Instituto de Investigación Biomédica de Sevilla (IBIS)
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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.Item Dual Independent Roles of the p24 Complex in Selectivity of Secretory Cargo Export from the Endoplasmic Reticulum.(MDPI AG, 2020-05-22) Lopez, Sergio; Perez-Linero, Ana Maria; Manzano-Lopez, Javier; Sabido-Bozo, Susana; Cortes-Gomez, Alejandro; Rodriguez-Gallardo, Sofia; Aguilera-Romero, Auxiliadora; Goder, Veit; Muñiz, ManuelThe cellular mechanisms that ensure the selectivity and fidelity of secretory cargo protein transport from the endoplasmic reticulum (ER) to the Golgi are still not well understood. The p24 protein complex acts as a specific cargo receptor for GPI-anchored proteins by facilitating their ER exit through a specialized export pathway in yeast. In parallel, the p24 complex can also exit the ER using the general pathway that exports the rest of secretory proteins with their respective cargo receptors. Here, we show biochemically that the p24 complex associates at the ER with other cargo receptors in a COPII-dependent manner, forming high-molecular weight multireceptor complexes. Furthermore, live cell imaging analysis reveals that the p24 complex is required to retain in the ER secretory cargos when their specific receptors are absent. This requirement does not involve neither the unfolded protein response nor the retrograde transport from the Golgi. Our results suggest that, in addition to its role as a cargo receptor in the specialized GPI-anchored protein pathway, the p24 complex also plays an independent role in secretory cargo selectivity during its exit through the general ER export pathway, preventing the non-selective bulk flow of native secretory cargos. This mechanism would ensure receptor-regulated cargo transport, providing an additional layer of regulation of secretory cargo selectivity during ER export.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 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.Item Key considerations on the potential impacts of the COVID-19 pandemic on antimicrobial resistance research and surveillance.(Oxford University Press, 2021-03-27) Rodriguez-Baño, Jesus; Rossolini, Gian Maria; Schultsz, Constance; Tacconelli, Evelina; Murthy, Srinivas; Ohmagari, Norio; Holmes, Alison; Bachmann, Till; Goossens, Herman; Canton, Rafael; Roberts, Adam P; Henriques-Normark, Birgitta; Clancy, Cornelius J; Huttner, Benedikt; Fagerstedt, Patriq; Lahiri, Shawon; Kaushic, Charu; Hoffman, Steven J; Warren, Margo; Zoubiane, Ghada; Essack, Sabiha; Laxminarayan, Ramanan; Plant, Laura; Plan Nacional de I+D+i 2013–2016 and the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades; Instituto de Salud Carlos III; German Federal Ministry of Education and ResearchAntibiotic use in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients during the COVID-19 pandemic has exceeded the incidence of bacterial coinfections and secondary infections, suggesting inappropriate and excessive prescribing. Even in settings with established antimicrobial stewardship (AMS) programmes, there were weaknesses exposed regarding appropriate antibiotic use in the context of the pandemic. Moreover, antimicrobial resistance (AMR) surveillance and AMS have been deprioritised with diversion of health system resources to the pandemic response. This experience highlights deficiencies in AMR containment and mitigation strategies that require urgent attention from clinical and scientific communities. These include the need to implement diagnostic stewardship to assess the global incidence of coinfections and secondary infections in COVID-19 patients, including those by multidrug-resistant pathogens, to identify patients most likely to benefit from antibiotic treatment and identify when antibiotics can be safely withheld, de-escalated or discontinued. Long-term global surveillance of clinical and societal antibiotic use and resistance trends is required to prepare for subsequent changes in AMR epidemiology, while ensuring uninterrupted supply chains and preventing drug shortages and stock outs. These interventions present implementation challenges in resource-constrained settings, making a case for implementation research on AMR. Knowledge and support for these practices will come from internationally coordinated, targeted research on AMR, supporting the preparation for future challenges from emerging AMR in the context of the current COVID-19 pandemic or future pandemics.Item Interplay between IncF plasmids and topoisomerase mutations conferring quinolone resistance in the Escherichia coli ST131 clone: stability and resistance evolution(Springer, 2021-11-17) Rodriguez-Martinez, Jose-Manuel; Lopez-Cerero, Lorena; Garcia-Duque, Ana; Rodriguez-Bano, Jesus; Pascual, Alvaro; [Rodriguez-Martinez, Jose-Manuel] Univ Seville, Dept Microbiol, Avda Sanchez Pizjuan S-N, Seville 41009, Spain; [Lopez-Cerero, Lorena] Univ Seville, Dept Microbiol, Avda Sanchez Pizjuan S-N, Seville 41009, Spain; [Garcia-Duque, Ana] Univ Seville, Dept Microbiol, Avda Sanchez Pizjuan S-N, Seville 41009, Spain; [Rodriguez-Bano, Jesus] Univ Seville, Dept Microbiol, Avda Sanchez Pizjuan S-N, Seville 41009, Spain; [Pascual, Alvaro] Univ Seville, Dept Microbiol, Avda Sanchez Pizjuan S-N, Seville 41009, Spain; [Rodriguez-Martinez, Jose-Manuel] Univ Seville, Hosp Univ Virgen Macarena, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain; [Lopez-Cerero, Lorena] Univ Seville, Hosp Univ Virgen Macarena, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain; [Rodriguez-Bano, Jesus] Univ Seville, Hosp Univ Virgen Macarena, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain; [Pascual, Alvaro] Univ Seville, Hosp Univ Virgen Macarena, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain; [Rodriguez-Martinez, Jose-Manuel] Inst Salud Carlos III, Red Espanola Invest Patol Infecciosa REIPI, Madrid, Spain; [Lopez-Cerero, Lorena] Inst Salud Carlos III, Red Espanola Invest Patol Infecciosa REIPI, Madrid, Spain; [Rodriguez-Bano, Jesus] Inst Salud Carlos III, Red Espanola Invest Patol Infecciosa REIPI, Madrid, Spain; [Pascual, Alvaro] Inst Salud Carlos III, Red Espanola Invest Patol Infecciosa REIPI, Madrid, Spain; [Lopez-Cerero, Lorena] Hosp Univ Virgen Macarena, Unidad Enfermedades Infecciosas Microbiol & Med P, Seville, Spain; [Rodriguez-Bano, Jesus] Hosp Univ Virgen Macarena, Unidad Enfermedades Infecciosas Microbiol & Med P, Seville, Spain; [Pascual, Alvaro] Hosp Univ Virgen Macarena, Unidad Enfermedades Infecciosas Microbiol & Med P, Seville, Spain; Plan Nacional de I + D + i 2013-2016 - Joint Programming Initiative on Antimicrobial Resistance, JPIAMR; Instituto de Salud Carlos III - Joint Programming Initiative on Antimicrobial Resistance, JPIAMR; Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI); European Development Regional Fund "A way to achieve Europe," Operative program Intelligent Growth 2014-2020The Escherichia coli ST131 H30-Rx subclone vehicles CTX-M-15 plasmids and mutations in gyrA and parC conferring multidrug resistance successfully in the clinical setting. The aim of this study was (1) to investigate the relationship of specific topoisomerase mutations on the stability of IncF (CTX-M producing) plasmids using isogenic E. coli mutants and (2) to investigate the impact of the IncF-type plasmids present in the E. coli clone ST131 on the evolution of quinolone resistance. E. coli ATCC 25922 (background strain) and derived mutants encoding specific QRDR substitutions were used. Also, NGS-characterized IncFIA and IncFIB plasmids (encoding CTX-M genes) were included. Plasmid stability was evaluated by sequential dilutions into Luria broth medium without antibiotics for 7 days. Mutant frequency to ciprofloxacin was also evaluated. Moderate differences in the IncF plasmids stability were observed among E. coli ATCC 25922 and isogenic mutants. Under our experimental conditions, the fluctuation of bacteria harboring plasmids was less than 0.5-log((10)) in all cases. In the mutant frequency tests, it was observed that the presence of these IncF plasmids increased this value significantly (10-1000-fold). Quinolone resistance substitutions in gyrA or parC genes, frequently found associated with E. coli clone ST131, do not modify the stability of ST131-associated IncFIA and IncFIB plasmids under in vitro conditions. IncF-type plasmids present in E. coli clone ST131 facilitate the selection of resistance to quinolones. These results are consistent with the clinical scenario in which the combination of resistance to quinolones and beta-lactams is highly frequent in the E. coli clone ST131.Item Does Online Search Behavior Coincide with Candida auris Cases? An Exploratory Study.(MDPI AG, 2019-06-04) Saris, Katja; Meis, Jacques F; Rodriguez-Baño, Jesus ; Tacconelli, Evelina; van-de-Belt, Tom H; Voss, Andreas; European Union Seventh Framework Programme; EPI-Net COMBACTE-MAGNETCandida auris is an emerging multidrug resistant infectious yeast which is challenging to eradicate and despite available laboratory methods is still difficult to identify especially in less developed countries. To limit the rapid spread of C. auris, quick and accurate detection is essential. From the perspective of disease surveillance, additional methods of tracking this yeast are needed. In order to increase global preparedness, we explored the use of online search behavior to monitor the recent global spread of C. auris. We used Google Trends to assess online search behavior on C. auris from January 2016 until August 2018. Weekly Google Trends results were counted as hits and compared to confirmed C. auris cases obtained via publications and a global expert network of key opinion leaders. A total of 44 countries generated a hit, of which 30% (13/44) were confirmed known cases, 34% (15/44) were missed known cases, 34% (15/44) were hits for unknown cases, and 2% (1/44) were confirmed unknown cases. Conclusions: Google Trends searches is rapidly able to provide information on countries with an increased search interest in C. auris. However, Google Trends search results do not generally coincide with C. auris cases or clusters. This study did show that using Google Trends provides both insight into the known and highlights the unknown, providing potential for surveillance and tracking and hence aid in taking timely precautionary measures.Item Gender differences in quality of life in adults with long-standing type 1 diabetes mellitus.(BioMed Central Ltd., 2020-07-17) Castellano-Guerrero, Ana Maria; Guerrero, Raquel; Ruiz-Aranda, Desiree; Perea, Sofia; Pumar, Alfonso; Relimpio, Federico; Mangas, Miguel Angel; Losada, Fernando; Martinez-Brocca, Maria Asuncion; Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF)To assess gender differences in Quality of life (QoL) and in sociodemographic, clinical and psychological factors associated with impaired QoL in adults with long-standing type 1 diabetes mellitus (DM1). Cross-sectional evaluation in a random cohort of DM1 adult patients from a tertiary care hospital. QoL was evaluated using translated and validated self-administered Diabetes QoL questionnaire (Es-DQoL), and results transformed into a 0-100 scale. Psychological assessment included a planned psychological interview and self-reported questionnaires (Beck Depression Inventory II, State-Trait Anxiety Inventory Form Y, Fear of hypoglycaemia Scale, Medical Outcomes Study Social Support Survey). A total of 312 patients (51.6% male; 38.2 ± 12.7 years; HbA1c 7.5 ± 1.1% (58.5 ± 14.2 mmol/mol); 20.4 ± 12.0 years of DM1) were included in the analysis. Male and female subgroups showed similar sociodemographic and diabetes-related features and comparable social support. Among female patients, higher frequency of depression [31.7% (IC95% 26.2-40.8) vs. 14.9% (IC95% 10.1-20.8), p Adult women with long-standing DM1 showed lower QoL probably related to higher frequency and severity of psychopathological syndromes. Depressive and anxious symptoms and, among women, exposure to glycemic excursions were identified as modifiable, QoL-related variables. Educational, technological and psychological interventions are needed in order to improve QoL in DM1 patients.Item Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson's Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up.(MDPI AG, 2021-12-17) Santos Garcia, Diego; Naya-Rios, Lucia; de-Deus-Fonticoba, Teresa; Cores-Bartolome, Carlos; Garcia-Roca, Lucia; Feal-Painceiras, Maria; Martinez-Miro, Cristina; Canfield, Hector; Jesus, Silvia; Aguilar, Miquel; Pastor, Pau; Cosgaya, Marina; Garcia-Caldentey, Juan; Caballol, Nuria; Legarda, Ines; Hernandez-Vara, Jorge; Cabo, Iria; Lopez-Manzanares, Lydia; Gonzalez-Aramburu, Isabel; Avila-Rivera, Maria A; Gomez-Mayordomo, Victor; Nogueira, Victor; Puente, Victor; Dotor, Julio; Borrue, Carmen; Solano-Vila, Berta; Alvarez-Sauco, Maria; Vela, Lydia; Escalante, Sonia; Cubo, Esther; Carrillo-Padilla, Francisco; Martinez-Castrillo, Juan C; Sanchez-Alonso, Pilar; Alonso-Losada, Maria G; Lopez-Ariztegui, Nuria; Gaston, Itziar; Kulisevsky, Jaime; Blazquez-Estrada, Marta; Seijo, Manuel; Ruiz-Martinez, Javier; Valero, Caridad; Kurtis, Monica; de-Fabregues, Oriol; Gonzalez-Ardura, Jessica; Alonso-Redondo, Ruben; Ordas, Carlos; Lopez-Diaz, Luis M; McAfee, Darrian; Martinez-Martin, Pablo; Mir, Pablo; Spanish Government; Junta de Andalucia; Consejeria de Salud y Bienestar Social de la Junta de AndaluciaDiplopia is relatively common in Parkinson's disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as "with diplopia" or "without diplopia" according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.Item Predictors of Loss of Functional Independence in Parkinson's Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up and Comparison with a Control Group(MDPI AG, 2021-09-29) Santos-Garcia, Diego; de-Deus-Fonticoba, Teresa; Cores-Bartolome, Carlos; Naya-Rios, Lucia; Garcia-Roca, Lucia; Martinez-Miro, Cristina; Canfield, Hector; Jesus, Silvia; Aguilar, Miquel; Pastor, Pau; Cosgaya, Marina; Garcia-Caldentey, Juan; Caballol, Nuria; Legarda, Ines; Hernandez-Vara, Jorge; Cabo, Iria; Lopez-Manzanares, Lydia; Gonzalez Aramburu, Isabel; Avila-Rivera, Maria A.; Gomez-Mayordomo, Victor; Nogueira, Victor; Puente, Victor; Dotor, Julio; Borrue, Carmen; Solano-Vila, Berta; Alvarez-Sauco, Maria; Vela, Lydia; Escalante, Sonia; Cubo, Esther; Carrillo-Padilla, Francisco; Martinez-Castrillo, Juan C.; Sanchez-Alonso, Pilar; Alonso-Losada, Maria G.; Lopez-Ariztegui, Nuria; Gaston, Itziar; Kulisevsky, Jaime; Blazquez-Estrada, Marta; Seijo, Manuel; Ruiz-Martinez, Javier; Valero, Caridad; Kurtis, Monica; de-Fabregues, Oriol; Gonzalez-Ardura, Jessica; Alonso-Redondo, Ruben; Ordas, Carlos; Lopez-Diaz, Luis M.; McAfee, Darrian; Martinez-Martin, Pablo; Mir, Pablo; [Santos Garcia, Diego] Complejo Hosp Univ A Coruna, CHUAC, La Coruna 15006, Spain; [Cores Bartolome, Carlos] Complejo Hosp Univ A Coruna, CHUAC, La Coruna 15006, Spain; [Naya Rios, Lucia] Complejo Hosp Univ A Coruna, CHUAC, La Coruna 15006, Spain; [Garcia Roca, Lucia] Complejo Hosp Univ A Coruna, CHUAC, La Coruna 15006, Spain; [Martinez Miro, Cristina] Complejo Hosp Univ A Coruna, CHUAC, La Coruna 15006, Spain; [Canfield, Hector] Complejo Hosp Univ A Coruna, CHUAC, La Coruna 15006, Spain; [de Deus Fonticoba, Teresa] Complejo Hosp Univ Ferrol, CHUF, La Coruna 15405, Spain; [Jesus, Silvia] Hosp Univ Virgen del Rocio CSIC Univ Sevilla, Inst Biomed Sevilla, Serv Neurol & Neurofisiol Clin, Unidad Trastornos Movimiento, Seville 41009, Spain; [Mir, Pablo] Hosp Univ Virgen del Rocio CSIC Univ Sevilla, Inst Biomed Sevilla, Serv Neurol & Neurofisiol Clin, Unidad Trastornos Movimiento, Seville 41009, Spain; [Jesus, Silvia] CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Madrid 28031, Spain; [Gonzalez Aramburu, Isabel] CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Madrid 28031, Spain; [Kulisevsky, Jaime] CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Madrid 28031, Spain; [Martinez-Martin, Pablo] CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Madrid 28031, Spain; [Mir, Pablo] CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Madrid 28031, Spain; [Aguilar, Miquel] Hosp Univ Mutua Terrassa, Barcelona 08221, Spain; [Pastor, Pau] Hosp Univ Mutua Terrassa, Barcelona 08221, Spain; [Cosgaya, Marina] Hosp Clin Barcelona, Barcelona 08036, Spain; [Garcia Caldentey, Juan] Ctr Neurol Oms 42, Palma De Mallorca 07003, Spain; [Caballol, Nuria] Hosp Moises Broggi, Consorci Sanitari Integral, Barcelona 08970, Spain; [Legarda, Ines] Hosp Univ Son Espases, Palma De Mallorca 07120, Spain; [Hernandez Vara, Jorge] Hosp Univ Vall dHebron, Barcelona 08035, Spain; [de Fabregues, Oriol] Hosp Univ Vall dHebron, Barcelona 08035, Spain; [Cabo, Iria] Complejo Hosp Univ Pontevedra CHOP, Pontevedra 36071, Spain; [Seijo, Manuel] Complejo Hosp Univ Pontevedra CHOP, Pontevedra 36071, Spain; [Lopez Manzanares, Lydia] Hosp Univ La Princesa, Madrid 28006, Spain; [Gonzalez Aramburu, Isabel] Hosp Univ Marques de Valdecilla, Santander 39011, Spain; [Avila Rivera, Maria A.] Hosp Gen Hosp, Consorci Sanitari Integral, Barcelona 08906, Spain; [Gomez Mayordomo, Victor] Hosp Univ Clin San Carlos, Madrid 28040, Spain; [Nogueira, Victor] Hosp Costa, Lugo 27880, Spain; [Puente, Victor] Hosp del Mar, Barcelona 08003, Spain; [Dotor, Julio] Hosp Univ Virgen Macarena, Seville 41009, Spain; [Borrue, Carmen] Hosp Infanta Sofia, Madrid 28702, Spain; [Solano Vila, Berta] Inst Catala Salut, Inst Assistencia Sanitaria IAS, Girona 17190, Spain; [Alvarez Sauco, Maria] Hosp Gen Univ Elche, Elche 03203, Spain; [Vela, Lydia] Fdn Hosp Alcorcon, Madrid 28922, Spain; [Escalante, Sonia] Hosp Tortosa Verge de la Cinta HTVC, Tarragona 43500, Spain; [Cubo, Esther] Complejo Asistencial Univ Burgos, Burgos 09006, Spain; [Carrillo Padilla, Francisco] Hosp Univ Canarias, San Cristobal La Laguna 38320, Spain; [Martinez Castrillo, Juan C.] Hosp Univ Ramon y Cajal, IRYCIS, Madrid 28034, Spain; [Sanchez Alonso, Pilar] Hosp Univ Puerta de Hierro, Madrid 28222, Spain; [Alonso Losada, Maria G.] Complejo Hosp Univ Vigo CHUVI, Hosp Alvaro Cunqueiro, Vigo 36213, Spain; [Lopez Ariztegui, Nuria] Complejo Hosp Toledo, Toledo 45071, Spain; [Gaston, Itziar] Complejo Hosp Navarra, Pamplona 31008, Spain; [Kulisevsky, Jaime] Hosp Santa Creu & Sant Pau, Barcelona 08041, Spain; [Blazquez Estrada, Marta] Hosp Univ Cent Asturias, Oviedo 33011, Spain; [Ruiz Martinez, Javier] Hosp Univ Donostia, San Sebastian 20009, Spain; [Valero, Caridad] Hosp Arnau Vilanova, Valencia 46015, Spain; [Kurtis, Monica] Hosp Ruber Int, Madrid 28034, Spain; [Gonzalez Ardura, Jessica] Hosp Cabuenes, Gijon 33394, Spain; [Alonso Redondo, Ruben] Univ Lucus Augusti HULA, Lugo 27002, Spain; [Ordas, Carlos] Hosp Rey Juan Carlos, Madrid 28933, Spain; [Lopez Diaz, Luis M.] Complejo Hosp Univ Orense CHUO, Orense 32005, Spain; [McAfee, Darrian] Univ Penn, Lab Cognit & Neural Stimulat, Philadelphia, PA 19104 USA; Fundacion Curemos el Parkinson; COPPADIS Study GrpBackground and objective: The aim of this study was to compare the progression of independence in activities of daily living ( ADL ) in Parkinson’s disease (PD) patients versus a control group , as well as to identify predictors of disability progression and functional dependency (FD). Patients and Methods : PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%. Results: In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen’s effect size = −0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2. Conclusions: In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment , gait problems, fatigue , depressive symptoms , more advanced disease , and a non- tremor phenotype are independent predictors of FD in the short-term.Item Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study.(Wolters Kluwer Health, 2020) Muñoz-Hernandez, Rocio; Ampuero, Javier; Millan, Raquel; Gil-Gomez, Antonio; Rojas, Angela; Macher, Hada C; Gallego-Duran, Rocio; Gato, Sheila; Montero-Vallejo, Rocio; Rico, Maria C; Maya-Miles, Douglas; Sanchez-Torrijos, Yolanda; Carmona-Soria, Isabel ; Stiefel, Pablo; Romero-Gomez, ManuelHepatitis C virus (HCV) infection has been related to increased cardiovascular (CV) risk. The aim of this study was to analyze the impact of sustained virological response (SVR) on endothelial dysfunction and subclinical atherosclerosis in patients with hepatitis C virus treated with direct-acting antiviral agents. A total of 114 patients were prospectively recruited and underwent CV risk assessment including (i) endothelial dysfunction determined through laser Doppler flowmetry and (ii) subclinical atherosclerosis, elucidated by the ankle-brachial index (ABI). Atherogenic lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides); markers of oxidative stress (oxidized low-density lipoprotein antibodies [OLAbs]), soluble markers of adhesion (vascular cell adhesion molecule [VCAM], e-selectin, and soluble markers of angiogenesis; and vascular endothelial growth factor, endothelial [EMPs] and platelet [PMPs] apoptotic microparticles, and cell-free DNA [cfDNA]) were measured. All determinations were performed at baseline, 12 weeks (SVR time), and 1 year after treatment. In patients with endothelial dysfunction, area of hyperemia improved after virus clearance (P = 0.013) and was related to significant decrease in VCAM, e-selectin (P HCV clearance improved not only liver function but also endothelial dysfunction and subclinical atherosclerosis promoted by decrease in levels of VCAM, e-selectin, cfDNA, and PMPs and EMPs.Item Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease(Bmc, 2021-12-08) Martinez-Horta, Saul; Bejr-Kasem, Helena; Horta-Barba, Andrea; Pascual-Sedano, Berta; Santos-Garcia, Diego; De Deus-Fonticoba, Teresa; Jesus, Silvia; Aguilar, Miquel; Planellas, Lluis; Garcia-Caldentey, Juan; Caballol, Nuria; Vives-Pastor, Barbara; Hernandez-Vara, Jorge; Cabo-Lopez, Iria; Lopez-Manzanares, Lydia; Gonzalez-Aramburu, Isabel; Asuncion Avila-Rivera, Maria; Jose Catalan, Maria; Manuel Lopez-Diaz, Luis; Puente, Victor; Manuel Garcia-Moreno, Jose; Borrue, Carmen; Solano-Vila, Berta; Alvarez-Sauco, Maria; Vela, Lydia; Escalante, Sonia; Cubo, Esther; Carrillo-Padilla, Francisco; Carlos Martinez-Castrillo, Juan; Sanchez-Alonso, Pilar; Gema Alonso-Losada, Maria; Lopez-Ariztegui, Nuria; Gaston, Itziar; Blazquez-Estrada, Marta; Seijo-Martinez, Manual; Ruiz-Martinez, Javier; Valero-Merino, Caridad; Kurtis, Monica; De Fabregues-Boixar, Oriol; Gonzalez-Ardura, Jessica; Prieto-Jurczynska, Cristina; Martinez-Martin, Pablo; Mir, Pablo; Kulisevsky, Jaime; COPPADIS Study; [Martinez-Horta, Saul] Hosp Santa Creu & Sant Pau, Movement Disorders Unit, Neurol Dept, Mas Casanovas 90, Barcelona 08041, Spain; [Bejr-Kasem, Helena] Hosp Santa Creu & Sant Pau, Movement Disorders Unit, Neurol Dept, Mas Casanovas 90, Barcelona 08041, Spain; [Horta-Barba, Andrea] Hosp Santa Creu & Sant Pau, Movement Disorders Unit, Neurol Dept, Mas Casanovas 90, Barcelona 08041, Spain; [Pascual-Sedano, Berta] Hosp Santa Creu & Sant Pau, Movement Disorders Unit, Neurol Dept, Mas Casanovas 90, Barcelona 08041, Spain; [Kulisevsky, Jaime] Hosp Santa Creu & Sant Pau, Movement Disorders Unit, Neurol Dept, Mas Casanovas 90, Barcelona 08041, Spain; [Martinez-Horta, Saul] IIB St Pau, Biomed Res Inst St Pau, Barcelona, Spain; [Bejr-Kasem, Helena] IIB St Pau, Biomed Res Inst St Pau, Barcelona, Spain; [Horta-Barba, Andrea] IIB St Pau, Biomed Res Inst St Pau, Barcelona, Spain; [Pascual-Sedano, Berta] IIB St Pau, Biomed Res Inst St Pau, Barcelona, Spain; [Kulisevsky, Jaime] IIB St Pau, Biomed Res Inst St Pau, Barcelona, Spain; [Martinez-Horta, Saul] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Madrid, Spain; [Bejr-Kasem, Helena] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Madrid, Spain; [Horta-Barba, Andrea] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Madrid, Spain; [Pascual-Sedano, Berta] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Madrid, Spain; [Jesus, Silvia] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Madrid, Spain; [Martinez-Martin, Pablo] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Madrid, Spain; [Mir, Pablo] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Madrid, Spain; [Kulisevsky, Jaime] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Madrid, Spain; [Santos-Garcia, Diego] Complejo Hosp Univ A Coruna, CHUAC, La Coruna, Spain; [De Deus-Fonticoba, Teresa] Complejo Hosp Univ Ferrol CHUF, Ferrol, A Coruna, Spain; [Jesus, Silvia] Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla,CSIC, Unidad Trastornos Movimiento,Serv Neurol & Neuro, Seville, Spain; [Mir, Pablo] Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla,CSIC, Unidad Trastornos Movimiento,Serv Neurol & Neuro, Seville, Spain; [Aguilar, Miquel] Hosp Univ Mutua de Terrassa, Barcelona, Spain; [Planellas, Lluis] Hosp Clin Barcelona, Barcelona, Spain; [Garcia-Caldentey, Juan] Hosp Quiron Palmaplanas, Clin Rotger, Palma De Mallorca, Spain; [Garcia-Caldentey, Juan] Ctr Neurol Oms 42, Palma De Mallorca, Spain; [Caballol, Nuria] Hosp Moises Broggi, Consorci Sanitari Integral, Barcelona, Spain; [Asuncion Avila-Rivera, Maria] Hosp Moises Broggi, Consorci Sanitari Integral, Barcelona, Spain; [Vives-Pastor, Barbara] Hosp Univ Son Espases, Palma De Mallorca, Spain; [Hernandez-Vara, Jorge] Vall DHebron Univ Campus, Neurol Dept, Barcelona, Spain; [De Fabregues-Boixar, Oriol] Vall DHebron Univ Campus, Neurol Dept, Barcelona, Spain; [Hernandez-Vara, Jorge] Vall DHebron Univ Campus, Neurodegenerat Dis Res Grp, Barcelona, Spain; [De Fabregues-Boixar, Oriol] Vall DHebron Univ Campus, Neurodegenerat Dis Res Grp, Barcelona, Spain; [Cabo-Lopez, Iria] Complejo Hosp Univ Pontevedra CHOP, Pontevedra, Spain; [Seijo-Martinez, Manual] Complejo Hosp Univ Pontevedra CHOP, Pontevedra, Spain; [Lopez-Manzanares, Lydia] Hosp Princesa, Madrid, Spain; [Gonzalez-Aramburu, Isabel] Hosp Univ Marques de Valdecilla, Santander, Spain; [Jose Catalan, Maria] Hosp Univ Clin San Carlos, Madrid, Spain; [Manuel Lopez-Diaz, Luis] Hosp Costa de Burela, Lugo, Spain; [Puente, Victor] Hosp Mar, Barcelona, Spain; [Manuel Garcia-Moreno, Jose] Hosp Univ Virgen Macarena, Seville, Spain; [Borrue, Carmen] Hosp Univ Infanta Sofia, Madrid, Spain; [Solano-Vila, Berta] Hosp Univ Josep Trueta, Girona, Spain; [Solano-Vila, Berta] Hosp Santa Caterina, Girona, Spain; [Alvarez-Sauco, Maria] Hosp Gen Univ Elche, Alicante, Spain; [Vela, Lydia] Fdn Hosp Alcorcon, Madrid, Spain; [Escalante, Sonia] Hosp Tortosa Verge de la Cinta HTVC, Tarragona, Spain; [Cubo, Esther] Complejo Asistencial Univ Burgos, Burgos, Spain; [Carrillo-Padilla, Francisco] Hosp Univ Canarias, Serv Neurol & Neurofisiol Clin, Unidad Trastornos Movimiento, Tenerife, Spain; [Carlos Martinez-Castrillo, Juan] Hosp Ramon & Cajal, Madrid, Spain; [Sanchez-Alonso, Pilar] Hosp Univ Puerta de Hierro, Madrid, Spain; [Gema Alonso-Losada, Maria] Complejo Hosp Univ Vigo CHUVI, Hosp Alvaro Cunqueiro, Vigo, Spain; [Lopez-Ariztegui, Nuria] Complejo Hosp Univ Toledo, Serv Neurol, Toledo, Spain; [Gaston, Itziar] Complejo Hosp Navarra, Pamplona, Spain; [Blazquez-Estrada, Marta] Hosp Univ Cent Asturias, Oviedo, Spain; [Ruiz-Martinez, Javier] Hosp Univ Donostia, San Sebastian, Spain; [Valero-Merino, Caridad] Hosp Arnau Vilanova, Serv Neurol, Valencia, Spain; [Kurtis, Monica] Hosp Ruber Int, Madrid, Spain; [Gonzalez-Ardura, Jessica] Hosp Lucus Augusti, Lugo, Spain; [Prieto-Jurczynska, Cristina] Hosp Rey Juan Carlos, Madrid, Spain; [Martinez-Martin, Pablo] Inst Salud Carlos III, Ctr Nacl Epidemiol, Madrid, Spain; [Martinez-Martin, Pablo] Inst Salud Carlos III, CIBERNED, Madrid, Spain; [Mir, Pablo] Univ Seville, Fac Med, Dept Med, Seville, Spain; Fundacion Curemos el ParkinsonBackground Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. Methods Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. Results Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (pItem Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease.(BioMed Central Ltd., 2021-12-08) Martinez-Horta, Saul; Bejr-Kasem, Helena; Horta-Barba, Andrea; Pascual-Sedano, Berta; Santos-Garcia, Diego; de Deus-Fonticoba, Teresa; Jesus, Silvia; Aguilar, Miquel; Planellas, Lluis; Garcia-Caldentey, Juan; Caballol, Nuria; Vives-Pastor, Barbara; Hernandez-Vara, Jorge; Cabo-Lopez, Iria; Lopez-Manzanares, Lydia; Gonzalez-Aramburu, Isabel; Avila-Rivera, Maria Asuncion; Catalan, Maria Jose; Lopez-Diaz, Luis Manuel; Puente, Victor; Garcia-Moreno, Jose Manuel; Borrue, Carmen; Solano-Vila, Berta; Alvarez-Sauco, Maria; Vela, Lydia; Escalante, Sonia; Cubo, Esther; Carrillo-Padilla, Francisco; Martinez-Castrillo, Juan Carlos; Sanchez-Alonso, Pilar; Alonso-Losada, Maria Gema; Lopez-Ariztegui, Nuria; Gaston, Itziar; Blazquez-Estrada, Marta; Seijo-Martinez, Manual; Ruiz-Martinez, Javier; Valero-Merino, Caridad; Kurtis, Monica; de Fabregues-Boixar, Oriol; Gonzalez-Ardura, Jessica; Prieto-Jurczynska, Cristina; Martinez-Martin, Pablo; Mir, Pablo; Kulisevsky, Jaime; COPPADIS Study GroupIdentifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD.Item An International Prospective Cohort Study To Validate 2 Prediction Rules for Infections Caused by Third-generation Cephalosporin-resistant Enterobacterales(Oxford univ press inc, 2020-07-09) Deelen, J. W. Timoteus; Rottier, Wouter C.; Giron-Ortega, Jose A. ; Rodriguez-Bano, Jesus; Harbarth, Stephan; Tacconelli, Evelina; Jacobsson, Gunnar; Zahar, Jean-Ralph; van-Werkhoven, Cornelis H.; Bonten, Marc J. M.; [Deelen, J. W. Timoteus] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Huispostnummer STR 6-131,Postbus 85500, NL-3508 GA Utrecht, Netherlands; [Rottier, Wouter C.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Huispostnummer STR 6-131,Postbus 85500, NL-3508 GA Utrecht, Netherlands; [van Werkhoven, Cornelis H.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Huispostnummer STR 6-131,Postbus 85500, NL-3508 GA Utrecht, Netherlands; [Bonten, Marc J. M.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Huispostnummer STR 6-131,Postbus 85500, NL-3508 GA Utrecht, Netherlands; [Ortega, Jose A. Giron] Univ Seville, Hosp Univ Virgen Macarena, Dept Med, Inst Biomed Sevilla IBIS,Unidad Clin Enfermedades, Seville, Spain; [Rodriguez-Bano, Jesus] Univ Seville, Hosp Univ Virgen Macarena, Dept Med, Inst Biomed Sevilla IBIS,Unidad Clin Enfermedades, Seville, Spain; [Harbarth, Stephan] Geneva Univ Hosp, Infect Control Program, Geneva, Switzerland; [Harbarth, Stephan] Fac Med, Geneva, Switzerland; [Tacconelli, Evelina] Univ Verona, Dept Diagnost & Publ Hlth, Div Infect Dis, Verona, Italy; [Jacobsson, Gunnar] Skaraborg Hosp, Dept Infect Dis, Reg Vastra Gotaland, Skovde, Sweden; [Zahar, Jean-Ralph] Univ Paris 13, Infect Antimicrobials Modelling Evolut IAME, Unite Mixte Rech UMR 1137, Paris, France; [Zahar, Jean-Ralph] Grp Hosp Paris Seine St Denis, AP HP, Serv Microbiol Unique & Unite Controle & Prevent, Bobigny, France; [Bonten, Marc J. M.] Univ Med Ctr Utrecht, Dept Med Microbiol, Utrecht, Netherlands; Plan Nacional de I+D+i 2013-2016; Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Ciencia, Innovacion y Universidades, Spanish Network for Research in Infectious Diseases; European Development Regional Fund "A Way to Achieve Europe," Operative Program Intelligent Growth 2014-2020; ESBL-PREDICT Study TeamBackground. The possibility of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacterales (3GC-R-BSI) leads to a trade-off between empiric inappropriate treatment (IAT) and unnecessary carbapenem use (UCU). Accurately predicting 3GC-R-BSI could reduce IAT and UCU. We externally validate 2 previously derived prediction rules for community-onset (CO) and hospital-onset (HO) suspected bloodstream infections.Methods. In 33 hospitals in 13 countries we prospectively enrolled 200 patients per hospital in whom blood cultures were obtained and intravenous antibiotics with coverage for Enterobacterales were empirically started. Cases were defined as 3GC-R-BSI or 3GC-R gram-negative infection (3GC-R-GNI) (analysis 2); all other outcomes served as a comparator. Model discrimination and calibration were assessed. Impact on carbapenem use was assessed at several cutoff points.Results. 4650 CO infection episodes were included and the prevalence of 3GC-R-BSI was 2.1% (n = 97). IAT occurred in 69 of 97 (71.1%) 3GC-R-BSI and UCU in 398 of 4553 non-3GC-R-BSI patients (8.7%). Model calibration was good, and the AUC was.79 (95% CI,.75-.83) for 3GC-R-BSI. The prediction rule potentially reduced IAT to 62% (60/97) while keeping UCU comparable at 8.4% or could reduce UCU to 6.3% (287/4553) while keeping IAT equal. IAT and UCU in all 3GC-R-GNIs (analysis 2) improved at similar percentages. 1683 HO infection episodes were included and the prevalence of 3GC-R-BSI was 4.9% (n = 83). Here model calibration was insufficient.Conclusions. A prediction rule for CO 3GC-R infection was validated in an international cohort and could improve empirical antibiotic use. Validation of the HO rule yielded suboptimal performance.Item Predictors of clinically significant quality of life impairment in Parkinson's disease(Nature portfolio, 2021-12-16) Santos-Garcia, D.; de-Deus-Fonticoba, Teresa; Cores, Carlos; Munoz, Guillermo; Paz-Gonzalez, Jose M.; Martinez-Miro, Cristina; Suarez, Ester; Jesus, Silvia; Aguilar, Miquel; Pastor, Pau; Planellas, Lluis; Cosgaya, Marina; Garcia-Caldentey, Juan; Caballol, Nuria; Legarda, Ines; Hernandez-Vara, Jorge; Cabo, Iria; Lopez-Manzanares, Luis; Gonzalez-Aramburu, Isabel; Avila-Rivera, Maria A.; Catalan, Maria J.; Nogueira, Victor; Puente, Victor; Ruiz-de-Arcos, Maria; Borrue, Carmen; Solano-Vila, Berta; Alvarez-Sauco, Maria; Vela, Lydia; Escalante, Sonia; Cubo, Esther; Carrillo-Padilla, Francisco; Martinez-Castrillo, Juan C.; Sanchez-Alonso, Pilar; Alonso-Losada, Maria G.; Lopez-Ariztegui, Nuria; Gaston, Itziar; Clavero, Pedro; Kulisevsky, Jaime; Blazquez-Estrada, Marta; Seijo, Manuel; Ruiz-Martinez, Javier; Valero, Caridad; Kurtis, Monica; de-Fabregues, Oriol; Gonzalez-Ardura, Jessica; Ordas, Carlos; Lopez-Diaz, Luis M.; McAfee, Darrian; Martinez-Martin, Pablo; Mir, Pablo; [Garcia, Santos D.] Complejo Hosp Univ A Coruna, CHUAC, La Coruna, Spain; [Cores, Carlos] Complejo Hosp Univ A Coruna, CHUAC, La Coruna, Spain; [Munoz, Guillermo] Complejo Hosp Univ A Coruna, CHUAC, La Coruna, Spain; [Paz Gonzalez, Jose M.] Complejo Hosp Univ A Coruna, CHUAC, La Coruna, Spain; [Martinez Miro, Cristina] Complejo Hosp Univ A Coruna, CHUAC, La Coruna, Spain; [de Deus Fonticoba, Teresa] Complejo Hosp Univ Ferrol, CHUF, La Coruna, Spain; [Suarez, Ester] Complejo Hosp Univ Ferrol, CHUF, La Coruna, Spain; [Jesus, Silvia] Univ Seville, Unidad Trastornos Movimiento, Serv Neurol & Neurofisiol Clin,CSIC, Inst Biomed Sevilla,Hosp Univ Virgen del Rocio, Seville, Spain; [Mir, Pablo] Univ Seville, Unidad Trastornos Movimiento, Serv Neurol & Neurofisiol Clin,CSIC, Inst Biomed Sevilla,Hosp Univ Virgen del Rocio, Seville, Spain; [Jesus, Silvia] CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Alava, Spain; [Gonzalez Aramburu, Isabel] CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Alava, Spain; [Kulisevsky, Jaime] CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Alava, Spain; [Martinez-Martin, Pablo] CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Alava, Spain; [Mir, Pablo] CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Alava, Spain; [Aguilar, Miquel] Hosp Univ Mutua Terrassa, Barcelona, Spain; [Pastor, Pau] Hosp Univ Mutua Terrassa, Barcelona, Spain; [Planellas, Lluis] Clin Pilar, Neurol, Barcelona, Spain; [Cosgaya, Marina] Hosp Clin Barcelona, Barcelona, Spain; [Garcia Caldentey, Juan] Ctr Neurol Oms 42, Palma De Mallorca, Spain; [Caballol, Nuria] Hosp Moises Broggi, Consorci Sanitari Integral, Barcelona, Spain; [Legarda, Ines] Hosp Univ Son Espases, Palma De Mallorca, Spain; [Hernandez Vara, Jorge] Hosp Univ Vall dHebron, Barcelona, Spain; [de Fabregues, Oriol] Hosp Univ Vall dHebron, Barcelona, Spain; [Cabo, Iria] Complejo Hosp Univ Pontevedra CHOP, Pontevedra, Spain; [Seijo, Manuel] Complejo Hosp Univ Pontevedra CHOP, Pontevedra, Spain; [Lopez Manzanares, Luis] Hosp Univ La Princesa, Madrid, Spain; [Gonzalez Aramburu, Isabel] Hosp Univ Marques de Valdecilla, Santander, Spain; [Avila Rivera, Maria A.] Hosp Gen Hospitalet, Consorci Sanitari Integral, Barcelona, Spain; [Catalan, Maria J.] Hosp Univ Clin San Carlos, Madrid, Spain; [Nogueira, Victor] Hosp Costa, Lugo, Spain; [Puente, Victor] Hosp del Mar, Barcelona, Spain; [Ruiz de Arcos, Maria] Hosp Univ Virgen Macarena, Seville, Spain; [Borrue, Carmen] Hosp Infanta Sofia, Madrid, Spain; [Solano Vila, Berta] Inst Assistencia Sanitaria IAS, Inst Catala Salut, Girona, Spain; [Alvarez Sauco, Maria] Hosp Gen Univ Elche, Elche, Spain; [Vela, Lydia] Fdn Hosp Alcorcon, Madrid, Spain; [Escalante, Sonia] Hosp Tortosa Verge de la Cinta HTVC, Tarragona, Spain; [Cubo, Esther] Complejo Asistencial Univ Burgos, Burgos, Spain; [Carrillo Padilla, Francisco] Hosp Univ Canarias, San Cristobal La Laguna, Santa Cruz De T, Spain; [Martinez Castrillo, Juan C.] Hosp Univ Ramon y Cajal, IRYCIS, Madrid, Spain; [Sanchez Alonso, Pilar] Hosp Univ Puerta de Hierro, Madrid, Spain; [Alonso Losada, Maria G.] Complejo Hosp Univ Vigo CHUVI, Hosp Alvaro Cunqueiro, Vigo, Spain; [Lopez Ariztegui, Nuria] Complejo Hosp Toledo, Toledo, Spain; [Gaston, Itziar] Complejo Hosp Navarra, Pamplona, Spain; [Clavero, Pedro] Complejo Hosp Navarra, Pamplona, Spain; [Kulisevsky, Jaime] Hosp Santa Creu & Sant Pau, Barcelona, Spain; [Blazquez Estrada, Marta] Hosp Univ Cent Asturias, Oviedo, Spain; [Ruiz Martinez, Javier] Hosp Univ Donostia, San Sebastian, Spain; [Valero, Caridad] Hosp Arnau Vilanova, Valencia, Spain; [Kurtis, Monica] Hosp Ruber Int, Madrid, Spain; [Gonzalez Ardura, Jessica] Hosp Univ Cabuenes, Gijon, Spain; [Ordas, Carlos] Hosp Rey Juan Carlos, Madrid, Spain; [Lopez Diaz, Luis M.] Complejo Hosp Univ Orense CHUO, Orense, Spain; [McAfee, Darrian] Univ Penn, Philadelphia, PA 19104 USA; COPPADIS Study GrpQuality of life (QOL) plays an important role in independent living in Parkinson's disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months +/- 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 >= 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 +/- 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 +/- 13 to 20.3 +/- 16.4; p = 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 +/- 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 +/- 13 to 20.3 +/- 16.4; p = 5 and >= 10 points of BDI-II and NMSS total score at V2 multiplied the probability of presenting clinically significant HRQoL impairment by 5 (OR = 5.453; 95% CI 1.663-17.876; p = 0.005) and 8 (OR = 8.217; 95% CI, 2.975-22.696; p = 0.002), respectively. In conclusion, age, gender, mood, and non-motor impairment were associated with clinically significant HRQoL impairment after the 2-year follow-up in PD patients.Item Weekly nab-paclitaxel for progressive or symptomatic desmoid tumors: A multicenter single arm phase II trial from the Spanish Group for Research on Sarcoma (GEIS)(Elsevier, 2020-09-01) Martin Broto, J.; Hindi, N.; Redondo, A.; Morales, J. M.; Marcilla, D.; Valverde, C.; Luna, P.; Diaz-Beveritge, R.; Martinez-Trufero, J.; Lopez-Martin, J. A.; Martinez, V.; Gutierrez, A.; Lopez-Pousa, A.; [Martin Broto, J.] Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBIS, Dept Med Oncol, Seville, Spain; [Hindi, N.] Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBIS, Dept Med Oncol, Seville, Spain; [Redondo, A.] Hosp Univ La Paz, Dept Oncol Med, Madrid, Spain; [Martinez, V.] Hosp Univ La Paz, Dept Oncol Med, Madrid, Spain; [Morales, J. M.] Hosp Univ Virgen del Rocio, Dept Radiol, Seville, Spain; [Marcilla, D.] Hosp Univ Virgen del Rocio, Dept Pathol, Seville, Spain; [Valverde, C.] Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain; [Luna, P.] Hosp Univ Son Espases, Med Oncol, Palma De Mallorca, Spain; [Diaz-Beveritge, R.] Hosp Univ La Fe, Med Oncol, Valencia, Spain; [Martinez-Trufero, J.] Hosp Univ Miguel Servet, Med Oncol, Zaragoza, Spain; [Lopez-Martin, J. A.] Hosp Univ Doce Octubre, Med Oncol, Madrid, Spain; [Gutierrez, A.] Hosp Univ Son Espases, Hematol, Palma De Mallorca, Spain; [Lopez-Pousa, A.] Hosp Santa Creu & Sant Pau, Med Oncol, Barcelona, Spain; Spanish Group for Research on Sarcoma (GEIS); Celgene