pau, carried out at the National Cardiovascular Research Center (CNIC), reveals a key factor that protects the heart after a heart attack.

The research, led by Dra. Pilar Martín, head of the Inflammatory Processes Regulatory Molecules Group of the CNIC and published today in the Journal of Clinical Investigation, describes that the expression of the CD69 receptor in regulatory T lymphocytes confers protection after suffering a myocardial infarction, since it acts as a control point for the exacerbated inflammation responsible for heart damage in the medium term.

In addition, the work in which researchers from the Cardiovascular Diseases area of the CIBER (CIBERCV) from the group of Dr. Francisco Sánchez-Madrid at the CNIC and the La Princesa University Hospital have also participated, reveals that expression levels of this CD69 receptor in peripheral blood could predict the development of heart failure, that is, serious sequelae in the functionality of the heart.

Regulatory T lymphocytes, explains Dr. Rafael Blanco-Domínguez, first signatory of the work, “are cells in charge of controlling other elements of the immune system to prevent uncontrolled inflammatory responses from ending up causing unwanted damage”.

The researchers, through the analysis of blood immunologic markers of 283 patients with myocardial infarction, ischemic heart disease and the main cause of death in the world, have discovered that there is an increase in the expression of this receptor CD69 in regulatory T lymphocytes in the first hours after the ischemic event.

Thanks to experiments with mouse models, this team of scientists has revealed that the absence of CD69 leads to an increase in inflammation, cardiac dysfunction and the death rate after a heart attack.

This phenomenon, explains Dra. Martín, “this is because the regulatory T cells that express CD69 are recruited at the site of the infarction and are necessary to inhibit the gamma-delta T cells, which secrete the pro-inflammatory interleukin-17. The presence of CD69 makes the regulatory T cells more efficient in inducing death and inhibiting the secretion of interleukin-17 by means of a novel mechanism independent of specific antigens”.

Research has also shown that a very relevant fact: therapy with regulatory T cells that express CD69 after a heart attack in mice deficient in CD69 is sufficient to compensate for the deficiency of this molecule and thus reduce cardiac inflammation and improve survival.

The follow-up of patients with heart attacks in two independent cohorts, in close collaboration with the Cardiology Services of the University Hospital of La Princesa in Madrid and the Hospital de la Santa Creu i Sant Pau in Barcelona, revealed another very promising result for the clinic.

The levels of expression of CD69 in peripheral blood serve to predict the development of heart failure, that is to say, serious sequelae in the functionality of the heart. In other words, explains Dr. Blanco-Domínguez, those patients with low levels of CD69 in the first hours after a heart attack “had a greater risk of developing heart failure during the first two and a half years after hospital admission”.

The authors conclude that this work reveals a new regulatory mechanism of inflammation after myocardial infarction and opens the door to the development of CD69 as a prognostic and therapeutic candidate for this global cardiac affectation.

This study has had the support of the Ministry of Science and Innovation (MCIN), through the Carlos III Health Institute (ISCIII) – Health Research Fund; Scholarships Community of Madrid; Foundation La Marató TV3; CIBERFES, Human Frontier Science Program; Leducq Transatlantic Networks; Marie Skłodowska-Beca, and support from the University Teacher Training program of the Ministry of Education, Culture and Sports.

Reference article

Blanco-Domínguez … José Martínez-González, Pilar Martín. CD69 expressió on regulador T cells protects from immune damage after myocardial infarction. J Clin Invest. 2022. https://doi.org/10.1172/JCI152418.

“El temps és cervell”, afirma el Dr. Joan Martí-Fàbregas, cap de la Unitat d’Ictus del Servei de Neurologia de Sant Pau. Una frase que va en línia amb el lema del Dia Mundial de l’Ictus d’enguany: Els minuts poden salvar vides, però amb el missatge de que “l’èxit en ictus no només és sobreviure, sinó fer-ho amb qualitat de vida, de manera que els pacients tornin a ser funcionalment independents”.

L’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, té dos grups dedicats a l’estudi de l’ictus: Malaltia Vascular Cerebral i Farmacogenòmica i Genètica Neurovascular.

El primer, dirigit pel Dr. Martí-Fàbregas, lidera estudis en ictus isquèmic:  beneficis i riscos de la trombòlisi intravenosa; beneficis i riscos del tractament endovascular (trombectomia mecànica), maneig de la pressió arterial post-trombectomia, circulació col·lateral en el pacient amb oclusió de gran vas, paper de les estatines en l’ictus isquèmic i hemorràgic; cèl·lules progenitores endotelials en ictus, vulnerabilitat de la placa carotídea ateroscleròtica; monitoratge no invasiu del flux cerebral amb mètodes òptics aplicats. També en hemorràgia intracerebral: prevenció de l’hemorràgia cerebral per anticoagulants; rellevància de l’edema perihematoma, influència de la microbiota, factors associats al creixement de l’hematoma, influència del tipus d’hospital i altres aspectes logístics en els resultats clínics.

El segon, que lidera el Dr. Israel Fernández, es focalitza en estudis genètics i epigenètics de l’ictus, participa en diversos consorcis internacionals i coordina un consorci estatal sobre el mateix tema que engloba el treball d’uns 15 hospitals i centres de recerca de l’Estat. Un dels darrers estudis publicats, en la revista Clinical Epigenetics, ha analitzat possibles canvis epigenètics que expliquin perquè no tots els pacients pateixen les mateixes alteracions neurològiques i la mateixa evolució. El treball conclou que podria ser degut a alteracions en la metilació d’un gen anomenat EXOC4, implicat en el procés conegut com a excitotoxicitat, pel qual les neurones són danyades i destruïdes en l’ictus.

El grup està duent a terme diversos projectes en el vessant farmacogenètic, sobre fàrmacs que s’utilitzen per prevenir l’ictus o per millorar la resposta dels pacients. L’equip està investigant si hi ha factors de risc genètic associats a l’evolució d’aquests pacients després de l’administració d’aquests fàrmacs i d’altra banda s’investiga sobre els factors genètics que predisposen a una resposta als fàrmacs que serveixen per prevenir l’aparició d’altres ictus en el mateix pacient.

Cada minut és important

Per això són cabdals la informació i les campanyes a la població per saber-ne identificar els primers símptomes i sol·licitar atenció mèdica urgent, rebre els tractaments apropiats a la fase aguda, l’ingrés en Unitats d’Ictus amb un equip de professionals multidisciplinari. També cal remarcar que l’ictus es pot prevenir, i tenim mesures per la prevenció primària i també en la prevenció secundària de l’ictus. Tant la prevenció com el tractament de la fase aguda són d’especial importància donat que l’ictus és la primera causa de discapacitat i la segona de mort.

Cal considerar l’ictus com una emergència mèdica tractable. “Quant més aviat arriba el pacient a l’Hospital, més podem fer per ell. Hem de poder revertir el procés i evitar possibles seqüeles per assolir una màxima capacitat de recuperació, és a dir, que el pacient torni a fer tot el que feia abans a nivell laboral, social, personal… Sobreviure no és un èxit, sí fer-ho amb qualitat de vida. Per això la població, des del mateix malalt fins a la seva família, els companys de feina… tothom ha de saber identificar els símptomes de sospita d’ictus”, segons el Dr. Martí-Fàbregas.

“El millor tractament aplicable per a tots els malalts és l’ingrés en una Unitat d’Ictus, com la que tenim a Sant Pau, igual que els malalts amb infart agut de miocardi ingressen en una Unitat Coronària. Està demostrat que això serveix per canviar l’evolució dels malalts”. A més, l’Hospital té una Comissió Multidisciplinària de l’Ictus, de manera que els professionals dels diferents Serveis i àmbits de tractament avaluen els casos un a un i proposen accions de millora que més tard es posen en pràctica en casos reals. Això ha permès avenços en la rapidesa d’administració de tractaments, esdevenint un dels hospitals amb millor temps de resposta i resultats clínics i un protocol compartit de derivació de pacients procedents del Sistema de Salut d’Andorra.

El Dr. Martí-Fàbregas destaca que “un element clau en l’abordatge de l’ictus és el treball multidisciplinari i coordinat entre els professionals” de Neurologia, Urgències, Anestèsia, Neuroradiologia, Radiologia Intervencionista, Infermeria quirúrgica, Infermeria d’Urgències, Fisioteràpia i Rehabilitació, Logopèdia, trasllat, i l’estreta col·laboració amb el Servei d’Emergències Mèdiques de Catalunya (SEM).

Sant Pau també participa en el Codi Ictus, el protocol d’actuació urgent del Sistema de Salut Públic de Catalunya que comprèn una xarxa de dispositius assistencials per donar una atenció immediata i adequada als pacients amb sospita d’ictus. Hi participen 29 hospitals.

Prevenció primària, però també secundària

L’ictus és el resultat d’una alteració de la circulació de la sang al cervell. Es classifiquen en ictus isquèmic (quan és degut a una obstrucció arterial i l’arribada de la sang a una zona del cervell s’altera i provoca que les cèl·lules cerebrals de l’àrea afectada morin per manca d’irri­gació sanguínia), i ictus hemorràgics (quan es trenca una artèria i s’acumula la sang en forma d’un hematoma a l’interior del cervell).

Es calcula que 1 de cada 6 persones tindrà un ictus en algun moment de la seva vida. Aquesta malaltia és més freqüent en homes, però més mortal en dones – en elles és la primera causa de mort per sobre dels 65 anys i, en ells, la tercera per sobre dels 75 anys.

A l’hora de prevenir-lo, hi ha una sèrie de factors no modificables, com l’edat i la genètica, per exemple, però també n’hi ha d’altres que podem canviar, com la hipertensió arterial, la diabetis, el sedentarisme, l’augment de colesterol, l’obesitat, el tabaquisme… “La feina comença quan donem d’alta els malalts amb ictus i tornen a casa seva, intentar que no tingui un segon episodi”.

Segons el Dr. Martí-Fàbregas, “afortunadament tenim tractaments molt eficaços en la fase aguda, de reperfusió, que tornen a enviar sang al teixit que s’ha quedat sense circulació com a conseqüència de l’ictus. Utilitzem fàrmacs com la trombòlisi intravenosa o altres que administrem de forma endovascular, com la trombectomia mecànica en la fase aguda”.

The Sant Pau Biomedical Research Institute (IIB Sant Pau) hosted the first edition of the ÀGORA BRN 2022 Meeting Point for Research Projects in Respiratory Health, organized by the Barcelona Respiratory Network (BRN) Foundation. The meeting was opened by Dr. Vicente Plaza, president of the BRN Foundation and director of the Pneumology and Allergy Department; and Dr. Jordi Surallés, director of the Sant Pau Research Institute. Mrs. Montserrat Llavayol, Deputy Director General of Research and Innovation in Health of the Generalitat de Catalunya, participates in the conference “Investigation in health in Catalonia. Present and future”.

ÀGORA BRN 2022 awards the 5 best posters, 2 of which are from Sant Pau professionals. The first, “Project CASSANDRA (Cancer Screening Smoking Cessation and Respiratory Assessment)”, is by Dr. Juan Carlos Trujillo, clinical head of the Thoracic Surgery Department. And, the second, “Electronic biopsy of lung tissue in-vivo based on electrical impedance spectroscopy”, by Dra. Virginia Pajares, deputy of the Bronchoscopy Unit of the Pulmonology and Allergy Service.

It has also given the RECERCAD’OR Award to Dr. Josep Maria Antó, director of the Environmental Epidemiology Research Center (CREAL) and of the Biomedical Research Network of the Center of Epidemiology and Public Health (CIBERESP) and professor of Medicine at Pompeu Fabra University (for his track record of excellence) and the RECERCADOC Award to Dr. Clara Martín Ontiyuelo, from the Pneumology Service of the Hospital del Mar (as a young researcher and with the best thesis published in the last two years).

The clinical profiles of the post-COVID syndrome, that is, of the sequelae left by this disease after suffering it, are different depending on whether the patients have required hospital admission, if they have been in the ICU or if they have had the disease at home .

According to the results of a study led by Dr. Rosa Güell, a researcher at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and an expert in pulmonary rehabilitation, the patients who presented a more severe disease, that is, those who needed to go through the Intensive Care Unit, have a greater loss of muscle strength -especially of the lungs- and their effort capacity is lower compared to less severe patients. On the other hand, patients who were not admitted to the ICU presented more emotional sequelae and anxiety.

“Surprisingly, we have found that non-admitted patients, and even those admitted to the hospital but nor at the ICU, are worse from an emotional point of view. In other words, they have much more anxiety and depression compared to those admitted to the ICU”, details Dr. Güell.

“We do not know the explanation. Our hypothesis is that ICU patients received a lot of support from the beginning: from the physical therapist, from the medical team, from the nursing staff. Everyone was very attentive to them. So, it is very likely that they have had the feeling of accompaniment, in addition to the psychological effect of having overcome something very serious. This fact may have helped them reduce anxiety while those who have been in the room or at home may have felt more alone”, adds Dr. Güell.

Retrospective study

The article, published in the prestigious journal PLoS One, retrospectively compares the different symptom patterns in relation to the severity of acute COVID-19 in patients seen in the Post-COVID Rehabilitation Unit of the Hospital de Sant Pau.

The researchers studied different measures of respiratory, muscular, cognitive, emotional, and health-related quality of life in three groups of post-COVID patients: those who had not required hospitalization for the acute illness, those who had been admitted to a general hospital, and those who had been admitted to the ICU.

Specifically, the data of 178 post-COVID patients (91 admitted to the ICU, 60 on the ward and 27 who had not required admission) on their first visit to the Post-COVID Rehabilitation Unit were analyzed. The most frequent symptoms in all groups were fatigue (78.2%) and dyspnea or respiratory distress (75.4%). Muscle strength and exercise capacity were lower than the ICU group. The mental component and the level of anxiety were worse in patients not admitted to the ICU. No differences were found between groups in respiratory pressure, but 30 of 57 patients with a decrease in peak inspiratory pressure had not required mechanical ventilation.

Dr. Güell explains that it’s common for patients to lose muscle strength after being treated with mechanical ventilation for any reason. However, in this case, it has been found that many patients with COVID-19 who had not required mechanical ventilation had respiratory muscle weakness. “This finding makes us think that, possibly, this effect is not only due to muscle rest that favors mechanical ventilation and that there is surely a direct effect of the virus on the lung muscles.”

Reference article

Perrot JC, Segura M, Beranuy M, Gich I, Nadal MJ, Pintor A, Terra J, Ramirez E, Paz LD, Bascuñana H, Plaza V, Güell-Rous MR. Comparison of post-COVID symptoms in patients with different severity profiles of the acute disease visited at a rehabilitation unit. PLoS One. 2022 Sep 16;17(9):e0274520. doi: 10.1371/journal.pone.0274520. PMID: 36112577; PMCID: PMC9481013.

Continuous renal clearance techniques are a fundamental element for the treatment of many patients with acute renal failure associated with hemodynamic instability. To guarantee its proper administration and avoid complications, the work of the nursing staff of the intensive care units is key.

Despite the fact that there is more and more training on this subject aimed at nurses in ICUs, until now there has been no specific book on the subject. That is why Almudena Mateos Dávila, nurse manager of patients in the adult ICU of the Hospital de la Santa Creu i Sant Pau and researcher of the Nursing Care Research Group of the Hospital de la Santa Creu i Sant Pau Research Institute – IIB Sant Pau was given the task of writing the manual Conceptos fundamentales en terapias continuas de depuración renal para enfermeras (Círculo Rojo).

Throughout her professional career, the author has treated patients with many pathologies, but kidney failure has particularly caught her attention. She has specialized in this field as a student and now as a teacher. She coordinates the extracorporeal therapies working group at the Spanish Society of Intensive Nursing and Coronary Units (SEEIUC). She is a teacher of the renal subject in the Master’s Degree in Intensive Nursing at the Escola Universitaria de Infermeria (EUI) of the IIB Sant Pau, Barcelona. She is also a teacher and coordinates various courses, among which is the one on continuous depurative treatment in critical patients, which has completed its tenth edition within the Penélope program, at the Hospital de la Santa Creu i Sant Pau. Currently, she is researching citrate applied to continuous purifying therapies. This work is the subject of her doctoral thesis.

The project “Endometriosis in the first person: participatory research on the experiences and recommendations of women with endometriosis for the improvement of health services”, in which the Gynecology Service of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau has participated , is an innovative pilot that applies citizen science to women’s health within the framework of the European Project H2020 TRANSFORM. Women with endometriosis have been involved in it to delve into their experiences of the disease and their experiences regarding health services.

In the investigation, 20 patients diagnosed with endometriosis participated as co-investigators, having an active role in the data collection phases, in the formulation of recommendations and in the dissemination of the results.

Marta Fonseca has had endometriosis for 18 years, has undergone four surgeries and has participated in the pilot. “The fact of being in this group does not cure, but it helps a lot to share this experience and contribute to these recommendations. Yes, it is a complex disease, but if there are so many women who suffer from it, more attention must be paid to the various areas that endometriosis involves. You have to know that endometriosis exists and have better ways to deal with it with more informed professionals and resources dedicated to research.”

With the results of the research, a policy brief has been written for political decision-makers and health personnel, presenting the recommendations co-created by women for the improvement of health services.

The policy brief was presented yesterday at an event at the Hospital de Sant Pau that was attended by the women participating in the research and Gynecology professionals from the Hospital.

“The pilot and the policy brief aim to give voice and raise awareness about how endometriosis is experienced and its effects on people’s global health, as well as present recommendations to improve diagnostic and health care services.” Diana Reinoso, Project Manager at Science for Change.

The six general recommendations contained in the policy brief are:

1. Increase the degree of knowledge of endometriosis at the health level;

2. Develop strategies to achieve an early diagnosis of endometriosis;

3. Improve the process of transmitting information to patients to increase self-knowledge and contribute to shared decision-making;

4. Define and implement a comprehensive approach model for endometriosis;

5. Improve care for people with endometriosis in health services;

6. Develop more personalized treatment models that take into account the opinion of the patient.

The ultimate goal of the policy brief is to influence public health policies at regional and local level, and specifically, to influence the Endometriosis Care Model of Catalonia, in addition to the new model of innovative approach to the disease in the Hospital of Sant Pau.

Dr. Ramon Rovira, surgical coordinator of the Gynecology and Obstetrics Service of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, in Barcelona, comments that “with the TRANSFORM project we have really put the patient at the center. It has been an opportunity, as a professional, to know first-hand what patients need and a possibility of radical improvement to face changes in the therapeutic approach to this pathology at all levels”.

In addition, he adds that the results of this initiative are “a clear example for new projects in different areas of health that allow a paradigmatic change in patient care, in general. Knowing what the patient needs is one of the obligations of the medical care of the future”.

For Nora Salas Seoane, Head of the Health Area of Science for Change, this pilot project is a clear example of how we can use citizen science, participatory strategies and co-creation in health to incorporate the patient’s experience and transform together with them certain health practices and their healthcare services.

“We are helping to understand women’s health from their perspective and their feelings, taking into account gender barriers in health. This pilot demonstrates that the patient’s experience is key and necessary to improve care services and influence the planning of health policies”, says Salas Seoane.

Dr. Teresa Padró, head of the Research Group on Biomarkers of the evolution of cardiovascular disease at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, has been appointed coordinator of the Coronary Pathophysiology Working Group and microcirculation from the European Society of Cardiology (ESC). She takes over from Prof. Dimitris Tousoulis, from the School of Medicine of the National and Kapodistrian University of Athens, in Greece.

This ESC working group, which includes both basic and clinical researchers, has among its main objectives the promotion of research to advance the integrative understanding of the physiology and pathophysiology of coronary vessels, better understand the mechanisms of prevention, diagnosis and treatment of coronary artery pathology through the promotion and coordination of preclinical and clinical studies.

In addition, its mission is to carry out informative tasks to offer professionals and the general population reliable and contrasted information related to coronary pathophysiology, microcirculation and ischemia. Also promote the participation of the members of this group in all kinds of scientific activities.

Sant Pau has a very active participation in this scientific society. Dr. Gemma Vilahur, from the group of Molecular and Therapeutic Pathology of Atherothrombotic and Ischemic Diseases of the Research Institute of the Hospital de la Santa Creu i Sant Pau, has been the coordinator, for the last two years, of the Working Group on Thrombosis of the ESC.

The scientific committee of the Congress of Neurological Surgeons (CNS) has chosen a study by the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau as the best manuscript of the year 2022 in the area of Neurofunctional and Stereotaxic Surgery. This is a study published in the journal Neurosurgery, whose main authors are Juan Ángel Aibar-Durán, from the Neurosurgery Service, and Francisco Javier de Diego, from the Psychiatry Service of this hospital.

This scientific meeting was held from October 7 to 11 in the city of San Francisco, United States, and is one of the obligatory dates of the specialty that brings together the most outstanding specialists from countries around the world to address scientific news in the field of neurosurgery.

The work, directed by Joan Molet, analyzes the long-term results of deep brain stimulation for the treatment of patients with major depression that did not respond to conventional treatments. In addition, it provides new clues about the mechanisms of action of this type of surgery.

As explained by Dr. Aibar-Durán, at 5 years of follow-up, of the patients with refractory depression included in this study, 80% showed improvement, so it could be concluded that this surgery is clearly effective in some patients.

Currently, deep brain stimulation is approved in some countries for the treatment of some disorders such as dystonia, tremors or Parkinson’s disease.

Sant Pau is the leading center in Spain and one of the main references in the world in this type of surgery and is the only public center in which neuromodulation is offered as an alternative in some selected patients with refractory severe depression. It is currently being tested in other indications as well, such as the treatment of schizophrenia.

Reference article

Aibar-Durán, Juan Ángel MD^*; Rodríguez Rodríguez, Rodrigo MD^*; de Diego Adeliño, Francisco Javier MD, PhD^‡; Portella, María J. MD, PhD^‡; Álvarez-Holzapfel, María Jesús MD^*; Martín Blanco, Ana MD^‡; Puigdemont Campos, Dolors MD^‡; Molet Teixidó, Joan MD, PhD^*. Long-Term Results of Deep Brain Stimulation for Treatment-Resistant Depression: Outcome Analysis and Correlation With Lead Position and Electrical Parameters. Neurosurgery: January 2022 – Volume 90 – Issue 1 – p 72-80 doi: 10.1227/NEU.0000000000001739

The Research Institute of the Hospital de la Santa Creu i Sant Pau, as a CERCA center, is part of the new CERCAGINYS project. It is an access plataform to the different scientific and technical infrastructures of the research institutes and other centers that have this certification.

A total of 196 platforms are available from the 41 CERCA centers that are classified by category and by quality accreditation, among which are those of IR Sant Pau.

The initiative wants to optimize access to these facilities for the entire scientific and technological community, and, especially, it wants to demonstrate the possibility that the private business and industrial sector can also make use of them and be able to access the services of highly technical personnel qualified

This proposal is part of a wider project, linked to the Infrastructure Action Plan funded by the Ministry of Science and Innovation through I-CERCA. The agreement with the Ministry recognizes the existence of a system of centers in Catalonia and opens the door to the future creation of a virtual Singular Scientific and Technical Infrastructure (ICTS).

This research, published in the prestigious journal Nature, analyzed data through genome-wide association studies (GWAS) from more than 100,000 patients who had suffered a stroke and more than one and a half million healthy controls. In addition, it is the first time that a study of these characteristics analyzes different ethnic groups, something that had not been done previously because most of the studies had only included samples of people of European origin. Although genetic risk factors are correlated between different ethnicities, this study has shown that the use of different populations makes it easier to find new genetic risk factors.

An international study, in which the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau has participated, has found 89 genes involved in the risk of developing a stroke, of which 61 had not been previously described. This is the largest and most comprehensive study conducted ever.

Israel Fernández Cadenas, of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, is one of the co-authors of this work and the coordinator of the analysis of the data from the Spanish cohort. He explains that these results provide very important information that is useful not only to predict which people have a high risk of stroke and thus be able to take the necessary preventive measures, but also offers relevant information that contributes to a better understanding of the biological bases of the disease. In addition, these data allow us to propose the use of new therapies through drugs not used until now in stroke.

Until now, it was known that inflammatory or coagulation processes played an important role in stroke. “Now we have seen, for example, that the lipid levels that we thought might be relevant may not be so essential in the development of this disease. Instead, we are seeing that some genes related to other processes, such as arterial hypertension, the formation of blood vessels (angiogenesis), have a more important role in the risk of stroke”, comments Fernández Cadenas.

More than double the data analyzed

Stroke is one of the leading causes of death worldwide. Until now, studies of genetic risk factors for this disease had mainly analyzed samples from people of European origin and the largest study had data from 67,000 patients and 500,000 healthy controls.

In this study, genome-wide association analisis were performed on 1.503,898 participants, including 110.182 stroke patients from five different ancestries with the participation of the International Stroke Genetics Consortium, one of which is the Spanish GeneStroke Consortium and the Spanish cohort GCAT|Genomes for Life.

The researchers identified a total of 89 loci or independent chromosomal regions associated with stroke risk, of which 61 were new. In addition, it was found that a large part of these genetic characteristics were shared by all people, regardless of their origin.

“This finding will be important for medical professionals to identify the risks and the best treatments on the road to predictive and precision medicine,” says Rafael de Cid, scientific director of GCAT| Genomes For Life, IGTP researcher, and co-author of the study.

Therapeutic targets

The researchers further analyzed data from 52.600 people with cardiometabolic disease and showed that the sum of genetic risk factors predicted future risk of stroke, independent of clinical risk factors.

The IIB Sant Pau researcher, Israel Fernández, explains that genetic association studies are very useful tools for research because the data they offer are not biased. “That is, we look at polymorphisms spread throughout the genome without a prior hypothesis. And what we see is that those mutations and those genes that we find are actually associated with the disease that we’re studying.”

This is much more precise the more patients and healthy controls are analyzed, and it is also very important to be able to analyze data from people of different backgrounds and ethnic origins, since some mutations are more common in some regions of the world and otherwise would be needed to analyze much larger samples to be able to find them. “All the genes we found help us to better understand which biological processes are really important in the disease.”

The important thing about knowing better the mechanisms involved in the development of stroke is that not only can new treatments aimed at these processes be sought, but studies can also be carried out with drugs already approved for other diseases that can be used to treat these patients and to make prevention in people who are at high risk due to their genetic characteristics. “And the research process in the case of existing drugs -which is what we call pharmacological repositioning- is much more agile, being easier and faster to reach its application in a patient”, recalls this researcher.

About the GCAT

Led by the Germans Trias i Pujol Research Institute (IGTP), GCAT|Genomes For Life (Cohort Study of the Genomes of Catalonia) is a cohort study of the Catalan population created with the aim of studying genomic, epigenomic and environmental factors in the development of multifactorial chronic diseases. It is a multipurpose cohort of the resident population in Catalonia with 20.000 volunteers from all over Catalonia.

The GCAT cohort has clinical, epidemiological, environmental, genomic and multi-omic data. Since 2018, it has collaborated with the international scientific community by making its access available under the European FAIR guidelines (Guidelines for locatable, accessible, interoperable and reusable data). To date, GCAT has participated in more than 30 projects contributing to remarkable biomedical discoveries (http://www.genomesforlife.com).

 Reference article

Stroke genetics informs drug discovery and risk prediction across ancestries (2022). Aniket Mishra, Rainer Malik, Tsuyoshi Hachiya, Tuuli Jürgenson, Shinichi Namba, Daniel C. Posner, et al. Nature. doi: 10.1038/s41586-022-05165-3

Nanoligent SL, spin-off of the Autonomous University of Barcelona and the Research Institute of the Hospital de Santa Creu i Sant Pau, focuses on developing new drugs for the treatment of more than 20 types of metastatic cancer. His treatment proposal is based on the targeted elimination of cancer cells that overexpress the CXCR4 receptor, a biomarker of poor prognosis and resistance to conventional therapy that is considered key in the processes of metastasis development. The company is developing a new patented nanotechnology platform, with the potential to overcome the limitations of current treatments based on conjugates of cytotoxic drugs with antibodies.

The company has just closed its first round of financing for 2,800,000 euros, which will allow it to encourage the development of multiple drug candidates and advance the preclinical development of its lead candidate in a variety of tumor types.

The latest investment has been provided by i&i Biotech Fund, an early-stage life sciences fund with offices in Luxembourg and Prague that is supported by the European Investment Fund. The new fund joins Nanoligent’s previous investors Italian Angels for Growth and AVANTECA Partners, both of which specialize in supporting innovative early-stage scientific companies.

“Less than a third of newly diagnosed metastatic patients respond to current therapies, making metastasis one of the most pressing unsolved challenges in cancer. With the support of i&i Biotech Fund, together with our existing investors, we will reach our current milestone focused on the selection of the best candidate from our portfolio of therapies aimed at metastasis”, highlights Montserrat Cano, CEO of Nanoligent.

“Nanoligent is the fifth investment of our fund and belongs to a group of targeted oncology therapies in our portfolio. We are very pleased with the uniqueness of its technology. The platform is developed by a team of highly motivated, experienced and fully committed scientists and managers. Their project has great potential to become an effective treatment for multiple types of metastatic cancer”, says Jaromir Zahrádka, managing partner of i&i Biotech Fund.

Two of the previous investors have already joined Nanoligent’s Board of Directors, which currently consists of Michele Marzola (Italian Angels for Growth), Michael Milos (Avanteca Partners), Manuel Rodríguez (president) and Montserrat Cano (secretary).

“We are delighted to welcome the i&i Biotech Fund to Nanoligent. Due to his scientific diligence and professionalism in his management, he will be an important partner for Nanoligent and we are happy to be able to continue investing together”, emphasizes Michele Marzola, from Italian Angels for Growth.

In the other hand, Michael Milos of AVANTECA Partners considers that i&i Biotech “is the right partner for the development of Nanoligent. He has demonstrated deep scientific knowledge, in addition to enjoying a good connection with the pharmaceutical industry. Together, we hope to take Nanoligent’s development plan effectively into the next stages.”

The Research Institute of the Hospital de la Santa Creu i Sant Pau has obtained the ISO 9001:2015 certification follow-up audit for its Scientific-Technical Service Platforms, initially obtained in 2019.

This quality standard is the international standard that regulates quality management systems and is based on the continuous improvement of processes, evidencing an organization’s commitment to service quality and user satisfaction.

The certification includes the technical service provision activities of the Support Platforms in the field of medical research. Specifically for:

– Animal Experiment Service.

– Cell Culture Service.

– Radioactive Installation.

– Genomics and Transcriptomics Platform.

– Cytometry platform.

– Confocal Microscopy Platform.

– Biobank and Immunohistochemistry platform

The certification represents a recognition of the quality of services provided to users that is not only maintained, but continuously improved in the Scientific-Technical Platforms. In addition, it demonstrates the robustness of the Institute’s Integrated Quality Management System.

The certification, achieved and maintained through the joint work of the staff of the Scientific-Technical Services Platforms and the Quality Unit of the IIB Sant Pau, highlights the work and expertise in the provision of services by all professionals who work in this field every day.

The World Health Organization (WHO) proclaimed September 21 World Alzheimer’s Day in 1994 under the auspices of Alzheimer’s Disease International (ADI).

The Sant Pau Biomedical Research Institute (IIB Sant Pau) is one of the most prominent European centers in the diagnosis, treatment and research of this disease and a pioneer in the introduction of early diagnosis through the analysis of patients’ cerebrospinal fluid .

At the moment, the Sant Pau professionals are studying the possibility of obtaining good results in the diagnosis of Alzheimer’s through the proteins found in the blood, facilitating, even more, early diagnosis.

The Group of Neurological Diseases, Neuroscience and Mental Health of the Sant Pau Research Institute is a benchmark in the study of neurological, mental disorders and neurological development. There are several active lines of research working on different disorders such as stroke, neuromuscular diseases, neurodegenerative diseases, schizophrenia, depression or chronic pain.

Some groups work on the genetic basis of neurological diseases, biomarker identification, neuroimaging, neurosurgical methods, deep brain stimulation or omics, while other groups work on pain models, synapse biology or neuropharmacology. In this area, large population cohorts of patients with clinical follow-up are analyzed and numerous clinical trials are carried out. The Hospital also has the only Alzheimer-Down Unit in the entire State, a fact that means opening new paths in the knowledge of the disease.

Dr. Albert Lleó, director of the Neurology Service at Hospital de Sant Pau, and head of the Neurobiology of Dementia Research Group at the Hospital’s Research Institute, explains the moment in which the diagnosis, treatment and Alzheimer’s research in the world.

A study led by Víctor Montal, researcher at the Research Institute of the Hospital de Santa Creu i Sant Pau – IIB Sant Pau and Jorge Sepulcre, of the Massachusetts General Hospital and Harvard Medical School, in Boston (United States ) has described the association between the accumulation of the TAU protein in certain areas of the brain and the overexpression of the APOE and SLC1A2 genes in the same areas. The work has been published in the journal Science Translational Medicine.

The researchers studied the pattern of TAU spread in the brain using PET imaging techniques and studied its association with genetic data using high-resolution transcriptomic techniques. “We observed that there are specific gradients along the TAU propagation network in the brain. Specifically, we have identified 577 genes whose expression is associated with the spatial spread of TAU”, explains Víctor Montal, first signatory of the article.

Of these genes, the most relevant are APOE, which has been associated in multiple studies with Alzheimer’s disease, and SLC1A2, a glutamate transporter gene. “What we observed is that in those regions where TAU began to accumulate initially there were two genes that had much more expression compared to the regions where TAU accumulated later. In other words, the pattern of TAU accumulation was similar to the pattern of expression of these genes”, says Montal.

It has been known for years that the APOE gene is closely related to the accumulation of the beta-amyloid protein “and now several studies are showing that this gene is also closely related to the TAU protein. The function of APOE is to transport lipids in neurons and it is expressed especially in astrocytes”, explains the first author of the study.

“The other gene, SLC1A2, is a glutamate transporter. That is, it takes the neurotransmitter glutamate from the synaptic cleft and brings it into the neuron. This is very interesting because several studies have reported that excitatory neurons are more vulnerable to TAU pathology. In this way, what we have confirmed is that this gene may be responsible for this greater vulnerability in this neuronal group”.

In this sense, “the hyperexcitability of neurons has already been proposed as one of the theories that promote the accumulation of beta-amyloid protein and TAU. Our results support this theory, since those neurons where there is more expression of this glutamatergic recruiting gene are the first to accumulate TAU and to die”, in Montal’s words.

In summary, the researchers’ hypothesis is that both APOE and SLC1A2 may be responsible for promoting a selective vulnerability in some brain regions and specific neuronal populations to accumulate TAU (and not others), leading to the characteristic symptomatology of the disease Alzheimer’s This study helps to better understand the origin and development of the disease.

Therapeutic targets

The results of this work could be useful to search for new therapeutic targets for Alzheimer’s disease and strengthen some existing theories. In fact, some trials with drugs directed against APOE, for example, are already underway in several laboratories around the world.

Another important finding of this study is that it allows predicting the areas of the brain in which the TAU protein will accumulate in the brain at very early stages. This may help to better choose candidates for a given drug, for example, targeting APOE.

Reference article

Montal V, Diez I, Kim CM, Orwig W, Bueichekú E, Gutiérrez-Zúñiga R, Bejanin A, Pegueroles J, Dols-Icardo O, Vannini P, El-Fakhri G, Johnson KA, Sperling RA, Fortea J, Sepulcre J. Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes. Sci Transl Med. 2022 Jul 27;14(655): eabn7273. doi: 1126/scitranslmed.abn7273

Inhibition of miR-148a reduces the progression of atherosclerosis in a “humanized” mouse model. This is the main conclusion reached by a recent investigation led by CIBERDEM by Dr. Noemi Rotllan, researcher of the Physiopathology of Lipid-Related Diseases Group of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau that has just been published in Biomedicine & Pharmacotherapy.

Started at Yale University and completed at the IIB-Sant Pau, “this work has confirmed that anti-miR-148a therapy reduces both the size of the atherosclerotic plaque and vascular inflammation in a “humanized” mouse model such as the APOBTG Apobec-/- Ldlr+/.- mouse”, explains the researcher.

Dr. Rotllan also points out that “the antiatherogenic effect observed is mediated by the anti-inflammatory effects observed in macrophages treated with said therapy and independent of changes in the concentration of LDL and HDL cholesterol”.

The role of miRNAs

miRNAs are molecules capable of regulating the expression of multiple genes involved in multifactorial pathologies such as atherosclerosis, and the use of therapies directed towards these miRNAs is widespread.

The importance of miR-148 in the regulation of lipid metabolism in macrophages, in cholesterol homeostasis and in inflammation was already known, but until now no study had been carried out on the contribution of miR-148a in the progression of the disease. atherosclerosis.

Specifically, prolonged inhibition with LNA 148a resulted in smaller plaques with reduced macrophage content but no change in vascular smooth cell content, and also decreased neutral lipid content in the aortic arch. Furthermore, such plaques were more stable as they had a thicker fibrous cap and smaller necrotic nuclei.

The work also shows that the inhibition of miR-148a in primary murine macrophages increases the expression of anti-inflammatory genes such as Arg1, Retlna and Mrc1, and decreases the expression of proinflammatory markers such as Nos2, Il6, Cox2 and Tnfa.

Thus, the inhibition of miR-148a decreases the inflammatory response of macrophages, polarizing them towards a phenotype known as M2 or antiatherogenic. In addition, they observed a decrease in cholesterol efflux using ApoA1 as acceptor in peritoneal macrophages treated with miR-148a. However, no significant changes in LDL or HDL cholesterol concentration were observed, as described above, although this is probably due to the use of a different mouse model and prolonged therapeutic treatment.

Taken together, these findings highlight the therapeutic potential of miR-148 inhibition to attenuate atherosclerosis progression and promote plaque stabilization, although more experiments with this type of molecule are still required for their possible application in this field.

Reference article

Noemi Rotllan, Xinbo Zhang, Alberto Canfráan-Duque, Leigh Goedeke, Raquel Griñán, Cristina M. Ramírez, Yajaira Suárez, Carlos Fernández-Hernando. “Antagonism of miR-148a attenuates atherosclerosis progression in APOBTGApobec-/-Ldlr+/- mice: A brief report” Biomedicine & Pharmacotherapy, Volume XX https://doi.org/10.1016/j.biopha.2022.113419

Showing the relationship between science and citizenship, social networks put the spotlight on new issues of Covid-19, such as the effects of the vaccine on menstruation. Science picked up on the new approach and showed that the SARS-CoV-2 vaccine could generate alterations in the length or pattern of menstrual cycle bleeding. Now, the analysis of more than 1,800 cycles of 371 users collected by a mobile application has made it possible to carry out a study that shows how vaccination during the luteal phase, i.e. after ovulation, could prevent the increase of the length of the menstrual cycle.

This study has been jointly developed by researchers from the Hospital de Santa Creu i Sant Pau – IIB Sant Pau, the IIIA-CSIC, the University of Geneva, and the Agency for Health Quality and Assessment of Catalonia (AQuAS). It is the result of a joint and multidisciplinary project. In this sense, Dr. Josep Perelló, assistant physician at Sant Pau’s Gynecology and Obstetrics Service, emphasizes that “the Hospital has brought the clinical vision to this work and, within this framework, the idea of stratifying the analysis by cycle phase, which has led to the main conclusion of the study”.

Everything was born following the comments of users on social networks where they highlighted alterations in the menstrual cycle after being vaccinated against COVID-19. Faced with the lack of data, App Lunar, a mobile application for monitoring the menstrual cycle, incorporated a new functionality to voluntarily record the dose, brand and country where the vaccine had been received. Among its users, 371 anonymous profiles were chosen who recorded at least five consecutive menstrual cycles, and who were in the third cycle at the time of vaccination. In total, 1855 cycles were recorded between September 2020 and February 2022.

To analyze the data, the study published in the American Journal of Obstetrics and Gynecology (one of the most relevant publications in its area), was based on the epidemiological method known as Self-Controlled Case Series, where the same person is the one who compares the previous and subsequent cycles at the time of vaccination. Therefore, the variables that were indicated were cycle length, duration of menstrual bleeding and variations in the intensity of bleeding and pain. Finally, a screening of the results was carried out according to the phase of the cycle in which the users had been vaccinated.

By observing that people who had been vaccinated during the follicular phase, i.e. before ovulation, had an average increase in cycle length of one day, while people who had been vaccinated during the luteal phase they did not show any increase. Among users vaccinated in the follicular phase, 11% experienced an increase in the duration of the menstrual cycle of more than 8 days, a clinically significant value.

Faced with these data, the study highlights the importance of the phase of the menstrual cycle at the time of vaccination to minimize the alterations of the said cycle, and concludes that vaccination during the luteal phase would avoid the potential increase in the duration of the cycle menstrual “These results, observed in the different types and brands of vaccines, are part of an important and new topic, on which there is still little evidence. Without the call to attention of so many people who menstruate and who reported these changes, studies like this would not be done”, explains Dr. Josep Perelló, who would like the analysis to be replicated with more data and with other methodologies to confirm the findings.

Dr. Perelló also emphasizes the fact that the message that needs to be conveyed to the population, and to women in particular, is “the importance of getting vaccinated. And inform women that if the vaccine is administered in the first phase of the menstrual cycle, that is, before ovulation, they may experience some type of alteration in their cycle. And that these possible alterations will be specific”.

Reference Article

Borja Velasco-Regulez, Jose L. Fernandez-Marquez, Nerea Luqui, Jesus Cerquides, Josep Lluis Arcos, Analia Fukelman, Josep Perelló. Is the phase of the menstrual cycle relevant when getting the covid-19 vaccine? American Journal of Obstetrics and Gynecology. 2022. ISSN 0002-9378. https://doi.org/10.1016/j.ajog.2022.07.052

Science will be the protagonist this year in the free entry day that the Recinto Modernista de Sant Pau has scheduled for the next September, 24th to celebrate the Fiestas de la Mercè and on the occasion of the 30th anniversary of the Research Institute of the Hospital de la Santa Creu i Sant Pau.

On Saturday September 24th, between 10.00 and 18.30 hours visitors will be able to enjoy for free the greatest work of the modernist architect Lluís Domènech i Montaner and participate in the different proposals and activities to know, first hand, the work the scientists of the San Pau Research Institute do in the five strategic research areas: cardiology, neurology, oncology, epidemiology and translational medicine.

In addition, visitors will be able to enjoy other cultural proposals between 12 and 14 hours, such as a swing dance and also a jam de lied organized in collaboration with the Victoria dels Àngels Foundation, which will be a unique opportunity to discover young people talents of that lyrical genre.

You can also visit the exhibition “Nurses in memory. The invisible force of a profession”, which reviews the history of nursing from the beginning of the 13th century until the creation of the university diploma in 1977.

The Mercè scientific and festive day will also be a great occasion to welcome collaborating entities and companies of the Sant Pau Research Institute, who will be offering their products in a charity market that will be located in the southern gardens of the Recinto Modernista. The brands are:

Pratta Barcelona

Kuali Cosmètics

Costumama

Rös’s Estètica

Mon

Alma infusions 

Fincafe

Baobag

Joidart

And you can also enjoy a tasting of oils from the 5 DOPs of Catalonia:

Empordà

Les Garrigues

Terra Alta

Baix Ebre – Montsià

Siurana

Access to Recinto Modernista will be through the main door of the Administration Pavilion, located at the confluence of Sant Antoni Maria Claret and Cartagena streets.

Science and culture, the two main axes of Sant Pau

The Research Institute of the Hospital de la Santa Creu i Sant Pau celebrates its 30th anniversary this year with a solid and consolidated trajectory. Its main objective is to promote basic, clinical, epidemiological and health services research in the field of health sciences and biomedicine, to contribute to improving the health of the population.

Currently, it is one of the most active Catalan centers in research production, especially in translational research and the integration of new discoveries in healthcare practice.

The Recinto Modernista is today home to nine leading organizations in the fields of education, sustainability, health, innovation and culture. In this way, Sant Pau has become a space where different institutions live together that develop their own programs and activities and undertake shared initiatives.

Free tickets can be requested through the Recinto Modernista de Sant Pau website from Wednesday 14 September.

The Board of Trustees of the Santa Creu i Sant Pau Hospital Research Institute Foundation (IR-Sant Pau) has approved the designation of Mr. Jaume Bacardit as new manager of the institute. He has more than 25 years of experience in the international biomedical research sector and is an expert in finance and economic management. His expertise will be key to facing the institute’s challenges.

Bacardit holds a degree in Economic and Business Sciences from the University of Barcelona and an Executive MBA from the IESE Business School. He studied Project Management and Process Reengineering at the Universitat Politècnica de Catalunya and Organization and Strategic Management at the London School of Economics. He also has a master’s degree in Tax Specialization at the College of Economists of Catalonia.

His professional career has been developed mainly at the Centre for Genomic Regulation (CRG), where he held the position of Head of Finance and Purchases for the last 6 years, from where he led the center’s financial management, including the finances of the Scientific and technical services and the National Center for Genomic Analysis (CNAG). He also contributed to the business development strategy, actively participating in the drafting of the first Strategic Plan and the impetus for the creation of several spin-offs.

Jaume Barcadit takes over from Mrs. Reyes Grases who held the position for the last two years. From the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, we thank Mrs. Reyes Grases his work during this period in which he led a management transformation and worked intensively to promote improvements in various areas of the institution with the aim of improving sustainability and excellence in all areas.

We wish them both much success in their new responsibilities.

The Alzheimer’s Association will finance three projects of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau within the framework of its international research grant program (International Research Grant Program). The winning projects are led by Olivia Belbin, Miguel Ángel Santos and María Carmona.