A combined vascular reconstruction and free-flap transfer offers an option for advanced limb salvage in a selected group of patients with CLI and a major tissue defect. Poor general condition, the involvement of the heel, and a large defect would indicate an amputation over extreme attempts for limb salvage.

The prognosis of patients with Type II (non-insulindependent) diabetes mellitus is primarily determined by the presence of macro-and microangiopathy. There is, however, a large variation in the propensity for the patient to develop these devastating complications. While poor glycaemic control and duration of diabetes are strong predictors of microangiopathy [1], their role as predictors of macroangiopathy is less clear [2±6]. In Type II diabetes, clustering of the metabolic syndrome (hyperglycaemia, obesity, hyper- Diabetologia (1998) Summary To test the hypothesis that interaction between genetic, immunological, clinical and metabolic risk factors influences the outcome of Type II (noninsulin-dependent) diabetes mellitus, we examined which of the above factors present at baseline were associated with mortality in 134 Type II diabetic patients followed for 9 years. Thirty-eight patients (29 %) died during the follow-up period; the majority of whom (68 %) died from cardiovascular disease. At baseline, the deceased patients had higher HbA 1 c values (p = 0.002), higher LDL-triglycerides (p = 0.007), lower HDL-cholesterol (p = 0.007), higher non-esterified fatty acid (NEFA) concentrations (p = 0.014), and higher albumin excretion rate (p < 0.0001) than the patients who survived. In addition, the frequency of HLA-DR4 (21 vs 39 %, p = 0.048) and of parietal cell antibodies (5 vs 14 %, p = 0.016) were decreased in the deceased as compared to the living patients.Patients who died during follow-up also had more retinopathy (42 vs 16 %, p = 0.002), neuropathy (57 vs 23 %, p < 0.001), microalbuminuria (45 vs 6 %, p < 0.0001), coronary heart disease (50 vs 13 %, p < 0.0001), and peripheral vascular disease (27 vs 9 %, p = 0.005) at baseline than patients who survived. In a multiple logistic regression analysis macroangiopathy (p = 0.004), neuropathy (p = 0.007), HbA 1 c (p = 0.018) and albumin excretion rate (p = 0.016) were independent risk factors for death. In patients free of cardiovascular disease at baseline, conventional risk factors such as LDL-cholesterol (p = 0.005) and age (p = 0.003) were associated with subsequent development of cardiovascular disease. In conclusion, in addition to coexisting macroangiopathy, increased albumin excretion rate, poor glycaemic control and neuropathy are risk factors for cardiovascular mortality in patients with Type II diabetes. The presence of HLA-DR4 and signs of autoimmunity may be associated with decreased risk of cardiovascular disease.[ Diabetologia (1998

OBJECTIVE -To assess the occurrence and development of new peripheral arterial occlusive disease (PAOD), its risk factors, and the outcome in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 130 type 2 diabetic patients (mean age 58 years) were examined at baseline and after a mean follow-up of 11 years (range 7-14). The ankle-brachial index (ABI) and toe-brachial index were used to detect PAOD. Blood and urine samples were taken at baseline, and a history of cardiovascular events was recorded during follow-up.RESULTS -PAOD was diagnosed in 21 (16%) patients at baseline. During follow-up, 21 of 89 (24%) patients developed new PAOD. There were 29 patients who died, 21 (72%) of them from cardiovascular disease. Patients with PAOD suffered an excess mortality compared with patients without PAOD (58 vs. 16%; P Ͻ 0.001). Logistic regression analysis showed that PAOD at baseline was associated with age, duration of diabetes, smoking, and urinary albumin excretion rate. Patients who developed new PAOD during follow-up had higher serum LDL cholesterol concentrations and lower HDL cholesterol concentrations and were older than the patients who remained free of PAOD.CONCLUSIONS -Objectively measured PAOD is frequent in type 2 diabetic patients. It presents the early clinical signs of atherosclerosis and is strongly associated with cardiovascular death. The risk factor pattern for PAOD was different at baseline and after a mean follow-up of 11 years. We consider routine ABI measurements and modification of risk factors necessary also in patients with asymptomatic PAOD. Diabetes Care 26:1241-1245, 2003I n patients with type 2 diabetes, peripheral arterial occlusive disease (PAOD) is a major contributor to diabetic foot problems. Identification of PAOD is essential because, in many cases, appropriate treatment saves the diabetic foot (1). Further, prevention of foot problems may be easier than treating foot problems. For this purpose, specific risk factors for the development of PAOD need to be recognized.Follow-up studies on risk factors for objectively measured PAOD in patients with type 2 diabetes are few, and the follow-up times are short (2-4 years) (2-4). Some evidence suggests that general risk factors of atherosclerosis such as systolic hypertension, smoking, dyslipidemia, and age are also risk factors for progression of PAOD (2,4). A recent study proposed that HbA 1c , LDL cholesterol, and smoking are risk factors for development of new PAOD in patients with type 1 diabetes (5), but no similar data are available for type 2 diabetes.Objectively measured PAOD predicts cardiovascular death and morbidity both in the general population and the diabetic population (2,6,7). Therefore, the following question arises: Could objectively measured PAOD be the first clinical sign of cardiovascular disease?The diagnosis of PAOD is critical. Palpation of pulses and a history of claudication detect PAOD inadequately; therefore, PAOD should be assessed by objective noninvasive measurements (8). The ankle-brachial...

a free muscle flap connected to an infrapopliteal bypass increases the distal outflow bed and thus decreases the outflow resistance and increases graft flow.

Background: Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status. Methods: We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD dependent on diabetic or smoking status. Results: We identified 5 genome-wide significant ( P association ≤5×10 −8 ) associations with PAD in 449 548 (N cases =12 086) individuals of European ancestry near LPA , CDKN2BAS1 , SH2B3-PTPN11 , HDAC9 , and CHRNA5 loci (which overlapped previously reported associations). Meta-analysis with variants previously association with PAD showed that 18 of 19 published variants remained genome-wide significant. In individuals with diabetes, rs116405693 at the CCSER1 locus was associated with PAD (odds ratio [95% CI], 1.51 [1.32–1.74], P diabetes =2.5×10 −9 , P interactionwithdiabetes =5.3×10 −7 ). Furthermore, in smokers, rs12910984 at the CHRNA3 locus was associated with PAD (odds ratio [95% CI], 1.15 [1.11–1.19], P smokers =9.3×10 −10 , P interactionwithsmoking =3.9×10 −5 ). Conclusions: Our analyses confirm the published genetic associations with PAD and identify novel variants that may influence susceptibility to PAD in the context of diabetes or smoking status.