Riesgo vascular, obesidad abdominal y resistencia insulínica en adultos con síndrome de Down

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 21-01-2015ANTECEDENTES: La esperanza de vida de las personas con síndrome de Down (SD) ha aumentado drásticamente en las últimas décadas. Estos adultos presentan un perfil de comorbilidades diferentes al de la población general. En concreto, aunque los adultos con SD parecen presentar un perfil de riesgo vascular incrementado respecto a la población general, sufren menos eventos vasculares. La evidencia previa es limitada y en ocasiones, contradictoria. OBJETIVO PRINCIPAL: Describir la prevalencia de los factores de riesgo vascular en los adultos con SD, y evaluar el impacto de los trastornos de peso (sobrepeso, obesidad y obesidad abdomina [OA]) sobre el metabolismo hidrocarbonado y lipídico de estos sujetos. PACIENTES Y MÉTODOS: Estudio transversal retrospectivo sobre personas con SD elegidas mediante muestreo consecutivo de entre las atendidas en el periodo entre enero 2012 y marzo 2013. Se realizó un subestudio transversal en 51 adultos con SD y 51 controles sanos (sujetos que no presentasen alto o muy alto riesgo vascular añadido). Cuarenta y cuatro hermanos de adultos con SD (44/51, 86%) fueron reclutados como controles. Se analizaron variables sociodemográficas, antropométricas, clínicas (patologías previas, medicación activas y cuestionario dietético) y de laboratorio. Los resultados se compararon entre grupos (SD vs controles), ajustados por edad y sexo. RESULTADOS: Se analizaron 144 adultos con SD de edad media 35 ± 12 años, con un rango de edad entre 17 y 65 años. Los grupos de patología más relevantes presentes en esta población fueron la patología oftalmológica (81% de los sujetos), fundamentalmente las cataratas y el queratocono, las alteraciones tiroideas (56%), fundamentalmente el hipotiroidismo, los problemas neurológicos (12.5%), como demencias y crisis comiciales, y la psicopatología (40%). Las alteraciones del peso también fueron extremadamente prevalentes. Nueve de cada diez adultos con SD de la población del subestudio comparativo presentó OA por índice cintura-altura, y más de dos tercios tuvo sobrepeso (37%) u obesidad (37%) por índice de masa corporal. La frecuencia del resto de factores clásicos de riesgo vascular fue baja (14 sujetos [10%] con dislipemia, dos con diabetes mellitus [1%], siete presentaron síndrome metabólico [5%] y ninguno con hipertensión arterial). CONCLUSIONES: Los adultos con SD presentan una elevada prevalencia de múltiples comorbilidades médicas tratables, propias de un proceso de envejecimiento precoz, incluso a partir de la tercera década de la vida. Entre ellas, destacan la patología oftalmológica, las alteraciones tiroideas, el deterioro cognitivo y la psicopatología. La prevalencia de trastornos de peso en los adultos con SD es muy elevada, pese a lo cual se ha encontrado una baja prevalencia de SM en la población adulta con SD y obesidad abdominal

A study on the relationship between serum beta 2-microglobulin levels, underlying chronic kidney disease, and peripheral arterial disease in high-vascular-risk patients

Background: Serum beta 2-microglobulin (B2M) levels have been found to be increased in patients with peripheral arterial disease (PAD), yet it is still unknown whether B2M correlates with PAD intensity. Objectives: We aim to evaluate the correlation between B2M and the ankle-brachial index (ABI) values in high-vascular-risk patients. Methods: This is a cross-sectional study of 63 high-vascular-risk patients admitted to the Cardiology Department or evaluated as outpatients in the Internal Medicine Department of our institution. Patients were classified into two groups according to their ABI: patients without PAD (n = 44, ABI values between 0.9 and 1.4) and patients with PAD (n = 19, ABI values lower than 0.9 or higher than 1.4). We performed univariate and multivariate analysis based on a multiple linear regression model. Results: Serum B2M levels were higher in patients with pathological ABI values than in those without PAD (2.36 ± 1.13 vs. 1.80 ± 0.65 mg/L; P<0.05). We found no correlation between B2M and ABI in our total population (r = –0.12) or in patients with PAD (r = –0.09; NS for both comparisons). Age, gender, arterial hypertension, estimated glomerular filtration rate (eGFR), uric acid, total cholesterol, and LDL-cholesterol correlated with B2M in the univariate analysis. In the final linear regression model, eGFR, uric acid and total cholesterol correlated independently with B2M (P<0.01). Conclusion: We found no correlation between B2M levels and ABI values in high-vascularrisk patients that could usefully help in the subsequent diagnosis of PAD. However, we observed a significant correlation between B2M and eGFR, even when renal function was only slightly impaired

Causes of mortality among adults with Down syndrome before and after the COVID-19 pandemic in Spain

Background: The life expectancy of people with Down syndrome (DS) is limited by Alzheimer's disease (AD)-related deaths, mainly due to respiratory infections. The emergence of the COVID-19 pandemic could have changed known, past trends in mortality in this population. We analysed the differences in causes of mortality between individuals with DS deceased before and after the onset of the pandemic. Method: This is a cross-sectional study of adults with DS recruited at a tertiary, university outpatient clinic in Madrid, Spain. Demographic and clinical data were retrospectively collected from their medical records, including information on their deaths, if any. Results: Five hundred seventy-two adults were included in the study, and 67 (11.7%) died. The main cause of death was respiratory infections, which occurred in 36 participants [9 (45.0%) before, and 27 (58.7%) after the appearance of COVID-19]. No significant differences were found in the determinants of pre-pandemic and post-pandemic death after adjusting for age and AD, except for an association between the use of psychotropic medication and death in the post-pandemic period (odds ratio: 2.24; 95% confidence interval: 1.04–4.82). Vaccination against COVID-19 showed a marked protective effect against mortality (odds ratio: 0.0002; 95% confidence interval: 6.7e10−6 to 0.004). Conclusions: The appearance of COVID-19 has not impacted the overall trend of increase in mean age of death of adults with DS in our milieu, probably thanks to the very important protective effect of vaccination, which supports prioritising people with DS in future immunisation campaigns. The association between psychotropic medication use and mortality requires further explorationThis work was supported by a grant to Beatriz Sánchez (grant no. 2021b-2088) and Diego Real de Asúa (grant no. 2021a-2069) from the Fondation Jérôme Lejeun

Clinical Ethics Consultation: current European models and novel approaches in Spain

Los Comités de Ética Asistencial (CEAS) han constituido hasta la actualidad el único modelo de resolución de conflictos éticos en el entorno hospitalario en España, aunque su utilidad para mejorar la práctica clínica diaria ha sido puesta en duda. La Consultoría individual en Ética Clínica (CEC) es un modelo complementario al CEAS, eficaz para ayudar a tomar decisiones ético-clínicas complejas a tiempo real. Aunque la CEC está muy extendida en el ámbito estadounidense, todavía goza de poca popularidad en Europa. En el presente trabajo se describen las características generales de los servicios de CEC, remarcando sus ventajas y potenciales riesgos comparándolos con los del modelo basado exclusivamente en los CEAS. En segundo lugar, se recogen las experiencias y modelos de CEC en diversos países europeos, y también presentamos las iniciativas más recientes llevadas a cabo en nuestro país. Tras ello, se propone una estrategia de implantación de un servicio de CEC para un hospital universitario de tamaño medio y se resumen las características mínimas que este servicio de CEC debe tener para poder llevar a cabo eficazmente su labor consultiva: flexibilidad organizativa, composición por profesionales formados en Bioética, con gran experiencia clínica, remunerados específicamente para esta tarea y con dependencia organizativa del CEAS.To date, healthcare ethics committees (HEC) have been the only ethics consultation model in the hospital setting in Spain, though their usefulness for ethical conflict resolution in daily practice has been questioned. Individual clinical ethics consultation (CEC) is a complementary ethics consultation model, which has proved efficacious in real-time ethical problem-solving. Although CEC is widely used in North America, its implementation in Europe is still marginal. In this document we present the general characteristics of CEC services, comparing their potential advantages and risks to those of HECs. We will then share relevant European experiences in CEC, as well as review the few CEC initiatives in Spain. Finally, we will share our recent CEC implementation strategy in a national, medium-sized, teaching hospital. We will summarise the minimum requirements that such a CEC service must meet in order to carry out its consulting activity: organisational flexibility, well-trained professionals, with sufficient clinical experience, economical support, and organisational dependency on HECs

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Why dedicate yourself to bioethics? Seven reasons to get you started

La bioética clínica se encarga de promover decisiones clínicas racionales teniendo en cuenta los hechos clínicos, las preferencias y valores de todos los individuos implicados en una situación que plantea un problema moral. La intención del presente trabajo es exponer algunas de las razones por las que consideramos esencial tener conocimientos y aptitudes bioéticas en la práctica diaria, así como potenciar una mentalidad proactiva en la investigación en bioética clínica. Entre los argumentos ofrecidos destacan la necesidad de adaptarse a los cambios en la relación clínica de las últimas décadas, la importancia de una actitud ética tanto para el médico como para el paciente, el papel de la bioética en la prevención del «burnout» del profesional, su capacidad para promover una distribución de los recursos más justa, y la posibilidad de desarrollar la investigación clínica en bioética, un territorio escasamente explorado en el ámbito español.The aim of clinical bioethics is to promote rational clinical decisions that take into account the clinical facts and the preferences and values of individuals involved in a situation that entails a moral problem. The objective of the present study is to list the reasons why we consider bioethics knowledge and skills to be essential in daily practice and to promote a proactive mindset in clinical bioethics research. The arguments set forth include the need to adapt to changes in the clinical relationship in recent decades, the importance of an ethical approach both for the physician and the patient, the role of bioethics in preventing professional burnout, the ability of ethics to promote a more equitable distribution of resources and the possibility of conducting clinical research in bioethics, a field that has scarcely been explored in Spain.Sin financiación0.971 JCR (2016) Q3, 100/155 Medicine, General & InternalUE