Circulating biomarkers are not associated wtih endoleaks after endovascular repair of abdominal aortic aneurysms

Objective: Endoleak is a common complication of endovascular repair (EVAR) for abdominal aortic aneurysm (AAA), but can only be detected through prolonged follow-up with repeated aortic imaging. This study examined the potential for circulating matrix metalloproteinase-9 (MMP9), osteoprotegerin (OPG), D-dimer, homocysteine (HCY) and C-reactive protein (CRP) to act as diagnostic markers for endoleak in AAA patients undergoing elective EVAR. Methods: Linear mixed effects models were constructed to assess differences in AAA diameter after EVAR, between groups of patients who did, and did not develop endoleak during follow-up, adjusting for potential confounders. Circulating MMP9, OPG, D-dimer, HCY and CRP concentrations were measured in pre- and post-operative plasma samples. The association of these markers with endoleak diagnosis was assessed using linear mixed effects adjusted as above. The potential for each marker to diagnose endoleak was assessed using receiver operator characteristic (ROC) curves. Results: Seventy-five patients were included in the current study, 24 of whom developed an endoleak during follow-up. Patients with an endoleak had significantly large AAA sac diameters than those that did not have an endoleak. None of the assessed markers showed a significant association with endoleak. This was confirmed through ROC curve analyses indicating poor diagnostic ability for all markers. Conclusions: Circulating concentrations of MMP9, OPG, D-dimer, HCY and CRP were not associated with endoleak in patients undergoing EVAR in this study

Seropositivity to Burkholderia pseudomallei does not\ud reflect the development of cell-mediated immunity

Cell-mediated immunity to Burkholderia pseudomallei, the causative agent of melioidosis, provides protection from disease progression. An indirect haemagglutination assay was used to detect antibodies to B. pseudomallei in 1500 healthy donors in an endemic region of Australia. Lymphocyte proliferation, activation and cytokine expression to B. pseudomallei antigen were determined in eight donors who were seropositive and in eight age- and sex-matched controls. In North Queensland, 2.5% of the population was seropositive for B. pseudomallei, which is less than half that which was previously described. Of clinical significance was the observation that while 75% of the seropositive individuals had increased lymphocyte proliferation to B. pseudomallei antigens, there were no significant differences observed in lymphocyte activation or production of cytokines

A Randomised Controlled Trial Assessing the Effects of Peri-operative Fenofibrate Administration on Abdominal Aortic Aneurysm Pathology: Outcomes From the FAME Trial

Objective: Experimental studies suggest that fenofibrate prevents abdominal aortic aneurysm (AAA) development by lowering aortic osteopontin (OPN) concentration and reducing the number of macrophages infiltrating the aortic wall. The current study examined the effects of a short course of fenofibrate on AAA pathology in people with large AAAs awaiting aortic repair. Methods: This randomised double blind parallel trial included male and female participants aged ≥ 60 years who had an asymptomatic AAA measuring ≥ 50 mm and were scheduled to undergo open AAA repair. Participants were allocated to fenofibrate (145 mg/day) or matching placebo for at least two weeks before elective AAA repair. Blood samples were collected at recruitment and immediately prior to surgery. AAA biopsies were obtained during aortic surgery. The primary outcomes were (1) AAA OPN concentration; (2) serum OPN concentration; and (3) number of AAA macrophages. Exploratory outcomes included circulating and aortic concentrations of other proteins previously associated with AAA. Outcomes assessed at a single time point were compared using logistic regression. Longitudinal outcomes were compared using linear mixed effects models. Results: Forty-three participants were randomised. After three withdrawals, 40 were followed until the time of surgery (21 allocated fenofibrate and 19 allocated placebo). As expected, serum triglycerides reduced significantly from recruitment to the time of surgery in participants allocated fenofibrate. No differences in any of the primary and exploratory outcomes were observed between groups. Conclusion: A short course of 145 mg of fenofibrate/day did not lower concentrations of OPN or aortic macrophage density in people with large AAAs

Depletion of CD11c+ dendritic cells in apolipoprotein E-deficient mice limits angiotensin II-induced abdominal aortic aneurysm formation and growth

Objective: The role of chronic inflammation in abdominal aortic aneurysm (AAA) is controversial. CD11c+ antigen-presenting cells (APCs) (dendritic cells (DCs)) have been reported in human AAA samples but their role is unclear. The effect of conditional depletion of CD11c+ cells on experimental AAA was investigated in the angiotensin II (AngII)-infused apolipoprotein E-deficient (ApoE–/–) mouse model. Approach: CD11c-diphtheria toxin (DT or D.tox) receptor (DTR), ovalbumin (OVA) fragment aa 140–386, and enhanced green fluorescent protein (eGFP)-ApoE–/– (CD11c.DOG.ApoE–/–) mice were generated and CD11c+ cell depletion achieved with D.tox injections (8 ng/g body weight, i.p., every-other-day). AAA formation and growth were assessed by measurement of supra-renal aortic (SRA) diameter in vivo by serial ultrasound and by morphometry assessment of harvested aortas at the end of the study. Results: Depletion of CD11c+ cells by administration of D.tox on alternative days was shown to reduce the maximum diameter of AAAs induced by 28 days AngII infusion compared with controls (D.tox, 1.58 ± 0.03 mm vs Vehicle control, 1.81 ± 0.06 mm, P<0.001). CD11c+ depletion commencing after AAA establishment by 14 days of AngII infusion, was also shown to lead to smaller AAAs than controls after a further 14 days (D.tox, 1.54 ± 0.04 mm vs Vehicle control, 1.80 ± 0.03 mm, P<0.001). Flow cytometry revealed significantly lower numbers of circulating CD44hi CD62Llo effector CD4 T cells, CD44hi CD62Llo effector CD8 T cells and B220+ B cells in CD11c+ cell-depleted mice versus controls. CD11c+ depletion attenuated SRA matrix degradation indicated by decreased neutrophil elastase activity (P=0.014), lower elastin degradation score (P=0.012) and higher collagen content (P=0.002). Conclusion: CD11c+ cell-depletion inhibited experimental AAA development and growth associated with down-regulation of circulating effector T cells and attenuated matrix degradation. The findings suggest involvement of autoreactive immune cells in AAA pathogenesis