RESUMEN
BACKGROUND: The impact of folate deficiency on global DNA methylation is uncertain. It also is unclear whether global DNA methylation is associated with outcome in HCC. LINE-1 methylation levels, as a surrogate marker of global methylation, may be influenced by folate deficiency. However, the interaction between LINE-1 methylation and folate level on overall survival (OS) in hepatocellular carcinoma (HCC) patients is unknown. We evaluated whether LINE-1 hypomethylation and folate deficiency are associated with HCC prognosis. METHODS: We prospectively recruited 172 HCC patients between 2008 and 2012. LINE-1 methylation levels in plasma and white blood cells (WBC) were measured by pyrosequencing, and plasma folate levels by a radioprotein-binding assay. RESULTS: Patients with plasma LINE-1 methylation <70.0% (hypomethylation) had significantly worse OS compared with those with ≥70.0% methylation (hypermethylation) [hazard ratio (HR) = 1.77; 95% confidence interval (CI) 1.12-2.79; P = 0.015]. HCC patients with lower plasma folate levels also had worse survival (<27.7 vs. ≥27.7 nmol/L; HR = 1.96; 95% CI, 1.24-3.09; P = 0.004). Furthermore, survival was poor in patients in whom both plasma LINE-1 methylation and folate levels were low compared with those patients in whom both levels were high (HR = 3.36; 95%CI, 1.77-6.40; P < 0.001). This interaction neared statistical significance (P = 0.057). No significant association was found between WBC LINE-1 methylation levels and survival. CONCLUSIONS: These findings suggest that both lower plasma levels of LINE-1 methylation and folate are associated with worse survival in HCC patients.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/mortalidad , Metilación de ADN , Ácido Fólico/sangre , Genoma Humano , Neoplasias Hepáticas/mortalidad , Elementos de Nucleótido Esparcido Largo , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/genética , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Pronóstico , Regiones Promotoras Genéticas , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
Background: Trauma team leadership is a core skill for the practice of emergency medicine (EM). In this study our goal was to explore EM residents' perception of their trauma leadership skill development through formal and informal processes and to understand factors that may impact the development and implementation of trauma leadership skills. Methods: Using qualitative semi-structured interviews, we explored the leadership experiences of 10 EM residents ranging from second to fourth postgraduate year. Interviews were conducted between July 26-October 31, 2019 and were audio-recorded, transcribed, and de-identified. We analyzed data using qualitative content analysis. Results: Residents discussed three main themes: 1) sources of leadership development; 2) challenges with simultaneously assuming a dual leader-learner role; and 3) contextual factors that impact their ability to assume the leadership role, including the professional hierarchy in the clinical environment, limitations in the physical environment, and gender bias. Conclusion: This study describes the complex factors and experiences that contribute to the development and implementation of trauma team leadership skills in EM residents. This includes three primary sources of leadership development, the dual role of leader and learner, and various contextual factors. Research is needed to understand how these factors and experiences can be leveraged or mitigated to improve resident leadership training outcomes.