Determinación de mutaciones (del E746-A750 exón 19 y L858R exón 21) en el gen receptor del factor de crecimiento epidérmico (EGFR) en muestras de suero y biopsia de carcinoma pulmonar no microcítico (CPNM)

Introducción: Las mutaciones, Del_E746_A750 exón 19 y L858R exón 21 del gen EGFR en células tumorales de CPNM representan biomarcadores de respuesta a fármacos inhibidores de tirosina cinasa (ITK). Pacientes con tumores positivos a mutaciones EGFR muestran mejor respuesta y mayor sobrevivencia. Estas mutaciones ocupan el 90% de las mutaciones en cancer de pulmón. Objetivo: Evaluar la frecuencia de las mutaciones Del_E746_A750-exon 19 y L858R-exon 21 del EGFR en muestras de biopsia de CPNM y en muestras de suero de población abierta de Yucatán. Material y métodos: Se seleccionaron 19 muestras de biopsia de CNPM y 101 sueros de sujetos sanos. Las mutaciones Del_E746_A750 y L858R en EGFR se determinaron mediante amplificación por PCR alelo específica (PCR-ASO). Se calcularon las frecuencias genotípicas y alélicas y su distribución según Hardy Weinberg, utilizando la plataforma SNPstats. Resultados: En muestras de suero se determinó el genotipo homocigoto (1/1) en 26.58%, 73.42% el heterocigoto (1/0) y ausencia del genotipo mutante con deleción (0/0) para Del E746_A750; en tanto que para L858R, el 21.78% resultó homocigoto (TT), 54.46% heterocigoto (T/G) y 23.76% mutantes GG. En las biopsias el heterocigoto fue más frecuente en ambas mutaciones 63.16% y 73.68% para Del_E746_A750 y L858R, respectivamente. Conclusión: La frecuencia de las mutaciones del gen EGFR en la población local de Yucatán (sueros) fue de 36.71% para la deleción Del746-750 en exón 19 y 50.99% para L858R en exón 21. La distribución de las mutaciones en muestras de biopsia CPNM  resultó en 42.11% para cada mutación estudiada

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Determinación de mutaciones (del E746-A750 exón 19 y L858R exón 21) en el gen receptor del factor de crecimiento epidérmico (EGFR) en muestras de suero y biopsia de carcinoma pulmonar no microcítico (CPNM)

Introduction. EGFR mutations, del E746-A750 in exon 19 and L858R in exon 21 in tumor cells of NMLC represent biomarkers of response to tyrosine kinase inhibitors (TKI) therapy. Patients with tumors positive for EGFR mutations show better response and greater survival. These mutations occupy 90% of mutations in lung cancer. Objective. To evaluate the frequency of mutations del E746-A750-exon 19 and L858R-exon 21 of EGFR gene in NMLC biopsy samples and in serum samples of the general population from Yucatán. Material and methods. 19 NMLC biopsy samples of adenocarcinoma type and 101 serum samples from healthy subjects were selected. EGFR mutations del E746-A750 and L858R were determined by allele-specific PCR amplification (PCR-ASO). The genotypic and allelic frequencies; and their distribution according to Hardy Weinberg expectations were calculated using the SNPstats software. Results. For serum, EGFR del E746-A750 mutation, homozygous genotype (1/1) was present in 26.58%, heterozygote (1/0) in 73.42% and absence of mutant genotype with deletion (0/0); whereas for L858R mutation, 21.78% were homozygous (TT), 54.46% heterozygous (T/G)and 23.76% GG mutants. For the NMLC biopsies, the heterozygote was the most frequent genotype for both mutations, 63.16% and 73.68% for del E746-A750 and L858R, respectively. Conclusion. The frequency of mutations of EGFR gene in serum samples was 36.71% for deletion delE746-A750 in exon 19 and 50.99% for L858R in exon 21. Distribution of mutations in biopsy samples NMLC resulted in 42.11% for each EGFR mutatio