Non-traumatic Lower Extremity Amputations Research Articles

Diabetic foot infection and its management: A review

Diabetic foot infections are common in patients with diabetes which leads to hospitalization and it is the most frequent cause of non-traumatic lower extremity amputation. Diagnosis of foot infections based on clinical signs and symptoms of inflammation. Infected lesion culturing discloses the pathogen and their susceptibilities. The predominant pathogen responsible for infection is gram-positive cocci, especially Staphylococci and also Streptococci. Gram-negative bacilli and anaerobes are mainly found in chronic or previously treated wounds. The infected wounds require antibiotic therapy, the agents, and duration of treatment are predicted based in the severity of infection and initial management of diabetic foot infection should do by empirical therapy which based on the susceptibility data. Preventive measures to control diabetic foot infections are patient education on foot care, glycemic control, use of prescription footwear, intensive care from a podiatrist, and evaluation of surgical interventions indicated. This article explains about Pathophysiology classification, assessing the severity and treatment of diabetic foot infections.

Trends of Nontraumatic Lower Extremity Amputation in End-Stage Renal Disease and Diabetes, U.S. 2000-2014

Non-traumatic lower extremity amputation (NLEA) is a complication of end-stage renal disease (ESRD) and diabetes mellitus (DM). Global data suggest hospitalization rates for NLEA among people with DM are declining. Contemporary data from the U.S. and among those with ESRD is lacking. We estimated NLEA hospitalizations during 2000-2014 in adults aged ≥18 years with ESRD and DM (ESRD-DM) and in the broader DM population. We determined NLEA hospitalisations rates (ICD-9 CM procedure codes: 8411-8419, excluding diagnosis codes 895-897) for ESRD-DM using the U.S. Renal Data System and for DM using the U.S. National Health Interview Survey and the National Inpatient Sample. We assessed trends over time using Joinpoint regression. In the ESRD-DM population, age-standardised NLEA rates per 1,000 persons decreased from 61.5 (95% CI: 59.8-63.2) in 2000 to 39.7 (38.4-41.0) in 2014 (Figure). In the DM population, NLEA rates decreased from 10.8 (9.2-12.4) in 2000 to 6.1 (5.1-7.0) in 2009, and then increased to 8.7 (7.7-9.6) by 2014. NLEA rates remained 4.6 times (95% CI: 4.5-4.7) higher in ESRD-DM compared with DM only. Rates of NLEA hospitalisations declined during 2000-2014 in ESRD-DM, while they declined then increased in the population with DM. Increased attention to preventive care among ESRD-DM and DM populations is needed. Disclosure J.L. Harding: None. M.E. Pavkov: None. N. Burrows: None. E.W. Gregg: None. I.A. Hora: None.

Keap1-Mediated Nrf2 Dysfunction as a Source of Oxidative Damage in Human Diabetic Wounds

Purpose: Despite advancements in disease management and wound therapies, chronic diabetic ulcers represent the leading cause of non-traumatic lower extremity amputations in the United States. The Nrf2 master antioxidant transcription factor has emerged as a promising target for combatting the oxidative stress underlying these wounds. We have previously implicated Keap1-mediated Nrf2 dysfunction in delayed diabetic wound healing, and as a therapeutic target, in mice. However, whether these findings extend to human diabetic wounds remains unknown. Methods: Intact skin (S) and wound tissue (W) was obtained from diabetic (D) and nondiabetic (ND) patients, and analyzed for reactive oxygen species (ROS) end products (8-OhDG DNA assay), and with immunohistochemistry (IHC), qPCR (gene expression), and western blot (protein expression). Student’s t-tests were used for statistical analysis. Results: Both DS and DW contained more than 2-fold ROS end products, respectively, compared to NDS and NDW (2.344 vs. 1.117 ng/mL and 4.648 vs. 1.866 ng/mL, p<0.008). DS and DW exhibited 2-fold and 2.5-fold decreases in epidermal Nrf2 staining, respectively, compared to NS and NW (p<0.001). Keap1-the cytoplasmic Nrf2 repressor-was overexpressed in DW when compared to NDW (p<0.04). DW showed a 75% reduction in nuclear Nrf2 protein expression (p<0.02) as compared to NDW. DW also exhibited a 25% relative reduction in gene expression of MnSOD, a key Nrf2 downstream antioxidant enzyme, and 5-fold decrease in epidermal cytoplasmic MnSOD staining compared to NDW, p<0.03. Conclusion: Here, we implicate Nrf2 dysfunction in impaired redox homeostasis and consequent oxidative damage in both human diabetic skin and diabetic wounds as compared to nondiabetics. We also identify Keap1 as a likely mediator of impaired healing in diabetic wounds. These results recapitulate our previous findings in mice, further validating this critical pathway as a promising target for understanding and treating diabetic wound healing. Disclosure J.A. David: None. A.P. Villarreal-Ponce: None. S.A. Abdou: None. D.L. Sultan: None. W.J. Rifkin: None. J. Kwong: None. P.S. Rabbani: None. D. Ceradini: None.

Short-term predictors of amputation in patients with diabetic foot ulcers

BackgroundDiabetic foot ulcers are the leading cause of non-traumatic lower extremity amputation. The aim of this study was to establish short-term predictors of lower extremity amputation (LEA) in patients with diabetic foot ulcers (DFU). MethodsA retrospective observational study was performed. Patients observed for the first time in a multidisciplinary outpatient diabetic foot clinic during 1-year were reviewed. We examined demographic and clinical data and the occurrence of LEA within 180 days. Bivariate descriptive analysis was performed and three logistic regression models were created to predict short-term LEA. ResultsDuring 1-year 613 patients were observed for the first time in our diabetic foot clinic. Relevant data and eligibility was available from 479 patients with DFU; 38.41%, 40,71% and 20,88% had neuropathic, neuroischemic and ischemic ulcers, respectively. Considering a follow-up of 180 days, amputation occurred in 10.02% (n = 48) of patients: 3.13% (n = 15) major amputation and 6.89% (n = 33) minor amputation. Independent predictors of short-term LEA included moderate to severe infection [OR 5.23 (IC 95% 2.51–10.80; p < 0.001)], previous history of LEA [OR 3.93 (IC 95% 1.81–8.53; p = 0.001)], peripheral arterial disease [OR 3.51 (IC 95% 1.29–9.58; p = 0.014)] and presence of any walking disability [OR 3.35 (IC 95% 1.58–7.13; p = 0.002)]. ConclusionIn DFU patients the risk of LEA at 180 days is associated to moderate to severe infection at the initial presentation, previous history of LEA, peripheral arterial disease and presence of any walking disability. To prevent future amputations these patients should be identified early and managed by a multidisciplinary team.Level of Clinical Evidence: Level 2.

Risk factors of amputation in diabetic foot infections

Background: Diabetes is the most common underlying cause of foot ulcers, infection, and ischemia, leading to hospitalization and the most frequent cause of non-traumatic lower extremity amputation. Despite well-defined risk factors for diabetic foot ulcer development, limited data are available as to which factors predict amputation in a diabetic foot ulcer episode. Therefore, to predict lower limb amputation occurrence and to determine the factors associated with the risk of amputation in diabetic patients, we conducted this study.Methods: A hospital based longitudinal study was carried out to assess the risk factors associated with amputation in diabetic foot infection. Patients with foot infections, who were either a diagnosed case of diabetes mellitus or were diagnosed at the institute were included in the study. We excluded patients receiving immunosuppressive therapy or radiotherapy, and infections at or above the ankle joint. Study factors were demographic details, biochemical parameters, Wagner grading, peripheral neuropathy as evaluated by nerve conduction test and vasculopathy as assessed by Ankle brachial index. The primary outcome factor was amputation. The data was presented as descriptive statistics and analyzed by dividing the patients into amputation and non-amputation group, and univariate and multivariate analysis was done.Results: A total of 64 patients were included in the study, out of which the amputation rate was 39.1%. Poor glycemic control, osteomyelitis, vasculopathy, peripheral neuropathy and Wagner grading were statistically significant.Conclusions: In the present study, poor glycemic control, vasculopathy, peripheral neuropathy and higher Wagner grade are significant risk factors for amputation in diabetic foot infections.

Spectrum of microbiota in diabetic foot infections in a teaching hospital of Uttar Pradesh

Background: Diabetic foot ulcer is the leading cause of non-traumatic lower extremity amputations. A prospective case–control study was carried out on 50 patients with diabetic foot ulcers (cases) and 50 with non-diabetic foot ulcers (controls) to determine the microbiological profile, their antibiotic sensitivity patterns along with different demographic parameters. The prevalence of extended-spectrum beta-lactamases (ESBLs) producers, carbapenemase producers, and methicillin-resistant Staphylococcus aureus among the isolates and the potential risk factors for infection of ulcers with these multidrug-resistant organisms (MDROs) was also studied along with the outcome of these infections. Objectives: The present study aims at identifying the microbiological spectrum in these diabetic foot infections and their antibiotic sensitivity pattern in a developing country, like India. Materials and Methods: Clinical specimens were taken from each patient with diabetic and non-diabetic foot ulcers. These specimens were processed for culture (aerobic and anaerobic), further identification and antibiotic sensitivity testing. ESBL and carbapenemase production was detected by phenotypic methods and automated VITEK-2 system, and the results were mutually compared by the two methods. Results: A total of 158 organisms (155 bacteria and 3 fungi) were isolated giving an average of two organisms/patient. Cases were mostly positive for polymicrobial growth (77%) as compared to controls, and tissue was the most yielding sample. Gram-negative aerobes were predominantly isolated, followed by Gram-positive aerobes. Anaerobic Gram-negative (3%) and fungal (3%) isolates were also seen in the case samples. Conclusion: Escherichia coli among the Gram-negative (33%) and S. aureus among the Gram-positive (7%) were the predominantly isolated organisms, while Candida was the most predominantly isolated fungus. A strong association of peripheral vascular disease (PVD), smoking (P = 0.001), as well as neuropathy (P 5 cm2, and osteomyelitis (P

Perioperative Outcomes after Regional Versus General Anesthesia for Above the Knee Amputations

Nontraumatic lower extremity amputation (LEA) remains a common procedure among patients who frequently have significant comorbidities. Patients undergoing above knee amputation (AKA) have the highest rates of mortality in this cohort, yet there is little evidence to support selection between peripheral nerve block or neuraxial regional anesthesia (RA) versus general anesthesia (GA) techniques. The objective of this study was to determine whether RA (neuraxial or peripheral nerve block) techniques were associated with more favorable outcomes versus general anesthesia among patients undergoing AKA. This is a retrospective cohort study using propensity-matched groups. Patients undergoing AKA were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data set and grouped according to anesthetic type as either RA or GA. Patients undergoing AKA with RA were propensity matched to similar patients who had GA. Primary outcome was 30-day mortality. Secondary outcomes were numerous and included cardiac, pulmonary, infectious, and bleeding complications, as well as length of stay. Among a subset of patients for whom readmission data were available, rate of readmission was compared as a secondary outcome. Nine thousand nine hundred ninety-nine patients were identified in the ACS-NSQIP database. One thousand three hundred twelve received a regional anesthetic, and the remainder had a general anesthetic. Factors significantly associated with GA included younger age (70 vs. 75years; P<0.001), higher body mass index (26.5 vs. 25.4; P<0.001), and ethnically white (62.4% vs. 57%; P<0.001). Before matching, patients receiving RA were less likely to be smokers (22% vs. 29%; P<0.001), have a bleeding disorder (15% vs 30%; P<0.001), or have a diagnosis of sepsis (26% vs 34%; P<0.001). Propensity score matching produced a cohort composed of 1,916 patients equally divided between RA and GA. We found no difference with respect to the primary end point of 30-day mortality (11.7% vs 11.7%; odds ratio [OR] 1.01; P=0.943) nor was there any difference with respect to secondary outcomes. Among patients for whom readmission data were available, there was no statistically significant difference between rates of readmission between the groups (15.6% for RA vs. 12.7% for GA; OR 1.26, confidence interval 0.87-1.828, P=0.221). The present investigation did not detect any difference between regional and general anesthetic with respect to morbidity or mortality among patients undergoing AKA. This data set did not allow us to address other relevant markers including pain control or phantom limb syndrome.

Clinical study of coexistence of fungal infections in diabetic foot ulcers and its management

Background: Presently 62 million Indians are diabetics and these numbers are on the rise. Amongst chronic complications of uncontrolled diabetes, foot ulcer is one. Diabetes is the leading cause of non-traumatic lower extremity amputation in developing countries with risk being 15 to 46 times higher. Infections are predominantly polymicrobial, predominantly Aerobic Gram-Positive cocci with higher incidence of anaerobic species and fungal infections. Treatment of fungal infections in diabetic foot ulcers might reduce the disability, morbidity and mortality in diabetic patients.Methods: A total of 100 diabetic foot ulcer patients admitted or who visited to JSS Hospital over a period of 2 years, meeting the inclusion/exclusion criteria of the study, formed the study population. Detailed history, clinical evaluation &amp; necessary investigations were done. Fungal isolation from the ulcer done by 10% KOH study, Gram stain, SDA culture and slide culture methods. Positive patients were treated with antifungal agents. Outcome of the disease studied based on ulcer progression, wound healing and tissue amputations.Results: Polymicrobial flora in diabetic foot ulcers was seen (137 organisms in 100 subjects), predominantly Enterobacteriaceae and Pseudomonas. Prevalence of fungal infections in present study was 19%, of which Candida species was the commonest.Conclusions: Present study signifies the need of mycological evaluation of nonhealing diabetic ulcer, with poor progression despite antibacterial therapy &amp; foot care, introduction of antifungal treatment for proved fungal infections in diabetic foot ulcers, considering fungal infection as significant risk factor.

Progression of disease preceding lower extremity amputation in Denmark: a longitudinal registry study of diagnoses, use of medication and healthcare services 14 years prior to amputation

ObjectivesPatients with non-traumatic lower extremity amputation are characterised by high age, multi-morbidity and polypharmacy and long-term complications of atherosclerosis and diabetes. To ensure early identification of patients at risk of...

Microbiome Analysis for Assessments of Treatment Response and Salvage Prognosis in Infected Diabetic Foot Ulcers

Category: Basic Sciences/Biologics, Diabetes Introduction/Purpose: Diabetic foot ulcers (DFUs) contribute to 80% of non-traumatic lower-extremity amputations. Surgeons are often forced to make surgical decision without adequate prognostic information. DFU infections are often polymicrobial, representing complex microbial communities. A microbiota is the ecological community of various microorganisms that share body space. Currently, the methods of detecting an active infection, identifying the pathogenic bacteria within the microbiome, measuring the response to therapy, and assessing prognosis are limited. Using a molecular genomic technique of 16 S rRNA sequencing, our goals are to assess the pathogenic bioburden of DFUs and to monitor the bacterial community changes in response to antibiotic treatment. Our hypothesis is that the microbiome in DFUs responding to debridement and antibiotics treatment is distinct from those that fail to respond. Methods: Patients with type I or II diabetes who presented with an infected DFU were enrolled. Infections were identified using clinical signs. The DFU size was measured and classified using the Wagner classification. Enrolled patients were initially managed with foot salvaging therapy (FST): irrigation and debridement followed by wet-to-dry dressings and 6 weeks of intravenous antibiotic treatment. Superficial and deep DFU samples were obtained and evaluated by 16 S rRNA microbiome analysis and qPCR for bacterial abundance. This was repeated at 4, 8, and 12 weeks following the initiation of FST. At 12 weeks, patients were divided into two groups, healed and non-healed, based on the change in the size of the wound and absence or presence of 12 secondary signs of infection. Alpha- and beta-diversity were measured by the Shannon index and Bray-Curtis dissimilarity index to evaluate changes in the microbiome between the healed and non-healed groups. Results: From July 2015 to August 2016, 21 patients were enrolled and 3 deceased due to medical comorbidities. Of the 18 patients available for follow-up, 10 failed FST and 8 healed. The qPCR and microbiome analysis revealed that the bacterial abundance and diversity of the bacterial community were substantially reduced following debridement and intravenous antibiotic treatment. At the initial enrollment, those group that healed versus non-healed showed significant differences in microbiome composition, with the healed group enriched with Actinomycetales and Staphylococcus, and the non-healed group enriched with Bacteroidales and Streptococcus. At week 4, such differences disappeared and bacterial abundance significantly decreased. New differences were evident at week 8: the healed group was enriched with Actinomycetales and non-healed group with Bacilli. Conclusion: Abundant presence of Bacteroidales and Streptococcus at the initial presentation of infected DFU maybe a poor prognostic sign for healing with FST. Through molecular analysis of the wound microbiome, we can identify pathogens of prognostic value at the initial cultures and assess response to therapy with significant differences at 8 weeks after. Our study provides useful information for counseling patients of treatment prognosis and determining to pursuit further foot salvage versus amputation.

Gait alterations in the UAE population with and without diabetic complications using both traditional and entropy measures

Diabetic foot, one of the most common and debilitating manifestations of type 2 diabetes mellitus (T2DM), is the leading cause of worldwide non-traumatic lower extremity amputations. Diabetics who are at risk of ulceration are currently mainly identified by a thorough clinical examination of the feet, which typically does not show clear symptoms during the early stages of disease progression. In this study, we used a non-linear dynamics tool, gait entropy (GaitEN), in addition to traditional linear gait analysis methods, to investigate gait alterations amongst diabetic patients with combinations of three types of T2DM related complications: retinopathy, diabetic peripheral neuropathy (DPN) and nephropathy. Peak plantar pressure (PPP) was not significantly different in the group with DPN as compared to the control group (diabetics with no complications, CONT) in the forefoot region (DPN: mean±SD: 396±69.4kPa, CONT: 409±68.9kPa), although it was significantly lower in the heel region (DPN: mean±SD: 285±43.1.4kPa, CONT: 295±61.8kPa). On the other hand, gait entropy was significantly lower for the DPN compared to CONT group (DPN: 0.95±0.34, CONT: 1.03±0.28, p<0.05). The significant low entropy was maintained when neuropathy was combined with either retinopathy or nephropathy. For the group with all three complications (ALL-C), the entropy was higher than CONT (ALL-C: 1.07±0.26). This may indicate an intrinsic sensorimotor feedback mechanism for the DPN patients to regulate their gait. However, this feedback gets weaker as patients develop multiple complications. Further analysis with longer walking time and different speeds is needed to verify the entropy results.

The hospitalization profiles of patients with or without diabetes treated for nontraumatic lower extremity amputation in Ribeirão Preto, São Paulo State, Brazil, 2001–2008

The aim of this retrospective study was to assess the hospitalizations of patients with or without diabetes mellitus (DM) who underwent nontraumatic lower extremity amputation (NLEA) with regard to demographic and hospitalization-related variables. It is a high proportion of hospital beds in developing countries, for patients with diabetes mellitus with lower extremity complications. Nontraumatic amputations of lower extremities rates is an important indicator to assess the effectiveness of efforts to reduce chronic complications related to diabetic foot.A total of 2,296 hospital admissions were analyzed with regard to gender, age, length of stay, type of financing, origin, diagnosis, number of hospital admissions and readmissions, and hospitalization outcome from 2001 to 2008 in a municipality of Southeast Brazil. The association between the independent variables and the number of hospitalizations of patients with or without diabetes was assessed using chi-square tests for gender, type of financing, and hospitalization outcome and using the Mann-Whitney U test for age and length of stay. A total of 58% were patients without diabetes, 62.6% were male, 74.5% were treated at a public health care service, and 7.6% died. The mean age was 62.7years, the mean length of stay was of 9.5days, and the mean number of readmissions was 2.29 times. The length of stay was higher (P<.001), and the number of men was lower (P=.001) among the patients with diabetes who were hospitalized compared with patients without diabetes.The number of hospitalizations related to NLEA increased among patients with diabetes but reduced among those without diabetes between 2001 and2008.

Nationwide diabetes-related lower extremity amputation rates in secondary care treated patients with diabetes in the Netherlands (DUDE-7)

AimsTo estimate the annual amputation rate in all secondary care treated patients with diabetes in the Netherlands and specifically in patients known with diabetic retinopathy. MethodsA nationwide population-based retrospective cohort study was performed including the years 2007–2011. Data of patients were retrieved from reimbursement registries for hospital care from a nationwide insurance database including codes for diabetes, retinopathy and amputation. Traumatic amputations were excluded. ResultsThe number of patients with secondary care treated diabetes increased from 132.499 to 137.049 over the years 2007–2011 in the Netherlands. The annual rate of non-traumatic lower-extremity amputations ranged from 4.32 to 5.28 amputations per 1.000 patients.For patients diagnosed with non-proliferative and (pre-) proliferative diabetic retinopathy, the mean amputation rates were 7.9 per 1.000 and 14.7 per 1.000, respectively. ConclusionThe Dutch annual incidence rates of non-traumatic lower extremity amputations in secondary care treated patients with diabetes is relatively low and remained stable over the years 2007 to 2011. The amputation rate in patients with retinopathy was substantially higher compared to patients without retinopathy.

Evaluation of hypolipidemic effect of stem part of Berberis aristata in Type 2 diabetes mellitus patients as add on therapy

Background: Diabetes mellitus (DM) is one of the oldest common metabolic disorders characterized by hyperglycemia, hyperlipidemia, negative nitrogen balance, and ketonemia. It is a one of the most important pathological conditions associated with dyslipidemia that affects the whole body system. Several types of DM exist and result by a complex interaction of genes and drugs, gestational diabetes, environmental factors such as stress and sedentary lifestyle choices. DM is the leading cause of end-stage renal disease, coronary artery disease, cerebrovascular disease, nontraumatic lower extremity amputations, and adult blindness. Aims and Objectives: This study was conducted to evaluate the hypolipidemic effect of stem part of Berberis aristata in patients of Type 2 DM with dyslipidemia as add on therapy. Materials and Methods: A prospective randomized open parallel group study was conducted in total 90 patients having high fasting blood sugar (FBS) and dyslipidemia of either sex in the age group of 30-60 years attending of outpatient/indoor Department of Medicine of Muzaffarnagar Medical College and Hospital, Muzaffarnagar, Uttar Pradesh, India. A total of 103 each Group 1 (N = 30) was taken as control while Group 2 (N = 30) and Group 3 (N = 30) was taken as study group who had received 1.5 and 3 g of B. aristata, respectively, as add on therapy along with their conventional antidiabetic and antihyperlipidemic (in certain number of patients) treatment. During the study, 13 patients (8 male and 5 female) did not complete the study and reason of premature withdrawal included protocol violation. Results: In our study, there were a statistically a highly significant improvement and stabilization of glycemic control in test Groups 2 and 3 when compared with control group (P 0.05) and highly significant in Group 3 (P < 0.001) as compared to control. The mean triglyceride level decreased highly significantly in the Group 2 and Group 3 (P < 0.001) as compared to control. The mean low density lipoprotein level decreased highly significant in the Group 2 and Group 3 (P < 0.001) as compared to control. Conclusion: It can be concluded that B. aristata as an add on therapy in Type 2 DM patients has a beneficial role with regard to the hyperglycemia and dyslipidemia very safe as no major side effects were observed affecting morbidity and mortality. Hence, B. aristata as an add on therapy could represent a good treatment option before initiating insulin and hypolipidemic therapy in diabetic patient with suboptional glycemic and lipideimic control to avoid unwanted adverse effects and can cut down cost of treatment.

Assessment of Knowledge and Practices of Diabetic Patients Regarding Diabetic Foot Care, in Makkah, Saudi Arabia

Background: 20.5% of Saudis between 20 and 79 years are diabetics. Diabetic foot is a chronic complication of diabetes. The incidence of non-traumatic lower extremity amputations is at least 15 times greater in those with diabetes than non-diabetics. Patient education is important to reduce lower extremity complications. Objective: To assess the knowledge and practices of the diabetic patients regarding foot care and diabetic foot complications. Methods: In Makkah hospitals, 350 diabetic patients who met the inclusion criteria were involved in this cross sectional study. Interviewing questionnaire and patients’ charts review were used to collect the data. Results: Mean age of patients was 53.0083±13.1 years, and mean duration of diabetes was 11.24±8.7 years. 35.1% had history of foot ulcer while 25.7% had ulcer on the time of interview. 11.7 % had history of amputation and 83.1% had numbness. 77.1 % examine their feet while 49.1% received foot care education and 34% read handouts on foot care. 34% walk around in bare feet. There is a significant statistical association between foot education, practices and diabetic foot ulcer (p-value < 0.05). Conclusion: Patient knowledge and practices regarding diabetic foot care is significantly associated with the reduction of diabetic foot ulcer.

SUN-P030: The European Working Group on Sarcopenia in Older People (EWGSOP) Definition of Low Muscle Mass is Associated with Functionality and Nutritional Status in Residents of a Nursing Home

Diabetic foot, one of the most common and debilitating manifestations of type 2 diabetes mellitus (T2DM), is the leading cause of worldwide non-traumatic lower extremity amputations. Diabetics who are at risk of ulceration are currently mainly identified by a thorough clinical examination of the feet, which typically does not show clear symptoms during the early stages of disease progression. In this study, we used a non-linear dynamics tool, gait entropy (GaitEN), in addition to traditional linear gait analysis methods, to investigate gait alterations amongst diabetic patients with combinations of three types of T2DM related complications: retinopathy, diabetic peripheral neuropathy (DPN) and nephropathy. Peak plantar pressure (PPP) was not significantly different in the group with DPN as compared to the control group (diabetics with no complications, CONT) in the forefoot region (DPN: mean ± SD: 396 ± 69.4 kPa, CONT: 409 ± 68.9 kPa), although it was significantly lower in the heel region (DPN: mean ± SD: 285 ± 43.1.4 kPa, CONT: 295 ± 61.8 kPa). On the other hand, gait entropy was significantly lower for the DPN compared to CONT group (DPN: 0.95 ± 0.34, CONT: 1.03 ± 0.28, p < 0.05). The significant low entropy was maintained when neuropathy was combined with either retinopathy or nephropathy. For the group with all three complications (ALL-C), the entropy was higher than CONT (ALL-C: 1.07 ± 0.26). This may indicate an intrinsic sensorimotor feedback mechanism for the DPN patients to regulate their gait. However, this feedback gets weaker as patients develop multiple complications. Further analysis with longer walking time and different speeds is needed to verify the entropy results.

Epidemiology of Methicillin-Resistant Staphylococcus aureus Diabetic Foot Infections in a Large Academic Hospital: Implications for Antimicrobial Stewardship

IntroductionDiabetic foot infections (DFIs) are the leading cause of non-traumatic lower extremity amputations in the United States. Antimicrobials active against methicillin-resistant Staphylococcus aureus (MRSA) are recommended in patients with associated risk factors; however, limited data exist to support these recommendations. Due to the changing epidemiology of MRSA, and the consequences of unnecessary antibiotic therapy, guidance regarding the necessity of empirical MRSA coverage in DFIs is needed. We sought to 1) describe the prevalence of MRSA DFIs at our institution and compare to the proportion of patients who receive MRSA antibiotic coverage and 2) identify risk factors for MRSA DFI.MethodsThis was a retrospective cohort study of all adult, culture-positive DFI patients managed at University Hospital, San Antonio, TX between January 1, 2010 and September 1, 2014. Patient eligibility included a principal ICD-9-CM discharge diagnosis code for foot infection and a secondary diagnosis of diabetes. The primary outcome was MRSA identified in the wound culture. Independent variables assessed included patient demographics, comorbidities, prior hospitalization, DFI therapies, prior antibiotics, prior MRSA infection, and laboratory values. Multivariable logistic regression was used to identify risk factors for MRSA DFI.ResultsOverall, 318 patients met inclusion criteria. Patients were predominantly Hispanic (79%) and male (69%). Common comorbidities included hypertension (76%), dyslipidemia (52%), and obesity (49%). S. aureus was present in 46% of culture-positive DFIs (MRSA, 15%). A total of 273 patients (86%) received MRSA antibiotic coverage, resulting in 71% unnecessary use. Male gender (OR 3.09, 95% CI 1.37–7.99) and bone involvement (OR 1.93, 1.00–3.78) were found to be independent risk factors for MRSA DFI.ConclusionsAlthough MRSA was the causative pathogen in a small number of DFI, antibiotic coverage targeted against MRSA was unnecessarily high.

Factors Affecting Mortality After Major Nontraumatic Lower Extremity Amputation.

Our aim was to evaluate the factors affecting the mortality of patients who underwent nontraumatic major lower limb amputation due to ischemic and/or diabetic causes. A total of 100 patients were included in the study. Among these patients, 70 (70%) underwent below-knee amputation, whereas 30 (30%) underwent above-knee amputation. Eleven (15.7%) of the 70 patients who underwent below-knee amputation and 12 (40%) of the 30 patients who underwent above-knee amputation (P = .008) were deceased. After multivariable Poisson regression analysis, female gender (risk ratio [RR] = 2.00, 95% CI = 1.07-3.74) and a neutrophil lymphocyte ratio (NLR) less than 6.8 (RR = 5.12, 95% CI = 1.86-14.08) were found to be independent risk factors for mortality. The value of 6.8 was used as a cutoff point for the NLR (area under the curve = 0.73, 95% CI = 0.62-0.85), with a sensitivity, specificity, positive predictive value, and negative predictive value of 83%, 66%, 57%, and 92%, respectively. The NLR and female gender were found to be independent factors that are related to increased mortality in patients who underwent lower limb amputation due to diabetic and/or ischemic causes. The coexistence of congestive heart failure and the amputation level (above knee) were found to be predictors of mortality in univariable analysis, but significance could not be demonstrated in multivariable analysis.

Variants in genes belonging to the fibroblast growth factor family are associated with lower extremity amputation in non-Hispanic whites: Findings from the chronic renal insufficiency cohort study.

Diabetes is the major risk factor for nontraumatic lower extremity amputation (LEA). The role of genetic polymorphisms in predisposing diabetics to impaired wound healing leading to LEA has not been sufficiently explored. We investigated the association between a set of genes belonging to the angiogenesis/wound repair pathway with LEA in the Chronic Renal Insufficiency Cohort, a study of adults with chronic kidney disease (CKD) that includes a subgroup with diabetes. This study was performed on 3,772 Chronic Renal Insufficiency Cohort participants who were genotyped on the ITMAT-Broad-CARe array chip. A total of 1,017 single-nucleotide polymorphisms (SNPs) in 22 genes belonging to the angiogenesis/would repair pathway were investigated. LEA was determined from patient self-report. The association between genetic variants and LEA status was examined using logistic regression and additive genetic models after stratifying the cohort by race/ethnicity and diabetic status. Unadjusted analyses as well as analyses adjusted for age, sex, estimated glomerular filtration rate, body mass index, peripheral vascular disease, hemoglobin A1c, and population stratification were performed. In non-Hispanic white participants with diabetes, rs11938826 and rs1960669, both intronic SNPs in the gene basic fibroblast growth factor-2 (FGF2), were significantly associated with LEA in covariate-adjusted analysis (OR: 2.83 (95% CI: 1.73, 4.62); p-value: 0.000034; Bonferroni adjusted p-value: 0.0006) and (OR: 2.61 (95% CI: 1.48, 4.61); p-value: 0.00095; Bonferroni adjusted p-value: 0.02). In the same subgroup, rs10883688, an FGF8 SNP of unknown functional effect, was also associated with LEA (OR: 1.72 (95% Confidence Interval: 1.14, 2.6); p-value: 0.00999; Bonferroni adjusted p-value: 0.04). No statistically significant associations were identified in the other ethnic groups. In conclusion, variant/s in FGF2 and FGF8 may predispose diabetics with CKD to LEA. Dysregulation of the FGF2 gene represents an opportunity to understand further, and possibly intervene upon, mechanisms of wound healing in diabetics with CKD.

Retrospective study of the evolution of the incidence of non-traumatic lower-extremity amputations (2007–2013) and risk factors of reamputation

AimDescribe the incidence of non-traumatic amputation in a Spain region and identify the risk factors associated with the level of amputation and reamputation. MethodsRetrospective study on non-traumatic lower-extremity amputees in a Spanish region between 2007 and 2013. A descriptive, bivariate and multivariate analysis was performed using bivariate logistic regression. Statistical significance p≤0.05, SPSS V.21. Results495 amputations were carried out in 353 patients. 81.0% (n=286) were men, mean age 68.7±10.8 years. The most frequent levels of amputation were digital (45.9%) and above-knee (40.5%). About 30% of the patients were reamputated. The multivariate analysis revealed that the factors independently related to the need for a minor lower-extremity amputation were DM [OR 3.79 (CI 95% 2.0–7.27)], foot ulcer [OR 5.82 (CI 95% 2.24–15.11)] and previous ipsilateral amputation [OR 3.19 (CI 95% 1.21–8.42)]. The risk factors independently related to the need for reamputation were DM [OR 2.21 (CI95% 1.09–4.49)], smoking [OR 2.45 (CI95% 1.33–4.50)] and previous revascularization [OR 2.75 (CI95% 1.57–4.83)]. ConclusionsDetermining the incidence of amputations in diabetic patients as an indicator of quality makes it possible for health services to be evaluated. In patients with DM the most common reamputations are minor and ipsilateral.