RESUMO
BACKGROUND: Promoter hypermethylation is one of the enabling mechanisms of hallmarks of cancer. Tumor suppressor genes like RARB and GSTP1 have been reported as hypermethylated in breast cancer tumors compared with normal tissues in several populations. This case-control study aimed to determine the association between the promoter methylation ratio (PMR) of RARB and GSTP1 genes (separately and as a group) with breast cancer and its clinical-pathological variables in Peruvian patients, using a liquid biopsy approach. METHODS: A total of 58 breast cancer patients and 58 healthy controls, matched by age, participated in the study. We exacted cell-free DNA (cfDNA) from blood plasma and converted it by bisulfite salts. Methylight PCR was performed to obtain the PMR value of the studied genes. We determined the association between PMR and breast cancer, in addition to other clinicopathological variables. The sensitivity and specificity of the PMR of these genes were obtained. RESULTS: A significant association was not found between breast cancer and the RARB PMR (OR = 1.90; 95% CI [0.62-6.18]; p = 0.210) or the GSTP1 PMR (OR = 6.57; 95% CI [0.75-307.66]; p = 0.114). The combination of the RARB + GSTP1 PMR was associated with breast cancer (OR = 2.81; 95% CI [1.02-8.22]; p = 0.026), controls under 50 years old (p = 0.048), patients older than 50 (p = 0.007), and postmenopausal (p = 0.034). The PMR of both genes showed a specificity of 86.21% and a sensitivity of 31.03%. CONCLUSION: Promoter hypermethylation of RARB + GSTP1 genes is associated with breast cancer, older age, and postmenopausal Peruvian patients. The methylated promoter of the RARB + GSTP1 genes needs further validation to be used as a biomarker for liquid biopsy and as a recommendation criterion for additional tests in asymptomatic women younger than 50 years.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Metilação de DNA , Glutationa S-Transferase pi/genética , PeruRESUMO
Introducción: El artículo resume el proceso de elaboración de la Guía de Práctica Clínica (GPC) para el manejo de las crisis glucémicas en pacientes adultos con diabetes mellitus de la Red de Clínicas AUNA. Métodos: Las preguntas PICO fueron priorizadas por el Grupo Elaborador de la GPC (GEG) luego de lo cual se concluyó en trabajar 10 preguntas PICO. Para dar respuesta a las preguntas se realizó una búsqueda sistemática de GPC, revisiones sistemáticas y estudios primarios. Se utilizó la metodología "GRADE-Adolopment" y los lineamientos de la normativa nacional para la formulación de recomendaciones. Resultados: Se formularon 10 recomendaciones (nueve fuertes y una débil), 18 puntos de buena práctica clínica, dos flujogramas para el manejo (uno para el diagnóstico y el otro para el tratamiento de crisis glucémicas), 5 tablas resumen sobre el manejo y 1 tabla para la vigilancia y seguimiento. Los temas que abarcaron las recomendaciones para el manejo de las crisis glucémicas fueron: crisis hiperglucémicas (evaluación de hemoglobina glucosilada; evaluación de b-hidroxibutirato; tratamiento con insulina, potasio, cloruro de sodio 0.9%, fósforo y bicarbonato de sodio) y crisis hipoglucémicas (administración de carbohidratos, monitoreo y programa educativo para evitar el reingreso). Conclusión: El presente artículo resume la metodología y las recomendaciones basadas en evidencia de la GPC para el manejo de la crisis glucémica en pacientes con diabetes mellitus de la Red de Clínicas AUNA.
Introduction: The manuscript summarizes the process of elaboration of the Clinical Practice Guide (CPG) for the management of glycemic crises in adult patients with diabetes mellitus of the AUNA Clinic Network. A multidisciplinary team of medical assistants and methodologists carried out the development of the CPG and then there was an external review by a specialist in the field. Methods: The Elaboration Group of the CPG (GEG) concluded on 10 PICO questions. A systematic search for CPG, systematic reviews and primary studies was carried out to answer these PICO questions. To make recommendations we used the "GRADE-Adolopment" methodology and the guidelines of the national regulations. Results: Ten recommendations were made (nine strong and one weak), 18 points of good clinical practice and two flowcharts for management (one for diagnosis and the other for the treatment of glycemic crises), 04 consensus tables on management and 01 table for surveillance and monitoring. The topics covered by the recommendations for the management of glycemic crises were hyperglycemic crises (glycosylated hemoglobin evaluation; b-hydroxybutyrate evaluation; insulin, potassium, 0.9% sodium chloride, phosphorus, sodium bicarbonate treatments) and hypoglycemic crises (carbohydrate administration, monitoring, educational program to avoid reentry). Conclusion: This article summarizes the methodology and evidence-based recommendations of the CPG for the management of glycemic crisis in patients with diabetes mellitus in AUNA.
RESUMO
The manuscript summarizes the process of elaboration of the Clinical Practice Guide (CPG) for the management of glycemic crises in adult patients with diabetes mellitus of the AUNA Clinic Network. A multidisciplinary team of medical assistants and methodologists carried out the development of the CPG and then there was an external review by a specialist in the field. The Elaboration Group of the CPG (GEG) concluded on 10 PICO questions. A systematic search for CPG, systematic reviews and primary studies was carried out to answer these PICO questions. To make recommendations we used the "GRADE-Adolopment" methodology and the guidelines of the national regulations. Ten recommendations were made (nine strong and one weak), 18 points of good clinical practice and two flowcharts for management (one for diagnosis and the other for the treatment of glycemic crises), 04 consensus tables on management and 01 table for surveillance and monitoring. The topics covered by the recommendations for the management of glycemic crises were hyperglycemic crises (glycosylated hemoglobin evaluation; b-hydroxybutyrate evaluation; insulin, potassium, 0.9% sodium chloride, phosphorus, sodium bicarbonate treatments) and hypoglycemic crises (carbohydrate administration, monitoring, educational program to avoid reentry)
El artículo resume el proceso de elaboración de la Guía de Práctica Clínica (GPC) para el manejo de las crisis glucémicas en pacientes adultos con diabetes mellitus de la Red de Clínicas AUNA. El proceso de elaboración se llevó a cabo con la participación de un equipo multidisciplinario de médicos asistenciales, metodólogos y un revisor externo (un especialista con dominio en la metodología y el tema). La priorización de preguntas PICO fue realizada por el Grupo Elaborador de la GPC (GEG) luego de lo cual se concluyó en trabajar 10 preguntas PICO. Para dar respuesta a las preguntas se realizó una búsqueda sistemática de GPC, revisiones sistemáticas y estudios primarios. Se utilizó la metodología "GRADE-Adolopment" y los lineamientos de la normativa nacional para la formulación de recomendaciones. Se formularon 10 recomendaciones (nueve fuertes y una débil), 18 puntos de buena práctica clínica, dos flujogramas para el manejo (uno para el diagnóstico y el otro para el tratamiento de crisis glucémicas), cinco (05) tablas resumen sobre el manejo y una (01) tabla para la vigilancia y seguimiento. Los temas que abarcaron las recomendaciones para el manejo de las crisis glucémicas fueron: crisis hiperglucémicas (evaluación de hemoglobina glucosilada; evaluación de b-hidroxibutirato; tratamiento con insulina, potasio, cloruro de sodio 0.9%, fósforo, bicarbonato de sodio) y crisis hipoglucémicas (administración de carbohidratos, monitoreo, programa educativo para evitar el reingreso).
