Lower Extremity Amputation Rates Research Articles

Impact of “Defensive Medicine” on the Costs of Diabetes and Associated Conditions

Geographic variation in health care spending is typically attributed to differences in patient health status and provider practice patterns. While medicolegal considerations (i.e., "defensive medicine") anecdotally impact health care spending, this phenomenon is difficult to measure. The purpose of this study was to explore the association between the medicolegal environment and Medicare costs for diabetes and associated conditions of interest to vascular surgeons. Specifically, we hypothesized that an adverse medicolegal environment is associated with higher per capita Medicare costs for diabetic patients. Medicare data including the most recent (2018) Medicare Geographic Variation Public Use Files and Chronic Conditions Data Files were linked to National Practitioner Data Bank files from the preceding 5years (2013-2017), in addition to the US census data and American Medical Association workforce statistics. The state-level medicolegal environment was characterized by K-means clustering across a panel of metrics related to malpractice payment magnitude and prevalence. Per capita Medicare spending for diabetes was compared across 5 distinct medicolegal environments. Costs were standardized and risk-adjusted to account for known geographic variation in health care costs and patient population. Analysis of variance was applied to unadjusted data, followed by multivariate regression modeling. Readmission rates, per capita imaging studies, per capita tests, per capita procedures, and lower extremity amputation rates were compared between the least litigious quintile from the K-means clustering and the 2 most litigious quintiles. The median unadjusted Medicare per capita expenditure on diabetic patients was $15,963 ($14,885-$17,673), ranging from $13,762 (Iowa) to $21,865 (D.C.). A 1.6-fold variation persisted after payment standardization. Cluster analysis based on malpractice-related variables yields 5 distinct medicolegal environments, based on litigation frequency and malpractice payment amounts. Per capita spending on diabetes varied, ranging from $15,799 in states with low payments and infrequent litigation to $18,838 in states with the most adverse medicolegal environment (P<0.05). After cost standardization and risk adjustment with multiple linear regression, malpractice claim prevalence (per 100 physicians) remained an independent predictor of states with the highest diabetes mellitus spending (P=0.022). Moreover, diabetic patients in states with adverse medicolegal environments had more procedures, imaging studies, and readmissions (P<0.05 for all) but did not have significant differences in amputation rates compared to less litigious states. An adverse medicolegal environment is independently associated with higher health care costs but does not result in improved outcome (i.e. amputation rate) for diabetic Medicare beneficiaries. Across states, a 1% increase in lawsuits/100 physicians was associated with a >10% increase in risk-adjusted standardized per capita costs. These findings demonstrate the potential contribution of "defensive medicine" to variation in health care utilization and spending in a population of interest to vascular surgeons.

Heterogeneity in the guidelines for the management of diabetic foot disease in the Caribbean.

The prevalence of diabetes mellitus, diabetic foot (DF) disease and, as a result, lower extremity amputation rates remain high in the Caribbean. This study was undertaken to determine whether Caribbean countries have designated individuals that monitor DF disease and whether there are DF protocols consistent with the International Working Group on the Diabetic Foot (IWGDF) guidance documents. Relevant DF health care personnel(s) from the CARICOM and Dutch Caribbean countries were called or sent questionnaires regarding the presence of structured programs to monitor and manage DF problems in the population. All 25 countries (100%) responded. 81% of respondents could not identify any Ministry, Hospital or individual initiatives that monitored the DF. Only 9 (36%) countries had any guidelines in place. Only 3 countries with guidelines in place utilized IWGDF guidelines. Only 6 (24%) countries had podiatrists and 10 (40%) had vascular surgery availability. 7 (28%) countries had the components for a multidisciplinary team. The presence or the appointment of a designated individual and/or a multidisciplinary approach within the countries for DF disease was absent in the majority of respondent countries. Only a minority of countries implemented DF guidelines or had expertise available to organize a DF multidisciplinary team. Vascular surgery and podiatric care were noticeably deficient. These may be critical factors in the variability and reduced success in implementation of strategies for managing DF problems and subsequent amputations amongst these Caribbean countries.

A Novel Marker Indicating Restenosis in Superficial Femoral Artery: C Reactive Protein to Albumin Ratio

In this study, we aimed to investigate the prognostic value of C-reactive protein (CRP) to albumin ratio (CAR) for predicting restenosis in superficial femoral artery (SFA) lesions and its association with subsequent clinical outcomes in patients undergoing endovascular intervention. The records of 685 consecutive patients who underwent endovascular intervention due to symptomatic peripheral artery disease were analyzed. Patients were divided into 2 groups, based on the CAR values. For each group, technical aspects of procedures and subsequent clinical outcomes were analyzed. According to our study, patients with high CAR values had higher rates of restenosis (30.2% vs. 10.3%, P<0.05) and mortality (31.3% vs. 12.9%, P<0.05). The rate of lower extremity amputations was also significantly higher in patients with high CAR values compared to those with low CAR values (9.1% vs. 3%, P<0.05). With respect to Receiver operating characteristic ROC curves of inflammatory markers, the area under the curve (AUC) value of CAR was statistically significant (AUC: 0.659; 95% confidence interval CI:0.611-0.706; P<0.01). Our data showed that CAR is an independent predictor of restenosis and poor clinical outcomes in patients undergoing endovascular intervention.

The relationship between lower extremity amputation and body mass index.

Non-traumatic lower extremity amputation (LEA) is associated with significant morbidity and mortality. Diabetes mellitus (DM) and peripheral vascular disease (PVD) are associated with increased risk for LEA. As such, DM and PVD account for 54% of all LEA's, performed in the United States annually. As obesity is highly associated with both DM and PVD, our study sought to explore the relationship between LEA and obesity defined by BMI. Using the National Inpatient Sample (NIS) database, a retrospective review of patients who underwent non-traumatic LEA (LEA) between 2008 and 2014 was performed. The International Classification of Diseases 9th edition (ICD-9) codes were utilized to determine the diagnoses, comorbidities, and procedures. Patient BMIs were classified as follows: Non-obese [BMI <30], Obesity class I [BMI 30-34.9], Obesity class II [BMI 35-39.9], and Obesity class III [BMI ≥40]. Predictors for LEA were compared between groups using chi-square test and binary logistic regression to identify possible underlying factors associated with LEA. We also conducted a multivariate analysis to measure the effect of multiple variables on LEA. We identified 16,259 patients with non-traumatic LEA and a mean age of 59.9 years. Rate of amputation in females was lower than males at 0.35% vs 0.87% respectively (p < 0.001). Of patients that underwent amputation there was a V-shape trend based on BMI, with 30.4% in non-obese patients, 18.2% in obesity class I, 17.3% in obesity class II, and 34.1% in obesity class III. The incidence of diabetes increased with obesity class, while the incidence of PVD decreased. Interestingly, of those with DM there was an inverse relationship between amputation rate and BMI class, with LEA rates in non-obese versus obesity class III patients were 1.63% vs 0.98% respectively (p < 0.001). Similarly, patients who had both diabetes and PVD showed a downward trend in LEA rate as obesity class increased; non-obese patients had a LEA rate of 8.01%, while obesity class III had 4.65% (p < 0.001). Patients in higher income bracket have lower odds of LEA (OR 0.77, p < 0.001) compared to the lowest income patients. Also, patients with comorbidities such as PVD (OR 10.78), diabetes (OR 5.02), renal failure (OR 1.41), and hypertension (OR 1.36) had higher odds to get an LEA (p < 0.001). Individuals with obesity class III are almost at half the odds (OR 0.52) to get an LEA compared to non-obese (p < 0.001). Higher BMI and female gender are protective factors against lower extremity amputation. Factors that predisposing to LEA include lower household income and certain comorbidities such as PVD, diabetes, renal failure, and hypertension. These findings warrant further research to identify patients at high risk for LEA and help develop management guidelines for targeted populations.

IDF21-0196 Study of peripheral arterial disease among type 2 diabetes mellitus patients

Background: Diabetes is a complex chronic metabolic disorder, characterized by persistent hyperglycemia because of lack of insulin secretion, insulin resistance, or both. Peripheral arterial disease (PAD) is one of the major recognised diabetic macro vascular complications. It is a marker of generalised systemic atherosclerosis and is closely associated with symptomatic coronary and cerebrovascular disease, hence significant morbidity and mortality. Aim: To study the various risk factors contributing to development of peripheral arterial disease in adult type2 diabetic patients and vasculopathy profile. Method: This was a retrospective analytical descriptive study conducted at internal medicine department on 13 months. Forty-seven type 2 diabetic patients were included. All patients underwent a detailed history which included age, gender, smoking intake, history of diabetes mellitus with duration and treatment. Biochemical characteristics were studied. Diagnosis of PAD was made by using color Doppler ultrasound. The statistical analysis was carried out using Epi-Info7. Results: The study was conducted on 47type2 diabetic patients with a mean age of 66±10 years with male predominance (77%) compared to females (23%). Mean duration of diabetes mellitus was15±9 years. Majority of patients were on insulin (n=22;46.81%). Eleven patients (23.40%) were on combined insulin and OHA. and ten were on oral hypoglycemic agents (OHA) (21.28%). Sixteen (34%) patients were cigarette smokers. Regarding hypertension status, 24 (51.06%) patients were hypertensive. Metabolic syndrome was prevalent in twenty patients, with mean of BMI 25±5 kg/m2. PAD was prevalent in 38(80.85%) patients. Of these, there were 27(57.45%) obliterating arteriopathy of the lower limbs,20(42.55 %) had mediacalcinosis, 10 (21.28 %) had acute arterial occlusion, 8 (17.02%) stenosis, and 2(4.26 %) arterial thrombosis. The prevalence of neuropathy was 46.81% (n=22) and diabetic foot was present in all patients (n=47) of patients. Regarding biochemical parameters: mean of fasting blood glucose was 1.73±0.76g/l, mean of post prandial blood glucose 2.45±0.77g/l, mean of HBA1C 9±3%, mean of HDLc 0.32±0.14 g/l, mean of triglycerides1.56±1.29g/l, mean of creatinine clearance according MDRD equation was 69±41 ml/min/1.73m2, mean of protein C reactive in this population was 88±80mg/l. Discussion: The increasing burden of diabetes is considered as one of the greatest global public health problem of our time. Diabetic patients with PAD are at high risk of increased morbidity and mortality from cardiovascular diseases and a high rate of lower extremity amputation. Various risk factors like age, gender persistant hyperglycemia, increased glycated hemoglobin, smoking and hypertension, and dyslipidaemia are associated with an increased risk of peripheral artery disease. This study documents a high prevalence of PAD among adult type2 diabetic patients. This strongly calls for aggressive screening for PAD be emphasised.

Thromboembolectomy for acute lower limb ischemia: Contemporary outcomes of two surgical methods from a single tertiary center.

The current treatment of acute lower limb ischemia (ALLI) includes open surgical and percutaneous pharmaco-mechanical thromboembolectomy (TE). We hereby report our results with open surgical TE over a 10-year period and compare our outcomes using routine fluoroscopic assisted TE (FATE) with blind and selective on demand fluoroscopic-assisted TE (BSTE). This is a retrospective analysis of all patients who underwent open surgical TE for acute lower limb ischemia at a single tertiary center between 2008 and 2018. Patients were divided into a group who underwent BSTE and another who underwent routine FATE. Data on presentation, medical history, surgery performed, and short-term outcomes were retrieved from medical record. Comparison between baseline characteristics and outcomes of both groups were made using t-test and chi-square analysis. Over 10years, 108 patients underwent surgical TE. Thirty-day mortality rate and 30-day major lower extremity amputation rate in the cohort were 12.0% and 6.5%, respectively. On subgroup analysis, 53 patients were treated by BSTE and 55 patients by FATE. There was no significant difference in 30-day mortality rate (11.3% vs 12.7%, p-value = .82) and 30-day major amputation rate (9.4% vs 3.6%, p-value = .454) between the two groups. Local anesthesia was more frequently performed in patients undergoing FATE (58.2% vs 24.5%, p-value < .001). More than one arteriotomy was more frequently required in patients undergoing BSTE (2.6% vs 45.5%, p-value < .001). Patients with infrapopliteal involvement undergoing FATE required less further interventions such as patch angioplasty (2.6% vs 36.4%, p-value < .001) and bypass (2.6% vs 22.7%, p-value = .01). ALLI remains a disease of high morbidity and mortality. Open surgical TE offers an effective approach to treat ALLI. The addition of fluoroscopy to the conduction of TE could be associated with valuable benefits, especially in patients with infra-popliteal involvement. Randomized controlled trials are needed to objectively assess the therapeutic potential of FATE.

The Role of Early Revascularization and Biomarkers in the Management of Diabetic Foot Ulcers: A Single Center Experience.

Diabetic neuropathy and Peripheral Arterial Disease (PAD) are the main etiological factors in foot ulceration. Herein, we report our experience of diabetic foot ulceration (DFU) management, with an analysis of the relationship between the rate of lower extremity amputation, in persons with infected DFU, after revascularization procedures performed to prevent major amputation. This study highlights the role of different biomarkers, showing their usefulness and potentiality in diabetic foot ulcer management, especially for the early diagnosis and therapy effectiveness monitoring. A retrospective analysis, from September 2016 to January 2021, of diabetic patients presenting diabetic foot with DFU, was performed. All patients were treated with at least one vascular procedure (endovascular, open, hybrid procedures) targeting PAD lesions. Outcomes measured were perioperative mortality and morbidity. Freedom from occlusion, primary and secondary patency, and amputation rate were registered. A total of 267 patients, with a mean age of 72.5 years, were included in the study. The major amputation rate was 6.2%, minor amputation rate was 17%. In our experience, extreme revascularization to obtain direct flow reduced the rate of amputations, with an increase in ulcer healing.

Two-year clinical outcomes following lower limb endovascular revascularisation for chronic limb-threatening ischaemia at a tertiary Asian vascular centre in Singapore.

Percutaneous transluminal angioplasty (PTA) is commonly used to treat patients with chronic limb-threatening ischaemia (CLTI). This study aimed to examine the mortality and functional outcomes of patients with CLTI who predominantly had diabetes mellitus in a multi-ethnic Asian population in Singapore. Patients with CLTI who underwent PTA between January 2015 and March 2017 at the Vascular Unit at Singapore General Hospital, Singapore, were studied. Primary outcome measures were 30-day unplanned readmission, two-year major lower extremity amputation (LEA), mortality rates, and ambulation status at one, six and 12 months. A total of 221 procedures were performed on 207 patients, of whom 184 (88.9%) were diabetics. The one-, six- and 12-month mortality rate was 7.7%, 16.4% and 21.7%, respectively. The two-year LEA rate was 30.0%. At six and 12 months, only 96 (46.4%) and 93 (44.9%) patients were ambulant, respectively. Multivariate analysis revealed that preoperative ambulatory status, haemoglobin, Wound Ischaemia and foot Infection (WIfI) score, and end-stage renal failure (ESRF) were independent predictors of one-year ambulatory status. Predictors of mortality at one, six and 12 months were ESRF, preoperative albumin level, impaired functional status and employment status. PTA for CLTI was associated with low one-year mortality and two-year LEA rates but did not significantly improve ambulation status. ESRF and hypoalbuminaemia were independent predictors of mortality. ESRF/CKD and WIfI score were independent predictors of loss of ambulation at six months and one year. We need better risk stratification for patients with CLTI to decide between initial revascularisation and an immediate LEA policy.

Lower Limb Amputation Rates in Germany.

Background and Objectives: The current epidemiology of lower limb amputations is unknown. Therefore, the purpose of this study was to determine (1) lower extremity amputation rates as a function of age, gender, and amputation level between 2015 and 2019, (2) main diagnoses indicating amputation, (3) revision rates after lower extremity amputation. Materials and Methods: Lower extremity amputation rates were quantified based on annual Operation and Procedure Classification System (OPS) and International Classifications of Disease (ICD)-10 codes from all German medical institutions between 2015 through 2019, provided by the Federal Statistical Office of Germany (Destatis). Results: In 2019, 62,016 performed amputations were registered in Germany. Out of these 16,452 procedures (26.5%) were major amputations and 45,564 patients (73.5%) underwent minor amputations. Compared to 2015, the incidence of major amputations decreased by 7.3% to 24.2/100,000 inhabitants, whereas the incidence of minor amputation increased by 11.8% to 67.1/100,000 inhabitants. Highest incidence was found for male patients aged 80–89 years. Patients were mainly diagnosed with peripheral arterial disease (50.7% for major and 35.7% for minor amputations) and diabetes mellitus (18.5% for major and 44.2% for minor amputations). Conclusions: Lower limb amputations remain a serious problem. Further efforts in terms of multidisciplinary team approaches and patient optimization strategies are required to reduce lower limb amputation rates.

Comparison of Rates of Lower Extremity Amputation in Patients With and Without Gout in the US Department of Veterans Affairs Health System

Cardiometabolic and other risk factors could render patients with gout more likely to undergo lower extremity amputation (LEA). To examine the rate of and factors associated with LEA in patients with gout. In this matched cohort study using national administrative data, multivariable Cox proportional hazards regression models were used to examine the associations of gout with LEA. In analyses limited to patients with gout, attributes of serum urate control and treatment with urate-lowering therapy were examined as factors associated with LEA. This study included patients who used US Department of Veterans Affairs services from January 1, 2000, to July 31, 2015. Patients with gout were identified using diagnostic codes and matched with up to 10 controls by age, sex, and year of benefit enrollment. Data analysis was performed from January 26, 2021, to September 3, 2021. Gout classification served as the primary independent variable of interest. In analyses limited to patients with gout, factors associated with serum urate control and urate-lowering therapy were examined. Overall LEA, as well as toe, transmetatarsal, below-the-knee, and above-the-knee amputation. This cohort study included 5 924 918 patients, 556 521 with gout (mean [SD] age, 67 [12] years; 550 963 (99.0%) male; 88 853 [16.0%] Black non-Hispanic; 16 981 [4.3%] Hispanic/Latinx; 345 818 [62.1%] White non-Hispanic; 80 929 [14.5%] with race and ethnicity data missing; and 23 940 [4.3%] classified as other) and 5 368 397 without gout (mean [SD] age, 67 [12] years; 5 314 344 [99.0%] male; 558 464 [10.4%] Black non-Hispanic; 204 291 [3.0%] Hispanic/Latinx; 3 188 504 [59.4%] White non-Hispanic; 1 257 739 [23.4%)] with race and ethnicity data missing; and 159 399 [3.0%] classified as other). Compared with patients without gout, patients with gout were more likely to undergo amputation, an increased rate that remained after adjustment (adjusted hazard ratio, 1.20; 95% CI, 1.16-1.24) and was highest for below-the-knee amputation (adjusted hazard ratio, 1.59; 95% CI, 1.39-1.81). In those with gout, poor serum urate control (mean >7 mg/dL during the preceding year) was associated with a 25% to 37% increase in the rate of amputation. In contrast, treatment with urate-lowering therapy was not associated with the LEA rate. In this matched cohort study, patients with gout were more likely to undergo LEA. This increase was independent of other comorbidities that have been associated with amputation, including diabetes and peripheral vascular disease. Serum urate control was independently associated with the LEA rate, suggesting the possibility that lower extremity amputation may be preventable in some patients.

Trends of limb amputation considering type, level, sex and age in Saskatchewan, Canada 2006\u20132019: an in-depth assessment

BackgroundMost epidemiologic reports focus on lower extremity amputation (LEA) caused specifically by diabetes mellitus. However, narrowing scope disregards the impact of other causes and types of limb amputation (LA) diminishing the true incidence and societal burden. We explored the rates of LEA and upper extremity amputation (UEA) by level of amputation, sex and age over 14 years in Saskatchewan, Canada.MethodsWe calculated the differential impact of amputation type (LEA or UEA) and level (major or minor) of LA using retrospective linked hospital discharge data and demographic characteristics of all LA performed in Saskatchewan and resident population between 2006 and 2019. Rates were calculated from total yearly cases per yearly Saskatchewan resident population. Joinpoint regression was employed to quantify annual percentage change (APC) and average annual percent change (AAPC). Negative binomial regression was performed to determine if LA rates differed over time based on sex and age.ResultsIncidence of LEA (31.86 ± 2.85 per 100,000) predominated over UEA (5.84 ± 0.49 per 100,000) over the 14-year study period. The overall LEA rate did not change over the study period (AAPC -0.5 [95% CI − 3.8 to 3.0]) but fluctuations were identified. From 2008 to 2017 LEA rates increased (APC 3.15 [95% CI 1.1 to 5.2]) countered by two statistically insignificant periods of decline (2006–2008 and 2017–2019). From 2006 to 2019 the rate of minor LEA steadily increased (AAPC 3.9 [95% CI 2.4 to 5.4]) while major LEA decreased (AAPC -0.6 [95% CI − 2.1 to 5.4]). Fluctuations in the overall LEA rate nearly corresponded with fluctuations in major LEA with one period of rising rates from 2010 to 2017 (APC 4.2 [95% CI 0.9 to 7.6]) countered by two periods of decline 2006–2010 (APC -11.14 [95% CI − 16.4 to − 5.6]) and 2017–2019 (APC -19.49 [95% CI − 33.5 to − 2.5]). Overall UEA and minor UEA rates remained stable from 2006 to 2019 with too few major UEA performed for in-depth analysis. Males were twice as likely to undergo LA than females (RR = 2.2 [95% CI 1.99–2.51]) with no change in rate over the study period. Persons aged 50–74 years and 75+ years were respectively 5.9 (RR = 5.92 [95% Cl 5.39–6.51]) and 10.6 (RR = 10.58 [95% Cl 9.26–12.08]) times more likely to undergo LA than those aged 0–49 years. LA rate increased with increasing age over the study period.ConclusionThe rise in the rate of minor LEA with simultaneous decline in the rate of major LEA concomitant with the rise in age of patients experiencing LA may reflect a paradigm shift in the management of diseases that lead to LEA. Further, this shift may alter demand for orthotic versus prosthetic intervention. A more granular look into the data is warranted to determine if performing minor LA diminishes the need for major LA.

Effect of SGLT2 inhibitors versus DPP4 inhibitors or GLP-1 agonists on diabetic foot-related extremity amputation in patients with T2DM: A meta-analysis

AimTo compare the contribution of sodium-glucose cotransporter-2 inhibitors (SGLT2is) with that of DPP4i or GLP-1ra toward lower extremity amputation rate. MethodsElectronic databases were searched for articles published on the differences between the rates of lower extremity amputation among patients with type 2 diabetes mellitus (T2DM) undergoing SGLT2i treatment and those undergoing other anti-hyperglycemic agent (dipeptidyl peptidase-4 inhibitors [DPP4is], glucagon-like peptide-1 receptor agonist [GLP-1as], or sulfonylurea [SUs]) treatments. Random-effect models were used to generate data if heterogeneity was detected. ResultsEight studies based on retrospective case-control designs with propensity matching were included. The propensity score-matching method increased credibility. Compared with SGLT2i treatment, DPP4i or GLP-1a treatment tended to result in a higher amputation rate (pooled hazard ratio [HR] = 1.1, 95% confidence interval [CI]: 0.98–1.23), whereas SU treatment resulted in similar amputation rates (pooled HR = 0.92, 95% CI: 0.74–1.13). After excluding the heterogeneous study, the meta-analysis of the remaining studies attained a statistical value (pooled HR = 0.81, 95% CI: 0.65–1.01). ConclusionThe study findings suggest that, with respect to diabetic foot-related limb amputations, SGLT2is are not superior to novel anti-hyperglycemic agents (DPP4is and GLP-1as) or other types of oral hypoglycemic agents (SUs). Therefore, SGLT2is may not have significantly positive effects on the prognosis for T2DM patients with complicated diabetic foot.

National Rates of Lower Extremity Amputation in People With and Without Diabetes in a Multi-Ethnic Asian Population: a Ten Year Study in Singapore

Population level data from Asia on amputation rates in people with and without diabetes are extremely limited. Hence it is unclear how the rising diabetes prevalence in Asia has affected the amputation burden. The present study examined national amputation rates in people with and without diabetes in Singapore from 2008 to 2017 in the context of increasing diabetes prevalence and health system changes. This was a retrospective observational study using national population data for ages 16 - 100 years obtained from the Ministry of Health Singapore administrative datasets. Age sex standardised major and toe/ray amputation rates per 100 000 people with diabetes and per 100 000 people without diabetes were calculated. Rates were calculated overall and in each ethnic group (Chinese, Malay, Indian, Others), with trends over time calculated using joinpoint trend analysis. In addition, age specific rates, relative risk (RR) of amputation in diabetics compared with non-diabetics and proportion of amputations in the population attributable to diabetes were also calculated. Between 2008 and 2017, the database included 3.6 million unique individuals, of whom 75% were Chinese, 8.6% Malay, 7.9% Indian, and 8.4% Others. Of those, 413 486 (11%) had diabetes. Major amputation rates in people with diabetes remained stable (2008: 99.5/100 000; 2017: 95.0/100 000 people with diabetes, p= .91) as did toe/ray amputation rates. Rates in people without diabetes were substantially lower, with major amputation rates decreasing significantly (2008: 3.0/100 000; 2017: 2.1/100 000 people without diabetes, 3% annual reduction, p= .048). Diabetes related amputation rates were highest in Malays and lowest in Chinese. Diabetes related major amputation rates declined significantly among Chinese (3.1% annual reduction, p < .038). While the RR for amputations in diabetes remained stable, the proportion of major amputations attributable to diabetes increased from 63.6% in 2008 to 81.7% in 2017 (3% annual increase, p= .003). Diabetes related major and toe/ray amputation rates have remained stable but relatively high in Singapore compared with other countries, and the proportion of amputations attributable to diabetes has increased over time. More research is needed to understand the aetiopathological, sociocultural, and health system factors that may underlie the continued high rates of diabetes related amputations in this population.

Geographic and Socioeconomic Disparities in Major Lower Extremity Amputation Rates in Metropolitan Areas.

BackgroundRates of major lower extremity amputation in patients with peripheral artery disease are higher in rural communities with markers of low socioeconomic status, but most Americans live in metropolitan areas. Whether amputation rates vary within US metropolitan areas is unclear, as are characteristics of high amputation rate urban communities.Methods and ResultsWe estimated rates of major lower extremity amputation per 100 000 Medicare beneficiaries between 2010 and 2018 at the ZIP code level among ZIP codes with ≥100 beneficiaries. We described demographic characteristics of high and low amputation ZIP codes, and the association between major amputation rate and 3 ZIP code–level markers of socioeconomic status—the proportion of patients with dual eligibility for Medicaid, median household income, and Distressed Communities Index score—for metropolitan, micropolitan, and rural ZIP code cohorts. Between 2010 and 2018, 188 995 Medicare fee‐for‐service patients living in 31 391 ZIP codes with ≥100 beneficiaries had a major lower extremity amputation. The median (interquartile range) ZIP code–level number of amputations per 100 000 beneficiaries was 262 (75–469). Though nonmetropolitan ZIP codes had higher rates of major amputation than metropolitan areas, 78.2% of patients undergoing major amputation lived in metropolitan areas. Compared with ZIP codes with lower amputation rates, top quartile amputation rate ZIP codes had a greater proportion of Black residents (4.4% versus 17.5%, P<0.001). In metropolitan areas, after adjusting for clinical comorbidities and demographics, every $10 000 lower median household income was associated with a 4.4% (95% CI, 3.9–4.8) higher amputation rate, and a 10‐point higher Distressed Communities Index score was associated with a 3.8% (95% CI, 3.4%–4.2%) higher amputation rate; there was no association between the proportion of patients eligible for Medicaid and amputation rate. These findings were comparable to the associations identified across all ZIP codes.ConclusionsIn metropolitan areas, where most individuals undergoing lower extremity amputation live, markers of lower socioeconomic status and Black race were associated with higher rates of major lower extremity amputation. Development of community‐based tools for peripheral artery disease diagnosis and management targeted to communities with high amputation rates in urban areas may help reduce inequities in peripheral artery disease outcomes.

Racial, Rural, and Regional Disparities in Diabetes-Related Lower-Extremity Amputation Rates, 2009-2017.

To examine the racial/ethnic, rural-urban, and regional variations in the trends of diabetes-related lower-extremity amputations (LEAs) among hospitalized U.S. adults from 2009 to 2017. We used the National Inpatient Sample (NIS) (2009-2017) to identify trends in LEA rates among those primarily hospitalized for diabetes in the U.S. We conducted multivariable logistic regressions to identify individuals at risk for LEA based on race/ethnicity, census region location (North, Midwest, South, and West), and rurality of residence. From 2009 to 2017, the rates of minor LEAs increased across all racial/ethnic, rural/urban, and census region categories. The increase in minor LEAs was driven by Native Americans (annual percent change [APC] 7.1%, P < 0.001) and Asians/Pacific Islanders (APC 7.8%, P < 0.001). Residents of non-core (APC 5.4%, P < 0.001) and large central metropolitan areas (APC 5.5%, P < 0.001) experienced the highest increases over time in minor LEA rates. Among Whites and residents of the Midwest and non-core and small metropolitan areas there was a significant increase in major LEAs. Regression findings showed that Native Americans and Hispanics were more likely to have a minor or major LEA compared with Whites. The odds of a major LEA increased with rurality and was also higher among residents of the South than among those of the Northeast. A steep decline in major-to-minor amputation ratios was observed, especially among Native Americans. Despite increased risk of diabetes-related lower-limb amputations in underserved groups, our findings are promising when the major-to-minor amputation ratio is considered.

Lower Limb Amputation Rates in Patients With Diabetes and an Infected Foot Ulcer: A Prospective Observational Study

Lower extremity amputation is a serious complication of diabetes mellitus and occurs most commonly in persons who have a foot ulcer. To examine variables that affect the rate of lower extremity amputation in patients with diabetes and infected foot ulcers. A prospective observational study was performed including all consecutive patients who were 18 to 65 years, had a diagnosis of diabetes, and a foot ulcer showing clinical signs of infection. Patients were followed for 6 months or until ulcer healing, minor, or major amputation. A total of 81 persons were enrolled. Demographic variables were obtained, and clinical assessments, blood tests, and radiological investigations were performed. Ulcers were categorized using the Perfusion, Extent, Depth, Infection and Sensation classification system. Differences between variables and outcomes were assessed using the Wilcoxon test, Fisher's exact test, Chi-square test, and t-test. Mean patient age was 54.58 ± 9.04 years, and the majority (61, 75%) were male. After 6 months, 33 (41%) were healed, 2 patients died, and 17 (21%) underwent major and 24 (30%) minor amputations. Major amputation rates were significantly higher in patients with a high Perfusion, Extent, Depth, Infection and Sensation score (6.92 ± 1.36; P = .005), elevated HbA1c (%) (9.43 ± 2.19; P = .049), presence of growth on wound culture (41 [64.1%]; P = .016), culture sensitivity to beta lactam (20 [31.2%]; P = .012), and presence of peripheral arterial disease seen on arterial Doppler ultrasound (P < .001). Minor amputation rates were higher in men (P = .02) and in the presence of peripheral arterial disease (P = .01). The presence of the above factors in persons with diabetes and foot ulcer with clinical signs of infection should alert the clinician to the need for focused and individualized treatment to attempt to prevent amputation.

Enhanced Post-Operative Recovery with Continuous Peripheral Nerve Block After Lower Extremity Amputation

Despite progress in perioperative care standards, there has not been a significant risk reduction in morbidity and mortality rates of lower extremity amputations, an intermediate risk surgery performed on high risk patients. The single-shot peripheral nerve block has shown equivocal impact on postoperative course following lower extremity amputation. Hence, we assessed the potential of preemptive use of continuous catheter-based peripheral nerve block in lower extremity amputations for reduction in pulmonary complications, acute post-operative pain scores, and opioid use in post-operative period. A retrospective review of a quality improvement project initiated in 2018 was conducted to compare outcomes amongst general anesthesia in combination with a catheter-based peripheral nerve block (catheter group) and general anesthesia alone in patients receiving lower extremity amputation. The rate of postoperative pulmonary complications was identified as a primary endpoint. The secondary outcomes assessed were acute post-operative pain scores and opioid consumption up to 48 hours. Our analysis was adjusted for potential confounding variables inclusive of demographics, medical comorbidities, type of surgical procedure and smoking status. Ninety-six patients were included in the study (61 in the general anesthesia group, 35 in the catheter group). After adjusting for baseline demographics, comorbidities, surgical technique and smoking status, the odds of postoperative pulmonary complications were significantly lower with catheter-based peripheral nerve block in comparison to general anesthesia alone, OR 0.11 [95% CI, 0.01- 0.88] (P = 0.048). The decrease in acute pain scores was also observed in the catheter group when compared to general anesthesia alone, OR 0.72 [95% CI, 0.56 - 0.93] (P = 0.012). Similarly, the opioid consumption was also lower in the catheter group in comparison to general anesthesia alone, OR 0.97 [95% CI, 0.95 - 0.99] (P = 0.025). Preemptive use of continuous peripheral nerve block in patients undergoing lower extremity amputation reduces the incidence of pulmonary complications, acute postoperative pain scores and narcotic use in post-operative period.

543 Escharotomy Incisions in the Burn Foot and Toe with Compartment Syndrome

Abstract Introduction Patients with burn injuries are at risk for lower extremity compartment syndrome, especially if the injury is circumferential. The hypothesis was that two dorsal escharotomy incisions to release foot and toe compartment syndrome would be most efficacious in the prevention of lower extremity amputations. Methods This was a retrospective chart review of foot compartment syndrome in burn patients between January 2001 and May 2019. Results The study consisted of 59 feet from 32 patients who had been admitted to the Burn Center for thermal injury. The patient age was a mean±sd of 29±30 years, and 41±29 as the % total body surface area (%TBSA); there were 19 males and 13 females. All patients had received fluid resuscitation on admission. Twenty-one (66%) of the patients did not require amputations after undergoing a median of two incisions (range 1–5); 6 of 59 (11%) required fasciotomies. Compared to medial or dorsal or multiple echarotomies, the majority of patients who underwent two dorsal foot escharotomies did not require amputations, p = .0001. Significantly more patients were alive with no amputation 15 (50%) compared to 4 (13%) (dead with amputations), p = .02. Survivors were significantly younger than the non-survivors (median 20 and range1-69) compared to the non-survivors (48, 12–59), p =.04. The survivors also had significantly less severe %TBSA median 22 (range 2–75) versus 83 (35–95) %TBSA, p &amp;lt; .0002. Dorsal/Lateral incisions had the highest number of amputations. Conclusions Foot dorsal compartment release is the most effective site for escharotomies in the treatment of burn-induced compartment syndrome. It does not require more than two incisions at the skin/fat level and over the second and fourth metatarsal bones on the dorsal part of the foot to decrease the lower extremity amputation rate in the majority of cases.

Pyridoxamine ameliorates methylglyoxal-induced macrophage dysfunction to facilitate tissue repair in diabetic wounds.

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading to cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the lower extremity amputation rate. Here, we aimed to identify the mechanisms of MGO‐induced dysfunction. We observed that the accumulation of MGO‐derived AGEs in human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a key metabolic enzyme of MGO, decreased. We show for the first time that topical application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the accumulation of MGO‐derived AGEs in the wound tissue of type‐2 diabetic mice, promoted the influx of macrophages in the early stage of tissue repair, improved the dysfunctional inflammatory response, and accelerated wound healing. In vitro, MGO damaged the phagocytic functions of M1‐like macrophages induced by lipopolysaccharide (LPS), but not those of M0‐like macrophages induced by PMA or of M2‐like macrophages induced by interleukins 4 (IL‐4) and 13 (IL‐13); the impaired phagocytosis of M1‐like macrophages was rescued by PM administration. These findings suggest that the increase in MGO metabolism in vivo might contribute to macrophage dysfunction, thereby affecting wound healing. Our results indicate that PM may be a novel therapeutic approach for treating diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. These adducts cause cell and organ dysfunction that is common in diabetes. Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound healing. Pyridoxamine could be used therapeutically to treat non‐healing diabetic wounds.

Using machine learning to identify diabetes patients with canagliflozin prescriptions at high-risk of lower extremity amputation using real-world data.

Canagliflozin, a sodium-glucose cotransporter 2 inhibitor indicated for lowering glucose, has been increasingly used in diabetes patients because of its beneficial effects on cardiovascular and renal outcomes. However, clinical trials have documented an increased risk of lower extremity amputations (LEA) associated with canagliflozin. We applied machine learning methods to predict LEA among diabetes patients treated with canagliflozin. Using claims data from a 5% random sample of Medicare beneficiaries, we identified 13 904 diabetes individuals initiating canagliflozin between April 2013 and December 2016. The samples were randomly and equally split into training and testing sets. We identified 41 predictor candidates using information from the year prior to canagliflozin initiation, and applied four machine learning approaches (elastic net, least absolute shrinkage and selection operator [LASSO], gradient boosting machine and random forests) to predict LEA risk after canagliflozin initiation. The incidence rate of LEA was 0.57% over a median 1.5 years follow-up. LASSO produced the best prediction, yielding a C-statistic of 0.81 (95% CI: 0.76, 0.86). Among individuals categorized in the top 5% of the risk score, the actual incidence rate of LEA was 3.74%. Among the 16 factors selected by LASSO, history of LEA [adjusted odds ratio (aOR): 33.6 (13.8, 81.9)] and loop diuretic use [aOR: 3.6 (1.8,7.3)] had the strongest associations with LEA incidence. Our machine learning model efficiently predicted the risk of LEA among diabetes patients undergoing canagliflozin treatment. The risk score may support optimized treatment decisions and thus improve health outcomes of diabetes patients.