RESUMEN
BACKGROUND: Atrial fibrillation (AF) is common after cardiac surgery and contributes to increased morbidity and mortality. Our objective was to derive and validate a predictive model for AF after CABG in patients, incorporating novel echocardiographic and laboratory values. METHODS: We retrospectively reviewed patients at our institution without preexisting dysrhythmia who underwent on-pump, isolated CABG from 2011-2015. The primary outcome was new onset AF lasting >1 hour on continuous telemetry or requiring medical treatment. Patients with a preoperative echocardiographic measurement of left atrial diameter were included in a risk model, and were randomly divided into derivation (80%) and validation (20%) cohorts. The predictors of AF after CABG (PAFAC) score was derived from a multivariable logistic regression model by multiplying the adjusted odds ratios of significant risk factors (P < .05) by a factor of 4 to derive an integer point system. RESULTS: 1307 patients underwent isolated CABG, including 762/1307 patients with a preoperative left atrial diameter measurement. 209/762 patients (27%) developed new onset AF including 165/611 (27%) in the derivation cohort. We identified four risk factors independently associated with postoperative AF which comprised the PAFAC score: age > 60 years (5 points), White race (5 points), baseline GFR < 90 mL/min (4 points) and left atrial diameter > 4.5 cm (4 points). Scores ranged from 0-18. The PAFAC score was then applied to the validation cohort and predicted incidence of AF strongly correlated with observed incidence (r = 0.92). CONCLUSION: The PAFAC score is easy to calculate and can be used upon ICU admission to reliably identify patients at high risk of developing AF after isolated CABG.
Asunto(s)
Fibrilación Atrial/etiología , Puente de Arteria Coronaria/efectos adversos , Medición de Riesgo/métodos , Fibrilación Atrial/diagnóstico , Puente de Arteria Coronaria/métodos , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: TDP-43 proteinopathy is a prominent pathological feature that occurs in a number of human diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and inclusion body myositis (IBM). Our recent finding that TDP-43 represses nonconserved cryptic exons led us to ask whether cell type-specific cryptic exons could exist to impact unique molecular pathways in brain or muscle. METHODS: In the present work, we investigated TDP-43's function in various mouse tissues to model disease pathogenesis. We generated mice to conditionally delete TDP-43 in excitatory neurons or skeletal myocytes and identified the cell type-specific cryptic exons associated with TDP-43 loss of function. RESULTS: Comparative analysis of nonconserved cryptic exons in various mouse cell types revealed that only some cryptic exons were common amongst stem cells, neurons, and myocytes; the majority of these nonconserved cryptic exons were cell type-specific. CONCLUSIONS: Our results suggest that in human disease, TDP-43 loss of function may impair cell type-specific pathways.
Asunto(s)
Proteínas de Unión al ADN/genética , Exones/genética , Células Musculares/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Neuronas/metabolismo , Animales , Modelos Animales de Enfermedad , Immunoblotting , Inmunohistoquímica , Ratones , Ratones Noqueados , Ratones Transgénicos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteinopatías TDP-43/genéticaRESUMEN
Sickle cell disease is a life-limiting inherited hemoglobinopathy that poses inherent risk for surgical complications following cardiac operations. In this review, we discuss preoperative considerations, intraoperative decision-making, and postoperative strategies to optimize the care of a patient with sickle cell disease undergoing cardiac surgery.