WHAT THIS PAPER ADDS A meta-analysis was performed of randomized placebo controlled trials on bone marrow -derived cell therapy in critical limb ischemia. This is an update of the meta-analysis by Teraa et al., published in Annals of Surgery in 2013. Since the publication of that article, the results of five additional placebo controlled trials involving 276 patients have been published. The 2013 meta-analysis found an advantage of cell therapy, with a divergent effect between the placebo controlled and non-placebo controlled trials. In the current analysis of only placebo controlled trials, no improvement with cell therapy was observed in amputation rates, survival, or amputation free survival.Objective/Background: Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease (PAD), and many patients with CLI are not eligible for conventional revascularization. In the last decade, cell based therapies have been explored as an alternative treatment option for CLI. A meta-analysis was conducted of randomized placebo controlled trials investigating bone marrow (BM) derived cell therapy in patients with CLI. Methods: The MEDLINE, Embase, and the Cochrane Controlled Trials Register databases were systematically searched, and all included studies were critically appraised by two independent reviewers. The meta-analysis was performed using a random effects model. Results: Ten studies, totaling 499 patients, were included in this meta-analysis. No significant differences were observed in major amputation rates (relative risk [RR] 0.91; 95% confidence interval [CI] 0.65e1.27), survival (RR 1.00; 95% CI 0.95e1.06), and amputation free survival (RR 1.03; 95% CI 0.86e1.23) between the cell treated and placebo treated patients. The ankle brachial index (mean difference 0.11; 95% CI 0.07e0.16), transcutaneous oxygen measurements (mean difference 11.88; 95% CI 2.73e21.02), and pain score (mean difference e0.72; 95% CI e1.37 to e0.07) were significantly better in the treatment group than in the placebo group. Conclusions: This meta-analysis of placebo controlled trials showed no advantage of stem cell therapy on the primary outcome measures of amputation, survival, and amputation free survival in patients with CLI. The potential benefit of more sophisticated cell based strategies should be explored in future randomized placebo controlled trials. Ó

Objective/Background: Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease (PAD), and many patients with CLI are not eligible for conventional revascularization. In the last decade, cell based therapies have been explored as an alternative treatment option for CLI. A meta-analysis was conducted of randomized placebo controlled trials investigating bone marrow (BM) derived cell therapy in patients with CLI.Methods: The MEDLINE, Embase, and the Cochrane Controlled Trials Register databases were systematically searched, and all included studies were critically appraised by two independent reviewers. The metaanalysis was performed using a random effects model.Results: Ten studies, totaling 499 patients, were included in this meta-analysis. No significant differences were observed in major amputation rates (relative risk [RR] 0.91; 95% confidence interval [CI] 0.65-1.27), survival (RR 1.00; 95% CI 0.95-1.06), and amputation free survival (RR 1.03; 95% CI 0.86-1.23) between the cell treated and placebo treated patients. The ankle brachial index (mean difference 0.11; 95% CI 0.07-0.16), transcutaneous oxygen measurements (mean difference 11.88; 95% CI 2.73-21.02), and pain score (mean difference À0.72; 95% CI À1.37 to À0.07) were significantly better in the treatment group than in the placebo group.Conclusions: This meta-analysis of placebo controlled trials showed no advantage of stem cell therapy on the primary outcome measures of amputation, survival, and amputation free survival in patients with CLI. The potential benefit of more sophisticated cell based strategies should be explored in future randomized placebo controlled trials.

The available evidence comparing DAPT with MAPT after endovascular arterial revascularization is limited and the majority of trials were conducted in the cardiology field. No significant evidence for superiority of DAPT compared with MAPT was found, but there was also no evidence of an increased bleeding risk with DAPT over MAPT.

clopidogrel treatment, some patients still display high platelet reactivity (HCPR). Tailored antiplatelet therapy, based on platelet reactivity testing, might overcome HCPR. However, more data are warranted regarding the proportion of patients with HCPR in the PAD population, different platelet reactivity tests, their correlation, and the optimal timing for these tests as a stepping stone for a future trial investigating the potential benefit of tailored antiplatelet therapy in PAD patients. Methods: Thirty patients on DAPT after percutaneous transluminal angioplasty underwent platelet reactivity testing by VerifyNow, vasodilatorstimulated phosphoprotein (VASP) and platelet activation assay, and CYP2C19-polymorphism testing. Results: The proportion of patients with HCPR measured by VerifyNow varied between 43.3% and 83.3%, depending on the cut off values used. Testing within 24 hours of initiation of DAPT gave a higher proportion of HCPR than testing after more than 24 hours. According to DNA testing, 14.8% were CYP2C19*2 homozygote, 22.2% heterozygote, and 63% CYP2C19*2 negative. VASP assay revealed 24% HCPR. The highest HCPR rate was found with a VerifyNow cut off of less than 40% inhibition, whereas the lowest HCPR rate was found with the VASP assay. There was a low correlation between the tests. Conclusion: HCPR is present in PAD patients and research on HCPR is needed in this population; timing of tests is relevant and standardisation of tests is needed. The optimal conditions for platelet function testing should be determined.

The increased QoL in patients with no option severe limb ischemia persisted until 3 years after inclusion, but did not differ between the BMMNC and placebo arms or between patients with and without a major amputation.

Experience with the use of bioresorbable stents in PAD is still limited and is investigated only in small studies. The use of bioresorbable stents in PAD appears to be feasible and safe. With current published results, we are unable to fully answer all of the questions about the future use of bioresorbable stents in PAD, and use should be limited to study-related cases in PAD.

Objective/Background: The objective was to investigate renal outcomes following endovascular repair of thoraco-abdominal aortic aneurysms (TAAA) comparing fenestrations with branches for the renal arteries. Methods: Renal outcomes following TAAA endovascular repair performed with renal branches were collected from five high volume European centers and compared with renal outcomes following TAAA endovascular repair performed with renal fenestrations at one center. Renal re-intervention and occlusion rates, and freedom from any renal outcome and death were analyzed by patient and target vessel. Estimated glomerular filtration rate (eGFR) was calculated and collected pre-operatively and at the last available follow up. Results: In total, 449 patients were included in this retrospective study (235 treated with branched devices [BEVAR] and 214 with fenestrated devices [FEVAR]). Altogether, 856 renal vessels were analyzed (445 perfused by branches and 411 by fenestrations). Both groups were comparable except for sex and smoking habits. Technical success rates were 95% and 99%, respectively. Mean 6 SD follow up was 19 6 18 months after BEVAR and 24 6 20 months after FEVAR. During follow up, renal re-intervention rates were similar in both groups (4.7% vs 5.2%). The renal occlusion rate was significantly higher following BEVAR (9.6% vs 2.3%; P < .01), and the 2 year freedom for renal occlusion rate was 90.4% (SE 85.8%-95.3%) following BEVAR and 97.1% (SE 94.6%-99.7%) following FEVAR (P < .01). During follow up, a 12% median decrease in eGFR was observed following BEVAR versus 9% following FEVAR (non-significant). The 2 year survival rates were 73.4% (SE 66.6%-80.9%) and 81.8% (SE 76.1%-87.9%) following BEVAR and FEVAR, respectively. Conclusion: Mid-term renal outcomes following endovascular repair of TAAA are satisfactory. Endograft designs incorporating renal fenestrations rather than renal branches are associated with significantly lower occlusion rates. A prospective trial is now required to confirm these results.

HCPR is present in PAD patients and research on HCPR is needed in this population; timing of tests is relevant and standardisation of tests is needed. The optimal conditions for platelet function testing should be determined.