Genetics of dementia: insights from Latin America / Genética das demências: percepção a partir da América Latina

ABSTRACT. Alzheimer's disease (AD) and frontotemporal dementia (FTD) are neurodegenerative disorders that result in a significant burden to both patients and caregivers. By 2050, the number of people with dementia in Latin America will increase 4-fold. A deep understanding of the relevant genetic factors of AD and FTD is fundamental to tackle this reality through prevention. A review of different genetic variants that cause AD or FTD in Latin America was conducted. We searched Medline and PubMed databases using the keywords "Alzheimer's disease," "frontotemporal dementia," "mutation," "America," and "Latin America," besides specific Latin American countries. Forty-five items were chosen and analyzed. PSEN1 mutations are the commonest cause of genetic early-onset Alzheimer's disease (EOAD), followed by PSEN2 and APP mutations. Genetic FTD can be mainly explained by GRN and MAPT mutations, as well as C9orf72 G4C2 repeat expansion. APOE ε4 can modify the prevalence and incidence of late-onset Alzheimer's disease (LOAD), in addition to the cognitive performance in affected carriers.

RESUMO. A doença de Alzheimer (DA) e a demência frontotemporal (DFT) são distúrbios neurodegenerativos que causam uma sobrecarga significativa para pacientes e cuidadores. Em 2050, o número de pessoas com demência na América Latina aumentará 4 vezes. Uma compreensão profunda dos fatores genéticos relevantes da DA e da DFT é fundamental para enfrentar essa realidade por meio da prevenção. Foi realizada uma revisão de diferentes variantes genéticas que causam a DA ou a DFT na América Latina. Pesquisamos os bancos de dados Medline e PubMed usando as palavras-chave "doença de Alzheimer", "demência frontotemporal", "mutação", "América" e "América Latina", além de países latino-americanos específicos. Quarenta e cinco itens foram escolhidos e analisados. As mutações do PSEN1 são a causa mais comum da doença de Alzheimer genética de início precoce (DAIP), seguida pelas mutações do PSEN2 e da APP. A DFT genética pode ser explicada principalmente por mutações no GRN, MAPT e expansões repetidas da C9orf72 G4C2. O APOE ε4 pode modificar a prevalência e a incidência da doença de Alzheimer de início tardio (DAIT), mas também o desempenho cognitivo em portadores afetados.

Factores asociados a falla en el manejo no operatorio de lesiones hepáticas o esplénicas secundarias a trauma abdominal cerrado en niños / Associated factors to non-operative management failure of hepatic and splenic lesions secondary to blunt abdominal trauma in children

Introducción: El manejo no operatorio (MNO) es el manejo estándar del trauma cerrado esplénico y hepático en el paciente pediátrico. Se han identificado como fallas a este manejo inestabilidad hemodinámica y transfusiones masivas. Pocos trabajos evalúan si existen factores que permitan una anticipación a estos eventos. El objetivo fue determinar la existencia de factores asociados a la falla en MNO de las lesiones esplénicas y/o hepáticas secundarias al trauma abdominal cerrado. Pacientes y Método: Análisis retrospectivo 2007 a 2015 de los pacientes que ingresaron al servicio de Cirugía infantil del Hospital Universitario San Vicente Fundación con trauma hepático y/o esplénico cerrado. Resultados: Ingresaron 70 pacientes con trauma cerrado de abdomen, 3 fueron excluidos por cirugía inmediata (2 inestabilidad hemodinámica y 1 irritación peritoneal). De 67 pacientes que recibieron MNO, 58 tuvieron éxito y 9 presentaron falla (8 inestabilidad hemodinámica y 1 lesión de víscera hueca). Encontramos 3 factores asociados a la falla MNO: presión arterial (PAS) < 90 mmHg al ingreso (p=0,0126; RR =5,19), caída de la Hemoglobina (Hb) > 2 g/dl en las primeras 24 h (p=0,0009; RR= 15,3), y transfusión de 3 o más unidades de glóbulos rojos (UGR) (0,00001; RR= 17,1). Mecanismo del trauma, severidad e Índice de Trauma Pediátrico no se asociaron con fallo MNO. Conclusiones: Los niños con trauma cerrado hepático o esplénico responden al MNO. Los factores como PA menor de 90 al ingreso, caída de la Hb >2 g/dl en las primeras 24 h y la transfusión de 3 o más UGR pueden asociarse con la falla en el MNO.

Introduction: The non operative management (NOM) is the standard management of splenic and liver blunt trauma in pediatric patients.Hemodynamic instability and massive transfusions have been identified as management failures. Few studies evaluate whether there exist factors allowing anticipation of these events. The objective was to identify factors associated with the failure of NOM in splenic and liver injuries for blunt abdominal trauma. Patients and Method: Retrospective analysis between 2007-2015 of patients admitted to the pediatric surgery at University Hospital Saint Vincent Foundation with liver trauma and/or closed Spleen. Results: 70 patients were admitted with blunt abdominal trauma, 3 were excluded for immediate surgery (2 hemodynamic instability, 1 peritoneal irritation). Of 67 patients who received NOM, 58 were successful and 9 showed failure (8 hemodynamic instability, 1 hollow viscera injury). We found 3 factors associated with failure NOM: blood pressure (BP) < 90 mmHg at admission (p = 0.0126; RR = 5.19), drop in hemoglobin (Hb) > 2 g/dl in the first 24 hours (p = 0.0009; RR = 15.3), and transfusion of 3 or more units of red blood cells (RBC) (0.00001; RR = 17.1). Mechanism and severity of trauma and Pediatric Trauma Index were not associated with failure NOM. Conclusions: Children with blunted hepatic or splenic trauma respond to NOM. Factors such as BP < 90 mmHg at admission, an Hb fall > 2 g/dl in the first 24 hours and transfusion of 3 or more units of RBC were associated with the failure in NOM.