Research involving pregnant women, children, and infants represents a significant challenge for science, as safety requirements and study criteria are particularly strict. This often translates into an obstacle to obtaining new evidence-based results that allow for advancements and provide solutions to improve clinical practice in these population groups.

Although these cooperation networks have existed for several years, this situation can take a significant leap forward thanks to the renewal and innovation that this new network brings. Eighteen Spanish entities have signed a framework agreement within the Maternal and Child Health and Development Network (SAMID) of the Health Research Cooperative Networks for Health Outcomes (RICORS) program, coordinated by Dr. Elisa Llurba, the principal investigator of the Perinatal and Women’s Medicine Group at the Research Institute of the Hospital de Santa Creu i Sant Pau – IIB Sant Pau, director of the Obstetrics and Gynecology Department at the same hospital, and professor at the Autonomous University of Barcelona (UAB).

This RICORS-SAMID maternal and child consortium, established in 2008 and renewed in 2021 with the support of the Carlos III Health Institute of the Ministry of Health, consists of a total of 20 research groups and 27 associated clinical groups from different Spanish research institutes and healthcare centers. This means the participation of more than 300 researchers, including neonatology/pediatrics and obstetrics specialists, primary care pediatricians, biologists, anthropologists, specialists in perinatal mental health, midwives, nurses, primary care and NICU nurses, nutritionists, educators, graphic designers, physical education professionals, among others, who join forces to promote a comprehensive and collaborative plan to improve the health of women, mothers, and babies.

With this new framework agreement, the centers that are part of the RICORS-SAMID network will share research objectives and projects, as well as clinical data, images, and samples, allowing for the creation of the largest information bank in Spain. This will facilitate large-scale clinical trials, innovative studies such as big data and artificial intelligence, and contribute to leadership in this field at the European level.

According to Dr. Llurba, “the agreement signed within the RICORS-SAMID Network is a decisive step in promoting research through collaborative work in the field of maternal and child health, which will also attract talent and access competitive public and private funding.”

The coordinator of the RICORS-SAMID network explains that with this agreement, “we have achieved a legal framework that not only aims to facilitate research among different groups but also intends to be a tool to disseminate advancements so that users themselves and society, in general, can play a more active role in the process. For this reason, an open mailbox has been set up where citizens can express their needs and get involved in the research process through a co-creation and idea incubation process.”

IMPACTFUL PROJECTS

One example of the projects being developed within the RICORS-SAMID network is a study evaluating neurological development in newborns affected by congenital heart disease. Samples from both mothers and infants, as well as prenatal resonance and ultrasound images, and follow-up data during the first years of life, are being analyzed. The goal is to find neonatal and postnatal predictors associated with neurological development and the quality of life of these children.

“Congenital heart diseases are a relatively rare type of congenital malformation, but their impact on health is significant, and we need a lot of data that can be translated into clinical responses and truly improve the health of these children in their daily lives,” says Dr. Llurba.

Furthermore, other projects are underway, studying, for example, prognostic and diagnostic markers for preeclampsia and prematurity, intrauterine growth restriction and its long-term consequences, the effects of environmental pollution and prenatal exposure to substance abuse on maternal and child health, early reproductive losses and their impact on mental health, renal impairment in mothers with preeclampsia, improving the diagnosis of early gestational diabetes during the first trimester of pregnancy and its effect on child neurodevelopment, nutrition and its effects on childhood obesity, neonatal circulatory failure biomarkers, treatment of bacterial sepsis in newborns, resuscitation of premature infants, treatment of complications of neonatal hypoxic-ischemic encephalopathy, hypoxic-ischemic brain injuries, diabetes, and the experiences, needs, and expectations of families and patients. Additionally, projects focusing on health education, promoting healthy habits at any age, preventing sudden death and the sequelae of cardiorespiratory arrest through training actions aimed at professionals and citizens, as well as research on clinical and ethical aspects of pediatric palliative care, are also being developed within the network.

The hospitals and research institutes participating in the framework agreement are:

• Instituto de Investigación del Hospital de la Santa Creu i Sant Pau – IIB Sant Pau
• Instituto de Investigación Biosanitaria (IMIB) – Fundación para la Formación e Investigación Sanitarias de la Región de Murcia (FFIS)
• Instituto de Investigación Sanitaria La Fe – Fundación para la Investigación del Hospital Universitario La Fe de la Comunidad Valenciana
• Instituto de Investigación Hospital 12 de Octubre – Fundación Investigación Biomédica Hospital Universitario 12 de Octubre
• Instituto de Investigación Sant Joan de Déu (IRSJD) – Fundación Privada per a la Recerca i la Docència Sant Joan de Déu
• Instituto Biocruces Bizkaia – Asociación Instituto de Investigación Sanitaria Biocruces Bizkaia
• Grupo de Investigación AFIN – Universitat Autònoma de Barcelona – UAB
• Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) – Fundación para la Investigación Biomédica del Hospital Universitario La Paz
• Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) – Fundació de Recerca Clínic Barcelona
• Instituto de Investigación Sanitaria Gregorio Marañón – Fundación para la Investigación Biomédica del Hospital Gregorio Marañón
• Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA) – Fundación Pública Andaluza para la Investigación Biosanitaria de Andalucía Oriental – Alejandro Otero
• Instituto de Investigación Sanitaria Aragón – Fundación Instituto De Investigación Sanitaria Aragón
• Instituto de Investigación Sanitaria Hospital Clínico San Carlos – Fundación para la Investigación Biomédica del Hospital Clínico San Carlos
• Instituto de Investigación Sanitaria Valdecilla (IDIVAL) – Fundación Instituto de Investigación Marqués de Valdecilla
• Instituto de Investigación Sanitaria de Santiago de Compostela – Fundación Instituto de Investigación Sanitaria de Santiago de Compostela
• Fundació Puigvert
• Instituto de Investigación Sanitaria del Principado de Asturias – Fundación para la Investigación y la Innovación Biosanitaria del Principado de Asturias

The phase I clinical trials unit of the Medicines Research Center (CIM) of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau has renewed the Certificate of compliance with the rules of good clinical practice (BPC) after having passed the inspection by the Direcció General d’Ordenació i Regulació Sanitària of the Generalitat de Catalunya.

This certificate recognizes compliance with the requirements necessary to carry out phase I clinical trials or first administration of medicines in humans, in accordance with the principles of good clinical practice (GCP) in force in the European Union and the technical and sanitary requirements of the phase I units published by the Department of Health of the Generalitat de Catalunya.

The CIM carries out phase I efficacy and tolerability clinical trials, pharmacokinetics, drug metabolism and interaction studies, bioequivalence studies and first studies in humans.

La participació de l’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau a la Festa de la Ciència enguany va ser tot un èxit. Durant aquest esdeveniment, que s’ha consolidat com una trobada pública anual amb la ciència i la recerca a la nostra ciutat, molta gent ens va venir a veure i es va divertir amb les activitats de divulgació científica, jocs, micro xerrades i tallers que l’IIB Sant Pau va preparar.

Centenars de petits i grans van col·laborar per fer el nostre trencaclosques científic gegant. A més, la periodista Cristina Junyent va fer una entrevista per a Ràdio Farró amb la Dra. Elena Roselló-Díez, investigadora del Grup de Recerca Associat IIB Sant Pau en Cirurgia Cardíaca i especialista en Cirurgia Cardíaca a l’Hospital de Sant Pau que va parlar sobre la innovació tecnològica en cirurgia cardíaca.

La Dra. Roselló-Díez també va liderar el taller “Descobreix com funciona el cor i l’aparell circulatori”, en el qual va explicar els components de l’aparell cardiovascular i les seves funcions amb diferents objectes i l’ajuda de material gràfic on els participants van poder reconstruir una maqueta del nostre sistema cardiovascular i aprendre com funciona.

A més, es van dur a terme diverses microxerrades, una d’elles a càrrec de l’Ana Novoa, investigadora de l’IIB Sant Pau al Departament ASPB Servei de Sistemes d’Informació en Salut (SeSIS) de l’Agència de Salut Pública de Barcelona (ASPB) amb el títol “Viure juntes per viure millor: habitatge cooperatiu i salut”. El Dr. Robert Belvís i la Dra. Noemi Morellón, professionals de l’IIB Sant Pau i de l’Hospital de Sant Pau van parlar sobre “Elèctrodes al cervell per combatre el mal de cap multiresistent” i el Dr. Israel Fernández-Cadenas, investigador principal del Grup de Farmacogenòmica i Genètica Neurovascular de l’IIB Sant Pau va oferir la microxerrada: “Com la genètica ens ajuda a trobar nous tractaments per a malalties molt comunes”.

The Inter-American Society of Cardiology has awarded the Academic and Scientific Career Award to Prof. Lina Badimon, Director of the Cardiovascular Disease Research Area and the Molecular Pathology and Therapeutics Research Group of Atherothrombotic and Ischemic Diseases at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau.

This award, which represents recognition from the international scientific community for the work of this outstanding researcher, was presented during the annual congress of this scientific society, which is currently taking place in Panama.

Prof. Badimon expressed her gratitude for this distinction and commented that one of the achievements in her career that she is most satisfied with are “the original research papers carried out over the years that are leading to the transfer of knowledge to clinical practice for the benefit of patients.”

Furthermore, among her tasks, she highlights the training of research personnel as one of the most satisfying aspects, as well as the collaborative work with groups “from other countries and continents who are also developing their own research programs and projects.”

Prof. Lina Badimon views the future of cardiology research with optimism. “I believe we will have a period of great value in the coming years thanks to the incorporation of new technologies that facilitate molecular and genetic studies, allowing knowledge to be increasingly applied in clinical practice.”

Finally, Prof. Badimon commented that scientific activity “requires sustained dedication, often in silence, and in many cases, it is not widely recognized. That is why awards like the one I am receiving now are very gratifying.”

Núñez C, García-Alix A, Arca G, Agut T, Carreras N, Portella MJ, Stephan-Otto C. Breastfeeding duration is associated with larger cortical gray matter volumes in children from the ABCD study. J Child Psychol Psychiatry. 2023 Mar 22. doi: 10.1111/jcpp.13790. Epub ahead of print. PMID: 36946606.

Dr. Margarita Majem Tarruella, 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 in two studies that have been published in the prestigious journal The New England Journal of Medicine and presented at the American Society of Clinical Oncology (ASCO) conference currently taking place in Chicago, United States.

On one hand, the results of the ADAURA clinical trial have revealed that adjuvant therapy with osimertinib, an inhibitor of the epidermal growth factor receptor (EGFR), has significantly prolonged overall survival in patients with early-stage non-small cell lung cancer with EGFR gene mutations.

The randomized, double-blind, phase III clinical trial analyzed data from 682 patients, of whom 339 received osimertinib and 343 received a placebo. Among patients with stage II to IIIA disease, the overall 5-year survival rate was 85% in the osimertinib group and 73% in the placebo group.

According to these data, adjuvant therapy with osimertinib has demonstrated a significant benefit in overall survival among patients with non-small cell lung cancer with EGFR gene mutations.

These results offer new hope for patients in the early stages of the disease, as they represent the largest reduction in mortality ever recorded in the field of lung cancer and highlight how targeted therapies against tumor alterations are driving oncology towards more effective treatments for specific groups of patients.

EGFR alterations are the most common type of mutation in lung tumors in non-smokers, while they are not as frequent in people who have smoked, as detailed by Dr. Majem.

“This is the first time we have seen such a magnitude of improvement in lung cancer survival, and we believe it is a very hopeful outcome that will translate into an improved prognosis for these patients.”

Combination of immunotherapy before and after surgery

On the other hand, another study in which Dr. Majem participated concluded that patients with early-stage non-small cell lung cancer who are candidates for surgery and receive neoadjuvant treatment with pembrolizumab in combination with chemotherapy followed by surgical resection and adjuvant treatment with pembrolizumab show a better therapeutic response and longer progression-free survival compared to conventional treatment, which consists of neoadjuvant chemotherapy followed by surgery.

This is a randomized, double-blind clinical trial called KEYNOTE-671, which analyzed follow-up data from 797 patients over 25.2 months. The results showed that the 24-month progression-free survival rate was 62.4% in the pembrolizumab-treated group compared to 40.6% in the placebo group. Additionally, a greater pathological response was observed in 30.2% of participants in the pembrolizumab group compared to 11.0% in the placebo group.

According to Dr. Majem, “these results provide a new perspective on the treatment of early-stage lung cancer and could have a significant impact on how this disease is approached in the future.”

Reference articles

• Tsuboi M, Herbst RS, John T, Kato T, Majem M, Grohé C, Wang J, Goldman JW, Lu S, El seu WC, de Marinis F, Shepherd FA, Lee KH, NT, Dechaphunkul A, Kowalski D, Poole L, Bolanos A, Rukazenkov I, Wu YL; ADAURA Investigators. Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. N Engl J Med. 2023 Jun 4. doi: 10.1056/NEJMoa2304594. Epub ahead of print. PMID: 37272535.
• Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodríguez-Abreu D, Chaft JE, Novell S, Yang J , Keller SM, Samkari A, Spicer JD; KEYNOTE-671 Investigators. Perioperative Pembrolizumab per Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Jun 3. doi: 10.1056/NEJMoa2302983. Epub ahead of print. PMID: 37272513.

Els resultats d’un estudi, liderat per Maria Galán Arroyo, investigadora de l’Institut de Recerca de l’Hospital de Santa Creu i Sant Pau (IIB Sant Pau) i de la Universitat Rey Juan Carlos (URJC), i Cristina Rodríguez, investigadora de l’IIB Sant Pau, mostren que l’acció d’una molècula (el pèptid SS-31) sobre els mitocondris cel·lulars disminueix la incidència i la mortalitat d’aquesta malaltia.

El pèptid SS-31 dirigit al mitocondri té la capacitat de limitar el remodelat vascular que condueix al desenvolupament de l’aneurisma d’aorta abdominal (AAA). Aquesta és la principal conclusió de l’estudi publicat a la revista científica British Journal of Pharmacology.

L’AAA és una malaltia degenerativa que afecta el 6-9% dels homes més grans de 65 anys. És una condició en què l’aorta abdominal, l’artèria principal que subministra sang a l’abdomen i les cames, es dilata i es debilita. A mesura que l’aneurisma creix, augmenta el risc que es trenqui, cosa que pot causar una hemorràgia interna potencialment mortal.

“Fins ara, no hi ha un tractament farmacològic eficaç per a l’aneurisma d’aorta abdominal. Tot i això, aquest treball revela una nova estratègia terapèutica per al tractament d’aquesta malaltia”, explica Cristina Rodríguez, una de les investigadores que ha liderat l’estudi.

Els resultats mostren que el tractament amb el pèptid SS-31 limita la disfunció mitocondrial, l’estrès de reticle endoplàsmic (que suposa una alteració a la síntesi de proteïnes i condueix a la producció de proteïnes defectuoses) i l’estrès oxidatiu vascular en un model experimental de la malaltia. “Això resulta en una disminució de la incidència i gravetat de l’AAA, una reducció del diàmetre aòrtic i de la mortalitat, així com una millora en múltiples processos associats al desenvolupament de l’aneurisma, com una inflamació menor i millora de la integritat de la matriu extracel·lular”, afegeix María Galán Arroyo, coautora de l’estudi i investigadora de la URJC i de l’IIB Sant Pau.

Estudis clínics previs també han demostrat l’eficàcia del SS-31 en el tractament d’altres malalties. Per exemple, s’ha demostrat que el pèptid SS-31 és efectiu en la reducció del dany cerebral després d’un accident cerebrovascular i la millora de la funció cardíaca en pacients amb insuficiència cardíaca.

Aquest nou treball suggereix que la SS-31 podria ser una estratègia terapèutica interessant per al tractament de l’AAA. “Els nostres resultats representen un important avenç en la investigació sobre el tractament de l’aneurisme d’aorta abdominal i ens acosta un pas més a trobar una cura efectiva per a aquesta malaltia”, subratlla la Dra. Galán.

L’estudi ha estat liderat per Maria Galán i Cristina Rodríguez, investigadores de l’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau (IIB Sant Pau), del grup de l’Àrea de Malalties Cardiovasculars (CIBERCV), dirigit per José Martínez González ( Institut d’Investigacions Biomèdiques de Barcelona (CSIC) amb la col·laboració d’un equip de l’Àrea CIBER de Diabetis i Malalties Metabòliques Associades (CIBERDEM) i de la Universitat Autònoma de Barcelona.

Article de referència

Navas-Madroñal, M., Almendra-Pegueros, R., Puertas-Umbert, L., Jiménez-Altayó, F., Julve, J., Pérez, B., Consegal-Pérez, M., Kassan, M., Martínez-González, J., Rodriguez, C., & Galán, M. (2023). Targeting mitochondrial stress with Szeto-Schiller 31 prevents experimental abdominal aortic aneurysm: Crosstalk with endoplasmic reticulum stress. British Journal of Pharmacology, 1– 20. https://doi.org/10.1111/bph.16077

The executive committee of the Spanish Society of Psychiatry and Mental Health (SEPSM) has appointed Dr. Justo Pinzón Espinosa, a researcher at the Mental Health Group of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, and a psychiatrist at the same hospital, as one of the two coordinators of the recently created Young Psychiatrists Working Group. In this new section, he will represent and advocate for the interests of psychiatrists up to the age of 35 and will serve as a link between this group and the rest of the scientific society.

“For me, this appointment is a logical and natural step after my tenure as president of the Spanish Society of Psychiatry Residents in 2019 and 2020,” says Dr. Pinzón, who explains that “during this period, we developed strategies, with the board of directors, to promote research, teaching, and the improvement of the quality of care for psychiatry residents in Spain. I also strengthened the presence and participation of Spanish residents in the European Federation of Psychiatry Residents, where I served as national coordinator of residents’ associations and leader of the ‘Psychiatry Across Borders’ working group until 2021.”

Among the main objectives of the new Young Psychiatrists section of the SEPSM, Dr. Pinzón highlights that “the first step will be to establish the functional and organizational foundations, as well as to establish formal collaborations and strengthen ties with the young sections of other psychiatric societies in Europe, such as the European College of Neuropsychopharmacology, the European Psychiatric Association, or the Royal College of Psychiatrists, and internationally with institutions such as the American Psychiatric Association or the World Psychiatric Association.” Additionally, they aim to “promote spaces for the exchange of ideas and socialization during important events in the field of Spanish Psychiatry to foster collaborations throughout the country.”

Women and older patients with atypical presentations of ST-segment elevation myocardial infarction (STEMI) experience greater delays in diagnosis and treatment activation in emergency departments, according to the results of a study led by Gemma Berga Congost from the Nursing Research Group at the Research Institute of Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and a nurse at the same hospital.

The study, which included 330 patients with STEMI admitted to the Emergency Department of Hospital de Sant Pau, revealed that age over 65 and presentation of the first medical contact outside the Emergency Department were associated with an increase in treatment activation time. In addition, women over 65 showed the longest activation time. The results highlight the need to develop strategies to reduce the time to initiate treatment in these specific patient groups.

ST-segment elevation myocardial infarction is more common in men than in women, and the average age of patients admitted for myocardial infarction in Spain is around 65 years. “In contrast, the average age of women is 10 years older than that of men, probably due to the protective effect of estrogen,” emphasizes this expert.

The delay in diagnosis experienced by these groups “may be attributable to the atypical symptoms they most frequently present. Therefore, in addition to typical symptoms, other manifestations identified in our registry should be considered in order to establish an early diagnosis.”

It is also important to note that both women and the elderly have a lower perception of risk, which delays the request for medical assistance, resulting in delayed diagnosis and treatment.

The study from IIB Sant Pau has also identified that age over 65 is a predictor of delay in diagnosis and provides new data regarding the age and gender gap. As Berga points out, “there is no positive association between gender and age in patients under 65. However, if the age is over 65, it is observed that women have a longer emergency-activation time than men.”

These findings underline the importance of addressing the specific needs of these patient groups to improve activation time. Developing targeted strategies to accelerate activation time in these subgroups is crucial to improve the quality of care provided in the Emergency Department.

Reference article

Gemma Berga Congost, Maria Antonia Martinez Momblan, Jonatan Valverde Bernal, Adrián Márquez López, Judit Ruiz Gabalda, Joan Garcia-Picart, Mireia Puig Campmany, Salvatore Brugaletta. Association of sex and age and delay predictors on the time of primary angioplasty activation for myocardial infarction patients in an emergency department. Heart & Lung (2023). https://doi.org/10.1016/j.hrtlng.2022.10.014

En el marc de la 24a Jornada de Nefrologia i Atenció Primària, organitzada per la Unitat d’Hipertensió i Prevenció de Mal Renal de la Fundació Puigvert – IIB Sant Pau, s’ha posat de manifest la necessitat d’una atenció coordinada i multidisciplinària a les gestants que presenten HTA perquè pot estar associada a una malaltia renal i ser un factor predictiu de sofrir preeclàmpsia. A més, confirmen les expertes, les dones que hagin sofert una complicació obstètrica com la preeclàmpsia tindran un risc alt de desenvolupar una malaltia cardiovascular com HTA, diabetis, obesitat i tromboembolisme, entre altres patologies.

La preeclàmpsia és una malaltia específica de l’embaràs i d’afectació multisistèmica (sobretot, ronyó, fetge i cervell), definida com una hipertensió que apareix a partir de les 20 setmanes de gestació. Actualment, és necessari realitzar proves de detecció a totes les embarassades i el garbellat del primer trimestre de la preeclàmpsia prematura s’inclou en el Protocol de Seguiment de l’Embaràs a Catalunya des de 2018.

La Dra. Elisa Llurba, directora del Servei de Ginecologia i Obstetrícia de l’Hospital de Sant Pau i Cap del Grup de Medicina Perinatal i de la Dona de l’Institut de Recerca de l’Hospital de Sant Pau – IIB Sant Pau, ha afirmat que “a l’Hospital de Sant Pau disposem d’un Programa de Garbellat de Preeclàmpsia que es realitza amb criteris d’història clínica materna (per exemple, haver-la sofert anteriorment), més la pressió arterial alta i l’avaluació del flux en les artèries uterines. Aquest garbellat és capaç d’identificar a un 65-70% de les dones que desenvoluparan preeclàmpsia preterme”.

Embaràs, HTA i malaltia renal

Un dels casos més comuns de la consulta de nefrologia de la Fundació Puigvert és la de dones amb poliquistosis renal autosòmica dominant (PQRAD), la malaltia renal hereditària més freqüent, quan es plantegen el desig gestacional. Es tracta d’una malaltia congènita que es diagnostica a través d’antecedents familiars de primer grau i es descarta mitjançant una ecografia. La Dra. Patrícia Fernández-Llama, cap de la Unitat d’Hipertensió Arterial del Servei de Nefrologia de la Fundació Puigvert, afirma que “les dones amb malalties renals tenen més risc de complicacions greus tant per a elles com per al futur nadó. És per aquest motiu que obstetres i nefròlogues de l’Hospital Sant Pau i la Fundació Puigvert, respectivament, treballem, coordinadament en una consulta multidisciplinària per a abordar aquests embarassos d’alt risc: si es planifica l’embaràs amb la malaltia renal estabilitzada, el risc de complicacions es redueix perquè ens permet anticipar-nos i aplicar estratègies d’intervenció precoces per a minimitzar els riscos.”

Preeclàmpsia, avantsala d’una malaltia cardiovascular

Un estudi retrospectiu de l’Institut Català de la Salut (ICS) a la ciutat de Barcelona ha registrat un total de 1976 episodis de preeclàmpsia en 1329 dones (algunes van tenir dos o més episodis) en els últims vint anys. L’anàlisi i seguiment d’aquestes pacients durant aquest període posa de manifest que les dones que han sofert un o més episodis de preeclàmpsia desenvolupen al cap dels anys alguna malaltia cardiovascular greu com HTA, diabetis, obesitat, esdeveniments cardiovasculars i fins i tot malaltia renal, amb molta més freqüència que les dones que mai van presentar preeclàmpsia.

La conclusió continua sent la mateixa: una bona comunicació i coordinació entre pacients, mèdics/as de família, obstetres i nefròlegs/as per a la detecció, control i seguiment de les dones en edat reproductiva amb HTA i desig gestacional és vital per a prevenir la preeclàmpsia i la seva morbimortalitat associada.

The Cellular Cultures Platform of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, coordinated by Estefanía Segalés, is a service that offers different facilities where you can work with both primary cultures obtained from human tissues and experimental animal cultures, as well as continuous cell lines and Genetically Modified Organisms (GMOs) of levels I and II.

Users have the necessary basic equipment to obtain and maintain cell cultures: 25 laminar flow hoods and biological safety cabinets, 28 CO2 incubators, ovens, centrifuges, water baths, inverted microscopes, balances, vacuum traps, cell counters, refrigerators, freezers (-20 and -80°C), hybridization ovens, and autoclaves.

As a user of this platform, Dr. Alba Tristán Noguero, a postdoctoral researcher in the Molecular Pathophysiology of Synaptic Plasticity Group at IIB Sant Pau, explains that they mainly use it to maintain primary mouse neuron cultures and human neurons in co-culture with murine astrocytes.

“The infrastructure of the Cellular Cultures Service has helped us in the project of the Molecular Physiology of Synaptic Plasticity laboratory, allowing the study of SYNGAP1-related developmental epileptic encephalopathy. With the establishment and maintenance of these human and murine cultures, we have been able to better understand the pathophysiology of the disease and test different treatments.”

What Dr. Tristán apreciates the most about the Cellular Cultures Platform is “the perfect organization and management, as well as the availability to answer questions and adapt to the users’ needs.”

On the other hand, David Santos, a researcher in the group studying diseases characterized by lipid alterations, explains that he spends at least one-third of his working day in the Cellular Cultures Platform. “Most of the experimental work I do depends on cell cultures, from cellular metabolism studies to the injection of labeled foam cells with isotopes into animal models of experimentation.”

For him, this service is indispensable, “without this platform, it would be impossible for me to carry out these experiments. On the other hand, having this platform has allowed me to carry out important collaborations with other research groups, both nationally and internationally.”

This researcher highlights that reliability is one of the aspects he values the most about this platform. “Knowing that I leave my cultures in a secure area where regulations are met, both to protect the user and the cells, in terms of contamination control, equipment supervision and maintenance, PPE administration, among others, gives me peace of mind when performing my experiments and validating the results I obtain.”

A study co-led by researchers from the Neurobiology of Dementia group at the Research Institute of Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, published in the prestigious journal Neuron, of Cell group, describes that harmful proteins that accumulate in the brains of people with Alzheimer’s disease spread through synapses.

The research, led by Professor Tara Spires-Jones’ team at the UK Dementia Research Institute at the University of Edinburgh and carried out by IIB Sant Pau in collaboration with the Institute of Advanced Chemistry of Catalonia (IQAC) of the Spanish National Research Council (CSIC), provides new evidence that could be the key to stopping the progression of Alzheimer’s disease. The study was conducted under the European COEN project, funded by CIBERNED and coordinated by Dr. Alberto Lleó, a researcher in the Neurobiology of Dementia group at IIB Sant Pau and head of the Neurology department of the same hospital.

The accumulation of the Tau protein in neurons in the form of neurofibrillary tangles is one of the most characteristic aspects of Alzheimer’s disease. The deposits of this protein spread through brain circuits, disrupting communication between brain cells, leading to altered brain functions. It is the first time that these abnormal forms can be observed in human brains spreading through synapses.

Synapses are the points of connection between brain cells that allow chemical and electrical messages to flow, and this process is vital for normal brain function. Synapses are lost in Alzheimer’s disease, and the loss of these connections significantly predicts memory loss and other intellectual functions in these patients.

The research team examined over one million synapses from 42 individuals using innovative techniques with high-powered and super-resolution microscopes in collaboration with the IQAC-CSIC, which allowed them to visualize the flow of proteins within individual synapses. The researchers were able to observe that small deposits of the Tau protein, known as oligomers, were present on both sides of the synapses in individuals who died from Alzheimer’s. That is, both in the neuron that sends signals and in the one that receives them, indicating that synapses have the ability to transmit toxic Tau proteins from one part of the brain to another.

According to Dr. Sílvia Pujals, Ramón y Cajal researcher at IQAC-CSIC, “this study demonstrates how super-resolution microscopy, capable of visualizing nano-scale structures, has great potential in the study of the molecular mechanisms involved in diseases.”

These data reinforce the hypothesis that stopping the spread of the toxic form of the Tau protein in synapses may be a promising strategy for treating Alzheimer’s disease in the future, explains Dr. Lleó. “If we can block the passage of the most pathological form of the Tau protein, which are the oligomers, from one neuron to another, we could probably stop the progression of Alzheimer’s disease. Because we know that the progression of the disease is related to the expansion of the protein throughout the brain.”

The principal investigator, Professor Tara Spires-Jones from the UK Dementia Research Institute at the University of Edinburgh, indicates that “We have known for over 30 years that tangles spread through the brain during Alzheimer’s disease, but how they spread has remained a mystery. Wherever tangles appear in the brain, neuron death follows, contributing to the decline in cognitive ability. Stopping the spread of toxic tau is a promising strategy to stop the disease in its tracks.”

Dr. Sònia Sirisi Dolcet, postdoctoral researcher in the Neurobiology of Dementia group at the IIB Sant Pau, explains that Tau oligomers, which travel through synapses, “are a very early form in the aggregation process of this protein. That is, they are present in very early stages of Alzheimer’s disease.” Therefore, if strategies can be developed to prevent the spread of this protein throughout the brain in these early stages, its progression could be prevented or stopped.

Image: 3D reconstruction of super-resolution microscopy images, where it is seen that the Tau protein in its oligomeric form (in yellow) is located where there are pre-synapses (in magenta).

Reference Article  

Colom-Cadena et al., Synaptic oligomeric tau in Alzheimer’s disease — A potential culprit in the spread of tau pathology through the brain, Neuron (2023), https://doi.org/10.1016/j.neuron.2023.04.020

L’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau ha posat en marxa un nou programa transversal de recerca per fomentar la perspectiva de gènere en totes les seves àrees i grups de investigació.

Amb aquest nou programa, creat en el marc del Pla de Recerca i Innovació Responsable (RRI), l’IIB Sant Pau implementarà accions adreçades a fomentar la incorporació de la perspectiva de gènere en el contingut de la recerca i a promoure la investigació específica de gènere per cobrir els buits de coneixement, posant en marxa els mitjans i recursos necessaris per facilitar-ho.

Malgrat que les diferències de sexe i gènere tenen un impacte significatiu en la salut, la investigació biomèdica continua originant-se  principalment en estudis realitzats en material cel·lular, models animals masculins o homes i sovint no té en compte els diferents patrons de salut i malaltia en dones i homes en funció del sexe i el gènere.

Aquesta manca de perspectiva de gènere pot tenir greus conseqüències. Per exemple, les dones solen estar infrarepresentades en els assaigs clínics, cosa que pot provocar que les dosis de medicaments no siguin les adequades, problemes de seguretat, com ara efectes adversos no esperats i també pot emmascarar diferències importants en la progressió de la malaltia i la resposta al tractament.

A més, el biaix de gènere en la investigació pot provocar una manca de comprensió dels problemes de salut específics de les dones, com ara els trastorns relacionats amb la menstruació, les complicacions relacionades amb l’embaràs i els símptomes relacionats amb la menopausa. Encara, més enllà del sexe, cal incorporar la dimensió de gènere en la recerca, amb intereseccionalitat, que ens permeti obtenir resultats científics que responguin a les necessitats reals, contribuint a incrementar l’equitat i la justícia social.

El director de l‘IIB Sant Pau, Dr. Jordi Surrallés, comenta que “es crucial que la investigació biomèdica adopti una perspectiva de gènere per entendre millor l’impacte del sexe i el gènere en els resultats de salut. Perquè això passi, és imprescindible que des dels centres de recerca creem estructures que facilitin les sinèrgies entre els grups, com aquest nou programa, i que fomentem el canvi impulsant projectes i dedicant recursos a acompanyar i formar el personal científic en aquest àmbit. No n’hi ha prou amb adherir-se a manifestos o signar declaracions si això no s’incorpora a l’estratègia del centre i es tradueix en accions concretes”.

També destaca que la perspectiva de gènere també ha d’estar present en “la governança dels centres, ja sigui fomentant la paritat en el lideratge dels grups de recerca i els comitès científics interns i externs que assessoren la direcció de l’Institut, com en les polítiques institucionals. Alhora, tenim la responsabilitat d’impulsar i visibilitzar models femenins en recerca, en l’entorn científic, en congressos i actes, i especialment en l’entorn social, mitjançant les activitats de difusió i divulgació de la ciència. Des de l’IIB Sant Pau treballem activament per garantir la igualtat de gènere en tots aquests àmbits”.

El nou programa transversal de recerca en Salut de la Dona i Gènere està coordinat per la Dra. Elisa Llurba, cap del grup de medicina perinatal i de la dona a l’IIB Sant Pau i directora del servei de ginecologia i obstetrícia a l’Hospital de Sant Pau, i per la Dra. Ma Rosa Ballester, cap de la unitat de Recerca i Innovació Responsable a l’IIB Sant Pau.

“Prioritzant la perspectiva de sexe i de gènere en la investigació biomèdica, augmentem la reproductibilitat dels estudis, fent-los lliures de biaixos, afegim valor a la recerca fent-la més ètica i responsable, augmentant la equitat i la justícia social. Amb aquesta visió contribuïm a optimitzar els resultats de salut per a totes les persones, independentment del seu sexe o  gènere, amb un enfocament interseccional com element explicatiu de les desigualtats sistèmiques”, explica la Dra. Ma Rosa Ballester. Amb aquest nou enfocament transversal, l’IIB Sant Pau esdevé un centre pioner i aposta decididament per incorporar la perspectiva de gènere en totes les seves àrees de recerca, per tal de contribuir a la consecució dels objectius en aquest àmbit.

“Cal incorporar la perspectiva de gènere en tot el procés, això inclou augmentar la representació de les dones en els assaigs clínics, plantejar-nos de quin sexe son les línies  cel·lulars o els models animals que es fan servir en recerca bàsica, analitzar les diferències de sexe i gènere en accés al sistema sanitari, la percepció de la malaltia o la salut, el diagnòstic, la progressió de la malaltia i la resposta al tractament. Per tant, cal  abordar el biaix de gènere ja en el disseny de qualsevol projecte de recerca, i també en l’anàlisi i com ho expliquem a els i les usuàries finals”, afegeix la Dra. Elisa Llurba.

Els principals objectius d’aquest programa transversal són:

• Promoure la investigació en la salut amb perspectiva de gènere i en malalties que afecten a dones.
• Disminuir la bretxa en la representació sexe femení en qualsevol tipus d’estudi, ciència bàsica fins a recerca aplicada en humans.
• Fomentar la col·laboració entre els grups de recerca de les 5 àrees de recerca per investigar tenint en compte la perspectiva de gènere.
• Impulsar la realització d’assaigs clínics amb fàrmacs i eines tecnològiques per a patologies que afecten les dones.
• Atraure talent amb interès per investigar en gènere.
• Captació de finançament públic i privat en aquest àmbit.
• Esdevenir un centre referent en recerca de gènere.
• Tancar la bretxa de gènere en la recerca.

“Aquest programa ha de servir de catalitzador d’una necessitat real. Amb aquest programa l’IIB Sant Pau posa el marc i els instruments per fomentar-ho”, conclou la Dra. Llurba.

Sant Pau compromès amb la salut i el gènere

Sant Pau està compromès i aborda l’agenda de gènere a tots els nivells. La creació del nou programa transversal de recerca en Salut de la Dona i Gènere és un exemple de la confluència del treball conjunt entre l’institut de recerca i l’hospital.

D’una banda, l’Hospital de la Santa Creu i Sant Pau va ser un dels primers centres catalans en crear la Comissió de Salut i Gènere, que impacta en l’assistència, la recerca i la docència.  En paral·lel, l’Institut de Recerca de Sant Pau – IIB Sant Pau, va elaborar el Pla de Recerca i Innovació i Responsable (RRI) prioritzant  l’agenda de gènere , amb mesures i accions que impliquen, per exemple, la gestió del talent i el foment de la carrera científica en les dones, l’acompanyament metodològic i la formació en la incorporació de la perspectiva de gènere en recerca, i la creació del grup transversal de recerca que avui es presenta.

Línies de recerca en salut i gènere: alguns exemples

L’IIB Sant Pau té en marxa cada cop més projectes que incorporen la perspectiva de gènere des del seu plantejament inicial. Un dels exemples paradigmàtics són les malalties cardiovasculars. Cada vegada hi ha més evidència de les diferències tan importants que existeixen tant en l’evolució com en les manifestacions clíniques de diferents trastorns cardiovasculars i que aquestes seves variables poden tenir un impacte en la prevenció i el seu tractament.

En l’àrea de Malalties Cardiovasculars estan en marxa projectes com ara el RETROVE, que busca algoritmes matemàtics per definir el risc individual de patir trombosi venosa, o un altre estudi que analitza el tractament amb betabloquejants en pacients amb fibril·lació auricular en funció del sexe.

Per exemple, el grup que lidera la Dra. Lina Badimon està duent a terme un projecte de medicina personalitzada en una cohort en l’àmbit nacional amb diagnòstic genètic d’hipercolesterolèmia familiar i on l’especificitat de sexe és un dels objectius de l’estudi a l’hora d’identificar i determinar la importància de nous biomarcadors moleculars.

En aquest àmbit de salut cardiovascular, la Dra. Elisa Llurba, lidera conjuntament amb investigadores del Grup de Recerca en Medicina Perinatal i de la Dona, del Grup de Recerca en Bioquímica i el Grup de Malalties Cardiovasculars, tres estudis amb finançament de l’Instituto de Salud Carlos III sobre l’impacte de diferents processos reproductius en la salut cardiovascular en tres etapes clau: prèvia a la gestació en dones en procés de reproducció assistida, durant la gestació, i als 3-6 anys després del part. Un dels objectius és estudiar com les malalties d’origen placentari poden tenir un impacte en la salut cardiovascular materna i neonatal.

A l’àrea de recerca de Malalties neurològiques, neurociències i salut mental, que dirigeix el Dr. Juan Fortea, també hi ha diversos projectes plantejats amb perspectiva de gènere. Entre ells, s’estan estudiant les diferències de gènere en la demència frontotemporal i també en el vincle entre la malaltia d’Alzheimer i síndrome de Down, o la resposta terapèutica a la malaltia de Parkinson en funció del sexe. En ictus també s’estan realitzant estudis d’estratificació per sexe i la recerca de factors genètics específics en malalties complexes.

Al grup de malalties genètiques hi ha diversos estudis en marxa que tenen en compte la perspectiva de gènere, com ara la detecció -prèvia a l’embaràs- de dones amb alt risc de tenir fills afectes de malalties genètiques, la identificació de variants predictores de toxicitat greu en pacients amb càncer colorectal tractats amb fluoropirimidines, l’estudi farmacogenètic en pacients psiquiàtrics atesos en centres de salut mental, o l’estudi farmacogenètic i farmacocinètic en pacients amb trasplantament de progenitors hematopoiètics que reben un acondicionament amb busulfan, entre d’altres.

A més, hi ha projectes específics que parteixen directament de diferències de gènere, com ara la recerca en la malaltia endocrinològica i metabòlica en la gestació o l’estudi dels canvis neurològics en la dona perimenopàusica, així com la totalitat dels projectes de recerca de Ginecologia i Obstetrícia que lidera la Dra. Llurba, en el que la perspectiva de gènere va encara mes enllà i treballa aspectes psico-bio-socials com el impacte de les pèrdues reproductives precoces, la co-creació ciutadana en l’experiència de les dones que pateixen una endometriosi o l’estudi de la violència obstètrica. I també la recerca que es fa des del Grup de Oncologia Ginecològica i Peritonetal, dirigit per la Dra. Virtudes Céspedes, que estudia els càncers d’endometri i ovari amb beques de la Marató de TV3 i de l’Instituto de Salud Carlos III, entre d’altres.

En recerca en salut pública, des de fa anys, els grups de recerca de l’Agència de Salut Pública de Barcelona de l’IIB Sant Pau incorporen la perspectiva de gènere en bona part dels seus estudis. A començaments de 2023 es va publicar l’informe “Desigualtats de gènere en la salut a Barcelona” en què s’examinen les desigualtats de gènere en els determinants socials de la salut, els problemes de salut, els hàbits relacionats amb la salut i la utilització de serveis sanitaris amb una perspectiva interseccional que considerava la classe social i el país de naixement, i de curs de vida. També han examinat les desigualtats de gènere des d’una perspectiva interseccional en salut mental, recollides en l’informe “Situació de la salut mental de la població de Barcelona i els seus determinants”. La interseccionalitat és clau en els estudis amb perspectiva de gènere en salut, ja que la majoria inclouen determinants com el treball, l’habitatge i la violència. Per exemple, la recerca liderada per la Dra. Lucía Artazcoz, investiga desigualtats de gènere en la salut relacionades amb la compaginació de vida laboral i familiar, el treball a temps parcial o llargues jornades de treball.

Aquests exemples mostren clarament la necessitat d’incorporar la perspectiva de gènere en tots els estadis de la recerca: disseny, execució i anàlisi de resultats; però també en tots els seus àmbits: recerca bàsica, preclínica, clínica i salut pública.

Un estudi coliderat pel Dr. Daniel Alcolea, investigador de l’Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau i la Unitat de Memòria – Unitat Alzheimer-Down de l’Hospital de Sant Pau, i la Dra. Laia Montoliu-Gaya, de la Universitat de Gothenburg i en què també han col·laborat la Ludwig-Maximilians-Universität de Munic, i la Unitat d’Alzheimer i altres trastorns cognitius de l’Hospital Clínic, postula la proteïna glial fibril·lar àcida (GFAP) com un biomarcador que podria ser útil per avaluar el diagnòstic i pronòstic de la malaltia d’Alzheimer en persones amb síndrome de Down.

Se sap que la població amb síndrome de Down té un elevat risc de desenvolupar la malaltia d’Alzheimer. De fet, als 70 anys més del 95% de les persones amb síndrome de Down desenvoluparan la malaltia d’Alzheimer, que és la principal causa de mort en aquesta població. Aquesta forta associació es deu a la triplicació d’un gen que està involucrat en el desenvolupament de la malaltia d’Alzheimer anomenat proteïna precursora d’amiloide i localitzat al cromosoma 21. En persones amb síndrome de Down, la detecció primerenca de la malaltia d’Alzheimer és un desafiament clínic. El canvi en el funcionament cognitiu pot ser difícil de determinar a causa dels diferents nivells de discapacitat intel·lectual associats amb la síndrome.

Aquest estudi, que publica la revista eBioMedicine, ha estudiat el potencial de la proteïna GFAP, en sang (plasma) i líquid cefaloraquidi com a biomarcador diagnòstic i pronòstic per a la malaltia d’Alzheimer en persones amb síndrome de Down comparant-ho amb els canvis en la malaltia de Alzheimer autosòmica dominant i esporàdica.

S’han analitzat mostres de 997 participants de les cohorts DABNI i SPIN juntament amb mostres de participants de l’hospital Clínic i la Ludwig-Maximilians-Universität. “Incloem mostres de persones amb síndrome de Down, persones amb Alzheimer autosòmic dominant, persones amb malaltia d’Alzheimer esporàdica i voluntaris sense problemes cognitius. Es van mesurar les concentracions de GFAP en líquid cefaloraquidi i en sang dels participants i es va avaluar la seva relació amb la presència de patologia amiloide i canvis en l’estructura del cervell mitjançant proves de neuroimatge”, detalla el Dr. Alcolea.

Els resultats mostren que la concentració de GFAP al plasma és el biomarcador que més canvia al llarg de la progressió de la malaltia d’Alzheimer, augmentant des de les primeres etapes preclíniques (més de dues dècades abans que apareguin els primers símptomes) fins a la fase de demència. A més, les determinacions de GFAP en plasma també van resultar útils per discriminar entre persones amb malaltia d’Alzheimer simptomàtica i asimptomàtica i per predir la progressió de la malaltia i el deteriorament cognitiu a l’etapa de demència. A més, la concentració de GFAP al plasma es va associar amb els dipòsits d’amiloide cerebral mesurats per PET.

Aquestes troballes són importants tant per al disseny de nous assaigs clínics com per a la pràctica clínica, ja que la proteïna GFAP es podria utilitzar per identificar aquelles persones que estan en risc de desenvolupar la malaltia i per avaluar l’eficàcia dels tractaments en desenvolupament.

“L’estudi de marcadors plasmàtics longitudinals és una de les revolucions a Alzheimer dels darrers 5 anys”, comenta el Dr. Juan Fortea, director de la Unitat Alzheimer-Down de Sant Pau i director de l’Àrea de Malalties Neurològiques, Neurociència i Salut Mental de l’IIB Sant Pau, que afegeix que el desenvolupament d’aquests marcadors a la sang és molt important perquè “un PET pot costar milers d’euros, la punció lumbar és invasiva i implica molts més recursos mentre que una anàlisi de sang és molt fàcil de fer” .

Aquest expert detalla que la proteïna GFAP és un marcador astrocitari que s’altera molt aviat a la malaltia d’Alzheimer i que està molt relacionat amb l’amiloïdosi i que continua avançant als diferents estadis de la malaltia. “És, curiosament, l’única proteïna que funciona millor en plasma que en líquid cefaloraquidi i té un rendiment excel·lent per al diagnòstic de la malaltia. Aleshores probablement és una de les millors candidates per al panell de proteïnes que necessitem en un futur”.

Finalment, el Dr. Fortea destaca que actualment “ja està demostrat que aquests marcadors funcionen meravellosament en estudis de recerca. Ara el que hem de desenvolupar són els algorismes d’ús d’aquests marcadors plasmàtics per al diagnòstic de la malaltia de l’Alzheimer a la pràctica clínica”.

Aquest estudi ha rebut finançament de la Fundació “La Caixa”, l’Instituto de Salud Carlos III, el National Institute on Aging, el Wellcome Trust, el Jérôme Lejeune Foundation, l’AC Immune, la Medical Research Council, l’Alzheimer’s Association, el National Institute for Health Research, l’EU Joint Programme –Neurodegenerative Disease Research, Alzheimer’s society i Deutsche Forschungsgemeinschaft, Stiftung für die Erforschung von Verhaltens und Umwelteinflüssen auf die menschliche Gesundheit.

Article de referència

Montoliu-Gaya L, Alcolea D, Ashton NJ, Peguerols J, Levin J, Bosch B, Llanter-Rodriguez J, Carmona-Iragui M, Wagemann O, Balassa M, Kac PR, Barroeta I, Lladó A, Brum WS, Videla L , Gonzalez-Ortiz F, Benejam B, Arranz Martínez JJ, Karikari TK, Nübling G, Bejanin A, Benedet AL, Blesa R, Lleó A, Blennow K, Sánchez-Vall R, Zetterberg H, Fortea J. Plasma i cerebrospinal fluid glial fibrillary acidic protein levels in adults with Down syndrome: a longitudinal cohort study. EBioMedicine. 2023 Apr;90:104547. doi: 10.1016/j.ebiom.2023.104547. Epub 2023 Mar 30. PMID: 37002988; PMCID: PMC10070083.

Huntington’s disease is a hereditary neurodegenerative disease caused by a mutation in a gene, which severely affects the cognitive ability of those who suffer from it. Traditionally, the way in which cognitive decline behaves over time in the disease has been considered very homogeneous. However, according to a new study led by Dr. Saül Martínez-Horta, a researcher in the Parkinson’s Disease and Movement Disorders group led by Dr. Jaume Kulisevsky at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, there are at least two distinct patterns of cognitive decline progression in people affected by this disease.

The study, published in the European Journal of Neurology, analyzes data obtained over a 3-year follow-up in over 500 people affected by the disease and participating in the international Enroll-HD study, excluding those cases that presented juvenile or late-onset forms or had clearly established dementia.

“Through a statistical approach, we were able to demonstrate that the trajectory of cognitive decline was very different and that, in practically half of the cases, there was a very aggressive pattern of progression without any differences between the two groups in terms of clinical, demographic or genetic characteristics,” explains Dr. Martínez-Horta.

The authors of the study conclude that the progression of Huntington’s disease varies significantly even among patients with similar characteristics, thus confirming the existence of at least two cognitive phenotypes that differ significantly in terms of the rate of progression. These findings open up new avenues for studying additional mechanisms that contribute to the heterogeneity of Huntington’s disease beyond the known genetic mutation that causes the disease.

“Unlike what the data usually show us, direct contact with affected individuals perfectly illustrates that, despite being a genetically determined disease, cases vary greatly in terms of appearance and progression pattern.”

In addition, the researchers developed a mathematical model that allows them to predict, by observing the behavior of cognitive decline during the first year, which patients will be in the group that progresses rapidly, which is very useful for classifying these individuals before it is evident that they are deteriorating much more.

These findings will be useful for improving prognosis and “anticipating what will happen to these individuals.” This is very useful for improving the design of clinical trials with potential treatments since “if you do not consider that the behavior of the disease will be different, you cannot adequately evaluate the effect of a drug because it is not the same as what you would expect to happen to someone who will remain more or less stable than someone who would actually have to deteriorate a lot.”

Reference article

Martínez-Horta, S, Perez-Perez, J, Oltra-Cucarella, J, et al. Divergent cognitive trajectories in early stage Huntington’s disease: A 3-year longitudinal study. Eur J Neurol. 2023; 00: 1- 9. doi:10.1111/ene.15806 https://onlinelibrary.wiley.com/doi/10.1111/ene.15806

The Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau has developed a new CAR-T 19 immunotherapy drug that has just begun to be administered, as part of a clinical trial, to patients with certain types of lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma) who have not responded to other treatments. With this new and unique therapeutic proposal in Spain for these patients, Sant Pau offers its second academic advanced therapy medicinal product, which means that it has been entirely produced and developed at Sant Pau. This new CAR-T 19 is characterized by being enriched in memory T lymphocytes, which are longer-lasting over time, with the aim of having greater efficacy against the disease.

In the clinical trial, promoted, coordinated, and directed from Barcelona by Dr. Javier Briones, director of the Cellular Immunotherapy and Gene Therapy Research Group of IIB-Sant Pau and head of the Clinical Hematology Unit of the Hematology Service of the Hospital de Sant Pau, the Hematology Service of the Hospital Virgen del Rocío de Sevilla collaborates, within the framework of the Advanced Therapies Network, one of the Cooperative Research Networks Oriented to Health Outcomes (RICORS) promoted by the Carlos III Health Institute (ISCIII).

In this project, which has received a €2 million grant from “la Caixa” Foundation, the ISCIII, the Josep Carreras Leukaemia Research Institute and Banc de Sang i Teixits (Blood and Tissue Bank) also collaborate. In the current phase of the trial (Phase I), 10 patients will be recruited, and the goal is to include 30 more in Phase II, with the aim of treating around 40 patients in total in the next two years.

Lymphoma is the most common blood cancer in Spain, as noted in the Spanish Society of Medical Oncology (SEOM) annual report, which estimates that nearly 10,000 new cases of non-Hodgkin’s lymphomas will be diagnosed in 2023. It is an oncological disease of the lymphatic system that mainly contributes to forming and activating the body’s defenses. Most patients manage to completely eliminate the disease after undergoing intensive cycles of chemotherapy and often a bone marrow transplant. However, many of these patients relapse after a while, and when this happens, they have very few therapeutic options.

Sant Pau’s therapeutic proposal addresses more than 80% of all lymphomas. Currently, there is no approved and commercially available CAR-T immunotherapy treatment in Spain for follicular lymphoma or mantle cell lymphoma in patients refractory to at least 2-3 conventional treatments.

The advanced therapy medicinal product produced at Sant Pau is based on selecting a specific type of T lymphocytes, called memory T lymphocytes, which are few in number but extremely effective. These cells are generated as a defense mechanism of the body against a primary infection and are responsible for mediating defense against successive infections of the same pathogen. That is, they remember it. Furthermore, it is known that they possess a powerful effect against tumor cells.

According to Dr. Javier Briones, the clinical project manager, “We select these memory T lymphocytes from the patient’s own and train them so that every time they detect a tumor cell, they eliminate it. Thus, in a lasting way, there would be a ‘detector and eliminator’ of any lymphoma cell that reappeared in the patient’s body. In short, it is the genetic modification of the patient’s own T lymphocytes so that they attack cancer cells.”

Cutting-edge technology for the production of advanced therapies

Sant Pau, which is part of the European T2Evolve project, is one of the accredited centers in Spain that has authorization to use CAR-T drugs, granted by the Dirección General de Cartera Básica de Servicios del Sistema Nacional de Salud y Farmacia, which depends on the Ministry of Health. This center has top-level facilities, as well as highly qualified and specialized professionals, which allows them to develop unique CAR-T immunotherapy projects in Europe.

The Clean Room of the IIB Sant Pau has the certification of compliance with Good Manufacturing Practices for Advanced Therapy Medicinal Products, issued by the Spanish Agency of Medicines and Medical Devices (AEMPS), initially obtained in 2020 in collaboration with the Banc de Sang i Teixits (Blood and Tissue Bank), and renewed in 2022, doubling its production capacity.

This equipment has been specially designed for the development of advanced therapy medicinal products and allows Sant Pau researchers to offer innovative treatments to their patients. In 2020, the first trial with a CAR-T immunotherapy drug, a pioneer in Europe, for the treatment of classical Hodgkin lymphoma and CD30+ non-Hodgkin T lymphoma in relapse or refractory, was initiated. This study, whose first results were presented last year at the most prestigious international Hematology congresses, is currently in phase II and constitutes the first CAR-T30 immunotherapy drug (academic), totally produced in Sant Pau, which has attracted patients from various countries, such as Italy, Austria, Poland, Russia, among others.

In phase I, it was demonstrated that CAR30 memory T cells (HSP-CAR30) have an excellent safety profile, that is, they have very little toxicity, in addition to achieving high efficacy, since 50% of patients had a complete response to treatment with disappearance of the lymphoma.

Inflammation of the carotid plaque is an important factor in the risk of recurrent stroke in patients with carotid artery disease. A study led by Dr. Vicenta Llorente, coordinator of the Lipids and Cardiovascular Pathology Group of the CSIC, and Dr. Sonia Benitez, researcher of the Cardiovascular Biochemistry Group of the Research Institute of the Hospital de la Santa Creu i Sant Pau -IIB Sant Pau, has evaluated the efficacy of soluble low-density lipoprotein receptor 1 (sLRP1) as an indicator of carotid plaque inflammation. The study was conducted in collaboration with Dr. Pol Camps-Renom from the Cerebrovascular Diseases group of the IIB Sant Pau and the Stroke Unit of the same hospital.

The study analyzed data from 64 adult patients who had presented with an ischemic stroke associated with carotid atherosclerosis in the internal carotid artery in the last seven days. The analysis showed a significant association between sLRP1 levels and carotid plaque inflammation measured by 18F-FDG PET. In addition, a direct relationship was observed between sLRP1 levels and the risk of stroke recurrence within one year after stroke in these patients.

Dr. Llorente explains that this marker has previously been associated with a higher risk of cardiovascular disease and its relationship with inflammation in the coronary artery and the extent of epicardial fat affecting cardiac function has been demonstrated. This study provides new evidence that the sLRP1 protein is also a reliable indicator of carotid plaque inflammation, which could help predict stroke recurrence in these patients.

The research provides an innovative approach to evaluating carotid plaque inflammation, which is more accessible than imaging techniques and could provide a valuable tool to integrate the risk of both carotid and coronary events in patients with cardiovascular disease.

Reference article

Garcia E, Camps-Renom P, Puig N, Fernández-Leon A, Aguilera-Simón A, Benitez-Amaro A, Solé A, Vilades D, Sanchez-Quesada JL, Martí-Fàbregas J, Jiménez-Xarrié E, Benitez S, Llorente-Cortés V. Soluble low-density lipoprotein receptor-related protein 1 as a surrogate marker of carotid plaque inflammation assessed by 18F-FDG PET in patients with a recent ischemic stroke. J Transl Med. 2023 Feb 19;21(1):131. doi: 10.1186/s12967-022-03867-w. PMID: 36805772; PMCID: PMC9940334.

Electronic inhaler monitoring devices can significantly improve patient adherence to inhaled therapy in adults with asthma or chronic obstructive pulmonary disease (COPD), according to a study by researchers from the Pharmacy and Pneumology Services of the Hospital de la Santa Creu i Sant Pau – IIB Sant, published in Pharmaceuticals.

The researchers evaluated whether using sensors to monitor the use of maintenance and rescue inhalers was useful for making interventions to improve the health outcomes of these patients. This is the first systematic review and meta-analysis on the topic. Eight observational studies and ten clinical trials were included, and the results indicate that the use of these devices improves adherence to inhalers. The results also indicated an improvement in the asthma control test score, but the effects on other clinical variables were mixed.

Inadequate adherence to pharmacological treatment is common in both asthma and COPD and is associated with an increased risk of exacerbations, increased use of systemic corticosteroids, and increased disease-related mortality. Electronic monitoring of inhalers can be an effective solution to improve adherence and clinical outcomes in these patients.

The study authors note that although there are different measures of adherence used in clinical practice, many of them are based on patient self-report and can be imprecise. Therefore, the use of these sensors can provide an objective and accurate way to measure adherence to inhalers in some patients. The electronically recorded information can be used for educational and clinical interventions in patients and the healthcare team.

Reference article

Noe Garin, Borja Zarate-Tamames, Laura Gras-Martin, Raimon Milà, Astrid Crespo-Lessmann, Elena Curto, Marta Hernandez, Conxita Mestres, Vicente Plaza. Clinical Impact of Electronic Monitoring Devices of Inhalers in Adults with Asthma or COPD: A Systematic Review and Meta-Analysis. Pharmaceuticals 2023, 16(3), 414; https://doi.org/10.3390/ph16030414

This week marked the start of the INNOPAU program, the idea incubator of IB Sant Pau, which aims to promote an innovation culture and provide value-added tools within the IIB Sant Pau ecosystem.

This immersive program will work on eight selected projects from among all those presented by the research groups of IIB Sant Pau and will conclude with the “Innovation Day” in November, where all participating teams will showcase their projects to a public audience that will bring together key actors from the innovation ecosystem.

The program, coordinated and organized by the Transfer and Innovation Unit of the institute, has a duration of 6 months and is framed within the objectives established in the ITEMAS platform of the Carlos III Institute (2021-2023), whose goal is to effectively stimulate the industrial capacity generated from the National Health System and the real transfer of results.

This week, the first kick-off presentation was held online, and the first module’s Hackathon-format training sessions were held at the Barcelona Health Hub facilities by scientific consultant Iolanda Marchueta. During this module, teams will work with the core of the project, the clinical need.

Of the 8 selected teams, half are biologically-based and the other half are technology and digital-based. The therapeutic areas they address are: oncology, neurodegenerative medicine, respiratory health, kidney pathologies, neuromuscular disorders, cardiovascular, and reproductive systems.

The organizers want to thank the collaborators who have already interacted with the program and evaluated the different projects. These are the external and internal Evaluation Committee formed by: Arvor, SDLI i Connectem, the Sant Pau Hospital (Més Sant Pau Office), and the Sant Pau Research Institute (Transfer and Innovation Unit).

The Confocal Microscopy Platform of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, coordinated by Dr. Esther Peña Sendra and in collaboration with the platform’s senior technician Dr. Josep Oriol Juan, is a biomedical research support platform specialized in image analysis that offers a wide range of services.

The mission of this platform, which is certified with ISO 9001:2015, is to advise on the experimental design, the choice of equipment according to the needs and training in the use of each group or research project, as well as the acquisition, quantification, and analysis of images to perform biomedical studies.

The professionals on this platform, in addition to advising on the preparation and/or approach of the studies, also offer training in the different techniques they use, such as immunofluorescence of 2 to 5 fluorochromes, the reconstruction of 3D images and 4D, colocalization studies, fluorescence microscopy, time lapse or anatomopathological studies of different tissues.

As a user of this platform, Dr. Eduard Gallardo, researcher at the Neuromuscular Diseases Research Group, explains that one of his lines of research is the discovery of new autoantibodies in seronegative myasthenia gravis.

“Confocal microscope analysis is becoming very important to evaluate the reactivity of both whole serum and purified IgG from patients against antigens located in the motor plate both in muscle biopsy sections and in human primary myoblasts. The insightful comments of Dr. Esther Peña have been very helpful in improving the quality of the images of our experiments.”

There are groups that practically do all their research in collaboration with this platform. It is the case of Dr. Gemma Arderiu, researcher in the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases group at IIB Sant Pau. He explains that “in 99% of our articles ‘Confocal Microscopy’ appears. We use it for many things, such as locating proteins at the level of the membrane, cytoplasm or nucleus, by seeing fluorescents. But what we use more is to see the interaction between two cells”.

This group studies the process of angiogenesis and for many of their studies they need to observe how the vessels are formed. “For example, we analyze endothelial cells and muscle cells to find out how they are organized with each other. Or, adipose tissue stem cells, which we have differentiated into endothelial cells and we want to see how these vessels are formed with different staining can be functional”.

Dr. Arderiu highlights that the Confocal Microscopy Platform is a strategic partner of its research group that brings excellence to its research. “Since I have been in Sant Pau I have collaborated very closely with Dr. Esher Peña and she has always made very valuable contributions to us. He gives us added value not only in terms of technique, but also with his conceptual knowledge which, without a doubt, helps us greatly improve the quality of our articles”.