No abstract

We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P < 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step.

Frailty was independently associated with 2-year overall survival and amputation-free survival in patients with critical limb ischemia treated with revascularization, irrespective of age, revascularization mode, and chronic renal failure status.

Patients with CLI on dialysis enjoyed satisfactory freedom from MALE and limb salvage, but survival and AFS were significantly less than reported for IBG in patients with CLI who did not receive dialysis. In addition, patients with an EF <40%, lower serum albumin (<3.0 g/dL), or non-ambulatory status experienced particularly poor clinical outcomes after IBG.

on behalf of the RECANALISE Registry Investigators Background: Although endovascular therapy (EVT) has advanced, few reports have compared EVT and bypass surgery in claudication patients with femoropopliteal disease. The present study used data from a multicenter registry in Japan to analyze outcomes of EVT and bypass surgery for claudication patients with Trans-Atlantic InterSociety Consensus (TASC)-II C and D femoropopliteal lesions. Methods and Results:Of 1,156 patients who underwent revascularization, 696 patients were treated for intermittent claudication. A total of 263 patients with femoropopliteal lesion were classified into TASC-II C and D. The primary and secondary patency rates of the EVT and bypass surgery groups were analyzed. The overall complication rate was 14.4% in the bypass surgery group and 3.5% in the EVT group (P<0.01). The 1-and 5-year primary patency rates were 82.1% and 69.4% in the bypass surgery group and 67.8% and 45.2% in the EVT group, respectively. Although the bypass surgery group had a higher primary patency rate than the EVT group (P<0.01, log-rank test), secondary patency rates did not differ significantly between the two groups. Conclusions:Although bypass surgery is clearly feasible for claudication patients with TASC-II C and D femoropopliteal disease, EVT is also a good option because of its lower complication rate and good secondary patency rate in patients in poor condition for bypass. (Circ J 2014; 78: 457 -464)