Hospital General Universitario Gregorio Marañón

About: Hospital General Universitario Gregorio Marañón is a healthcare organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Transplantation. The organization has 11975 authors who have published 12386 publications receiving 244847 citations.

Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study.

Abstract: Summary Background Investigations of myelin oligodendrocyte glycoprotein (MOG) antibodies are usually focused on demyelinating syndromes, but the entire spectrum of MOG antibody-associated syndromes in children is unknown. In this study, we aimed to determine the frequency and distribution of paediatric demyelinating and encephalitic syndromes with MOG antibodies, their response to treatment, and the phenotypes associated with poor prognosis. Methods In this prospective observational study, children with demyelinating syndromes and with encephalitis other than acute disseminated encephalomyelitis (ADEM) recruited from 40 secondary and tertiary centres in Spain were investigated for MOG antibodies. All MOG antibody-positive cases were included in our study, which assessed syndromes, treatment and response to treatment (ie, number of relapses), outcomes (measured with the modified Rankin scale [mRS]), and phenotypes associated with poor prognosis. We used Fisher's exact and Wilcoxon rank sum tests to analyse clinical features, and survival Cox regression to analyse time to antibody negativity. Findings Between June 1, 2013, and Dec 31, 2018, 239 children with demyelinating syndromes (cohort A) and 296 with encephalitis other than ADEM (cohort B) were recruited. 116 patients had MOG antibodies, including 94 (39%) from cohort A and 22 (7%) from cohort B; 57 (49%) were female, with a median age of 6·2 years (IQR 3·7–10·0). Presenting syndromes in these 116 patients included ADEM (46 [68%]), encephalitis other than ADEM (22 [19%]), optic neuritis (20 [17%]), myelitis (13 [11%]), neuromyelitis optica spectrum disorders (six [5%]), and other disorders (nine [8%]). Among the patients with autoimmune encephalitis in cohort B (n=64), MOG antibodies were more common than all neuronal antibodies combined (22 [34%] vs 21 [33%]). After a median follow-up of 42 months (IQR 22–67), 33 (28%) of the 116 patients had relapses, including 17 (17%) of 100 diagnosed at first episode. Steroids, intravenous immunoglobulin, or plasma exchange were used in 100 (86%) patients at diagnosis, and 32 (97%) of 33 at relapses. Rituximab was mainly used at relapses (11 [33%]). 99 (85%) of 116 patients had substantial recovery (mRS 2; one died). Phenotypes of poor prognosis included ADEM-like relapses progressing to leukodystrophy-like features, and extensive cortical encephalitis evolving to atrophy. Time to antibody negativity was longer in patients with relapses (HR 0·18, 95% CI 0·05–0·59). Interpretation The spectrum of paediatric MOG antibody-associated syndromes is wider than previously reported and includes demyelinating syndromes and encephalitis. Recognition of these disorders has important clinical and prognostic implications. Funding Mutua Madrilena Foundation; ISCIII–Subdireccion General de Evaluacion y Fomento de la Investigacion Sanitaria; Fondo Europeo de Desarrollo Regional; Pediatrics Spanish Society; Departament de Salut, Generalitat de Catalunya; Marato TV3 Foundation; Red Espanola de Esclerosis Multiple; La Caixa Foundation; and Fundacio CELLEX.

Gender and survival in patients with heart failure: interactions with diabetes and aetiology. Results from the MAGGIC individual patient meta-analysis.

Abstract: The aim of this study was to investigate the relationship between gender and survival of patients with heart failure, using data from both randomized trials and observational studies, and the relative contribution of age, left ventricular systolic function, aetiology, and diabetes to differences in prognosis between men and women. Methods Data from 31 studies (41 949 patients; 28 052 men, 13 897 women) from the Meta-Analysis Global Group In Chronic Heart Failure (MAGGIC) individual patient meta-analysis were used. We performed survival analysis to assess the association of gender with mortality, adjusting for predictors of mortality, including age, reduced or preserved ejec- tion fraction (EF), and ischaemic or non-ischaemic aetiology. Women were older (70.5 ( standard deviation 12.1) vs. 65.6 (standard deviation 11.6) years), more likely to have a history of hypertension (49.9% vs. 40.0%), and less likely to have a history of ischaemic heart disease (46.3% vs. 58.7%) and reduced EF (62.6% vs. 81.6%) compared with men. During 3 years follow-up, 3521 (25%) women and 7232 (26%) men died. After adjustment, male gender was an in- dependent predictor of mortality, and the better prognosis associated with female gender was more marked in patients with heart failure of non-ischaemic, compared with ischaemic, aetiology (P-value for interaction ¼ 0.03) and in patients without, compared with those with, diabetes (P-value for interaction ,0.0001). Conclusion This large, individual patient data meta-analysis has demonstrated that survival is better for women with heart failure compared with men, irrespective of EF. This survival benefit is slightly more marked in non-ischaemic heart failure but is attenuated by concomitant diabetes.

DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients.

Abstract: // Noemi Garcia-Romero 1, 2, * , Josefa Carrion-Navarro 1, 3, * , Susana Esteban-Rubio 1, 3, * , Elisa Lazaro-Ibanez 4 , Maria Peris-Celda 5 , Marta M. Alonso 6 , Juan Guzman-De-Villoria 7 , Carlos Fernandez-Carballal 8 , Ana Ortiz de Mendivil 1 , Sara Garcia-Duque 1 , Carmen Escobedo-Lucea 4 , Ricardo Prat-Acin 9 , Cristobal Belda-Iniesta 1, 3 , Angel Ayuso-Sacido 1, 2, 3 1 Fundacion de Investigacion HM Hospitales, HM Hospitales, Madrid, Spain 2 IMDEA Nanoscience, Madrid, Spain 3 Facultad de Medicina (IMMA), Universidad San Pablo-CEU, Madrid, Spain 4 Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland 5 Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA 6 Clinica Universidad de Navarra, CIMA, Pamplona, Spain 7 Servicio de Radiodiagnostico, Hospital General Universitario Gregorio Maranon, Madrid, Spain 8 Servicio de Neurocirugia, Hospital General Universitario Gregorio Maranon, Madrid, Spain 9 Departamento de Neurocirugia, Hospital Universitario la Fe, Valencia, Spain * These authors have contributed equally to this work Correspondence to: Angel Ayuso-Sacido, email: ayusosacido@gmail.com Keywords: extracellular vesicles, brain tumors, blood-brain barrier, biomarkers Received: September 20, 2016 Accepted: November 07, 2016 Published: November 26, 2016 ABSTRACT Tumor-cell-secreted extracellular vesicles (EVs) can cross the disrupted blood-brain barrier (BBB) into the bloodstream. However, in certain gliomas, the BBB remains intact, which might limit EVs release. To evaluate the ability of tumor-derived EVs to cross the BBB, we used an orthotopic xenotransplant mouse model of human glioma-cancer stem cells featuring an intact BBB. We demonstrated that all types of tumor cells-derived EVs−apoptotic bodies, shedding microvesicles and exosomes−cross the intact BBB and can be detected in the peripheral blood, which provides a minimally invasive method for their detection compared to liquid biopsies obtained from cerebrospinal fluid (CSF). Furthermore, these EVs can be readily distinguished from total murine EVs, since they carry human-specific DNA sequences relevant for GBM biology. In a small cohort of glioma patients, we finally demonstrated that peripheral blood EVs cargo can be successfully used to detect the presence of IDH1 G395A , an essential biomarker in the current management of human glioma

Type 2 Diabetes Mellitus in Youth Exposed to Antipsychotics: A Systematic Review and Meta-analysis

Abstract: Importance Antipsychotics are used increasingly in youth for nonpsychotic and off-label indications, but cardiometabolic adverse effects and (especially) type 2 diabetes mellitus (T2DM) risk have raised additional concern. Objective To assess T2DM risk associated with antipsychotic treatment in youth. Data Sources Systematic literature search of PubMed and PsycINFO without language restrictions from database inception until May 4, 2015. Data analyses were performed in July 2015, and additional analyses were added in November 2015. Study Selection Longitudinal studies reporting on T2DM incidence in youth 2 to 24 years old exposed to antipsychotics for at least 3 months. Data Extraction and Synthesis Two independent investigators extracted study-level data for a random-effects meta-analysis and meta-regression of T2DM risk. Main Outcomes and Measures The coprimary outcomes were study-defined T2DM, expressed as cumulative T2DM risk or as T2DM incidence rate per patient-years. Secondary outcomes included the comparison of the coprimary outcomes in antipsychotic-treated youth with psychiatric controls not receiving antipsychotics or with healthy controls Results Thirteen studies were included in the meta-analysis, including 185 105 youth exposed to antipsychotics and 310 438 patient-years. The mean (SD) age of patients was 14.1 (2.1) years, and 59.5% were male. The mean (SD) follow-up was 1.7 (2.3) years. Among them, 7 studies included psychiatric controls (1 342 121 patients and 2 071 135 patient-years), and 8 studies included healthy controls (298 803 patients and 463 084 patient-years). Antipsychotic-exposed youth had a cumulative T2DM risk of 5.72 (95% CI, 3.45-9.48; P P P P P P P P P = .002) ( r 2 = 1.00, P P ≤ .050) and less autism spectrum disorder diagnosis ( P = .048) ( r 2 = 0.21, P = .044). Conclusions and Relevance Although T2DM seems rare in antipsychotic-exposed youth, cumulative risk and exposure-adjusted incidences and IRRs were significantly higher than in healthy controls and psychiatric controls. Olanzapine treatment and antipsychotic exposure time were the main modifiable risk factors for T2DM development in antipsychotic-exposed youth. Antipsychotics should be used judiciously and for the shortest necessary duration, and their efficacy and safety should be monitored proactively.