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

Flow cytometry is a technology that provides rapid multi-parametric analysis of single cells in solution. It has a wide range of applications allowing unprecedented detail in immunology, haematology and cell biology studies.

“Flow cytometry allowed us to perform multiparametric analysis of blood extracellular vesicles at single level and high sensitivity, which would have been really difficult to measure with other traditional techniques”, explains Rosa Suades, post-doctoral researcher at the Molecular Pathology and Therapeutic of Ischaemic and Atherothrombotic Diseases group. Suades, who participates in the European project COVIRNA, was willing to characterise and quantify specific subpopulations of extracellular vesicles in COVID-19 patients and with different clinical severity.

On the other hand, cell sorters are able to isolate one or more cell populations from the pool. As an example, in the framework of a FIS and “La Marató” project, senior postdoctoral researcher at Neuromuscular Diseases group, Xavier Suárez-Calvet, needed to isolate and purify a small cell population from the skeletal muscle in mice, so they could functionally analyse them in vitro later.

“The large number and combination of markers needed to identify these cells made the use of the cell sorter essential”, says Suárez-Calvet. “This technology allowed us to have viable and highly pure cell cultures from an enzymatically dissociated tissue”, concludes the researcher.

A combination of state-of-the-art technology and technical expertise

The Flow Cytometry Core Facility at IIB Sant Pau offers support, hands-on service and tailored training sessions to users inside and outside the institute. From experimental design to data analysis, the team provides comprehensive service to the users and is constantly evolving to meet researchers’ specific needs.

The flow cytometry unit staff, Lia Ros (technician), and Marta Soler (coordinator) provide support and training to users.

The facility hosts six flow cytometers, one cell sorter, an Automacs Pro and a MAGPIX (Luminex). This state-of-the-art equipment together with the technical expertise of the staff facilitate researchers to design and develop efficient and reliable flow cytometric assays.

“Lia and Marta contribution has been crucial to help us developing the micronucleus assay”, states María José Ramírez, CIBERER researcher at the Cancer Predisposition and DNA Repair Syndromes group. “Our group was interested in chromosome fragility, an essential biomarker for Fanconi anemia and flow cytometry allowed us to advance in our research more quickly and effectively”.

Find here more information about the IIB Sant Pau Flow Cytometry Core Facility or contact Marta Soler, our Flow Cytometry Core Facility Coordinator.

IIB Sant Pau researchers lead the development of a new reporting tool to improve healthcare guidelines. RIGHT-Ad@pt Checklist is the new reporting tool, which ensures transparency and standardization of adapted healthcare guidelines. It facilitates the creation of recommendations that have been adapted for use in different healthcare systems.

Healthcare guidelines are evidence-based statements containing the main indications and recommendations for health professionals when facing a health problem. These guidelines use to be developed by different countries and organizations, which can be cost and time consuming. To maximize the efficiency of resources and reduce redundancy, organizations and countries may decide to adapt an existing practice guideline rather than developing a new one. But adaptation can be difficult.

A scientific workgroup developed a new reporting tool designed to improve standardization and transparency of adapted healthcare guidelines. Called RIGHT-Ad@pt Checklist, the tool focuses on improving the clarity and explicitness of recommendations that have been adapted for use in different health care systems, and of their development process. Authors at IIB Sant Pau in the Iberoamerican Cochrane Centre and the American University of Beirut, in collaboration with 119 expert researchers from 6 continents and 42 countries, describe the Checklist in an article published in Annals of Internal Medicine.

Until now, it was only available the RIGHT (Reporting Items for practice Guidelines in HealThcare) statement, which informs the reporting of the guideline development; however, it does not cover reporting of steps that are specific to guideline adaptation.

“We have now developed an extension of RIGHT to facilitate the adaptation of an existing guideline to another context, focusing on the standardization, rigor, and transparency of the process and the clarity and explicitness of adapted recommendations”, explain Laura Martínez and Pablo Alonso, lead authors and researchers from the Clinical Epidemiology and Healthcare Services group at IIB Sant Pau and Iberoamerican Cochrane Centre.

The RIGHT-Ad@pt Checklist was developed as an extension of the RIGHT statement through a multi-step process involving literature reviews and consensus building involving a range of stakeholders including guideline adaptation experts, users, journal editors, and policy makers. The checklist was designed to be used to guide the reporting of adapted guidelines, including adaptation process and the adapted recommendations. It can also be applied to assess the completeness of reporting and, in combination with available adaptation frameworks, to inform adaptation processes.

“The publication of this new tool will allow us to check how it works and how is being used by different organisations,” states Yang Song, first author of the paper and researcher at the same IIB Sant Pau group.

According to Song, future research should address the completeness of adapted guidelines and whether the publication of RIGHT-Ad@pt will have an influence on reporting, the quality of adapted guidelines, or the efficiency of the adaption process.

Authors also highlight that several audiences may use the RIGHT-Ad@pt checklist for different purposes:

• Guideline developers could use the checklist to report their adapted guidelines;
• Journal editors and reviewers could use the checklist to ensure the completeness and transparency of the reporting in the publication of adapted guidelines;
• Clinicians could accurately identify and apply adapted recommendations to their clinical practice based on detailed and clear reporting; and
• Policymakers could evaluate the feasibility of adapted recommendations for local implementation based on the reporting contents suggested by the checklist.

Reference article
Song Y et al. A Reporting Tool for Adapted Guidelines in Health Care: The RIGHT-Ad@pt Checklist. Ann Intern Med. 2022;175. doi:10.7326/M21-4352 A https://doi.org/10.7326/M21-4352

Researchers from the Research Institute of the Hospital de Sant Pau – IIB Sant Pan, the Hospital Clínic-IDIBAPS and the CIBERER, propose a biomarker that could accurately and non-invasively identify whether the origin of a psychotic outbreak is autoimmune or psychiatric. Their results, which have been published in Neurology, confirm for the first time that this marker is suitable to diagnose psychosis caused by autoimmune encephalitis and could have a major impact on clinical practice.

The reasons why someone may suffer a psychotic outbreak are diverse and knowing the origin of this outbreak in order to differentiate whether it is a psychiatric or autoimmune disease is key to propose the most appropriate treatment and monitoring of the disease. Currently, the diagnosis of autoimmune psychosis due to anti-NMDAR encephalitis is made by means of an antibody test that requires a spinal tap, which is not easy to obtain in psychiatric facilities and is not common in a first assessment.

In an article published in the journal Neurology, scientists from the Hospital de Sant Pau Research Institute – IIB Sant Pau, Hospital Clínic-IDIBAPS and the Centre for Biomedical Research Network on Rare Diseases (CIBERER), propose the use of a biomarker of neuronal damage in blood that will make it possible to identify accurately and non-invasively whether the origin of the psychotic break is autoimmune or psychiatric.

“Our study can have a major impact on clinical practice. We offer for the first time a non-invasive marker that allows us to identify those patients who are most at risk of NMDAR encephalitis, something that was not available until now,” explains Dr. Luis Querol, neurologist at the Hospital de Sant Pau and researcher in the Neuromuscular Diseases group of the Research Institute of the Hospital de Sant Pau – IIB Sant Pau and CIBERER.

“Having an immediate diagnosis thanks to this marker allows us to propose the most appropriate treatment and to know when it is necessary to do more tests or monitor the progress of the disease,” adds Lorena Martín, researcher in the same group and one of the first authors of the article.

Most patients arriving with a first episode of psychosis require antipsychotic drugs, which in turn can trigger adverse neurological events indistinguishable from anti-NMDAR encephalitis. Treating them without a diagnosis of the origin of psychosis makes differential diagnosis very difficult because new symptoms may be attributed to a neuroleptic-induced complication in a psychiatric patient when it could possibly be an evolving autoimmune encephalitis. Also, delaying therapeutic interventions while waiting for antibody results would not be a valid option, as early treatment is an important factor in the prognosis of these patients.

NfL protein, an increasingly widespread biomarker in neuroscience

The biomarker proposed by the researchers is NfL (Neurofilament light chain) protein. Levels of this protein in the blood indicate neuronal damage and this makes it a good marker for diagnosing and assessing progression or treatment in many neurological diseases, such as multiple sclerosis, dementia or neuropathy. The main benefit is that it can be obtained with a blood test and thus avoid more invasive diagnostic techniques, such as spinal tap.

The paper shows that young patients with a first psychotic outbreak and NfL levels above 15 pg/ml are 120 times more likely to have NMDAR encephalitis than a psychiatric outbreak. Therefore, blood NfL levels can accurately determine which patients with a first psychotic outbreak need further neurological assessment and spinal tap.

“Until now, this biomarker has not been proposed for the diagnosis of autoimmune encephalitis, and only a few studies have evaluated it in relation to the prognosis and severity of the disease,” says Mar Guasp, a pre-doctoral researcher at Hospital Clínic-IDIBAPS and one of the first authors of the study.

“Our results show not only that it is an excellent candidate for a first diagnosis and screening, but also that it could be a good marker to obtain better results in the long-term monitoring of patients when they leave the ICU or are discharged from hospital,” adds Dr. Josep Dalmau, at Hospital Clínic-IDIBAPS and CIBERER.

First authors of this paper are researchers Lorena Martín Aguilar, from the Research Institute of the Hospital de Sant Pau – IIB Sant Pau, and Mar Guasp, from the Clínic-IDIBAPS as first authors. They counted with the participation of other members at both institutions led by Dr. Luis Querol and Dr. Josep Dalmau. The study has been supported and funded by Instituto de Salud Carlos III (ISCIII), ERA-NET Neuron, CIBERER, “la Caixa” Foundation, Edmond J. Safra Foundation, Cellex Foundation, Torrons Vicens Foundation, and the strategic plan for research and innovation in health (PERIS) of the Generalitat de Catalunya.

Reference article

Mar Guasp, Lorena Martín-Aguilar, Lidia Sabater, et al. Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis. Neurology. February 10, 2022. DOI: https://doi.org/10.1212/WNL.0000000000200021

A study by IIB Sant Pau, CIBERDEM and IDIBELL shows that miR-125b affects the ability of HDL lipoproteins to extract colesterol from macrophages and smooth muscle cells of the arterial wall, accelerating the development of atherosclerotic plaque. The study opens the way to the potential use of inhibitors of this miRNA as a therapeutic strategy to stop the progression of this vascular condition.

Micro-RNAs are molecules capable of regulating the expression of multiple genes involved in the development of different diseases. One of these miRNAs, specifically miR-125b, could play a key role in the progression of atherosclerosis by blocking the expression of a gene that mediates the ability of HDL lipoproteins to capture cholesterol accumulated in macrophages and vascular smooth muscle cells of the artery wall and transport it to the liver, thus accelerating the formation of atherosclerotic plaque. This is the main conclusion of a new study carried out by scientists from the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, the Diabetes and Metabolic Diseases CIBER (CIBERDEM) and the Bellvitge Biomedical Research Institute (IDIBELL), which is published in the journal Biomedicine & Pharmacotherapy.

Cardiovascular diseases are one of the most important causes of disability and premature death worldwide. The main underlying problem in many of them is atherosclerosis, a condition characterized by an accumulation of lipids and an inflammatory response in the arteries, which leads to the formation of atherosclerotic plaque. Over time, this plaque ends up reducing the capacity of the blood vessel and, in addition, it can rupture and detach, causing a thrombotic event.

Loss of HDL’s function of removing cholesterol, a key fact

The accumulation of foam cells in the blood vessel wall constitutes a significant component of the early lesions of atherosclerosis. These foam cells, which form a kind of fatty streak in the wall of the blood vessels, can be derived from macrophages or smooth muscle cells of the arterial wall, which have been accumulating lipids in a pathologic way.

“The loss of the high-density lipoprotein (HDL) particles’ ability to stimulate the release of cholesterol from these cells and transport it to the liver to be eliminated through the intestine, a process called reverse cholesterol transport, is a key mechanism for the progress of the disease”, explain two of the study coordinators, Joan Carles Escolà-Gil and Noemí Rotllan, researchers of the Pathophysiology of Lipid-related Disease group at IIB Sant Pau and CIBERDEM. For this reason, this new work tries to elucidate the pathological mechanisms involved in the loss of this function of HDL.

The study focuses on a specific microRNA, miR-125b, which they point to as the main culprit: “Our work shows that miR-125b is expressed in human aortas from patients with coronary heart disease, specifically in macrophages and vascular smooth muscle cells, where it can promote the development of atherosclerosis”, points out Miguel Hueso, a researcher at IDIBELL and Bellvitge University Hospital, who has also led this work.

To clarify the role of this miRNA, a bioinformatic study was carried out to identify possible miR-125b target genes related to cholesterol metabolism in arterial wall cells. This way, they discovered the interaction of miR-125b with the SR-BI receptor gene, and its ability to block its gene expression. “The research has shown for the first time that miR-125b negatively regulates the expression of the SR-BI receptor in macrophages and smooth muscle cells of the arterial wall and its ability to extract cholesterol from these vascular cells and transfer it to HDL,” they point out.

In addition, they found that the expression of miR-125b in macrophages and vascular cells reduced the expression of the receptor both at the messenger RNA and protein levels. “This decrease was associated with a reduction in the ability of HDL to extract cholesterol from macrophages and transport it to the liver to be eliminated through the intestine,” they say.

 Therapeutic target

“The study could open the way to new therapeutic strategies based on the use of miR-125b inhibitors to prevent or slow down the development of atherosclerotic plaque, although more experiments with such type of molecule are still required in order to consider a possible application in this field.”, conclude the main authors of the investigation, Miguel Hueso and Noemi Rotllan.

Reference article:

Miguel Hueso, Raquel Griñán, Adrián Mallen, Estanislao Navarro, Elvira Purqueras, Montse Gomá, Fabrizio Sbraga, Arnau Blasco-Lucas, Giovanna Revilla, David Santos, Marina Canyelles, Josep Julve, Joan Carles Escolà-Gil, Noemi Rotllan. “MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport” Biomedicine & Pharmacotherapy, Volume 146, 2022, 112596, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2021.112596.

Nanoligent SL, a biotech company spin-off of the Sant Pau Research Institute and Universitat Autònoma de Barcelona specialized in the development of nanotechnology-based cancer treatments, today announces the completion of the first closing of a Seed financing round of €1M.

Nanoligent, a spin-off from the Research Institute of the Hospital de Sant Pau – IIB Sant Pau and Universitat Autònoma de Barcelona, is focused on the development of new drugs for the treatment of more than 20 different metastatic cancer types. The lead molecule is based on the targeted elimination of cancer cells overexpressing the CXCR4 receptor, a recognized biomarker for poor prognosis and therapy resistance. Nanoligent is developing a new proprietary nano-technological platform, with the potential to overcome current limitations of Antibody-Drug-Conjugates. The CXCR4 is overexpressed in a significant number of patients of more than 20 different tumors.

The research team behind Nanoligent technology is led by Prof. Ramon Mangues, group leader of the Oncogenesis and Antitumour Drugs at IIB Sant Pau and Prof. Antonio Villaberde and Dr. Esther Vázquez, both at the Biotechnology and Biomedicine Institute UAB, and all of them members of the CIBER-BBN.

In its first financing round, Nanoligent has raised €1M, which will allow them to complete the pre-clinical development in a variety of tumor types and to move its lead candidate into pre-IND stage. The round has been led by members of Italian Angels for Growth, the largest network of business angels in Italy, through the investment vehicle Nanolinvest, and AVANTECA Partners, a Swiss privately held asset management firm, both specialized in supporting innovative early-stage life-science companies primarily in Europe. An equity campaign, is still ongoing on Doorway, an online investment platform, thus promising to provide additional funding for the company.

The investor syndicate will join the Nanoligent’s Board which will consist of: Michele Marzola (IAG), Michael Milos (Avanteca Partners), Manuel Rodríguez (Chairman) and Montserrat Cano (CEO).

“It is our great pleasure to welcome Michele Marzola and Michael Milos, whose expertise and experience will be a valuable addition to the company to accomplish its ambitious development plans over the next 18 months” said Montserrat Cano, CEO of Nanoligent.

“We started the evaluation of a possible investment in Nanoligent one year ago and since then we have received enthusiastic responses from Key Opinion Leaders and Industry Experts. It has been a real pleasure working with the team at Nanoligent; we are impressed by their scientific depth and professional responses. We are continuing the fundraise for this deal together with Doorway, a fintech investing platform”, said Michele Marzola who together with Alessandro Toniolo are co-champions from IAG in this investment.

“We are fascinated by the technological capabilities of the platform and the professionalism of the team. The whole process was an intense, productive and very professional exchange. We are looking forward to partner with the management of Nanoligent to develop this highly innovative platform, which has the potential to transform cancer therapy” said Michael Milos from AVANTECA Partners.

Doorway, at its turn, is very happy to continue fundraising with its qualified community for such an innovative technology that can achieve a significant impact in the treatment of many cancers, being Nanoligent a perfect example of Doorway’s vision of “business with an impact”.

A multicenter study, led by neurologists at the Research Instituto of the Sant Pau Hospital and with the participation of the main Catalan hospitals, analyses the relationship between stroke and COVID.

It is known that 57% of patients with COVID-19 experience some neurological manifestation and also that the risk of mortality and morbidity from COVID-19 is increased in those patients who have vascular risk factors. However, to date, there have been no studies on the relationship between COVID-19 and stroke in terms of vital and functional prognosis. On the other hand, if there is indeed a relationship and the prognosis is worse, it should be differentiated whether this is due to the viral infection itself or to pandemic interference in the outpatient and inpatient care systems.

A team of researchers led by Dr. Joan Martí Fàbregas, chief clinician of the Neurology Service of the Hospital de Sant Pau and head of the research group on cerebrovascular diseases at the Research Institute of the Hospital de Sant Pau – IIB Sant Pau, has just published a study on the prognostic relationship between stroke and COVID-19. This is a multicenter study in which neurologists from most hospitals in Catalonia have participated and which could be carried out during the peak of the pandemic from March to May 2020. The study, published in the December issue of the prestigious journal Stroke, collects data from 701 ischemic stroke patients, 91 of whom had COVID-19 infection.

“We found that strokes with concomitant COVID-19 infection were more severe than those without COVID-19 infection. Likewise, the mortality of the group of patients with stroke and COVID-19 is three times that of the mortality in the patients without COVID-19”, explains Dr. Martí Fàbregas.

“Despite the worst prognosis we see in patients with stroke and COVID-19, our study also concludes that if the patient overcomes COVID-19 infection, the likelihood of having a good functional prognosis, that is, being independent for the basic activities of daily living such as personal hygiene, eating or dressing, is the same as that of patients without COVID-19”, adds Martí Fàbregas. “On the other hand, although the pandemic compromised the care of patients with stroke due to hospital collapse, this study showed that the poor prognosis is due to the virus infection itself, not to logistical difficulties.” he concludes.

This work is the first to address the prognostic relationship between ischemic stroke and COVID-19 and is a first step in understanding the extent to which the pathophysiology of stroke in patients with COVID-19 is different from patients without COVID-19 infection. Future studies will allow to translate this into specific treatment proposals for each type of patient or into recommendations to improve the response of health systems in pandemic situations.

One of the strengths of the study is the amount and consistency of the data that have been included. The collaboration of many hospitals at critical times allowed access to a large amount of data and rigorous information on stroke patients in 19 Catalan hospitals. The study, led by Sant Pau, has had the collaboration of Bellvitge Hospital, Vall d’Hebron Hospital, Germans Trias i Pujol Hospital, Clínic Hospital, Joan XXIII Hospital, Moisès Broggi Hospital, Dr. Josep Trueta, Hospital Arnau de Vilanova, Hospital del Mar, Hospital comarcal de l’Alt Penedès, Hospital Parc Taulí, Hospital de Mataró, Hospital Mútua de Terrassa, Hospital de Tortosa Verge de la Cinta, Hospital General de Granollers, Hospital d’Igualada , Hospital de Figueres, the Terrassa Health Consortium and the Catalan Health Quality and Assessment Agency.

Reference article

Joan Martí-Fàbregas et al. Impact of COVID-19 Infection on the Outcome of Pacients with Ischemic Stroke. Stroke. 2021; 52:3908-3917. DOI: https://doi.org/10.1161/STROKEAHA.121.034883

The Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, the Autonomous University of Barcelona and the Private Foundation Hospital de la Santa Creu i Sant Pau make possible the Joint Research Unit in Genomic Medicine UAB – IR Sant Pau, which was officially inaugurated today.

Eighteen years after the publication of the human genome, we know that there is still a long way to go in studying the genome and its relationship to health. Today, the Sant Pau Research Institute – IIB Sant Pau and the Autonomous University of Barcelona have taken a step forward to shorten this path and bring genomic research closer to medicine and clinical practice, with the creation of the Joint Research Unit in Genomic Medicine UAB – IR Sant Pau. The new unit was inaugurated today in an event attended by Dr. Javier Lafuente, rector of the UAB; Dr. Manel Balcells, chairman of the board of the Research Institute, Dr. Jordi Bachs, managing director of the Private Foundation Hospital de la Santa Creu i Sant Pau and Dr. Jordi Surrallés, director of the Sant Pau Research Institute.

The Joint Research Unit in Genomic Medicine UAB – IR Sant Pau has had the support of the Private Foundation Hospital de la Santa Creu i Sant Pau, which has funded the works of adaptation of the space for the laboratory making possible 177 m2 for state-of-the-art research. For its part, the UAB will also contribute to the Sant Pau Research Institute in the next six years, the equivalent of the cost of the work for the creation and start-up of this unit. In this new space, the joint research unit focuses, above all, on the diagnosis, pathophysiology and development of new therapies for genetic diseases and tumor predisposition syndromes.

“The research we do at the Sant Pau Research Institute is translational and by our nature, we connect research with clinical practice. The creation of the joint research unit in Genomic Medicine UAB – IR Sant Pau further strengthens our mission by incorporating basic research, training professionals in this important field for personalized and precision medicine and completing the cycle” says Dr. Jordi Surrallés, director of the Sant Pau Research Institute and professor ICREA Academia at the UAB.

“It is important to bridge academia, biomedical research institutes and hospitals to reinforce the triple mission of high-complexity hospitals such as Hospital de Sant Pau: care, research and teaching; and to create spaces, such as this unit, where this interaction happens”, he concludes.

On his behalf, the Rector of the UAB, Javier Lafuente, explains: “The UAB is a benchmark in the field of biomedicine and genetics, being the only university in Spain to offer a degree in Genetics, and the creation of the Joint Research Unit in Genomic Medicine UAB – IR Sant Pau reaffirms the University’s commitment to this field”.

The rector highlights the satisfaction of “having a unit of this nature, the first joint unit of the UAB in this field, with researchers from both institutions working together in the research of genetic diseases, their diagnosis and treatment”.

The unit becomes a reality today, but was under the mandate of the previous director of the Research Institute, Dr. Jaume Kulisevsky, when the project began to take shape in 2017 as Dr. Jordi Surrallés joined the Sant Pau Hospital as Director of the Genetics Service and integrated his research group. In October 2019, a collaboration agreement was signed between the three institutions that have made it possible. And now, once the works are completed, the research group coordinated by Dr. Jordi Surrallés is occupying this new space of 177 m2 from where they will carry out their research projects. The team of the unit currently consists of 17 people with multidisciplinary profiles including experts in biology, genetics, medicine, biochemistry, biotechnology, bioinformatics or data science.

Understanding genomic instability to protect us from cancer and advance in personalized medicine

The research group that forms the unit works in the field of human genetic diseases, characterized by a high predisposition to cancer. Many of these syndromes are caused by mutations in genes involved in DNA repair. These genes are important in preventing the buildup of mutations and preventing tumor transformation.

Research on these syndromes is important to unravel the mechanisms that protect us from cancer. There are increasingly new therapeutic strategies based on deep knowledge of the genetic causes of the disease. Therefore, proper genetic diagnosis is important not only to provide good genetic counselling and clinical follow-up on patients and their families, but also to provide personalized medicine based on genomic information.

The Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, the Hospital de la Santa Creu i Sant Pau, and the Fundació Puigvert presented a pioneer scientific project that includes physical exercise and Mediterranean diet based on the intake of extra virgin oil, or the introduction of low-dose aspirin. The project has the collaboration of the five Protected Denominations of Origin of oil of Catalonia.

About 20% of couples have fertility problems and half of these problems could be modified by introducing changes in lifestyle, such as exercising or adopting a healthy diet. Based on this knowledge and taking profit of the advantages that we have in our territory, such as extra virgin olive oil, the research group in Perinatal and Women’s Medicine of the IIB Sant Pau, begins a research project to study to what extent introducing a healthy lifestyle could improve the metabolic and cardiovascular status of women who undergo in vitro fertilization.

The Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, the Hospital de la Santa Creu i Sant Pau and the Fundació Puigvert have presented today the scientific project MEDITATE-IVF (Impact of Exercise and Mediterranean diet vs Aspirin on live-birth rate and cardiovascular programming in In Vitro Fertilization), which studies the relationship of the Mediterranean diet and healthy lifestyle habits with success in IVF treatments, with the collaboration of the five Protected Denominations of Origin of oil in Catalonia.

Currently, similar interventions in the at-risk population have shown improvements in several highly prevalent diseases, such as cardiovascular diseases, but a study of these characteristics has never been done in women of reproductive age with the idea of improving fertility and the health of next generations.

“We want to go further and take advantage of a time when future mothers and families consider substantial changes in their lifestyle. We propose them to adopt a healthy diet, which includes the antioxidant qualities of extra virgin olive oil and adequate suugar and protein levels while incorporating physical exercise into their routine “, explains Dr. Elisa Llurba, Director of the Gynecology and Obstetrics Service of the Hospital de la Santa Creu i Sant Pau, and researcher at the IIB Sant Pau. “We understand the monitoring and treatment of women’s health from a holistic and comprehensive approach, therefore we want to study to what extent a healthy lifestyle can help in an in vitro fertilization process”, she concludes.

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Dr. Ana Polo, Director of the Reproductive Medicine program at the Hospital de la Santa Creu i Sant Pau and Fundació Puigvert and principal co-investigator of the study at the IIB Sant Pau., explains that MEDITATE-IVF will count on a group of 750 volunteering women waiting to undergo in vitro fertilization. Participants will be randomly assigned into three intervention groups. The first group will have a program of physical exercise and a Mediterranean diet that will include the intake of extra virgin olive oil and other dietary measures recommended by experts in physical education and in diet and nutrition. The second group will receive a small-dose supplement of aspirin, and the third group will not receive either of the two interventions and will be the control group.

The objective of this project is twofold. On the one hand, it aims to increase the possibility that healthy women of reproductive age obtain better results in in vitro fertilization treatments, but also that the development of the fetus is healthier, the so-called fetal programming.

“Although the main objective of the study is to increase the rate of live newborns, this is closely related to the decrease in complications during pregnancy, mainly pre-eclampsia and low birth weight, factors that condition a higher risk of cardiovascular problems both the mother as well as the baby. Reducing the presence of pre-eclampsia in these pregnancies would lead to a lower risk of heart attack in women in the long run. Low birth weight has been related to an increased risk of developing cardiovascular and metabolic diseases in childhood, adolescence and adulthood. Therefore, reducing these complications would have an impact on the health of both the mother and the baby, in the long term”, says Dr. Mónica Cruz-Lemini, specialist in Fetal Medicine and Fetal Programming of the Gynecology and Obstetrics Service of the Hospital de la Santa Creu i Sant Pau and principal co-investigator of the study at the IIB Sant Pau.

A proposal rooted in the territory, but with global benefits

The project has the collaboration of the five Protected Denominations of Origin (PDO) of oil from Catalonia (DOP Oli del Baix Ebre Montsià, DOP Oli de l’Empordà, DOP Les Garrigues, DOP Siurana i DOP Oli Terra Alta) The project has the collaboration of the five Protected Denominations of Origin (PDO) of oil from Catalonia

Several studies in cardiovascular health for example, already support the benefits of extra virgin olive oil, especially for its antioxidant properties.

“We are fortunate to have these oils of superior category and with a certificate of origin and quality among our local produc range. Favoring the consumption of extra virgin olive oil protects our health, but also our tradition and culture, contributing to the sustainability of our own territory and environment”, says Mr. Enric Dalmau, president of the Les Garrigues PDO and spokesperson for the five Protected Denominations of Origin for oil in Catalonia. “Collaboration in projects like the one that starts today, strengthen our positioning and commitment to health, and help us to spread the qualities and properties of this exceptional product that we have in Catalonia,” he adds.

Possibly the results of this study will show the need to change habits in women who undergo these techniques. Likewise, the study is expected to allow the identification of therapeutic options for the future related to the success of fertilization, the health of the mother and the development of the fetus, or to serve as a starting point for other studies related to the prevention of cardiovascular risk in later life. As in all research projects, the results of the study will be published and shared in the scientific environment so that they are available to the entire clinical and scientific community, thus achieving a global impact.

Collaborators 

Financing 

The MEDITATE-IVF study (Impact of Exercise and Mediterranean diet vs Aspirin on live-birth rate and cardiovascular programming in In Vitro Fertilization) is financed by the Carlos III Health Institute, Acción Estratégica en Salud, Proyectos de Investigación en Salud, PI20 / 001504.

Dr Elba Pascual-Goñi, researcher of the Neuromuscular Diseases Group of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau has described a new subgroup of patients with chronic inflammatory demyelinating polyradiculoneuropathy based on clinical and immunological characteristics. Her results have just been published in the journal Brain, the oldest journal in neurology.

Inflammatory neuropathies are a heterogeneous group of diseases characterized by the presence of an autoimmune attack on the peripheral nerves. They are rare diseases and very little is known about their pathophysiology, so there are no specific biological markers and, therefore, they are diseases that can be difficult to diagnose or go unnoticed.

In some cases, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the diagnosis is based exclusively on clinical and electrophysiological criteria, as there are no specific diagnostic biomarkers. CIDP is the most common chronic immune-mediated neuropathy, with a prevalence of around 2 per 100,000 people.

The Sant Pau neuromuscular diseases team works to find biomarkers in inflammatory neuropathies that help diagnose the disease and guide its treatment. This team has pioneered the description of antibodies against proteins of the Ranvier nodes, which are the small spaces between the myelin plates that we find throughout neurons and that are necessary for the nerve impulse to propagate correctly. “The description of these antibodies has represented a revolution in the field of immunomediated neuropathies, because it has allowed the identification of subgroups of patients that share common clinical characteristics and immunopathogenic mechanisms, highlighting the heterogeneity of this disease”, says Dr.. Luis Querol, principal investigator of the Autoimmune Neurology group of the Neuromuscular Diseases Unit in which this work was carried out.

In the recent study published in the journal Brain, researchers have described the clinical and immunological characteristics of CIDP with antibodies against the Caspr1 / CNTN1 complex, which is key to the proper functioning of the Ranvier node. “Investigating a set of specific antibodies has allowed us to identify a new subgroup of patients, who share clinical and immunological characteristics”, explains Dr Elba Pascual Goñi, neurologist and researcher at the Neuromuscular Diseases Unit of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau de Barcelona and first author of the article. “Apart from identifying a unique population within the CIDP spectrum, the detection of these antibodies allows us to optimize the management of patients with this neuropathy”, concludes the researcher.

Sant Pau Biomedical Research Institute (IIB Sant Pau) is a partner in the COVIRNA project. The project aims to generate an innovative diagnostic tool to identify COVID-19 patients at risk of developing fatal cardiovascular complications in the context of the current pandemic, ultimately leading to their improved surveillance and care. The COVIRNA video outlines the project objectives and the methodology used to achieve them. It has been produced in cooperation with Science Animated.

The overall goal of the COVIRNA project is to generate a diagnostic test based on cardiovascular RNA biomarkers highly predictive of the clinical outcomes of COVID-19 patients and to enable its rapid market uptake with the aim to improve individualised surveillance, care and follow-up of these patients in the context of the current pandemic.

Watch the video to learn more about the COVIRNA Project:

International collaboration led by researchers at the Sant Pau Reseach Institute – IIB Sant Pau in Barcelona, Spain, shows effectiveness of a plasma biomarker to detect Alzheimer’s Disease in Down syndrome individuals. Their results, which have been published in Nature Communications, will enhance diagnostic capability in this particular population. In parallel, researchers have also published another study in JAMA Neurology where they analyzed the influence of the most important genetic factor for Alzheimer’s disease (APOE) on the mechanisms of this pathology in the population with Down syndrome

Scientists worldwide are immersed in the race for accurate, non-invasive and accessible biomarkers to detect and diagnose Alzheimer’s Disease. To date, major scientific advances allowed the identification of several biomarkers in cerebrospinal fluid or using positron emission tomography (PET). Yet, these methods are expensive, invasive and not accessible so they are not included in clinical routine and only restricted to a few.

Most recently, blood biomarkers have emerged as an easy and cost-effective alternative for the screening of Alzheimer’s disease. One of these new plasma biomarkers is protein p-tau 181, which was firstly described as potential biomarker by scientists at the University of Gothenburg.

Now, researchers at the Hospital de Sant Pau Research Institute – IIB Sant Pau in Barcelona in collaboration with scientists at University of Gothenburg and University of Montpellier, assessed the accuracy of p-tau 181 in plasma to detect Alzheimer’s disease in Down Syndrome individuals. As reported in Nature Communications, they have studied suitability and effectiveness of this biomarker in a cohort of 400 people, 366 of whom are adults with Down syndrome.

“In our study, we found that this biomarker actually works to detect Alzheimer’s among people with Down syndrome too. Discerning cognitive impairment in people who already have an intellectual disability or other dementias is difficult, and having biological markers available will improve our ability to diagnose”, says Dr. Albert Lleó, head of the Dementia Neurobiology Group at IIB Sant Pau and director of the Memory Unit of the Neurology Service at the Hospital de la Santa Creu i Sant Pau. “It is an important milestone to us because it will allow us to make early detection and provide appropriate care and treatment to address the progression of the disease”.

Down Syndrome and Alzheimer’s disease, a tandem to consider

Alzheimer’s disease is currently the leading medical problem for adults with Down syndrome and it is also the leading cause of death. Down syndrome is a condition in which a person has three copies of chromosome 21, which also led to have an additional copy of the amyloid precursor protein (APP) gene, making these people, therefore, much more likely to suffer Alzheimer’s disease.

IIB Sant Pau’s team, which has long experience and is an intenational benchmark in the relationship between Alzheimer’s disease and Down syndrome, includes the Alzheimer-Down unit, led by Dr. Juan Fortea. This pioneering unit, resulted from a collaboration between the Catalan Down Syndrome Foundation and the Hospital de la Santa Creu i Sant Pau.

“Understanding the pathophysiology of Alzheimer’s disease and being able to have tools for early diagnosis becomes even more relevant when we talk about people with Down syndrome”, says Juan Fortea, head of the Alzheimer-Down unit.

Deepening the mechanisms of Alzheimer’s to understand its progression

Also, researchers Florencia Iulita and Alexandre Bejanin from this unit have studied the pathophysiological processes involved in the development and progression of Alzheimer’s in Down syndrome individuals.

Researchers have focused on a particular gene encoding for the apolipoprotein APOE ɛ4, which is associated with an increased risk of Alzheimer’s. In their study, recently published in JAMA Neurology, they characterized the association of this gene with various Alzheimer’s biomarkers and segmented it by age groups of study. The main findings show that the risk of Alzheimer’s is much higher in people with Down syndrome and to what extent this risk increases with age. The study also provides information on the mechanisms by which this happens

“We believe that our work comes timely considering the large number of studies available related to the prevention and diagnosis of Alzheimer’s disease. Considering genetics and the APOE genotype may be important when designing new drugs and clinical trials”, concludes Dr. Fortea.

Advancing Alzheimer’s research from many different angles

These two works highlight the relevance of multidisciplinarity when addressing neurodegenerative diseases. IIB Sant Pau’s team approached Alzheimer’s disease from many angles and the team includes experts in neurology, neuropsychology, biology, engineering, nursing and research. They tackle several research projects aimed at improving diagnosis, at better understanding the disease and its progression, as well as at identifying therapeutic targets while improving the clinical care of patients and their caregivers.

Papers cited

• Lleó, A., Zetterberg, H., Pegueroles, J. et al.Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer’s disease in adults with Down syndrome. Nat Commun 12, 4304 (2021). https://doi.org/10.1038/s41467-021-24319-x

• Bejanin A, Iulita MF, Vilaplana E, et al. Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome. JAMA Neurol.Published online July 06, 2021. https://doi.org/10.1001/jamaneurol.2021.1893

An international collaboration uncovers several genetic markers associated with SARS-CoV-2 infection and COVID-19 severity. These results, which have been published in Nature, come from one of the largest genome-wide association studies ever performed. The findings could help provide targets for future therapies and illustrate the power of genetic studies in learning more about infectious disease.
IIB Sant Pau researcher, Israel Fernández Cadenas is one of the over 3,500 scientists co-authoring this paper and is the only Spanish researcher in the writing group.

Barcelona, (July 8, 2021)— In March of 2020, thousands of scientists around the world united to answer a pressing and complex question: what genetic factors influence why some COVID-19 patients develop severe, life-threatening disease requiring hospitalization, while others escape with mild symptoms or none at all?

A comprehensive summary of their findings to date, published in Nature, reveals 13 loci, or locations in the human genome, that are strongly associated with infection or severe COVID-19. The researchers also identified causal factors such as smoking and high body mass index. These results come from one of the largest genome-wide association studies ever performed, which includes nearly 50,000 COVID-19 patients and two million uninfected controls.

The findings could help provide targets for future therapies and illustrate the power of genetic studies in learning more about infectious disease.

IIB Sant Pau researcher, Israel Fernández Cadenas, is one of the scientists co-authoring this paper and the only Spanish researcher participating in the writing group.

“This is an unprecendented major collaboration including researchers, biobanks, hospitals and private companies sharing data and working in a truly transparent way,” states the researcher. “Collaboration and data sharing allowed us to quickly get the big picture of the COVID host genetics but more importantly, such effort and initiative will facilitate and foster many research projects related to other pathologies, infectious diseases, as well as to better understand COVID patients with persistent symptoms or to identify targets for drug development and treatment”, Dr. Fernández Cadenas concludes.

This global effort, called the COVID-19 Host Genomics Initiative, was founded in March 2020 by Andrea Ganna, group leader at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki and Mark Daly, director of FIMM and institute member at the Broad Institute of MIT and Harvard. The initiative has grown to be one of the most extensive collaborations in human genetics and currently includes more than 3,500 authors and 61 studies from 25 countries.

Ben Neale, co-director of the Program in Medical and Population Genetics at the Broad and co-senior author of the study, said that while vaccines confer protection against infection, there is still substantial room for improvement in COVID-19 treatment, which can be informed by genetic analysis. He added that improving treatment approaches could help shift the pandemic — which has necessitated large shutdowns in much of the world — to an endemic disease that is more localized and present at low but consistent levels in the population, much like the flu.

“The better we get at treating COVID-19, the better equipped the medical community could be to manage the disease,” he said. “If we had a mechanism of treating infection and getting someone out of the hospital, that would radically alter our public health response.”

Harnessing diversity

To do their analysis, the consortium pooled clinical and genetic data from the nearly 50,000 patients in their study who tested positive for the virus, and 2 million controls across numerous biobanks, clinical studies, and direct-to-consumer genetic companies such as 23andMe. Because of the large amount of data pouring in from around the world, the scientists were able to produce statistically robust analyses far more quickly, and from a greater diversity of populations, than any one group could have on its own.

Of the 13 loci identified so far by the team, two had higher frequencies among patients of East Asian or South Asian ancestry than in those of European ancestry, underscoring the importance of diversity in genetic datasets. “We’ve been much more successful than past efforts in sampling genetic diversity because we’ve made a concerted effort to reach out to populations around the world,” said Daly. “I think we still have a long way to go, but we’re making very good progress.”

The team highlighted one of these two loci in particular, near the FOXP4 gene, which is linked to lung cancer. The FOXP4 variant associated with severe COVID-19 increases the gene’s expression, suggesting that inhibiting the gene could be a potential therapeutic strategy. Other loci associated with severe COVID-19 included DPP9, a gene also involved in lung cancer and pulmonary fibrosis, and TYK2, which is implicated in some autoimmune diseases.

Mari Niemi, FIMM researcher and lead analyst for the study, says the consortium prioritized communication as the scientists analyzed data, immediately releasing results on their website after they had been checked for accuracy. The team hopes their results might point the way to useful targets for repurposed drugs.

The researchers will continue to study more data as they come in and update their results through the “Matters Arising” format at Nature. They will begin to study what differentiates “long-haulers”, or patients whose COVID-19 symptoms persist for months, from others, and continue to identify additional loci associated with infection and severe disease.

“We’d like to aim to get a good handful of very concrete therapeutic hypotheses in the next year,” Daly said. “Realistically, we will most likely be addressing COVID-19 as a serious health concern for a long time. Any therapeutic that emerges this year, for example from repurposing an existing drug based on clear genetic insights, would have a great impact.”

A new space for genetics

Scientists were able to find robust genetic signals because of their collaborative efforts, a cohesive spirit of data-sharing and transparency, and the urgency that comes with knowing the entire world faces the same threat at the same time. Geneticists, who regularly work with large datasets, have known the benefits of open collaboration for a long time. “This only illustrates just how much better science is — how much faster it goes and how much more we discover — when we work together,” Ganna said.

“These discoveries have been really informative and that has made us realize that there’s a lot of untapped potential in using genetics to understand and potentially develop therapeutics for infectious disease,” Daly said. “I hope this sets an example for how we might bring population genetics approaches to a new set of problems that are especially important in developing parts of the world.”

For more information on the Host Genetics Initiative, please visit

https://www.covid19hg.org/

Paper cited

The COVID-19 Host Genetics Initiative. Mapping the human genetic architecture of COVID-19. Nature. Online July 8, 2021. https://www.nature.com/articles/s41586-021-03767-x

• Blood and vascular levels of various molecules related to oxidative stress can be good predictors of aneurysm rupture.

•  The research, developed by researchers from the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and the CIBERCV together with the CSIC and the CIBEROBN at the Rey Juan Carlos University, has been published in the journal Antioxidants

Blood levels of various molecules related to oxidative stress may be useful biomarkers in predicting the risk of ruptured abdominal aortic aneurysm. This is confirmed by a study carried out by researchers from the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and the CIBER for Cardiovascular Diseases (CIBERCV) in collaboration with scientists from the Barcelona Institute for Biomedical Research (IIBB-CSIC), and the CIBER of Obesity and Nutrition (CIBEROBN) of the Rey Juan Carlos University, which has been published in the journal Antioxidants.

Abdominal aortic aneurysm (AAA) is a life-threatening condition that consists of a localized and permanent dilation of the abdominal aorta, the prevalence of which can reach 4-7% of men over 65 years of age. Over time, the aortic diameter tends to expand and the risk of rupture increases, the most serious complication of this disease, which produces extensive internal bleeding. This event is responsible for between 1% and 2% of all deaths and constitutes one of the main triggers of death in men over 70 years of age.

The implementation of ultrasound detection programs has improved the early diagnosis of this pathology, but finding new indicators for the prognosis of its evolution is key in the management of the disease. In this sense, although the incidence of rupture increases with the aortic diameter, this parameter is not in all cases a good predictor of risk, since small aneurysms can also have a poor outcome. Therefore, the identification of biomarkers in the blood to assess the progression of AAA, will play a key role in improving the recognition of patients at higher risk.

This has been the objective of this new research, which focused on analysing the prognostic value of circulating (blood) levels of various molecules related to oxidative stress and inflammation. “In order to identify new circulating biomarkers, we selected a battery of immune inflammatory and oxidative stress markers that we know are involved in the pathological mechanisms of abdominal aortic aneurysm progression,” says María Galán, researcher at the Research Institute of the Hospital de the Santa Creu i Sant Pau – IIB Sant Pau, that has led the study.

To achieve this, an analysis of the correlation of these markers with two risk parameters was carried out: the diameter of the aneurysm and the value of maximum arterial wall tension. The researchers had the participation of the Angiology, Vascular and Endovascular Surgery service of the Hospital de la Santa Creu i Sant Pau to study aneurysmal aortic samples and blood samples from 94 AAA patients, comparing them with abdominal aortic samples and blood from healthy people.

The results showed that the blood levels of superoxide anion, IgM, IgG, CD38, GDF15, S100A4, as well as its expression in the abdominal aorta of patients with AAA, were altered compared to healthy controls.

“The levels of IgG, CD38 and GDF15 were positively correlated with the diameter of the abdominal aorta and with the values of maximum wall tension, showing that they have the potential to help predict the risk of rupture and growth of the aneurysm in patients with AAA”, points out David Sánchez-Infantes, first author of the work.

“These findings suggest the usefulness of these biomarkers, which can be measured in a blood sample, to help the management of patients with aneurysm, along with other tools already used in prognosis such as aortic diameter and maximum wall tension”, the researchers conclude.

Reference article:

Sánchez-Infantes D, Nus M, Navas-Madroñal M, Fité J, Pérez B, Barros-Membrilla AJ, Soto B, Martínez-González J, Camacho M, Rodriguez C, Mallat Z, Galán M. Oxidative Stress and Inflammatory Markers in Abdominal Aortic Aneurysm. Antioxidants. (2021) https://doi.org/10.3390/antiox10040602

Professor Lina Badimón, head of 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 – IIB Sant Pau, has joined the Royal Academy of Medicine of Catalonia (RAMC) as a Numerary Academician.

Her admission ceremony was held on Sunday, May 16th , 2021, in an extraordinary public session at the headquarters of the Royal Academy of Medicine of Catalonia, in which Dr. Badimon read the speech “Precision Medicine in Cardiology”. Dr. Badimon is attached to the first section in basic, diagnostic and therapeutic sciences and entered to receive the 48 medal, that Dr. Soledat Woessner i Casas had previously held, now Emeritus Academic, who together with Dr. Miquel Vilardell i Tarrés acted as godparents. The answer to her speech on behalf of the Academy was in charge of the numerary academic, Dr. Antoni Bayés de Luna.

On precision medicine, research and cardiology

In her entrance speech, Dr. Badimon presented the so-called Precision Medicine and explained, how this new approach to medicine that relies on science – omics and data (big data) as its main support – will shape clinical practice of the future. Not only did she take a tour of this discipline and present the main benefits and challenges, but she also contextualized this type of medicine in the field of cardiovascular diseases, an area in which she is an internationally renowned expert. She showed through examples how precision medicine can contemplate many variables to the same problem, and how the integration of all these data can result in a better characterization of patients, in better defined clinical trials and in responses that allow us to offer personalized prevention tools and treatments.

As Dr. Badimon pointed out, the challenge now is to incorporate this into clinical practice.

The session and the speech of Dr. Badimon are available on the RAMC YouTube channel, at  this link.

About Dr. Lina Badimon

Lina Badimon Maestro, directs the research group of Molecular and Therapeutic Pathology of Atherothrombotic and Ischemic diseases. She is a research professor at the Higher Council for Scientific Research and Director of the Chair for Cardiovascular Research at the UAB, and the UNESCO Chair for biomedicine, Deputy Lecturer Associate Professor of Medicine – Cardiology – at the Mount Sinai School of Medicine, New York and Visiting Professor at Manchester Metropolitan University, UK and Paris-Est University, France.

Her career includes posts and positions of responsibility at the former Institute of Cardiovascular Sciences, the CSIC, the Massachusetts General Hospital in Boston, the Harvard Medical School in Boston, and the Mount Sinai School of Medicine in New York. She has been President of the Spanish Society of Arteriosclerosis, President of the European Society for Clinical Investigation, Vice President of the Spanish Society of Cardiology (SEC) and of the European Society of Cardiology (ESC), Chair of the Council on Basic Science of the ESC and of various working groups in both organizations.

Currently, she is a member of the Board of the European Society of Cardiology, Chair of the Patient Forum and Women @ ESC. She is also the President of the European Mediterranean League Against Thromboembolic Diseases Foundation (EMLTDF).

A team of researchers at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, together with scientists at École Polythecnique Fédérale de Lausanne (EPFL), describe the brain network responsible for minor hallucinations in Parkinson’s disease. Scientists developed a robotic device that allows the induction of hallucinations and the study of the brain networks that are involved. The study, which has been published in Science Translational Medicine, shows the relationship of such hallucinations in the context and progression of Parkinson’s disease, which could be relevant for early diagnostic.

Researchers at theInstitut de Receca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau in collaboration with scientists at the École Polythecnique Fédérale de Lausanne (EPFL) have described the brain network responsible for minor hallucinations in Parkinson’s disease and its possible relation with the progression of the disease.

A team led by Jaume Kulisevsky, director of the Parkinson disease and movement disorders research group at IIB Sant Pau and of the socalled Unit at the Neurology Service of the Hospital de la Santa Creu i Sant Pau,  and by Olaf Blanke, principal investigator at EPFL in Geneva, has desenvoled a robotic device that allows the induction of hallucinations in healthy subjects and Parkinson disease patients. By combining this robot with MRI imaging, scientists have been able to study the brain networks involved in hallucinations. They identified these networks and confirmed that are the same ones related to major hallucinations in Parkinson disease, which are one of the most disturbing non-motor symptoms for these patients.

Hallucinations that were not considered but could be significant

Parkinson’s disease is the second neurode

Parkinson’s disease is the second most prevalent neurodegenerative disease worldwide after Alzheimer’s and affects primarily the elderly. It is a progressive neurodegenerative disease that has been traditionally defined as a movement disorder, characterized by tremor, rigidity and slowness of movement. But many patients also suffer from a wide array of symptoms that are not associated with movement and some may go on to suffer from mental symptoms like psychosis, depression, apathy, cognitive decline and even dementia. Hallucinations are frequent in the disease but only major hallucinations were considered real symptoms in the past.

Did you ever felt a presence behind you? Did you ever felt someone else in an empty room? Or maybe, have you ever seen animals or other things quickly passing by next to you? These kind of events are named minor hallucinations. They are very frequent in Parkinson’s disease, becoming more and more frequents as the disease progresses, even they are also present amongst the 5-10% of healthy population.

“In the past, we did not consider these hallucinations a symptom. They were attributed to medication or maybe they were not reported because many patients are hesitant to report them, and questions remain about the neurobiology at play. Our research group already identified the key role of these hallucinations in Parkinson’s disease and now, with this new paper we can conclude that the brain networks behind them are the same that will later cause major hallucinations. Thus, it can be a powerful indicator of the progression of this disease as well as of cognitive damage,” explains Jaume Kulisevsky, principal investigator at IIB Sant Pau and co-corresponding author of the paper published in Science Translational Medicine.

Practical implications

The study, which has been done with healthy individuals and with Parkinson’s disease patients at the Hospital de Sant Pau in Barcelona, and in other hospitals in Switzerland and France, confirms the funcional basis of the hallucinations phenomena and it could be a good marker to study the disease progression. The expertise of the Kulisevsky group on these kind of events and their previous work about the key role of minor hallucinations in Parkinson’s disease as a pre-motor symptom, as well as the description of the attention networks and visual connectivity in the brain, contributed the use this new device as a tool for a better understanding and diagnostic of Parkinson’s disease.

As in other neurodegenerative diseases, it is important to focus in early detection and in the identification fo new targets to develop treatments in order to stop the progression of the disease.By combining this robot with MRI imaging, scientists have been able to study the brain networks involved in hallucinations and to determine its level of severity and damage.

Reference:  Bernasconi et al., Sci. Transl. Med., 13, eabc8362 (2021) 28 April 2021. 10.1126/scitranslmed.abc8362

The partners of the European project CARDIOPATCH will present the website of the initiative the 30th of April in a virtual event. The interactive platform is a dynamic environment that aims to promote the networking and cooperation between the agents of the biomedical industry and 3D printing technologies in Southwestern Europe

CARDIOPATCH (Network of Excellence for the development of Advanced Therapies of Myocardial Infarction treatment based on regenerative medicine and 3D printing), which aims to create a new treatment through regenerative medicine and 3D printing for patients who have suffered a myocardial infarction, has developed a digital platform to connect the key actors of the biotechnology sector and the 3D printing technologies from Southwestern Europe.

This project involves the participation of Prof. Lina Badimon and Dr. Gemma Vilahur from the Institut de Recerca Hospital de la Santa Creu i Sant Pau – IIB Sant Pau. “The achievement of this project will allow us to get functionalised patches with therapeutic proteins and enriched with stem cells. As a result, we will gain the capacity to regenerate damaged tissues in heart attack patients“, stated both researchers.

The characteristics and services of this interactive platform, which is integrated in its official website, will be presented today, 30th of April, at 4:00 P.M. CEST in a virtual encounter. The event is open to the public and the inscriptions can be made following this link.

During the webinar, not only the website of CARDIOPATCH project will be presented officially, but also the main services that are included. Specifically, the members of the consortium of the project will explain the functioning of the funding opportunities search tool and the space dedicated to encourage and impulse synergies and collaborative projects.

Besides, it will be presented the map of capacities as well. This interactive environment allows the user to travel geographically through Southwestern Europe searching for research institutions and entities focused on the biomedical sector and 3D printing technologies, as well as research projects working in these fields.

CARDIOPATCH platform will allow joining the network to all the entities interested in it in order to enjoy the project’s services and be able to develop new collaborations and innovation projects.

“With this virtual network, CARDIOPATCH will foster cooperation between the different actors that work in the R&D applied to the biomedical sector in Southwest Europe. The platform is provided by tools and services that will help to create synergies and impulse the networking. It will also be an informative space where the project’s advances in cardiac regenerative medicine will be shared”, explains Felipe Prósper, director of the Navarra University Clinic Cell Therapy Department and project chief scientific officer.

Co-funded by the EU Interreg Sudoe Programme, via the European Regional Development Fund (ERDF), CARDIOPATCH is led by Clínica Universidad de Navarra. The project’s consortium is also made up by CIMA University of Navarra, via the Foundation for Applied Medical Research, the Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, LEARTIKER technology centre, communication agency GUK, Centre Hospitalier Universitaire de Toulouse, the University of Montpellier (UM) – Institut des Biomolécules Max Mousseron (IBMM), GenIbet Biopharmaceuticals and the Instituto de Biologia Experimental e Tecnológica.

The project also has the support of associate partners Viscofan, Sodena and the Nouvelle-Aquitaine, Euskadi, Navarre Euroregion (NAEN), among others.

An international team with participation of the Cerebrovascular Diseases group at IIB Sant Pau and led by ICFO researchers, has carried out a pooled analysis, combining the results of three studies about the cerebral blood flow in cerebrovascular disease patients. The analysis concludes that the response of their cerebral blood flow to changes of the head-of-bed position can indicate failures in the brain’s autoregulation.

Ischemic stroke and brain self-regulation

Approximately 80% of the strokes that occur are of the ischemic type. An ischemic stroke is a cerebrovascular disease condition, caused by damage in the arteries (a narrowing or blockage of the vessels) that carry blood to the brain. The damage can cause a severe reduction in the blood flow, called ischemia, which can lead to the death of the brain tissue.

Cerebral autoregulation is a biological process working as a neural protection tool, carried out by our bodies to maintain the blood supply to the brain despite blood pressure changes, as occurs during the drug administration after injuries. Although many processes are involved in the cerebral autoregulation, the exact control mechanism is still unknown.

For patients who have suffered cerebrovascular accidents such as stroke, clinicians use different inclinations of the head-of-bed during the early stages of stroke, in order to improve the perfusion of blood flow to the brain. It is a non-invasive technique that does not require patient cooperation and the study of the cerebral response to this procedure may help to estimate  the functioning of the mechanisms of cerebral autoregulation

Previous studies have indicated that approximately 25% of ischemic stroke patients respond to posture changes in an unexpected way. After changing the head-of-bed between lying flat and a degree of inclination, the blood flow of the brain does not return to the initial levels.

Researchers Clara Gregori, Igor Blanco, Peyman Zirak, Lisa Kobayashi, Stella Avtzi, Federica Maruccia and Giacomo Giacalone, led by ICREA Prof. at ICFO Turgut Durduran, have collaborated with researchers of the Cerebrovascular Diseases Group at IIB Sant Pau, consisted in the following neurologists from the Cerebrovascular Diseases Unit in the Hospital de Sant Pau, Pol Camps-Renom, Joan Martí-Fàbregas, Luís Prats-Sánchez and Alejandro Martínez-Domeño, led by Raquel Delgado-Mederos. The analysis, published recently in BMC Neurology, also includes researchers from the University of Pennsylvania, the Massachusetts General Hospital, the University of Campinas, and the Washington University of St. Louis. It investigates the relationship between these changes in blood flow and blood pressure, one of its main drivers.

Meta-analysis of seventy-two patients

To do a proper analysis on the matter, the team gathered data from three different studies, carried out between 2005 and 2017 in the United States and Spain, that included seventy-two patients with cerebrovascular disease. With this data, they performed a systematic analysis of the cerebral blood flow measurements.

All the data was obtained using diffuse correlation spectroscopy (DCS) techniques. The team measured the changes in cerebral blood flow, in response to a specific protocol for handling patients in bed, from three study subgroups: healthy individuals, patients with carotid stenosis (a narrowing of the carotid artery) and patients with ischemic stroke.

The head-of-bed protocol consisted of placing the patients in a supine position – lying on their backs -, then raising the head of the bed to an angle of 30º, and finally returning them to the initial position, maintaining each position for five minutes. During this process, researchers monitored the cerebral blood flow and blood pressure to see if there were any changes in the parameter.

Mobilizing patients could backfire

They analysed the data from all the patients of the subgroups and showed that, in healthy individuals, cerebral blood flow increases when they pass from a supine position to an elevated posture and then decreases to initial levels when they are lying down again. In contrast, in ischemic stroke and carotid stenosis patients, the cerebral blood flow and the blood pressure values do not return to baseline after postural changes.

Researchers observed that, during the first 48 hours after the stroke, the cerebral blood flow of these patients is correlated with the mean arterial pressure, only in the injured hemisphere of the brain.

These two observations suggest that these posture changes in stroke patients may be used to identify deficits or errors in the brain’s autoregulation response.

Helping to improve the management of stroke patients

Early mobilization of patients with ischemic stroke promotes the motor recovery. But the data provided by this analysis could suggest that moving patients during the first hours after the stroke may have an effect on the cerebral blood flow perfusion of the ischemic damage.

To study this issue in-depth, the team of ICFO researchers in collaboration with clinicians from the Hospital de Sant Pau and IIB-Sant Pau will carry out a clinical trial on 200 individuals who have suffered an ischemic stroke. They aim to clarify the role of cerebral autoregulation and provide more information to improve their clinical management.

Reference: Gregori-Pla et al. Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease. BMC Neurology (2021) 21:154. https://doi.org/10.1186/s12883-021-02179-8