SAS - Hospital Universitario Virgen del Rocío
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Publication Fibrilación y flutter auricular: proceso asistencial.(Consejería de Salud y Consumo, 2025) Pérez Cabeza, Alejando Isidoro; Fernández Gutiérrez, Beatriz; Castillo Moraga, Maria José; Del Río Lechuga, Ana; Gil Pérez, Rocío; Montecatine Alonso, Elena; Morano Venegas, Francisco José; Moya Roldán, Susana; Pérez Sánchez, Soledad; Rodríguez Martorell, Francisco Javier; Romero Ruiz, Adolfo; Suero Méndez, Coral; Forcada Falcón, Mercedes; [Pérez Cabeza,AI; Romero Ruiz,A] Hospital Universitario Virgen de la Victoria.; [Fernández Gutiérrez,B; Suero Méndez,C] Hospital Axarquía.; [Castillo Moraga,MJ] Zona básica Sanlúcar de Barrameda. Jerez-Costa Noroeste de Cádiz.; [Del Río Lechuga,A] Hospital Universitario de Jerez de la Frontera.; [Gil Pérez,R] Distrito Guadalhorce. Málaga.; [Montecatine Alonso,E; Rodríguez Martorell,FJ] Hospital Universitario Virgen del Rocío.; [Morano Venegas,FJ] DCCU Móvil Condado Campiña. Huelva.; [Moya Roldán,S] Hospital Universitario San Cecilio.; [Pérez Sánchez,S] Hospital Universitario Virgen Macarena.; [Forcada Falcón,M] Consejería de Salud y Consumo.Los Procesos Asistenciales son las herramientas que desde la Consejería de Salud y Consumo se ponen a disposición de las personas y profesionales para conseguir disminuir la variabilidad y facilitar la coordinación mediante una serie de recomendaciones que aportan calidad a la asistencia sanitaria. Fibrilación y flutter auricular ya fueron incluidos en el Proceso Asistencial Integrado Arritmias en 2003 como un subproceso. Actualmente debido a la evolución de los conocimientos y evidencias surgidas en los últimos años, se ha considerado necesaria la elaboración de un Proceso Asistencial específico.Publication Assessing the value of moderate‐to‐severe atopic dermatitis treatment using multi‐criteria decision analysis (MCDA)(Wiley, 2024-01-01) Pereyra-Rodriguez, Jose Juan; Poveda, José Luis; Rivero, Alvaro; Serra-Baldrich, Esther; Silvestre, Juan Francisco; Armario-Hita, José Carlos; Calleja, Miguel Angel; Carrascosa, Jose Manuel; Florez, Angeles; Herranz, Pedro; Comellas, Marta; Ortiz de Frutos, Francisco Javier; [Pereyra-Rodríguez,JJ] Dermatology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain.; [Armario-Hita,JC] Dermatology Department, Hospital Universitario de Puerto Real, University of Cádiz, Cádiz, Spain.; [Carrascosa,JM] Pharmacy Department, Hospital Universitario Virgen Macarena, Sevilla, Spain.The increased understanding of atopic dermatitis (AD) pathophysiology has shed light on the underlying immunologic mechanisms and spurred the development of novel, more precisely targeted therapies. As new agents become available, assessing their added value is advisable. Yet the value of novel health interventions sometimes remains largely unmeasured and inadequately understood. Value assessment is challenging since it involves assessing the extent to which it meets current unmet needs. Therefore, it is necessary to establish the most relevant health outcomes from different stakeholders' perspectives.Publication Embarazo, parto y puerperio: proceso asistencial. 4ª ed(Consejería de Salud y Consumo, 2024) Cerrillos González, Lucas; Gallardo Avilés, Raquel; Arribas Mir, Lorenzo; Baeyens Fernández, Jose Antonio; Cedeño Benavides, Tania; Peña Caballero, Manuela; Rodríguez Soto, Carmen; Urbano Priego, Manuela; Forcada Falcón, Mercedes; [Cerrillos González,L] Hospital Universitario Virgen del Rocío.; [Gallardo Avilés,R; Forcada Falcón,M] Consejería de Salud y Consumo.; [Arribas Mir,L; Cedeño Benavides,T] Distrito Sanitario de Atención Primaria Granada Metropolitano.; [Baeyens Fernández,JA] Área de Gestión Sanitaria Granada Nordeste.; [Peña Caballero,M] Hospital Universitario Materno-infantil Virgen de las Nieves.; [Rodríguez Soto,C] Distrito Sanitario de Atención Primaria Sevilla.; [Urbano Priego,M] Distrito Sanitario de Atención Primaria Córdoba-Guadalquivir.El Proceso Asistencial se ha reafirmado como una herramienta de mejora continua, ordenando los diferentes flujos de trabajo, integrando el conocimiento actualizado y mejorando los resultados en salud, todo ello gracias a la implicación de los profesionales y a su capacidad para introducir la idea de mejora continua en la calidad de sus procesos.Publication Vol. 30, nº 12. Análisis de situación epidemiológica de enfermedad neumocócica invasiva causada por serotipo 4 en Andalucía: 2022-2024.(Consejería de Salud y Consumo, 2025-03-21) Servicio de Vigilancia y Salud LaboralEnfermedades de Declaración Obligatoria por provincias. Semana 11/2025 y acumulado desde la semana 01/2025. Datos provisionales. Incluye además el artículo titulado “Análisis de situación epidemiológica de enfermedad neumocócica invasiva causada por serotipo 4 en Andalucía: 2022-2024”, de “Elvira Marín Caba, Esteban Pérez Morilla, Virtudes Gallardo García, Enrique Pérez Ostos, Nicola Lorusso”.Publication Vol. 30, nº 09-10. Informe sobre adicciones comportamentales y otros trastornos adictivos en España: 2024(Consejería de Salud y Consumo, 2025-03-07) Servicio de Vigilancia y Salud LaboralEnfermedades de Declaración Obligatoria por provincias. Semana 09/2025 y acumulado desde la semana 01/2025. Datos provisionales. Incluye además el artículo titulado “Informe sobre adicciones comportamentales y otros trastornos adictivos en España: 2024”, de “Carla Torralba Suárez”.Publication Aumento de la incidencia del cáncer testicular en España a pesar del descenso de la mortalidad: un análisis edad-periodo-cohorte(Elsevier España, 2024-10-01) Cayuela, L; Cabrera Fernández, S.; Pereyra-Rodriguez, Jose Juan; Hernandez-Rodriguez, J.C; Cayuela, A; [Cabrera-Fernández,S] 061 Centro de Emergencias Sanitarias, Servicio Andaluz de Salud, Andalucía, España; [Hernandez-Rodriguez,JC] Servicio de Dermatología, Hospital Universitario Virgen del Rocío, Sevilla, España; [Cayuela,A] Unidad de Salud Pública, Prevención y Promoción de la Salud, Área de Gestión Sanitaria Sur de Sevilla, Sevilla, EspañaObjetivo Actualizar la información sobre la incidencia y mortalidad por cáncer testicular (TC) en España entre 1990 y 2019. Métodos Se analizaron datos de la Carga Global de Enfermedades (GBD) para calcular las tasas de incidencia y mortalidad estandarizadas por edad (TIEE y TMEE). Se utilizó la regresión Joinpoint y el modelo edad-periodo-cohorte (EP- C ) para analizar las tendencias y los efectos de la edad, el período y la cohorte de nacimiento. Resultados Se observó una sorprendente duplicación de la incidencia de CT, de 3,09 a 5,40 por 100.000 hombres (aumento anual del 1,9%), mientras que las tasas de mortalidad se mantuvieron estables e incluso disminuyeron en los grupos de menor edad (de 0,34 a 0,26 por 100.000, disminución anual del 0,8%). El análisis Joinpoint reveló cuatro periodos distintos de aumento de la incidencia, con una ralentización reciente. El modelo EPC puso de manifiesto un aumento constante del riesgo de incidencia con cada generación sucesiva nacida después de 1935, que contrasta con un descenso progresivo del riesgo de mortalidad en todas las cohortes, especialmente marcado para los nacidos a partir de los años sesenta. Conclusiones La incidencia del CT aumenta en España, mientras que la mortalidad se mantiene estable o incluso disminuye. Existe un efecto generacional en la incidencia, con mayor riesgo para las generaciones más jóvenes. Se necesitan más investigaciones para comprender las causas del aumento de la incidencia y desarrollar estrategias de prevención.Publication Impact on hospital mortality of catheter removal and adequate antifungal therapy in Candida spp. bloodstream infections(Oxford University Press, 2013-05) Garnacho-Montero, José; Diaz-Martin, Ana; García-Cabrera, Emilio; Ruiz Perez de Pipaon, Maite; Hernandez-Caballero, Clara; Lepe-Jimenez, Jose A.; [Garnacho-Montero,J; Diaz-Martin,A; Hernandez-Caballero,C] Critical Care and Emergency Department, Intensive Care Unit, Virgen del Rocio University Hospital, Sevilla, Spain.; [Garcia-Cabrera,E; Ruiz-PerezdePipaon,M; Hernandez-Caballero,C; Lepe-Jimenez,A] Instituto de Biomedicina de Sevilla (IBIS) Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Sevilla, Spain.; [Garnacho-Montero,J;Diaz-Martin,A; Garcia-Cabrera,E] Spanish Network for Research in Infectious Disease (REIPI), Virgen del Rocio University Hospital, Sevilla, Spain.; [Ruiz-PerezdePipaon,M; Lepe-Jimenez,A] Infectious Disease, Microbiology and Preventive Medicine Clinical Unit, Virgen del Rocio University Hospital, Sevilla, Spain.; Ministerio de Ciencia e Innovacion; Instituto de Salud Carlos III; European Development Regional Fund ‘A way to achieve Europe’ ERDF; Spanish Network for Research in Infectious DiseasesWe set out to identify the prognostic factors in adult patients with Candida spp. bloodstream infection, assessing the impact on in-hospital mortality of catheter removal and adequacy of antifungal therapy.Patients with positive blood culture for Candida spp. and a central venous catheter in place at the time of candidaemia were included. Data collected included demographics, underlying diseases, severity of illness, clinical presentation, catheter withdrawal and adequacy of empirical therapy.We included 188 patients (mortality 36.7). The mortality rate was 34.9 (23/66) in patients with early adequate antifungal treatment and 18.9 (7/37) in patients with early adequate antifungal therapy and catheter withdrawal in the first 48 h. The APACHE (Acute Physiology and Chronic Health Evaluation) II score on the day of candidaemia [adjusted hazard ratio (aHR) 1.12; 95 CI 1.061.17; P0.001] was associated with death whereas early adequate therapy (aHR 0.4; 95 CI 0.230.83; P0.012) and catheter withdrawal (aHR 0.34; 95 CI 0.160.70; P0.03) were protective factors. In primary candidaemia, mortality was 28 (14/50) in patients with adequate therapy and decreased to 17.7 (6/34) in patients with both interventions in the first 48 h. Catheter removal was a protective factor and adequacy of antifungal therapy in the first 48 h showed a strong tendency to protection against death (aHR 0.46; 95 CI 0.191.08; P0.07). In secondary non-catheter-related candidaemia, only early adequate therapy was a protective factor for mortality.Delay in catheter withdrawal and in administration of adequate antifungal therapy was associated with increased mortality in candidaemic patients. Catheter management did not influence the prognosis of secondary non-catheter-related candidaemia.Publication Determinants of outcome in patients with bacteraemic pneumococcal pneumonia: importance of early adequate treatment.(Taylor&Francis, 2009-10-14) Garnacho-Montero, José; García-Cabrera, Emilio; Diaz-Martín, Ana; Lepe, José Antonio; Iraurgi-Arcarazo, Patricia; Jiménez-Alvarez, Rocio; Revuelto-Rey, Jaume; Aznar, Javier; [Garnacho-Montero,J; Diaz-Martín,A; Jiménez-Alvarez,R; Revuelto-Rey,J] Intensive Care Unit, Hospital Universitario Virgen del Rocío, Seville, Spain.; [Lepe-Jiménez,JA; Iraurgi-Arcarazo,P; Aznar-Martín,J] Microbiology Department, Hospital Universitario Virgen del Rocío, Seville, Spain.; Consejería de Salud de la Junta de Andalucía; Ministerio de Sanidad y Consumo; Instituto de Salud Carlos IIIWe set out to determine the factors influencing mortality in 125 adult patients with bacteraemic pneumococcal community-acquired pneumonia (CAP), assessing the impact on outcomes of early adequate therapy in particular. Presumed prognostic factors with p < 0.1 in the unadjusted model were subjected to multivariate Cox regression analysis, with in-hospital and 90-day mortalities as the dependent variables. A time period of >4 h from admission to start of adequate antibiotic treatment (adjusted hazard ratio (aHR) 2.62, 95% confidence interval (CI) 1.06-6.45; p =0.037) and severe sepsis or septic shock (aHR 5.06, 95% CI 1.63-15.71; p = 0.005) were independently associated with in-hospital mortality. Variables associated with 90-day mortality were Charlson comorbidity index (aHR 1.17, 95% CI 1.02-1.34; p = 0.018), severe sepsis or septic shock (aHR 3.03, 95% CI 1.22-7.51; p = 0.016) and delay of adequate antibiotic therapy >4 h (aHR 2.21, 95% CI 1.01-4.86; p = 0.048). The use of combination therapy was not included in these models but was a protective factor for delayed adequate therapy (aHR 0.53, 95% CI 0.29-0.95; p = 0.033). Administration of adequate antimicrobial therapy within 4 h of arrival is a critical determinant of survival in patients with bacteraemic pneumococcal CAP.Publication Surgical treatment for infective endocarditis in elderly patients(Elsevier, 2011-06-06) Ramirez-Duque, N.; García-Cabrera, Emilio; Ivanova-Georgieva, R.; Noureddine, Mariam; Lomas, J. M.; Hidalgo-Tenorio, Carmen; Plata, A.; Gálvez-Acebal, Juan; Ruiz-Morales, J.; de la Torre-Lima, J.; Reguera-Iglesias, José María; Martinez-Marcos, F. J.; de Alarcón, Arístides; [Ramirez-Duque,N; Garcia-Cabrera,E; Alarcon,A] Hospital Virgen del Rocio, Sevilla, Spain.; [Ivanova-Georgieva,R; Ruiz-Morales;J;] Hospital Virgen de la Victoria, Málaga, Spain.; [Noureddine,M; de la Torre-Lima,J;] Hospital Costa del Sol, Marbella, Spain.; [Lomas,JM; Martinez-Marcos,FJ] Hospital Juan Ramón Jiménez, Huelva, Spain.; [Hidalgo-Tenorio,C] Hospital Virgen de las Nieves, Granada, Spain.; [Plata,A; Reguera,JM] Hospital Carlos Haya, Malaga, Spain.; Ministerio de Sanidad y Consumo; Instituto de Salud Carlos III; Spanish Network for the Research in Infectious Diseases; Grupo para el Estudio de las Infecciones Cardiovasculares de la Sociedad Andaluza de Enfermedades Infecciosas (SAEI)Objectives: We evaluate the clinical, echographic and prognostic characteristics of infective endocarditis (IE) in a large population of elderly patients, and the results of surgical approach.Methods: Multicentric, prospective, observational cohort study with 961 consecutive left-sided IE: ;356 patients aged >= 65 years were compared with 605 younger. Indications for cardiac surgery, potential surgical risk, time and outcome, were compared.Results: Hospital-acquired endocarditis, comorbidity, renal failure and septic shock were more frequent in elderly, but embolisms were less. Intracardiac destruction and ventricular failure were similar in both groups, but significantly fewer elderly patients underwent cardiac surgery (36% vs 51%; p < 0.01), and this group showed a worse outcome (43.2% of mortality vs 27% in younger; p < 0.01), resulting age as an independent predictor of mortality (OR: 1.02 CI95%: 1.01-1.03). Compared with medical treatment, surgery showed lower percentages ofmortality compared with medical treatment (23.3% vs 31.3%; p = 0.03) in younger group, but a high mortality was observed with both procedures (47.6% vs 40.3%; p = 0.1) in the elderly.Conclusions: Although similar percentages of heart failure and intracardiac complications, increasing age is associated with higher mortality in IE. Lower rates of surgical treatment and a worse outcome after operation are common features in elderly patients.Publication Genetic variants of the MBL2 gene are associated with mortality in pneumococcal sepsis(Elsevier, 2012-05) Garnacho-Montero, José; García-Cabrera, Emilio; Jiménez-Álvarez, Rocio; Díaz-Martín, Ana; Revuelto-Rey, Jaume; Aznar-Martín, Javier; Garnacho-Montero, Carmen; [Garnacho-Montero,J; Jimenez-Alvarez,R; Diaz-Martin,A; Revuelto-Rey,J] Critical Care and Emergency Department, Hospital Universitario Virgen del Rocío, Seville, Spain.; [Garnacho-Montero,J; Garcia-Cabrera,E; Aznar-Martin,J] Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, Spain.; [Garcia-Cabrera,E] Spanish Network for Research in Infectious Disease (REIPI), Hospital Universitario Virgen del Rocío, Seville, Spain.; [Aznar-Martin,J] Infectious Disease, Microbiology and Preventive Medicine Clinical Unit, Hospital Universitario Virgen del Rocío, Seville, Spain.; [Garnacho-Montero,C] Department of Cytology and Histology, Faculty of Medicine, University of Seville, Seville, Spain.Studies evaluating associations between polymorphisms of innate immunity genes and prognosis of infectious diseases have yielded conflicting results. Our aim was to assess the impact on mortality of different genotypic variants of the innate immunity in patients with pneumococcal sepsis. All adults admitted to the hospital with diagnosis of sepsis caused by Streptococcus pneumoniae were enrolled and single-nucleotide polymorphisms (SNP) in mannose-binding lectin 2 (MBL2), toll-like receptor (TLR) 2, TLR4, and Fcγ receptor IIa genes were genotyped. Underlying diseases, severity of illness, and antibiotic management were also recorded. We included 117 patients: 98 pneumonias (83.6%), 17 meningitis (14.5%), and 2 patients (1.9%) with primary pneumococcal bacteremia. Allelic variants of the MBL2 gene (individuals heterozygous or homozygous for one of the 3 allelic variants B, C, and D: AO/OO) were present in 37 patients (32%), T399I polymorphism in TLR4 in 19 (16.2%), TLR4 D299G/T399I in 11 (9.4%), TLR2 R753Q in 3 (2.5%), and FcγRIIa-R/R131 in 26 patients (23%). Factors associated independently with in-hospital mortality were SNP MBL2 AO/OO (adjusted hazard ratios [aHR] 3.2, 95% confidence interval [CI] 1.01-9.8) and septic shock (aHR 15.3, 95% CI 3.5-36.5), whereas first adequate antibiotic dose ≤ 4 h was a protective factor (aHR 0.2, 95% CI 0.06-0.8). SNP MBL2 AO/OO (aHR 2.2, 95% CI 1.1-8.1) remained as a variable independently associated with 90-day mortality. In conclusion, variant alleles in the MBL2 gene are independently associated with in-hospital and medium-term mortalities in patients admitted to the hospital with pneumococcal sepsis.Publication Risk Factors for Fluconazole-Resistant Candidemia(American Society for Microbiology, 2010-08) Garnacho-Montero, José; Diaz-Martin, Ana; García-Cabrera, Emilio; Perez de Pipaon, Maite Ruiz; Hernandez-Caballero, Clara; Aznar-Martin, Javier; Cisneros, José Miguel; Ortiz-Leyba, Carlos; [Garnacho-Montero,J; Diaz-Martin,A; Hernandez-Caballero,C; Ortiz-Leyba,C] Critical Care and Emergency Department, Intensive Care Unit, Virgen del Rocío University Hospital, Seville, Spain.; [Garcia-Cabrera,E] Spanish Network for Research in Infectious Disease (REIPI).; [Ruiz-Pérez-de-Pipaon,M; Aznar-Martin,J; Cisneros,JM] Infectious Disease, Microbiology and Preventive Medicine Clinical Unit, Virgen del Rocío University Hospital, Seville, Spain.; [Garnacho-Montero,J; Diaz-Martin,A; Garcia-Cabrera,E; Aznar-Martin,J; Cisneros,JM; Ortiz-Leyba,C] The Seville Biomedical Research Institute, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla,Seville, Spain.; Spanish Network for the Research in Infectious Diseases; Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III; European Development Regional FundPrevious studies have sought to determine the risk factors associated with candidemia caused by non-albicans Candida spp. or with potentially fluconazole-resistant Candida spp. (C. glabrata and C. krusei). Non-albicans Candida strains are a heterogeneous group that includes species with different levels of virulence, and only a limited number of C. glabrata isolates are resistant to fluconazole. We set out to identify the risk factors associated with microbiologically proven fluconazole-resistant candidemia. A prospective study including adult patients with candidemia was performed. Data were collected on patient demographics; underlying diseases; exposure to corticosteroids, antibiotics, or fluconazole; and invasive procedures. Risk factors associated either with non-albicans Candida spp. or potentially fluconazole-resistant Candida spp. (C. glabrata or C. krusei) or with Candida spp. with microbiologically confirmed fluconazole resistance were assessed using logistic regressions. We included 226 candidemia episodes. Non-albicans Candida isolates accounted for 53.1% of the fungal isolates, but only 18.2% of the cases were caused by potentially fluconazole-resistant organisms. Thirty isolates exhibited microbiologically confirmed fluconazole resistance. The multivariate analysis revealed that independent predictors associated with fluconazole-resistant Candida spp. were neutropenia (odds ratio [OR] = 4.94; 95% confidence interval [CI] = 1.50 to 16.20; P = 0.008), chronic renal disease (OR = 4.82; 95% CI = 1.47 to 15.88; P = 0.01), and previous fluconazole exposure (OR = 5.09; 95% CI = 1.66 to 15.6; P = 0.004). Independently significant variables associated with non-albicans Candida bloodstream infection or with potentially fluconazole-resistant Candida spp. did not include previous fluconazole exposure. We concluded that prior fluconazole treatment is an independent risk factor only for candidemia caused by microbiologically confirmed fluconazole resistant species. Our findings may be of value for selecting empirical antifungal therapy.Publication Superinfection during treatment of nosocomial infections with tigecycline(Springer, 2010-05-16) García-Cabrera, Emilio; Jiménez-Mejías, Manuel E.; Gil-Navarro, María Victoria; Gómez-Gómez, M J; Ortiz-Leyba, C; Cordero, Elisa; Pachón, J; [García-Cabrera,E; Jiménez-Mejías,ME; Gil Navarro,MV; Gómez-Gómez,MJ; Ortiz-Leyba,C; Cordero,E; Pachón,J] Hospital Universitario Virgen del Rocío, Seville, Spain.; Instituto de Salud Carlos III-FEDER; Ministerio de Ciencia e InnovaciónWe performed a retrospective and observational study of 51 patients treated with tigecycline, as the treatment for nosocomial infections due to multidrug-resistant microorganisms, to evaluate the superinfection rate and their etiologies. Superinfections were diagnosed in 12 (23.5%) patients (seven due to Pseudomonas aeruginosa, 13.7%) and one patient had P. aeruginosa colonization. Five patients with superinfection died (41.6%), three due to superinfections and two to underlying diseases. The superinfection rate observed during tigecycline treatment is higher than that previously reported. Pseudomonas aeruginosa is the most frequent agent, being the cause of 58.5% of all superinfections.Publication Modified sequential multiplex PCR for determining capsular serotypes of invasive pneumococci recovered from Seville.(Elsevier, 2010-09) Iraurgui, P; Torres, María José; Vazquez, I; García-Cabrera, Emilio; Obando, Ignacio; Garnacho-Montero, José; Aznar, Javier; [Iraurgui,P; Gandia,A; Vazquez,I; Garnacho,J; Aznar,J] Microbiology Service, Hospital Universitario Virgen del Rocío, Sevilla, Spain; [Torres,MJ; Cabrera,EG; Aznar,J] Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Sevilla, Spain; [Obando,I] Paediatric Service,, Hospital Universitario Virgen del Rocío, Sevilla, Spain; [Garnacho,J] Intensive Care Unit, Hospital Universitario Virgen del Rocío, Sevilla, SpainThe heptavalent pneumococcal vaccine's introduction resulted in a decline in invasive disease caused by Streptococcus pneumoniae, but was accompanied by an increase in non-vaccine serotypes. We evaluated a modified scheme of the sequential multiplex PCRs adapted to the prevalence of serotypes in Seville (Spain) for determining capsular serotypes of S. pneumoniae invasive clinical isolates. In adults, the modified scheme allowed us to type 73% with the first three reactions, and 92% with two additional PCRs. In paediatric patients, it allowed us to type 73.5% with the first three reactions, and 90% with the two additional PCRs. The multiplex PCR approach was successfully adapted to target the serotypes most prevalent in Seville.Item Overexpression of Canonical Prefoldin Associates with the Risk of Mortality and Metastasis in Non-Small Cell Lung Cancer.(MDPI AG, 2020-04-24) Peñate, Xenia; Praena-Fernandez, Juan Manuel; Romero-Pareja, Pedro; Enguix-Riego, María Del Valle; Payan-Bravo, Laura; Vieites, Begoña; Gomez-Izquierdo, Lourdes; Jaen-Olasolo, Javier; Rivin-Del-Campo, Eleonor; Reyes, Jose Carlos; Chavez, Sebastian; Lopez-Guerra, Jose Luis; Spanish Ministry of Economy and Competitiveness; the Andalusian Government; University of SevilleCanonical prefoldin is a protein cochaperone composed of six different subunits (PFDN1 to 6). PFDN1 overexpression promotes epithelial-mesenchymal transition (EMT) and increases the growth of xenograft lung cancer (LC) cell lines. We investigated whether this putative involvement of canonical PFDN in LC translates into the clinic. First, the mRNA expression of 518 non-small cell LC (NSCLC) cases from The Cancer Genome Atlas (TCGA) database was evaluated. Patients with PFDN1 overexpression had lower overall survival (OS; 45 vs. 86 months; p = 0.034). We then assessed the impact of PFDN expression on outcome in 58 NSCLC patients with available tumor tissue samples. PFDN1, 3, and 5 overexpression were found in 38% (n = 22), 53% (n = 31), and 41% (n = 24) of tumor samples. PFDN1, 3, and 5 overexpression were significantly associated with lower OS, lower disease-free survival (DFS), and lower distant metastasis-free survival (DMFS) for PFDN1 and 3 with a trend for PFDN5. In multivariate analysis, PFDN5 retained significance for OS (hazard ratio (HR) 2.56; p = 0.007) and PFDN1 for DFS (HR 2.53; p = 0.010) and marginally for DMFS (HR 2.32; p = 0.053). Our results indicate that protein response markers, such as PFDN1, 3, and 5, may complement mRNA signatures and be useful for determining the most appropriate therapy for NSCLC patients.Item Analysis of Common Pathways and Markers From Non-Alcoholic Fatty Liver Disease to Immune-Mediated Diseases.(Frontiers Research Foundation, 2021-11-24) Gallego-Duran, Rocio; Montero-Vallejo, Rocio; Maya-Miles, Douglas; Lucena, Ana; Martin, Franz; Ampuero, Javier; Romero-Gomez, Manuel; Consejería de Salud de la Junta de Andalucía; Ministerio de Economía y Competitividad; Instituto de Salud Carlos III; Fondo Europeo de Desarrollo Regional (FEDER)Metabolic associated fatty liver disease (MAFLD) is the most prevalent form of liver disease worldwide, accounting for a high liver-related mortality and morbidity with extensive multi-organ involvement. This entity has displaced viral hepatitis as the main cause of severe forms of hepatic diseases, although the onset and transition of MAFLD stages still remains unclear. Nevertheless, innate and adaptive immune responses seem to play an essential role in the establishment and further progression of this disease. The immune system is responsible of safeguard and preserves organs and systems function, and might be altered under different stimuli. Thus, the liver suffers from metabolic and immune changes leading to different injuries and loss of function. It has been stablished that cell-cell crosstalk is a key process in the hepatic homeostasis maintenance. There is mounting evidence suggesting that MAFLD pathogenesis is determined by a complex interaction of environmental, genetic and host factors that leads to a full plethora of outcomes. Therefore, herein we will revisit and discuss the interplay between immune mechanisms and MAFLD, highlighting the potential role of immunological markers in an attempt to clarify its relationship.Item AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis.(MDPI AG, 2019-02-24) Trillo-Contreras, Jose Luis; Toledo-Aral, Juan Jose; Echevarria, Miriam; Villadiego, JavierAquaporin 1 (AQP1), expressed in epithelial cells of the choroid plexus, and aquaporin 4 (AQP4) present in ependymal cells and glia limitants have been proposed to play a significant role in cerebrospinal fluid (CSF) production and homeostasis. However, the specific contribution of each water channel to these functions remains unknown, being a subject of debate during the last years. Here, we analyzed in detail how AQP1 and AQP4 participate in different aspects of the CSF homeostasis such as the load and drainage of ventricles, and further explored if these proteins play a role in the ventricular compliance. To do that, we carried out records of intraventricular pressure and CSF outflow, and evaluated ventricular volume by magnetic resonance imaging in AQP1-/-, AQP4-/-, double AQP1-/--AQP4-/- knock out and wild type mice controls. The analysis performed clearly showed that both AQPs have a significant participation in the CSF production, and additionally revealed that the double AQP1-AQP4 mutation alters the CSF drainage and the ventricular compliance. The data reported here indicate a significant extra-choroidal CSF formation mediated by AQP4, supporting the idea of an important and constant CSF production/absorption process, sustained by efflux/influx of water between brain capillaries and interstitial fluid. Moreover, our results suggest the participation of AQPs in structural functions also related with CSF homeostasis such as the distensibility capacity of the ventricular system.Item The role of bronchoscopy in patients with SARS-CoV-2 pneumonia.(2021-07-12) Arenas-De Larriva, Marisol; Martín-DeLeon, Roberto; Urrutia Royo, Blanca; Fernández-Navamuel, Iker; Gimenez Velando, Andrés; Nuñez García, Laura; Centeno Clemente, Carmen; Andreo García, Felipe; Rafecas Codern, Albert; Fernández-Arias, Carmen; Pajares Ruiz, Virginia; Torrego Fernández, Alfons; Rajas, Olga; Iturricastillo, Gorane; Garcia Lujan, Ricardo; Comeche Casanova, Lorena; Sánchez-Font, Albert; Aguilar-Colindres, Ricardo; Larrosa-Barrero, Roberto; García García, Ruth; Cordovilla, Rosa; Núñez-Ares, Ana; Briones-Gómez, Andrés; Cases Viedma, Enrique; Franco, José; Cosano Povedano, Javier; Rodríguez-Perálvarez, Manuel Luis; Cebrian Gallardo, Jose Joaquin; Nuñez Delgado, Manuel; Pavón-Masa, María; Valdivia Salas, Maria Del Mar; Flandes, JavierThe role of bronchoscopy in coronavirus disease 2019 (COVID-19) is a matter of debate. This observational multicentre study aimed to analyse the prognostic impact of bronchoscopic findings in a consecutive cohort of patients with suspected or confirmed COVID-19. Patients were enrolled at 17 hospitals from February to June 2020. Predictors of in-hospital mortality were assessed by multivariate logistic regression. A total of 1027 bronchoscopies were performed in 515 patients (age 61.5±11.2 years; 73% men), stratified into a clinical suspicion cohort (n=30) and a COVID-19 confirmed cohort (n=485). In the clinical suspicion cohort, the diagnostic yield was 36.7%. In the COVID-19 confirmed cohort, bronchoscopies were predominantly performed in the intensive care unit (n=961; 96.4%) and major indications were: difficult mechanical ventilation (43.7%), mucus plugs (39%) and persistence of radiological infiltrates (23.4%). 147 bronchoscopies were performed to rule out superinfection, and diagnostic yield was 42.9%. There were abnormalities in 91.6% of bronchoscopies, the most frequent being mucus secretions (82.4%), haematic secretions (17.7%), mucus plugs (17.6%), and diffuse mucosal hyperaemia (11.4%). The independent predictors of in-hospital mortality were: older age (OR 1.06; p Bronchoscopy may be indicated in carefully selected patients with COVID-19 to rule out superinfection and solve complications related to mechanical ventilation. The presence of haematic secretions in the distal bronchial tract may be considered a poor prognostic feature in COVID-19.Item The economic burden of metastatic breast cancer in Spain.(2018-07-30) Bermejo de Las Heras, Begoña; Cortes Ramon Y Cajal, Javier; Galve Calvo, Elena; de la Haba Rodriguez, Juan; Garcia Mata, Jesus; Moreno Anton, Fernando; Pelaez Fernandez, Ignacio; Rodriguez-Lescure, Alvaro; Rodriguez Sanchez, Cesar A; Ruiz-Borrego, Manuel; Remak, Edit; Barra, Magdolna; Rivero, Maria; Soto Alvarez, JavierThe study aimed to estimate the burden of metastatic breast cancer (mBC) in Spain over 5 years. An incidence-based cost-of-illness model was developed in which a cohort of patients with mBC was followed from the diagnosis of metastatic disease over 5 years or death. Resource use data were collected through a physician survey conducted with 10 clinical experts in Spain. The model distinguished patients according to HER2 and hormonal receptor (HR) status, and followed the patient cohort in monthly cycles. The incident cohort was estimated to be 2,923 patients with mBC, consisting of 1,575 HER2-/HR+, 520 HER2+/HR+, 324 HER2+/HR-, and 503 triple negative patients. The estimated mean survival over the 5-year time period was 2.51 years, on average, with longer survival of 3.36 years for HER2+/HR+, 2.41 years for HER2-/HR+, 2.82 years for HER2+/HR- and shortest mean survival of 1.74 years for triple negative patients. The total costs were €469,92,731 for the overall population, €190,079,787 for the HER2-/HR+, €151,045,260 for the HER2+/HR+, €80,827,171 for the HER2+/HR- and €47,540,512 for the triple negative subgroups over 5 years. Per patient total costs were €160,642 on average, €120,664 for HER2-/HR+, €290,346 for HER2+/HR+, €249,152 for HER2+/HR-and €94,572 for triple negative patients over 5 years. The economic burden of mBC in Spain is significant, but differs by HER2 and HR status. HER2-/HR +patients account for the highest burden due to the prevalence of this category, but HER2+/HR +patients have the highest per patient costs.Item Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens.(Nature Publishing Group, 2021-10-20) Castaño-Bonilla, Tamara; Alonso-Dominguez, Juan M; Barragan, Eva; Rodriguez-Veiga, Rebeca; Sargas, Claudia; Gil, Cristina; Chillon, Carmen; Vidriales, Maria B; Garcia, Raimundo; Martinez-Lopez, Joaquin; Ayala, Rosa; Larrayoz, Maria J; Anguita, Eduardo; Cuello, Rebeca; Cantalapiedra, Alberto; Carrillo, Estrella; Soria-Saldise, Elena; Labrador, Jorge; Recio, Isabel; Algarra, Lorenzo; Rodriguez-Medina, Carlos; Bilbao-Syeiro, Cristina; Lopez-Lopez, Juan A; Serrano, Josefina; De-Cabo, Erik; Sayas, Maria J; Olave, Maria T; Sanchez-Garcia, Joaquin; Mateos, Mamen; Blas, Carlos; Lopez-Lorenzo, Jose L; Lainez-Gonzalez, Daniel; Serrano, Juana; Martinez-Cuadron, David; Sanz, Miguel A; Montesinos, PauFLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.Item A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine.(Wolters Kluwer Health, 2018-04-16) Cabrera-Serrano, Macarena; Mavillard, Fabiola; Biancalana, Valerie; Rivas, Eloy; Morar, Bharti; Hernandez-Lain, Aurelio; Olive, Montse; Muelas, Nuria; Khan, Eduardo; Carvajal, Alejandra; Quiroga, Pablo; Diaz-Manera, Jordi; Davis, Mark; Avila, Rainiero; Dominguez, Cristina; Romero, Norma Beatriz; Vilchez, Juan J; Comas, David; Laing, Nigel G; Laporte, Jocelyn; Kalaydjieva, Luba; Paradas, Carmen; ISCIII; FEDER “a way to achieve Europe”; AEI-MINEICO/FEDER; Australian National Health; Medical Research CouncilTo describe a large series of BIN1 patients, in which a novel founder mutation in the Roma population of southern Spain has been identified. Patients diagnosed with centronuclear myopathy (CNM) at 5 major reference centers for neuromuscular disease in Spain (n = 53) were screened for BIN1 mutations. Clinical, histologic, radiologic, and genetic features were analyzed. Eighteen patients from 13 families carried the p.Arg234Cys variant; 16 of them were homozygous for it and 2 had compound heterozygous p.Arg234Cys/p.Arg145Cys mutations. Both BIN1 variants have only been identified in Roma, causing 100% of CNM in this ethnic group in our cohort. The haplotype analysis confirmed all families are related. In addition to clinical features typical of CNM, such as proximal limb weakness and ophthalmoplegia, most patients in our cohort presented with prominent axial weakness, often associated with rigid spine. Severe fat replacement of paravertebral muscles was demonstrated by muscle imaging. This phenotype seems to be specific to the p.Arg234Cys mutation, not reported in other BIN1 mutations. Extreme clinical variability was observed in the 2 compound heterozygous patients for the p.Arg234Cys/p.Arg145Cys mutations, from a congenital onset with catastrophic outcome to a late-onset disease. Screening of European Roma controls (n = 758) for the p.Arg234Cys variant identified a carrier frequency of 3.5% among the Spanish Roma. We have identified a BIN1 founder Roma mutation associated with a highly specific phenotype, which is, from the present cohort, the main cause of CNM in Spain.