Diabetic foot (DF) disease continues to be a major cause of mortality and disability. The pathophysiology of DF is multifactorial and includes neuropathy, infection, ischemia, and abnormal foot structure and biomechanics. Current therapies are limited; however, based on recent research efforts, there is rising hope for promising and more effective stem cell therapeutic approaches for these patients. In this review, we discuss mesenchymal stem cells as tools for cell/scaffold-based therapies for nonhealing wounds. We have reviewed the main clinical trials dividing them based on their clinical applications and taken into account the ethical issue associated with the stem cell therapy.

BACKGROUND: Diabetes is a major risk factor for peripheral artery disease (PAD). Infrainguinal bypass surgery (IBS) has been the modality of choice for limb salvage in PAD patients. It is well known that diabetic patients have different disease progression than nondiabetics. Therefore, it is important to assess the outcomes and to determine the efficacy of current surgical practices for limb salvage in the diabetic population. The aim of this study is to evaluate short-term and long-term outcomes after IBS in diabetic patients. MATERIALS AND METHODS: We identified all patients who underwent IBS at our hospital from 2007 to 2014. Explanatory analysis using Pearson's Chi-square test, Fischer's exact test, and Student's t-test was performed. Kaplan–Meier analysis was used to evaluate primary patency, primary-assisted patency, and limb loss. Multivariate Cox regression analysis was implemented to examine loss of patency and amputation after adjusting for patients' demographics and comorbidities. RESULTS: A total of 428 IBSs were performed. Out of those, 264 (62%) were diabetic. Diabetic patients presented on average of 3 years earlier than nondiabetics (66.3 [11.0] vs. 68.9 [11.9], P = 0.03) and had significantly higher comorbidities including dyslipidemia (58% vs. 45% P = 0.01), coronary artery disease (70% vs. 46%, P = 0.01), and chronic kidney disease (20% vs. 2%, P = 0.001). There were more diabetics who presented with critical limb ischemia (CLI) (92% vs. 80%, P < 0.001). There was no difference in all-cause mortality over the study period between the two groups (35% vs. 27%, P = 0.11), but diabetics had three times higher major amputation rates (17% vs. 6%, P = 0.001). After adjusting for potential confounders, the risk of amputation was 2.7 times higher in diabetics (hazard ratio [HR] =2.66, 95% confidence interval [CI]: 1.24–5.72, P = 0.001) with no statistically significant difference in loss of primary patency (HR = 1.23, 95% CI: 0.78–1.94, P = 0.37) or primary-assisted patency (HR = 0.98, 95% CI: 0.58–1.64, P = 0.94). CONCLUSIONS: In this study, we found no significant difference in graft patency between diabetic and nondiabetic patients; however, limb loss was almost four folds higher in diabetics with CLI after IBS. This suggests that additional factors after revascularization play an important role in limb salvage in diabetics. Further prospective study in a larger cohort of patients is suggested to evaluate the outcomes of IBS and endovascular therapy in diabetic patients.

Background: Vascular identity is genetically determined but can be altered during surgical procedures. Methods: We hypothesized that the environment of the procedure critically alters the identity of autologous tissue patches implanted into the arterial or venous environment. Results: Autologous jugular vein or carotid artery was used as a patch to repair a rat aorta or inferior vena cava. In the aortic environment, patches contained neointimal cells that were CD34/ephrin-B2-dual positive but not CD34/Eph-B4-dual positive; patches expressed ephrin-B2, notch-4, and dll-4 but not Eph-B4 and COUP-TFII. In the venous environment, patches contained neointimal cells that were CD34/Eph-B4-dual positive but not CD34/ephrin-B2-dual positive; patches expressed Eph-B4 and COUP-TFIIbut not ephrin-B2, notch-4, and dll-4. Conclusion: These data show that autologous tissue patches heal by acquisition of the vascular identity determined by the environment into which they are implanted, suggesting some plasticity of adult vascular identity.

INTRODUCTION: Studies have shown poor outcomes following infra-inguinal bypass in African-American patients compared with Caucasians. The aim of this study was to investigate the racial disparity in a cohort of patients who underwent infra-inguinal bypass surgery at our institute. METHODS: We retrospectively reviewed data of all patients who underwent infra-inguinal bypass performed with autogenous vein grafts for symptomatic peripheral artery disease from 2007–2014 at a single tertiary care institution. Univariate (Chi-square test and Student's t-test) and multivariable analyses (logistic and Cox regression) were used to evaluate the association between race and the outcomes of mortality, primary and primary-assisted patency, and limb loss following infra-inguinal bypass. RESULTS: The study included 412 autogenous bypass grafts, of which 312 (76%) were performed in Caucasians and 100 (24%) in African-Americans. African-American patients had significantly higher comorbidities including diabetes (74% vs. 57%, P = 0.002) and chronic kidney disease on dialysis (22% vs. 10%, P = 0.002) as compared with Caucasians. The majority of patients in both groups underwent bypass for critical limb ischemia (88% vs. 87%, P = 0.71). Mean follow-up time was 1.8 ± 1.8 years. The rates of major amputation were not significantly different between two groups (17% vs. 10%, P = 0.07). Moreover, no significant differences in primary and primary assisted were seen between African-Americans and Caucasians (hazard ratio [HR] [95% confidence interval [CI]: 0.90 [0.56–1.44], P = 0.66 and 1.21 [0.72–2.03], P = 0.46), respectively. Hyperlipidemia was shown to be significantly associated with primary-assisted patency, while diabetes was a significant risk factor for limb loss [HR (95% CI): 2.73 (1.26–5.93), P = 0.01). CONCLUSION: In this study, there were no significant differences in bypass patency and limb salvage between African-Americans and Caucasians following infra-inguinal bypass over 5-year follow-up. These findings suggest that the outcomes of infra-inguinal bypass can be optimized in African-American patients with the use of autogenous vein conduits and comprehensive medical management including the control of diabetes and hyperlipidemia.

CONTEXT: Sleep disturbance and proinflammatory markers were reported to link to the development of type 2 diabetes mellitus and glucose homeostasis. METHODS: A clinical laboratory–based analysis was performed on 14 normal volunteers, 11 diabetic patients and 16 non-diabetic patients form department of vascular surgery conducted between January 2013 and March 2013. Continuous polysomnographic monitoring was performed on 2 nights in the intensive care unit (IUC). Blood glucose level was controlled by insulin infusion. Concentrations of IL-6 and CRP levels were determined by enzyme-linked immunoassays. OBJECTIVE: To raise awareness of risk factors among postsurgery type 2 diabetes with foot ulcers. DESIGN: A clinical laboratory-based analysis was performed on 14 normal volunteers, 11 diabetic patients, and 16 nondiabetic patients from Department of Vascular Surgery conducted between January 2013 and March 2013. SETTING: This trial was admitted to Siping hospital affiliated to China Medical University, China. PATIENTS: Twenty-seven patients were postthrombolytic therapy and 14 healthy controls. INTERVENTIONS: Continuous polysomnographic monitoring was performed on 2 nights in the Intensive Care Unit (ICU). Blood glucose level was controlled by insulin infusion. Concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP) levels were determined by enzyme-linked immunoassays. MAIN OUTCOME MEASURE: Changes in exogenous insulin requirements, while IL-6 and CRP levels. RESULTS: Insulin requirements on admission in ICU 48-h treatment increased 21.2% in diabetic patients compared to 24-h postsurgery. All postsurgical patients elevated IL-6 and CRP levels compared to normal individuals in the morning after 24 h and 48 h of sleep restriction. Fasting concentrations of IL-6 were distinctly increased 23.6% and 42.9%, respectively, after 24 h and 48 h of sleep restriction in diabetic patients compared to normal individuals and 18.5% and 21.8%, respectively, compared to nondiabetic patients. CRP levels are similar to IL-6 levels among these partners. CONCLUSIONS: Our study elucidated that sleep disruption aggravates disturbed glucoregulatory and systemic inflammation among postsurgical diabetic patients, which might contribute to understand these disorders for diabetic patients in immunological pathways.

BACKGROUND: Intravenous drug abusers (IVDA) are at an increased risk of developing infected peripheral pseudoaneurysms. The aim of this study is to describe a group of IVDA patients who present with infected peripheral pseudoaneurysms and to evaluate the outcomes of vascular surgery reconstruction in this population. MATERIALS AND METHODS: A retrospective study of all IVDA patients presenting with peripheral pseudoaneurysms between 2009 and 2015 in the premier healthcare vascular surgery database 2009–2015 were identified. Patients' demographics, comorbidities, along with the vascular procedures performed, and in-hospital complications were reported. RESULTS: Out of 2012 vascular surgery patients known to be opioid abusers, 71 (3.5%) presented with infected peripheral pseudoaneurysms (mean age: 44.8 years, standard deviation: 15.0). The majority of these patients were Caucasians or Whites (64.8%) and underwent resection of the upper or lower limb arteries (29.7%), clipping of aneurysm (21.9%), or bypass procedures (9.4%). Two patients (3.1%) underwent primary major amputation. In-hospital mortality was observed in 1.4% of patients, hemorrhage/shock in 12.7% and cardiac arrhythmias in 7%. Four patients (5.6%) underwent secondary major amputation during the same hospitalization. Median length of hospital stay was 8 days. Around 24% of these patients were discharged to a skilled nursing facility or a rehabilitation center. The median cost of hospitalization for these patients was 21,807 (USD) with a median fixed and variable cost of 10,392 and 9356 (USD), respectively. CONCLUSION: IVDA patients with infected pseudoaneurysms are at high risk for postoperative complications, major morbidity, extended length of stay, and nonhome discharge destination which poses a huge medical, social, and economic burden.