NEWS

Suicidal behaviors increased by over 50% in Catalonia after the COVID-19 pandemic

The COVID-19 pandemic has sparked extensive discussions about its effect on mental health. While global suicide rates remained stable during the pandemic, the specific impact on non-lethal suicidal behaviors, namely, ideation or suicide attempts that are survived, during and after the pandemic had not been explored.

A new study, led by Dr. Víctor Serrano-Gimeno from the Mental Health Research Group of the Sant Pau Research Institute (IR Sant Pau), reveals a significant increase in these behaviors after the lockdown. The study, published in The Lancet Psychiatry, analyzes data from a Catalan cohort from all hospitals in Catalonia collected through the Catalan Suicide Risk Code in three periods: the pre-lockdown period (January 1, 2018, until the implementation of the lockdown in Spain on March 14, 2020); the lockdown period (March 14, 2020, until the end of the lockdown on June 21, 2020); and the post-lockdown period (June 21, 2020, until December 31, 2022).

The results reveal a slight increasing trend in non-lethal suicidal behaviors from January 1, 2018, until March 13, 2020, followed by a reduction during the lockdown period and a 50.77% increase after the lockdown measures. These results highlight the prolonged impact of the pandemic on the population’s mental health. Dr. Serrano-Gimeno explains that “this study provides a comprehensive examination of non-lethal suicidal behaviors in Catalonia, highlighting the dynamics of the different phases of the COVID-19 pandemic.

The initial reduction during the strict quarantine may be explained because people have less access to methods of suicide, among other reasons. And the subsequent increase after the lockdown reflects complex factors, including social isolation and economic challenges.” Specifically, stratified data analyses indicated that the relaxation of the lockdown resulted in a significant increase in non-lethal suicidal behaviors among women – especially in the 18 to 30 age group – and among minors under 18.

These results underscore the need for preventive strategies targeted at these groups. Dr. Maria Portella, head of the Mental Health Research Group at IR Sant Pau, emphasizes the importance of this study because “it quantifies what we already suspected about mental health during the pandemic. It highlights the need for a perspective beyond mental illness to address suicidality, addressing it as a fundamental aspect of public health.”

For her, “this article highlights the much longer-term consequences of the decisions made during the pandemic. We quantify it, but it also puts a much broader focus on mental health in the sense that it wasn’t necessarily people with a psychiatric diagnosis. And this is very important because it shows that suicide is a much more global public health issue.”

In this regard, Dr. Narcís Cardoner, researcher from the Mental Health Research Group at IR Sant Pau and head of the Psychiatry Department at Sant Pau Hospital, adds that these results tell us many things that should be used to face similar situations better in the future. “It’s interesting that throughout the pandemic, physical health was markedly prioritized. And all strategies, for example, the lockdown itself, were aimed at reducing the risk of people getting infected with the virus. But we knew that the impact of these situations would go beyond. And there’s always talk of a fourth wave, which is the mental health problem. And it seems that we were somewhat oblivious to this situation. Data like those derived from this study say that physical health is very important, but there is no health without mental health, and it would have been essential to have made some provision for these impacts.”

He also emphasized that “sometimes what’s good for physical health isn’t always good for mental health. So here, looking to the future, we must propose more holistic approaches to similar situations. I think it’s an important lesson from what happened with the pandemic, especially considering that it mainly affected young women and minors. It’s a lesson whose effects we knew, we were aware of, but we were absolutely turning our backs on it. We somewhat overlooked it or denied it.”

In fact, the three experts agree that during the pandemic, other countries had more lenient lockdown measures “that seemed to not have a differentiated impact in the field of physical health, and we don’t know why because it’s true that mental health data seem to be quite generalizable worldwide.The impact of the pandemic, for example, in terms of the risk of depression, anxiety disorders, has been very marked worldwide. Rates, the prevalence of depression, and anxiety have increased. So, we’re identifying a very generalizable phenomenon.”

For them, it’s necessary that in future occasions much more global measures are considered “and to think of mental health as an essential part of health. Since the effects are not so immediate, perhaps we think they’re like second-level issues, as if they weren’t so important.”

Finally, Dr. Cardoner emphasizes the current pressure on the healthcare system: “You just have to go through our emergency rooms to see the saturation. This demonstrates that the pandemic has been a brutal stress test for an already fragile society. This study is important because it quantifies it. We all had this idea that mental health was doing terribly. And here we can confirm it with numbers. the situation has evolved as it has evolved.”

Dr. Serrano concludes that “the results show us that the consequences of large-scale social phenomena are profound, and this must be addressed from a public health perspective, not just psychiatry.”

Reference Article

Víctor Serrano-Gimeno, Alba Diestre, Marina Agustin-Alcain, Maria J Portella, Javier de Diego-Adeliño, Thaïs Tiana, Nora Cheddi, Alejandro Distefano, Guillermo Dominguez, Marina Arias, Victor Cardoner, Dolors Puigdemont, Victor Perez, Narcís Cardoner. Non-fatal suicide behaviours across phases in the COVID-19 pandemic: a population-based study in a Catalan cohort, The Lancet Psychiatry. Volume 11, Issue 5, 2024, Pages 348-358, ISSN 2215-0366, https://www.sciencedirect.com/science/article/abs/pii/S2215036624000658?via%3Dihub


Un estudi pioner de Sant Pau i el Barça Innovation Hub descriu, per primer cop, com l’esport d’alta intensitat afecta l’expressió genètica

Un estudi pioner realitzat per investigadors de l’Institut de Recerca Sant Pau i la Universitat Politècnica de Catalunya (UPC), en col·laboració amb el Barça Innovation Hub -l’àrea de recerca i innovació del FC Barcelona-, ha permès relacionar, per primer cop, com afecta l’esport d’alta intensitat a l’expressió genètica. Concretament, s’han detectat alteracions al sistema immune, el metabolisme dels aminoàcids, la generació d’energia i els nivells d’estrès oxidatiu de l’organisme just després de practicar exercici d’alta intensitat.

L’estudi, que publica la prestigiosa revista científica PlosOne Journals, ha identificat diferents perfils de recuperació de l’esforç físic realitzat durant l’exercici d’alta intensitat que permet, de manera personalitzada, establir una nova forma innovadora de distingir, en un mateix equip, esportistes en funció de si són recuperadors ràpids o lents en funció de l’expressió dels seus gens.

La investigació s’ha centrat a analitzar el perfil d’expressió dels gens dels jugadors d’equip d’handbol del FC Barcelona, examinant quins gens s’activen o inhibeixen en funció de l’esforç físic de cada jugador durant el partit i relacionant-lo amb la preparació física i la capacitat de recuperació després d’un partit.

L’objectiu era relacionar els nivells de càrrega externa dels esportistes, ocasionats per l’activitat esportiva d’alta intensitat, amb l’activació de tots els gens del genoma de cadascun dels individus.

Tècnica pionera de darrera generació

Aquest estudi es distingeix per ser dels primers a utilitzar tècniques avançades de seqüenciació mitjançant NGS (Next-Generation Sequencing) que permeten analitzar l’expressió de tots els gens del genoma en sang mitjançant l’anàlisi dels nivells d’ARNm, recolzant-se en algoritmes sofisticats d’intel·ligència artificial per interpretar les dades obtingudes.

El Dr. José Manuel Soria, cap del grup de Genòmica de les malalties complexes a l’Institut de Recerca Sant Pau, comenta que: “la transcriptòmica (expressió dels nostres gens) exerceix un paper crucial a l’hora de desentranyar els mecanismes moleculars associats amb el rendiment i la recuperació a l’esport, com demostren els nostres resultats”.

Aquest expert, que és l’autor principal de l’estudi, afegeix que “amb aquesta informació -la identificació de gens clau i l’alteració de les vies involucrades- aplicada a l’esport, els professionals de la salut podran desenvolupar intervencions específiques i personalitzades per millorar el rendiment, la recuperació, així com per reduir el risc de lesions a cada esportista. Aquests resultats també tindran un alt impacte als esportistes no professionals que vulguin millorar els seus objectius o, simplement, millorar la seva salut”.

Una porta a la medicina esportiva del futur

La tecnologia utilitzada en aquest estudi obre la porta a un gran ventall d’aplicacions a l’àmbit de la medicina personalitzada i a la personalització d’intervencions clíniques. Analitzat el perfil transcriptòmic dels esportistes, es poden detectar aquelles alteracions en l’expressió dels gens de cada individu que en dificulten els processos de recuperació esportiva i permet optimitzar el rendiment dels jugadors a través d’intervencions personalitzades adaptatives, basant-se en les característiques específiques de cadascun dels esportistes.

Aquest avenç no només beneficia els atletes d’alt rendiment, sinó que també té implicacions potencials en l’àmbit de la salut i el benestar general, ja que proporciona un enfocament més holístic i personalitzat en la cura de la salut esportiva.

Article de referència

Ezquerra Condeminas P, Mallol M, Font R, Tremps V, Gutiérrez JA, et al. (2024) Unraveling athletic performance: Transcriptomics and external load monitoring in handball competition. PLOS ONE 19(3): e0299556. https://doi.org/10.1371/journal.pone.0299556


Psychosis in Parkinson’s disease is not only associated with the use of dopaminergic medications, but it is also part of the disease process itself

A study conducted by researchers from the Parkinson’s Disease and Movement Disorders Research Group at the Sant Pau Research Institute, led by Drs. Jaume Kulisevsky and Javier Pagonabarraga, has concluded that psychosis associated with Parkinson’s disease (PDP) not only arises as a complication of dopaminergic drug use but is intimately related to the brain alterations caused by the disease itself.

The study, published in the journal Nature Reviews Neurology, has identified a pattern of cortical atrophy involving various brain regions that would explain how new stimuli are incorrectly categorized and how aberrant hierarchical predictive processing can produce false perceptions that intrude on consciousness flow.

Psychosis associated with Parkinson’s disease (PDP) is a condition that causes illusions, hallucinations, and delusions in more than half of patients with this neurodegenerative disorder. Although it was long believed to appear in advanced stages of the disease and as a result of treatments, it is now known that it can manifest from early stages and follow a continuum ranging from minor hallucinations to structured hallucinations and delusions.

Dr. Javier Pagonabarraga, the lead researcher of the study, explains that “Parkinson’s patients not only face mobility problems but also mood disorders such as anxiety, depression, and apathy. During the course of the disease, between 40-60% of patients may also experience hallucinations, and less frequently some delusional episodes. Hallucinations and delusions are a hallmark of the disease, which has driven research towards a neurobiological model to better understand these phenomena.”

Initially, it was believed that Parkinson’s disease psychosis was mainly related to the use of dopaminergic medications. However, neuroimaging studies have provided a new perspective, demonstrating that this condition develops from the evolution of brain alterations. It has been discovered that the combined dysfunction of various brain systems, including attention control, sensory processing, limbic structures, along with anomalies in the default mode network and thalamo-cortical connections, create a conceptual framework for understanding how new stimuli can be misinterpreted, causing false perceptions that disrupt consciousness flow. Additionally, this brain dysfunction is exacerbated by the use of dopaminergic medications.

Dr. Pagonabarraga explains that “long before people experience severe hallucinations, they already begin to have more subtle and mild hallucinatory phenomena, which often go unnoticed. Thanks to our studies and those of other researchers, we can now identify these phenomena at an earlier stage, allowing us to intervene and address them before they become severe. It is much better to treat these manifestations when they start to emerge than when they have already fully developed and there is a significant loss of reality consciousness.”

This expert details that psychosis has two different types of symptoms: hallucinations – which are the most frequent in these patients – and delusions. It is a clinical characteristic unique to Parkinson’s disease “that has a very clear impact on the quality of life and has even been shown to increase mortality; therefore, understanding the neurobiological bases, that is, which circuits or which parts of the brain are the ones that cause or trigger a person to have hallucinations, is relevant beyond the disease.”

An Opportunity Window

Up to 60% of Parkinson’s patients present psychosis at some point in the disease, but symptoms do not start abruptly. Long before people have severe hallucinations, they already start to have more subtle and mild hallucinatory phenomena that often go unnoticed. “This, in a way, opens a temporal window where we can intervene by treating them before they evolve and become severe. It is much more effective to treat them when they begin to manifest than when they are already severe and involve the loss of reality consciousness,” adds Dr. Pagonabarraga.

Minor hallucinations are subtle forms of the disorder and can be primarily of two types. On the one hand, those known as presence hallucinations, “which is the sensation that someone is behind you, for example, near a shoulder, even though you know there is no one there. The other type is passage hallucinations, which is the sensation that something is passing by the sides of your body. And it happens, moreover, in a very stereotyped way: from behind forward. Patients have the sensation that there is something passing by the side of their body. Most of the time they say it’s the shadow of a person.”

A previous study by this same research group had already observed that these minor hallucinations were present in 40% of Parkinson’s patients from the first visit, that is, before taking any dopamine-raising drugs.

Dr. Pagonabarraga adds that as the disease progresses, the next step is structured visual hallucinations, “not in the periphery, but in the patient’s visual field. They see animals, people, they can sometimes see faces flying as if they had the silhouette of a flying person or sometimes they see elongated people with an indefinite face and a more defined body. Sometimes they can see small children, for example. And these hallucinations occur mainly inside their home. Initially, patients see them, but they know they are not true and it causes them some discomfort. But if we don’t treat them and do nothing, they tend to progress to more severe forms where they see them much more frequently and are no longer aware that they are false. That’s when they do generate a lot of agitation, concern, distress that needs to be treated with drugs that have a negative effect on the evolution of the disease and on the mortality of patients.” This is why it is important to start treating psychosis early.

These findings not only provide a better understanding of psychosis in Parkinson’s disease but also open the door to new therapeutic strategies that could significantly improve the quality of life of affected patients.

Reference Article:

Pagonabarraga J, Bejr-Kasem H, Martinez-Horta S, Kulisevsky J. Parkinson disease psychosis: from phenomenology to neurobiological mechanisms. Nat Rev Neurol. 2024 Jan 15. doi: 10.1038/s41582-023-00918-8.


Dr. Juan Fortea addresses the challenges and advances in health care for people with Down syndrome in a featured editorial in ‘The Lancet’

The prestigious journal The Lancet has invited Dr. Juan Fortea, director of the research area in Neurological Diseases, Neuroscience, and Mental Health at the Sant Pau Research Institute, and director of the Memory Unit of the Neurology Service at the same hospital, to write the editorial published on the occasion of World Down Syndrome Day, highlighting the significant advancements in the quality of life and life expectancy of people with this condition. Dr. Fortea emphasizes the improvements achieved thanks to advances in healthcare and research, as well as increased social participation. However, he points out that inequalities in health outcomes still persist, attributable to a lack of awareness and training on Down syndrome among healthcare professionals, families, and other stakeholders, a problem exacerbated by structural factors such as social discrimination and inadequate service provision.

The editorial emphasizes the importance of overcoming these inequalities and appeals for a global approach that includes research, awareness, and inclusive policies. It highlights the urgent need for epidemiological data and resources specifically directed at meeting the health needs of people with Down syndrome worldwide, especially in low- and middle-income countries. Through the publication of this editorial in The Lancet, Dr. Fortea and his collaborators seek to inspire positive change, fostering a renewed commitment among researchers, healthcare professionals, policy makers, and the global community, to ensure a full and equitable life for all individuals with Down syndrome.

Reference article

Juan Fortea, Eimear McGlinchey, Joaquín M Espinosa, Michael S Rafii. Addressing challenges in health care and research for people with Down syndrome. The Lancet, 2024. ISSN 0140-6736, https://doi.org/10.1016/S0140-6736(24)00478-1.


Sant Pau initiates a pioneering study on the potential benefits of sports in Parkinson’s patients

The Parkinson’s Disease and Movement Disorders Research Group at the Sant Pau Research Institute (IR Sant Pau) has launched a scientific study to evaluate the potential cognitive, motor, and emotional effects and benefits of sports in patients with this neurodegenerative disease. The study is supported by the Golf with Parkinson Association, the Barcelona Golf Club, the Barcelona Golf Academy, and the Catalan Golf Federation. Over a period of two and a half months, a group of volunteer patients will engage in weekly sports sessions lasting an hour and a half, every Friday morning, at the Barcelona Golf Club. Additionally, on April 12, coinciding with World Parkinson’s Day, a charity tournament will be organized to raise funds for this study with the participation of patients.

The Golf with Parkinson Association was founded by Juan Carlos Campillo, a passionate golfer who was diagnosed with the disease three years ago. “I didn’t know what was happening to me. I was a handicap 5 and my game deteriorated so much that I couldn’t even count the strokes anymore.” Parkinson’s was already affecting his movements, much slower, with a swing speed nowhere near his usual. However, he sought ways to continue training and adapt his new physical condition to this sport. He asserts that “maintaining body mobility and physical activity is fundamental. And practicing sports helps a lot.”

With this objective in mind, the Sant Pau Research Institute and the Golf with Parkinson Association have initiated a pioneering study to analyze the benefits that playing this sport can bring to these patients. The research team is led by Dr. Carmen García-Sánchez, a researcher at the Sant Pau Research Institute and a neuropsychologist at the Neurology Service of the Hospital.

The doctor explains that “while there are pharmacological treatments and rehabilitation therapies available, it is important to explore complementary approaches that can improve the quality of life of these patients. Interventions based on sports and social activities are a therapeutic resource used to treat motor, emotional, and behavioral disorders in patients with Parkinson’s disease, and in this sense, sports could provide benefits. But it needs to be investigated to support its inclusion in their management.”

Rigorous methodology for evaluating potential benefits

It is estimated that 1 in every 100,000 people over 60 years of age will suffer from Parkinson’s disease. It is a chronic, progressive, and multisystemic pathology. Symptoms worsen over time – although the progression varies greatly among patients – and in the late stages, complications such as motor and non-motor fluctuations, dyskinesias (disorders of voluntary movements and appearance of involuntary abnormal movements), cognitive disorders, and behavioral disturbances may appear.

There are different causes that intervene in the onset of Parkinson’s disease. Mainly, the degeneration of neurons called dopaminergic, which produce abnormal patterns of nerve activation in the brain and cause deterioration of movement. But there are also other known and unknown causes. “Between 10% and 15% of cases are genetic – dominant and recessive – and these cases usually affect very young people, around 40 years old or even younger. We often think it is a disease of older people, from the age of 60 onwards, but young people also suffer from it,” explains Dr. Jaume Kulisevsky, director of the Parkinson’s Disease and Movement Disorders Research Group at the Sant Pau Research Institute and director of the Parkinson’s Disease and Movement Disorders Unit at the Neurology Service of Sant Pau Hospital.

Practicing a low-impact sport (walking, yoga, pilates, swimming, skating, cross-country skiing, golf, etc.) provides a comprehensive workout that promotes range of motion, activates muscles in the upper and lower body, flexibility, and balance, which has been shown to be useful in reducing falls in people with Parkinson’s disease. Additionally, it combines moderate physical activity, fine motor coordination, concentration, and strategy, elements that could help improve motor function, coordination, flexibility, balance, cognition, and mood.

 

How will the study be conducted?

The research, entitled “Observational Pilot Study of Golf Practice on Gait, Cognition, and Behavior in Parkinson’s Disease”, involves a group of volunteer patients with the pathology in an early or moderate and stable stage recruited from the Movement Disorders Unit and the Neuropsychology Unit of Sant Pau Hospital.

The study is financially supported by the Golf with Parkinson Association and has the support of the Barcelona Golf Club, the Catalan Golf Federation, and the Barcelona Golf Academy, which provides the technology and software necessary for data capture and measurement that will allow the analysis of patients’ progress.

Every Friday morning, a bus will pick them up at the Hospital and take them to the Barcelona Golf Club based in Sant Esteve Sesrovires, which will provide all the necessary materials: clubs, putters, balls, etc. Once there, they will have a 90-minute session – with regular breaks to avoid fatigue – for 12 weeks led by coach Carlos Vivas. At the end of each session, the same bus will make the return trip to Sant Pau.

Regarding the study methodology, before and after each weekly session, researchers from the Sant Pau Research Institute will use a mood questionnaire to detect short-term emotional changes in these patients. Specifically, and for this purpose, they will use the Scale for Mood Assessment (EVEA) as a self-assessment of emotional state and feelings.

At the end of the 12-week study period, a final evaluation will be carried out, and the analysis and publication of the results are scheduled for June-July 2024.

 

Sant Pau, a reference in care and research in Parkinson’s disease

Sant Pau Hospital focuses a significant part of its care and research activity on movement disorders, where the Neurology Service Unit is CSUR (Centers, Services, and Units of Reference) and has extensive experience dedicated to all types of rare neurological diseases of great complexity characterized by the development of abnormal movements – such as Huntington’s disease, atypical parkinsonisms, early-onset Parkinson’s disease, ataxias, or Tourette syndrome, among others.

In Parkinson’s care, it provides cognitive stimulation in the Clinical School of Neuropsychology and Language Pathology, and among other initiatives, it has a patient choir composed of more than 30 people. Additionally, it is a reference center in deep brain stimulation for Parkinson’s disease, a technique it has been applying for 25 years and where it was a pioneer.

In research, it carries out various projects: the Sant Pau Research Institute was a pioneer in describing and designing specific tools to assess cognitive impairment in Parkinson’s, such as the Parkinson’s Disease Cognitive Rating Scale (PD-CRS) used in all studies focused on this area, and promotes studies independently or in collaboration.

One of the most recent, published this year, has evaluated the medical and emotional benefits of theater in twenty patients diagnosed with Parkinson’s, an initiative that included workshops on body awareness, movement, and improvisation conducted in collaboration with the Open University of Catalonia and the Teatre Lliure of Barcelona. The results showed an improvement in mood and anxiety and depression disorders and in immediate memory – with better concentration capacity.


Myasthenia gravis meeting at Sant Pau

Dr. Eduard Gallardo, a researcher from the Neuromuscular Diseases group at the Sant Pau Research Institute, hosted the “F2F meeting OptiMyG,” a gathering that brought together various professionals to kick off the Characterization and optimization of myasthenia gravis care (OptiMyG) project. The project, coded EJPD AC23_2/00030, was granted to the consortium in the 2023 call for the European Joint Programme on rare diseases. Myasthenia gravis is a rare chronic autoimmune disease that causes weakness and fatigue in voluntary muscles, including those used for eye and eyelid movement. The event took place at the Sant Pau Research Institute on March 14 and 15 with the participation of experts from Sweden, Poland, Switzerland, Italy, Spain, and Finland.

Dr. Gallardo explains that “the project is an initiative of the EJPD Consortium for rare diseases, which includes several countries. The purpose is to contribute to improving the way this disease is treated, establishing protocols for data and sample collection. It is important to share data because it is a rare disease, and with larger samples, it is easier to reach conclusions.”

Currently, there is no consensus or clinical guideline that collects detailed clinical, epidemiological, treatment, and immunological parameter data from various countries for the diagnosis and treatment of myasthenia gravis. “One of the objectives of OptiMyG is to contribute to harmonizing and standardizing criteria to improve the way this rare disease is treated because it has been observed that different countries approach patients somewhat differently.”

During the event, administrative issues such as consortium agreement, ethics, and data management were addressed. Discussions also revolved around the collection of clinical data, both retrospective and prospective, related to myasthenia gravis. Additionally, plans for experimental studies, establishment of timelines, as well as consideration of ethical issues and management and exchange of samples (serum, cells, etc.) were discussed.


Anna Aulinas, recognized within the European sphere as a Rising Star

Dr. Anna Aulinas, coordinator of the Pituitary Diseases Unit at the Hospital de Sant Pau, researcher in the Pituitary Diseases group at the Sant Pau Research Institute, and member of Unit 747 of CIBERER (Rare Diseases Research Network in Spain), has recently been distinguished on the European stage with the 2024 Rising Star Award from the European Journal of Endocrinology (EJE).

This award is granted to individuals selected by the editors of this prestigious journal for demonstrating promising potential, achievement, and trajectory in establishing themselves as clinical and translational researchers in the field of endocrinology, with high potential to serve as future editors of the EJE. The award consists of membership in the EJE Rising Star Evaluation Council for two years, a dedicated mentoring program for future editors of the journal.

Dr. Aulinas specialized in endocrinology at the Hospital de Sant Pau and later completed a two-year postdoctoral stay in the Neuroendocrinology Unit at Massachusetts General Hospital (Harvard Medical School) in Boston (United States), obtaining a Juan Rodés contract. Currently, she works as a researcher at the Sant Pau Research Institute, in the Pituitary Diseases research group – led by Dr. Susan Webb –, and coordinates the Pituitary Diseases Unit at the Hospital de Sant Pau, a National Reference Center accredited in Pituitary Diseases and a center recognized by the European Reference Network for Rare Endocrine Diseases (EndoERN).

Dr. Aulinas has been awarded several young investigator prizes from national and international scientific societies for her research and contributions in the field of neuroendocrinology. Her work and dedication are an example of the excellence that defines the staff of the Sant Pau research institute, reinforcing its reputation as a reference center in the treatment of endocrine diseases.


A study describes the relationship between primary progressive apraxia of speech and agrammatic aphasia

An international study conducted by researchers from the dementia neurobiology group at the Sant Pau Research Institute and the Memory Unit of the same hospital suggests that primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) are disorders that could be part of a clinical continuum rather than being completely distinct entities. The research, which focused on patients with progressive speech impairment and/or agrammatism, sought to identify distinct sets of symptoms that do not naturally overlap, such as PPAOS and PAA.

Dr. Ignacio Illan Gala, a researcher at the Biomedical Research Networking Center for Neurodegenerative Diseases (CIBERNED) at IR Sant Pau and lead author of the study, explains that “there are various solutions for these patients. We can, for example, provide speech therapy and interventions to try to improve patients’ speech and articulation, which may temporarily alleviate symptoms, although it will not alter the progression of these diseases.”

The study, published in the prestigious journal Brain, was conducted by specialists in speech pathology and included 98 participants, 43 of whom had a neuropathological diagnosis confirmed by autopsy. Researchers evaluated characteristics indicative of dysarthria and apraxia of speech. In addition, quantitative measures of expressive/receptive agrammatism were taken and compared with healthy controls. The severity of the disease at onset and progression was assessed using the sum of scores from the Clinical Dementia Rating (CDR-SB). Dr. Illan explains that “the diagnosis of this syndrome is general and interpretative; what is needed are objective markers that are not clinical to reach a definitive diagnosis.”

The results revealed that 93 out of 98 participants matched previously documented clinical profiles, with 75 of them diagnosed with apraxia of speech (AOS) and agrammatism, 12 with PPAOS, and 6 with PAA. However, five participants showed a different pattern, with no clear evidence of apraxia of speech or agrammatism, characterized by non-fluent speech, executive dysfunction, and dysarthria. “We are working to understand these diseases in order to identify the specific pathology causing the symptoms in each patient. Once identified, we will then propose treatments specifically targeted at that pathology,” says Dr. Illan.

Statistical analysis revealed a low tendency toward clustering in the dataset, indicating a lack of clear separation between subgroups. Only two solid subgroups were identified, differentiated by the presence of agrammatism, executive dysfunction, and overall disease severity. Furthermore, three latent clinical dimensions were identified based on the following data: severity-agrammatism, prominent presence of Apraxia of Speech (AOS), and prominent presence of dysarthria. These dimensions explained 71% of the variability observed in the patients’ symptoms.

Although none of these dimensions enabled precise prediction of neuropathology, it was observed that the intensity of agrammatism acted as an independent predictor of faster increase in CDR-SB score in all participants. Additionally, the severity of dysarthria, reduction in words per minute, and intensity of expressive/receptive agrammatism at onset also independently predicted accelerated disease progression.

In conclusion, this study suggests that PPAOS and PAA, rather than being completely distinct entities, constitute a clinical continuum. The findings highlight the need for new biological markers and consensus on updated terminology and clinical classification within the spectrum of non-fluent/agrammatic primary progressive aphasia.

 

Reference Article

Illán-Gala I, Lorca-Puls DL, Tee BL, Ezzes Z, de Leon J, Miller ZA, Rubio-Guerra S, Santos-Santos M, Gómez-Andrés D, Grinberg LT, Spina S, Kramer JH, Wauters LD, Henry ML, Boxer AL, Rosen HJ, Miller BL, Seeley WW, Mandelli ML, Gorno-Tempini ML. Clinical dimensions along the non-fluent variant primary progressive aphasia spectrum. Brain. 2023 Nov 21:awad396. doi: 10.1093/brain/awad396. Epub ahead of print. PMID: 37988272. DOI: 10.1093/brain/awad396


A new research group on artificial intelligence applied to medicine is born at Sant Pau

The Sant Pau Research Institute announces the creation of the new research group in Advanced Medical Imaging, Artificial Intelligence, and Image-Guided Therapy. Dr. Josep Munuera, a researcher with a broad trajectory in the use of artificial intelligence applied to medicine and director of the Radiodiagnosis Service at Hospital Sant Pau, will lead this cross-sectional and multidisciplinary project that seeks to go beyond traditional specializations.

The approach of this new group goes beyond traditional currents by integrating experts from various medical and technological disciplines, both from the research institute and the hospital. This project is structured in two main areas: the first one focuses on quantitative vascular imaging, exploring more effective methods for extracting and analyzing data. The second one is based on the use of generative artificial intelligence in radiology and medical imaging, opening up new possibilities in data analysis and transformation.

Medical imaging is crucial in the research of virtually all medical specialties. The application of artificial intelligence will maximize the potential of data obtained through imaging tests, contributing significantly to advancing research and, therefore, improving clinical practice,” says Dr. Munuera.

The strength of this group lies precisely in its cross-sectional, heterogeneous, and multidisciplinary nature. “We invite researchers from different areas of the institute to join and create a unique collaboration environment. Although radiology and medical imaging are fundamental, we want to break down knowledge silos and foster collaboration among professionals from all specialties such as computer vision, physics, or bioengineering, as well as various medical branches, allowing for comprehensive and enriching collaboration. Medical imaging is a unique universe of data, and we want our experts to explore all its potential,” emphasizes this researcher.

In addition, the new group will not be limited to internal research but will also offer consultancy to other research groups both inside and outside the institute. “The vision is broad, ranging from the role of imaging in specific diseases to the application of artificial intelligence in surgical planning and 3D image design, diagnosis, and treatment of multiple diseases.”

Dr. Munuera explains that medical imaging is a transversal tool in the research of virtually all medical specialties, and now, the application of artificial intelligence will serve to harness the potential of the data obtained through imaging tests and achieve their maximum performance. “It is true that this group covers many areas, but it also brings the value of integrating them all for the benefit of research.”

A distinguished trajectory

Dr. Josep Munuera is a reference in research on artificial intelligence applied to medicine. This radiologist specialized in neuroradiology at the Hospital del Mar in 2005. He worked as an associate in neuroradiology at the Vall d’Hebron and Sant Pau Hospitals between 2005 and 2012. Subsequently, he was head of the Magnetic Resonance Unit at the Germans Trias i Pujol Hospital from 2012 to 2016; Health Director at the Institute of Diagnostic Imaging (CatSalut) from 2016 to 2017, and later, head of the Radiology Department at the Hospital Sant Joan de Déu, from 2017 to 2023. Since April 2023, he has been the Director of the Radiology Service at the Hospital de Sant Pau.

His academic and professional work has focused on the study of neuroradiology, especially in cerebrovascular diseases in adults and the innovative development of imaging biomarkers. He is the author of 85 scientific articles and 11 book chapters. He has led several national and international projects, such as the Expert3D program (EIT Health Campus for 3 consecutive years), CARONTE for cardiovascular risk assessment tools in pediatric oncology patients (Next Generation), and Vasculomics, a clinical decision support system for evaluating pediatric cerebral vascular diseases, highlighting his commitment to integrating AI and machine learning technologies in radiology to improve the accuracy and effectiveness of medical diagnoses and treatments. He currently directs the postgraduate course “Expert3D: AI and 3D in health” at the Polytechnic University of Barcelona.

With the impetus of this new research group, Sant Pau consolidates itself as a reference in the integration of artificial intelligence and medical imaging and reaffirms its commitment not only to advance research in this field but also to improve the clinical application of medical imaging.


Magnetic resonance surveillance reduces mortality in women at high risk of BRCA1 breast cancer as an alternative to preventive mastectomy

According to the results of an international study involving researchers from the Clinical Oncology group at the Sant Pau Research Institute, led by Dr. Teresa Ramon y Cajal, the follow-up with magnetic resonance imaging in women with mutations in the BRCA1 genes who have a high risk of developing breast cancer throughout their lives significantly reduces mortality without the need for preventive mastectomy.

The study, published today in the JAMA Oncology journal, analyzes data from women with pathogenic variants of the BRCA1 or BRCA2 genes and shows that those with BRCA1 sequence variations undergoing magnetic resonance imaging follow-up have a significantly lower breast cancer mortality rate. These results highlight the importance of early detection strategies, especially in women with a high genetic risk, and open the door to the need to evaluate the impact of this type of surveillance in women with variations in the BRCA2 gene.

The research includes data from patients from 59 different centers in 11 countries, among which Sant Pau stands out as the only center in the entire country. A total of 2.488 women with a mean entry age of 41,2 years were included. Of these, 1.756 (70,6%) underwent at least one magnetic resonance imaging test as part of the surveillance program, while 732 (29,4%) did not undergo any magnetic resonance imaging tests. After an average follow-up of 9,2 years, 344 women (13.8%) developed breast cancer, and 35 (1,4%) died from this disease.

“These results are important because these women have a very high risk of developing breast cancer. At Sant Pau, we have followed almost 200 patients for over a decade and have been able to verify that surveillance with magnetic resonance imaging significantly reduces their mortality because we detect tumors in very early stages when treatments are very effective,” explains Dr. Ramon y Cajal.

This expert adds that, “the alternative for these women at high genetic risk is to undergo a double radical mastectomy as a preventive measure. This is a very invasive technique, and it is important to remember that we are talking about individuals without any disease.”

Reference article:

  • Jan Lubinski, MD, PhD; Joanne Kotsopoulos, PhD; Pal Moller, MD; Tuya Pal, MD; Andrea Eisen, MD; Larissa Peck, MSc; Beth Y. Karlan, MD; Amber Aeilts, MSc; Charis Eng, MD, PhD; Louise Bordeleau, MD; William D. Foulkes, MBBS, PhD; Nadine Tung, MD; Fergus J. Couch, PhD; Robert Fruscio, MD; Teresa Ramon y Cajal,MD; Christian F. Singer, MD, MPH; Susan L. Neuhausen, PhD; Dana Zakalik, MD; Cezary Cybulski, MD, PhD; Jacek Gronwald, MD, PhD; Tomasz Huzarski, MD; Klaudia Stempa, MD, PhD; Jeffrey Dungan, MD; Carey Cullinane, MD; Olufunmilayo I. Olopade, MD; Kelly Metcalfe, PhD; Ping Sun, PhD; Steven A. Narod, MD; for the Hereditary Breast Cancer Clinical Study Group. MRI Surveillance and Breast Cancer Mortality in Women With BRCA1 and BRCA2 Sequence Variations. JAMA Oncol. doi:10.1001/jamaoncol.2023.6944

Professor Lina Badimon has been admitted to the Royal National Academy of Pharmacy.

Professor Lina Badimon, director of the Research Area on Cardiovascular Diseases at the Sant Pau Research Institute, has been inducted as a full member into Medal 11 of the Royal National Academy of Pharmacy, thus reaffirming her commitment to the promotion and advancement of pharmacology.

This distinction represents recognition of her contributions to pharmacological research. During the solemn ceremony, Prof. Badimon delivered her speech titled “Pharmacology in the era of precision medicine: Pharmacotherapy in cardiovascular diseases,” a highly relevant and current topic that promised to enrich knowledge and discussion within the scientific community.

The response on behalf of the Academy was given by the Full Member and President of Section 4th, His Excellency Mr. Juan Tamargo Menéndez. His intervention was a perfect complement to this celebration, emphasizing the importance and impact of pharmacological research in today’s society. This event not only marked a new milestone in Prof. Badimon’s career but also strengthened the Royal National Academy of Pharmacy’s commitment to academic excellence and significant contributions to scientific advancement in the field of cardiology.


Sant Pau Research Institute and Banc de Sang i Teixits sign an agreement to promote research in advanced therapies

The Sant Pau Research Institute (IR Sant Pau) and the Blood and Tissue Bank (BST) have signed a collaboration agreement aimed at promoting the development and production of innovative drugs.

The agreement, which represents a pioneering alliance between two leading institutions in the health field, establishes the basis for the creation of a joint node that will have facilities prepared for the production of advanced therapies, including CAR-T cells.

 Within the framework of this agreement, the IR Sant Pau undertakes to involve the Blood and Tissue Bank in the production of its CAR-T cells in clinical trials, consolidating them as an alternative facility for these advanced therapies.

 The signing of this agreement represents a fundamental step towards achieving common goals in research and the development of cutting-edge therapies. With this collaboration, the technical knowledge of the BST is merged with the research expertise of the Sant Pau Institute, enhancing innovation capacity in the field of advanced therapies.

One of the main functions of the Blood and Tissue Bank is to provide research teams worldwide with professional expertise and manufacturing capacity for advanced therapy medicines, leveraging the knowledge granted by unique facilities in the country, with 10 white rooms and a leading track record in technological advancements dedicated to serving this type of therapy for over 15 years.

 The BST headquarters has the laboratory, equipment, and necessary technology, especially cryopreservation tanks, to maintain these advanced therapy medicines, and above all, experts trained to handle these products. A network model of expertise that has been a pioneer in implementing innovative cancer therapies across the entire public hospital network.

 Dr. Jordi Surrallés, director of the IR Sant Pau, highlighted the importance of this alliance: “This agreement represents a unique opportunity to advance in the field of personalized medicine and advanced therapies. We are convinced that, together, we will achieve important milestones to promote research and improve the health and well-being of patients.”

 On their part, the CEO of the Blood and Tissue Bank, Anna Millan Álvarez, emphasizes that the signed agreement is the consolidation of a collaborative relationship between both institutions that has been going on for many years, and thanks to which “we have achieved milestones in the field of research that help position the Catalan ecosystem of health innovation at the forefront.”

 She added that, “alliances like the ones we maintain with the Sant Pau Research Institute, help us as a country to continue acting as a driver of advanced therapies beyond the Catalan scope and to work towards providing new solutions with medicine based on cellular therapy, which brings hope to many patients for whom there were previously no effective treatments, such as certain types of cancers.”

 The work teams of both institutions have already begun to coordinate to launch the first projects that will mark a before and after in the field of advanced therapies.

 A new stage of collaboration

 The Sant Pau Research Institute and the Blood and Tissue Bank previously signed an agreement to launch the Sant Pau White Room. The agreement served as a framework to design procedures and accredit it for the manufacturing of drugs in advanced therapies.

 The Sant Pau White Room 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 and renewed in 2022, doubling its production capacity.

 “Now we begin a new stage of collaboration with the Blood and Tissue Bank to position both institutions for the future production of advanced drugs expanding horizons beyond research, in order to reach all patients in need,” adds Dr. Surrallés.

 The Sant Pau Research Institute has developed two academic CAR-T drugs so far: HSP-CAR30 and HSP-CAR19M. In 2020, the first trial began with a CAR-T immunotherapy drug, pioneering in Europe, for the treatment of classical Hodgkin lymphoma and CD30+ relapsed or refractory non-Hodgkin T lymphoma, in collaboration with the Josep Carreras Foundation against Leukemia and the Josep Carreras Leukemia Research Institute. This drug is currently in phase II of research and constitutes the first CAR-T30 immunotherapy drug (academic), completely produced at Sant Pau, attracting patients from various countries such as Italy, Austria, Poland, Russia, among others.

 On the other hand, a clinical trial is currently underway with its second academic advanced therapy drug, produced and developed entirely at Sant Pau, the HSP-CAR19M. This drug is characterized by being enriched in memory T lymphocytes, more long-lasting, with the aim of being more effective against the disease and is being administered to patients with the most common types of B-cell lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma) who have not responded to other treatments.

 The clinical trial, promoted, coordinated, and directed from Barcelona by Dr. Javier Briones, director of the Cellular Immunotherapy and Gene Therapy Research Group at the IR-Sant Pau and head of the Clinical Hematology Unit of the Hematology Service at the Hospital de Sant Pau, collaborates with the Hematology Service of the Virgen del Rocío Hospital in Seville, within 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 grant of 2 million euros from the “la Caixa” Foundation, the ISCIII, the Josep Carreras Leukemia Research Institute, and the Blood and Tissue Bank of Catalonia also collaborate.

 Sant Pau, which is part of the European project T2Evolve, is one of the accredited centers in the country authorized to use CAR-T drugs, by the General Directorate of Basic Portfolio of Services of the National Health System and Pharmacy, which depends on the Ministry of Health. This center has top-notch facilities, as well as highly qualified and specialized professionals, which allows the development of unique CAR-T immunotherapy projects in Europe.


Albumin at 4% could benefit patients with chronic kidney disease undergoing cardiac surgery under extracorporeal circulation

A clinical trial conducted by Dr. Jordi Miralles, from the Anesthesiology and Resuscitation department at the Hospital de Sant Pau, analyzed the influence of albumin on the development of acute kidney injury associated with cardiac surgery under extracorporeal circulation (ECC) in patients with preserved preoperative renal function, compared to the strategy of purging the circuit with a balanced crystalloid solution versus a balanced crystalloid solution with 4% albumin.

The work, in which Dr. Alejandra Espinosa Guerrero, responsible for the Clinical Trials Clinical Research Unit (UICEC) at the Sant Pau Research Institute, participated through the performance of a pharmacoeconomic substudy, revealed a potential benefit of using 4% albumin as a purge for ECC in patients with preoperative renal function values at the lower limit, according to a post hoc analysis of the study data.

The results confirmed that the use of 4% albumin in ECC in patients with preserved renal function significantly reduces the direct costs associated with cardiac surgery, although clinically significant differences in the development of kidney injury were not detected overall in patients during the first five days after intervention between the two studied groups, according to the results found by Dr. Miralles.

Specifically, one of the most noteworthy aspects of the pharmacoeconomic study was the evidence that the use of 4% albumin as a purge for ECC reduces costs per patient per year by up to €650 compared to conventional treatment with crystalloid solution alone, making 4% albumin potentially more cost-effective in the long term.

Dr. Espinosa explains that it was found that in patients with preserved renal function, no clinical benefit was observed but an economic one, and it would be interesting to continue with a line of research focused on evaluating the effect of albumin in patients undergoing cardiac surgery under ECC with preoperative chronic kidney disease, since “the results of the post-hoc analysis in patients with lower glomerular filtration rate values from the study reveal a trend towards a benefit not only at the clinical level but also in terms of quality of life for the patient, possibly increasing up to 1 month of life in full health”.

In addition to studying the potential clinical benefit, the new study would incorporate a pharmacoeconomic substudy to assess the potential incorporation of albumin into daily clinical practice in these types of patients within the National Health System.


Sant Pau, present at the Annual Congress of the International Neuropsychological Society

Dr. Carmen García-Sánchez, neuropsychologist at the Neurology Service of Sant Pau Hospital and researcher at the Sant Pau Research Institute (IR Sant Pau), has presented the findings of a study on persistent COVID-19 and the potential relationship between body mass index and cognitive performance at the 52nd Annual Congress of the International Neuropsychological Society, recently held in New York (United States).

More information

The study, titled “Body Mass Index (BMI) and Psychological Health in Long-COVID-19 Patients: An Exploration of Cognitive Function, Anxiety, Depression, Apathy, Fatigue, and General Health Status,” was conducted on a total of 118 patients with persistent COVID-19, aiming to analyze the potential association between body mass index (BMI) and cognitive performance, anxiety, depression, apathy, and fatigue among these individuals. The study also explored whether BMI influences the overall health perception of these patients. The results obtained by the research team have shown that BMI may not be a direct determinant of these psychological aspects in the context of prolonged COVID-19.

According to Dr. Carmen García-Sánchez, fatigue has been associated “with medical conditions such as post-viral infections or neurological diseases. But there is no universally accepted definition of this clinical condition, and our knowledge of its underlying pathogenic mechanism is limited, which is why it represents a clinical challenge for experts.”For this reason, “it is necessary to thoroughly assess the sequelae in post-COVID-19 patients and continue studying their evolution to reduce cognitive deterioration and promote recovery.”

This new study presented at the Congress of the International Neuropsychological Society represents another step in the research line developed by IR Sant Pau, which has already published other studies revealing a connection between fatigue, depression, anxiety, and other cognitive deficits in patients with post-COVID syndrome. One of them, published in the journal Brain and Behavior, showed that the disease had a widespread impact on attention skills, executive functions, learning, and long-term memory. And another, published in the Journal of Neurology, revealed that fatigue in post-COVID patients was associated with anxiety, depression, and apathy.


The Sant Pau Research Institute reinforces its scientific excellence with the stabilization of two researchers

The Sant Pau Research Institute has stabilized two researchers from the Miguel Servet program of the Carlos III Institute of Health (ISCIII): Dr. Mª Virtudes Céspedes and Dr. Mª José Martínez Zapata. This stabilization responds to the Miguel Servet evaluation policy carried out by the Institute and which both researchers have successfully passed, standing out for their excellence in research, leadership and innovation.

Dr. Céspedes, a graduate in Biology from the Complutense University of Madrid, a doctor in Neurosciences from the Institute of Neurosciences of the CSIC-Universidad Miguel Hernández (2001), and a master’s degree in Analysis and Quality Control from the Technological Institute of the Chemical and Pharmaceutical Industry, has been a pioneer in identifying new therapeutic targets in peritoneal cancers, mainly in the most aggressive endometrial and ovarian cancers.

Her dedication to studying the influence of the nervous system on tumor progression and the application of high-throughput screening platforms and artificial intelligence aims to open new avenues for improving diagnostic and therapeutic strategies in oncology, consolidating her role as principal investigator of the emerging Gynecological and Peritoneal Oncology Group.

Since joining the IR Sant Pau in 2001, in the Oncogenesis and Antitumor Drugs group led by Dr. Ramon Mangues, Dr. Céspedes has evolved from a postdoctoral student to the leader of an innovative research group, obtaining a Miguel Servet researcher position in 2016. Her research line, which crosses the boundaries between neuroscience and oncology, seeks to develop advanced therapies that can transform the care of patients with these devastating cancers.

Her research lines focus on modeling highly metastatic gynecological cancers, using 2D and 3D systems, and xenotransplants derived from patient mice, to better understand the tumor’s pathophysiology and for use in preclinical evaluation of antimetastatic therapies based on nanoparticles, and tumor neuromodulation, both aimed at eliminating cancer stem cells.

On the other hand, and jointly with clinical researchers from the gynecology and obstetrics department of the Hospital de Sant Pau, she is working on identifying new prognostic markers and therapeutic targets using high-throughput screening platforms, big data, and artificial intelligence to improve the prognostic and therapeutic stratification of patients with endometrial cancer.

Over the past 5 years, she has obtained 7 competitive projects as PI and human resources from ISCIII and private institutions, actively contributed to drug development through contracts with the pharmaceutical industry. Among her most outstanding achievements, she is also a co-inventor of 3 patents covering the use of T22-targeted nanoparticle vehicles to deliver drugs and diagnostic agents into CXCR4+ cells (cancer stem cells).

On the other hand, Dr. Martínez Zapata, a medical graduate from the University of Barcelona (1988), specialized in Clinical Pharmacology trained at the Vall d’Hebron Hospital (HVH, 1993-96), and obtained her doctorate from the Autonomous University of Barcelona (UAB, 2006). Since 2016, as a senior associate researcher Miguel Servet, she has developed a line of clinical research on patient safety during surgery. She has conducted studies as PI, funded by competitive public grants, and has obtained human resources from ISCIII. She is also a researcher in group 43 of the CIBER of Epidemiology and Public Health (CIBERESP), and the Consolidated Catalan Group of Clinical Research and Applied Health. She is a member of the Ibero-American Cochrane Network, Cochrane Collaboration, and the Spanish Society of Clinical Pharmacology.

With an exceptional academic and professional background, she has focused her research on evaluating the safety and efficacy of clinical interventions, including the use of tranexamic acid to reduce bleeding in orthopedic surgery, platelet-rich plasma for wound healing, and the treatment of chronic venous insufficiency. Throughout her career, she has led several independent randomized clinical trials and has collaborated on international research projects, consolidating herself as a key figure within group 43 of the CIBER of Epidemiology and Public Health and the Consolidated Catalan Group of Clinical Research and Applied Health.

On the other hand,

The consolidation of Drs. Martínez Zapata and Céspedes symbolizes not only the recognition of their excellence and commitment to quality research, but also the commitment of the Sant Pau Research Institute to retaining talent and promoting scientific advancement in the field of health. Their stabilization will allow the continuation and expansion of initiated research projects, with the hope of reaching new discoveries that can transform the treatment and care of patients in the coming years.


Differences found in gut microbiota between men and women with ischemic stroke.

The Pharmacogenomics and Neurovascular Genetics Group of the Sant Pau Research Institute (IR Sant Pau) has conducted a pioneering study that reveals significant differences in gut microbiota between men and women who have suffered an ischemic stroke. This research highlights the importance of biological sex in studies related to cerebrovascular disorders and gut microbiota.

The study, published in the European Journal of Neurology, was carried out within the framework of the Maestro project, granted to Dr. Israel Fernández-Cadenas, head of this research group, by the Carlos III Health Institute.

Ischemic stroke, a cerebrovascular disease affecting blood flow to the brain, maintains a well-established connection with gut microbiota through the bidirectional gut-brain axis. Until now, no data were available relating the intestinal microbiota to the sex of ischemic stroke patients. According to Dr. Miquel Lledós, from the Pharmacogenomics and Neurovascular Genetics Group of IR Sant Pau and principal investigator of the study, “the vast majority of microbiota research related to stroke does not delve into specific microbial species. We wanted to work with more specific techniques that allow us to study these species, which are ultimately the most important.

The study involved a cohort of 89 patients who had suffered an ischemic stroke and included 12 healthy individuals as a control group. Researchers analyzed taxonomic differences in gut microbiota between men and women with ischemic stroke using complete metagenomic sequencing.

Analysis results revealed that men who have suffered an ischemic stroke exhibit greater species diversity compared to affected women. Additionally, sex differences were found in ischemic stroke patients regarding the Fusobacteriaceaefamily. It was also observed that these bacteria were not a consequence of the stroke but were already present before experiencing it, thus constituting a risk factor for the manifestation of this disease.

Dr. Fernández-Cadenas comments that the bacteria found in the group of women who had suffered an ischemic stroke “were different from the controls, and we don’t see this in men. In the group of men, there were no differences between stroke patients and controls; therefore, these bacteria were specific to stroke risk in women. Additionally, we validated this with bioinformatics studies, where we saw that these bacteria were not a consequence of having had a stroke but were present before it, and therefore, were a risk factor.”

This study is the first to indicate that there are differences in gut microbiota between men and women who have suffered an ischemic stroke, identifying high levels of Fusobacteriaceae in women as a specific risk factor for the disease. This finding underscores the importance of including biological sex in the design, analysis, and interpretation of studies on stroke and gut microbiota.

 

Reference article

  • Miquel Lledós, Luís Prats-Sánchez, Laia Llucià-Carol, Jara Cárcel-Márquez, Elena Muiño, Natalia Cullell, Cristina Gallego-Fabrega, Jesús M. Martín-Campos, Ana Aguilera-Simón, Marina Guasch-Jiménez, Daniel Guisado-Alonso, Anna Ramos-Pachón, Alejandro Martínez-Domeño, Artur Izquierdo, Rebeca Marín, Pol Camps-Renom, Joan Martí-Fàbregas, Israel Fernández-Cadenas. Ischaemic stroke patients present sex differences in gut microbiota. European Journal of Neurology. Volume30, Issue11. November 2023. Pages 3497-3506 https://doi.org/10.1111/ene.15931

Deferred prescription of antibiotics: an efficient and useful strategy to reduce the problem of bacterial resistance

The so-called deferred prescription of antibiotics is a strategy to reduce the inappropriate use of these medications, which can be helpful in addressing the serious global problem of bacterial resistance. This strategy has been shown to be slightly more efficient than immediate prescription and non-prescription of antibiotics and is perceived as a useful tool by professionals in situations of uncertainty, according to two new studies published by researchers from the Sant Pau Research Institute and the Ibero-American Cochrane Center.

In the first study, researchers conducted a cost-effectiveness analysis, comparing deferred prescription to immediate prescription and non-prescription of antibiotics. The analysis included data from a clinical trial conducted by the research group, showing that deferred prescription was slightly more efficient than immediate prescription and non-prescription of antibiotics.

Dr. Pablo Alonso, Director of the Epidemiology and Public Health and Primary Care Area at IR Sant Pau, researcher at the Ibero-American Cochrane Center, and principal investigator of this line of work, states that “deferred treatment in the pediatric population showed slightly superior results than other strategies, even when considering the costs of bacterial resistance”.

In the second study, researchers explored the perceptions and attitudes of primary care professionals regarding antibiotics and deferred prescription as a treatment for adult patients with respiratory infections. The study showed that this prescription strategy was useful for professionals in situations of diagnostic uncertainty, providing patients with a safety net in managing their health problem and representing an opportunity to educate patients about the proper use of antibiotics, giving them greater autonomy.

Researcher Gemma Mas, professor at the Sant Pau Nursing School, coordinator of the Nursing Care Research Group, and first author of both studies, points out that “deferred prescription is used by professionals in cases of doubt and, in very specific situations, such as before the weekend when the patient cannot consult their primary care center again in case of deterioration.” She adds, “deferred prescription is an opportunity to educate the population about these types of infections, antibiotics, and when they are necessary“.

 

Patients more involved in their treatment

These Sant Pau experts explain that deferred prescription implies that, in cases where the pediatrician or family doctor is unsure whether the infection is bacterial or viral and, therefore, uncertain about the need to prescribe antibiotics to a patient based on their clinical condition at that time, a prescription is given, and the patient or responsible person is also informed about the natural history of the disease and when they should consider using the prescription. “The days during which the child may have these symptoms and what the warning signs would be. Thus, parents or the affected person can assess whether, after a few days, they need to use this prescription or not. In other words, they are given structured advice and guidelines based on the progression of the disease“,emphasizes Dr. Gemma Mas, who highlights that this strategy provides a safety net, empowers patients, and educates them about the proper use of antibiotics.

For example, in the case of an ear infection, we can explain that if the patient does not improve after 3 days, or if they are much worse after 24 hours, it is necessary to consider using the prescription we have given them“. In this example, if the child improves, unnecessary use of an antibiotic is avoided – with its associated adverse effects and the risk of resistance – or the need to return to the doctor to seek a prescription in case of worsening, as explained by Dr. Gemma Mas.

Dr. Pablo Alonso comments that, although deferred prescription is only relatively implemented in primary care centers in Catalonia, there is still room for improvement. Lack of specificity in clinical guidelines and the need for more detailed tools were identified as areas for improvement for a more effective implementation of this strategy.

In summary, deferred prescription of antibiotics emerges as a valuable tool, not only to reduce costs and bacterial resistance but also to empower patients and educate about the real need for antibiotics in specific cases.

These experts emphasize that this deferred prescription strategy “is a patient-centered approach, providing us with a great opportunity to educate and empower them for decision-making“.

 

Patient satisfaction, resistance, and system sustainability

Dr. Joaquín López-Contreras, director of the Infectious Diseases Unit and responsible for the Nosocomial Infections and Antibiotic Policy Program at Sant Pau Hospital, indicates that “the use of deferred prescription in primary care is a strategy that has shown savings in the use of unnecessary antibiotics and, therefore, should have an impact on the progression of bacterial resistance in the community“.

From his point of view, these studies provide scientific evidence, “now it is necessary to analyze why this strategy, which has already demonstrated its effectiveness, is not implemented one hundred percent, and we must try to generalize it since, in addition to being positive in terms of patient satisfaction and resistance evolution, it is efficient in an economic sense, and this is also important to contribute to the sustainability of the health system“.

Dr. López-Contreras has emphasized that there is a correlation between the use of antibiotics and the percentage of resistance in different geographical areas of the world. “Southern European countries and countries in South Asia are very important consumers of antibiotics. Performing these types of interventions in Primary Care that educate citizens about the importance of the proper use of antibiotics and also help reduce their use seems to me a good strategy, with a global approach, to reduce the significant health problem posed by bacterial resistance”.

Trust and a good doctor-patient relationship are key factors in implementing this strategy, explains Dr. María Quinteiro, a pediatrician at the Sardenya Primary Care Center, who regularly uses deferred prescription in her practice. “I think it is very important that as a professional, you know the patient to whom you are explaining this, that you are able to trust them and provide adequate support, and that they also trust you to carry out what you are explaining correctly. Education is key“.

This pediatrician explains that the more active patients are and the more they are involved in their disease, the better clinical outcomes are usually achieved. “But that’s why previous education and support are needed; otherwise, it is impossible“.

 

Especially useful tool in primary care

Dr. Albert Boada Valmaseda, a reference in Primary Care in the Care Area of Catsalut, recalls that antibiotic resistance is a global problem, considered one of the main threats to health and humanity by the WHO. “Primary Care is the main prescriber of antibiotics in the community, and respiratory infections are the main etiology for which they are prescribed. Often, this prescription is inappropriate, given the main viral origin of these infections. That is why it is necessary to provide strategies to reduce the inappropriate prescription of antibiotics“.

From the perspective of this expert, “deferred prescription of antibiotics should be a strategy to promote in primary care for respiratory infections, as it is the area of ​​ highest prescription and is well accepted by professionals and patients. These studies increase knowledge about professionals’ perception of its use and cost-effectiveness”.

 

Reference Articles

  • Mas-Dalmau G, Pérez-Lacasta MJ, Alonso-Coello P, Gorrotxategi-Gorrotxategi P, Argüelles-Prendes E, Espinazo-Ramos O, Valls-Duran T, Gonzalo-Alonso ME, Cortés-Viana MP, Menéndez-Bada T, Vázquez-Fernández ME, Pérez-Hernández AI, Muñoz-Ortiz L, Villanueva-López C, Little P, de la Poza-Abad M, Carles-Lavila M; DAP Paediatrics Group. A trial-based cost-effectiveness analysis of antibiotic prescription strategies for non-complicated respiratory tract infections in children. BMC Pediatr. 2023 Oct 2;23(1):497. doi:1186/s12887-023-04235-3. PMID: 37784098; PMCID: PMC10544479.
  • Mas-Dalmau G, Pequeño-Saco S, de la Poza-Abad M, Borrell-Thió E, Besa-Castellà M, Alsina-Casalduero M, Cuixart-Costa L, Liroz-Navarro M, Calderón-Gómez C, Martí J, Cruz-Gómez I, Alonso-Coello P. Perceptions and attitudes regarding delayed antibiotic prescription for respiratory tract infections: a qualitative study. BMC Prim Care. 2023 Oct 4;24(1):204. doi: 10.1186/s12875-023-02123-4. PMID: 37794330; PMCID: PMC10548630.

Deciphering Brain Connections between Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia

A group of scientists from various hospitals and research centers in Catalonia, led by Drs. Álvaro Carbayo and Ricard Rojas, researchers from the Neuromuscular Diseases Group at the Sant Pau Research Institute, in collaboration with Dr. Sergi Borrego-Écija and Dr. Ellen Gelpi from the Alzheimer’s Disease and other Cognitive Disorders Group and the Neurological Tissue Bank of IDIBAPS, have published a study in the journal Brain that reveals connections between two devastating brain diseases: Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia.

The study examines the relationship and the full spectrum of these two neurodegenerative diseases, which share more similarities than initially thought. ALS, a disease affecting motor neurons, and frontotemporal dementia, characterized by cognitive and behavioral problems, exhibit a common but highly heterogeneous clinical, genetic, and pathological spectrum, as explained by Dr. Ricard Rojas, researcher at IR Sant Pau and head of the Neurodegenerative Diseases Unit at the Neurology Service of Sant Pau Hospital.

Clinical studies revealed that up to 50% of ALS patients may develop cognitive and behavioral symptoms, with 10 to 15% specifically meeting diagnostic criteria for frontotemporal dementia. Now, through neuropathological examination of a large series of ALS cases, it has been discovered that the actual figure may be much higher: 35.5% of cases also presented pathological features of frontotemporal dementia. Findings show that the pathological aggregation of the TDP-43 protein was present in 93.6% of ALS cases and was more extensive in those with the coexistence of frontotemporal dementia pathology.

While it is known that most cases share the presence of TDP-43 protein aggregates, the study highlights the marked heterogeneity of neuropathological characteristics, suggesting possible different pathophysiological mechanisms. It’s important to note that, currently, the identification of these proteins is done post-mortem, in the absence of a precise biomarker.

Neuropathological studies and correlation with clinical characteristics help us expand our knowledge of the basis of diseases such as ALS and frontotemporal dementia, opening doors to future studies on biomarkers and specific therapies,” says Dr. Carbayo, the study’s lead author.

The research included all cases that met the neuropathological criteria for frontotemporal dementia from the Neurological Tissue Bank of the FRCB-IDIBAPS-Clinic Hospital of Barcelona between 1994 and 2022, regardless of their final clinical diagnosis. Clinical and neuropathological data were retrospectively reviewed, allowing analysis of the main clinical, genetic, and pathogenic characteristics, comparing patient groups with and without pathological changes of frontotemporal dementia, attempting to define specific subgroups.

We have observed astonishing heterogeneity in the clinical presentation and pathological and genetic characteristics of patients, with a higher frequency of frontotemporal dementia than described in other series,” says Dr. Carbayo.

From his perspective, these results emphasize the importance of interdisciplinary collaboration between ALS and frontotemporal dementia professionals and units. “It is crucial that we work together to better understand this spectrum of neurodegenerative diseases and to better care for our patients. In fact, at Sant Pau, we have been working with this structure for 6 or 7 years,” concludes Dr. Carbayo.

Reference article:

– Álvaro Carbayo, Sergi Borrego-Écija, Janina Turon-Sans, Elena Cortés-Vicente, Laura Molina-Porcel, Jordi Gascón-Bayarri, Miguel Ángel Rubio, Mónica Povedano, Josep Gámez, Javier Sotoca, Raúl Juntas-Morales, Miriam Almendrote, Marta Marquié, Raquel Sánchez-Valle, Ignacio Illán-Gala, Oriol Dols-Icardo, Sara Rubio-Guerra, Sara Bernal, Marta Caballero-Ávila, Ana Vesperinas, Ellen Gelpi, Ricard Rojas-García, Clinicopathological correlates in frontotemporal lobar degeneration: motor neuron disease spectrum, Brain, 2024;, awae011, https://doi.org/10.1093/brain/awae011


The manager of Personalized and Precision Medicine of the Catalan Health Service visits the IR Sant Pau

Ms. Gemma Valeta, manager of Personalized and Precision Medicine of the Catalan Health Service, visited the Sant Pau Research Institute this morning. She was received by the director of this institution, Dr. Jordi Surrallés.

Ms. Valeta wanted to learn more about the work carried out in Sant Pau to look for synergies that contribute to promoting research, which is a fundamental pillar to achieve a more precise and individualized approach to the treatment of various diseases.

Without a doubt, research institutes are the epicenter of scientific innovation and the discovery of new therapies. Their ability to explore new scientific frontiers and develop new technologies is essential to advancing the field of personalized medicine.

The synergistic union between research institutes and government authorities can generate an environment conducive to the development and effective implementation of personalized medicine. The creation of spaces for collaboration between researchers and policy makers can facilitate the definition of policies that reflect the needs and opportunities offered by this new scientific frontier.


Blood test diagnoses Alzheimer’s with over 90% accuracy

The detection of phosphorylated TAU 217 protein (p-tau217) in plasma has shown high precision in identifying pathological accumulations of beta-amyloid and TAU proteins. This precision is comparable to traditional biomarker detection in cerebrospinal fluid, as revealed by a recent study published in JAMA Neurology. Researchers from the Research Area in Neurological Diseases, Neuroscience, and Mental Health at the Sant Pau Research Institute, led by Dr. Juan Fortea, Director Sof the Memory Unit at the Neurology Department of the same hospital, participated in the study. These results pave the way for diagnosing Alzheimer’s disease through a blood test.

A few years ago, the only way to diagnose this neurodegenerative disease was through post-mortem brain samples. Subsequently, effective biomarkers were found for identification in cerebrospinal fluid. Now, research is focused on discovering blood biomarkers for less invasive diagnostic methods, as explained by Dr. Daniel Alcolea, researcher at the Dementia Neurobiology Group at the Sant Pau Research Institute and head of the biomarkers platform at the Memory Unit of the same hospital.

The researchers analyzed data from three observational cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) in Canada, the Wisconsin Registry for Alzheimer’s Prevention (WRAP) in the United States, and the Sant Pau Initiative on Neurodegeneration (SPIN) in Barcelona. The study involved samples from a total of 786 participants with an average age of 66.3 years, analyzed in Sweden, revealing an excellent accuracy of around 95% for detecting the presence of Alzheimer’s disease.

The results show that the p-tau217 biomarker offers precision comparable to cerebrospinal fluid biomarkers and proves to be particularly effective in detecting longitudinal changes, even in preclinical stages of the disease. An outstanding aspect of this technique is its ability to significantly reduce the need for additional confirmations, decreasing the number of tests required to confirm the diagnosis of the disease by 80%.

Dr. Alcolea explains that “this biomarker has shown very high performance in detecting Alzheimer’s in blood, with an accuracy between 90 and 95%. Of all the biomarkers currently being studied for diagnosing Alzheimer’s disease, this one has shown the best results.”

This discovery may open new avenues in the research and treatment of Alzheimer’s disease, offering an accessible and reliable tool for the medical community and patients. Dr. Alberto Lleó, researcher at the Dementia Neurobiology Group at the Sant Pau Research Institute and Director of the Neurology Department at the same hospital, explains that “this advance is particularly significant, as blood biomarkers could provide a more accessible and less invasive alternative for early diagnosis and monitoring of Alzheimer’s disease. Additionally, implementing this type of test could significantly improve clinical assessment and recruitment for clinical trials, as well as facilitate patient management and provide timely access to disease-modifying therapies.”

 

Reference article:

  • Ashton NJ, Brum WS, Di Molfetta G, et al. Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology. JAMA Neurol. Published online January 22, 2024. doi:10.1001/jamaneurol.2023.5319

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