Circulating microRNAs signature correlates with positive [18F]fluorodeoxyglucose-positron emission tomography in patients with abdominal aortic aneurysm.

BACKGROUND: Prediction of abdominal aortic aneurysm (AAA) rupture is a challenging issue. Small noncoding microRNAs (miRNAs) are potent regulators of gene expression and are considered as valuable circulating biomarkers. Recently, [18F]fluorodeoxyglucose (FDG) uptake detected by positron emission tomography (PET) in AAA was correlated with cellular and molecular alterations involved in wall instability and its potential rupture. Our study aimed at identifying circulating miRNAs correlated with a positive PET that could help discriminate patients at high risk of rupture. METHODS: The level of 372 miRNAs was evaluated by polymerase chain reaction array in plasma from 35 AAA patients displaying no FDG uptake (A0) and 22 patients with a positive PET uptake (A+). The modulated miRNAs were validated by quantitative polymerase chain reaction and measured in aneurysmal tissues from both groups of patients. RESULTS: Six circulating miRNAs were found significantly modulated in A+ vs A0 patients. They were significantly correlated not only between them but also with the intensity of FDG uptake. Two of them correlated also with the AAA diameter. These miRNAs displayed significant discriminating power between the A+ and A0 groups as determined by receiver operating characteristic curves. Three downregulated circulating miRNAs (miR-99b-5p, miR-125b-5p, and miR-204-5p) were also significantly reduced in the aneurysmal tissue, specifically in the FDG-uptake site, compared with a negative zone in the same aneurysm and with A0 aneurysms. They were further significantly inversely correlated with the expression, at the positive uptake site, of some of their potential gene targets, most notably matrix metalloproteinase 13. CONCLUSIONS: Six miRNAs were identified as potential new circulating biomarkers of PET+ AAA. Three of these were similarly modulated in the metabolically active aneurysmal wall and might be directly involved in AAA instability.

Disease-specific mortality burdens in a rural Gambian population using verbal autopsy, 1998-2007.

OBJECTIVE: To estimate and evaluate the cause-of-death structure and disease-specific mortality rates in a rural area of The Gambia as determined using the InterVA-4 model. DESIGN: Deaths and person-years of observation were determined by age group for the population of the Farafenni Health and Demographic Surveillance area from January 1998 to December 2007. Causes of death were determined by verbal autopsy (VA) using the InterVA-4 model and ICD-10 disease classification. Assigned causes of death were classified into six broad groups: infectious and parasitic diseases; cancers; other non-communicable diseases; neonatal; maternal; and external causes. Poisson regression was used to estimate age and disease-specific mortality rates, and likelihood ratio tests were used to determine statistical significance. RESULTS: A total of 3,203 deaths were recorded and VA administered for 2,275 (71%). All-age mortality declined from 15 per 1,000 person-years in 1998-2001 to 8 per 1,000 person-years in 2005-2007. Children aged 1-4 years registered the most marked (74%) decline from 27 to 7 per 1,000 person-years. Communicable diseases accounted for half (49.9%) of the deaths in all age groups, dominated by acute respiratory infections (ARI) (13.7%), malaria (12.9%) and pulmonary tuberculosis (10.2%). The leading causes of death among infants were ARI (5.59 per 1,000 person-years [95% CI: 4.38-7.15]) and malaria (4.11 per 1,000 person-years [95% CI: 3.09-5.47]). Mortality rates in children aged 1-4 years were 3.06 per 1,000 person-years (95% CI: 2.58-3.63) for malaria, and 1.05 per 1,000 person-years (95% CI: 0.79-1.41) for ARI. The HIV-related mortality rate in this age group was 1.17 per 1,000 person-years (95% CI: 0.89-1.54). Pulmonary tuberculosis and communicable diseases other than malaria, HIV/AIDS and ARI were the main killers of adults aged 15 years and over. Stroke-related mortality increased to become the leading cause of death among the elderly aged 60 years or more in 2005-2007. CONCLUSIONS: Mortality in the Farafenni HDSS area was dominated by communicable diseases. Malaria and ARI were the leading causes of death in the general population. In addition to these, diarrhoeal disease was a particularly important cause of death among children under 5 years of age, as was pulmonary tuberculosis among adults aged 15 years and above.