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.

Alzheimer’s disease has become the leading medical problem in adults with Down syndrome due to the chromosomal alteration and the increase in life expectancy of this population, with a risk of more than 90% of developing dementia throughout their lives

A study led by Juan Fortea and Laura Videla, researchers at the Hospital de la Santa Creu i Sant Pau Research Institute – IIB Sant Pau and the Catalan Down Syndrome Foundation (FCSD) have described the risk of developing the clinical symptoms of Alzheimer’s disease over time and the influence of age from the preclinical phase, as well as the associated progressive cognitive deterioration.

These results, published in the journal JAMA Network Open, reinforce the importance of developing specific health plans and monitoring people with Down syndrome to assess their cognitive performance before the fourth decade of life.

The researchers examined the clinical progression of a cohort of 632 adults with Down syndrome. In the first evaluation, a total of 436 individuals with Down syndrome without clinical symptoms of Alzheimer’s disease, 69 patients with Alzheimer’s disease in the prodromal phase, that is, with cognitive impairment but without functional interference, and 127 with Alzheimer’s disease were included. Alzheimer’s disease.

At 5 years of follow-up, it was found that 17% of all asymptomatic participants had progressed to symptomatic phases of the disease (prodromal or dementia). When studying the influence of age on the asymptomatic phase of Alzheimer’s disease, they found that the progression to symptomatic phases before the age of 40 was practically nil, but that it progressively increased to rates of almost 60% in those over 50 years of age . However, this relationship with age was not observed in the group of patients with prodromal Alzheimer’s disease, who progressed to the stage of dementia regardless of age.

According to Laura Videla, a neuropsychologist at the IIB Sant Pau and the FCSD, among the patients who were in the prodromal phase of the disease at the start of the study, it was found that half of them had progressed to dementia after two years of follow-up and , at 5 years, practically all.

These estimates of the risk of progression are important data to take into account when designing specific health plans for adults with Down syndrome and for the design of clinical trials for Alzheimer’s disease. “These results reinforce the hypothesis that these patients do not deteriorate due to age, but due to Alzheimer’s itself. Now we know that in asymptomatic phases age does matter, but in prodromal phases it really doesn’t.”

Cognitive evolution over time

People with Down syndrome have an underlying intellectual disability that can be mild, moderate, severe, or profound. It is also known that from 35-40 years of age the cognitive performance of these patients begins to decline.

Another conclusion of this study is that both mild and moderate cases have a similar cognitive loss. As detailed by Laura Videla, “what we have seen is that, transversally, at the first visit people with mild intellectual disability score higher than those with moderate intellectual disability, but we wanted to see if the longitudinal cognitive impairment was also greater in one group than in another. And what we saw is that no, that they overlap here. In other words, the group of people with mild intellectual disability and the group of people with moderate intellectual disability lose the same number of points in the neuropsychological tests over time regardless of whether they start from a higher or lower baseline level”.

These findings could also be useful for the design of new clinical trials. For example, “to assess the effect of a certain treatment, it would not be necessary to divide the sample into two groups and, therefore, the sample size could be smaller and, with it, the study more efficient”, concludes the researcher.

Reference article

Videla L, Benejam B, Pegueroles J, et al. Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome. JAMA Netw Open. 2022;5(8):e2225573. doi:10.1001/jamanetworkopen.2022.25573

The Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau has obtained 9 places for the INVESTIGO 2022 Program for the recruitment of young people seeking employment. These grants are intended for carrying out research and innovation activities within the framework of the Recovery, Transformation and Resilience Plan of the Generalitat de Catalunya – AGAUR.

This program makes possible to finance the salary costs for a period between 12 and 24 months of the contracts of a researcher under 30 years old, registered as a job seeker and who has not developed any kind of research activity in the same entity in the previous 6 months.

The beneficiary groups in this call are:

– Dementia Neurobiology Group

– Group of Genomic Instability Syndromes and Predisposition to Cancer

– Molecular and therapeutic pathology group of atherothrombotic and ischemic diseases

– Group of Genomics of complex diseases

– Research group in perinatal and women’s medicine

– Gynecological and peritoneal Oncology Group

– Digestive Pathology Group

– Group of Parkinson’s Disease and other movement disorders

The National Projects Unit of the Sant Pau Research Institute is currently managing other INVESTIGO requests from the Ministry and pending the next calls from the AGAUR in order to strengthen this institution’s commitment to maintain excellence and attract talent.

Dr. Juan Fortea, researcher at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and head of the Memory Unit of the Neurology Service of the same hospital, has been elected coordinator of the Down Syndrome Study Group and Alzheimer from the International Society for the Advancement of Alzheimer’s Research and Treatment (ISTAART).

The announcement has been made public during the International Conference of the Alzheimer’s Association (AAIC2022) which is being held these days in a hybrid, face-to-face and online format. “I’m proud to be able to lead this working group at ISTAART. Networking with other scientists from around the world is essential to strengthen knowledge in this area and to be able to advance, in benefit of our patients”, comments this expert.

Dr. Fortea has a wide experience in dementias and cognitive neurology field. The Memory Unit that he lead in Sant Pau has developed a pioneering plan worldwide for population screening for Alzheimer’s disease in adults with Down syndrome. This unit evaluates one of the world’s largest cohorts of adults with Down syndrome and multimodal studies of Alzheimer’s biomarkers.

The board of directors of the Sant Pau Biomedical Research Institute – IIB Sant Pau has just unanimously appointed Prof. Josep Santaló as research ombudsperson of the IIB Sant Pau, at the proposal of the institute’s management.

The research ombudsperson or ombudsman acts as an independent mediating agent in a suspicion of possible scientific misconduct or professional conflicts. This figure ensures compliance with the Code of Good Research Practices and acts to ensure the integrity of the institution’s research. He will chair and collaborate with the Research Integrity Committee of the IIB Sant Pau (CIR-IIB) and will act as a mediator between the institute’s research staff who detect possible scientific misconduct and any person from the one suspected. This position guarantees independence from other institutional bodies, the confidentiality of the institute’s actions and proven experience in the scientific world.

About Dr. Josep Santaló

Dr. Josep Santaló is Professor of Cell Biology at the Faculty of Biosciences of the Autonomous University of Barcelona, where he teaches Cell Biology, Reproductive Biology and Bioethics. He has been general coordinator of Biology studies, Vice-Dean of the Faculty of Sciences and Vice-Rector for Research at this university.

His research has focused on the genetic characterization and freezing of mammalian preimplantation embryos, with the development of Preimplantation Genetic Diagnosis participating in the pioneering group that established it in Spain, oocyte maturation in vitro, animal production transgenics, nuclear reprogramming and the derivation of embryonic stem cells in mice and humans. He is the author of 123 articles in scientific journals, 72 indexed, 27 book chapters and 13 Bioethics documents. He has participated in 27 funded research projects, 12 of which as principal investigator.

He is a member of the Observatory of Bioethics and Law of the University of Barcelona and of the Ethics Committee for Animal and Human Research and of the Biosecurity Committee of the Autonomous University of Barcelona, which he chaired for more than 10 years, as well as from the Hinxton Group: An International Consortium on Stem Cells, Ethics and Law. He has been the editor of the Code of Good Scientific Practices of the Autonomous University of Barcelona.

He has also been a member of the Advisory Committee of ESHRE (European Society of Human Reproduction and Embryology) and other societies such as ASEBIR (Association for the Study of the Biology of Reproduction), the International Society for Stem Cell Research, la Societat Catalana de Biologia, la Societat Espanyola de Fertilitat i la British Society for the Study of Fertility.

Update of the Code of Good Research Practices of the IIB Sant Pau

The appointment coincides with the update of the “Good Scientific Practices Code” which is now called the “Good Research Practices Code”. The new version has been updated and adapted to the CERCA conduct code and includes, among other improvements, wording with inclusive language, the RRI principles and the institute’s RRI plan, as well as various legal aspects and institutional. The new code is also aligned with the mandatory European scientific integrity framework (ALLEA code).

The Sant Pau Biomedical Research Institute (IIB Sant Pau) receives a researcher from Ukraine through the #ScienceForUkraine platform. This initiative arises from an international movement promoted by volunteer scientists, academics and students to support the Ukrainian academic community by offering them opportunities for scientific stays or jobs in the international arena.

Dr. Oleksandra Yukhymchuk arrived in Barcelona a few weeks ago to collaborate with the Research Institute’s Pituitary Diseases Research Group led by Dr. Susan Webb and with the hospital’s Endocrinology Service.

In addition to participating in the group’s research projects, in her day-to-day life Dr. Yukhymchuk also carries out her activity in outpatient clinics, where she takes part in medical consultation of patients with different diseases of the pituitary gland, thyroid, obesity, pregnancy and diabetes. as well as other endocrine diseases. She is also collaborating in the management of the pituitary disease databases in Catalonia.

When the war broke out, in February of this year, Sasha -which is what her colleagues at Sant Pau affectionately call her- was  a  resident medical practitioner in Endocrinology at the V.P. Komisarenko Institute of Endocrinology and Metabolism, Kyiv.

Due to the crisis and security problems in her country, activities at her hospital were suspended and Sasha was left “unable to study or work”, as she herself explains. She and her family moved to a town located in the westernmost region of the country, bordering Poland,  to escape the bombs that fell on her hometown, Kyiv. “I began to search for possibilities to go to study somewhere so that I could take advantage and gain a bit of experience that could later be useful in my hometown, in my clinic.”

It was then that a friend of hers told her about the #ScienceForUkraine initiative. There she found offers in different countries such as Poland, the United States or Lithuania. And also the IIB Sant Pau, which was the only site from which she received a response. The Pituitary Diseases Research Group of the Sant Pau Biomedical Research Institute (IIB Sant Pau) led by Dr. Susan Webb offered accommodation to a person who would like to spend 3 months in Barcelona.

“Sant Pau’s offer seemed very interesting to me, especially because there was the possibility of collaborating in the area of Endocrinology, which is my field of interest. I want to work with orphan diseases and I felt very lucky to be able to come here and be able to work with the databases to do research”.

Sasha explains that one of the things that motivates her most about her stay at Sant Pau is that she can work with all diseases of the pituitary gland, since in Ukraine she does not have access to such specific lines of research in this area.

“For me it was a very good opportunity to come here to Sant Pau. I am very grateful for the opportunity to share this experience. The people are very friendly and have welcomed me very well”.

Dr. Webb explains that this experience has been very enriching for the entire research group that she leads at the IIB Sant Pau.

“In our group, we did not have the possibility of offering a salary or a scholarship, so I thought I could offer the possibility to live in my home and not have to pay for accommodation or maintenance. We could share our clinical and research experience and facilities, but we had no salary to offer”.

Sasha details that she is learning a lot, since in addition to having the opportunity to see patients, she is able to learn how the IIB Sant Pau works. “For example, we do not have a clinical trial center in Kyiv. We participate in clinical trials, but we do not have an institute where it is promoted or an infrastructure dedicated to it like the CIM (Centre for Drug Research) that you have here. It’s really very interesting.”

Sasha plans to return to Ukraine when her stay at IIB Sant Pau ends and return to work at the hospital in Kyiv. She is sure that her visit to Barcelona “will be of great help in the future to work there”. Although she is skeptical about the future of research in her country, she is hopeful that in a couple of years research can be reactivated and the bridges that have been opened with Sant Pau can bear fruit in possible collaborations.

The IIB Sant Pau currently has two other collaboration offers open on the #ScienceForUkraine platform. One in the Pharmacogenomics and Genetics of Stroke research group, which offers a 3-month stay to a researcher or doctoral student, and another in the Cerebrovascular Diseases Research group, which offers funding for 3 months (€1,000/month) for an investigator.

An international macro-study in which researchers from the Hospital de la Santa Creu i Sant Pau Research Institute – IIB Sant Pau have participated has located 11 new chromosomal regions involved in susceptibility to SARS-CoV-2 infection and in severity COVID-19 clinic. The work is published in the journal Nature.

The identification of these genetic determinants involved in the response to SARS-CoV-2 is essential to understand the biological mechanisms that underlie the disease, to find effective treatments and to protect potentially more vulnerable people. Among the genes found in this study, it is worth highlighting certain genes encoding pulmonary surfactants that play a key role in lung function.

The present work is an update with a larger number of patients of a study that this consortium published in July 2021. It now presents a meta-analysis of genome-wide association studies (GWAS) of 125,584 cases of infection and more than 2.5 million controls collected in 25 countries through 60 different studies. The data analysis of this cohort has been led by Israel Fernández Cadenas, from the Sant Pau Hospital Research Institute – IIB Sant Pau.

“In this new work we expand the map that we began last year and almost double the number of regions and chromosomes studied, going from 13 to 23. In addition, samples from all over the world have been included, improving our knowledge of the biological processes that cause the severe symptoms of COVID-19”, affirms the Sant Pau researcher.

The results obtained in this study are the result of the COVID Host Genetic Initiative international consortium, which searches for common genetic variants in the population that may increase the risk of infection or of developing severe covid-19. To do this, the consortium conducts studies on thousands of patients.

“The susceptibility and response to viral infections varies between people, as the current SARS-COV-2 pandemic has shown,” explains CSIC researcher Anna Planas, from the Barcelona Biomedical Research Institute (IIBB- CSIC). “Environmental and social factors contribute to the risk of contracting the infection, while male gender, advanced age and the presence of other diseases contribute to the risk of developing severe covid-19,” he adds. “However, genetic factors of people also increase the probability of contracting the infection, of needing hospitalization or of developing critical covid-19.”

Reference article

Gita A. Pathak et al. A first update on mapping the human genetic architecture of COVID-19. Nature. DOI: 10.1038/s41586-022-04826-7

Researchers from the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, the Immunology Department and the Geriatrics Unit of the Internal Medicine Department of the same hospital have identified that the increased levels of CD28+ CD27+ T lymphocytes early differentiated is associated with a better prognosis in patients older than 65 years who are admitted for pneumonia.

This is the conclusion of a prospective study -carried out as a FIS project of the Carlos III Health Institute- published by Journal of Leukocyte Biology, whose principal authors are Laura Martínez Martínez, Olga H. Torres and Teresa Franco – Leyva.

These researchers have verified that patients who had a higher count of these immune system cells at the time of hospital admission had better survival rates, as well as a lower rate of readmission, both at two months and one year follow-up after hospital admission.

These findings suggest that levels of early differentiated CD28+ CD27+ T lymphocytes could be a biomarker that can help better stratifying risk and monitoring these patients.

The work analyzes data from 97 patients admitted to the Hospital de Sant Pau during the years 2019 and 2020.

Reference article

Franco-Leyva T, Torres OH, Saez Prieto ME, et al. Early differentiated CD28+ CD27+ T lymphocytes as a biomarker for short and long-term outcomes in older patients with pneumonia. J Leukoc Biol. 2022;1-8. https://doi.org/10.1002/JLB.5MA0422-370R

The Sant Pau Biomedical Research Institute (IIB Sant Pau) has obtained the UNE 166002:2021 certification, granted by AENOR, for its Research, Technological Development and Innovation (R&D&i) management system.

This certification establishes the requirements and practical guidelines for the formulation and development of policies that guarantee the proper management of the entire R&D&i process, systematizing it and integrating it into the rest of the organization’s activities through specific objectives.

It is important to highlight that the accreditation includes all the strategic areas, as well as all the transversal programs of the institute, which represents a recognition of the quality with which it works in all the research groups and other management areas.

Miriam Ors Griera, head of the Innovation and Transfer Unit and deputy director of IIB Sant Pau, says “this certification highlights the great work that is being done in all the R&D activities of the institute. At the same time, it shows the robustness of the integrated quality management system that allows us to maintain the standards defined by our R&D&i policy”.

This certification has been achieved thanks to the joint and coordinated work of the Innovation and Transfer Unit -which forms part of the ITEMAS Platform- and the IIB Sant Pau Quality Unit.

A team of researchers from the UOC and the Research Institute of Hospital de la Santa Creu i Sant Pau shows that there is a link between fatigue, depression, anxiety and other cognitive deficits in patients with post-COVID-19 syndrome

The most common symptoms of the post-COVID-19 condition known as long covid include fatigue, shortness of breath and cognitive dysfunction, according to the World Health Organization (WHO). To be considered symptoms of long COVID, they must be present for at least two months during the three months after the onset of the disease.

A recent study in Brain and Behavior leaded by Research Institute of Hospital de Sant Pau showed that the disease had a generalized impact on attention skills, executive functions, learning and long-term memory. Furthermore, the scientific literature estimates that between 9% and 49% of patients present fatigue four weeks after the onset of symptoms, and it may even persist for a year in at least a third of patients.

Nevertheless, a possible link between fatigue and anxiety or depression in patients with long covid had not been studied in laboratories. Now, a study by the Universitat Oberta de Catalunya (UOC), in collaboration with Sant Pau, which has been published in open access format in the Journal of Neurology, has now shown that fatigue in long covid patients is related to anxiety, depression and apathy.

“Persistent fatigue is very disabling and greatly limits people’s quality of life. If someone suffers from fatigue as a result of COVID-19, it’s important to study this situation in further depth, and to determine what other symptoms or disorders are associated with this condition,” said Marco Calabria, lead researcher of the article, a member of the Cognitive NeuroLab group at the UOC and a member of the Faculty of Health Sciences. According to the author, now that we know the link between fatigue and depression, “clinicians should explore these aspects to provide a focus for therapeutic guidelines”. However, something that this research has not clarified is the direction of the effect: “it’s unclear whether fatigue leads to depression, or vice versa,” he explained.

Scientists studied a sample of 136 patients with COVID-19 who came to Hospital de Sant Pau and were suffering from cognitive deficits eight months after contracting the virus. “We found that fatigue is linked to sustained attention, which we use to perform a task for a long period of time and which keeps us focused, and to executive functions, which enable us to temporarily store information in order to perform tasks such as calculating, or reproducing a phrase that we’ve heard,” said Calabria.

“Our results show there’s a cognitive deficit in some patients after COVID-19 and chronic fatigue may have and important rol”, says Dr. Carmen García-Sánchez, autor of both articles and specialist at Neurology department of Hospital de Sant Pau – IIB Sant Pau. “It’s important to evaluate accurately the sequelae in post-COVID patients and study their evolution to minimize the cognitive impairment and promote their recovery”, he add.

Both studies were possible thanks to the collaboration between departments and research groups during the pandemia, with special rol of infectious diseases department and specifically of Dr. Pere Domingo, coordinator of COVID-19 hospitalization and program chief at Infectious Disease Unit at Sant Pau, who helped to enrole patients and take part of the study design.

Studying fatigue: a clinical challenge

Fatigue is characterized by excessive tiredness and physical and/or cognitive and muscular weakness. It has been associated with medical conditions such as post-viral infection and neurological diseases. Nevertheless, although it could be broadly outlined in these terms, there is no universally accepted definition of this clinical condition, and knowledge of its underlying pathogenic mechanism is limited, which is why it represents a clinical challenge for experts.

Another challenge for the scientists was to separate post-COVID-19 fatigue from the consequences of the specific situation experienced during the pandemic. “Fatigue is a symptom related to viral infections, and this suggested that it’d be one of the possible symptoms of SARS-CoV-2 infection“, said Calabria, who believes that it is possible that, in the first waves of the pandemic, isolation may have contributed to the increase in some symptoms.

“But some observations tell us that this isn’t always the case: fatigue prevents many people from going back to their previous lifestyle, while others continue to suffer from fatigue despite being able to return to pre-pandemic conditions and we found that the prevalence of apathy associated with COVID-19 increased from 17% before infection to 62% after infection“.

According to its authors, the results of the study highlight the importance of a holistic approach when evaluating and considering a potential treatment for COVID-19 patients experiencing fatigue. However, there are still many unanswered questions: “how these changes are reflected at the brain level, how long they last, who’s more likely to suffer from these symptoms for a long time, and what the individual characteristics that predict recovery are. We’ll answer all these questions in the long term, because this area’s something new and unknown“, concluded the researcher.

Reference articles

Calabria, M., García-Sánchez, C., Grunden, N., et al. Post-COVID-19 fatigue: the contribution of cognitive and neuropsychiatric symptoms. Journal of Neurology (2022). https://doi.org/10.1007/s00415-022-11141-8

García-Sánchez,C.,Calabria,M.,Grunden,N.,Pons,C.,Arroyo,J.A.,Gómez-Anson,B., Lleó,A., Alcolea,D., Belvís,R., Morollón,N., Mur,I., Pomar,V.,& Domingo,P.(2022). Neuropsychological deficits in patients with cognitive complaints after COVID-19. Brain and Behavior, 12,e2508. https://doi.org/10.1002/brb3.2508

The Research Institute of the Hospital de Sant Pau – IIB Sant Pau has just acquired a new automated digital pathology scanner to the Biobank and Immunohistochemistry core facility. It responds to the growing demand from IIB Sant Pau researchers, who expressed it through the user committee.

The new equipment – Pannoramic Scan II (3D Histech) has a 150-slide capacity and supports two objectives, 20x and 40x, as well as a fluorescence lamp, which allows high resolution and high speed digitization of slides under brightfield, fluorescence and FISH conditions, both automated and manually. It has filters for the main fluorochromes, making it a device capable of digitizing multiplexed preparations.

The software allows the serial capture of images in z, in both modes, allowing the digitization of thick tissues. It also has a license for the automated analysis of the images obtained, to help the interpretation and quantification of the expression of biomarkers within the tissue sections.

Therefore, the incorporation of this equipment to the Biobank and Immunohistochemistry facility offers a very complete solution for the digitization and analysis of slides for the analysis of histological, proteomic markers, subcellular, molecular and in situ hybridization probes.

This equipment has been acquired thanks to the contribution of the Institut de Recerca contra la leucèmia Josep Carreras, and to the mediation of Dr. R. Mangues and Dr. I. Casanova.

For more information about the equipment and the conditions of service, please contact Dr. Elena Serrano, head of the Biobank and Immunohistochemistry core facility.

Dr Elba Pascual Goñi has been awarded the Benson Clinical Research Fellowship by GBS CIDP International Foundation in the United States. Dr. Pascual is a neurologist and researcher at the neuromuscular diseases group in the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau.

The project that Dr Pascual will carry out for three years is entitled “Biomarkers in the diagnosis and follow up of chronic inflammatory demyelinating polyneuropathies (CIDP)” and aims to investigate new antibodies, CIDP-activity biomarkers, as well as to develop wearable biomechanical technology to improve both diagnosis and monitoring of this disease.

The fellowship, endowed with nearly US$ 400,000, is the third awarded by the GBS CIDP Foundation International in honour of Robert Benson, a survivor of Guillain-Barré syndrome, and his wife. The GBS CIDP Foundation International is a global nonprofit organization supporting individuals and their families affected by Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and related conditions through a commitment to support, education, research and advocacy.

About CIDP and the funded project

CIDP is a clinically heterogeneous and pathophysiologically diverse group of autoimmune diseases of the peripheral nerves. Autoantibodies have proven useful as disease-specific biomarkers to group these diseases according to their pathogenesis. Also, CIDP lacks disease-activity biomarkers. Finding disease-specific biomarkers informing about nerve status and correlating with response to therapies is crucial to optimize patient care and clinical research in CIDP. Finally, technological aids, such as wearable systems of biomechanical sensors, may improve clinical monitoring assessment in CIDP patients.

“Having new biomarkers that allow us to know the progression and/or response of the disease to treatments, as well as having wearable biomechanical monitoring devices, will help improve patient monitoring and therapeutic decision-making”” explains Dr Pascual Goñi.

An international trial, published The New England Journal of Medicine, concludes that the administration of tranexamic acid in patients with cardiovascular risk in patients undergoing non-cardiac surgery significantly reduces the risk of major bleeding without increasing major vascular complications. These findings may result not only into clinical benefits for patients but also into global benefits for health systems and public health, by drastically reducing the number of necessary transfusions.

Bleeding is a common problem in patients undergoing non-cardiac surgery, which often require blood transfusions. Now, an international multicentre study coordinated at Spanish level by researchers from the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, shows that the administration of tranexamic acid could prevent this problem. The results of the study have just been published in the prestigious journal The New England Journal of Medicine.

The study, led by Dr. Devereaux of the Population Health Research Institute, the McMaster University and the Hamilton Health Sciences (HHS) in Canada, included participation of 114 hospitals in 22 different countries. Dr. Mª José Martínez, Miquel Servet II researcher from the Clinical Epidemiology and Healthcare Services group at IIB Sant Pau, has coordinated the project in Spain and Dr. Pilar Paniagua, from the Anaesthesiology and Resuscitation Service and the Anesthesiology research group, has been the principal investigator at the Hospital de la Santa Creu i Sant Pau. Other members of the Anaesthesiology and Nursing services, as well as members of the Pharmacy, Cardiology, Orthopaedic Surgery and Traumatology, General Surgery and Vascular Surgery services collaborated in the study.

A safe, effective and cheap drug that could solve both a global health and economic problem

Tranexamic acid (TXA) is an antifibrinolytic drug used to reduce bleeding. The POISE3 study has evaluated the efficacy and safety compared to placebo of TXA given at the beginning and end of surgery, in patients at risk of cardiovascular complications undergoing non-cardiac surgery. The study has had a total of 9,535 patients, more than 700 in Spain and 200 in the Hospital de la Santa Creu i Sant Pau, which has been the Spanish hospital with most patients in the study, followed by the Clinical Hospital University Hospital of Valladolid and the Vall d’Hebron University Hospital.

The results show that TXA significantly decreases the primary composite endpoint of bleeding compared to placebo. They also demonstrate its safety, since it does not increase the risk of deep vein thrombosis, heart attack, non-haemorrhagic stroke, or other major vascular complications in the 30 days after surgery.

Most patients undergoing non-cardiac surgery do not receive TXA, but this study could change it. Every year up to 300 million surgeries are performed worldwide and surgical bleeding accounts for more than 40% of transfusions. There is a huge demand for blood products, which is up to 30 million units worldwide. The POISE-3 results may be relevant to healthcare systems around the world, since they identified that the use of TXA could annually prevent more than 8 million bleeding events resulting in transfusion.

Based on the results of the study, Dr. Maria José Martínez, coordinator of the POISE-3 study in Spain and IIB Sant Pau researcher explains that “incorporating the administration of TXA into routine clinical practice of non-cardiac surgery could benefit the health of patients while contributing to a global health problem such as the availability of blood products and their consequent economic cost”.

Reference article

Devereaux PJ, Marcucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI, Chan MTV, Borges FK, Martínez-Zapata MJ, Wang CY, Xavier D, Ofori SN, Wang MK, Efremov S, Landoni G, Kleinlugtenbelt YV, Szczeklik W, Schmartz D, Garg AX, Short TG, Wittmann M, Meyhoff CS, Amir M, Torres D, Patel A, Duceppe E, Ruetzler K, Parlow JL, Tandon V, Fleischmann E, Polanczyk CA, Lamy A, Astrakov SV, Rao M, Wu WKK, Bhatt K, de Nadal M, Likhvantsev VV, Paniagua P, Aguado HJ, Whitlock RP, McGillion MH, Prystajecky M, Vincent J, Eikelboom J, Copland I, Balasubramanian K, Turan A, Bangdiwala SI, Stillo D, Gross PL, Cafaro T, Alfonsi P, Roshanov PS, Belley-Côté EP, Spence J, Richards T, VanHelder T, McIntyre W, Guyatt G, Yusuf S, Leslie K; POISE-3 Investigators. Tranexamic Acid in Patients Undergoing Noncardiac Surgery. N Engl J Med. 2022 Apr 2. doi: 10.1056/NEJMoa2201171. https://www.nejm.org/doi/10.1056/NEJMoa2201171