Next-Generation Sequencing of microRNAs in Small Abdominal Aortic Aneurysms: MiR-24 as a Biomarker.

BACKGROUND: Small abdominal aortic aneurysms (AAAs) are asymptomatic but can potentially lead to rupture if left undetected. To date, there is a lack of simple nonradiologic routine tests available for diagnosing AAAs. MicroRNAs (miRNAs) have been proven to be good-quality biomarkers in several diseases, including AAA. METHODS: An attempt to identify a panel of circulating miRNAs with differential expression in AAAs via next-generation sequencing (NGS) was performed in serum samples: small AAAs (n = 3), large AAAs (n = 3), and controls (n = 3). For miR-24, validation with real-time polymerase chain reaction (PCR) was undertaken in a larger group (n = 80). RESULTS: In the NGS study, 23 miRNAs were identified as differentially expressed (with statistical significance) in small AAAs in comparison with controls. Among them, miR-24 showed the largest upregulation with 23-fold change (log2FC 4.5, P = 0.024). For large AAAs compared with controls, and small AAAs compared with large AAAs, a panel of 33 and 131 miRNAs showed statistically significant differential expression, respectively. Based on the results of the NGS stage, a literature search was performed, and information regarding AAA pathogenesis, coronary artery disease, and peripheral arterial disease was documented where applicable: miR-24, miR-103, miR-193a, miR-486, miR-582, and miR-3663. Of these 6 miRNAs, miR-24 was chosen for further validation with real-time PCR. Additionally, in the NGS study analysis, 17 miRNAs were common between the small-large AAAs, small AAAs-controls, and large AAAs-controls comparisons: miR-7846, miR-3195, miR-486-2, miR-3194, miR-5589, miR-1538, miR-3178, miR-4771-1, miR-5695, miR-6504, miR-1908, miR-6823, miR-3159, miR-23a, miR-7853, miR-496, and miR-193a. Interestingly, in the validation stage with real-time PCR, miR-24 was found downregulated in small and large AAAs compared with controls (fold-changes: 0.27, P = 0.015 and 0.15, P = 0.005, respectively). No correlation was found between average Ct values, aneurysm diameter, and patients' age. CONCLUSIONS: Our findings further highlight the importance of miR-24 as a potential biomarker as well as a therapeutic target for abdominal aneurysmal disease. Future research and validation of a panel of miRNAs for AAA would aid in diagnosis and discrimination between diseases with overlapping pathogeneses.

Network meta-analysis of trials comparing first line endovascular treatments for arteriovenous fistula stenosis.

OBJECTIVE: We investigated the comparative effectiveness of different endovascular treatments for patients with failing autogenous arteriovenous fistulas (AVFs) with outflow vein stenosis. METHODS: The Medline (via PubMed) and SCOPUS databases were searched. We performed a systematic review and network meta-analysis of randomized controlled trials that had investigated the effectiveness of plain balloon angioplasty (PBA), cutting balloon angioplasty, and drug-coated balloon angioplasty (DCBA) to treat vein stenoses in autogenous AVFs. Studies of central vein stenosis were excluded. The main outcome measures were the failure rates at 6 months and 1 year after treatment. RESULTS: Eleven randomized controlled trials were included, with 814 patients, 395 of whom had undergone PBA. The network meta-analysis showed that DCBA at 6 months was significantly more effective than PBA (odds ratio, 0.39; 95% confidence interval, 0.18-0.81) and ranked as the best treatment option, although the difference was not statistically significant compared with cutting balloon angioplasty (odds ratio, 0.65; 95% confidence interval, 0.20-2.12). The differences among the three treatments at 1 year were not statistically significant. Additional conventional pairwise meta-analyses did not find significant differences at 1 year. CONCLUSIONS: In failing AVFs with outflow stenosis, DCBA was significantly superior to PBA, with improved 6-month failure rates. However the effectiveness of DCBA in the long term deserves further investigation.

Editor's Choice - Network Meta-Analysis of Carotid Endarterectomy Closure Techniques.

OBJECTIVE: There is discordance between reviews comparing eversion endarterectomy (EvE) with conventional carotid endarterectomy (CEA) mostly because under this term various "closure" techniques are included, from direct closure to a wide spectrum of patches with different materials. DATA SOURCES: MEDLINE (via PubMed) and SCOPUS. REVIEW METHODS: This was a systematic review of the Medline (via PubMed) and SCOPUS databases for randomised controlled trials (RCTs) comparing different CEA closure techniques. Network meta-analysis (NMA) was performed with a frequentist approach. The primary and the secondary outcome measures were the 30 day combined stroke and death rate and the late restenosis rate, respectively. RESULTS: Twenty-three RCTs were finally included in the NMA with a total of 4440 patients randomised, representing seven different techniques (primary carotid closure, n = 753; EvE, n = 431; vein patch closure, n = 973; polytetrafluoroethylene [PTFE] patch, n = 948; Dacron patch, n = 828; bovine pericardium patch, n = 249; and polyurethane patch, n = 258). NMA showed that EvE had a decreased 30 day combined stroke and death rate vs. all other methods of arterial closure, with the exception of PTFE and bovine pericardium patching. Additionally, EvE was associated with the lowest restenosis rate vs. all other methods of arterial closure after CEA. EvE was significantly superior to Dacron patches with regard to late restenosis, with the prediction intervals (PIs) lying completely on the beneficial side (risk ratio 0.06; PI 0.01-0.58) and increasing confidence of this comparison. Rare catastrophic complications of vein patch blow out or synthetic patch infection were reported in 0.2% of the total (n = 9/4 400) and no comparisons were made. CONCLUSION: EvE and patching with bovine pericardium or PTFE is associated with a lower incidence in both short term and late undesired outcomes following CEA and seems to represent the best choice compared with other carotid closure techniques. These results may support the vascular surgeon's choice of technique/patch material.

Plain versus paclitaxel-coated balloon angioplasty in arteriovenous fistula and graft stenosis: An umbrella review.

An umbrella review was performed to synthesize the evidence from systematic reviews/meta-analyses of clinical trials investigating the efficacy and safety of paclitaxel-coated balloons (PCB) vs. conventional balloon angioplasty in arteriovenous fistulas (AVFs) and grafts stenosis.Medline (via PubMed) and SCOPUS databases were searched up to July 15th 2020. All meta-analyses that enrolled randomized controlled trials (RCTs) comparing PCB with plain balloons in AVFs and grafts were included. Re-analysis of original data was performed assessing predictive intervals (PI). Quality of the included meta-analyses was assessed using AMSTAR score. Eight meta-analyses were included and four clinical outcomes [target lesion primary patency (TLPP), circuit primary patency, mortality, complication rate] derived from 14 RCTs, were analyzed. There were no significant differences in the TLPP in meta-analyses providing data purely from autologous AVFs. Significant benefits regarding TLPP and circuit primary patency at 3, 6, and 12-months in favor of PCB were reported in four meta-analyses mixing AVFs and grafts; however when PI were assessed, in all but one meta-analysis these included the null value, indicating no significant benefit. In only one meta-analysis significant difference of TLPP at 12-months in favor of PCB was noticed. (Odds Ratio 0.0009 PI: 0.28-0.85) No mortality difference was noticed in four meta-analyses providing data up to 24 months. In conclusion this overview revealed a modest benefit of using PCB angioplasty compared to plain angioplasty in AVFs and graft stenosis. No increased mortality was noticed in the PCB group.