RESUMO
PURPOSE: Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis-related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes. METHODS: Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies. RESULTS: The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies. CONCLUSION: We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.
Assuntos
Fibrose Cística , Diabetes Mellitus , Biomarcadores , Canadá , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/genética , Estudo de Associação Genômica Ampla , Humanos , Recém-NascidoAssuntos
Cirurgia de Mohs , Neoplasias Cutâneas/patologia , Pele/patologia , Manejo de Espécimes/métodos , Inclusão do Tecido/métodos , Temperatura Baixa , Procedimentos Cirúrgicos Dermatológicos , Humanos , Neoplasias Cutâneas/cirurgia , Manejo de Espécimes/instrumentação , Inclusão do Tecido/instrumentaçãoRESUMO
Major depressive disorder is associated with increases in infectious disease risk as well as the incidence of inflammatory disorders. Declines of natural killer (NK) cell activity are reliably found in depression, whereas other studies report evidence of inflammation in depressed patients. The potential association between NK activity and circulating markers of immune activation has not been previously examined in the context of major depression. In this study, we measured levels of NK activity, circulating levels of interleukin-6 (IL-6), soluble interleukin-2 receptor, and acute phase proteins in 25 male patients with current major depressive disorder and 25 age, gender, and body weight comparable controls. As compared to controls, patients with major depressive disorder showed lower NK activity (p = .05) and higher circulating levels of IL-6 (p < .05). Levels of NK activity were not correlated with IL-6 or with other markers of immune activation. The independent effect of depression on inflammatory markers and natural killer immune responses has implications for understanding individual differences in the adverse health effects of major depressive disorder.