Background There is no drug therapy for abdominal aortic aneurysm ( AAA ). FAME‐2 (Fenofibrate in the Management of Abdominal Aortic Aneurysm 2) was a placebo‐controlled randomized trial designed to assess whether administration of 145 mg of fenofibrate/d for 24 weeks favorably modified circulating markers of AAA. Methods and Results Patients with AAA s measuring 35 to 49 mm and no contraindication were randomized to fenofibrate or identical placebo. The primary outcome measures were the differences in serum osteopontin and kallistatin concentrations between groups. Secondary analyses compared changes in the circulating concentration of AAA ‐associated proteins, and AAA growth, between groups using multivariable linear mixed‐effects modeling. A total of 140 patients were randomized to receive fenofibrate (n=70) or placebo (n=70). By the end of the study 3 (2.1%) patients were lost to follow‐up and 18 (12.9%) patients had ceased trial medication. A total of 85% of randomized patients took ≥80% of allocated tablets and were deemed to have complied with the medication regimen. Patients’ allocated fenofibrate had expected reductions in serum triglycerides and estimated glomerular filtration rate, and increases in serum homocysteine. No differences in serum osteopontin, kallistatin, or AAA growth were observed between groups. Conclusions Administering 145 mg/d of fenofibrate for 24 weeks did not significantly reduce serum concentrations of osteopontin and kallistatin concentrations, or rates of AAA growth in this trial. The findings do not support the likely benefit of fenofibrate as a treatment for patients with small AAA s. Clinical Trial Registration URL : http://www.anzctr.org.au . Unique identifier: ACTRN 12613001039774.

This study investigated the effect of 72 h of road transport on the immune status of Bos indicus steers (n = 10; age = 15 to 18 mo). Total and differential leukocyte numbers and lymphocyte function were determined at 2 d before transport (-48 h), immediately after 72 h of transport (72 h), and 6 d after transport (216 h). Phytohemagglutinin (PHA)-stimulated lymphocyte proliferation, interferon-gamma production, and tetanus-toxoid specific antibody levels were determined. Total leukocyte and eosinophil numbers showed a transient decrease at 72 h (immediately after transport; P < 0.05) and returned to baseline values by 6 d after transport. Lymphocyte numbers and antibody titers were unaffected by transportation. The PHA-stimulated lymphocyte proliferation decreased (P < 0.05) at 72 h and returned to baseline levels 6 d after transport. This study demonstrated that transportation of mature Bos indicus steers caused transient decreases in leukocyte numbers and lymphocyte function, although all measures recovered by 6 d after transport. Therefore, Bos indicus cattle may be vulnerable to infection during this period.

Circulating concentrations of MMP9, OPG, D-dimer, HCY, and CRP were not associated with endoleak in patients undergoing EVAR in this study.

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.

WHAT THIS PAPER ADDSNo drug therapy has been demonstrated to be effective in slowing abdominal aortic aneurysm (AAA) growth. Prior laboratory data suggest that fenofibrate may protect against AAA formation and progression in rodent models. This is the first trial to directly assess the impact of fenofibrate on AAA pathology through assessment of aortic biopsies. The findings suggest that a short course of fenofibrate administered in the weeks preceding elective open surgical repair did not influence hallmarks of AAA wall pathology. Despite promising pre-clinical data, findings from this study suggest that fenofibrate is an unlikely to be beneficial as an AAA treatment.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.