Discovery of novel DNA methylation biomarkers for non-invasive sporadic breast cancer detection in the Latino population.

Human diversity is one of the main pitfalls in the development of robust worldwide biomarkers in oncology. Epigenetic variability across human populations is associated with different genetic backgrounds, as well as variable lifestyles and environmental exposures, each of which should be investigated. To identify potential non-invasive biomarkers of sporadic breast cancer in the Uruguayan population, we studied genome-wide DNA methylation using Illumina methylation arrays in leukocytes of 22 women with sporadic breast cancer and 10 healthy women in a case-control study. We described a panel of 38 differentially methylated CpG positions that was able to cluster breast cancer patients (BCP) and controls, and that also recapitulated methylation differences in 12 primary breast tumors and their matched normal breast tissue. Moving forward, we simplified the detection method to improve its applicability in a clinical setting and used an independent well-characterized cohort of 80 leukocyte DNA samples from BCP and 80 healthy controls to validate methylation results at specific cancer-related genes. Our investigations identified methylation at CYFIP1 as a novel epigenetic biomarker candidate for sporadic breast cancer in the Uruguayan population. These results provide a proof-of-concept for the design of larger studies aimed at validating biomarker panels for the Latin American population.

The Correlation Between Obesity-Related Diseases and Non-alcoholic Fatty Liver Disease in Women in the Pre-operative Evaluation for Bariatric Surgery Assessed by Transient Hepatic Elastography.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common, severe disease in obese patients. However, NAFLD is usually underestimated by ultrasonography. Liver biopsy is not routinely done in bariatric surgery or during the follow-up. This study therefore examined the correlation between metabolic syndrome and NAFLD in morbidly obese patients based on an assessment using transient hepatic elastography (THE). MATERIAL AND METHODS: This study involved 50 female patients in the pre-operative phase for bariatric surgery. Before surgery, we collected clinical, laboratory, and anthropometric variables. THE measurements were obtained using a FibroScan® device (Echosens, Paris, France), and steatosis was quantified using Controlled Attenuation Parameter software (CAP). Statistical analyses were done using linear correlation and the Kruskal-Wallis test. RESULTS: The mean of THE and CAP values were 7.56 ± 4.78 kPa and 279.94 ± 45.69 dB/m, respectively, and there was a significant linear correlation between the two measurements (r = 0.651; p < 0.001). The numbers of metabolic syndrome parameters did not influence the THE (p = 0.436) or CAP (p = 0.422) values. HbA1c and HOMA-IR showed a strong linear correlation with CAP (r = 0.643, p = 0.013 and r = 0.668, p = 0.009, respectively) and a tendency to some linear correlation with THE (r = 0.500, p = 0.05 and r = 0.500, p = 0.002, respectively). CONCLUSION: Morbidly obese women submitted to FibroScan® presented a high prevalence of severe steatosis and advanced fibrosis in our sample. Insulin resistance parameters were correlated with steatosis, but less with fibrosis.

Experiencia con Ecocardiograma de estrés dipiridamol y Reserva coronaria no invasiva: Comunicación preliminar / Dipyridamol Stress Echocardiography and Non-invasive Coronary Reserve: Preliminary report

Antecedentes: El Ecocardiograma de Estrés (EE) es una técnica ampliamente utilizada en el estudio de pacientes con Enfermedad Coronaria conocida o sospechada Recientemente se ha preconizado efectuar el test vasodilatador, método recomendado para evaluar no invasivamente la reserva de flujo coronario (RFC). Objetivos: Mostrar la experiencia preliminar con el EE Dipiridamol, con un seguimiento inicial, así como el estudio de la RFC en la porción distal de la arteria Descendente Anterior (ADA). Métodos: Se analizaron 164 pacientes (101 hombres, edad promedio 65 años) a los que se les efectuó un EE Dipiridamol entre Julio 2011 y Septiembre 2012, con una dosis de 0.84mg/kg en 6 minutos, que incluyó el estudio de RFC. Todos los pacientes completaron la prueba sin efectos secundarios significativos, y en un tiempo menor a 25 minutos. El seguimiento se hizo con miras a la aparición de eventos cardiovasculares mayores (revascularización, infarto al miocardio y muerte cardíaca). Resultados: EE resultó positivo para isquemia en 19 (21 por ciento) pacientes. En 19 (12 por ciento) el EE resultó alterado por motilidad parietal; 29 (15 por ciento) presentaron respuesta anormal en la RFC, con una coincidencia de 12 pacientes (7 por ciento) con ambos tipo de alteración; En 142 (88 por ciento) pacientes se logró medir la RFC en ADA. En 151 pacientes se obtuvo datos confiables del seguimiento, que fue en promedio 10 meses (6 a 18); entre estos, 10 pacientes tuvieron alguna revascularización. No hubo infartos ni fallecidos por causa cardio-vascular. Dado el corto período de seguimiento y baja incidencia de eventos, no se pudo establecer el valor predictivo del resultado de la prueba en esta muestra. Conclusiones: Esta experiencia permitió familiarizarse con la técnica del EE con Dipiridamol y estudiar en un alto porcentaje la RFC en la ADA. La técnica es segura y consume muy poco tiempo. Queda pendiente la determinación del valor predictivo de estos resultados en nuestras manos.

Background: Stress Echocardiography is a common technique in the study of patients with known or suspected Coronary artery disease (CAD). Recently the vasodilation test has been recommended for the non invasive study of Coronary Flow Reserve (CFR). Aim: to report our preliminary experience with Di-pyridamol Stress Echocardiography (DSE), an initial follow-up, and the study of CFR in the distal portion of the left anterior descending coronary artery (LAD). Methods: 164 consecutive patients (101 men, mean age 65) with suspected or known CAD underwent a high-dose DSE (0.84 mg/kg over 6 min) between July 2011 and September 2012. The test included a study of CFR. All patients completed the test within 25 min. Prospective follow-up regarding major adverse cardiovascular events(revascularization, cardiac mortality and infarction) was conducted for a mean of 10 months (range 6-18) Results: DSE was positive for ischemia in 34 (21 percent) patients, showed abnormal wall motion in 19 (12 percent), abnormal CFR in 29 (15 percent) , and both abnormalities in12 (7 percent). 142 patients (88 percent) had a normal CFR in the LAD. 151 patients were followed for a mean of 10 months (6 to 18). Ten of these patients required some type of revascularization. There were no myocardial infarctions or cardiac deaths. Due to the short follow up period and the low incidence of events, it was not possible to estimate the predictive value of abnormal CFR. Conclusion: The dipyridamol echo stress test with a study of coronary flow reserve is safe and brief. The predictive value for cardiac events remains to be determined.