IR Sant Pau - Instituto de Investigación Sant Pau (Cataluña)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/16972

Creado el 4 de junio de 1992, el Instituto de Investigación es una fundación privada de carácter científico que tiene por misión promover la investigación básica, clínica, epidemiológica y de servicios sanitarios en el campo de las ciencias de la salud y la biomedicina, con el último objetivo de contribuir a la mejora de la salud de la población. El 17 de mayo de 2009, los esfuerzos del Instituto de Investigación y de otras nueve entidades de su entorno convergieron en la creación del Instituto de Investigación Sant Pau (IIB SantPau), centro de investigación de alto nivel orientado a desarrollar nuevas técnicas y procesos que permitan mejorar la calidad de vida del ciudadano. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2011, 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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Genicular artery embolization for knee osteoarthritis: a systematic review with meta-analysis and cost-analysis
(Elsevier, 2025-02-17) Hernández-Yumar, Aránzazu; González-Hernández, Yadira; Del Pino-Sedeño, Tasmania; Valcárcel-Nazco, Cristina; de Armas-Castellano, Aythami; Herrera-Ramos, Estefanía; Portero Navarro, Julián; Carmona, Montserrat; Rojas-Reyes, María Ximena; Trujillo-Martín, María M; Ministerio de Sanidad (España); Instituto de Salud Carlos III
Objective: To assess the effectiveness, safety, and cost-effectiveness of genicular artery embolization (GAE) for the treatment of mild or moderate knee osteoarthritis (KO) refractory to standard treatment, and/or severe KO in individuals not eligible for surgery. Method: We conducted a systematic review with meta-analysis, supplemented by a cost-analysis, comparing GAE and standard treatment, from the perspective of the Spanish National Health System (NHS) over a one-year time horizon. The health improvement required for GAE to be deemed cost-effective was quantified, considering a willingness-to-pay threshold of 25 000 €/quality-adjusted life year (QALY). Results: We included two randomized controlled trials in our analysis. Pain estimates showed inconsistent results, and no significant effects were observed for overall function, health-related quality of life, or changes in the need for pain management medication. No serious complications or major adverse events were observed. GRADE quality of evidence ranged from moderate to low. No economic evaluations were identified. Our cost-analysis revealed that GAE would result in an incremental cost of € 3432.37 per patient, requiring a health improvement of 0.137 QALY per patient to be deemed a cost-effective technology. Conclusions: In summary, based on moderate to low-certainty evidence, it remains inconclusive whether there is any difference between GAE and standard treatment for KO. However, the use of GAE would increase the costs. Larger randomized controlled trials are needed to determine the effects of using GAE for chronic pain secondary to KO and, consequently, to ascertain whether this technology could potentially become cost-effective from the NHS perspective.
Healthcare and Epidemiological Surveillance Costs of Hepatitis A Outbreaks in Spain in Regions with and without Universal Hepatitis A Vaccination of Children during 2010-2018
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-06-11) Plans-Rubió, Pedro; Pericas, Carles; Avellón, Ana; Izquierdo, Concepción; Martínez, Ana; Torner, Núria; Martínez, Alejandro; Borràs, Eva; Roig, Francisco; Godoy, Pere; Rius, Cristina; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Instituto de Salud Carlos III
The aim of this study was to evaluate and compare hepatitis A outbreak-associated healthcare and epidemiological surveillance costs in Spain in two types of autonomous regions during 2010-2018: (1) regions with a prevention strategy based on universal hepatitis A vaccination of children and vaccination of high-risk population groups (Catalonia) and (2) regions with a prevention strategy based on vaccinating high-risk population groups (Castile and Leon, Murcia, Navarra, Community of Madrid, Community of Valencia). Healthcare costs were determined based on the resources used to treat hepatitis A outbreak-associated cases and hospitalizations. Epidemiological surveillance costs were calculated from the resources used during surveillance activities. The ratios for total, healthcare and epidemiological surveillance costs (regions without universal hepatitis A vaccination of children vs. Catalonia) were used to compare the two hepatitis A prevention strategies. From 2010 to 2018, the total, healthcare and epidemiological surveillance costs per million population were 1.75 times (EUR 101,671 vs. EUR 58,032), 1.96 times (EUR 75,500 vs. EUR 38,516) and 1.34 times greater (EUR 26,171 vs. EUR 19,515) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. The ratios tended to increase over time during 2010-2018. In 2015-2018, total, healthcare and epidemiological surveillance costs per million population were 2.68 times (EUR 69,993 vs. EUR 26,158), 2.86 times (EUR 53,807 vs. EUR 18,825) and 2.21 times greater (EUR 16,186 vs. EUR 7333) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. These findings suggest that universal hepatitis A vaccination of children could reduce hepatitis A outbreak-associated costs.
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.
Novel risk loci for COVID-19 hospitalization among admixed American populations
(eLife Sciences Publications, 2024-10-03) Diz-de Almeida, Silvia; Cruz, Raquel; Luchessi, Andre D; Lorenzo-Salazar, José M; López de Heredia, Miguel; Quintela, Inés; González-Montelongo, Rafaela; Nogueira Silbiger, Vivian; Porras, Marta Sevilla; Tenorio Castaño, Jair Antonio; Nevado, Julián; Aguado, José María; Aguilar, Carlos; Aguilera-Albesa, Sergio; Almadana, Virginia; Almoguera, Berta; Alvarez, Nuria; Andreu-Bernabeu, Álvaro; Arana-Arri, Eunate; Arango, Celso; Arranz, María J; Artiga, Maria-Jesus; Baptista-Rosas, Raúl C; Barreda-Sánchez, María; Belhassen-García, Moncef; Bezerra, Joao F; Bezerra, Marcos A C; Boix-Palop, Lucía; Brion, María; Brugada, Ramón; Bustos, Matilde; Calderón, Enrique J; Carbonell, Cristina; Castano, Luis; Castelao, Jose E; Conde-Vicente, Rosa; Cordero-Lorenzana, M Lourdes; Cortes-Sanchez, Jose L; Corton, Marta; Darnaude, M Teresa; De Martino-Rodríguez, Alba; Del Campo-Pérez, Victor; Diaz de Bustamante, Aranzazu; Domínguez-Garrido, Elena; Eirós, Rocío; Fariñas, María Carmen; Fernandez-Nestosa, María J; Fernández-Robelo, Uxía; Fernandez-Rodriguez, Amanda; Fernández-Villa, Tania; Gago-Dominguez, Manuela; Gil-Fournier, Belén; Gómez-Arrue, Javier; González Álvarez, Beatriz; González Bernaldo de Quirós, Fernan; González-Neira, Anna; González-Peñas, Javier; Gutiérrez-Bautista, Juan F; Herrero, María José; Herrero-Gonzalez, Antonio; Jimenez-Sousa, Maria Angeles; Lattig, María Claudia; Liger Borja, Anabel; Lopez-Rodriguez, Rosario; Mancebo, Esther; Martín-López, Caridad; Martín, Vicente; Martinez-Nieto, Oscar; Martinez-Lopez, Iciar; Martinez-Resendez, Michel F; Martinez-Perez, Angel; Mazzeu, Juliana F; Merayo Macías, Eleuterio; Minguez, Pablo; Moreno Cuerda, Victor; Oliveira, Silviene F; Ortega-Paino, Eva; Pompa-Mera, Ericka N; Parellada, Mara; Paz-Artal, Estela; Santos, Ney PC; Pérez-Matute, Patricia; Perez, Patricia; Pérez-Tomás, M Elena; Perucho, Teresa; Pinsach-Abuin, Mel·lina; Pita, Guillermo; Porras-Hurtado, Gloria L; Pujol, Aurora; Ramiro León, Soraya; Resino, Salvador; Fernandes, Marianne R; Rodríguez-Ruiz, Emilio; Rodríguez-Artalejo, Fernando; Rodriguez-Garcia, José A; Ruiz-Cabello, Francisco; Ruiz-Hornillos, Javier; Ryan, Pablo; Soria, José Manuel; Souto, Juan Carlos; Tamayo, Eduardo; Tamayo-Velasco, Álvaro; Taracido-Fernandez, Juan Carlos; Teper, Alejandro; Torres-Tobar, Lilian; Urioste, Miguel; Valencia-Ramos, Juan; Yáñez, Zuleima; Zarate, Ruth; de Rojas, Itziar; Ruiz, Agustín; Sánchez, Pascual; Real, Luis Miguel; SCOURGE Cohort Group; Guillén-Navarro, Encarna; Ayuso, Carmen; Parra, Esteban; Riancho, José A; Rojas-Martinez, Augusto; Flores, Carlos; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Banco Santander; Fundación La Caixa; Agencia Estatal de Investigación (España); Gobierno de Canarias (España); Fundación Canaria de Investigación Sanitaria; Xunta de Galicia (España); Fundación Amancio Ortega; Estrella de Levante; Colabora Mujer
The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations ( and ). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in . Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.
Impact of the Universal Implementation of Adolescent Hepatitis B Vaccination in Spain
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-05-01) Domínguez, Angela; Avellón, Ana; Hernando Sebastian, Victoria; Soldevila, Núria; Borràs, Eva; Martínez, Ana; Izquierdo, Conchita; Torner, Núria; Pericas, Carles; Rius, Cristina; Godoy, Pere; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Instituto de Salud Carlos III
The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991-1993 and in 1994-1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 ( < 0.001). The incidence in 2014-2021 was lower for regions that started adolescent vaccination in 1991-1993 rather than in 1994-1996 (IRR 0.76; 95% CI 0.72-0.83; < 0.001). In the 20-29 age group, incidence in regions that started adolescent vaccination in 1991-1993 was also lower (IRR 0.87; 95% CI 0.77-0.98; = 0.02 in 2005-2013 and IRR 0.71; 95% CI 0.56-0·90; < 0.001 in 2014-2021). Anti-HBc prevalence in the 35-39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant ( = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030.
Hepatitis B Virus-Related Cirrhosis and Hepatocellular Carcinoma Hospital Discharge Rates from 2005 to 2021 in Spain: Impact of Universal Vaccination
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-11-04) Domínguez, Angela; Avellón, Ana; Hernando Sebastian, Victoria; Soldevila, Núria; Borràs, Eva; Martínez, Ana; Izquierdo, Conchita; Torner, Núria; Pericas, Carles; Rius, Cristina; Godoy, Pere; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Instituto de Salud Carlos III
Background: The main consequences of chronic hepatitis B virus (HBV) infections are cirrhosis and hepatocellular carcinoma (HCC), both associated with frequent hospitalization. The aim of this study was to analyze the impact of universal HBV vaccination in Spain on chronic HBV-related hospital discharges from 2005 to 2021. Methods: Using data from the Minimum Basic Data Set of the Spanish National Health System, we calculated the hospital discharge rate ratio (HDRR) and 95% confidence interval (CI) values for chronic HBV-related discharges between 2005 and 2021. For comparative purposes, we calculated the HDRR and 95% confidence interval (CI) values for the early (2005-2013) and later (2014-2021) periods and the vaccinated compared with unvaccinated cohorts for the 20-39 age group. Results: The hospital discharge rate per 1,000,000 people was 3.08 in 2005 and 4.50 in 2021 for HCC, and 4.81 in 2005 and 1.92 in 2021 for cirrhosis. Comparing the early and later periods, values were higher for HCC (HDRR 1.13; 95% CI: 1.06-1.20) and lower for cirrhosis (HDRR 0.56; 95% CI: 0.51-0.60). The rate for the 20-39 age group was lower for the vaccinated compared with the unvaccinated cohorts overall (HDRR 0.53; 95% CI: 0.45-0.62), for HCC (HDRR 0.66; 95% CI: 0.53-0.82), and for cirrhosis (HDRR 0.41; 95% CI: 0.33-0.53). Conclusions: This study describes the important impact, after 25 years, of universal HBV vaccination in Spain: cirrhosis hospital discharge rate was reduced, and the vaccinated cohorts, compared with the unvaccinated cohorts in the 20-39 age group, had a lower hospital discharge rate of both HCC and cirrhosis.
Evaluation of the Let's Focus! (Posem el Focus) Socioeducational Intervention: Promoting Healthy and Equitable Relationships in High Schools
(Wiley, 2024-10) Forcadell-Díez, Lluís; Pérez-Martínez, Vanesa; Guitart, Elisabeth; Sanz-Barbero, Belén; Vives-Cases, Carmen; López, María José; Juárez, Olga; Pérez, Glòria; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Unión Europea. Fondo Social Europeo (ESF/FSE); Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública)
Introduction: Gender-based violence is a worldwide problem. School-based socio-educational interventions could be effective in preventing gender-based violence. We assessed the effectiveness of the Let's focus! program, aimed at health and equitable interpersonal relationships among high school students. Methods: We conducted a quasi-experimental study in an intervention group (IG, n = 560) and a comparison group (CG, n = 366) of secondary school students in Terrassa, Spain between 2019 and 2021. Specifically, we performed an online questionnaire on sexism, acceptance of violence and machismo at baseline and after the intervention. We calculated multivariate linear regression models including satisfaction with the intervention, to evaluate the change in the variables' mean between CG and IG. Results: In comparison to the CG, in the IG hostile and benevolent sexism, and acceptance of violence decreased from baseline to after-intervention, in the group of participants highly satisfied with the intervention (42.4%); machismo did not vary. The multivariate regression analyses showed that the intervention was effective in reducing hostile sexism (β = -6.40; CI95% (-11.92; -0.88)), benevolent sexism (β = -5.57; CI95% (-10.52;-0.61)), and acceptance of violence (β = -4.79; CI95% (-9.50; -0.09)) in highly satisfied students from the IG, in comparison to the ones from the CG, regardless of their age or gender. Discussion: Let's Focus! was effective in reducing sexism and decreasing acceptance of violence among students that were highly satisfied with the intervention.
Typing of isolates from vectors and leporids of the Madrid (Spain) outbreak
(Cambridge University Press, 2024-02) Fernández-Arévalo, Anna; Gonzalez, Estela; Ballart, Cristina; Martin-Martin, Ines; Tebar, Silvia; Muñoz, Carme; Jimenez, Maribel; Molina, Ricardo; Gállego, Montserrat; Agència de Gestió d´Ajuts Universitaris i de Recerca (AGAUR); RETICS-Investigación colaborativa en Enfermedades Tropicales (RICET-ISCIII) (España); Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (España); Unión Europea. Comisión Europea. NextGenerationEU; Agencia Estatal de Investigación (España); Government of Catalonia (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
In 2009, a large outbreak of leishmaniasis, associated with environmental changes, was declared near Madrid (Spain), in which Phlebotomus perniciosus was the vector, whereas the main reservoirs were hares and rabbits. Analysis of isolates from humans, vectors and leporids from the focus identified the Leishmania infantum ITS-Lombardi genotype. However, multilocus enzyme electrophoresis (MLEE), the reference technique for Leishmania typing, and sequencing of the hsp70 gene, a commonly used marker, were not performed. In the present study, 19 isolates from P. perniciosus (n = 11), hares (n = 5) and rabbits (n = 3) from the outbreak area, all characterized as ITS-Lombardi in previous studies, were analysed by MLEE and hsp70 sequencing. The hsp70 results confirmed that all the analysed strains are L. infantum. However, by MLEE, 4 different zymodemes of L. infantum were identified based on variable mobilities of the NP1 enzyme: MON-34 (NP1100, n = 11), MON-80 (NP1130, n = 6), MON-24 (NP1140, n = 1) and MON-331 (NP1150, n = 1). The relative frequency of these zymodemes does not correspond to their usual occurrence in Spain. Moreover, MON-34 and MON-80 were found in P. perniciosus, hares and rabbits for the first time. These findings continue to provide insights into the outbreak and call for further studies with a higher number of strains.
Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain.
(2020-05-11) Gonzalez-Quereda, Lidia; Rodriguez, Maria Jose; Diaz-Manera, Jordi; Alonso-Perez, Jorge; Gallardo, Eduard; Nascimento, Andres; Ortez, Carlos; Natera-de Benito, Daniel; Olive, Montse; Gonzalez-Mera, Laura; Munain, Adolfo Lopez de; Zulaica, Miren; Poza, Juan Jose; Jerico, Ivonne; Torne, Laura; Riera, Pau; Milisenda, Jose; Sanchez, Aurora; Garrabou, Gloria; Llano, Isabel; Madruga-Garrido, Marcos; Gallano, Pia
The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients' clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.
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.
Increased grey matter volumes in the temporal lobe and its relationship with cognitive functioning in euthymic patients with bipolar disorder.
(Elsevier, 2024-02-15) Porta-Casteràs, D; Vicent-Gil, M; Serra-Blasco, M; Navarra-Ventura, Guillem; Solé, B; Montejo, L; Torrent, C; Martinez-Aran, A; De la Peña-Arteaga, V; Palao, D; Vieta, E; Cardoner, N; Cano, M
Background: Bipolar disorder (BD) is characterized by episodic mood dysregulation, although a significant portion of patients suffer persistent cognitive impairment during euthymia. Previous magnetic resonance imaging (MRI) research suggests BD patients may have accelerated brain aging, observed as lower grey matter volumes. How these neurostructural alterations are related to the cognitive profile of BD is unclear. Methods: We aim to explore this relationship in euthymic BD patients with multimodal structural neuroimaging. A sample of 27 euthymic BD patients and 24 healthy controls (HC) underwent structural grey matter MRI and diffusion-weighted imaging (DWI). BD patient's cognition was also assessed. FreeSurfer algorithms were used to obtain estimations of regional grey matter volumes. White matter pathways were reconstructed using TRACULA, and four diffusion metrics were extracted. ANCOVA models were performed to compare BD patients and HC values of regional grey matter volume and diffusion metrics. Global brain measures were also compared. Bivariate Pearson correlations were explored between significant brain results and five cognitive domains. Results: Euthymic BD patients showed higher ventricular volume (F(1, 46) = 6.04; p = 0.018) and regional grey matter volumes in the left fusiform (F(1, 46) = 15.03; pFDR = 0.015) and bilateral parahippocampal gyri compared to HC (L: F(1, 46) = 12.79, pFDR = 0.025/ R: F(1, 46) = 15.25, pFDR = 0.015). Higher grey matter volumes were correlated with greater executive function (r = 0.53, p = 0.008). Limitations: We evaluated a modest sample size with concurrent pharmacological treatment. Conclusions: Higher medial temporal volumes in euthymic BD patients may be a potential signature of brain resilience and cognitive adaptation to a putative illness neuroprogression. This knowledge should be integrated into further efforts to implement imaging into BD clinical management.
Myocardial injury after major non-cardiac surgery evaluated with advanced cardiac imaging: a pilot study
(BioMed Central (BMC), 2023-02-10) Álvarez-Garcia, Jesús; Popova, Ekaterine; Vives-Borrás, Miquel; de Nadal, Miriam; Ordonez-Llanos, Jordi; Rivas-Lasarte, Mercedes; Moustafa, Abdel-Hakim; Sole-Gonzalez, Eduard; Paniagua-Iglesias, Pilar; Garcia-Moll, Xavier; Viladés-Medel, David; Leta-Petracca, Rubén; Oristrell, Gerard; Zamora, Javier; Ferreira-González, Ignacio; Alonso-Coello, Pablo; Carreras-Costa, Francesc
Background: Myocardial injury after non-cardiac surgery (MINS) is a frequent complication caused by cardiac and non-cardiac pathophysiological mechanisms, but often it is subclinical. MINS is associated with increased morbidity and mortality, justifying the need to its diagnose and the investigation of their causes for its potential prevention. Methods: Prospective, observational, pilot study, aiming to detect MINS, its relationship with silent coronary artery disease and its effect on future adverse outcomes in patients undergoing major non-cardiac surgery and without postoperative signs or symptoms of myocardial ischemia. MINS was defined by a high-sensitive cardiac troponin T (hs-cTnT) concentration > 14 ng/L at 48-72 h after surgery and exceeding by 50% the preoperative value; controls were the operated patients without MINS. Within 1-month after discharge, cardiac computed tomography angiography (CCTA) and magnetic resonance imaging (MRI) studies were performed in MINS and control subjects. Significant coronary artery disease (CAD) was defined by a CAD-RADS category ≥ 3. The primary outcomes were prevalence of CAD among MINS and controls and incidence of major cardiovascular events (MACE) at 1-year after surgery. Secondary outcomes were the incidence of individual MACE components and mortality. Results: We included 52 MINS and 12 controls. The small number of included patients could be attributed to the study design complexity and the dates of later follow-ups (amid COVID-19 waves). Significant CAD by CCTA was equally found in 20 MINS and controls (30% vs 33%, respectively). Ischemic patterns (n = 5) and ischemic segments (n = 2) depicted by cardiac MRI were only observed in patients with MINS. One-year MACE were also only observed in MINS patients (15.4%). Conclusion: This study with advanced imaging methods found a similar CAD frequency in MINS and control patients, but that cardiac ischemic findings by MRI and worse prognosis were only observed in MINS patients. Our results, obtained in a pilot study, suggest the need of further, extended studies that screened systematically MINS and evaluated its relationship with cardiac ischemia and poor outcomes. Trial registration Clinicaltrials.gov identifier: NCT03438448 (19/02/2018).
Impact of adherence to individual quality-of-care indicators on the prognosis of bloodstream infection due to Staphylococcus aureus: a prospective observational multicentre cohort
(Elsevier, 2023-04) Escrihuela-Vidal, Francesc; Kaasch, Achim J; Von Cube, Maja; Rieg, Siegbert; Kern, Winfried V; Seifert, Harald; Song, Kyoung-Ho; Liao, Chun-Hsing; Tilley, Robert; Gott, Hannah; Scarborough, Matt; Gordon, Claire; Llewelyn, Martin J; Kuehl, Richard; Morata, Laura; Soriano, Alex; Edgeworth, Jonathan; Ruiz de Gopegui-Bordes, Enrique; Nsutebu, Emmanuel; Cisneros, José Miguel; Fowler, Vance G.; Thwaites, Guy; López-Contreras, Joaquín; Barlow, Gavin; Ternavasio-De La Vega, Hugo Guillermo; Rodriguez-Bano, Jesus; Lopez-Cortes, Luis Eduardo
Objectives: To analyse the adherence and impact of quality-of-care indicators (QCIs) in the management of Staphylococcus aureus bloodstream infection in a prospective and multicentre cohort. Methods: Analysis of the prospective, multicentre international S. Aureus Collaboration cohort of S. Aureus bloodstream infection cases observed between January 2013 and April 2015. Multivariable analysis was performed to evaluate the impact of adherence to QCIs on 90-day mortality. Results: A total of 1784 cases were included. Overall, 90-day mortality was 29.9% and mean follow-up period was 118 days. Adherence was 67% (n = 1180/1762) for follow-up blood cultures, 31% (n = 416/1342) for early focus control, 77.6% (n = 546/704) for performance of echocardiography, 75.5% (n = 1348/1784) for adequacy of targeted antimicrobial therapy, 88.6% (n = 851/960) for adequacy of treatment duration in non-complicated bloodstream infections and 61.2% (n = 366/598) in complicated bloodstream infections. Full bundle adherence was 18.4% (n = 328/1784). After controlling for immortal time bias and potential confounders, focus control (adjusted hazard ratio = 0.76; 95% CI, 0.59-0.99; p 0.038) and adequate targeted antimicrobial therapy (adjusted hazard ratio = 0.75; 95% CI, 0.61-0.91; p 0.004) were associated with low 90-day mortality. Discussion: Adherence to QCIs in S. Aureus bloodstream infection did not reach expected rates. Apart from the benefits of application as a bundle, focus control and adequate targeted therapy were independently associated with low mortality.
Characteristics and impact of interventions to support healthcare providers' compliance with guideline recommendations for breast cancer: a systematic literature review
(BioMed Central (BMC), 2023-05-22) Ricci-Cabello, Ignacio; Carvallo-Castañeda, Darla; Vásquez-Mejía, Adrián; Alonso-Coello, Pablo; Saz-Parkinson, ZuleiKa; Parmelli, Elena; Morgano, Gian Paolo; Rigau, David; Solà, Ivan; Neamtiu, Luciana; Niño-de-Guzmán, Ena
Background: Breast cancer clinical practice guidelines (CPGs) offer evidence-based recommendations to improve quality of healthcare for patients. Suboptimal compliance with breast cancer guideline recommendations remains frequent, and has been associated with a decreased survival. The aim of this systematic review was to characterize and determine the impact of available interventions to support healthcare providers' compliance with CPGs recommendations in breast cancer healthcare. Methods: We searched for systematic reviews and primary studies in PubMed and Embase (from inception to May 2021). We included experimental and observational studies reporting on the use of interventions to support compliance with breast cancer CPGs. Eligibility assessment, data extraction and critical appraisal was conducted by one reviewer, and cross-checked by a second reviewer. Using the same approach, we synthesized the characteristics and the effects of the interventions by type of intervention (according to the EPOC taxonomy), and applied the GRADE framework to assess the certainty of evidence. Results: We identified 35 primary studies reporting on 24 different interventions. Most frequently described interventions consisted in computerized decision support systems (12 studies); educational interventions (seven), audit and feedback (two), and multifaceted interventions (nine). There is low quality evidence that educational interventions targeted to healthcare professionals may improve compliance with recommendations concerning breast cancer screening, diagnosis and treatment. There is moderate quality evidence that reminder systems for healthcare professionals improve compliance with recommendations concerning breast cancer screening. There is low quality evidence that multifaceted interventions may improve compliance with recommendations concerning breast cancer screening. The effectiveness of the remaining types of interventions identified have not been evaluated with appropriate study designs for such purpose. There is very limited data on the costs of implementing these interventions. Conclusions: Different types of interventions to support compliance with breast cancer CPGs recommendations are available, and most of them show positive effects. More robust trials are needed to strengthen the available evidence base concerning their efficacy. Gathering data on the costs of implementing the proposed interventions is needed to inform decisions about their widespread implementation. Trial registration: CRD42018092884 (PROSPERO).
Epidemiology, monitoring, and treatment strategy in cardiogenic shock. A multinational cross-sectional survey of ESC-acute cardiovascular care association research section
(Oxford University Press, 2022-09-29) Tavazzi, Guido; Rosselló, Xavier; Grand, Johannes; Gierlotka, Marek; Sionis, Alessandro; Ahrens, Ingo; Hassager, Christian; Price, Susanna
Aims: Cardiogenic shock (CS) is a life-threatening condition burdened by mortality in up to 50% of cases. Few recommendations exist with intermediate-low level of evidence on CS management and no data on adherence across centres exist. We performed a survey to frame CS management at multinational level. Methods and results: An international cross-sectional survey was created and approved by European Society of Cardiology-Acute Cardiovascular Care Association board. A total of 337 responses from 60 countries were obtained. Data were assessed by the hospital level of care of the participants. The most common cause of CS was AMI (AMI-CS-79.9%) with significant difference according to hospital levels (P = 0.001), followed by acutely decompensated heart failure (HF) (13.4%), myocarditis (3.5%), and de novo HF (1.75%). In 37.8%, percutaneous coronary intervention (PCI) is performed to all CS-patients as a standard approach, whereas 42.1% used PCI if electrocardiogram suggestive of ischaemia and 20.1% only if Universal definition of myocardial infarction criteria are fulfilled. Management (catecholamine titration and mechanical circulatory support escalation) is driven by mean arterial pressure (87.1%), echocardiography (84.4%), and lactate levels (83.4%). Combination of vasopressor and inotrope is chosen with the same frequency (37.7%) than inotrope alone as first-line pharmacological therapy (differences amongst hospital levels; P > 0.5). Noradrenaline is first-line vasopressor (89.9%) followed by dopamine (8.5%), whereas dobutamine is confirmed as the first-line inotrope (65.9%). Conclusion: Cardiogenic shock management is heterogenous and often not adherent to current recommendations. Quality improvement on an international level with evidence-based quality indicators should be developed to standardize diagnostic and therapeutic pathways.
A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype
(Frontiers Media, 2022) Cárcel-Márquez, Jara; Muiño, Elena; Gallego-Fabrega, Cristina; Cullell, Natalia; Lledós, Miquel; Llucià-Carol, Laia; Sobrino, Tomas; Campos, Francisco; Castillo, José; Freijo Guerrero, Maria del Mar; Arenillas, Juan Francisco; Obach, Victor; Álvarez-Sabín, José; Molina, Carlos A; Ribo, Marc; Jiménez-Conde, Jordi; Roquer, Jaume; Muñoz-Narbona, Lucia; Lopez-Cancio, Elena; Millán, Mònica; Diaz Navarro, Rosa; Vives-Bauza, Cristofol; Serrano-Heras, Gemma; Segura, Tomas; Ibañez, Laura; Heitsch, Laura; Delgado, Pilar; Dhar, Rajat; Krupinski, Jerzy; Delgado-Mederos, Raquel; Prats-Sánchez, Luis; Camps-Renom, Pol; Blay, Natalia; Sumoy, Lauro; de Cid, Rafael; Montaner, Joan; Cruchaga, Carlos; Lee, Jin-Moo; Martí-Fàbregas, Joan; Fernandez-Cadenas, Israel; Cárcel-Márquez, Jara; Muiño, Elena; Gallego-Fabrega, Cristina; Cullell, Natalia; Lledós, Miquel; Llucià-Carol, Laia; Sobrino, Tomas; Campos, Francisco; Castillo, José; Freijo Guerrero, Maria del Mar; Arenillas, Juan Francisco; Obach, Victor; Álvarez-Sabín, José; Molina, Carlos A; Ribo, Marc; Jiménez-Conde, Jordi; Roquer, Jaume; Muñoz-Narbona, Lucia; Lopez-Cancio, Elena; Millán, Mònica; Diaz Navarro, Rosa; Vives-Bauza, Cristofol; Serrano-Heras, Gemma; Segura, Tomas; Ibañez, Laura; Heitsch, Laura; Delgado, Pilar; Dhar, Rajat; Krupinski, Jerzy; Delgado-Mederos, Raquel; Prats-Sánchez, Luis; Camps-Renom, Pol; Blay, Natalia; Sumoy, Lauro; de Cid, Rafael; Montaner, Joan; Cruchaga, Carlos; Lee, Jin-Moo; Martí-Fàbregas, Joan; Fernandez-Cadenas, Israel
Background: Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification. Methods: Multitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (n = 362,661) and AF cohort (n = 1,030,836). We considered significant variants and replicated those variants with MTAG p-value < 5 × 10-8 influencing both traits (GWAS-pairwise) with a p-value < 0.05 in the original GWAS and in an independent cohort (n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort. Results: We found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1, and ZEB2. KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension. Conclusion: The loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF.
Effect of a mobile-based intervention on mental health in frontline healthcare workers against COVID-19: Protocol for a randomized controlled trial
(Wiley, 2021-06) Serrano-Ripoll, Maria Jesus; Ricci-Cabello, Ignacio; Jiménez, Rafael; Zamanillo Campos, Rocío; Yañez, Aina M; Bennasar-Veny, Miquel; Sitges, Carolina; Gervilla Garcia, Elena; Leiva Rus, Alfonso; García-Campayo, Javier; García-Buades, M Esther; Garcia Toro, Mauro; Pastor-Moreno, Guadalupe; Ruiz-Perez, Isabel; Alonso-Coello, Pablo; Llobera Cànaves, Joan; Fiol-deRoque, Maria Antonia
To evaluate the impact of a psychoeducational, mobile health intervention based on cognitive behavioural therapy and mindfulness-based approaches on the mental health of healthcare workers at the frontline against COVID-19 in Spain. We will carry out a two-week, individually randomized, parallel group, controlled trial. Participants will be individually randomized to receive the PsyCovidApp intervention or control App intervention. The PsyCovidApp intervention will include five modules: emotional skills, lifestyle behaviour, work stress and burnout, social support, and practical tools. Healthcare workers having attended patients with COVID-19 will be randomized to receive the PsyCovidApp intervention (intervention group) or a control App intervention (control group). A total of 440 healthcare workers will be necessary to assure statistical power. Measures will be collected telephonically by a team of psychologists at baseline and immediately after the 2 weeks intervention period. Measures will include stress, depression and anxiety (DASS-21 questionnaire-primary endpoint), insomnia (ISI), burnout (MBI-HSS), post-traumatic stress disorder (DTS), and self-efficacy (GSE). The study was funded in May 2020, and was ethically approved in June 2020. Trial participants, outcome assessors and data analysts will be blinded to group allocation. Despite the increasing use of mobile health interventions to deliver mental health care, this area of research is still on its infancy. This study will help increase the scientific evidence about the effectiveness of this type of intervention on this specific population and context. Despite the lack of solid evidence about their effectiveness, mobile-based health interventions are already being widely implemented because of their low cost and high scalability. The findings from this study will help health services and organizations to make informed decisions in relation to the development and implementation of this type of interventions, allowing them pondering not only their attractive implementability features, but also empirical data about its benefits. NCT04393818 (ClinicalTrials.gov identifier). May 2020.
Vitamin D recommendations in clinical guidelines: A systematic review, quality evaluation and analysis of potential predictors.
(Wiley, 2021-11) Fraile Navarro, David; López García-Franco, Alberto; Niño de Guzmán, Ena; Rabassa, Montserrat; Zamanillo Campos, Rocío; Pardo-Hernández, Héctor; Ricci-Cabello, Ignacio; Canelo-Aybar, Carlos; Meneses-Echavez, Jose F; Yepes-Nuñez, Juan José; Kuindersma, Jesse; Gich Saladich, Ignasi; Alonso-Coello, Pablo
Background: Vitamin D has been widely promoted for bone health through supplementation and fortification of the general adult population. However, there is growing evidence that does not support these strategies. Our aim is to review the quality and recommendations on vitamin D nutritional and clinical practice guidelines and to explore predictive factors for their direction and strength. Methods: We searched three databases and two guideline repositories from 2010 onwards. We performed a descriptive analysis, a quality appraisal using AGREE II scores (Appraisal of Guidelines Research and Evaluation) and a bivariate analysis evaluating the association between direction and strength of recommendations, AGREE II domains' scores and pre-specified characteristics. Results: We included 34 guidelines, 44.1% recommended, 26.5% suggested and 29.4% did not recommend vitamin D supplementation. Guidelines that scored higher for "editorial independence" and "overall quality score" were less likely to recommend or suggest vitamin D supplementation (median 68.8 vs 35.4; P = .001 and 58.3 vs 37.5; P = .02). Guidance produced by government organisations and those that reported source of funding were associated with higher AGREE II scores. Unclear role of source of funding was associated with recommending or suggesting vitamin D supplementation (P = .034). Editorial independence was an independent predictor for recommending or suggesting vitamin D supplementation (OR 1.09; CI95% 1.02 to 1.16; P = .006). Conclusions: Policymakers, clinicians and patients should be aware that lower quality guidelines and those reporting conflicts of interest are more likely to promote vitamin D supplementation. Guideline organisations should improve the quality of their recommendations' development and the management of conflicts of interest. Users and editors should be aware of these findings when using and appraising guidelines.
Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial
(Oxford University Press, 2021-05-01) Pujol, Miquel; Miró, José María; Shaw, Evelyn; Aguado, José María; San-Juan, Rafael; Puig-Asensio, Mireia; Pigrau, Carles; Calbo, Esther; Montejo, Miguel; Rodriguez-Alvarez, Regino; Garcia-Pais, Maria-Jose; Pintado, Vicente; Escudero-Sanchez, Rosa; Lopez-Contreras, Joaquin; Morata, Laura; Montero, Milagros; Andres, Marta; Pasquau, Juan; Arenas, Maria-del-Mar; Padilla, Belen; Murillas, Javier; Jover-Saenz, Alfredo; Lopez-Cortes, Luis Eduardo; Garcia-Pardo, Graciano; Gasch, Oriol; Videla, Sebastian; Hereu, Pilar; Tebe, Cristian; Pallares, Natalia; Sanllorente, Mireia; Dominguez, Maria-Angeles; Camara, Jordi; Ferrer, Ana; Padulles, Ariadna; Cuervo, Guillermo; Carratalà, Jordi; MRSA Bacteremia (BACSARM) Trial Investigators
Background. We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. Methods. A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. Results. of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). Conclusions. Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events.
RP11-362K2.2:RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis
(Multidisciplinary Digital Publishing Institute (MDPI), 2021-07) Muiño, Elena; Carcel-Marquez, Jara; Carrera, Caty; Llucia-Carol, Laia; Gallego-Fabrega, Cristina; Cullell, Natalia; Lledos, Miquel; Castillo, Jose; Sobrino, Tomas; Campos, Francisco; Rodriguez-Castro, Emilio; Millan, Monica; Muñoz-Narbona, Lucia; Bustamante, Alejandro; Lopez-Cancio, Elena; Ribo, Marc; Alvarez-Sabin, Jose; Jimenez-Conde, Jordi; Roquer, Jaume; Giralt-Steinhauer, Eva; Soriano-Tarraga, Carolina; Vives-Bauza, Cristofol; Diaz Navarro, Rosa; Tur Campos, Silvia; Obach, Victor; Arenillas, Juan Francisco; Segura, Tomas; Serrano-Heras, Gemma; Marti-Fabregas, Joan; Delgado-Mederos, Raquel; Camps-Renom, Pol; Prats-Sanchez, Luis; Guisado, Daniel; Guasch, Marina; Marin, Rebeca; Martinez-Domeno, Alejandro; Freijo Guerrero, Maria del Mar; Moniche, Francisco; Cabezas, Juan Antonio; Castellanos, Mar; Krupinsky, Jerzy; Strbian, Daniel; Tatlisumak, Turgut; Thijs, Vincent; Lemmens, Robin; Slowik, Agnieszka; Pera, Joanna; Heitsch, Laura; Ibañez, Laura; Cruchaga, Carlos; Dhar, Rajat; Lee, Jin-Moo; Montaner, Joan; Fernandez-Cadenas, Israel; International Stroke Genetic Consortium; Spanish Stroke Genetic Consortium
Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 x 10(-8)) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 x 10(-8)) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer's disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-beta, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.

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