BackgroundDiabetic foot ulcer (DFU) is a severe complication of diabetes, preceding most diabetes-related amputations. DFUs require over US$9 billion for yearly treatment and are now a global public health issue. DFU occurs in the setting of ischemia, infection, neuropathy, and metabolic disorders that result in poor wound healing and poor treatment options. Recently, stem cell therapy has emerged as a new interventional strategy to treat DFU and appears to be safe and effective in both preclinical and clinical trials. However, variability in the stem cell type and origin, route and protocol for administration, and concomitant use of angioplasty confound easy interpretation and generalization of the results.MethodsThe PubMed, Google Scholar, and EMBASE databases were searched and 89 preclinical and clinical studies were selected for analysis.ResultsThere was divergence between preclinical and clinical studies regarding stem cell type, origin, and delivery techniques. There was heterogeneous preclinical and clinical study design and few randomized clinical trials. Granulocyte-colony stimulating factor was employed in some studies but with differing protocols. Concomitant performance of angioplasty with stem cell therapy showed increased efficiency compared to either therapy alone.ConclusionsStem cell therapy is an effective treatment for diabetic foot ulcers and is currently used as an alternative to amputation for some patients without other options for revascularization. Concordance between preclinical and clinical studies may help design future randomized clinical trials.

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Introduction. Patients with systemic lupus erythematosus (SLE) have recognized reduction in endothelium-dependent vasodilation. Evidence demonstrates that statins are able to improve endothelial function independently on their hypolipemic action. Objectives. To evaluate the efficacy of atorvastatin in improving vasodilation in SLE patients with and without conventional risk factors for coronary heart disease (CHD). Patients and methods. Sixty-four SLE women, mean age 31 AE 8 yrs, received atorvastatin 20 mg/day during 8 weeks. Thirty-one patients in this intervention group did not have conventional risk factors for CHD, while 33 others had hypertension, dyslipidaemia and/or obesity. Twenty-four SLE control patients, mean age 34 AE 7.5 yrs, not receiving atorvastatin were followed during the same time period. Highresolution ultrasound was used to measure brachial artery diameter in resting conditions, during reactive hyperaemia and after sub-lingual glyceryl trinitrate (GTN). Measurements were performed at baseline and at the end of the study (8 weeks). Results. Atorvastatin was associated with a significant increase in flow-mediated dilation (FMD) [3.8 (2.8-7.9%) vs 6.9 (4.2-10.7%), P < 0.001] while GTN-mediated dilation (GTND) was unaffected [20.9 (16.6-26.1%) vs 20.1(16.6-25.4%), P ¼ 0.514]. FMD increase was observed in patients with conventional risk factors [4.1 (3.1-8.7%) vs 6.5 (4-10%), P ¼ 0.046] and also for those without conventional risk factors for CHD [3.6 (2.6-7.3%) vs 7.1 (4.5-10.9%), P ¼ 0.001]. Resting brachial artery diameter also increased significantly in patients receiving atorvastatin (2.79 AE 0.30 mm vs 2.92 AE 0.40 mm, P < 0.001). No significant difference in artery diameter and FMD was seen in control patients at the end of the study. When compared to the control patients, atorvastatin treatment was associated with significant increase in resting diameter (þ0.13 AE 0.1 mm vs -0.02 AE 0.07 mm, P < 0.001) and FMD (þ1.9 AE 3.9% vs -0.3 AE 1.8%, P ¼ 0.009).Conclusion. Our results demonstrate that an 8-week 20 mg/day atorvastatin series improved endothelium-dependent vasodilation in SLE patients independently on the presence of conventional risk factors for atherosclerotic disease.

Hypothesis: As the compliant greater saphenous vein (GSV) adjusts its luminal size to the level of transmural pressure, measurement of its diameter, reflecting the severity of hemodynamic compromise in limbs with GSV reflux, may simplify the hemodynamic criteria of patient selection for saphenectomy. Objective: To evaluate the clinical significance of GSV diameter determined in the thigh and calf as a marker of global hemodynamic impairment and clinical severity in a model comprising patients with saphenofemoral junction and truncal GSV incompetence. Design: A cohort study. Setting: University-associated tertiary care hospitals in Brazil and England. Patients: Eighty-five consecutive patients, aged 28 to 82 (mean, 46.2) years; 112 lower limbs with saphenofemoral junction and truncal GSV incompetence were investigated. Interventions: Clinical examination was followed by clinical, etiological, anatomical, and pathophysiological classification (CEAP), vein duplex, and air plethysmography. The GSV diameter was measured on standing at the knee, and at 10, 20, and 30 cm above and below the knee, and in the thigh and calf, respectively, using Bmode imaging. The venous filling index (VFI), venous volume (VV), and residual volume fraction (RVF) were measured by air plethysmography. Main Outcome Measures: The GSV diameter was correlated with the VFI, VV, RVF, and CEAP. The value of the GSV diameter for predicting the presence of critical reflux (VFI Ͼ7 mL/s) or the absence of abnormal reflux (VFI Ͻ2 mL/s) was determined with receiver-operator curves. Results: The GSV diameter increased significantly overall with CEAP (PϽ.001) and also increased progressively with proximity to the saphenofemoral junction. The VFI, VV, and RVF increased significantly from CEAP 0 through CEAP 4-6 ; the VFI correlated well with VV, RVF, and CEAP (PϽ.001 for all). The GSV diameter at all 7 limb levels studied correlated well with VV (except at the distal calf), VFI, RVF, and CEAP (PՅ.009 for all). A GSV diameter of 5.5 mm or less predicted the absence of abnormal reflux, with a sensitivity of 78%, a specificity of 87%, positive and negative predictive values of 78%, and an accuracy of 82%. A GSV diameter of 7.3 mm or greater predicted critical reflux (VFI Ͼ7 mL/s), with an 80% sensitivity, an 85% specificity, and an 84% accuracy. Conclusion: The GSV diameter proved to be a relatively accurate measure of hemodynamic impairment and clinical severity in a model of saphenofemoral junction and GSV incompetence, predicting not only the absence of abnormal reflux, but also the presence of critical venous incompetence, assisting in clinical decision making before considering greater saphenectomy.