Prospective study on microangiopathy in type 2 diabetic foot ulcer.

AIMS/HYPOTHESIS: We investigated the significance of microangiopathy in the development of foot ulcer, which is still disputed. METHODS: We assessed microangiopathy by histological analysis of the capillary ultrastructure using transmission electron microscopy and capillary density and arteriolar morphology in paraffin-embedded sections from the skin of type 2 diabetic patients: 30 neuroischaemic patients (Isc) revascularised with peripheral angioplasty and 30 neuropathic patients (Neu) with foot ulcer, compared with ten non-diabetic volunteers. RESULTS: In the diabetic patients, capillaries in the dermal papillary layer were fewer (-22.2%, 159 ± 43 vs 205 ± 52 mm(2) in non-diabetic volunteers, p < 0.01). They also showed detrimental remodelling, with a 2.2-fold increase in capillary basement membrane thickness (3.44 ± 1.19 vs 1.53 ± 0.34 µm in non-diabetic volunteers, p < 0.001) and a 57.7% decrease in lumen area (14.6 ± 11.1 vs 34.7 ± 27.5 µm(2), p < 0.001). No differences were observed between the diabetic Isc or Neu patients. Isc were more prone to develop arteriolar occlusion than Neu (16.8 ± 6.9% vs 6.7 ± 3.7%, respectively, p < 0.001). No patient had been amputated at 30 days and healing time was significantly longer in Isc (180 ± 120 vs 64 ± 50 days in Neu, p < 0.001). CONCLUSIONS/INTERPRETATION: Capillary microangiopathy is present in equal measure in neuroischaemic and neuropathic diabetic foot skin. The predominance of arteriolar occlusions with neuroischaemia indicated the existence of an additional 'small vessel disease' that did not affect an effective revascularisation and did not worsen the prognosis of major amputations but slowed the healing process of the neuroischaemic foot ulcer. TRIAL REGISTRATION: ClinicalTrials.gov NCT02610036.

Outcomes of Chopart Amputation in a Tertiary Referral Diabetic Foot Clinic: Data From a Consecutive Series of 83 Hospitalized Patients.

The purpose of the present retrospective study was to evaluate the outcomes (ie, ulcer recurrence, major amputation, death) in diabetic patients undergoing Chopart amputation because of deep infection or gangrene extending to the midfoot. From 2009 to 2011, 83 patients, aged 71.4 ± 9.3 years, underwent a midtarsal amputation and were followed up until December 31, 2012 (mean follow-up 2.8 ± 0.8 years). Of the 83 patients, 26 were female, 61 required insulin, 47 had renal insufficiency, 19 underwent hemodialysis, 65 had hypertension, 34 had a history of cardiac disease, and 4 had a history of stroke. Chopart amputation was performed in 38 patients (45.8%) with gangrene, 31 (37.4%) with abscess, and 14 (16.9%) with osteomyelitis. Urgent surgery was performed in 56 patients (67.5%). Effective revascularization was performed in 64 patients (77.1%) patients. Of the 83 patients, 47 had healed at a mean period of 164.7 (range 11 to 698) days. Ulcer recurrence developed in 15 patients (31.9%). A major amputation was necessary in 23 patients (27.7%), with an annual incidence of 13.0%. None of the included variables on logistic regression analysis was significantly associated with proximal amputation. Of the 83 patients, 38 (45.8%) died, with an annual incidence of 25.8%. On logistic regression analysis, age (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.01 to 1.16), history of stroke (OR 9.94, 95% CI 3.16 to 31.24), and urgent surgery (OR 2.60, 95% CI 1.14 to 5.93) were associated with mortality. Chopart amputation represents the last chance to avoid major amputation for diabetic patients with serious foot complications. Our success rate was great enough to consider Chopart amputation a viable option for limb salvage in this high-risk population.

Saving the limb in diabetic patients with ischemic foot lesions complicated by acute infection.

Ischemia and infection are the most important factors affecting the prognosis of foot ulcerations in diabetic patients. To improve the outcome of these patients, it is necessary to aggressively treat 2 important pathologies--namely, occlusive arterial disease affecting the tibial and femoral arteries and infection of the ischemic diabetic foot. Each of these 2 conditions may lead to major limb amputation, and the presence of both critical limb ischemia (CLI) and acute deep infection is a major risk factor for lower-extremity amputation. Thus, the management of diabetic foot ulcers requires specific therapeutic approaches that vary significantly depending on whether foot lesions are complicated by infection and/or ischemia. A multidisciplinary team approach is the key to successful treatment of a diabetic foot ulcer: ischemic diabetic foot ulcers complicated by acute deep infection pose serious treatment challenges because high levels of skill, organization, accuracy, and timing of intervention are required to maximize the chances of limb salvage: these complex issues are better managed by a multidisciplinary clinical group.

Severity of demographic and clinical characteristics, revascularization feasibility, major amputation, and mortality rate in diabetic patients admitted to a tertiary diabetic foot center for critical limb ischemia: comparison of 2 cohorts recruited at a 10-year distance.

BACKGROUND: To compare demographic and clinical characteristics, revascularization, major amputation, and mortality among patients admitted to a diabetic foot center because of critical limb ischemia (CLI) during 1999-2003 (cohort 1) and 2009 (cohort 2). METHODS: During 1999-2003, 564 diabetic patients with CLI (cohort 1) were admitted to our center, and 344 patients (360 affected limbs) were admitted during 2009 (cohort 2). Data on demographic and clinical characteristics, revascularization by peripheral angioplasty (PTA) or bypass graft (BPG), major amputation, and mortality were recorded. RESULTS: Patients belonging to cohort 2 were older than patients of cohort 1 (P = 0.001). In cohort 2, there were more subjects requiring insulin (P = 0.008) and duration of diabetes was longer (P = 0.001); moreover, there were more patients requiring dialysis (P = 0.001), patients with history of stroke (P = 0.004), or foot ulcer (P = 0.001). No significant difference between the 2 groups was found concerning gender, metabolic control, hypertension, lipid values, neuropathy, and retinopathy. Occlusion was more frequent than stenosis in the posterior tibial (P < 0.001) and peroneal (P = 0.016) arteries. However, the revascularization rate did not differ (P = 0.318) between the 2 groups. Restenosis after PTA was not significantly different (P = 0.627), whereas BPG failure was significantly more frequent (P = 0.010) in cohort 2 (2009). Major amputation (P = 0.222) and mortality rate (P = 0.727) did not differ between the 2 groups. CONCLUSIONS: The severity of either foot lesions or patients comorbidities should be concomitantly assessed and taken into proper consideration when evaluating changes in the amputation rate among different studies or in different temporal settings.

Migratory activity of circulating mononuclear cells is associated with cardiovascular mortality in type 2 diabetic patients with critical limb ischemia.

OBJECTIVE: Prediction of clinical outcome in diabetic patients with critical limb ischemia (CLI) is unsatisfactory. This prospective study investigates if the abundance and migratory activity of a subpopulation of circulating mononuclear cells, namely, CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells, predict major amputation and cardiovascular death in type 2 diabetic patients undergoing percutaneous transluminal angioplasty for CLI. RESEARCH DESIGN AND METHODS: A consecutive series of 119 type 2 diabetic patients with CLI was enrolled. CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells were assessed by flow cytometry upon isolation and also after spontaneous or stromal cell-derived factor 1α-directed migration in an in vitro assay. The association between basal cell counts and migratory activity and the risk of an event at 18-month follow-up was evaluated in a multivariable regression analysis. RESULTS: Time-to-event analysis of amputation (n = 13) showed no association with the candidate predictors. Sixteen cardiovascular deaths occurred during 18 months of follow-up. Abundance of CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells was not associated with cardiovascular mortality. Interestingly, in vitro migration of CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells was higher in patients with cardiovascular death compared with event-free subjects (percentage of migrated cells median value and interquartile range, 0.03 [0.02-0.07] vs. 0.01 [0.01-0.03]; P = 0.0095). Multivariable regression model analysis showed that cell migration forecasts cardiovascular mortality independently of other validated predictors, such as age, diagnosed coronary artery disease, serum C-reactive protein, and estimated glomerular filtration rate. In this model, doubling of migrated cell counts increases the cardiovascular death hazard by 100% (P < 0.0001). CONCLUSIONS: The new predictor could aid in the identification of high-risk patients with type 2 diabetes requiring special diagnostic and therapeutic care after revascularization.

Effectiveness of combined therapy with angiotensin-converting enzyme inhibitors and statins in reducing mortality in diabetic patients with critical limb ischemia: an observational study.

AIMS: To investigate the effect of combined treatment with angiotensin-converting enzyme inhibitors (ACE) and statins on mortality in diabetic patients with critical limb ischemia (CLI). METHODS: Prospective observational study of 553 consecutive diabetic patients admitted because of CLI followed for a mean of 2.2 years. All patients underwent peripheral revascularization and antithrombotic therapy was prescribed or continued and therapy with statin and ACE was recorded. Mortality from any cause was assessed and Kaplan-Meier analyses were performed to compare the relationship between survival and recorded variables. RESULTS: One hundred thirty-nine patients did not have therapy with statin or an ACE, 78 had therapy with statin without ACE, 164 had therapy with ACE without statin and 172 patients had therapy with both statin and ACE. One hundred thirty-six patients died, 45/139 with neither statin nor ACE, 40/164 with ACE only, 26/78 with statin only, and 25/172 with both statin and ACE. Multivariate analysis confirmed the independent role of age, history of stroke, renal insufficiency and dialysis. Combined treatment with ACE and statin appeared to have a protective role. CONCLUSIONS: In patients with diabetes and CLI mortality after two years is high. Life expectancy was better in patients receiving combined therapy with ACE and statin but not with therapy with only a statin or an ACE.

Heel ulcer and blood flow: the importance of the angiosome concept.

A young female diabetic patient is reported, who presented with a double foot lesion. She presented with a first metatarsal head exposure concomitant with a heel wet gangrene. Magnetic resonance demonstrated osteomyelitis of the rear portion of the calcaneus. Transmetatarsal amputation was performed and a wide debridement was required to remove all gangrenous tissue from the heel wound. The pedal artery was palpable; the posterior tibial pulse was present, but weak.Transcutaneous oximetry (TcPO2) at the dorsum of the foot was TcPO2 = 56 mmHg despite significant oedema. Nevertheless, TcPO2 on the perilesional area of the heel ulcer (TcPO2 = 24mmHg) was suggestive for critical chronic ischemia. At angiographic examination, anterior tibial and peroneal arteries were patent, but the posterior tibial artery that showed severe stenosis then percutaneous angioplasty (PTA) was performed. Just the day after PTA, values of TcPO2 at the perilesional area of the heel ulcer increased to 41 mmHg. Heel osteomyelitis was subsequently treated by partial calcanectomy. The patient was discharged after a 21-day hospital stay. In the treatment of heel ulcers, it is clinically useful to use the angiosomic concept. The majority of the blood supply to the heel is provided by the posterior tibial artery, and only to a small extent by the posterior branch of peroneal artery. If the decrease in blood flow to this region is not detected, and direct flow based on the angiosome concept is not obtained, the healing of a heel ulcer may be delayed or impaired.

Influence of osteomyelitis location in the foot of diabetic patients with transtibial amputation.

BACKGROUND: To evaluate the prevalence of osteomyelitis in different areas of the foot and the possible correlation between localization and outcome of major amputation. METHODS: From January 2008 to December 2010, a total of 350 diabetic patients were admitted to our diabetic foot unit for the surgical treatment of osteomyelitis. Osteomyelitis was diagnosed when both the probe-to-bone maneuver and plain radiography were positive. In all of these patients, osteomyelitis was confirmed by histological examination. RESULTS: Osteomyelitis was localized to the forefoot in 300 (85.7%) patients, to the midfoot in 27 (7.7%) patients, and to the hindfoot in the remaining 23 (6.75) patients. On average, foot lesions had developed 6.6 ± 5.6 months before admission to our unit. Transtibial amputation was performed in 1 (0.33%) patient with forefoot osteomyelitis, in 5 (18.5%) patients with midfoot osteomyelitis, and in 12 (52.2%) patients with osteomyelitis of the heel (χ(2) = 128.4, P < .001). Multivariate analysis showed the independent role that osteomyelitis in the heel region had in major amputation outcome (odds ratio 15.3; P < .001; confidence interval, 17.4-5336.0), dialysis treatment (odds ratio 6.3; P = .012; confidence interval, 2.5-1667.2), and leukocyte count greater than 10(3) mm(3) (odds ratio 2.25; P = .036; confidence interval, 1.1-76.6). CONCLUSIONS: We found a higher rate of transtibial amputation when osteomyelitis involved the heel instead of the midfoot or forefoot in diabetic patients. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

MicroRNA-15a and microRNA-16 impair human circulating proangiogenic cell functions and are increased in the proangiogenic cells and serum of patients with critical limb ischemia.

RATIONALE: Circulating proangiogenic cells (PACs) support postischemic neovascularization. Cardiovascular disease and diabetes mellitus impair PAC regenerative capacities via molecular mechanisms that are not fully known. We hypothesize a role for microRNAs (miRs). Circulating miRs are currently investigated as potential diagnostic and prognostic biomarkers. OBJECTIVE: The objectives were the following: (1) to profile miR expression in PACs from critical limb ischemia (CLI) patients; (2) to demonstrate that miR-15a and miR-16 regulate PAC functions; and (3) to characterize circulating miR-15a and miR-16 and to investigate their potential biomarker value. METHODS AND RESULTS: Twenty-eight miRs potentially able to modulate angiogenesis were measured in PACs from CLI patients with and without diabetes mellitus and controls. miR-15a and miR-16 were further analyzed. CLI-PACs expressed higher level of mature miR-15a and miR-16 and of the primary transcript pri-miR-15a/16-1. miR-15a/16 overexpression impaired healthy PAC survival and migration. Conversely, miR-15a/16 inhibition improved CLI-PAC-defective migration. Vascular endothelial growth factor-A and AKT-3 were validated as direct targets of the 2 miRs, and their protein levels were reduced in miR-15a/16-overexpressing healthy PACs and in CLI-PACs. Transplantation of healthy PACs ex vivo-engineered with anti-miR-15a/16 improved postischemic blood flow recovery and muscular arteriole density in immunodeficient mice. miR-15a and miR-16 were present in human blood, including conjugated to argonaute-2 and in exosomes. Both miRs were increased in the serum of CLI patients and positively correlated with amputation after restenosis at 12 months postrevascularization of CLI type 2 diabetes mellitus patients. Serum miR-15a additionally correlated with restenosis at follow-up. CONCLUSIONS: Ex vivo miR-15a/16 inhibition enhances PAC therapeutic potential, and circulating miR-15a and miR-16 deserves further investigation as a prognostic biomarker in CLI patients undergoing revascularization.

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.

Soluble ST2 is regulated by p75 neurotrophin receptor and predicts mortality in diabetic patients with critical limb ischemia.

OBJECTIVE: The p75 neurotrophin receptor (p75(NTR)) contributes to diabetes mellitus-induced defective postischemic neovascularization. The interleukin-33 receptor ST2 is expressed as transmembrane (ST2L) and soluble (sST2) isoforms. Here, we studied the following: (1) the impact of p75(NTR) in the healing of ischemic and diabetic calf wounds; (2) the link between p75(NTR) and ST2; and (3) circulating sST2 levels in critical limb ischemia (CLI) patients. METHODS AND RESULTS: Diabetes mellitus was induced in p75(NTR) knockout (p75KO) mice and wild-type (WT) littermates by streptozotocin. Diabetic and nondiabetic p75KO and WT mice received left limb ischemia induction and a full-thickness wound on the ipsilateral calf. Diabetes mellitus impaired wound closure and angiogenesis and increased ST2 expression in WT, but not in p75KO wounds. In cultured endothelial cells, p75(NTR) promoted ST2 (both isoforms) expression through p38(MAPK)/activating transcription factor 2 pathway activation. Next, sST2 was measured in the serum of patients with CLI undergoing either revascularization or limb amputation and in the 2 nondiabetic groups (with CLI or nonischemic individuals). Serum sST2 increased in diabetic patients with CLI and was directly associated with higher mortality at 1 year from revascularization. CONCLUSIONS: p75(NTR) inhibits the healing of ischemic lower limb wounds in diabetes mellitus and promotes ST2 expression. Circulating sST2 predicts mortality in diabetic CLI patients.

Feasibility and effectiveness of internal pedal amputation of phalanx or metatarsal head in diabetic patients with forefoot osteomyelitis.

From January 2007 to December 2009, 207 diabetic patients were consecutively admitted to our foot center because of osteomyelitis of a phalanx or metatarsal head. The removal of infected bone was performed by internal bone resection in 110 patients (group A) and amputation in 97 patients (46.9%; group B). Dehiscence occurred in 15 patients (13.6%) patients in group A and 10 patients (10.3%) in group B (p = 0.464). A total of 206 patients (99.5%) were followed up from January 1, 2007 to December 31, 2011. Ulcer relapse occurred in 12 patients (12.4%) in group A and 18 patients (16.4%) in group B (p = .437). A contralateral ulcer occurred in 10 group A patients (10.3%) and 14 group B patients (12.7%; p = .667). The results of the present study have demonstrated that bone resection with preservation of the soft tissue envelope is feasible in approximately one half of diabetic patients with forefoot osteomyelitis and does not result in any risk of major dehiscence or ulcer recurrence compared with ray or toe amputation.

Antegrade approach for percutaneous interventions of ostial superficial femoral artery: outcomes from a prospective series of diabetic patients presenting with critical limb ischemia.

OBJECTIVES: This is a prospective evaluation of percutaneous interventions (PTAs) performed by the antegrade femoral approach in diabetic patients with critical limb ischemia (CLI) and ostial superficial femoral artery (SFA) lesions. METHODS: The puncture site was selected according to duplex scan analysis and physical examination (brachial, crossover, or antegrade). In cases of antegrade approach, a bare needle angiogram of the femoral bifurcation was performed in order to have an adequate distance (>2 cm) from the target lesion. RESULTS: Between January 2010 and August 2011, 64 diabetic patients underwent PTA for ostial SFA lesions. Crossover or brachial approach was electively adopted in 19/64 (30%) patients. The antegrade bare needle angiogram was performed in the remaining 45/64 (70%) patients. In two patients, the vascular anatomy was considered not suitable for antegrade approach, and they were treated in crossover. Technical success was achieved in 38/45 (84%) of patients. During hospital stay, one patient had SFA stent thrombosis treated with urgent bypass grafting. CONCLUSIONS: The antegrade approach can be safely performed in most patients presenting with CLI and ostial SFA lesions. The use of clinical and radiographic criteria correctly identifies patients with ostial SFA lesions suitable for an antegrade approach in 42/44 (95%) of cases.

Prognostic difference between soft tissue abscess and osteomyelitis of the foot in patients with diabetes: data from a consecutive series of 452 hospitalized patients.

From January 2008 to December 2010, 452 patients with diabetes were admitted to our diabetic foot unit because of deep soft tissue abscess (group A: n = 210) or chronic osteomyelitis (group B: n = 242). Patients from group A underwent emergency debridement in the operating room. Patients from group B underwent elective surgery. Twenty-six (5.8%) major amputations were performed: of these, 18 (8.57%) were performed in patients from group A and 8 (3.31%) were performed in patients from group B (p = .024). Multivariate analysis showed the independent role on amputation outcome of the abscess (odds ratio, 2.64; p = .029; confidence interval [CI] 1.11 to 6.28), dialysis treatment (odds ratio, 3.17; p = .039, CI 1.06-9.51), and C-reactive protein > 0.5 mg/dL (odds ratio, 3.75; p = .022, CI 1.21-11.64). In group A, 43 (22.6%) patients healed only with drainage, and 147 (70.0%) minor amputations were performed: 53 (36.1%) at the level of the forefoot and 94 (63.9%) at the level of the midfoot. In group B, 234 (96.7%) minor amputations were performed, 208 (88.9%) at the forefoot and 26 (11.1%) at the midfoot level (p < .001). Fourteen postoperative complications occurred in patients from group A and 2 in patients from group B (p < .001). In group A, 3 patients died during hospitalization, 1 from septic shock and 2 from sudden death. None of the group B patients died. This study demonstrates that the severity of a foot soft tissue abscess is not comparable with that of a chronic osteomyelitis not only because of a higher rate of major amputation, but also because of a much more proximal level of minor amputation.

Limb revascularization feasibility in diabetic patients with critical limb ischemia: results from a cohort of 344 consecutive unselected diabetic patients evaluated in 2009.

AIMS: To evaluate the feasibility of peripheral revascularization by angioplasty (PTA) or bypass grafting (BPG) in diabetic patients with critical limb ischemia (CLI). METHODS: All diabetic patients referred to our Diabetic Foot Centre for foot lesion or rest pain were assessed for the presence of CLI as assessed by the TASC criteria. All patients underwent angiography that was evaluated jointly by an interventional radiologist, a vascular surgeon and a diabetologist of the diabetic foot care team. RESULTS: During 2009, 344 diabetics were admitted because of CLI in a total of 360 limbs. PTA was performed in 308 (85.6%) limbs, and BPG was performed in 40 (11.1%) limbs in which PTA was not feasible. Revascularization could not be carried out in 12 (3.3%) limbs due to the lack of target vessel (9 limbs) or high surgical risk (3 limbs). According to the judgement of the vascular surgeon, BPG was anatomically feasible in 180 (58.4%) of the 308 limbs that underwent PTA. Therefore, considering also the 40 limbs that underwent BPG, surgical revascularization was judged anatomically possible in a total of 220 (61.1%) limbs. At 30 days, 19 (5.3%) above-the-ankle amputations were performed: 8 (66.7%) amputations were performed in the 12 non-revascularized limbs, 8 (2.6%) amputations were performed in the 308 limbs treated with PTA and 3 (7.5%) amputations were performed in the 40 limbs treated with BPG. CONCLUSIONS: Revascularization by PTA is highly feasible in diabetics with CLI. The feasibility of revascularization by BPG is lower but nonetheless consistent. In centres where both revascularization procedures are available, it is possible to revascularize more than 96% of diabetics with CLI.

Characteristics of peripheral arterial disease and its relevance to the diabetic population.

Peripheral arterial disease (PAD) is very frequent in diabetics, and it increases with age. Foot examination contributes poorly to diagnosis of PAD. The ankle-brachial index (ABI) measurement is considered the most accurate noninvasive diagnostic method when evaluating PAD: ABI evaluation is recommended in all diabetics aged >50 years. Many diabetic patients with PAD have a concomitant sensitive neuropathy: as a consequence, perception of ischemic pain is remarkably reduced or completely blocked. The result is that the prevalence of claudication in the diabetic population with PAD is lower than the prevalence of critical limb ischemia (CLI) in this population. CLI is a major risk factor for lower extremity amputation without revascularization. Ankle and toe pressures and oxygen tension at the foot are the noninvasive diagnostic parameters of CLI though the medial artery calcification inhibits accurate determination of the ankle and toe pressures, especially when a forefoot ulcer is present. In diabetics, the anatomical localization is mainly distal; arterial wall calcification is frequently observed and occlusion occurs more frequently than stenosis. Such anatomical features, along with the difficulties in the diagnostic approach, account for the fundamental role of CLI as the main prognostic indicator for major amputation. PAD is an expression of systemic atherosclerotic disease. Prognosis of patients with PAD is related to the presence and extent of underlying coronary artery disease (CAD) but also to the severity of PAD: in particular, patients in whom revascularization is not feasible have the highest mortality rate.

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.

The use of a dermal substitute to preserve maximal foot length in diabetic foot wounds with tendon and bone exposure following urgent surgical debridement for acute infection.

In this study, we evaluated the utility of a dermal substitute for preserving maximal foot length after urgent surgical debridement. Patients referred to our Diabetic Foot Center with foot lesions were assessed for sensory-motor neuropathy, infection and critical limb ischaemia. The presence of acute foot infection indicated the need for immediate surgical debridement. The degree of amputation, if necessary, was based on the amount of apparently non infected vital tissue. When vital tendon/bone tissue remained exposed, the lesion was covered with a dermal substitute. From January to December 2008, 393 patients underwent surgical treatment for diabetic foot syndrome; 30 patients underwent immediate surgical debridement resulting in exposed tendon and/or bone tissues. An average of 4.4 +/- 2.1 days following surgical debridement, all 30 patients underwent dermal regeneration template grafting to cover-exposed healthy tendon and bone tissues, instead of achieving primary wound closure with a proximal amputation. After 21 days, a skin graft was performed. Complete wound healing occurred in 26 patients (86.7%). In these patients, the amputation level was significantly more distal (P < 0.003) with respect to that potentially required for immediate wound closure. The average healing time was 74.1 +/- 28.9 days. Four patients underwent a more proximal amputation. No patients underwent major amputation. The use of the dermal substitute for treating exposed tendon and bone tissues allowed timely wound healing and preserved maximal foot length. Continued follow-up will allow assessment of long-term relapse and complication rates. Such treatment could constitute part of the comprehensive management of diabetic wounds.

Efficacy and safety of antegrade common femoral artery access closure using the Angio-Seal device: experience with 1889 interventions for critical limb ischemia in diabetic patients.

PURPOSE: To report a retrospective evaluation of the 6-F Angio-Seal closure device in antegrade and retrograde common femoral artery (CFA) punctures during endovascular procedures in diabetic patients with critical limb ischemia (CLI). METHODS: From January 2005 to March 2009, 2374 diabetic CLI patients underwent interventional procedures in the lower limbs at a single center under systemic anticoagulation (heparin 70 U/kg). In this population, 2016 patients (1184 men; mean age 69.6+/-9.1 years) had 2372 CFA punctures treated with either manual compression [205 punctures in 161 (8.0%) patients] or Angio-Seal deployment (2167 punctures in 1855 patients) and were eligible for this analysis. In the study cohort, there were 1889 antegrade CFA punctures closed with the device in 1626 (87.6%) patients compared to 278 retrograde punctures sealed in 229 (12.4%) patients. The complications from the antegrade CFA punctures were compared to those from retrograde closure and manual compression. RESULTS: The success rate for achieving hemostasis after antegrade and retrograde Angio-Seal placement was 97.9% and 97.8%, respectively. Major complications following antegrade Angio-Seal deployment, retrograde Angio-Seal deployment, and manual compression occurred in 20/1889 (1.1%), 5/278 (1.8%), and 4/205 (2.0%) cases, respectively. All complications developed within 24 hours of the procedure. No further complications were recorded in the 18-month follow-up (range 1-36). The overall complication rates after antegrade puncture closure, retrograde puncture closure, and manual compression at 30 days was 2.5%, 4.0%, and 4.9%, respectively (p = NS). CONCLUSION: This retrospective study shows that the 6-F Angio-Seal is a valuable and safe vascular closure device for percutaneous transfemoral antegrade access in diabetic patients undergoing interventional procedures for CLI.