IdisBa - Instituto de Investigación Sanitaria Illes Balears (Baleares)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/16967

El Instituto de Investigación Sanitaria Islas Baleares nace de la asociación y colaboración entre los diferentes centros y dispositivos que desarrollan actividades de investigación biosanitaria y biomédica en el territorio de las Islas Baleares. El Instituto se creó el 23 de diciembre de 2013, bajo la denominación Instituto de Investigación Sanitaria de Palma (IdISPa) y no es hasta el año 2017, cuando se modifican sus estatutos y razón social, que pasa a denominarse se Fundación Instituto de Investigación Sanitaria Illes Balears. Así pues, el IdISBa está formado por el Hospital Universitario Son Espases, Gerencia de Atención Primaria de Mallorca, el Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), el Hospital Universitario Son Llàtzer y la Fundación Banco de Sangre y Tejidos de las Islas Baleares. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2019, y renovando esta acreditación cada 5 años, forma parte así del total de 34 Institutos de Investigación Sanitaria acreditados existentes en la actualidad.

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Transferable AmpCs in Klebsiella pneumoniae: interplay with peptidoglycan recycling, mechanisms of hyperproduction, and virulence implications
(American Society for Microbiology (ASM), 2024-05-02) Barceló, Isabel M; Escobar-Salom, Maria; Cabot, Gabriel; Perelló-Bauzà, Pau; Jordana-Lluch, Elena; Taltavull, Biel; Torrens, Gabriel; Rojo-Molinero, Estrella; Zamorano, Laura; Perez Gomez, Astrid; Oliver, Antonio; Juan, Carlos; Govern de les Illes Balears (España); RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España); Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Chromosomal and transferable AmpC β-lactamases represent top resistance mechanisms in different gram-negatives, but knowledge regarding the latter, mostly concerning regulation and virulence-related implications, is far from being complete. To fill this gap, we used Klebsiella pneumoniae (KP) and two different plasmid-encoded AmpCs [DHA-1 (AmpR regulator linked, inducible) and CMY-2 (constitutive)] as models to perform a study in which we show that blockade of peptidoglycan recycling through AmpG permease inactivation abolished DHA-1 inducibility but did not affect CMY-2 production and neither did it alter KP pathogenic behavior. Moreover, whereas regular production of both AmpC-type enzymes did not attenuate KP virulence, when blaDHA-1 was expressed in an ampG-defective mutant, Galleria mellonella killing was significantly (but not drastically) attenuated. Spontaneous DHA-1 hyperproducer mutants were readily obtained in vitro, showing slight or insignificant virulence attenuations together with high-level resistance to β-lactams only mildly affected by basal production (e.g., ceftazidime, ceftolozane/tazobactam). By analyzing diverse DHA-1-harboring clinical KP strains, we demonstrate that the natural selection of these hyperproducers is not exceptional (>10% of the collection), whereas mutational inactivation of the typical AmpC hyperproduction-related gene mpl was the most frequent underlying mechanism. The potential silent dissemination of this kind of strains, for which an important fitness cost-related contention barrier does not seem to exist, is envisaged as a neglected threat for most β-lactams effectiveness, including recently introduced combinations. Analyzing whether this phenomenon is applicable to other transferable β-lactamases and species as well as determining the levels of conferred resistance poses an essential topic to be addressed. IMPORTANCE: Although there is solid knowledge about the regulation of transferable and especially chromosomal AmpC β-lactamases in Enterobacterales, there are still gaps to fill, mainly related to regulatory mechanisms and virulence interplays of the former. This work addresses them using Klebsiella pneumoniae as model, delving into a barely explored conception: the acquisition of a plasmid-encoded inducible AmpC-type enzyme whose production can be increased through selection of chromosomal mutations, entailing dramatically increased resistance compared to basal expression but minor associated virulence costs. Accordingly, we demonstrate that clinical K. pneumoniae DHA-1 hyperproducer strains are not exceptional. Through this study, we warn for the first time that this phenomenon may be a neglected new threat for β-lactams effectiveness (including some recently introduced ones) silently spreading in the clinical context, not only in K. pneumoniae but potentially also in other pathogens. These facts must be carefully considered in order to design future resistance-preventive strategies.
Monitoring of Pseudomonas aeruginosa mutational resistome dynamics using an enrichment panel for direct sequencing of clinical samples
(Elsevier, 2024-10) Cortes-Lara, Sara; Medina-Reatiga, Paola; Barrio-Tofiño, Ester Del; Gomis-Font, María A; Cabot, Gabriel; Gómez-Romano, Fernando; Ayestarán, Ignacio; Colomar, Asunción; Palou-Rotger, Alexandre; Oteo-Iglesias, Jesus; Campo, Rosa Del; Cantón, Rafael; Horcajada, Juan P; López-Causapé, Carla; Oliver, Antonio; Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (España); Unión Europea. Comisión Europea. NextGenerationEU
Background: Pseudomonas aeruginosa is a major cause of hospital-acquired and chronic infections, characterised by an extraordinary capacity to develop antimicrobial resistance through the selection of chromosomal mutations, leading to treatment failure. Here, we designed and tested a hybridisation-based capture system for the enrichment of genes of interest before sequencing to monitor resistant populations genomics directly from clinical samples. Methods: A panel for enrichment before sequencing of close to 200 genes related to P. aeruginosa antimicrobial resistance, multilocus sequence typing, mutability or virulence was designed, synthesised (KAPA HyperCap, Roche) and initially validated in vitro using a multidrug-resistant ST175 isolate and representative isolates from major P. aeruginosa clades. In vivo testing included ventilator associated pneumonia by MDR P. aeruginosa in ICU (3-10 sequential samples from 3 patients) and chronic respiratory infection by hypermutable P. aeruginosa in cystic fibrosis (8 sequential samples from a single patient covering a 4-year period). Results from direct sequencing with the enrichment panel were compared with those of whole genome sequencing (WGS) and phenotypic profiling of 10 isolated colonies per sample. Findings: In vitro assays confirmed the selectivity of the enrichment panel and the correct identification of the vast mutational resistome of ST175, including specific mutations even when introduced in a 1:100 proportion. In vivo performance was at least equivalent to sequencing 10 colonies per sample, including the accurate identification of the sequence types and the basal and acquired mutational resistome. To note, specific resistance mutations, such as those in ampC leading to resistance to novel β-lactams, could be traced even at frequencies of 1%. Moreover, the coselection of mutator populations and antibiotic resistance mutations, predicted in theoretical and in vitro studies, was evidenced in vivo. Interpretation: This proof-of-concept study demonstrates that resistance genomics of P. aeruginosa can be analysed directly from clinical samples, determining not only a considerable reduction in turnaround time and cost from a diagnostics perspective, but also an unprecedented potency for accurate monitoring of in vivo population dynamics in bacterial infections.
Executive Summary of the Spanish Guidelines for the Diagnosis and Management of Imported Febrile Illnesses from the Spanish Society of Tropical Medicine and International Health (SEMTSI), the Imported Pathology Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (GEPI-SEIMC), the Spanish Society of Family and Community Medicine (SEMFYC), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Emergency Medicine (SEMES)
(Elsevier, 2024) Camprubí-Ferrer, Daniel; Díaz Menendez, Marta; Crespillo-Andújar, Clara; Galparsoro, Harkaitz Azkune; Belhassen-García, Moncef; Cuadros González, Juan; Rubio Muñoz, Jose Miguel; Llenas-García, Jara; Oteo, José A; Gayoso Martín, Sara; Santos Larrégola, Laura; Salvador, Fernando; Rojo-Marcos, Gerardo; Balerdi-Sarasola, Leire; Kortajarena Urkola, Xabier; Soriano Pérez, Manuel Jesús; Onieva-García, María Ángeles; Alegría Coll, Iñaki; Arranz, Javier; Membrillo de Novales, Javier; Sociedad Española de Medicina Tropical y Salud Internacional
The Spanish Society of Tropical Medicine and International Health (SEMTSI), the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Family and Community Medicine (SEMFYC) have prepared a consensus statement on the diagnosis and management of patients with imported febrile illnesses. Twenty authors with different backgrounds and representing different healthcare perspectives (ambulatory primary care, travel and tropical medicine specialists, emergency medicine, hospital care, microbiology and parasitology and public health), identified 39 relevant questions, which were organised in 7 thematic blocks. After a systematic review of the literature and a thoughtful discussion, the authors prepared 125 recommendations, as well as several tables and figures to be used as a consulting tool. The present executive summary shows a selection of some of the most relevant questions and recommendations included in the guidelines.
Epidemiological and clinical characterization of community, healthcare-associated and nosocomial colonization and infection due to carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in Spain
(Springer, 2024-12) Salamanca-Rivera, Elena; Palacios-Baena, Zaira R; Cañada-Garcia, Javier Enrique; Moure García, Zaira; Perez-Vazquez, Maria; Calvo-Montes, Jorge; Martínez-Martínez, Luis; Cantón, Rafael; Ruiz Carrascoso, Guillermo; Pitart, Cristina; Navarro, Ferran; Bou, Germán; Mulet, Xavier; González-López, Juan José; Sivianes, Fran; Delgado-Valverde, Mercedes; Pascual, Álvaro; Oteo-Iglesias, Jesus; Rodríguez-Baño, Jesús; GEMARA/GEIRAS-SEIMC/REIPI CARB-ES-19 Study Group; Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (España); Unión Europea. Comisión Europea. NextGenerationEU; Plan Nacional de I+D+i (España); Ministerio de Economía y Competitividad (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Background: Community-acquired (CA) and healthcare-associated (HCA) infections caused by carbapenemase-producing Enterobacterales (CPE) are not well characterized. The objective was to provide detailed information about the clinical and molecular epidemiological features of nosocomial, HCA and CA infections caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp) and Escherichia coli (CP-Ec). Methods: A prospective cohort study was performed in 59 Spanish hospitals from February to March 2019, including the first 10 consecutive patients from whom CP-Kp or CP-Ec were isolated. Patients were stratified according to acquisition type. A multivariate analysis was performed to identify the impact of acquisition type in 30-day mortality. Results: Overall, 386 patients were included (363 [94%] with CP-Kp and 23 [6%] CP-Ec); in 296 patients (76.3%), the CPE was causing an infection. Acquisition was CA in 31 (8.0%) patients, HCA in 183 (47.4%) and nosocomial in 172 (48.3%). Among patients with a HCA acquisition, 100 (54.6%) had been previously admitted to hospital and 71 (38.8%) were nursing home residents. Urinary tract infections accounted for 19/23 (82.6%), 89/130 (68.5%) and 42/143 (29.4%) of CA, HCA and nosocomial infections, respectively. Overall, 68 infections (23%) were bacteremia (8.7%, 17.7% and 30.1% of CA, HCA and nosocomial, respectively). Mortality in infections was 28% (13%, 14.6% and 42.7% of CA, HCA and nosocomial, respectively). Nosocomial bloodstream infections were associated with increased odds for mortality (adjusted OR, 4.00; 95%CI 1.21-13.19). Conclusions: HCA and CA infections caused by CPE are frequent and clinically significant. This information may be useful for a better understanding of the epidemiology of CPE.
Impact of the COVID-19 pandemic on the self-care and health condition of the older adults. CUIDAMOS+75. A mixed methods study protocol
(Frontiers Media, 2024) Rico-Blazquez, Milagros; Esteban-Sepúlveda, Silvia; Sánchez-Ruano, Raquel; Aritztegui-Echenique, Ana María; Artigues-Barbera, Eva María; Brito-Brito, Pedro-Ruymán; Casado-Ramirez, Elvira; Cidoncha-Moreno, María Ángeles; Fabregat-Julve, María Inmaculada; Feria-Raposo, Isabel; Hernandez-Pascual, Montserrat; Lozano-Hernández, Cristina; Moreno-Casbas, Teresa; Otones-Reyes, Pedro; Palmar-Santos, Ana María; Pedraz-Marcos, Azucena; Romero-Rodriguez, Esperanza María; Solé-Agustí, María Cristina; Taltavull-Aparicio, Joana María; Vidal-Thomàs, María Clara; González-Chordá, Víctor M; Cuidamos+75 Group; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Aims: To assess the impact of the COVID-19 pandemic on the health condition of people ≥75 years of age and on their family caregivers in Spain. Design: Multicentric, mixed method concurrent study. Methods: This work, which will be conducted within the primary care setting in 11 administrative regions of Spain, will include three coordinated studies with different methodologies. The first is a population-based cohort study that will use real-life data to analyze the rates and evolution of health needs, care provision, and services utilization before, during, and after the pandemic. The second is a prospective cohort study with 18 months of follow-up that will evaluate the impact of COVID-19 disease on mortality, frailty, functional and cognitive capacity, and quality of life of the participants. Finally, the third will be a qualitative study with a critical social approach to understand and interpret the social, political, and economic dimensions associated with the use of health services during the pandemic. We have followed the SPIRIT Checklist to address trial protocol and related documents. This research is being funded by the Instituto de Salud Carlos III since 2021 and was approved by its ethics committee (June 2022). Discussion: The study findings will reveal the long-term impact of the COVID-19 pandemic on the older adults and their caregivers. This information will serve policymakers to adapt health policies to the needs of this population in situations of maximum stress, such as that produced by the COVID-19 pandemic. Trial registration: Identifier: NCT05249868 [ClinicalTrials.gov].
Severity of respiratory syncytial virus compared with SARS-CoV-2 and influenza among hospitalised adults ≥65 years.
(Elsevier, 2024-11) Vega-Piris, Lorena; Galindo Carretero, Silvia; Mayordomo, José Luis; Rumayor-Zarzuelo, Mercedes Belén; Álvarez Río, Virginia; Gallardo García, Virtudes; García Vázquez, Miriam; García Rodríguez, María Del Carmen; Basile, Luca; López González-Coviella, Nieves; Barranco Boada, Maria Isabel; Pérez-Martínez, Olaia; Lameiras Azevedo, Ana; Quiñones-Rubio, Carmen; Giménez Duran, Jaume; Fernández Ibáñez, Ana; García Rivera, María Victoria; Ramos Marín, Violeta; Castrillejo, Daniel; Voloria Raymundo, Luis Javier; Larrauri, Amparo; Monge Corella, Susana; SARI Sentinel Surveillance Group
Introduction: Our aim was to estimate the risk of pneumonia, admission to intensive care unit (ICU) or death in individuals ≥65 years old admitted to hospital with RSV, compared to influenza or COVID-19. Methods: We included hospitalised patients from Severe Acute Respiratory Infection Surveillance in Spain between 2021-2024, aged ≥65 years, laboratory confirmed for RSV, influenza or SARS-CoV-2. Using a binomial regression with logarithmic link, we estimated the relative risk (RR) of pneumonia, ICU admission and in-hospital mortality, in patients with RSV compared to influenza or SARS-CoV-2, adjusting for age, sex, season and comorbidities. We stratified the estimates by vaccination status for influenza or SARS-CoV2. Results: Among patients unvaccinated for influenza or SARS-CoV-2, those with RSV had similar or lower risk of pneumonia [vs. influenza: RR= 0.91 (95% Confidence Interval: 0.72-1.16); vs. SARS-CoV-2: 0.81 (0.67-0.98)], ICU admission [vs. influenza: 0.93 (0.41-2.08); vs. SARS-CoV-2: 1.10 (0.61-1.99)] and mortality [vs. influenza: 0.64 (0.32-1.28); vs. SARS-CoV-2: 0.56 (0.30-1.04)]. Among the vaccinated, results were largely similar except for a higher risk of ICU admission with RSV [vs. influenza: 2.13(1.16-3.89); vs. SARS-CoV-2: 1.83 (1.02-3.28)] CONCLUSIONS: RSV presented similar or lower intrinsic severity than influenza or SARS-CoV2. Among vaccinated patients, RSV was associated to higher ICU-admission, suggesting the potential for preventive RSV vaccination.
Effectiveness of influenza vaccines in children aged 6 to 59 months: a test-negative case-control study at primary care and hospital level, Spain 2023/24
(European Centre for Disease Prevention and Control (ECDC), 2024-10) Pérez-Gimeno, Gloria; Mazagatos, Clara; Lorusso, Nicola; Basile, Luca; Martínez-Pino, Isabel; Corpas-Burgos, Francisca; Batalla Rebolla, Noa; Rumayor-Zarzuelo, Mercedes Belén; Andreu Ivorra, Blanca; Giménez Duran, Jaume; Castrillejo, Daniel; Guiu Cañete, Inés; Huerta Huerta, Marta; García Becerril, Marta; Ramos Marín, Violeta; Casas Flecha, Inmaculada; Pozo Sanchez, Francisco; Monge Corella, Susana; SiVIRA group; Unión Europea. European Centre for Disease Prevention and Control (ECDC)
During 2023/24, all children aged 6 to 59 months were targeted for seasonal influenza vaccination in Spain nationally. Using a test-negative case-control design with sentinel surveillance data, we estimated adjusted influenza vaccine effectiveness (IVE) against any influenza type to be 70% (95% confidence interval (CI): 51 to 81%) for primary care patients with acute respiratory illness (ARI) and 77% (95% CI: 21 to 93%) for hospitalised patients with severe ARI. In primary care, where most subtyped viruses (61%; 145/237) were A(H1N1), adjusted IVE was 77% (95% CI: 56 to 88%) against A(H1N1)pdm09.
Learning, internalisation and integration of the COVID-19 pandemic in healthcare workers: A qualitative document analysis
(Wiley, 2024-09-19) Abad-Corpa, Eva; Rich-Ruiz, Manuel; Sánchez-López, Dolores; Solano Ruiz, Carmen; Casado-Ramirez, Elvira; Arregui-Gallego, Beatriz; Moreno-Casbas, Teresa; Muñoz-Jiménez, Daniel; Vidal-Thomàs, María Clara; Company-Sancho, María Consuelo; Orts-Cortes, Maria Isabel; Fundación BBVA
The COVID-19 pandemic triggered an unprecedented health crisis that impacted healthcare systems worldwide. This study explores how Spanish healthcare workers learned, internalised and integrated values and work behaviours during the COVID-19 pandemic and their impact on the personal sphere. This documentary research, using images, narratives and audiovisual content, was framed within the interpretative hermeneutic paradigm. Categories and subcategories emerged after a final theoretical sampling that focused on the analysis. Data triangulation between researchers favoured theoretical saturation. A total of 117 images and 27 texts were selected. The analysis identified three stages: bewilderment, seeking functionality in the chaos and integrating chaos into care. The data reflects how the need for security and knowledge, and the exhaustion and frustration caused by the initial working conditions, prompted adaptive responses. These responses involved focusing on problem-solving and strengthening group sentiments and solidarity. Subsequently, the data indicates the acceptance of new structural, organisational and communication aspects. The findings of the analysis will contribute towards finding a framework that can help understand community health crisis events.
Efficacy of the Otago-Exercise-Programme to reduce falls in community-dwelling adults aged 65-80 when delivered as group or individual training: Non-inferiority-clinical-trial
(BioMed Central (BMC), 2024-10-01) Albornos-Muñoz, Laura; Blanco-Blanco, Joan; Cidoncha-Moreno, María Ángeles; Abad-Corpa, Eva; Rivera-Álvarez, Araceli; López-Pisa, Rosa María; Caperos, José-Manuel; Otago Project Working Group Consortium; Moreno-Casbas, Teresa; Rich-Ruiz, Manuel; Rodriguez Baz; Agencia Estatal de Investigación (España); Instituto de Salud Carlos III; Fundación para la Formación e Investigación Sanitarias de la Región de Murcia; Basque Foundation for Health Innovation and Research
Background: The Otago Exercise Programme is an effective intervention for falls prevention. However, there is limited evidence in relation to studies that compare efficacy for falls prevention when delivered Otago Exercise Programme in a group or individual format in a primary care context. Objective: To compare the Otago Exercise Programme delivered as a group vs. individual format for community dwelling older adults, over a one year period. The hypothesis was that neither format would be inferior to the other. Methods: DESIGN: A four-year multicentre, randomized, non-inferiority clinical trial, with two arms- Otago Exercise Programme group training and individual Otago exercise training. Setting(s): 21 primary healthcare centers. Participants: A sample size of 728 participants was established. Participants were aged between 65 and 80 years; living in the community; able to walk independently; and agreed to take part in the study and provided signed informed consent. Intervention: The Otago Exercise Programme was delivered mainly by nurses in primary care, with five face to face sessions, and a reinforcement 6 months later. Participants were encouraged to exercise at home between face to face sessions. Data collection: at baseline and after 6 and 12 months from October 2017 to 2020. Primary outcome: people who reported at least one fall. Secondary outcomes: number of falls, cause of falls, consequences and assistance, adherence and satisfaction. Group allocation was blinded to the researchers involved in analysis. Reporting: Consolidated Standards of Reporting Trials recommendations for the Statement for Randomized Trials of Nonpharmacologic Treatments. Results: Eight hundred twenty-seven participants were randomized (226 were allocated in group training and 272 in individual training). The analysis of the proportion of people who reported at least one fall and number of falls showed no differences between individual and group training. Assessment of the equivalence between the interventions at 12 months showed that the confidence interval for the difference of people who reported at least one fall was found to be within the equivalence limit of 10% considered. However, in those participants with a previous history of falls, group format showed potentially greater benefit. The participants in individual training presented higher scores on the Exercise Adherence Rating Scale test. No differences were found in satisfaction between the groups. Conclusions: The group Otago Exercise Programme is equivalent to individually delivered Otago Exercise Programme in terms of prevention of falls over a 12-month follow up. Adherence was higher in individual training. Implications: Healthcare professionals could offer either Otago Exercise Programme format dependent on patient preference and be confident that that standardized intervention provides patient benefit. Trial registration: ClinicalTrials.gov (NCT03320668). Data registration 31/10/2017.
The impact of meteorological factors on tuberculosis incidence in Spain: a spatiotemporal analysis
(Cambridge University Press, 2024-03-20) Díez Galán, María Del Mar; Redondo-Bravo, Lidia; Gomez-Barroso, Diana; Herrera-Leon, Laura; Amillategui Dos Santos, Rocío; Gómez-Castellá, Javier; Herrador, Zaida; Spanish Working Group on Tuberculosis; Díez Galán, María Del Mar; Redondo-Bravo, Lidia; Gómez-Castellá, Javier; Spanish Working Group on Tuberculosis
Tuberculosis (TB) remains a global leading cause of death, necessitating an investigation into its unequal distribution. Sun exposure, linked to vitamin D (VD) synthesis, has been proposed as a protective factor. This study aimed to analyse TB rates in Spain over time and space and explore their relationship with sunlight exposure. An ecological study examined the associations between rainfall, sunshine hours, and TB incidence in Spain. Data from the National Epidemiological Surveillance Network (RENAVE in Spanish) and the Spanish Meteorological Agency (AEMET in Spanish) from 2012 to 2020 were utilized. Correlation and spatial regression analyses were conducted. Between 2012 and 2020, 43,419 non-imported TB cases were reported. A geographic pattern (north-south) and distinct seasonality (spring peaks and autumn troughs) were observed. Sunshine hours and rainfall displayed a strong negative correlation. Spatial regression and seasonal models identified a negative correlation between TB incidence and sunshine hours, with a four-month lag. A clear spatiotemporal association between TB incidence and sunshine hours emerged in Spain from 2012 to 2020. VD levels likely mediate this relationship, being influenced by sunlight exposure and TB development. Further research is warranted to elucidate the causal pathway and inform public health strategies for improved TB control.
Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination
(Elsevier, 2024-04) Varea-Jiménez, Elena; Aznar Cano, Esteban; Vega-Piris, Lorena; Martínez Sánchez, Elena Vanessa; Mazagatos, Clara; García San Miguel Rodríguez-Alarcón, Lucía; Casas Flecha, Inmaculada; Sierra Moros, María José; Iglesias-Caballero, Maria; Vázquez-Morón, Sonia; Larrauri, Amparo; Monge Corella, Susana; Working group for the surveillance and control of COVID-19; Arias-Bohigas, Pedro; Sastre García, María; Amillategui Dos Santos, Rocío; Delgado-Sanz, Concepcion; Oliva Dominguez, Jesus Angel; Pozo Sanchez, Francisco; Unión Europea. European Centre for Disease Prevention and Control (ECDC)
[EN] Background: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease. Methods: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June-July 2021; and Delta and Omicron during December 2021-January 2022. Adjusted odds ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls. Results: We included 5,345 Alpha and 11,974 Delta infections in June-July and 5,272 Delta and 10,578 Omicron in December-January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46-0.69) or Omicron (0.28; 0.21-0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13-0.21) and Delta (June-July: 0.16; 0.14-0.19; December-January: 0.36; 0.30-0.44) but lower from Omicron (0.63; 0.53-0.75) and individuals aged 65+ years. Conclusion: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups. [ES] Introducción: El objetivo es comprar la gravedad de las infecciones por las variantes Alfa, Delta y Ómicron del SARS-CoV-2 en periodos de co-circulación en España, y estimar la asociación entre vacunación y gravedad en cada variante. Métodos: Las infecciones por SARS-CoV-2 notificadas a la red nacional de vigilancia epidemiológica con información sobre la variante viral y el estado de vacunación se clasificaron como casos si habían requerido hospitalización, o como controles en caso contrario. Alfa y Delta se compararon durante junio-julio de 2021, y Delta y Ómicron durante diciembre de 2021-enero de 2022. Se estimaron odds ratios ajustadas (ORa) mediante regresión logística, comparando la variante y el estado de vacunación entre casos y controles. Resultados: Se incluyeron 5.345 infecciones por variante Alfa y 11.974 por Delta en junio-julio y 5.272 infecciones por Delta y 10.578 por Ómicron en diciembre-enero. Los casos no vacunados por Alfa (aOR: 0,57; IC 95%: 0,46-0,69) u Ómicron (0,28; IC 95%: 0,21-0,36) tuvieron menor probabilidad de hospitalización comparados con Delta. La vacunación completa se asoció a menor hospitalización de forma similar para Alfa (0,16; IC 95%: 0,13-0,21) y Delta (junio-julio: 0,16; IC 95%: 0,14-0,19; diciembre-enero: 0,36; IC 95%: 0,30-0,44) pero menor para Ómicron (0,63; IC 95%: 0,53-0,75) y para individuos con 65+ años. Conclusión: Los resultados indican una mayor gravedad intrínseca de la variante Delta comparada con Alfa u Ómicron, con menor diferencia entre personas vacunadas. La vacunación se asoció a menor hospitalización en todos los grupos.
Guiding Stem Cell Tenogenesis by Modulation of Growth Factor Signaling and Cell-Scale Biophysical Cues in Bioengineered Constructs
(Wiley, 2024-02-16) Teixeira, Simao PB; Pardo, Alberto; Bakht, Syeda M; Gomez-Florit, Manuel; Reis, Rui L; Gomes, Manuela E; Domingues, Rui MA
Tendon injuries and tendinopathies are increasingly prevalent health problems currently lacking effective treatments. Tissue engineering offers promising strategies to boost the low innate regenerative ability of tendons. Within this context, the simultaneous leveraging of both physical and biochemical cues by engineered scaffolding systems can be explored to promote a stronger tenogenic response from stem cells. Here, molecularly imprinted polymeric nanoparticles (MINPs) against transforming growth factor (TGF)-β3 are combined with bioinspired anisotropic hydrogels to produce tenogenesis-inductive constructs. MINPs are first solid phase-imprinted against a TGF-β3 epitope, achieving an affinity comparable to monoclonal antibodies. MINPs and magnetically-responsive microfibers are then encapsulated together with adipose-derived stem cells within gelatin-based hydrogels, applying a magnetostatic field during gelation to align the microfibers. The created anisotropic microstructure guides cell growth and elongation unidirectionally, while MINPs act as artificial receptors for TGF-β3, potentiating its paracrine action in the cellular microenvironment. The combination of both stimuli proves effective at increasing TGF-β signaling, which promotes the expression of tendon-associated genes and corresponding protein synthesis, suggesting that microstructural cues and biomolecule sequestration act in tandem to direct cell fate commitment. Overall, this system recapitulates several elements of tendon development, constituting a promising strategy for the regeneration of this tissue.
Pulmonary thrombosis associated with COVID-19 pneumonia: Beyond classical pulmonary thromboembolism
(Wiley, 2024-02-09) Suarez Castillejo, Carla; Calvo, Néstor; Preda, Luminita; Toledo Pons, Nuria; Millán-Pons, Aina Rosa; Martinez, Joaquin; Ramon, Luisa; Iglesias, Amanda; Morell Garcia, Daniel; Bauça, Josep Miquel; Núñez, Belén; Sauleda, Jaume; Sala Llinàs, Ernest; Alonso-Fernandez, Alberto
Background: Classical pulmonary thromboembolism (TE) and local pulmonary thrombosis (PT) have been suggested as mechanisms of thrombosis in COVID-19. However, robust evidence is still lacking because this was mainly based on retrospective studies, in which patients were included when TE was suspected. Methods: All patients with COVID-19 pneumonia underwent computed tomography and pulmonary angiography in a prospective study. The main objective was to determine the number and percentage of thrombi surrounded by lung opacification (TSO) in each patient, as well as their relationship with percentage of lung involvement (TLI), to distinguish classical TE (with a random location of thrombi that should correspond to a percentage of TSO equivalent to the TLI) from PT. We determined TLI by artificial intelligence. Analyses at patient level (TLI and percentage of TSO) and at thrombi level (TLI and TSO) were performed. Results: We diagnosed TE in 70 out of 184 patients. Three (2-8) thrombi/patient were detected. The percentage of TSO was 100% (75-100) per patient, and TLI was 19.9% (4.6-35.2). Sixty-five patients (92.9%) were above the random scenario with higher percentage of TSO than TLI. Most thrombi were TSO (n = 299, 75.1%). When evaluating by TLI (<10%, 10%-20%, 20%-30% and >30%), percentage of TSO was higher in most groups. Thrombi were mainly in subsegmental/segmental arteries, and percentage of TSO was higher in all locations. Conclusions: Thrombi in COVID-19 were found within lung opacities in a higher percentage than lung involvement, regardless of TLI and clot location, supporting the hypothesis of local PT rather than "classic TE".
Anaemia in patients with cardiogenic shock complicating acute myocardial infarction: Surrogate marker of poor outcome or therapeutic target?
(Wiley, 2024-01-21) Coughlan, JJ; Rosselló, Xavier
Microbial Phenolic Metabolites Are Associated with Improved Cognitive Health
(Wiley, 2024-01) Domínguez-López, Inés; Galkina, Polina; Parilli-Moser, Isabella; Arancibia-Riveros, Camila; Martínez-González, Miguel Ángel; Salas-Salvado, Jordi; Corella, Dolores; Malcampo, Mireia; Martínez, J Alfredo; Tojal-Sierra, Lucas; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, José; Estruch, Ramon; Tinahones, Francisco J; Santos-Lozano, José Manuel; Serra-Majem, Lluis; Bueno-Cavanillas, Aurora; Tur, Josep A; Rubín-García, María; Pintó, Xavier; Fernández-Aranda, Fernando; Delgado-Rodríguez, Miguel; Barabash-Bustelo, Ana; Vidal, Josep; Vazquez, Clotilde; Daimiel, Lidia; Ros, Emilio; Toledo, Estefanía; Atzeni, Alessandro; Asensio, Eva M; Vera, Natàlia; Garcia-Rios, Antonio; Torres-Collado, Laura; Pérez-Farinós, Napoleón; Zulet, Marian; Chaplin, Alice; Casas, Rosa; Martín-Peláez, Sandra; Vaquero-Luna, Jessica; Gómez-Pérez, Ana Maria; Vazquez-Ruiz, Zenaida; Shyam, Sangeetha; Ortega-Azorín, Carolina; Talens, Natàlia; Peña-Orihuela, Patricia J; Oncina-Canovas, Alejandro; Diez-Espino, Javier; Babio, Nancy; Fitó, Montserrat; Lamuela-Raventós, Rosa M
Scope: Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk. Methods and results: A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores. Conclusions: These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population.
Bronchoscopic segmental alveolar recruitment in a patient with spinal muscular atrophy and massive atelectasis
(Wiley, 2024-01-10) Atiénzar Esteban, Isabel; Osona Rodríguez, Borja; Salas Ballestin, Alberto; Clavero Rubio, María del Carmen; Flaquer Pérez de Mendiola, Joana Maria; Aguilar Gómez, Víctor; Echeverría López, Marina; de Carlos Vicente, Juan Carlos
Delving into public-expenditure elasticity: Evidence from a National Health Service acute-care hospital network
(Public Library of Science (PLOS), 2024) Comendeiro-Maaløe, Micaela; Ridao-Lopez, Manuel; Bernal-Delgado, Enrique; Sansó-Rosselló, Andreu
Introduction: The sustainability of public hospital financing in Spain is a recurring issue, given its representativeness in annual public healthcare budgets which must adapt to the macroeconomic challenges that influence the evolution of spending. Knowing whether the responsiveness of hospital expenditure to its determinants (need, utilisation, and quasi-prices) varies according to the type of hospital could help better design strategies aimed at optimising performance. Methods: Using SARIMAX models, we dynamically assess unique nationwide monthly activity data over a 14-year period from 274 acute-care hospitals in the Spanish National Health Service network, clustering these providers according to the average severity of the episodes treated. Results: All groups showed seasonal patterns and increasing trends in the evolution of expenditure. The fourth quartile of hospitals, treating the most severe episodes and accounting for more than 50% of expenditure, is the most sensitive to quasi-price factors, particularly the number of beds per hospital. Meanwhile, the first quartile of hospitals, which treat the least severe episodes and account for 10% of expenditure, is most sensitive to quantity factors, for which expenditure showed an elasticity above one, while factors of production were not affected. Conclusions: Belonging to one or another cluster of hospitals means that the determinants of expenditure have a different impact and intensity. The system should focus on these differences in order to optimally modulate expenditure not only according to the needs of the population, but also according to the macroeconomic situation, while leaving hospitals room for manoeuvre in case of unforeseen events. The findings suggest strengthening a network of smaller hospitals (Group 1)-closer to their reference population, focused on managing and responding to chronicity and stabilising acute events-prior to transfer to tertiary hospitals (Group 4)-larger but appropriately sized, specialising in solving acute and complex health problems-when needed.
Validation of the Italian version of the Parkinson's Disease- Cognitive Functional Rating Scale
(Springer, 2024-01-27) Garon, Michela; Weis, Luca; Siquier, Antònia; Fiorenzato, Eleonora; Pistonesi, Francesca; Cianci, Valeria; Canesi, Margherita; Pesce, Francesca; Reali, Elisa; Pozzi, Beatrice; Isaias, Ioannis Ugo; Siri, Chiara; Santangelo, Gabriella; Cuoco, Sofia; Barone, Paolo; Kulisevsky, Jaime; Antonini, Angelo; Biundo, Roberta
A key distinguishing factor between mild cognitive impairment (MCI) and dementia in Parkinson's disease (PD) lies in the notable decrease in functioning due to cognitive impairment. The Parkinson's Disease-Cognitive Functional Rating Scale (PD-CRFS) was developed to assess functional limitations caused by cognitive impairment, while reducing the influence of motor impairment. The aim of this multicenter study was to (i) validate the Italian version of the PD-CFRS in PD, (ii) determine optimal cut-off scores for detecting MCI and dementia in PD, (iii) compare its performances with the most established functional assessment tool (IADL). Six hundred and sixty nine PD participants were recruited from 4 Italian Movement Disorders centers (Venice, Milan, Gravedona, and Salerno). They underwent Level-II cognitive evaluation, which resulted in 282 PD-NC, 310 PD-MCI, and 77 PDD. The PD-CFRS's psychometric and clinimetric properties, applicability, and responsiveness were analyzed. The PD-CFRS showed high acceptability. Floor and ceiling effects were acceptable. It also displayed strong internal consistency (Cronbach's α = 0.738), and test-retest reliability (ICC = .854). The PD-CFRS demonstrated higher coefficient of variation to detect dysfunction in PD-MCI patients in comparison to the IADL scale (PD-CFRS 96% vs IADL 22.5%). Convergent validity with the IADL was r = - 0.638 and - 0.527 in males and females, respectively. PD-CFRS total score negatively correlated with global cognition (MoCA corrected score r = - 0.61; p < 0.001). A cut-off score > 6.5 identified PDD with a sensitivity of 90% and specificity of 88% (AUC = .959). A cut-off value of > 1 detected PD-MCI with a sensitivity of 68% and specificity of 69% (AUC = .695). The Italian version of the PD-CFRS demonstrated to be an easy, valid and reliable tool that properly captures functional impairment due to cognitive decline in PD. It also proved to be particularly effective in the advanced stages of PD, and would be a useful support for the diagnosis of PD-MCI and PDD.
Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population
(Springer, 2024-01-13) Baenas, I; Camacho-Barcia, L; Granero, R; Razquin, C; Corella, D; Gómez-Martínez, Carlos; Castañer-Niño, O; Martínez, JA; Alonso-Gómez, ÁM; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, J; Estruch, R; Tinahones, Francisco J; Lapetra, J; Serra-Majem, Lluis; Cano-Ibáñez, N; Tur, Josep A; Martín-Sánchez, V; Pintó, X; Gaforio, J J; Matía-Martín, P; Vidal, Josep; Vazquez, Clotilde; Daimiel, L; Ros, Emilio; Jiménez-Murcia, S; Dalsgaard, S; Garcia-Arellano, A; Babio, N; Sorli, Jose V; Lassale, C; García-de-la-Hera, M; Gómez-García, E; Zulet, MA; Konieczna, Jadwiga; Martín-Peláez, S; Tojal-Sierra, Lucas; Basterra-Gortari, FJ; de Las Heras-Delgado, S; Portoles, O; Muñoz-Pérez, MÁ; Arenas-Larriva, AP; Compañ-Gabucio, L; Eguaras, S; Shyam, Sangeetha; Fitó, M; Baños, RM; Salas-Salvado, Jordi; Fernández-Aranda, F
Objectives: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. Methods: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. Results: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. Conclusions: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.
Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis
(Nature Publishing Group, 2024-02-17) Medina-Dols, Aina; Cañellas, Guillem; Capó, Toni; Solé, Montse; Mola-Caminal, Marina; Cullell, Natalia; Jaume, Marina; Nadal-Salas, Laura; Llinàs, Jaume; Gómez, Lluis; Tur Campos, Silvia; Jiménez Martínez, Carmen; Diaz Navarro, Rosa; Carrera, Caty; Muiño, Elena; Gallego-Fabrega, Cristina; Soriano-Tarraga, Carolina; Ruiz-Guerra, Laura; Pol-Fuster, Josep; Asensio, Víctor José; Muncunill Farreny, Josep; Fleischer, Aarne; Iglesias, Amanda; Giralt-Steinhauer, Eva; Lazcano, Uxue; Fernández-Pérez, Isabel; Jiménez-Balado, Joan; Gabriel-Salazar, Marina; Garcia-Gabilondo, Miguel; Lei, Ting; Torres-Aguila, Nuria-Paz; Cárcel-Márquez, Jara; Lladó, Jerònia; Olmos, Gabriel; Rosell, Anna; Montaner, Joan; Planas, Anna M; Rabionet, Raquel; Hernández-Guillamon, Mar; Jiménez-Conde, Jordi; Fernández-Cadenas, Israel; Vives-Bauza, Cristofol
Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient's blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) ≤2), compared to those patients with marked disability (mRS = 4-5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1α also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, β-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.

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