Diabetic Limb Research Articles

Ablation of DUSP4 Exacerbates Blood Flow Reperfusion in Diabetic Limb

Collateral vessel formation, a normal response to artery occlusion, is impaired in patients with diabetes, rendering the tissue downstream more susceptible to critical ischemia. Thus, understanding of the mechanisms induced by diabetes on reduced collateral vessel formation may offer new therapeutic perspectives to prevent amputation. Our laboratory has discovered that diabetes decreased the expression of DUSP4, which was associated with elevated inflammation and vascular dysfunction.

A KCNQ4 c.546C>G Genetic Variant Associated with Late Onset Non-Syndromic Hearing Loss in a Taiwanese Population.

Clinical presentation is heterogeneous for autosomal dominant nonsyndromic hearing loss (ADNSHL). Variants of KCNQ4 gene is a common genetic factor of ADNSHL. Few studies have investigated the association between hearing impairment and the variant c.546C>G of KCNQ4. Here, we investigated the phenotype and clinical manifestations of the KCNQ4 variant. Study subjects were selected from the participants of the Taiwan Precision Medicine Initiative. In total, we enrolled 12 individuals with KCNQ4 c.546C>G carriers and 107 non-carriers, and performed pure tone audiometry (PTA) test and phenome-wide association (PheWAS) analysis for the patients. We found that c.546C>G variant was related to an increased risk of hearing loss. All patients with c.546C>G variant were aged >65 years and had sensorineural and high frequency hearing loss. Of these patients, a third (66.7%) showed moderate and progressive hearing loss, 41.7% complained of tinnitus and 16.7% complained of vertigo. Additionally, we found a significant association between KCNQ4 c.546C>G variant, aortic aneurysm, fracture of lower limb and polyneuropathy in diabetes. KCNQ4 c.546C>G is likely a potentially pathogenic variant of ADNSHL in the elderly population. Genetic counseling, annual audiogram and early assistive listening device intervention are highly recommended to prevent profound hearing impairment in this patient group.

Single Intraosseous Simvastatin Application Induces Endothelial Progenitor Cell Mobilization and Therapeutic Angiogenesis in a Diabetic Hindlimb Ischemia Rat Model.

Endothelial progenitor cells have shown the ability to enhance neovascularization. In this study, the authors tested whether intraosseous delivery of simvastatin could mobilize endothelial progenitor cells and enhance recovery in a hindlimb ischemia model. There are eight groups of rats in this study: normal control; type 1 diabetes mellitus control group control without drug intervention; and type 1 diabetes mellitus rats that randomly received intraosseous simvastatin (0, 0.5, or 1 mg) or oral simvastatin administration (0, 20, or 400 mg). All type 1 diabetes mellitus rats had induced hindlimb ischemia. The number of endothelial progenitor cells in peripheral blood, and serum markers, were detected. The recovery of blood flow at 21 days after treatment was used as the main outcome. The authors demonstrated that endothelial progenitor cell mobilization was increased in the simvastatin 0.5- and 1-mg groups compared with the type 1 diabetes mellitus control and simvastatin 0-mg groups at 1, 2, and 3 weeks. Serum vascular endothelial growth factor levels were significantly increased at 2 weeks in the simvastatin 0.5- and 1-mg groups, in addition to the increase of the blood flow and the gastrocnemius weight at 3 weeks. Similar increase can also been seen in simvastatin 400 mg orally but not in simvastatin 20 mg orally. These findings demonstrate that a single intraosseous administration of simvastatin mobilized endothelial progenitor cells at a dose one-hundredth of the required daily oral dose in rats, and this potent mobilization of endothelial progenitor cells markedly improved diabetic limb ischemia by means of neovascularization.

Combination of Antioxidant Enzyme Overexpression and N-Acetylcysteine Treatment Enhances the Survival of Bone Marrow Mesenchymal Stromal Cells in Ischemic Limb in Mice With Type 2 Diabetes.

BackgroundTherapy with mesenchymal stem cells remains a promising but challenging approach to critical limb ischemia in diabetes because of the dismal cell survival.Methods and ResultsCritical limb ischemia in type 2 diabetes mouse model was used to explore the impact of diabetic limb ischemia on the survival of bone marrow mesenchymal stromal cells (bMSCs). Inhibition of intracellular reactive oxygen species was achieved with concomitant overexpression of superoxide dismutase (SOD)‐1 and glutathione peroxidase‐1 in the transplanted bMSCs, and extracellular reactive oxygen species was attenuated using SOD‐3 overexpression and N‐acetylcysteine treatment. In vivo optical fluorescence imaging and laser Doppler perfusion imaging were used to track cell retention and determine blood flow in diabetic ischemic limb, respectively. Survival of the transplanted bMSCs was significantly decreased in diabetic ischemic limb compared with the control. In vitro study indicated that advanced glycation end products, not high glucose, significantly decreased the proliferation of bMSCs and increased their apoptosis associated with increased reactive oxygen species production and selective reduction of SOD‐1 and SOD‐3. In vivo study demonstrated that concomitant overexpression of SOD‐1, SOD‐3, and glutathione peroxidase‐1, or host treatment with N‐acetylcysteine, significantly enhanced in vivo survival of transplanted bMSCs, and improved critical limb ischemia in diabetic mice. Combination of triple antioxidant enzyme overexpression in bMSCs with host N‐acetylcysteine treatment further improved bMSC survival with enhanced circulatory and functional recovery from diabetic critical limb ischemia.ConclusionsSimultaneous suppression of reactive oxygen species from transplanted bMSCs and host tissue could additively enhance bMSC survival in diabetic ischemic limb with increased therapeutic efficacy in diabetes.

PRINCIPLES OF EVIDENCE MEDICINE IN COMPLEX THERAPY FOR DIABETIC POLYNEUROPATHY

Diabetic polyneuropathy (DPN) is the most common chronic complication of diabetes mellitus. It is known that DPN not only significantly reduces the quality of life of patients, but also causes more formidable consequences of the disease - diabetic foot syndrome and limb amputation. Given the key role of hyperglycemia in the pathogenesis of DPN, the main direction in the prevention and treatment of this condition is adequate control of blood glucose and glycosylated hemoglobin (HbA1c) levels.

Diagnostic value of dual-source spiral CT in patients with diabetic lower limb arteriosclerosis obliterans.

Diagnostic value of dual-source spiral CT in patients with diabetic lower limb arteriosclerosis obliterans.

Monitoring and Prevention the Risk of Diabetic Foot Ulcer Infection during Coronavirus Disease-19 Pandemic: A Narrative Review and Perspective Algorithm

BACKGROUND: The coronavirus disease (COVID)-19 pandemic leads to significant changes in the healthcare system and undermining best practices for maintaining a diabetic limb. A large number of patients with diabetic foot are left without timely medical care and are at increased risk of complications, hospitalization, lower limb amputation, and death. A new paradigm must be adopted for the transition from inpatient care to community-based care. The introduction of a pandemic remote management for patients with diabetic foot ulcer includes an assessment of the risk of complications through telemedicine and further stratification of patients according to the developed algorithm. METHODS: A literature review was performed for articles related to telemedicine. We used PubMed, Google Scholar, Cochrane Library, and Ovid MEDLINE to search published articles. We used the following keywords: “Telemedicine,” “diabetes mellitus,” “COVID-19,” “diabetic foot ulcer,” and “remote monitoring.” RESULTS: Implementation of the proposed pandemic care includes telemedicine for remote monitoring and treatment of patients with diabetic foot ulcers, as well as an algorithm for determining the risk of diabetic ulcer infection and patient management tactics according to the identified risk. CONCLUSION: The management of patients with diabetic foot ulcers during a pandemic includes the following goals – to reduce the burden on the health-care system, maintain the safety and functionality of diabetic foot at home, and reduce the risk of COVID-19 in patients with diabetic foot ulcers.

The Global Anatomic Staging System Does Not Predict Limb Based Patency of Tibial Endovascular Interventions

Anatomic grading systems have historically been poor predictors of patency after endovascular tibial interventions. The Global Vascular Guidelines proposed a new Global Anatomic Staging System (GLASS) to estimate one-year limb-based patency (LBP). The purpose of this study was to determine the association of GLASS with LBP following endovascular tibial interventions. We included all patients presenting to our multidisciplinary diabetic limb preservation service between 01/2012 and 8/2020 who underwent first-time endovascular tibial revascularization for chronic limb-threatening ischemia. Diagnostic angiograms were reviewed to define the preferred target artery pathway and assign a GLASS stage to each treated limb. One-year LBP was calculated and compared across GLASS stages using Kaplan-Meier curves with log-rank tests and Cox proportional hazards models. We performed tibial revascularization in 96 limbs (5.2% rest pain, 56.3% ulcer, 37.5% gangrene), including isolated tibial interventions in 61.5% and tibial + femoropopliteal interventions in 38.5%. 15.6% of limbs were GLASS stage 1, 28.1% were GLASS stage 2, and 56.3% were GLASS stage 3. Overall, one-year LBP was 43.2 ± 6.3%, and did not differ significantly across GLASS stages (P = 0.42). The hazard ratio for failed LBP was 1.94 (95% CI 0.70-5.41) for GLASS stage 2 and 1.49 (95% CI 0.56-3.94) for GLASS stage 3 limbs (versus GLASS stage 1). When analyzed excluding the calcium modifier, LBP remained similar across GLASS stages (P = 0.72). Major amputation was uncommon, occurring in 9.3 ± 3.4% of limbs at one year, and did not significantly differ by GLASS stage (P = 0.98). The Global Anatomic Staging System did not predict limb-based patency following tibial endovascular interventions. Given the low major amputation rates in this cohort, anatomic complexity should not preclude endovascular limb salvage efforts below the knee.

Free Tissue Transfer after Open Transmetatarsal Amputation in Diabetic Patients.

Transmetatarsal amputation (TMA) preserves functional gait while avoiding the need for prosthesis. However, when primary closure is not possible after amputation, higher level amputation is recommended. We hypothesize that reconstruction of the amputation stump using free tissue transfer when closure is not possible can achieve similar benefits as primarily closed TMAs. Twenty-eight TMAs with free flap reconstruction were retrospectively reviewed in 27 diabetic patients with a median age of 61.5 years from 2004 to 2018. The primary outcome was limb salvage rate, with additional evaluation of flap survival, ambulatory status, time until ambulation, and further amputation rate. In addition, subgroup analysis was performed based on the microanastomosis type. Flap survival was 93% (26 of 28 flaps) and limb salvage rate of 93% (25 of 27 limbs) was achieved. One patient underwent a second free flap reconstruction. In the two failed cases, higher level amputation was required. Thirteen flaps had partial loss or other complications which were salvaged with secondary intension or skin grafts. Median time until ambulation was 14 days following reconstruction (range: 9-20 days). Patients were followed-up for a median of 344 days (range: 142-594 days). Also, 88% of patients reported good ambulatory function, with a median ambulation score of 4 out of 5 at follow-up. There was no significant difference between the subgroups based on the microanastomosis type. TMA with free flap reconstruction is an effective method for diabetic limb salvage, yielding good functional outcomes and healing results.

Toward an Interdisciplinary Approach to Diabetic Limbs in the Era of Functional Limb Preservation: "Can We Preserve This Limb?" Meets "Should We Preserve This Limb?"

Toward an Interdisciplinary Approach to Diabetic Limbs in the Era of Functional Limb Preservation: "Can We Preserve This Limb?" Meets "Should We Preserve This Limb?"

Endothelial deletion of PKCδ prevents VEGF inhibition and restores blood flow reperfusion in diabetic ischemic limb.

Aims:Peripheral artery disease is a complication of diabetes leading to critical hindlimb ischemia. Diabetes-induced inhibition of VEGF actions is associated with the activation of protein kinase Cδ (PKCδ). We aim to specifically investigate the role of PKCδ in endothelial cell (EC) function and VEGF signaling.Methods:Nondiabetic and diabetic mice, with (ec-Prkcd−/−) or without (ec-Prkcdf/f) endothelial deletion of PKCδ, underwent femoral artery ligation. Blood flow reperfusion was assessed up to 4 weeks post-surgery. Capillary density, EC apoptosis and VEGF signaling were evaluated in the ischemic muscle. Src homology region 2 domain-containing phosphatase-1 (SHP-1) phosphatase activity was assessed in vitro using primary ECs.Results:Ischemic muscle of diabetic ec-Prkcdf/f mice exhibited reduced blood flow reperfusion and capillary density while apoptosis increased as compared to nondiabetic ec-Prkcdf/f mice. In contrast, blood flow reperfusion and capillary density were significantly improved in diabetic ec-Prkcd−/− mice. VEGF signaling pathway was restored in diabetic ec-Prkcd−/− mice. The deletion of PKCδ in ECs prevented diabetes-induced VEGF unresponsiveness through a reduction of SHP-1 phosphatase activity.Conclusions:Our data provide new highlights in mechanisms by which PKCδ activation in EC contributed to poor collateral vessel formation, thus, offering novel therapeutic targets to improve angiogenesis in the diabetic limb.

Long term functional outcomes of a permanent antibiotic cement spacer for chronic distal tibial osteomyelitis in a patient with diabetes

A 66-year-old male with chronic right distal tibial osteomyelitis presents with erythema and a draining sinus tract concerning for acute exacerbation. Previously stable on amoxicillin/clavulanate, worsening symptoms for 3–4 months prompted referral. Following evaluation, treatment consisted of debridement, insertion of an antibiotic cement spacer into the partial cortical tibial defect and free flap coverage. At five-year follow up, the antibiotic spacer remains in place without recurrence of osteomyelitis and with preserved function. Further investigation is needed to validate permanent retention of an antibiotic spacer as an alternative to vascularized or non-vascularized bone grafts for management of chronic tibial osteomyelitis in the comorbid diabetic limb salvage population.

Analysis of Disability due to Diabetes Mellitus in a Large City

Significance. A majority of people with diabetes are unaware of having diabetes complications. When not well managed, all types of diabetes can lead to complications in many parts of the body, resulting in disabilities and early death. Purpose. To study the dynamics of the disability of the population of Almaty (Republic of Kazakhstan) due to diabetes Material and methods. Data was collected from the registries of medical records in the Republic Center of Electronic Healthcare, Ministry of Health of the Republic of Kazakhstan and Department of Labor, social protection and migration in Almaty for the period from 2013 to 2017. The object of the study was 651 patients – residents of Almaty, suffering from diabetes mellitus, who were identified as a «disabled child», I, II and III disability groups during the initial examination in 2013-2017 by the territorial departments of medical and social expertise. There were 298 disabled people due to type 1 diabetes, and 353 disabled people due to type 2 diabetes. The study group consisted of 309 women and 342 men. The paper uses data from medical and social examination records, extracts from the medical history and outpatient cards of disabled people suffering from diabetes. Statistical methods the analysis in the research was carried out on the basis of descriptive statistics: average values and standard deviations. Results. Majority of disabled people had decompensated disease. Diabetic retinopathy observed in 29.63 ± 0.06%, including among disabled people of 1st degree is 12.0%, among disabled people of 2nd degree is 42.0%, among disabled people of 3rd degree - 46.0%. Diabetic nephropathy (stage 3 or more) was detected in 22.92% ± 0.03%, including chronic renal failure. Diabetic foot syndrome over five years averaged 19.69 ± 0.04%. Of these: 1st degree disabled people - 15.3%, 2nd degree - 76.3%, 3rd degree - 8.4%. In last 5 years amputations between people with disabilities due to diabetes averaged 12.63 ± 0.02%. Amputation of one or both lower limbs is an irreversible process; it is also the most serious complication of diabetes. Discussion. The results are stated that the indicator of disability due to diabetes among the population of the city of Almaty is affected by type II diabetes adult contingents of the population and type I diabetes more often by children and adolescents. Severe complications (diabetic retinopathy, diabetic nephropathy, diabetic foot syndrome and limb amputation), early disability, premature death put this disease on a par with global health problems.

Prevalence and Determinants of Diabetic Peripheral Neuropathy/Foot Syndrome in the Rural Population of North India

Introduction: Diabetic peripheral neuropathy (DPN), a common and troublesome complication of diabetes mellitus (DM), leads to a higher risk of diabetic foot ulcers and lower limb amputation. This study aimed to assess the prevalence of DPN among patients of type 2 DM from rural North India and associated risk factors for the condition. Materials and Methods: A facility-based cross-sectional study was carried out among type 2 diabetic patients attending the Non-Communicable Diseases (NCD) clinic of a secondary care hospital in rural North India. A questionnaire that included sociodemographic details, clinical and laboratory parameters, and the Michigan Neuropathy Screening Instrument (MNSI) for detecting peripheral neuropathy was administered to 100 consecutive eligible patients. Statistical Package for Social Sciences (SPSS) version 25.0 was used for entering and analyzing data. Bivariate analysis was performed to determine the factors significantly associated with the presence of DPN. Results: The prevalence of DPN was found to be 42.0%. Male gender, advancing age (≥60 years), longer duration of diabetes (>10 years), smoking, physical inactivity, obesity, uncontrolled blood pressure, poor glycemic control and altered lipid profile were found to be significantly associated with the presence of DPN. Conclusions: The prevalence of DPN among type 2 diabetes patients from rural northern India is alarmingly high. There is a need for essential screening of all diabetic patients by their primary care provider for early detection of DPN, particularly in rural India.

An Extension of the Bollinger Scoring System to Analyse the Distribution of Macrovascular Disease of the Lower Limb in Diabetes

While it is generally considered that patients with diabetes mellitus (DM) have more distal peripheral arterial disease (PAD), there is little information on how individual vessels are affected. The aim of this study was to adapt Bollinger's scoring system for lower limb angiograms (DSAs) to include the distal and planter vessels. The reliability of this extension was tested and was used to compare the distribution of disease in two cohorts of patients with and without DM. Patients who had undergone DSA±angioplasty for PAD at a single centre between September 2010 and April 2014 were identified. Twenty-five patients' images were reviewed by four clinicians and scored using an extended version of the Bollinger score. A total of 153 patients with DM were matched, for age, sex, ethnicity, smoking, and hypertension, with 153 patients without DM. The infrainguinal vessels were divided into 16 arterial segments, including plantar vessels, and scored using the Bollinger score. The score ranges from 0 to 15. Fifteen represents an arterial segment with more than 50% of its length occluded. Interobserver reliability was tested using interclass correlation (ICC) and Cohen's kappa coefficient. The ICC demonstrated good agreement between observers (0.76 [0.72-0.79]) with good internal consistency (Cronbach's alpha 0.93). When the Bollinger scores were categorised, the results were weaker, Cohen's kappa ranged from 0.39 (standard error 0.033) to 0.54 (0.030). Patients with DM had a higher burden of disease in the anterior tibial and posterior tibial arteries with relative sparing of the peroneal artery and no difference in the plantar vessels. It has been demonstrated that the Bollinger score can be extended to include the distal vessels. This amended scoring system can be used to compare the burden of distal disease in patients with PAD. How the score relates to clinical presentation and outcomes needs further investigation.

Combined physical therapy for diabetic angiopathy

Background. The problem of diabetic angiopathy is characteristic of countries even with a high level of development of medicine. The high frequency of complications of diabetes with high biological and social significance determines the need for their correction.
 The purpose of the work was to increase the effectiveness of rehabilitation treatment for patients with diabetic angiopathy through the combined use of therapeutic exercises and functional electrical stimulation of the lower extremities.
 Methods. A prospective cohort study was conducted, in which 90 patients (63 men and 27 women) with an established diagnosis of type 2 diabetes took part.
 Results. It was found that the use of therapeutic gymnastics and training walking on a treadmill and functional neuroelectrostimulation of the lower extremities increase the motor capabilities of patients due to the analgesic effect, improved neurogenic control of vasoconstriction of arteriovenous anastomoses and increased capillary blood flow.
 Conclusion. Functional electrical stimulation method can be effectively used in physical therapy programs for patients with diabetic lower limb angiopathies at the inpatient and outpatient stages.

TUG1 enhances high glucose-impaired endothelial progenitor cell function via miR-29c-3p/PDGF-BB/Wnt signaling

BackgroundDiabetes is associated with the dysfunction of endothelial progenitor cells (EPCs), characterized as impaired angiogenesis, a phenomenon thought to be involved in the development of diabetic foot. lncRNA plays an essential role in microvascular dysfunction and signaling pathways in patients with diabetes. lncRNA taurine upregulated gene 1 (TUG1) participates in angiogenesis in various cells. However, the mechanisms of TUG1 activity in EPCs have not been elucidated.MethodsWe isolated and then characterized EPCs from the peripheral blood of mice using immunofluorescence and flow cytometry. Western blot detected the wnt/β-catenin pathway in high glucose-treated EPCs. Bioinformatics analysis predicted a putative binding site for TUG1 on miR-29c-3p. The interactions among TUG1, platelet-derived growth factor-BB (PDGF-BB), and miR-29c-3p were analyzed by luciferase assays. In vivo, diabetic mouse ischemic limb was treated with normal saline or TUG1 overexpression lentiviruses.ResultsWe found that EPC migration, invasion, and tube formation declined after treatment with high glucose, but improved with TUG1 overexpression. Mechanically, wnt/β-catenin pathway and autophagy were involved in the function of TUG1 overexpression in high glucose-treated EPCs. Moreover, TUG1 regulates the PDGF-BB/wnt pathway and function of high glucose-treated EPCs via miR-29c-3p. In vivo, injection of TUG1 lentivirus in a diabetic mouse ischemic limb model stimulated angiogenesis.ConclusionsOur findings suggest that TUG1 restores high glucose-treated EPC function by regulating miR-29c-3p/PDGF-BB/Wnt signaling.

Who, What, Where: Demographics, Severity of Presentation, and Location of Treatment Drive Delivery of Diabetic Limb Reconstructive Services within the National Inpatient Sample: Correction.

Who, What, Where: Demographics, Severity of Presentation, and Location of Treatment Drive Delivery of Diabetic Limb Reconstructive Services within the National Inpatient Sample: Correction.

Duplex Ultrasound Defined Angiosome With the Use of Pedal Acceleration Time as a Predictor to Wound Healing

We have established that pedal acceleration time (PAT) in nondiabetic limbs are highly correlative with ankle-brachial indices. We propose that PAT can be utilized in diabetic patients with noncompressible vessels and is an excellent predictor of wound healing. We performed a retrospective analysis in a prospective data base of diabetic patients with chronic limb-threatening ischemia (CLTI). We focused on patients with diabetes and isolated infrapopliteal arterial occlusive disease. Fifty-four limbs with WIFI score and documented CLTI who underwent angiographic interventions were analyzed. A complete pedal arch duplex was performed, PAT (milliseconds) was measured in the arcuate artery, dorsal metatarsal artery, medial, lateral, and deep plantar arteries. These measurements correspond to the angiosome of tissue loss which were obtained before and after interventions. A Fisher's exact test was used for data analysis. Based on previous report, PAT was categorized into four classes (Table). All CLTI patients were in class 4, which is defined as a PAT of greater than 225 ms. Of the 54 diabetic limbs, 44 achieved wound healing and 10 required higher level amputation. Patients with wounds prior to intervention had a mean PAT 237.6 + ms in the targeted artery of the foot. Complete wound healing was associated with a mean PAT of 114.2+ ms in the target angiosomic artery of the foot, regardless of direct or in-direct revascularization of the tibial arteries (P < .001). Limb loss was associated with a mean PAT of 278.4+ ms (P < .001) following intervention. Our group established that PAT demonstrates a high correlation with ABI in patients with compressible arteries. Based on current data, PAT is also a reliable noninvasive examination for patients with CLTI. This novel use of duplex-specific angiosome in the area of foot wounds demonstrate high predictability of wound healing. We conclude that duplex imaging of the pedal vessels, using PAT in particular, should be performed in all CLTI patients to aid in treatment of these complex patients.TablePedal acceleration time (PAT) classificationNo ischemia class 1Mild ischemia class 2Moderate ischemia class 3Severe ischemia class 4Clinical SymptomsAsymptomatic>2 blocks claudication>2 blocks claudicationCritical Limb Ischemia (Tissue loss, rest pain)PAT20-120 ms121-180 ms181-224 msGreater than 225 msABI1.3-0.900.89-0.690.68-0.500.49-0.00 Open table in a new tab

Who, What, Where: Demographics, Severity of Presentation, and Location of Treatment Drive Delivery of Diabetic Limb Reconstructive Services within the National Inpatient Sample.

Technical advances have been made in reconstructive diabetic limb salvage modalities. It is unknown whether these techniques are widely used. This study seeks to determine the role of patient- and hospital-level characteristics that affect use. Admissions for diabetic lower extremity complications were identified in the 2012 to 2014 National Inpatient Sample using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. The study cohort consisted of admitted patients receiving amputations, limb salvage without flap techniques, or advanced limb salvage with flap techniques. Multinomial regression analysis accounting for the complex survey design of the National Inpatient Sample was used to determine the independent contributions of factors expressed as marginal effects. The authors' study cohort represented 155,025 admissions nationally. White non-Hispanic patients had the highest proportion of reconstruction without and with flaps, whereas black patients had the lowest. Multinomial regression models revealed that controlling for nongas gangrene and critical limb ischemia, both of which have a much greater incidence in minorities, the effect of race against receipt of reconstructive modalities was attenuated. Access to urban teaching hospitals was the strongest protective factor against amputation (9 percent reduction; p < 0.01) and predictor of receiving limb salvage without flaps (5 percent increase; p < 0.01) and with flaps (3 percent increase; p < 0.01). This study identified multiple patient- and hospital-level factors associated with decreased access to the gamut of reconstructive limb salvage techniques. Disparity reduction will likely require a multifaceted strategy that addresses the severity of disease presentation seen in minorities and delivery system capabilities affecting access and use of reconstructive limb salvage procedures. Risk, III.