Noticias

This randomised study shows that the drug reduces the mean stay of patients in the ICU and produces a radiological improvement in COVID-19-related pneumonia.

This multicentre clinical trial, which was sponsored and led by Navarrabiomed – Fundación Miguel Servet and conducted between April 2020 and October 2021, has allowed the safety and efficacy of the anti-inflammatory and antirheumatic drug anakinra to be evaluated for the treatment of severe cases of COVID-19. The international journal Jama Network Open has published the results, which show that anakinra does not result in significant improvement with respect to conventional treatment in very serious cases as it does not avoid the need for mechanical ventilation or reduce the comparative mortality. 

However, use of the drug reduces the mean stay of patients admitted to the ICU and produces a radiological improvement in COVID-19-related pneumonia. Moreover, it appears to be more effective in less severe cases as significant improvements are seen in this group of patients. 

The patient sample comprised 179 adults diagnosed with severe COVID-19 and a mean age of 60.5 years. Patients were enrolled at 12 hospitals from seven Autonomous Communities. Thirty six of the 179 patients enrolled in the trial were recruited at the Hospital Universitario de Navarra, with ages ranging from 38 to 81 years. None of these patients suffered any relevant adverse event.

Hospitals involved and funding

The national coordinating investigator for the study was Dr. Patricia Fanlo Mateo, an Internal Medicine consultant at the HUN, who, together with the Clinical Trials team at Navarrabiomed and supported by the Methodology Service, was able to launch and conduct the trial during the pandemic, including seeking the authorisations required and analysing the final results.

The trial was funded by way of COVID-19 projects from the Government of Navarra, which allowed the conduct of studies into coronavirus during the pandemic. 

The participating hospitals were: the Complejo Hospitalario Universitario de Santiago, Hospital Álvaro Cunqueiro (Vigo), Hospital Universitario Son Espases (Palma de Mallorca), Hospital Universitario y Politécnico La Fe (Valencia), Hospital Universitario Vall d’Hebron and Hospital Clínic (Barcelona), Hospital Universitario La Paz and Hospital Ramón y Cajal (Madrid), Hospital Clínico Universitario Lozano Blesa and Hospital Miguel Servet (Zaragoza), Hospital Universitario de Cabueñes (Gijón) and the Hospital Universitario de Navarra. The trial was also supported by the Spanish Society for Internal Medicine (SEMI)’s Systemic Autoimmune Diseases Group (GEAS).

Mikel Izquierdo, Principal Investigator of the Physical Exercise, Health and Quality of Life Unit (E-FIT) of Navarrabiomed and professor of the UPNA, was awarded yesterday at the VII SER Navarra Awards in the research category. Cadena SER Navarra recognised a total of 10 people or groups for their work in different areas of Navarra society at a ceremony held at the Baluarte Auditorium and presented by the journalists, Mamen García and Joaquim Torrents. 

In this 2023 edition, the pharmaceutical company Cinfa sponsored the research award and Alicia López de Ocáriz was the Corporate Medical Director, in charge of presenting the award that recognises the trajectory in numerous research projects in the field of Biomechanics and the Neuromuscular System with special emphasis on the effects of muscle strength training in different sports, aging and muscle performance. 

During his speech, Mikel Izquierdo thanked the radio station and the sponsor for the award and put the focus on a pandemic that existed before COVID-19: “Today, the pandemic of physical inactivity and sedentary lifestyle still persists, which causes 10 million deaths a year, 7 million myocardial infarctions and a total impact of 250 million dollars annually.” To reverse this situation, he stressed the importance of continuous physical exercise to achieve a higher quality of life. "Physical exercise should be done chronically throughout life. Currently we don't do enough, either in terms of quantity or intensity, and we must be aware that it is necessary to survive," he said during his speech. 

• Vanessa Arrieta Paniagua, predoctoral researcher at the Translational Cardiology Unit of Navarrabiomed - IdiSNA will present her doctoral thesis by the Public University of Navarra next Monday, November 28, at 12:00, in the Assembly Hall of Navarrabiomed. 

The doctoral work, entitled "Role of sST2 in myocardial fibrosis in severe aortic stenosis”, has been developed at the University Hospital of Navarra and Navarrabiomed under the direction of Natalia López Andrés, Principal investigator of the Translational Cardiology Unit.

Aortic stenosis is the most common valvular heart disease in Europe and North America affecting 2-7%, depending on the region, in population over 65 years of age. To date, there is no medical treatment that can slow down or reverse the evolution of the disease, so aortic valve replacement (surgical or percutaneous) is the only treatment when symptoms or ventricular dysfunction appear.

This disease produces an abnormal progressive narrowing of the aortic valve that, as a result of pressure overload, causes hypertrophy of the left ventricle. In this process, myocardial fibrosis has an important pathophysiological role, as well as a prognostic role. Initially, myocardial fibrosis is part of a compensatory mechanism, but in advanced stages a focal replacement fibrosis appears, leading to ventricular dysfunction and heart failure. The pathophysiological mechanisms underlying these processes are not fully understood. 

Focal replacement fibrosis can be detected and quantified by cardiac magnetic resonance imaging (MRI) with the delayed enhancement (DE) sequences. The presence of DE in patients with severe aortic stenosis has been shown to be an independent predictor of mortality and unfavourable clinical outcome in this group of patients. However, MRI is an expensive technique with limited availability, so it is not used in the follow-up of this group of patients in routine clinical practice.

The hypothesis of this thesis is that as the levels of soluble ST2 (sST2), a biomarker associated with the process of fibrosis and myocardial remodelling, are elevated in case of aortic stenosis, they may have a prognostic value. Specifically, this study addresses the role of sST2 in myocardial fibrosis in severe aortic stenosis. 
 

Research development 

The work is proposed from a translational point of view, and has a dual goal. First of all, to delve into the pathophysiological role of tSS2 in severe aortic stenosis. To this end, a proteomic study has been carried out to assess the proteins modulated by sST2 in human cardiac fibroblasts and the in vitro effects of sST2 on human cardiac fibroblasts have been investigated. The results have been validated in vitro in a rat model with pressure overload and in myocardial biopsies of patients with aortic stenosis that underwent surgery. 

Likewise, it has been demonstrated that sST2 exerts a deleterious role in human cardiac fibroblasts, on the one hand, affecting the mitochondrial function of the cell and thus increasing oxidative stress and the synthesis of proinflammatory molecules and on the other hand, promoting differentiation to myofibroblasts and increasing the synthesis of profibrotic molecules. These findings were validated in the animal model and in myocardial biopsies of patients with aortic stenosis.

Secondly, from the clinical point of view, a cohort of patients with severe aortic stenosis with surgical indication was analysed to check if the blood levels of sST2 are associated with the DE evaluated by MRI in patients with severe aortic stenosis. Thus, it is observed that patients with severe aortic stenosis with cardiac MRI DE have significantly higher blood levels of sST2 than those without RT. Blood sST2 levels are positively correlated with DE mass and with VI mass in patients with severe aortic stenosis. High levels of sST2 make it possible to identify patients with severe aortic stenosis with DE, without having to perform cardiac MRI, in a simple way that can be applied in routine clinical practice.
 

Dissemination of results 

The work carried out has led to several scientific publications: in 2019, in the journal Clinical Science, “Soluble ST2 promotes oxidative stress and inflammation in cardiac fibroblasts: an in vitro and in vivo study in aortic stenosis”, and in 2020 in the journal Cells, “Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1”.   

In addition, the results have been disclosed at several national and international congresses such as the SEC Congress in Bilbao (in 2015 and in 2017), at the 29th EACTS Annual Meeting in Amsterdam, in 2015 or at the Heart Failure Congress in Paris, in 2017.

• Navarrabiomed participates together with the Department of Rural Development and Environment, the UPNA, CSIC-IDAB and the public companies INTIA and Nasertic and the company Josenea

The Government of Navarra has approved at this Wednesday's session its initiative to join the Navarra Association for Hemp Research (ANIC), promoted by the Department of Rural Development and Environment and that will be established shortly together with the UPNA (and its two institutes, ISFOOD-Institute for Innovation and Sustainable Development of the Food Chain- and IMAB -Institute for Multidisciplinary Research in Applied Biology), Navarrabiomed (biomedical research centre), the CSIC-IDAB (Institute of Agrobiotechnology of the Higher Scientific Research Centre), the public companies INTIA and Nasertic and the private company Josenea.

The purpose of the Association is to obtain and manage, with a criterion of equity between the partners and with a territorial vision for Navarra, the relevant licenses or authorizations of the Spanish Agency for Medicines and Health Products (AEMPS) and, specifically, the authorization for the cultivation of hemp plants for research purposes; the authorization for the cultivation of these plants for medical and scientific purposes; and, subsequently and on an annual basis, the annual authorization of total area and plots for the cultivation of hemp plants.

In addition, the objectives of the ANIC are:

• To group and coordinate all those operating with industrial or medicinal hemp in Navarra, at present or in the future, providing them with a legal tool for coordination and sectoral dialogue for their institutional and intersectoral relations.
• To promote cooperation between companies, research and training centres and institutions for the boosting, growth and coordination of the industrial and medicinal hemp sector in Navarra, in its aspects of research, cultivation, industrial transformation and marketing of final product, encouraging the design and launch of collaborative projects.
• To contribute to the promotion of research, development and innovation in the industrial and medicinal hemp sector of Navarra, in all links of the value chain, and with special emphasis on: the development of new varieties of industrial and medicinal hemp and genetic research; in the research of medical, pharmacological, food, industrial and cosmetic properties of hemp; in the research of medicinal, industrial and commercial applications of its derivatives; in the research of the economic potentials of industrial and medicinal hemp as an alternative crop for economically disadvantaged areas and/or in risk of depopulation; and any new line of research that may be interesting for the sector and the territory of the Autonomous Community of Navarra.
• To create, consolidate and enhance a sectoral image for all the economic and research activity that is generated around industrial and medicinal hemp in Navarra, and that includes all aspects of research, agricultural, cultivation, industrial, biomedical and commercial aspects.
• And, finally, to facilitate and coordinate sectoral relations at the national and international levels.
   

Gómez: "Navarra has great potential in the entire value chain”

After its approval in the Government session, the Minister of Rural Development and Environment, Itziar Gómez, has presented this initiative accompanied by representatives from the various centres, societies and the company that will be part of the Association. The minister stressed that "Navarra has great potential in the entire value chain: a strong agricultural sector, personnel and reference centres in research, as well as important pharmaceutical and agri-food companies”.

“Therefore, we believe that the Regional Community can be a reference and be well positioned for the new regulatory framework in the matter that is planned for 2023. Interestingly those who want to operate in this area in Navarra are well established at the starting line of a new economic sector that can thrive and for which Navarra, as said, has potential throughout the value chain,” she explained.

As the minister has pointed out, the Department “has been working on this issue since 2020. Early that year we commissioned a study on the potentialities of hemp cultivation as a strategic circular economy and innovation project for Navarra and from there we continued to take steps”.
On the one hand, we contacted the AEMPS (Spanish Agency for Medicines and Health Products), “who grants the licenses, to verify with them the real possibilities of promoting a project with a research license and, on the other hand, making an appeal to different agents that we understood might be interested in hemp research to design together a project to carry out,” she explained.

As explained by Itziar Gómez, “The truth is that we had a very good reception in terms of forming a working group to boost research. In addition to those now present, we also contacted pharmaceutical companies and other private companies that do not rule out participating in the Association at a later stage. In fact, the association is open to the incorporation of new partners”.

The current phase of the association, in addition to its own incorporation, focuses on submitting a research project to the AEMPS to obtain a research license, so, at this moment in the process, the objective is not commercial cultivation.
Once the association is formally constituted and once approved the proposed statutes in the Government Agreement record approved at today's session, the Autonomous Community of Navarra will belong to the association as sponsor or founder, participating in the act of incorporation of the association.

Research project

In parallel to the steps for the constitution of the Association, its members have worked on a first research project that they are finalizing to present to the AEMPS once the ANIC is set up.

This is a variety testing project. It consists of selecting hemp varieties with a high CBD content (a non-psychoactive component of hemp) and a low THC content (psychoactive component), adapted to the growing conditions of Navarra, taking into account morphological, physiological, agronomic (phenotypic in general) and genotypic characteristics (by using molecular markers indicating the THC/CBD chemotype ratio of the varieties).
In addition, a second objective is the study and characterization of the derived products for their marketing by industries of the agri-food sector as proteins and lipids of nutritional interest and biocompounds from the selected varieties.

The project would be located on the Josenea de Lumbier farm that meets the prerequisites set by the AEMPS, that is, it is located in a closed, video-monitored environment, near a population centre and a police station or civil guard station.

Photo caption L-R: Ignacio Gil (General Directorate of Agriculture and Livestock); Luis Orcaray (INTIA); Maite Mendioroz (Navarrabiomed); Txus Cía (Josenea); Lucía Ramírez (IMAB-UPNA); Gonzalo Rodríguez (NASERTIC); Itziar Gómez (minister); José María González de Diego (CSIC-IDAB); Natxo Irigoien (UPNA); and Patxi Ibáñez (ISFOOD-UPNA) .

Carmen Gómez Arrebola, predoctoral researcher at the Microbial Pathogenesis Research Unit of Navarrabiomed, will be sitting her viva (Public University of Navarra) next Tuesday, July 5th at 11:30 in the examination hall of EDONA, Edificio El Sario (UPNA).

The doctoral work, entitled "Role of the two-component systems of Staphylococcus aureus in the susceptibility to complestatin and corbomycin and in gene regulation in the absence of phosphorylation”, has been developed at Navarrabiomed under the direction of Dr. Iñigo Lasa Uzcudun and Dra. Cristina Solano Goñi.

Staphylococcus aureus (S. aureus) is a versatile bacterium that can be found as a commensal on the skin of approximately 30% of the population without causing any problems. However, when it crosses the epithelial barrier and depending on the carrier's immune status, it can cause mild pathologies, such as abscesses, or severe ones, such as endocarditis or osteomyelitis. There is a wide range of drugs for the treatment of these pathologies, however, S. aureus has developed mechanisms that allow it to increase its resistance and evade the effect of these antibiotics. 

Bacteria have the ability to adapt to the changes that occur around them thanks to different detection and communication systems, including the so-called “two-component systems” (TCSs). Through them, the bacteria perceive what is happening around them and by modulating the expression of certain genes, can adapt to the changes occurred. The TCSs of S. aureus they have a very important role in the development of resistance to the various antimicrobials currently used in the clinical setting, as well as in the stimulation of growth in the form of biofilm, further increasing their resistance to antibiotics.
The appearance of strains of multidrug-resistant S. aureus has led to the alarming need to develop new antibiotics that allow the treatment of infections caused by these strains, as well as the need for progress in our knowledge on the molecular mechanisms that produce this increased resistance. 

Thesis abstract and results

During her doctoral thesis, Carmen Gómez has analysed the involvement of the TCSs of S. aureus in the susceptibility to two antibiotics of the glycopeptide family, complestatin and corbomycin, recently discovered. The results have shown that the VraSR system regulates elements of the bacterial wall that affect the susceptibility of this bacterium to both antibiotics. 

Another part of the study has been devoted to analyse the regulation by TCSs in their non-phosphorylated form. It has traditionally been considered that the response regulators of TCSs exercise their regulatory function in their phosphorylated state, and that in their non-phosphorylated state, they have no regulatory activity. However, considerable evidence shows that TCSs in their unphosphorylated state also exert gene expression modulation functions. After a review of the existing evidence regarding the regulation by TCSs in their non-phosphorylated state, the work has delved into the regulation of biofilm formation by ArlRS TCS. The results obtained suggest that ArlR regulates the expression of the main exopolysaccharide of the S. aureus biofilm in both its phosphorylated and non-phosphorylated state. 

Disclosure and financing

The work carried out has led to the scientific publication, “Regulation of gene expression by non-phosphorylated response regulators”, published in International Microbiology. A second publication entitled “Staphylococcus aureus susceptibility to corbomycin and complestatin depends on the VraSR two component system” has been submitted and is in the process of being reviewed. 

In addition, it has been disseminated at the 31st European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) and the XXVIII Congress of the Spanish Society of Microbiology.
For the development of the thesis, Carmen Gómez had a predoctoral contract from the UPNA. Research has received funding through the calls for Aid to R&D&i projects 2017 of the Ministry of Economy, Industry and Competitiveness and Aid to R&D&i projects 2020 of the Ministry of Science and Innovation, granted to the projects:

• “Functional characterization of the molecular determinants for the adaptation of Staphylococcus aureus to virulence”.  BIO2017-83035-R. 
• “Non-contiguous operons: a new level of gene regulation in bacteria”. PID2020-113494RB-100. 

The prize, with 10,000 euros, has been awarded ex aequo to a study on brain magnetic resonance imaging as a biomarker of ALS, developed by the University Hospital of Navarra in collaboration with Navarrabiomed, and an application designed by the University Clinic of Navarra to monitor the treatment of food allergies with oral immunotherapy.
 

The Scientific Directorate of IdiSNA has decided to grant the Technology and Health Foundation (FTyS) award ex aequo, with 10,000 euros, to two projects related to health technologies. The different entities that make up IdiSNA were able to apply for this award through an intramural call.
Dr. Teresa Cabada, Head of the Neuroradiology Section of the University Hospital of Navarra, leads one of the winning proposals. A study on brain magnetic resonance as a biomarker in degenerative motor neuron disease. As described by Cabada, “Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease whose diagnosis is difficult at an early stage, which translates into a delayed diagnosis and delayed administration of neuroprotective drugs”. All this highlights the importance of defining diagnostic and prognostic biomarkers in ALS.

To date, 33 patients have been recruited who have undergone a clinical and neuropsychological evaluation. The post-processing of the MRI is carried out by the Algebra and Applications Research Unit of Navarrabiomed, which analyses the images along with other clinical variables to find radiological markers associated with the disease or its evolution. "By using advanced sequencing techniques, mathematicians are able to detect subtle alterations and generate predictive models from the data obtained”, it concludes.

With this project, funded by the Government of Navarra and which now also has financial support from IdiSNA, magnetic resonance imaging is postulated as a promising test to predict the disease and its evolution.
The second acknowledgement has been awarded to an initiative of the University of Navarra Clinic. It is an application to monitor the treatment of food allergies with oral immunotherapy led by Dr. María José Goikoetxea, specialist of the Department of Allergology.
 

Caption (from left to right): Itiziar Uzqueda (Navarrabiomed), Marisol Gómez (Navarrabiomed), Javier Díaz (HUN), Ivonne Jericó (HUN), Juan Quizhpilema (HUN) Teresa Cabada (HUN), José Manuel Hidalgo (HUN), María José Goikoetxea (CUN), Sergio Sánchez (CUN), Maite Lacunza (CUN) and Amaia Izal ( CUN). 

Nicolás Martínez Velilla (HUN) takes over fromRosario Luquin in the position of scientific director in this new stage while Felipe Prósper (CUN) will be deputy director and Nuria Goñi (Osasunbidea/AP) completes the team as board member.

The Institute of Health Research of Navarra (IdiSNA) has renewed and reinforced its scientific management with a double change: the replacement of Rosario Luquín by Nicolás Martínez Velilla (HUN) and the creation of two new positions: that of deputy director -to be held by Felipe Prósper (CUN) - and that of board member, held by Nuria Goñi Ruiz (Osasunbidea/AP).

In this way, in addition to an original component of public-private collaboration, the vision of research in Primary Health Care is added at this first level of leadership as part of the start of a new stage in this institute formed by University Hospital of Navarra (HUN), the University of Navarra Clinic (CUN), the Public University of Navarra  (UPNA), University of Navarra, Navarrabiomed, Cima University of Navarra,  Institute of Public and Occupational Health and Primary Health Care of the Navarra Health Service - Osasunbidea.

The IdiSNA Board of Trustees addressed in its today's session the importance of disseminating this new trend in the scientific and healthcare community as the main reference in order to promote research in this new stage. The Minister of Health, Santos Induráin, who chairs the Board of Trustees, has recognized and thanked the involvement of the outgoing scientific director, Rosario Luquin (CUN), and highlighted the comprehensive vision of the new scientific structure and the curriculum of its three representatives who have already begun their work.

Nicolás Martínez Velilla is currently head of Geriatrics at the University Hospital of Navarra and an intensified researcher at Navarrabiomed-Miguel Servet Foundation since 2019.  Graduated in Medicine and Surgery from the University of Navarra (1996) he completed his training as a specialist in Geriatrics in England, Madrid (University Hospital of Getafe) and Pamplona, since he received his doctorate at UPNA with a thesis on multimorbidity in the elderly, studies he completed in the field of Probability and Statistics (UNED) and Health services (University of Alcalá).
These are the fields in which he has deepened in his research activity –compatible with healthcare - since he has been a member of the Research Network in Health Services and Chronic Diseases REDISSEC of the Carlos III Health Institute (ISCIII) and later in the CIBER frailty and healthy aging network of this same institute.
In 2013 he created the Geriatrics Research Group of Navarrabiomed-Miguel Servet Foundation with an extensive number of publications. He is a visiting professor in the subject of Geriatrics at the Faculty of Medicine of the University of Navarra and associate professor at the Public University of Navarra in the area of Preventive Medicine.
He has been a representative of the Spanish Geriatrics Society in various state and international organizations. Since 2019 he has been a member of the Board of the European Academy of Geriatric Medicine and Vice-President of the Spanish Society of Geriatrics and Gerontology.

For his part, Felipe Prósper is a reference in Haematology since he co-directs the Haematology Department and leads the Cell Therapy Area of the Navarra University Clinic, a clinic he joined after a time at the Hospital Clínico de Valencia. He also directs the Haemato-Oncology and Regenerative Medicine Programs at the Cima University of Navarra. Graduated in Medicine and Surgery (1989) and doctor (1994) from that university, he completed his training with a postdoctoral stay at the University of Minnesota.
He is one of the promoters of the National Cellular Therapy Network (TerCel) of the ISCIII, as well as the RICORS TERAV. He is a member of the Cancer CIBER (CIBERONC) of the ISCIII, as the main researcher of one of its groups. Since 2015 he has been a Professor of Haematology at the University of Navarra, has been a member of the Board of Directors of the Spanish Society of Haematology and Haemotherapy (SEHH) and the Spanish Society of Gene and Cell Therapy (SETGYC), and formerly coordinator of the Oncology department of IdiSNA.

Finally, Nuria Goñi Ruiz (graduated in Medicine from the UN in 2001) comes from the area of Primary and Community Care of Navarra, work that she has combined with her research vocation since she received a doctorate at the University of Navarra in parallel with a long professional career of eleven years in various health centres.
Her professional profile also includes experience in management since 2016, carrying out technical tasks in the Support Service for Clinical Management and Continuity of Care of the Primary Health Care Management unit, carrying out technical support tasks for the Health Centres of Navarra of training and coordination with hospitals seeking the reinforcement of Primary Health Care.
In the field of Primary Health Care she has also worked on the implementation of different strategies of the Department of Health (Navarra Strategy for Integrated Care for chronic and multi-pathological patients) and application protocols in Primary Health Care, especially in relation to Frailty Care in the elderly. This has led her to participate in different multidisciplinary coordination groups and in several strategies. Since 2021 she has also been an associate professor in the area of Medicine at UPNA.   

More than 1,000 researchers from 8 institutions

The purpose of the IdiSNA is to contribute to raising the quality of research, and, as a result of the biomedical care and teaching of the Foral Community of Navarra, as well as to optimize the existing human and material resources. To this end, synergies between clinical and basic groups will be promoted based on the models of already existing translational groups.

The research staff of IdiSNA in 2021 has 1,065 researchers, working in 96 research groups. These groups are allocated to nine research areas: Epidemiology and Public Health (EPSP); Primary Health Care, Health Services and Chronic Diseases (APSS); Mental Health (SMTAL); Digestive System and Metabolic Diseases (DEM); Inflammatory, Immune and Infectious Diseases (EIII); Neurosciences (NEUR); Onco-Haematology (OHEM); Cardiovascular and Renal Diseases (CVRDs); Advanced Therapies and Diagnostic Innovation (ATAID) and Bioengineering and Health Biotechnologies (BBS).
In the last year IdiSNA has been received a total of 61 research grants in competitive calls with a total funding of € 6,592,733.  The total scientific output of the institute is around one thousand contributions annually.