Lower Amputation Risk Research Articles

Contemporary national outcomes of hyperbaric oxygen therapy in necrotizing soft tissue infections.

The role of hyperbaric oxygen therapy (HBOT) in necrotizing soft tissue infections (NSTI) is mainly based on small retrospective studies. A previous study using the 1998-2009 National Inpatient Sample (NIS) found HBOT to be associated with decreased mortality in NSTI. Given the argument of advancements in critical care, we aimed to investigate the continued role of HBOT in NSTI. The 2012-2020 National Inpatient Sample (NIS) was queried for NSTI admissions who received surgery. 60,481 patients between 2012-2020 were included, 600 (<1%) underwent HBOT. Primary outcome was in-hospital mortality. Secondary outcomes included amputation, hospital length of stay, and costs. A multivariate model was constructed to account for baseline differences in groups. Age, gender, and comorbidities were similar between the two groups. On bivariate comparison, the HBOT group had lower mortality rate (<2% vs 5.9%, p<0.001) and lower amputation rate (11.8% vs 18.3%, p<0.001) however, longer lengths of stay (16.9 days vs 14.6 days, p<0.001) and higher costs ($54,000 vs $46,000, p<0.001). After multivariate analysis, HBOT was associated with decreased mortality (Adjusted Odds Ratio (AOR) 0.22, 95% CI 0.09-0.53, P<0.001) and lower risk of amputation (AOR 0.73, 95% CI 0.55-0.96, P = 0.03). HBO was associated with longer stays by 1.6 days (95% CI 0.4-2.7 days) and increased costs by $7,800 (95% CI $2,200-$13,300), they also had significantly lower risks of non-home discharges (AOR 0.79, 95%CI 0.65-0.96). After correction for differences, HBOT was associated with decreased mortality, amputations, and non-home discharges in NSTI with the tradeoff of increase to costs and length of stay.

In-patient characteristics of peripheral artery disease in Germany.

Background: Peripheral artery disease (PAD) frequently leads to hospital admission. Sex related differences in in-patient care are a current matter of debate. Patients and methods: Data were provided from the German national in-patient sample provided by the Federal Bureau of Statistics (DESTATIS). Trends on risk profiles, therapeutic procedures, and outcomes were evaluated from 2014 until 2019 stratified by sex and PAD severity. Results: Two-thirds of an annual >191,000 PAD in-patient cases applied to male sex. Chronic limb-threatening ischemia (CLTI) was recorded in 49.6% of male and 55.2% of female cases (2019). CLTI was as a major risk factor of in-hospital amputation (OR 229) and death (OR 10.5), whereas endovascular revascularisation (EVR) with drug-coated devices were associated with decreased risk of in-hospital amputation (OR 0.52; all p<0.001). EVR applied in 47% of CLTI cases compared to 71% in intermittent claudication (IC) irrespective of sex. In-hospital mortality was 4.3% in male vs. 4.8% in female CLTI cases, minor amputations 18.4% vs. 10.9%, and major amputation 7.5% vs. 6.0%, respectively (data 2019; all p<0.001). After adjustment, female sex was associated with lower risk of amputation (OR 0.63) and death (OR 0.96) during in-patient stay. Conclusions: Male PAD patients were twice as likely to be admitted for in-patient treatment despite equal PAD prevalence in the general population. Among in-patient cases, supply with invasive therapy did not relevantly differ by sex, however is strongly reduced in CLTI. CLTI is a major risk factor of adverse short-term outcomes, whereas female sex was associated with lower risk of in-patient amputation and/or death.

The role of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers: a systematic review with meta-analysis of randomized controlled trials on limb amputation and ulcer healing.

Hyperbaric oxygen therapy (HBOT) is increasingly being used in the treatment of as diabetic foot ulcers (DFU). However, definitive evidence regarding its beneficial effects is still scarce. The present systematic review aims to analyze the role of HBOT in the prevention of limb amputation along with improvement of ulcer healing in patients with lower limbs DFU. Three databases were searched: PubMed, Scopus, and ISI Web of Knowledge. The search was enrolled during October 2020. Both titles and abstracts were examined by two independent reviewers. Only randomized controlled trials (RCTs) reporting a comparison between standard DFU treatment and standard treatment associated with HBOT were included. In all studies eligibility was assessed and data regarding studies characteristics, methods and considered outcomes was obtained. Odds ratio (OR) was used to evaluate amputation and complete ulcer healing rates. Percentage of ulcer reduction at two weeks was evaluated using the inverse variance method, and the values were compared using mean difference values. Meta-analysis was done using a fixed-effect model if I2 values were under 50%, and a random-effects model if not. Eleven RCTs were included, with a total of 668 patients studied. Patients undergoing HBOT had lower risk of amputation (OR 0.53 95% CI 0.32-0.90, I2=31%). No difference was found in minor amputations (OR 0.89 95% CI 0.35-2.24, I2=69%). Regarding, healing rates, HBOT patients had greater chances of ulcer healing (OR 4,00 95% CI 1.54-10.44, I2=70%). It has also shown higher percentage of ulcer area reduction after two weeks of treatment in the HBOT group (mean difference 23.19%; 95% CI 14.86-31.52; I2=0%). The present review offers evidence that adjuvant HBOT decreases risk of major amputation while promoting wound healing when combined to standard treatment in the management of DFU. These findings may have clinical relevance in a selected group of patients, yet further larger studies are still needed.

Effect of Direct Endovascular Revascularization Based on the Angiosome Model on Risk of Major Amputations and Life Expectancy in Type 2 Diabetic Patients with Critical Limb Ischemia and Foot Ulceration.

We evaluated whether direct or indirect endovascular revascularization based on the angiosome model affects outcomes in type 2 diabetes and critical limb ischemia. From 2010 to 2015, 603 patients with type 2 diabetes were admitted for critical limb ischemia and submitted to endovascular revascularization. Among these patients, 314 (52%) underwent direct and 123 (20%) indirect revascularization, depending on whether the flow to the artery directly feeding the site of ulceration, according to the angiosome model, was successfully acquired; 166 patients (28%) were judged unable to be revascularized. Outcomes were healing, major amputation, and mortality rates. An overall healing rate of 62.5% was observed: patients who did not receive percutaneous transluminal angioplasty presented a healing rate of 58.4% (P < .02 versus revascularized patients). A higher healing rate was observed in the direct versus the indirect group (82.4% versus 50.4%; P < .001). The major amputation rate was significantly higher in the indirect versus the direct group (9.2% versus 3.2%; P < .05). The overall mortality rate was 21.6%, and it was higher in the indirect versus the direct group (24% versus 14%; P < .05). These data show that direct revascularization of arteries supplying the diabetic foot ulcer site by means of the angiosome model is associated with a higher healing rate and lower risk of amputation and death compared with the indirect procedure. These results support use of the angiosome model in type 2 diabetes with critical limb ischemia.

Risk of lower limb amputation in diabetes patients with and without coronary artery disease – a cohort study from Western Denmark

Abstract Background Diabetes patients are at greater risk of lower limb amputation due to a higher risk of peripheral artery disease (PAD) and peripheral neuropathy. The effect of concomitant coronary artery disease (CAD) is less explored. Purpose We examined the risk of PAD, lower limb revascularization, and lower limb amputation in diabetes and non-diabetes patients with and without CAD examined by coronary angiography. Methods We included all patients who underwent coronary angiography between 2003–2016 in Western Denmark. Patients with a history of PAD or previous lower limb revascularization or amputation were excluded. Patients were stratified by diabetes and CAD status and followed in prospective registries for a maximum of 10 years. Outcomes were PAD, lower limb revascularization, and lower limb amputation. We estimated 10-year cumulative incidence and adjusted hazard ratios (aHR) using patients with neither diabetes nor CAD as reference. We also examined the effect of CAD extent, insulin treatment, and duration of diabetes in the diabetes group. Results A total of 118,787 coronary angiography patients were included of whom 17,482 (14.7%) had diabetes. Median follow-up was 6.8 years. Patients with both diabetes and CAD had the highest risk of PAD (aHR 3.90, 95% CI 3.55–4.28), lower limb revascularization (aHR 4.61, 95% CI 3.85–5.52), and lower limb amputation (aHR 9.49, 95% CI 7.27–12.39), compared with patients with neither diabetes nor CAD. Extent of CAD, insulin treatment, and duration of diabetes were all associated with increased risks of PAD and amputation in the diabetes group. CAD only patients had higher 10-year risk of PAD compared to diabetes only patients (7.9% versus 6.9%), but had lower risk of amputation (0.6% versus 2.4%, Figure). CAD only patients were most often amputated at hip/femur level, while diabetes only patients most often were amputated at ankle/foot/toe level. Conclusions Presence of CAD in patients with diabetes was an indicator of high risk of PAD and lower limb amputation, and the risk depended on severity of both CAD and diabetes. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Department of Cardiology, Aarhus University Hospital

Frailty and Biomarkers of Frailty Predict Outcome in Veterans After Open and Endovascular Revascularization

BackgroundFrailty predicts poor outcome after vascular surgery. We determined the predictive utility of the modified frailty index (mFI) after first-time revascularization and identified biomarkers of frailty predictive of outcome in veterans with peripheral arterial disease. MethodsA retrospective study was performed of first-time revascularizations (open surgery [OS] and endovascular surgery [ES]) in male veterans (2003-2016). Preoperative mFI scores were calculated, and serum and nonserum biomarkers of frailty were recorded. The primary endpoint was 2-y incidence of reintervention, amputation, and mortality. Secondary endpoints included 30-day morbidity and readmissions. ResultsFour hundred and thirty one patients (OS, n = 188; ES, n = 243), mean age of 66 ± 9 y, and 16 mo of median follow-up were studied. Mean mFI was 0.39 ± 0.16 for OS and 0.38 ± 0.15 for ES (P = 0.43). 30-day complications (adjusted odds ratio, 4.89; 95% confidence interval [CI]: 1.67-14.33) and readmissions (adjusted hazard ratio [aHR] 3.32; 95% CI: 1.16-9.55) were increased in the OS versus ES group when stratified by mFI. Survival analysis showed a correlation between risk of amputation, death, and composite outcome with increasing mFI (P < 0.005) in both groups. Frailty independently predicted major amputation (aHR 2.16; 1.06-4.39), mortality (aHR 2.62; 95% CI: 1.17-5.88), and composite outcome (aHR 1.97; 95% CI: 1.06-3.68) when the groups are combined. Except for absolute neutrophil count, all preoperative lab values correlated with mFI (P < 0.5). Higher albumin was independently associated with lower risk of amputation (aHR: 0.58 [0.36-0.94]) and mortality (aHR: 0.45 [0.25-0.83]); higher hemoglobin predicted limb salvage (aHR 0.7 [0.62-0.84]). ConclusionsFrailty predicts short- and long-term outcomes after first-time revascularization in veterans. Hypoalbuminemia and anemia are associated with higher mFI and independently predict poor outcome, suggesting albumin and hemoglobin are viable biomarkers of frailty in veterans.

Long-Term Outcome and Prognostic Factors of Complications in Thromboangiitis Obliterans (Buerger's Disease): A Multicenter Study of 224 Patients.

BackgroundData regarding long‐term outcome of patients with thromboangiitis obliterans are lacking and most series come from India and Japan. In this study, we assess long‐term outcome and prognostic factors in a large cohort of thromboangiitis obliterans.Methods and ResultsRetrospective multicenter study of characteristics and outcomes of 224 thromboangiitis obliterans patients fulfilling Papa's criteria were analyzed. Factors associated with vascular events and amputations were identified. The median age at diagnosis was 38.5 (32–46) years, 51 (23.8%) patients were female, and 81.7% were whites. After a mean follow‐up of 5.7 years, vascular events were observed in 58.9%, amputations in 21.4%, and death in 1.4%. The 5‐, 10‐, and 15‐year vascular event‐free survival and amputation‐free survival were 41% and 85%, 23% and 74%, and 19% and 66%, respectively. Ethnic group (nonwhite) (hazard ratio 2.35 [1.30–4.27] P=0.005) and limb infection at diagnosis (hazard ratio 3.29 [1.02–10.6] P=0.045) were independent factors of vascular event‐free survival. Factor associated with amputation was limb infection (hazard ratio 12.1 [3.5–42.1], P<0.001). Patients who stopped their tobacco consumption had lower risk of amputation (P=0.001) than those who continued.ConclusionsThis nationwide study shows that 34% of thromboangiitis obliterans patients will experience an amputation within 15 years from diagnosis. We identified high‐risk patients for vascular complications and amputations.

Epidemiology of lower extremity peripheral artery disease in veterans

ObjectiveThe objective of this study was to describe the epidemiology, clinical features, outcomes, and predictors of mortality in veterans with peripheral artery disease (PAD). MethodsWe used national data from the Veterans Health Administration from fiscal years 2009 to 2011 to identify patients with a new diagnosis of PAD. Within this cohort, we describe characteristics of the patients, use of recommended medications, and clinical outcomes during a 3-year follow-up (fiscal year 2014). We used Cox proportional hazards regression to examine predictors of mortality and adverse limb outcomes (amputation and hospitalization for critical limb ischemia [CLI]) during follow-up. ResultsA total of 175,865 patients with a new diagnosis of PAD were included. The mean age was 69.9 years; 97.8% were male, and 67.7% were white. Nearly 77% of patients had hypertension, 46.5% had diabetes, 23% had chronic obstructive pulmonary disease, and 12.9% had renal failure. A prescription for statins was filled by 60.8%, and 34.9% received high-intensity statins within 90 days of PAD diagnosis. At 1 year, 2.6% underwent revascularization, 1.3% developed CLI, and 1.1% underwent amputation. During a median follow-up of 3.8 years, a total of 28.6% patients died (6.7% at 1 year), and 3.7% developed a limb outcome (2.0% at 1 year). Predictors of mortality included advanced age, comorbidities, and CLI or amputation at presentation. In contrast, prescription with statins was associated with lower mortality. Similar findings were present with regard to predictors of adverse limb outcomes, except that older age was associated with a lower risk of amputation or CLI. ConclusionsWe found that veterans with PAD have a high prevalence of comorbid conditions and have a significant risk of mortality and limb loss. A substantial proportion of veterans with PAD are not prescribed recommended medications, especially statin therapy. Our data highlight important opportunities for improving care of veterans with PAD.

Association of Statin Dose With Amputation and Survival in Patients With Peripheral Artery Disease.

Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality. Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003-2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate-intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score-matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding. In 155 647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy-only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy-only users (hazard ratio, 0.67; 95% confidence interval, 0.61-0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70-0.77, respectively). Low-to-moderate-intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75- 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81-0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins (P<0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score-matched, sensitivity, and subgroup analyses. Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate-intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well.

Abstract 109: Statins Have a Dose-dependent Effect on Amputation Risk and Survival in Peripheral Arterial Disease (PAD) Patients

Introduction: Statin dose guidelines for PAD patients are based on coronary artery disease and stroke data. The aim of our study was to determine the effect of statin dose (based on 2013 ACC/AHA guidelines) on PAD outcomes of amputation and mortality. Methods: Patients with PAD in the Veterans Affairs database were identified from 2003-2014. The exposure was highest statin dose usage (none, low-moderate and high intensity) around diagnosis of PAD (within 1 year). The outcomes were risk of incident amputation (below knee or above knee) and mortality at 1, 3 and 5 years. The effect of statin dose on the two outcomes was also analyzed using Cox proportional hazards modeling to adjust for covariates. Results: In 208,275 patients with PAD [Males: 98.1%; Mean age: 67.4 yrs (SD 9.9)], 17,643 amputations and 99,951 deaths occurred in a median follow up of 5.2 years. Almost a quarter (27.7%) of patients were not on a statin while 30.4% were on simvastatin 80 mg (no longer recommended due to drug toxicity). The risk of incident amputation declined significantly at the high intensity statin dose as seen in Table 1. In Cox models adjusting for age, gender, race, comorbidities, cholesterol levels and creatinine, the high intensity statins were associated with lower amputation risk and mortality as compared to no statin [HR 0.67; 95% CI (0.63, 0.72) and HR 0.71; 95% CI (0.68, 0.73), respectively]. Low-moderate-dose statins also had significant but smaller reductions in risk of amputation and mortality [HR amputation 0.78 (0.75, 0.82), HR death 0.78 (0.77, 0.80)]. Conclusion: This is one of the largest population based studies to examine the effect of statins on long-term PAD outcomes and the first to explore the dose-dependent effect of statins on amputation and mortality. High intensity statins are associated with a significant reduction in limb loss and mortality in PAD patients followed by a smaller risk reduction by low-moderate intensity statins as compared to no statin therapy.

Factors determining the risk of diabetes foot amputations – A retrospective analysis of a tertiary diabetes foot care service

AimsTo identify which factors predict the need for minor or major amputation in patients attending a multidisciplinary diabetic foot clinic (DFC). MethodsA retrospective analysis of patients who attended over a 27 month period were included. Patients had to have attended ≥3 consecutive consultant led clinic appointments within 6 months. Data was collected on HbA1c, clinic attendance, blood pressure, peripheral arterial disease (PAD), and co-morbidities. Patients were followed up for 1 year. Results165 patients met the inclusion criteria. 121 were male. 33 patients had amputations. There was an association between poor glycaemic control at baseline and risk of amputation when adjusted for other factors, with those patients having HbA1c ≤58mmol/mol (7.5%) at less risk of amputation with an odds of 0.14 (0.04–0.53) of amputation(p=0.0036). Other statistically significant factors predictive of amputation were: missing clinic appointments (p=0.0079); a high Charlson index (p=0.03314); hypertension (p=0.0216). No previous revascularisation was protective against amputation (p=0.0035). However PAD was not seen to be statistically significant, although our results indicated a lower risk of amputation with no PAD. Overall, 34.9% (n=58) of patients had good glycaemic control (HbA1c <58mmol/mol, [7.5%]) at baseline and 81.3% (n=135) had improved their glycaemic control at their last follow up appointment. ConclusionsIn this cohort poor glycaemic control, poor attendance, previous revascularisation and hypertension were associated with higher risk of amputation, with PAD showing a trend. Moreover, we demonstrated benefits in glycaemic control achieved by attending this DFC, which is likely to translate to longer term diabetes related health benefits.

Racial Disparities after Vascular Trauma Are Age-Dependent

Hicks, Caitlin W. MD; Canner, Joseph K. MHS; Zarkowsky, Devin S. MD; Schneider, Eric B. PhD; Arhuidese, Isibor MD, MPH; Obeid, Tammam MD; Qazi, Umair MD, MPH; Abularrage, Christopher J. MD, FACS; Malas, Mahmoud MD, MHS, FACS Author Information

Thrombolysis of peripheral arterial bypass grafts: Surgical thrombectomy compared with thrombolysis: A preliminary report

Twenty-two patients were selected from a group of 33 patients who underwent recombinant human tissue-type plasminogen activator (rt-PA) thrombolysis for thrombosed infrainguinal bypass grafts of the lower extremity and were compared with 38 matched patients who had undergone surgical thrombectomy during the same period. The proportion of persons with diabetes mellitus, smokers, and types of bypass grafts was similar in both groups. More patients in the rt-PA—treated group had hypertension (p = 0.01). To evaluate the different lengths of follow-up, Kaplan-Meier survival analysis was used with a log-rank test to compare the proportion of persons with patent grafts in the two treatment groups. At 30 days, 86% of the rt-PA—treated grafts were still patent compared with 42% of the surgically treated grafts (p = 0.001). When risk factors on the Kaplan-Meier curves were compared, there was no statistical difference with regard to graft patency among the groups. According to simultaneous Cox regression analysis, no risk factor was significantly associated with graft patency. When amputation was evaluated between treatment groups simultaneously with other risk factors in a logistic regression analysis, smoking and age of the graft were marginally significant (p = 0.07), whereas all other factors were clearly not significant. In 91% of the rt-PA—treated patients, a secondary surgical procedure was required to maintain patency of the graft segment. Eighty-nine percent of the surgically treated patients required similar graft revisions. Two patients in the surgical group and one patient in the rt-PA—treated group had major complications. This short clinical experience suggests that better 30-day patency rates and a lower risk of amputation can be achieved when thrombolysis is associated with surgical revision compared with surgical revision alone.