Investigadors de l’Institut de Recerca Sant Pau i del Servei de Cirurgia Vascular de l’Hospital del Mar, liderats per la Dra. Maria Sabater Lleal, investigadora Miguel Servet al grup de Genòmica de les Malalties Complexes de l’Institut d’Investigació Sant Pau, han participat en l’estudi genètic d’aneurisma més gran de l’aorta abdominal realitzat fins ara. L’etiopatogènesi d’aquesta malaltia és complexa i multifactorial i encara que roman essencialment desconeguda, se sap que hi ha un component genètic important.

L’estudi, que publica la revista Nature Genetics, ha analitzat les dades clíniques i genètiques de 14 cohorts de pacients (entre elles la cohort de l’Institut de Recerca Sant Pau), incloent-hi prop de 40.000 persones amb aneurisma i més d’un milió de controls sans , per identificar i investigar els determinants genètics de l’aneurisma de l’aorta abdominal. L’anàlisi ha localitzat 121 regions cromosòmiques associades amb l’aneurisma de l’aorta abdominal, de les quals 97 són descrites per primera vegada. La informació genètica derivada de la metaanàlisi permet explicar el risc d’aquesta malaltia més enllà dels factors de risc clínics tradicionals.

Una de les autores del treball, la Dra. Mercedes Camacho, del grup de Genòmica de les malalties complexes de l’Institut de Recerca Sant Pau, explica que l’aneurisma de l’aorta abdominal consisteix en una dilatació localitzada i progressiva de l’aorta abdominal, generalment a la zona infrarrenal. És una malaltia lligada a l’envelliment que afecta el 6-9% dels homes i l’1-2% de dones de més de 65 anys i tendeix a augmentar a la població paral·lelament a l’esperança de vida.

Aquesta malaltia en molts casos sol ser asimptomàtica, per la qual cosa el diagnòstic es produeix majoritàriament de manera casual. Actualment, no hi ha cap tractament farmacològic capaç de limitar la progressió de l’aneurisma o evitar-ne el trencament, associat a una alta taxa de mortalitat. La intervenció quirúrgica, sigui oberta o endovascular, és l’única opció terapèutica, procediment costós per al sistema sanitari i amb elevada morbimortalitat. “L’estudi genètic és fonamental per desxifrar la patogènesi de la malaltia i permetrà el diagnòstic precoç i el desenvolupament d’eines clíniques“, informa la Dra. Sabater.

El paper del metabolisme lipídic

Una de les troballes més destacades de l’estudi ressalta el paper fonamental dels lípids i el seu metabolisme en la patogènesi de la malaltia: 42 de les 121 regions cromosòmiques associades a risc d’aneurisma contenen gens associats amb lípids, fet que dona suport a les teràpies moduladores de la malaltia lípids poden tenir un paper en el tractament de la malaltia.

“Encara que les dades actuals sobre els efectes de les estatines en l’expansió aòrtica són contradictòries, l’evidència genètica d’aquest estudi suggereix que la reducció del colesterol-LDL mitjançant la inhibició de PCSK9 (proteïna relacionada amb els nivells de LDL-colesterol circulatori i la inhibició és el tractament més eficaç per reduir els seus nivells) podria també disminuir el risc de desenvolupar un aneurisma de l’aorta abdominal, encara que futurs estudis han de demostrar si aquest tractament redueix la progressió de la malaltia una vegada diagnosticada” afegeix la Dra. Sabater, coordinadora de la participació espanyola a l’estudi.

A més, afegeix la investigadora, conèixer les variants genètiques implicades en aquesta malaltia també permetrà desenvolupar un score genètic que ajudi a predir quines persones tindran més risc de patir-la i que, per tant, serien candidates a fer proves de cribratge més específiques.

Els processos de desenvolupament de fàrmacs i assaigs clínics són llargs, costosos i complexos, per la qual cosa cal triar amb cura les noves intervencions terapèutiques. Aquestes troballes contribueixen a canviar l’abordatge d’aquesta malaltia aportant informació genètica.

Article de referència

Roychowdhury T, Klarin D, Levin MG, Spin JM, Rhee YH, et al. Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target. Nat Genet. 2023 Oct 16. doi: 10.1038/s41588-023-01510-y. Epub ahead of print. PMID: 37845353.

Today, October 19th, is World Breast Cancer Day, a day established to raise awareness about the disease, give it visibility, and create tools and resources to confront it.

Breast cancer is the most common type of cancer in women worldwide. Raising awareness among the population about the importance of this disease is crucial to achieve early detection, one of the fundamental measures to combat it. That’s why it is recommended that women between the ages of 50 and 69 have a mammogram every two years.

Dr. Agustí Barnadas, head of the Clinical Oncology Research Group at the Sant Pau Research Institute and head of the Medical Oncology Service at the same hospital, has emphasized the importance of continuing to promote early cancer diagnosis and determining patient profiles to decide who is a candidate for screening studies.

Recently, a study led by Dr. Barnadas has suggested that certain microRNAs (miRNAs) can be useful as non-invasive biomarkers for the early diagnosis of lymph node metastasis in patients with early-stage breast cancer, specifically those with estrogen receptor-positive (ER-positive) breast cancer.

On the occasion of World Breast Cancer Day, Sant Pau is conducting various initiatives to contribute to raising awareness.

EVENT “PER A VOSALTRES”

The event, organized by the Activity Girls group, takes place on Thursday, October 19th, at the Sant Pau Hospital Auditorium, from 8:45 AM to 2 PM. Admission is free.

ACTIVITIES ON OCTOBER 19th

Photographic exhibition “The Challenge: The Fragility of Life.” Sant Quintí Hospital Atrium at Sant Pau Hospital. From October 19th to November 23rd.

Information tables about breast cancer Sant Quintí and Mas Casanova Hospital Atriums at Sant Pau Hospital. October 19th from 9 AM to 1 PM.

Today, October 10, is World Mental Health Day and this year the chosen motto is “Mental health is a universal right”, where the objectives are to improve knowledge, increase its visibility and promote measures to protect it . Sant Pau has a long history and expertise in research, care and treatment of people with mental illnesses and has the necessary devices to address the various pathologies and improve the quality of life of patients. Among the main research lines of the Mental Health Group of the Sant Pau Research Institute, led by Dr. Maria Portella, highlight psychotic disorders, affective disorders (such as depression) and borderline personality disorder.

The commemoration of World Mental Health Day began in 1992 at the hands of the World Federation of Mental Health with the challenge of raising public awareness of mental disorders, fighting the stigmatization of affected people and promoting initiatives to improve – the attention According to the World Health Organization (WHO), 1 in 4 people will experience a mental health problem during their lifetime.

The Department of Health of the Generalitat de Catalunya states that mental health and emotional well-being is a broad concept related to the way we feel, think or act in our day-to-day life. Therefore, it is the basis for the well-being and effective functioning of people and communities and becomes an inseparable aspect of the concept of health: you cannot have good health without good mental health.

In this sense, the Master Plan for Mental Health and Addictions (PdSMiA), is the instrument of information, study and proposal through which the Department of Health determines the guidelines to promote, plan, coordinate and evaluate the actions to be developed in the field of mental health promotion, prevention and treatment of diseases associated with mental health and addictions, and improving the quality of life of affected people.

All this in response to the objectives of the Catalan Health Plan 2021-2025, which provides some important data: a quarter of the population over the age of 15 has emotional distress (1 in 5 men and 1 in 3 women), a figure that increases with age and is more prevalent in the most disadvantaged social groups; in addition, 7.4% of men and 13.7% of women from the age of 15 suffer major or major depression, especially from the age of 75, and especially women.

The Catalan Foundation for Research and Innovation has published this interview with Dr. José Manuel Soria, head of the Genomics Group for Complex Diseases at the Research Institute Sant Pau, on the occasion of the Joan Roget Prize for the transfer of knowledge awarded to Beyond You (formerly Exheus) .

This company, which was born as a spin-off from the Sant Pau Research Institute, the Universitat Politècnica de Catalunya – BarcelonaTech (UPC) and Summit SL incubated at Venture Builder The Collider, is a pioneer in research and development of advanced genetic technology. Specialized in analyzing the expression of the more than 22,000 genes present in the transcriptome using artificial intelligence to detect and correct parameters that may be out of the ordinary with personalized recommendations.

The Joan Roget Awards recognize actions linked to the transfer of knowledge considered as success stories of the system for their contribution to the economic and social development of individual researchers or technicians, together with the institutions to which they belong.

A study coordinated by Dr. Vicenta Llorente-Cortés, a researcher at the CSIC and CIBERCV, and Dr. Antonio Pérez, director of the endocrinology unit and a member of CIBERDEM at the Research Institute Sant Pau, reveals that newly diagnosed patients with type II diabetes have elevated levels of soluble LRP1 receptor (sLRP1) and decreased levels of atrial natriuretic peptide (ANP).

The article, published in the journal Frontiers in Endocrinology, was conducted by analyzing liquid biopsies from newly diagnosed type II diabetes patients, in which it was found that strict glycemic and metabolic control over 12 months normalizes the sLRP1/ANP ratio after a year of treatment, and therefore, this index could be a reliable marker of cardiometabolic function.

Dr. Llorente explains that these findings open the door to search for new ways to intervene and personalize treatment to reduce the risk of heart disease in people with diabetes. She explains that sLRP1 is a marker that has been associated with coronary artery disease or atherosclerosis and also cardiovascular risk. “In other words, people with higher levels of this marker in their blood have a higher cardiovascular risk.”

It is known that atrial natriuretic peptide is very high in the blood when there is a situation of cardiac damage. “But, in addition, when these levels are very low, there is usually a metabolic problem behind it. So, both people with diabetes and those who are obese have very low levels of this peptide.”

The study was conducted in newly diagnosed patients with type II diabetes, meaning they had not yet been treated with any medication for this condition. The blood of these individuals was analyzed, and they were followed up for a year, and it was found that intervention through lifestyle changes and pharmacological interventions indicated by their metabolic condition normalized the levels of these two molecules.

“These markers could be useful for non-invasively assessing cardiovascular risk as well as the effectiveness of different therapies indicated to improve metabolic control and cardiovascular risk in patients with type II diabetes.”

Reference Article

García E, Gil P, Miñambres I, Benitez-Amaro A, Rodríguez C, Claudi L, Julve J, Benitez S, Sánchez-Quesada JL, Rives J, Garcia-Moll X, Vilades D, Perez A, Llorente-Cortes V. Increïen sLRP1 i decreixen atrial natriurètic peptide plasma de nivells en els nous diagnosis T2DM pacients són normalitzats per optimització de glycemic control. Front Endocrinol (Lausanne). 2023 Aug 10;14:1236487. doi: 10.3389/fendo.2023.1236487. PMID: 37635956; PMCID: PMC10450024.

Motor cortical stimulation could be a promising therapeutic alternative for patients with chronic neuropathic pain who do not respond to conventional treatments, according to the results of a multicenter study conducted by researchers from the Neurosurgery Group at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, in collaboration with the Hospital del Mar Research Institute, published in the journal Neurosurgery.

The study, led by Dr. Rodrigo Rodríguez Rodríguez, a researcher and neurosurgeon at Sant Pau, analyzes data from one of the world’s largest cohorts of patients with treatment-resistant neuropathic pain who underwent motor cortical stimulation as a rescue therapy. This technique involves the implantation of electrodes on the surface of the brain in specific areas indirectly related to pain circuits.

The results demonstrate the long-term effectiveness of motor cortical stimulation in the treatment of neuropathic pain, specifically trigeminal neuralgia. Of the evaluated patients, 42% showed a positive response to motor cortical stimulation after 6 months. Additionally, there was an average reduction of 34% in pain intensity.

Dr. Juan Aibar, from the Neurosurgery Group at IIB Sant Pau and a neurosurgeon at the same hospital, explains that neuropathic pain is a form of pain that persists even though the injury that caused it no longer exists. It is related to central or peripheral nervous system lesions and is especially difficult to control with conventional treatments. Patients suffering from this condition often experience associated problems such as anxiety, depression, and work-related issues, in addition to a significant impact on their quality of life.

“It is crucial that motor cortical stimulation is carried out in specialized centers with well-established headache and neuralgia units,” emphasizes this expert, adding that this is due to “the complexity of patients seeking this treatment and the need for a thorough evaluation before considering it as a suitable alternative.”

Dr. Aibar also highlights the importance of considering the pain’s semiology, meaning understanding the nuances of neuropathic pain and its underlying cause, as each case may have different outcomes with neuromodulation therapy. “For example, if it is multiple sclerosis, herpes, trauma, or trigeminal neuralgia at onset… all these conditions can cause this type of facial pain, and each one has a different outcome with neuromodulation therapy,” Dr. Aibar comments.

This is a highly specific cerebral neuromodulation treatment for patients with severe neuropathic pain, performed at very few centers in Spain. This is the reason that led the authors of these two Catalan centers, which have more experience in this neuromodulation technique in Catalonia, to gather and jointly analyze the data. “In cerebral neuromodulation, studies should be multicenter because it is the only way to obtain sufficient data to reach conclusions,” explains Dr. Gloria Villalba, coordinating neurosurgeon of the Neurosurgery Service at the Hospital del Mar and co-principal author of the publication, along with Dr. Juan Aibar and Dr. Rodrigo Rodríguez.

These findings highlight the importance of continuing to research motor cortical stimulation as a valuable option for the treatment of chronic neuropathic pain, especially trigeminal neuralgia. This study represents a significant step toward a more comprehensive and effective understanding of the treatment of treatment-resistant neurological conditions.

Reference article

Aibar-Durán, Juan Ángel MD; Villalba Martínez, Gloria MD; Freixer-Palau, Berta; Araus-Galdós, Elena; Morollón Sanchez-Mateos, Noemi; Belvis Nieto, Robert; Revuelta Rizo, Miren MD; Molet Teixeido, Joan; García Sánchez, Carmen; de Quintana Schmidt, Cristian; Muñoz Hernandez, Fernando; Rodríguez Rodríguez, Rodrigo. Long-Term Results of Cortical Motor Stimulation for Neuropathic Peripheral and Central Pain: Real-World Evidence From Two Independent Centers. Neurosurgery. August 28, 2023. | DOI: 1227/neu.0000000000002638

Today, September 29th, World Heart Day, Sant Pau celebrates it from the perspective of a hospital that has witnessed the development of Cardiology. It was the first center in the country to successfully perform a heart transplant in 1984 and the first to establish a specialized research institute specifically focused on the research and treatment of cardiovascular diseases. Currently, it continues to be an advanced reference in Cardiology research, with ongoing development of new therapeutic procedures, advancements in basic Cardiology knowledge, and care for cardiac patients. It pioneers programs aimed at improving the cardiovascular health of its users, such as the SCA (post-acute coronary syndrome prevention and education program) launched this year, which monitors around 300 patients annually.

The SCA program is an outpatient initiative for early monitoring of all patients admitted to Sant Pau Hospital with an acute myocardial infarction. It involves very close and early monitoring to control all risk factors for individuals admitted with a heart attack, such as hypertension, cholesterol levels, smoking, obesity, diabetes, stress, and more.

“The SCA program started with the collaboration of Nursing and Cardiology staff, back in February. We train between 5 and 10 patients from the hospital’s reference area who have been admitted due to a myocardial infarction on a weekly basis,” explains Dr. Miquel Gual, coordinator of the SCA program and associate of the Cardiology Service at Sant Pau. “At present, the program accommodates all these debut patients, meaning those who have had a first myocardial infarction, and therefore, we work with the goal of acting quickly. As the program grows, other groups with ischemic heart disease, angina, or other types of myocardial infarction will be included,” Dr. Gual specifies.

The program addresses a need arising from the improvement of treatment techniques or revascularization of myocardial infarctions. This advancement results in increasingly shorter hospital stays for this condition. Patients enter the hospital with a very severe condition, but the majority of these patients recover satisfactorily, leading to shorter hospitalizations. Consequently, patient awareness of the disease is low.

“In addition to this, while they are hospitalized, the time available for training, education, and initiating prevention measures to prevent the recurrence of ischemic diseases is also very limited. Consequently, it is necessary to restructure the post-hospitalization phase, organize, gather, and follow up on all patients with infarctions, and maintain an educational program to develop cardiovascular lifestyle habits,” states the program coordinator, who estimates that they will annually follow up with between 250 and 300 patients.

One of the key aspects of this initiative is ensuring continuous care, meaning the educational program, with a significant role played by specialized Nursing staff in cardiovascular care. “The program is finite, lasting six months; patients enter, but they also have to leave. A key factor that we believe is very important is to establish this continuous care, with a continuous flow of patients. Once the initial hospital phase is completed, we get in touch with each responsible person at each primary care center in the Sant Pau reference area, thus maintaining the flow of patients and facilitating direct and continuous communication between hospital professionals and primary care professionals,” Dr. Gual adds.

The age profile of patients admitted with myocardial infarctions ranges from around 50 to 70 years, as there is currently a selection of patients with the onset of cardiac diseases, meaning those who have experienced a first episode. The majority of the population is relatively young, regardless of gender. “This means that there is still a percentage of patients who are actively employed, and thanks to this early and comprehensive treatment monitoring, they can, among other things, return to their work activity earlier than usual,” concludes Dr. Miquel Gual.

Translational Research in Cardiology

Cardiology is one of the five strategic areas of the Sant Pau Hospital Research Institute – IIB Sant Pau and serves as a clear example of translational medicine, aiming to find answers to unmet needs directly emerging from the patient’s bedside “through research that encompasses preclinical genetic studies in cellular models to the most advanced clinical research. This is crucial for translating research results into therapeutic solutions for patients,” says Dr. José Guerra, from the Arrhythmia Unit of the Cardiology Service at Sant Pau.

With this goal in mind, they also promote knowledge transfer by fostering the creation of spin-off companies. “In this regard, a few years ago, we began investigations to discover new therapeutic targets that could address the remaining needs in the clinical field. One example is the research on cardioprotection we have been conducting in recent years, which has resulted in the creation of a company with several investors,” explains Prof. Lina Badimon, director of the Area of Cardiovascular Disease Research and the Molecular Pathology and Therapeutics Research Group of Atherothrombotic and Ischemic Diseases at IIB Sant Pau. “This is an example of how we want to provide solutions to patients through research.”

Specifically, this spin-off company is working on the development of an intravenous statin that will be useful for patients who require high doses of this medication, which is currently administered orally, which is not always sufficient “for patients undergoing transplantation, undergoing oncological treatments, or undergoing surgery.”

Gender and Cardiovascular Health

This year, IIB Sant Pau has launched a cross-cutting research program in Women’s Health and Gender to promote a gender perspective in all its areas and research groups. Created within the framework of the Responsible Research and Innovation (RRI) Plan, the program is an example of joint work between IIB Sant Pau and Sant Pau Hospital and is currently implementing actions to promote the incorporation of a gender perspective into research content and to encourage specific gender research to address existing knowledge gaps, by providing the necessary means and resources to facilitate it.

It should be noted that, in fact, Sant Pau Hospital was one of the first Catalan centers to create the Health and Gender Commission, which impacts healthcare, research, and teaching.

In Cardiology, there are increasing projects that incorporate the gender perspective from their initial planning. There is also growing evidence of significant differences in the evolution and clinical manifestations of various cardiovascular disorders and the impact that these variables can have on prevention and treatment. Several examples exist in this regard. The group led by Prof. Badimon is developing a personalized medicine project in a national cohort with a genetic diagnosis of familial hypercholesterolemia, where gender specificity is a goal to identify and determine the importance of new molecular biomarkers. Another notable initiative is the RETROVE program, which seeks mathematical algorithms to define individual risk of venous thrombosis, as well as a study analyzing the use of beta-blockers in patients with atrial fibrillation based on gender.

In the field of cardiovascular health, Dr. Elisa Llurba, in collaboration with researchers from the Perinatal and Women’s Medicine Research Group, the Biochemistry Research Group, and the Cardiovascular Diseases Group, is leading three studies funded by the Carlos III Health Institute on the impact of different reproductive processes on cardiovascular health at three key stages: before pregnancy in women undergoing assisted reproduction, during pregnancy, and 3-6 years after childbirth. The objective is to study how placental-origin diseases can impact maternal and neonatal cardiovascular health.

Diet influences the accumulation of fat in the arteries. This has been demonstrated by a recent study confirming that low adherence to the Mediterranean Diet is linked to a greater presence of fatty plaques in the arteries, specifically atherosclerosis. The study, conducted with the population from the ILERVAS project, known as ‘the Health Bus,’ which included 8,116 individuals, was recently published in the Atherosclerosis journal.

The research, jointly led by investigators from the IIB Sant Pau and IRBLleida, involved the participation of research personnel from Primary Care in Lleida, the Jordi Gol Research Institute for Primary Care (IDIAP Jordi Gol), the Biomedical Research Centre for Respiratory and Metabolic Diseases, the Washington University School of Medicine in the United States, and other research groups from IRBLleida, the University Hospital of Lleida, and the University of Lleida, among others.

“Current research on the association between dietary patterns and subclinical atherosclerotic disease (fatty plaques in the arteries) remains limited, and published results are inconsistent and based on a small population,” explained Minerva Granado, a researcher from the University of Lleida, the Institute of Biomedical Research of Lleida (IRBLleida), and the Biomedical Research Network on Diabetes and Metabolic Associated Diseases (CIBERDEM).

For this reason, this research was initiated to assess the dietary habits of the population in Lleida and their consequences. “Participants with atherosclerotic disease are older and have a higher frequency of smoking, hypertension, dyslipidemia, and waist circumference,” confirmed Granado, who added that the study showed that individuals with better dietary habits related to the Mediterranean diet had a lower number of fatty plaques in their arteries compared to those with low adherence to the diet.

Another confirmation from the study is that women had a lower frequency and number of atherosclerotic plaques. The research was conducted using the Mediterranean Diet Adherence Screener (MEDAS) questionnaire and non-invasive ultrasounds to assess the arteries.

“It is important to note that the population we studied has a low to moderate risk of cardiovascular disease, so the results cannot be fully extrapolated to the general population, let alone to populations with other pathologies,” stated Marina Idalia Rojo López, a researcher in the Endocrinology, Diabetes, and Nutrition Group at the Institute of Research at the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau.

This expert added that “nonetheless, these findings support the use of strategies aimed at reducing atherosclerotic disease through the promotion of the Mediterranean diet and emphasize the need for nutritionists at all levels of healthcare.”

Reference article

Rojo-López MI, Bermúdez-López M, Castro E, Farràs C, Torres G, Pamplona R, Lecube A, Valdivielso JoséManuel, Fernández E, Julve J, Castelblanco E, Franch-Nadal J, Alonso Nú, Granado-Casas M, Mauricio Dí, on behalf of the ILERVAS project collaborators, Miquel E, Ortega M, Barbé F, González J, Barril S, Sánchez-de-la-Torre M, Portero-Otín M, Jové M, Hernández M, Rius F, Godoy P, Alonso MM-, Low adherence to the Mediterranean diet is associated with increased prevalence and number of atherosclerotic plaques in the ILERVAS cohort, Atherosclerosis (2023), doi: https://doi.org/10.1016/j.atherosclerosis.2023.117191.

Professor Lina Badimon, Director of the Cardiovascular Disease Research Area and the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases research group at the Research Institute of Hospital Santa Creu i Sant Pau – IIB Sant Pau, has been awarded the Michael J. Davies Prize at the 10th Congress of the European Association of Cardiovascular Pathology (EACVP), which took place this week in Padua, Italy.

Coinciding with the presentation of this award, Professor Lina Badimon gave a lecture titled “A Journey into Atherosclerotic Plaque: From the Laboratory to the Patient.” The presentation will focus on advances in understanding and characterizing atherosclerotic plaque, the cellular, molecular, and genetic processes involved in its progression, and how these processes contribute to the transformation of this silent arterial lesion into clinical ischemic syndromes. Finally, existing therapeutic advances and targets that do not yet have treatment will be discussed.

Today, Professor Badimon is one of the world’s leading researchers in arteriosclerosis and thrombosis. After completing her postgraduate studies in Spain, she spent 15 years in the United States conducting various studies on atherosclerosis and myocardial lesions resulting from ischemic episodes at prestigious institutions such as the Mayo Clinic, Mount Sinai Medical Center, and Harvard Medical School. Upon her return to Spain in the mid-1990s, she continued to explore cardioprotection processes in the context of myocardial infarction.

Throughout her distinguished professional career, Professor Badimon has made significant advances in understanding the complexity of atherosclerosis, which plays a pivotal role in most cardiovascular diseases—the leading cause of death worldwide—and in identifying innovative and groundbreaking strategies.

A study conducted at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau suggests that certain microRNAs (miRNAs) may be useful as non-invasive biomarkers for the early diagnosis of lymph node metastasis in patients with early-stage breast cancer. The research, led by Dr. Agustí Barnadas, head of the Clinical Oncology research group at IIB Sant Pau and head of the Medical Oncology service at the same hospital, focused on patients with early-stage breast cancer with estrogen receptor-positive (ER-positive) tumors.

MiRNAs are small RNA molecules that play a crucial role in gene expression regulation and have been linked to different stages of the metastatic process. One particularly intriguing aspect of miRNAs is their stability in peripheral blood, making them ideal candidates to be biomarkers using non-invasive techniques such as a blood sample.

The study, which had a proof-of-concept approach, included 30 patients with early-stage breast cancer for whom plasma samples, sentinel lymph nodes, and tumor tissue samples were available. The researchers performed RNA sequencing on these samples and conducted differential expression analysis, gene ontology, and enrichment analysis.

The results of the study revealed that circulating miRNAs showed inverse expression compared to tumor tissue or sentinel lymph nodes obtained from the same patients. Overall, there was a trend toward downregulation of circulating miRNAs. However, two miRNAs, miR-643a-3p and miR-223, were highlighted, showing increased expression in patients with positive sentinel lymph nodes, suggesting a potential link to the presence of lymph node metastasis.

Additionally, the researchers observed significant enrichment of biological processes related to the regulation of epithelial cell proliferation and transcriptional regulation, processes associated with metastasis promotion.

These results indicate the potential role of various circulating miRNAs as markers of axillary lymph node involvement in patients with early-stage breast cancer.

As explained by Dr. Barnadas, this advancement in breast cancer research not only offers new perspectives for the early diagnosis of metastasis but also raises the possibility of designing stricter monitoring strategies or clinical studies to explore the value of new therapies.

Cancer Research at Sant Pau On the occasion of World Cancer Research Day on September 24th, Dr. Barnadas highlights that the Sant Pau Research Institute currently has more than 200 ongoing clinical trials in cancer with active recruitment, and about 15 in the Phase I trial unit of Onco-Hematology.

This expert believes that one of the main goals of cancer research at present is to find mechanisms to trigger immune responses against tumors. In this regard, Dr. Javier Briones, director of the Cellular Immunotherapy and Gene Therapy Research Group at IIB-Sant Pau and head of the Clinical Hematology Unit at Sant Pau Hospital, has developed a new immunotherapy drug, CAR-T 19, which is being administered in a clinical trial to patients with certain types of lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma) that have not responded to other treatments. It is the second academic advanced therapy medicinal product produced and developed entirely at Sant Pau.

Moreover, in 2020, the first trial with a CAR-T immunotherapy drug in Europe began for the treatment of classic Hodgkin lymphoma and CD30+ non-Hodgkin T-cell lymphoma in relapse or refractory cases.

The initial results of this study were presented last year at the most prestigious international Hematology congresses, and it is currently in Phase II. It represents the first CAR-T30 immunotherapy drug (academic), fully produced at Sant Pau, attracting patients from various countries, including Italy, Austria, Poland, Russia, among others.

“This is an area of research that has made significant progress in recent years in the treatment of onco-hematological diseases, but we hope that it will also have an important role in solid tumors in the future,” Dr. Barnadas comments.

Another strong focus in oncology research is the genetic characterization of tumors. Recently, Dr. José Pablo Maroto, a researcher from the Clinical Oncology Group at IIB Sant Pau and an oncologist at the same hospital, found very rare mutations in the USP9X protein, which regulates critical cellular processes for tumor growth, in a study conducted in collaboration with the National Center for Oncological Research (CNIO).

This discovery arose from the case of a patient with metastatic kidney cancer who was treated with the drug temsirolimus, which worked much better than expected. The patient successfully overcame cancer. Nine years later, she was diagnosed with bone metastasis, but once again, temsirolimus proved effective.

“Collaboration with many other centers is essential to generate knowledge and develop new therapeutic strategies that can decisively advance in the fight against cancer,” Dr. Barnadas emphasizes.

According to this expert, one of the major challenges in cancer research today is recognizing the mechanisms of resistance that develop during treatment to make a tumor stop responding to a specific treatment at a certain point.

“This is a challenge in oncology in general because patients with disseminated disease, despite initially showing very good responses to targeted treatments, eventually develop resistance. Being able to identify it early and having tools to reverse it can lead to better results in the medium or long term.”

Another challenge is to better understand the mechanisms involved in the host’s immune response against the disease. “Here, we need to make more progress to achieve better results, where immunotherapy alone or in combination with chemotherapy and other strategies can achieve a better and longer-lasting effect. Often, you can observe significant results in advanced disease, but the patient, after a few years, develops the disease again, and at that point, you have no option for immunotherapy treatment or to try to reverse it, but the strategies are less effective,” as Dr. Barnadas indicates.

A third challenge in cancer research, according to this expert, is early identification “not only of resistance but also of disease relapse through new strategies such as liquid biopsy.”

Finally, Dr. Barnadas has emphasized the importance of not lowering the guard to further promote early cancer diagnosis and to determine the patient profile more precisely to decide who is a candidate for specific screening studies.

Reference article

Escuin D, López-Vilaró L, Bell O, Mora J, García-Valdecasas B, Moral A, Clos M, Boronat L, Arqueros C, Barnadas A. Circulating miRNA Expression Is Inversely Correlated with Tumor Tissue or Sentinel Lymph Nodes in Estrogen Receptor-Positive Early Breast Cancer Patients. Int J Mol Sci. 2023 Aug 27;24(17):13293. doi: 10.3390/ijms241713293. PMID: 37686099; PMCID: PMC10487825.

Direct transport to a referral centre for endovascular treatment may not be the best option for patients with a final diagnosis of intracerebral haemorrhage or haemorrhagic stroke, according to the results of a study published in the journal JAMA Neurology. The research, which is part of a secondary analysis of the RACECAT study, was led by researchers from the Germans Trias i Pujol Research Institute (IGTP), the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and the University Hospital Dr. Josep Trueta – IDIBGI of Girona.

The results of this study have been accompanied by the publication of an editorial in this prestigious scientific journal, emphasizing the need to re-evaluate stroke patient triage and transfer protocols based on the type of stroke, symptom severity and location. It suggests that, in patients with a subtype of haemorrhagic stroke, timely stabilisation of patients in the nearest care centre, followed by transfer to more specialised treatment centres, may be an effective strategy to improve health outcomes.

RACECAT, a landmark clinical trial

The RACECAT study was conducted in Catalonia between March 2017 and June 2020 with the participation of all stroke receiving hospitals and the Medical Emergencies System (SEM). It analysed more than a thousand patients with severe stroke and evaluated two approaches: sending them directly to hospitals with the capacity to perform endovascular treatments or sending them to the nearest hospital, with a possible subsequent transfer if a thrombectomy is necessary. The project was led by researchers from the IGTP, Vall d’Hebron Research Institute (VHIR), and the neurology services of the Germans Trias i Pujol (HUGTiP) and Vall d’Hebron hospitals.

Dr Natalia Pérez de la Ossa, co-leader of the Neurovascular Research Group at IGTP and coordinator of the Stroke Unit at HUGTiP, comments: “RACECAT has shown us that the decision to transfer a patient cannot be the same for all cases, as it depends on many factors. It is necessary to individualise the decision and find tools that allow us to distinguish the type of stroke when the patient is in the ambulance to decide the best destination. Currently, the RACE scale is used, which assesses the severity of the stroke, but we continue to do research to optimise protocols and advance treatment according to the needs of each case”.

Haemorrhagic stroke

The secondary RACECAT study recently published in JAMA Neurology focuses on intracerebral haemorrhages, including the 302 haemorrhagic stroke patients included in the RACECAT study. This type of stroke is the least common, accounting for 15-20% of cases, and tends to have a more severe prognosis.

The study’s first author, Dr Anna Ramos, researcher of the Cerebrovascular Diseases Group at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and assistant vascular neurologist at the Neurology Department of the same hospital, explains that “in haemorrhagic stroke, caused by the rupture of an artery that causes bleeding, there are two strategies: a simple action, such as lowering blood pressure and controlling blood sugar, or a complex action, with the transfer of the patient to centres with specialised ICUs and neurosurgeons. This second strategy sometimes involves longer transfers and, therefore, a delay in treatment. For this reason, determining the circuit to follow in haemorrhagic stroke is very important in order to know which of these two strategies is necessary and to transfer patients safely”.

First-option transfer to a specialist centre under scrutiny

The study results indicate that direct transport to an endovascular treatment centre instead of the nearest local centre increases medical complications for haemorrhagic stroke patients and may have negative consequences later on. After 90 days, patients transferred directly to a referral centre for endovascular treatment showed a worse functional outcome and higher mortality rate compared to those sent to the nearest facility.

According to Dr Yolanda Silva, assistant of the Neurology Service of the Hospital Josep Trueta and researcher at the Girona Biomedical Research Institute (IDIBGI), one of the main conclusions of the study is the need to “continue to advance in the research of new methods for a more precise selection of stroke patients at source and, thus, make the most appropriate referral”. Silva also highlights how this study can improve current pre-hospital transport protocols in cases of stroke: “Many of these patients experience bronchoaspirations during transport, and previous antiemetic treatment can be a positive measure”.

These results provide evidence that will help improve current pre-hospital transport protocols in stroke cases, and raise questions about the effectiveness of taking patients directly to endovascular treatment centres when haemorrhagic stroke is suspected.

Reference article

• Ramos-Pachón A, Rodríguez-Luna D, Martí-Fábregas J, Millán M, Bustamante A, Martínez-Sánchez M, Serena J, Terceño M, Vera-Cáceres C, Camps-Renom P, Prats-Sánchez L, Rodríguez-Villatoro N, Cardona-Portela P, Urra X, Solà S, Escudero M, Salvat-Plana M, Ribó M, Abilleira S, Pérez de la Ossa N, Silva Y. Effect of Bypassing the Closest Stroke Center in Patients with Intracerebral Hemorrhage: A Secondary Analysis of the RACECAT Randomized Clinical Trial. JAMA Neurol. 2023 Aug 21. DOI: 10.1001/jamaneurol.2023.2754.

A group of researchers from various departments at the Hospital de Sant Pau and the Research Group in Clinical Epidemiology and Healthcare Services of the IIB Sant Pau has published a study in The Lancet that provides promising results regarding colchicine as a reducer of cardiovascular complications in patients undergoing major thoracic surgery. In this study, titled “Effect of Colchicine on Perioperative Atrial Fibrillation and Myocardial Injury after Non-Cardiac Surgery in Patients Undergoing Major Thoracic Surgery (COP-AF): An International Randomized Trial,” 45 hospitals from 11 countries around the world participated. In Spain, 7 centers and 765 patients took part, with 275 of them coming from Sant Pau Hospital, making it one of the primary recruiting centers.

The COP-AF study is a large international and multicenter clinical trial that included patients undergoing thoracic surgery who were administered an anti-inflammatory drug like colchicine versus a placebo to reduce the risk of perioperative atrial fibrillation (AF – a cardiac arrhythmia) or myocardial injury after non-cardiac surgery (MINS – Myocardial injury after non-cardiac surgery). Perioperative AF and MINS have approximate incidences of 10% and 20%, respectively, and are common complications following major thoracic surgery.

Elevated levels of inflammatory biomarkers have been associated with a higher risk of perioperative AF and MINS. In this regard, the COP-AF study tested the hypothesis that anti-inflammatory treatment could reduce the incidence of these two significant complications.

The trial included a total of 3,209 patients aged 55 years or older in 45 hospitals from 11 countries worldwide (Austria, Belgium, Canada, China, Colombia, Italy, Malaysia, Pakistan, Spain, Switzerland, and the United States). In Spain, 7 hospitals and a total of 765 patients participated, with 275 of them from Sant Pau Hospital, one of the primary recruiters for this study.

The research findings were presented at the European Society of Cardiology (ESC) Congress, held recently in Amsterdam, the Netherlands, by the lead international investigator, Dr. David Conen, a scientist at the Population Health Research Institute (PHRI) and associate professor of Medicine at McMaster University in Hamilton, Canada.

The primary investigators from Hospital de Sant Pau and IIB Sant Pau were Dr. Juan Carlos Trujillo and Dr. Elisabeth Martínez-Tellez from the Thoracic Surgery Department of the Hospital, and Dr. Ekaterine Popova from the Research Group in Clinical Epidemiology, Public Health, and Primary Care at IIB Sant Pau. They worked collaboratively with professionals from the departments of Thoracic Surgery (Dr. Josep Belda Sanchis, Dr. Alejandra Libreros, Dr. Georgina Planaz, Dr. Esther Cladellas, and Dr. Mauro Guarino), Epidemiology (Dr. Gerard Urrutia, Dr. Melixa Medina, and Ibell Araúz), Anesthesiology and Resuscitation (Dr. Ana Parera, Dr. Marta Argilaga, Dr. Josep Mª Gil, and Dr. Gracia Herranz), Nursing (Anna Rovira and Asunción Turró), Cardiology (Dr. Jose Guerra, Dr. Zoraida Moreno, Dr. Francisco Méndez, Dr. Jesús Àlvarez), Traumatology (Dr. Aranzazu González), Neurology (Dr. Anna Ramos-Pachón), Clinical Biochemistry (Dr. Álvaro García), and Pharmacy (Ainhoa Rodríguez-Arias and Nuria Berga).

Key Study Results

Half of the patients were randomly assigned to receive 0.5 mg of colchicine, while the other half received a matching placebo. Both the research staff and the patients were unaware of the treatment assignment. The first dose of the study treatment was administered within 4 hours before surgery and continued twice daily for a total of 10 days.

Clinically significant AF occurred in 103 out of 1,608 (6.4%) patients assigned to colchicine and in 120 out of 1,601 (7.5%) patients assigned to placebo, with a hazard ratio (HR) of 0.85 (95% confidence interval [CI] 0.65 to 1.10), p=0.22. MINS occurred in 295 (18.3%) patients assigned to colchicine and in 325 (20.3%) patients assigned to placebo, with an HR of 0.89 (95% CI 0.76 to 1.05), p=0.16. However, the composite outcome of clinically significant AF or MINS occurred in 360 (22.4%) patients in the colchicine group and 415 (25.9%) patients in the placebo group (HR 0.84; 95% CI 0.73 to 0.97), p=0.02.

Dr. Juan Carlos Trujillo, clinical head of the Thoracic Surgery Department at Sant Pau Hospital and one of the main investigators of the study, pointed out that “although colchicine did not significantly reduce the incidence of the co-primary outcomes of clinically significant perioperative AF or MINS, it did significantly reduce the composite of the two co-primary outcomes.”

Dr. Ekaterine Popova, researcher from the Group in Clinical Epidemiology and Healthcare Services at IIB Sant Pau, stated, “While not definitive, the overall results of the trial provide a hopeful signal of benefit for colchicine in reducing the incidence of adverse cardiovascular complications in patients undergoing major thoracic surgery.” She added that “colchicine significantly increased the risk of non-infectious diarrhea, but the data indicate that these episodes were temporary and mild.”

Adverse cardiovascular complications are the most common among the 300 million patients who undergo non-cardiac surgery each year worldwide. According to experts, urgent interventions are needed to reduce this risk. The results of this trial support the importance of further investigating the role of colchicine in preventing these episodes in patients undergoing non-cardiac surgery.

Reference article

David Conen, Michael Ke Wang, Ekaterine Popova, Matthew T V Chan, Giovanni Landoni, Juan P Cata, Cara Reimer, Sean R McLean, Sadeesh K Srinathan, Juan Carlos Trujillo Reyes, Ascension Martín Grande, Anna Gonzalez Tallada, Daniel I Sessler, Edith Fleischmann, Barbara Kabon, Luca Voltolini, Patrícia Cruz, Donna E Maziak, Laura Gutiérrez-Soriano, William F McIntyre, Vikas Tandon, Elisabeth Martínez-Téllez, Juan Jose Guerra-Londono, Deborah DuMerton, Randolph H L Wong, Anna L McGuire, Biniam Kidane, Diego Parise Roux, Yaron Shargall, Jennifer R Wells, Sandra N Ofori, Jessica Vincent, Lizhen Xu, Zhuoru Li, John W Eikelboom, Sanjit S Jolly, Jeff S Healey, P J Devereaux, on behalf of the COP-AF Investigators* “Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial”. Published online August 25, 2023 https://doi.org/10.1016/S0140-6736(23)01689-6    

Professor Lina Badimon, Director of the Research Area of Cardiovascular Diseases and the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases research group at the Research Institute of Hospital Santa Creu i Sant Pau – IIB Sant Pau, has been invited to deliver the “ESC William Harvey Lecture on Basic Science,” one of the most prominent and prestigious talks at the European Society of Cardiology (ESC) Congress 2023 to be held in Amsterdam, Netherlands, from August 25 to 28.

The lecture, which will also result in the publication of an article in the ESC-News journal from the Congress, is titled “Tissue Factor in the Continuum of Cardiovascular Disease Progression: Effects Beyond Thrombosis.”

Throughout her distinguished professional career, Professor Badimon has made significant advancements in understanding the complexity of atherosclerosis and identifying innovative and groundbreaking strategies.

Her research in cardiovascular investigation has focused on the critical role that atherosclerosis plays in most cardiovascular diseases, which constitute the leading cause of death worldwide.

After completing postgraduate studies in Spain, Professor Badimon spent 15 years in the United States conducting various studies on atherosclerosis and myocardial lesions resulting from ischemic episodes at prestigious institutions such as the Mayo Clinic, Mount Sinai Medical Center, and Harvard Medical School. Upon returning to Spain in the mid-1990s, she continued exploring cardioprotection processes in the context of myocardial infarction.

In her lecture, Professor Badimon will discuss a project she began developing in the United States: the role of tissue factor in the progression of cardiovascular diseases. This research serves as a clear example of how basic science can be instrumental in understanding a clinical problem and finding solutions that translate into improved prognosis and quality of life for patients.

Tissue factor is a key component of thrombotic events that, along with advanced atherosclerosis, are factors leading to myocardial infarction. Thanks to the use of advanced molecular technologies and funding from the Spanish Ministry of Health, Professor Badimon’s team at IIB Sant Pau has successfully produced a triple mutant model of tissue factor that lacks thrombotic activity but retains its angiogenic capacity. This modified protein is being used to better understand the effects of myocardial infarction and explore its therapeutic potential in microvascular regeneration, tissue reperfusion promotion, and damage prevention.

Future Outlook

Professor Badimon will discuss the importance of innovation in the development of new drugs for the prevention and treatment of cardiovascular diseases. In a field where cardioprotection is a fundamental unmet medical need, her research promises significant advancements. Following several successful studies in cell cultures and small animal models, among her upcoming goals is to demonstrate preclinical efficacy in a porcine model. “Being realistic about patent timelines and funding, we expect that the research findings will translate into clinical trials in the coming years,” comments Professor Badimon.

Regarding the future of research in the cardiovascular field, Professor Badimon highlights the importance of repurposing existing drugs and the use of new technologies in molecular and imaging fields to advance the understanding of heart diseases, identify patients requiring early intervention, and develop effective preventive strategies. Research into cardiogenic shock biomarkers and the pathophysiology and biomarkers of familial hypercholesterolemia are also topics of interest for Professor Badimon’s team at IIB Sant Pau.

Un nou estudi realitzat en persones amb diabetis tipus 2 ha revelat resultats interessants sobre el tractament de la hiperglucèmia i la seva relació amb la retinopatia diabètica, una complicació ocular que sovint afecta les persones amb diabetis. La investigació “Rapid Reduction of HbA1c and Early Worsening of Diabetic Retinopathy: A Real-World Population-Based Study in Subjects With Type 2 Diabetes”, publicada a la prestigiosa revista diabetològica Diabetes Care, suggereix que una reducció ràpida de l’HbA1c, una mesura clau en el control glucèmic de la diabetis, no empitjora la retinopatia en les persones que ja tenien una forma lleu o moderada d’aquesta complicació”. Això és una bona notícia per a les persones amb retinopatia i els professionals de la salut, ja que implica que la millora del control de la glucosa en sang no necessita ser retardada per por de l’empitjorament de la retinopatia diabètica en aquests casos. Aquesta troballa pot contribuir a millorar el control de la diabetis i  es seves complicacions .

En l’estudi hi han participat diferents grups de recerca, i ha estat liderat per Josep Franch Nadal, del Grup de Diabetis d’Atenció Primària (DAP_Cat) de l’Institut d’investigació en Atenció Primària Jordi Gol (IDIAPJGol), Dídac Mauricio, de l’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau (IIB Sant Pau), i Rafael Simó del Vall d’Hebron Institut de Recerca (VHIR). Tots ells, també pertanyen al Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM).

Saber si un descens ràpid dels nivells de glucosa en sang estava relacionat amb l’empitjorament precoç de la retinopatia diabètica és un tema que preocupa als professionals sanitaris, ja que la retinopatia diabètica és una de les complicacions més comunes de la diabetis i la primera causa de ceguesa evitable en la població adulta. La prevalença d’aquesta complicació és alta i afecta almenys a 2 de cada 10 persones amb diabetis i es preveu que aquesta xifra incrementi. En l’estudi es van analitzar les dades de més de 1.000 persones amb diabetis tipus 2 i retinopatia diabètica lleu o moderada. Els investigadors van estudiar la relació entre la reducció dels nivells de glucosa en sang (l’HbA1c) de més d’un 1.5% en menys de 12 mesos o més del 2% en menys de 6 mesos i l’empitjorament de la retinopatia diabètica.

Segons Josep Franch, coordinador del DAP_Cat, “molts facultatius tenien por de ser agressius a l’hora de fer baixar el sucre i podien pensar que era millor fer-ho a poc a poc, encara que això augmentés el risc de patir d’altres complicacions no retinopàtiques, però amb aquest estudi, que és el primer que es fa en condicions de pràctica clínica habitual, hem vist que no hi ha arguments per retardar el control de la glucèmia fins els objectius que desitgem per a cada pacient“.

L’HbA1c (hemoglobina glicosilada) és una prova clínica utilitzada per mesurar el control de la glucosa en sang al llarg del temps. És una fracció de l’hemoglobina (una proteïna que es troba a les cèl·lules vermelles de la sang i que transporta l’oxigen als teixits del cos) que s’uneix a la glucosa. Per a les persones amb diabetis, l’HbA1c és una mesura clau per avaluar el control de la glucosa en sang i la gestió de la malaltia. Un nivell d’HbA1c elevat indica un control deficient de la diabetis i un risc més alt de complicacions associades, com ara la retinopatia diabètica, que afecta els ulls.

Cal tenir en compte que aquest estudi es va centrar en persones amb retinopatia diabètica lleu o moderada, i no en persones en fases més avançades de retinopatia. En la situació menys freqüent d’una retinopatia diabètica greu, i davant la falta d’evidències en condicions habituals de pràctica clínica, no es pot establir la seguretat o el perill de la baixada ràpida de la glucèmia.

Un estudi liderat pel Dr. Jaume Baldirà, investigador del Grup de Recerca en Medicina Intensiva de l’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau i metge adjunt del mateix hospital, ha identificat un nou biomarcador que podria ajudar a distingir un subgrup de pacients amb sèpsia i millorar-ne així les estratègies de diagnòstic i tractament.

La sèpsia, també coneguda com a septicèmia, és una resposta inflamatòria generalitzada de l’organisme davant d’una infecció bacteriana, vírica o fúngica que pot danyar els òrgans, fer que deixin de funcionar i, fins i tot, arribar a produir la mort. És considerada un problema de salut pública molt greu i és àmpliament reconeguda com una de les causes principals de mortalitat global. Per això, la detecció precoç i l’inici immediat del tractament adequat són fonamentals per reduir la mortalitat entre els pacients.

“Actualment, per saber l’estat de gravetat del pacient amb sèpsia, utilitzem el sistema de puntuació SOFA (per les seves sigles en anglès, Sequential Organ Failure Assessment)” ens explica el Dr. Baldirà. Es tracta d’una eina que avalua la gravetat de la disfunció orgànica en pacients crítics tenint en compte variables de sis sistemes d’òrgans com, per exemple, la pressió arterial, l’estat fetge, el ronyó, etc. Per tant, com més baixa sigui la puntuació SOFA (inferior o igual a 6), menor risc de mortalitat.

No obstant, la puntuació SOFA no és infal·lible. En algunes ocasions, no té la sensibilitat necessària ja que s’ha vist que hi ha un subgrup de pacients amb sèpsia que, tot i tenir una puntuació SOFA baixa, experimenten taxes de mortalitat elevades per insuficiència orgànica. Per identificar aquest subgrup específic, s’estan començant a utilitzar biomarcadors de sang com a eina de cribratge complementària.

Aquest estudi, que publica la revista Biomedicines, avalua l’habilitat predictiva de quatre biomarcadors, la proadrenomedullina de la regió mitjana (MR-proADM), la procalcitonina (PCT), la proteïna C reactiva (CRP) i el lactat, que podrien ajudar a estratificar el risc de mortalitat en pacients amb sèpsia i una puntuació SOFA menor o igual a 6, un subgrup molt específic.

Per fer-ho, es va realitzar un anàlisi observacional prospectiu que va incloure 284 pacients que reunien els criteris per l’activació del codi sèpsia de l’Hospital Universitari Vall d’Hebrón i es van determinar els biomarcadors i altres paràmetres necessaris de les mostres de sang extretes del Banc de Sèpsia del mateix hospital.

Els resultats de l’estudi suggereixen que el biomarcador MR-proADM podria ajudar a identificar el risc de mortalitat als 28 dies en pacients amb sèpsia adquirida a la comunitat (fora d’hospital) i puntuació SOFA menor o igual a 6, mentre que el biomarcador lactat (lactacidèmia) seria més eficaç per predir la mortalitat als 28 dies en pacients amb infecció adquirida a l’hospital.

Així doncs, “la mesura inicial d’aquests biomarcadors podria facilitar estratègies de tractament precoç basades en la seva activació en pacients amb sèpsia o xoc sèptic i una puntuació SOFA baixa” afirma el Dr. Baldirà.

Tot i que l’estudi compta amb algunes limitacions com per exemple, una mostra de pacients petita i que el criteri d’activació del codi sèpsia pot variar segons l’hospital, “els resultats són consistents amb la literatura existent i aporten dades de suport addicionals per a aquests biomarcadors i el seu ús en diferents entorns hospitalaris i diferents nivells de malaltia” assenyala.

“Aquesta troballa és molt important perquè, en un futur, el biomarcador MR-proADM podria utilitzar-se en la pràctica estàndard per ajudar-nos a detectar subgrups de pacients amb sèpsia i tractar-los millor i més ràpid” conclou el doctor.

Aquest estudi ha estat realitzat en col·laboració amb el Servei de Medicina Intensiva, el Grup de Recerca de Xoc, Disfunció Orgànica i Ressuscitació de la Vall d’Hebrón Institut de Recerca, el Servei d’Anàlisis Clíniques i el Servei de Microbiologia de l’Hospital Vall d’Hebron  i ha estat finançat per una subvenció restringida de Thermo Fisher (Hennigsdorf, Alemanya).

Article de referència

Baldirà, J.; Ruiz-Rodríguez, J.C.; Ruiz-Sanmartin, A.; Chiscano, L.; Cortes, A.; Sistac, D.Á.; Ferrer-Costa, R.; Comas, I.; Villena, Y.; Larrosa, M.N.; et al. Use of Biomarkers to Improve 28-Day Mortality Stratification in Patients with Sepsis and SOFA ≤ 6. Biomedicines 2023, 11, 2149. https://doi.org/10.3390/ biomedicines11082149

Dr. Alba Tristán Noguero, postdoctoral researcher of the ‘Margarita Salas’ Program at the Department of Genetics, Microbiology, and Statistics of the Faculty of Biology at the University of Barcelona (UB), and a member of the Molecular Physiology of Synapses research group at the Sant Pau Research Institute – IIB Sant Pau, has been awarded the prestigious “EMBO Scientific Exchange Grant”.

This scholarship will enable her to undertake a stay at the University of Edinburgh, in the laboratory of Professor Peter C. Kind, to work on the project entitled “Calcium dynamics at the level of dendritic spines in an animal model of Syngap1 deficiency.” This project is part of the studies conducted by the IIB Sant Pau group on the neurodevelopmental disorder caused by the deficiency of the SYNGAP1 gene, an epileptic encephalopathy with an estimated prevalence of 1 case per 16,000 births.

The hypothesis of the research team led by Dr. Àlex Bayés is based on the premise that calcium dynamics at the level of synapses in the central nervous system would be altered. Excess calcium could be at the root of the synaptic dysfunction characteristic of SYNGAP1 deficiency, which in turn plays a central role in two of the main symptoms, epilepsy, and intellectual disability. If the hypothesis is confirmed, this stay will not only serve to deepen and establish new international research collaborations but also to investigate new therapies for SYNGAP1 patients focused on normalizing synaptic-scale calcium dynamics.

Double immunofluorescence with CD206 and CD68. The immunostaining shows CD206+ macrophages (green), CD68+ macrophages (red), and colocalization of CD206+ and CD68+ macrophages (yellow). Representative image of a localized infiltrate where most of CD68+ do not colocalize with CD206+ macrophages, showing an M1 predominance. Author: Andrea Bravo

Idiopathic inflammatory myopathies (IIM) are immune-mediated diseases characterized by muscle weakness and inflammatory infiltrates in muscle biopsies. Macrophages play a crucial role in skeletal muscle’s inflammatory response and tissue repair processes.

In a study performed by researcher Andrea Bravo Gómez and led by Anais Mariscal Rodríguez at the Inflammatory Diseases group, and Eduard Gallardo Vigo at the Neuromuscular Diseases group, researchers used a double immunofluorescence staining method to differentiate between pro-inflammatory (M1) and anti-inflammatory/repair (M2) macrophages.

Notably, idiopatic inflammatory myopathies biopsies had the lowest proportion of M2 macrophages, suggesting a prevailing pro-inflammatory environment in affected muscles.

This study enhances our understanding of macrophage involvement in muscle pathologies and highlights the potential of macrophage analysis for clinical applications. Larger cohort studies are needed to validate these findings and explore macrophage subtypes in specific muscle pathology subgroups.

Patients with locally advanced or metastatic urothelial cancer who are unable to receive cisplatin chemotherapy, which is the conventional first-line treatment for this disease, face very limited options to combat their condition. Unfortunately, this is not an exceptional situation, as renal insufficiency, for example, is among the factors that contraindicate this therapeutic alternative when dealing with a tumor that affects the urinary system.

Now, a study in which Dr. José Pablo Maroto, a researcher from the Clinical Oncology Group at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and an oncologist at the same hospital, has participated, has been able to verify that the combination of two drugs, enfortumab vedotin and pembrolizumab, which had previously shown benefits in survival in second-line treatment and in cases of advanced urothelial cancer, offers results comparable to cisplatin chemotherapy.

It is a Phase II study, called EV-103, which analyzes data from a specific cohort of patients with locally advanced or metastatic urothelial cancer who were not suitable to receive cisplatin. The results are published in the Journal of Clinical Oncology, with Dr. Maroto as the sole Spanish author.

The main conclusion of the study is that patients who received this new therapeutic combination – enfortumab vedotin and pembrolizumab – showed a high response rate, and the effects were long-lasting, which positions it as a good option for first-line treatment. These results represent a significant advancement in the treatment of advanced urothelial cancer and offer new hope for patients facing this disease who cannot undergo cisplatin chemotherapy.

Until now, patients with advanced or metastatic urothelial cancer who could not receive cisplatin chemotherapy, either due to renal insufficiency, peripheral neuropathy, hearing problems, cardiac issues, or poor overall condition, were given a carboplatin-derived drug that offered much inferior results. “Cisplatin is a drug that is eliminated through the renal route and therefore requires patients to be well-hydrated. In the case of frail patients or those with renal problems, we cannot prescribe it, and thus, we cannot offer the optimal treatment,” comments Dr. Maroto.

Currently, the confirmatory Phase III clinical trial is underway. If its results are positive as expected, they would lay the groundwork for the approval of this therapeutic combination in Spain, which is currently under investigation.

Reference article

O’Donnell PH, Milowsky MI, Petrylak DP, Hoimes CJ, Flaig TW, Mar N, Moon HH, Friedlander TW, McKay RR, Bilen MA, Srinivas S, Burgess EF, Ramamurthy C, George S, Geynisman DM, Bracarda S, Borchiellini D, Geoffrois L, Maroto Rey JP, Ferrario C, Carret AS, Yu Y, Guseva M, Homet Moreno B, Rosenberg JE. Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. J Clin Oncol. 2023 Jun 27:JCO2202887. doi: 1200/JCO.22.02887. Epub ahead of print. PMID: 37369081.

Un estudi multicèntric en què han participat, investigadors del Grup de Cirurgia General i Digestiva de l’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, que dirigeix el Dr. Antonio Moral, han guanyat el XXIV Premi Dr. Lino Torre en investigació quirúrgica.

A l’estudi han participat el Dr. Eduardo Mª Targarona, que és també director de la Unitat de Cirurgia Hematològica i Gastrointestinal del mateix hospital; el Dr. Jesús Manuel Bollo Rodríguez; la Dra. Maria Pilar Hernández Casanovas; la Dra. María Del Carmen Martínez Sánchez, i la Dra. Anna Sánchez López.

Aquest premi reconeix la tasca dels cirurgians que hagin publicat un treball de recerca a la literatura mèdica durant l’any natural precedent al de l’atorgament del premi. El treball premiat, en què van participar diversos hospitals d’Espanya, es titula “Resultats a curt termini de la quimiorradioteràpia i l’escissió local davant de l’escissió total del mesorrecte al càncer de recte T2-T3ab,N0,M0: un assaig multicèntric , aleatoritzat, controlat, de fase III”.

L’estudi, conegut com a TAU-TEM, buscava demostrar la no inferioritat de la recurrència local i la millora en la morbiditat assolida amb la combinació de quimiorradioteràpia preoperatòria i microcirurgia endoscòpica transanal en comparació de l’excisió total del mesorrecte.

El càncer rectal és una malaltia que ha presentat altes taxes de recurrència local, fet que ha portat a l’aplicació estàndard de la microcirurgia endoscòpica transanal. Tot i això, informes inicials sobre la combinació amb quimioteràpia han suggerit una reducció en la recurrència local. Amb l’objectiu de validar aquestes troballes i comparar-les amb el tractament convencional, els investigadors van fer aquest assaig clínic aleatoritzat i controlat.

El tractament combinat va demostrar taxes elevades de resposta patològica completa –gairebé un 45%– i una alta taxa de compliment amb la quimiorradioteràpia (98,8%) en pacients amb càncer rectal. A més, es van observar taxes significativament més baixes de complicacions postoperatòries i hospitalització en comparació del grup que només va rebre la cirurgia.

Aquestes troballes són encoratjadores, ja que suggereixen que la combinació de les dues tècniques podria representar una estratègia de tractament efectiva i menys invasiva per als pacients amb càncer rectal en etapes primerenques. Tanmateix, cal fer un seguiment a llarg termini per avaluar l’eficàcia i la seguretat a llarg termini d’aquest enfocament.

A study coordinated by Dr. Vicenta Llorente-Cortés, a researcher at CIBERCV in the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and the Biomedical Research Institute of Barcelona (IIBB-CSIC), reveals that LRP1-based immunotherapy reduces cardiac extracellular matrix (ECM) remodeling induced by intracellular accumulation of esterified cholesterol in cardiomyocytes. The research, which involved collaboration from CIBERDEM, UB, the CIRIMAT Institute in Toulouse (France), and the University of Córdoba (Argentina), has been published in the Journal of Medicinal Chemistry.

The study analyzed the effect of anti-P3 antibodies on the biological alterations of cardiac ECM induced by a cholesterol-enriched diet. The study demonstrates that immunizing rabbits with the P3 sequence of the LRP1 receptor produces specific anti-P3 antibodies in the blood that selectively and specifically block the entry of esterified cholesterol transported by lipoproteins into cardiomyocytes.

The results show that a cholesterol-rich diet increases intracellular levels of esterified cholesterol and triglycerides in cardiomyocytes, the extracellular level of collagen, the degree of fibrosis, water retention, and plasticization of the ECM in the heart. It is noteworthy that in immunized animals, anti-P3 antibodies specifically reduce intracellular accumulation of esterified cholesterol within cardiomyocytes, and this effect is sufficient to reduce collagen accumulation, water retention in the ECM, and cardiac fibrosis.

These findings demonstrate that anti-P3 antibodies improve cardiac extracellular matrix remodeling by reducing the accumulation of intracellular esterified cholesterol in cardiomyocytes.

This study, along with others published by the same group on this LRP1-based immunotherapy model (Actis-Dato V et al. Biomed Pharmacother. 2022), provides a solid foundation for the development of immune-based therapies focused on reducing esterified cholesterol accumulation in the heart as a potentially useful therapeutic strategy in the management of heart failure.

Reference article

Samouillan V, Garcia E, Benitez-Amaro A, La Chica Lhoëst MT, Dandurand J, Actis Dato V, Guerra JM, Escolà-Gil JC, Chiabrando G, Enrich C, Llorente-Cortes V. Inhibitory Effects of LRP1-Based Immunotherapy on Cardiac Extracellular Matrix Biophysical Alterations Induced by Hypercholesterolemia. J Med Chem. 2023 May 11;66(9):6251-6262. doi: 10.1021/acs.jmedchem.2c02103. Epub 2023 Apr 28. PMID: 37116069; PMCID: PMC10184115.