Incidence of critical limb ischemia and amputation outcome in contralateral limb in diabetic patients hospitalized for unilateral critical limb ischemia during 1999-2003 and followed-up until 2005.

We studied the incidence of critical limb ischemia (CLI) and amputation outcome of the contralateral limb in 533 diabetic patients hospitalized in our diabetic foot centre because of CLI from 1999 to 2003 and followed-up until 2005. The cumulative incidence rate during the 6-year period reached 49.8% (CI confidence interval=40.6-59.6). All patients underwent arteriography and in 181 (98.4%) the revascularization was performed without different feasibility (p=0.077) compared to that (95.3%) in the initial patients. The severity of lesion evaluated with Wagner grade was lower (chi(2)=33.5, p<0.001) and also the frequency of midfoot and above-the-ankle amputations was lower (p<0.001 and p=0.022, respectively) in contralateral patients. There was no evidence from the logistic analysis to support the association between any of the investigated variables and incidence of CLI in the contralateral limb. Over a 6-year period, almost 50% of the diabetic patients with unilateral CLI developed a CLI in the contralateral limb: however, both severity of foot lesion and amputation level was significantly lower. This fact can be due to prompt therapeutic interventions, made possible thanks to an increased patient awareness acquired by training during the treatment of the unilateral limb.

HYAFF 11-based autologous dermal and epidermal grafts in the treatment of noninfected diabetic plantar and dorsal foot ulcers: a prospective, multicenter, controlled, randomized clinical trial.

OBJECTIVE: To evaluate the clinical efficacy and safety of HYAFF 11-based autologous dermal and epidermal grafts in the management of diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A total of 79 patients with diabetic dorsal (n = 37) or plantar (n = 42) ulcers were randomized to either the control group with nonadherent paraffin gauze (n = 36) or the treatment group with autologous tissue-engineered grafts (n = 43). Weekly assessment, aggressive debridement, wound infection control, and adequate pressure relief (fiberglass off-loading cast for plantar ulcers) were provided in both groups. Complete wound healing was assessed within 11 weeks. Safety was monitored by adverse events. RESULTS: Complete ulcer healing was achieved in 65.3% of the treatment group and 49.6% of the control group (P = 0.191). The Kaplan-Meier mean time to closure was 57 and 77 days, respectively, for the treatment versus control groups. Plantar foot ulcer healing was 55% and 50% in the treatment and control groups, respectively. Dorsal foot ulcer healing was significantly different, with 67% in the treatment group and 31% in the control group (P = 0.049). The mean healing time in the dorsal treatment group was 63 days, and the odds ratio for dorsal ulcer healing compared with the control group was 4.44 (P = 0.037). Adverse events were equally distributed between the two groups, and none were related to the treatments. CONCLUSIONS: The autologous tissue-engineered treatment exhibited improved healing in dorsal ulcers when compared with the current standard dressing. For plantar ulcers, the off-loading cast was presumably paramount and masked or nullified the effects of the autologous wound treatment. This treatment, however, may be useful in patients for whom the total off-loading cast is not recommended and only a less effective off-loading device can be applied.

Effect of normalization of fasting glucose by intensified insulin therapy and influence of eNOS polymorphisms on the incidence of restenosis after peripheral angioplasty in patients with type 2 diabetes: a randomized, open-label clinical trial.

Primary objective was to evaluate whether an intensified insulin therapy (IIT) incorporating the target of normal fasting glucose and HbA1c levels could halve the incidence of restenosis/amputation/SCA/death at 6 months after peripheral angioplasty compared with standard care (SC) in patients with type 2 diabetes (DMT2) affected by critical limb ischemia (CLI). Forty-six consecutive patients with DMT2 and CLI were randomly assigned to a parallel, open-label study with IIT (basal-bolus glulisine + glargine administrations) or SC (glargine administration + oral antidiabetic drugs). A SNP of eNOS (rs753482-A>C) and circulating CD34(+) and CD34(+)KDR(+) progenitor cells were determined. At the end of the study, although HbA1c levels were lower in IIT than in SC (6.9 ± 1.3 % vs. 7.6 ± 1.2 %, p < 0.05), IIT did not reduce the cumulative incidence of restenosis/amputation/SCA/death (52 and 65 %, respectively, odd ratio 0.59; CI 95 %: 0.21-1.62, p = 0.59). rs753482AC+CC as compared with rs753482AA increased the cumulative incidence of restenosis/amputation/SCA/death (79 and 42 %; odd ratio 5.3; CI 95 %: 1.41-19.5, p < 0.02). Baseline CD34(+)KDR(+) were higher in rs753482AA (166.2 ± 154.0 × 10(6) events) than in rs753482AC+CC (63.1 ± 26.9 × 10(6) events, p < 0.01). At the end of the study, the highest circulating CD34(+)KDR(+) were found in IIT rs753482AA (246.9 ± 194.0 × 10(6) events) while the lowest levels were found in SC rs753482AC+CC (70.9 ± 45.0 × 10(6) events). IIT did not decrease the cumulative incidence of restenosis/amputation/SCA/death in DMT2 and CLI patients. These patients correspond to a class of fragile subjects at high risk of cardiovascular events, and new predictors of restenosis should be contemplated, such as of eNOS polymorphism, (rs753482-A>C SNP) and circulating endothelial progenitor cells.

Revascularization by angioplasty of type D femoropopliteal and long infrapopliteal lesion in diabetic patients with critical limb ischemia: are TASC II recommendations suitable? A population-based cohort study.

Feasibility of revascularization of type D femoropopliteal and long infrapopliteal lesions by angioplasty (peripheral translumenal angioplasty [PTA]) in diabetic patients with critical limb ischemia (CLI) according to the TransAtlantic Inter-Society Consensus (TASC) II recommendations was studied. A total of 292 diabetic patients were admitted for CLI; 308 limbs underwent a PTA. Out of 211 femoropopliteal lesions treated with PTA, 44 were TASC II type A, 45 type B, 48 type C, and 76 type D lesions. In 44 of the 76 patients with type D lesions revascularized by PTA, no artery was patent down to the foot before the PTA. In 172 limbs with all infrapopliteal arteries occluded, revascularization was carried out down to the foot in 167 limbs. Follow-up was 3.1 ± 0.3 years. A first episode of restenosis occurred in 66/308 limbs with an incidence/year of 7.9. PTA procedures were successfully repeated in 57/66 restenosis episodes: secondary patency was 97.1%. The incidence/year of type D femoropopliteal lesions was 5.4, the incidence/year in others was 5.0, without statistically significant differences: P = .417. The only variable found significantly associated with restenosis occurrence on logistic analysis was the presence of lesions in both femoropopliteal and infrapopliteal axes. A total of 26/308 above-the-ankle amputations were performed, with an incidence/year of 2.5. Multivariate analysis showed the independent role of only crural artery occlusion after PTA. These data show that the choice to refer to angioplasty diabetic patients with type D and/or long infrapopliteal lesions without good run-off at the foot and/or high surgical risk allowed high revascularization feasibility, with an optimal amputation outcome.

A novel device for true lumen re-entry after subintimal recanalization of superficial femoral arteries: first-in-man experience and technical description.

Subintimal angioplasty (SAP) is frequently performed for the treatment of critical limb ischemia (CLI) and has been recognized as an effective technique for these patients. Nevertheless, this approach is limited by the lack of controlled re-entry into the true lumen of the target vessel. We describe a novel device for true lumen re-entry after subintimal recanalization of superficial femoral arteries (SFA). We report our experience with six patients treated between April 2009 and January 2010 with a novel system designed to facilitate true lumen re-entry. The device was advanced by ipsilateral antegrade approach through a 6-French sheath. Successful reaccess into the true lumen was obtained in five of six patients without complications. The patient in whom the reaccess to the true lumen was not possible underwent successful bypass surgery. At 30 days follow-up, the SFA was patent in all patients according to echo-Doppler examination. Our preliminary experience indicates that this novel re-entry device increases the success rate of percutaneous revascularization of chronically occluded SFA.

Long-term prognosis of diabetic patients with critical limb ischemia: a population-based cohort study.

OBJECTIVE: To evaluate the long-term prognosis of critical limb ischemia (CLI) in diabetic patients. RESEARCH DESIGN AND METHODS: A total of 564 consecutive diabetic patients were hospitalized for CLI from January 1999 to December 2003; 554 were followed until December 2007. RESULTS: The mean follow-up was 5.93 +/- 1.28 years. Peripheral angioplasty (PTA) was performed in 420 (74.5%) and bypass graft (BPG) in 117 (20.6%) patients. Neither PTA nor BPG were possible in 27 (4.9%) patients. Major amputations were performed in 74 (13.4%) patients: 34 (8.2%) in PTA, 24 (21.1%) in BPG, and 16 (59.2%) in a group that received no revascularization. Restenosis occurred in 94 patients, bypass failures in 36 patients, and recurrent ulcers in 71 patients. CLI was observed in the contralateral limb of 225 (39.9%) patients; of these, 15 (6.7%) required major amputations (rate in contralateral compared with initial limb, P = 0.007). At total of 276 (49.82%) patients died. The Cox model showed significant hazard ratios (HRs) for mortality with age (1.05 for 1 year [95% CI 1.03-1.07]), unfeasible revascularization (3.06 [1.40-6.70]), dialysis (3.00 [1.63-5.53]), cardiac disease history (1.37 [1.05-1.79]), and impaired ejection fraction (1.08 for 1% point [1.05-1.09]). CONCLUSIONS: Diabetic patients with CLI have high risks of amputation and death. In a dedicated diabetic foot center, the major amputation, ulcer recurrence, and major contralateral limb amputation rates were low. Coronary artery disease (CAD) is the leading cause of death, and in patients with CAD history the impaired ejection fraction is the major independent prognostic factor.