Comparison of limb outcomes between bypass surgery and endovascular therapy in dialysis-dependent and -independent patients with chronic limb-threatening ischemia.

OBJECTIVE: To examine limb salvage (LS) and wound healing in dialysis-dependent and -independent patients with chronic limb-threatening ischemia (CLTI) after infrainguinal bypass surgery or endovascular therapy (EVT). METHODS: We retrospectively analyzed the multi-center data of patients who underwent infrainguinal revascularization for CLTI with Wound, Ischemia, and foot Infection (WIfI) stage 2 to 4 between 2015 and 2020. The primary endpoint was LS. The secondary endpoint included wound healing, amputation-free survival (AFS), periprocedural complications, and 2-year survival. Comparison of these outcomes were made after propensity score matching. RESULTS: We analyzed 252 dialysis-dependent (318 limbs) and 305 dialysis-independent (354 limbs) patients. Propensity score matching extracted 202 pairs with no significant differences in characteristics. The LS rate in bypass surgery was better than that in EVT in dialysis-dependent patients (P < .001). There was no significant difference in the LS rates between bypass surgery and EVT in dialysis-independent patients (P = .168). The wound healing rate of bypass surgery was better than that of EVT both dialysis-dependent and -independent patients with CLTI. The AFS rate of bypass surgery was better than that of EVT in dialysis-dependent patients (P < .001). There was no significant difference in the AFS rates between bypass surgery and EVT in dialysis-independent patients (P = .099). There was no significant difference in the occurrence of Clavien-Dindo ≥ IV and V between bypass surgery and EVT in dialysis-dependent and -independent patients. Age ≥75 years, serum albumin levels <3.5 g/dL, and non-ambulatory status were risk factors for 2-year mortality in dialysis-dependent patients. The 2-year survival rates in dialysis-dependent patients with risk factors of 0, 1, 2, and 3 were 82.5%, 67.1%, 49.5%, and 10.2%, respectively (P < .001). CONCLUSIONS: For LS and wound healing, bypass surgery was preferred for revascularization in dialysis-dependent patients with WIfI stage 2 to 4. Although dialysis dependency was one of the risk factors for 2-year mortality, dialysis-dependent patients, who have 0 to 1 risk factors, may benefit from bypass surgery, as 2-year survival of >50% is expected.

Development of an Education Material Targeting Patients Undergoing Lower Extremity Amputation due to Severe Limb Ischemia-A Qualitative Study.

INTRODUCTION: Critical limb-threatening ischemia (CLTI) is associated with a high risk of amputation, yet patients undergoing amputation due to CLTI have little knowledge of the amputation process and the rehabilitation that awaits. The aim of the present study was to develop and validate information material for patients undergoing amputation. METHODS: Nine participants were included in the study. Two focus group interviews were performed with seven patients who had undergone lower extremity amputation due to CLTI within the past 2 y. Additionally, two individual interviews were carried out. A semistructured interview guide was used, and the interviews were transcribed verbatim and analysed using qualitative content analysis with a deductive approach. RESULTS: Three themes were identified as essential for the design of the written information: Perspectives on design and formatting, Providing information to enhance participation in care, and Accessibility to information and support. The prototyped information leaflet was perceived as acceptable, useable, relevant, and comprehensible by the participants. CONCLUSIONS: For patients to actively engage in their care, it is vital that their information needs are met and that they are provided with psychosocial support when needed. Written and oral information should be provided by a trusted healthcare professional.

Development of a major amputation prediction model and nomogram in patients with diabetic foot.

BACKGROUND: Diabetes mellitus, as one of the world's fastest-growing diseases, is a chronic metabolic disease that has now become a public health problem worldwide. The purpose of this research was to develop a predictive nomogram model to demonstrate the risk of major amputation in patients with diabetic foot. METHODS: A total of 634 Type 2 Diabetes Mellitus (T2DM) patients with diabetic foot ulcer hospitalized at the Air Force Medical Center between January 2018 and December 2023 were included in our retrospective study. There were 468 males (73.82%) and 166 females (26.18%) with an average age of 61.64 ± 11.27 years and average body mass index of 24.45 ± 3.56 kg/m2. The predictive factors were evaluated by single factor logistic regression and multiple logistic regression and the predictive nomogram was established with these features. Receiver operating characteristic (subject working characteristic curve) and their area under the curve, calibration curve, and decision curve analysis of this major amputation nomogram were assessed. Model validation was performed by the internal validation set, and the receiver operating characteristic curve, calibration curve, and decision curve analysis were used to further evaluate the nomogram model performance and clinical usefulness. RESULTS: Predictors contained in this predictive model included body mass index, ulcer sites, hemoglobin, neutrophil-to-lymphocyte ratio, blood uric acid (BUA), and ejection fraction. Good discrimination with a C-index of 0.957 (95% CI, 0.931-0.983) in the training group and a C-index of 0.987 (95% CI, 0.969-1.000) in the validation cohort were showed with this predictive model. Good calibration were displayed. The decision curve analysis showed that using the nomogram prediction model in the training cohort and validation cohort would respectively have clinical benefits. CONCLUSION: This new nomogram incorporating body mass index, ulcer sites, hemoglobin, neutrophil-to-lymphocyte ratio, BUA, and ejection fraction has good accuracy and good predictive value for predicting the risk of major amputation in patients with diabetic foot.

Treatment outcomes between bypass surgery and endovascular therapy in patients with chronic limb-threatening ischemia classified as bypass-preferred category based on Global Vascular Guidelines.

OBJECTIVE: The aim of this study was to examine outcomes between bypass surgery and endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI), classified as bypass-preferred according to the Global Vascular Guidelines (GVG). METHODS: We retrospectively analyzed the multi-center data of patients who underwent infrainguinal revascularization for CLTI with Wound, Ischemia, and foot Infection (WIfI) Stage 3 to 4 and Global Limb Anatomical Staging System (GLASS) Stage III, which is classified as bypass-preferred category by the GVG between 2015 and 2020. The endpoints were limb salvage and wound healing. RESULTS: We analyzed 301 patients and 339 limbs following 156 bypass surgeries and 183 EVTs. The 2-year limb salvage rates were 92.2% in the bypass surgery group and 76.3% in the EVT group, respectively (P < .01). The 1-year wound healing rates were 86.7% in the bypass surgery group and 67.8% in the EVT group (P < .01). Multivariate analysis shows decreased serum albumin level (P < .01), increased wound grade (P = .04), and EVT (P < .01) were risk factors for major amputation. Decreased serum albumin level (P < .01), increased wound grade (P < .01), GLASS infrapopliteal grade (P = .02), inframalleolar (IM) P grade (P = .01), and EVT (P < .01) were risk factors for impaired wound healing. Subgroup analysis of limb salvage in patients after EVT, decreased serum albumin level (P < .01), increased wound grade (P = .03), increased IM P grade (P = .04), and congestive heart failure (P < .01) were risk factors for major amputation. According to scoring by existence of these risk factors, 2-year limb salvage rates following EVT were 83.0% and 42.8% for the total score of 0 to 2 and of 3 to 4, respectively (P < .01). CONCLUSIONS: Bypass surgery provides better limb salvage and wound healing in patients with WIfI Stage 3 to 4 and GLASS Stage III, which is classified as bypass-preferred category by the GVG. In patients after EVT, serum albumin level, wound grade, IM P grade, and congestive heart failure were related to major amputation. Although bypass surgery may be considered as initial revascularization procedure in patients classified as bypass-preferred category, in case that EVT has to be selected, relatively acceptable outcomes can be expected in patients with less of these risk factors.

Clinical Outcomes of Additional Below-The-Ankle Intervention Compared to Below-The-Knee Intervention Alone: A Post-Hoc Analysis of a Prospective Multicenter Study.

PURPOSE: To investigate the clinical implication of additional below-the-ankle (BTA) intervention in patients with chronic limb-threatening ischemia (CLTI) undergoing below-the-knee (BTK) intervention. MATERIALS AND METHODS: A sub-analysis was performed using data from the LIBERTY trial (ClinicalTrials.gov identifier NCT01855412), a prospective, observational, core-laboratory adjudicated, multicenter study of endovascular intervention in 1204 patients. Patients with CLTI (Rutherford Classification 4-6) who underwent BTK intervention were included in this sub-analysis. Participants were then stratified into 2 treatment groups according to whether at least one lesion intervened on was BTA (n=66) or not (n=273). The decision on whether and where to intervene was made during the procedure. The main outcome measures included major amputation, target vessel revascularization (TVR), major adverse events (MAE), survival, amputation-free survival, major adverse limb events or peri-operative death (MALE-POD), and all-cause death. Other outcome measures included procedural success, procedural complications, and wound healing rate. RESULTS: There were no differences in procedural success or severe angiographic complications between the 2 groups. At 1-year post-procedure, patients in the BTK group had a higher rate of freedom from major amputation (95.0% vs. 86.9%, respectively; HR: 2.87, 95% CI: 1.17-7.03), a higher rate of freedom from TVR (80.1% vs. 66.9%, respectively; HR: 1.94, 95% CI: 1.14-3.32), a higher rate of freedom from MALE-POD (94.6% vs. 86.9%, respectively; HR: 2.65, 95% CI: 1.10-6.41), and a higher rate of freedom from MAE at both 1 (76.0% vs. 60.1%, respectively; HR: 2.00, 95% CI: 1.24-3.22) and 3 years post procedure (67.5% vs. 55.8%, respectively; HR: 1.69, 95% CI: 1.08-2.65). There was a significantly lower rate of survival in the BTK group at 3 years (74.3% vs. 91.1%, respectively; HR: 0.35, 95% CI: 0.14-0.87). After risk adjustment, there was a higher rate of all-cause death in the BTK group at 3 years (19.4% vs. 9.1%, respectively; p=0.023) post-intervention. CONCLUSION: Patients with disease requiring intervention to BTA lesions have a potential increased amputation rate in the short term, but BTA intervention carries a potential survival benefit in the long term when compared to BTK intervention alone.

Global Limb Anatomic Staging System Inframalleolar Modifier Predicts Limb Salvage and Wound Healing in Patients with Chronic Limb Threatening Ischaemia Undergoing Endovascular Infrainguinal Revascularisation.

OBJECTIVE: This study aimed to analyse the influence of the Global Anatomic Staging System (GLASS) and inframalleolar (IM) disease on the treatment outcomes of patients with chronic limb threatening ischaemia (CLTI) who undergo endovascular treatment (EVT) METHODS: Data of patients who underwent infrainguinal endovascular therapy (EVT) for CLTI between 2015 and 2019 at two centres were analysed retrospectively. The endpoints were major amputation, major adverse limb events (MALE), and wound healing. RESULTS: Overall, 276 patients and 340 limbs were analysed. The number of revascularisations for an infrapopliteal lesion was 48 (70.6%), 63 (63.0%), and 142 (82.6%) in the GLASS I, GLASS II, and GLASS III stages, respectively (p < .001). There was no statistically significant difference in limb salvage among the GLASS stages (p = .78). The limb salvage rates at one year were 94.6%, 88.0%, and 70.0% in the IM P0 P1, and P2 groups, respectively (p < .001). Multivariable analysis showed that Wound, Ischemia, and foot Infection (WIfI) stage, and IM grade were risk factors for major amputation. The freedom from MALE rates at two years were 60.5%, 45.3%, and 41.1% in the GLASS I, II, and III stages, respectively (p = .003) and 64.1%, 43.5%, and 18.4% in the IM P0, P1, and P2 groups, respectively (p < .001). Multivariable analysis demonstrated that WIfI stage, GLASS stage, IM grade, and infrapopliteal revascularisation were risk factors for MALE. There was no significant difference in wound healing among GLASS I - III (p = .75). The wound healing rates at 365 days were 78.6%, 68.6%, and 42.0% in the IM P0, P1, and P2 groups, respectively (p = .065). Multivariable analysis showed that WIfI stage and IM P2 were risk factors for incomplete wound healing. CONCLUSION: GLASS IM was associated with major amputation, MALE, and wound healing, while GLASS stage was associated with only MALE.

An index to prevent major limb amputations in diabetic foot.

Objective. Besides the early detection and treatment of diabetic foot ulcers, being aware of the risk factors for major amputation plays a crucial role in preventing the major lower limb amputations. Major lower limb amputations are not just mentally and physically hard for patients, but also have an effect on patient's survival and are a financial burden on both patients and healthcare systems. Subjects and Methods. We defined 37 potential risk factors for major amputation and these risk factors were investigated among 507 patients who had ulcers in their feet and were seen by the diabetic foot ulcer council at Ege University Faculty of Medicine. In our study, 106 (20.9%) patients ended up undergoing major lower limb amputation. Results. The univariate analysis showed that 24 defined risk factors were statistically significant. In the multivariate analysis using the Cox regression model, 6 risk factors remained statistically significant. Multivariate-adjusted hazard ratios were 4.172 for hyperlipidemia, 3.747 for albumin <3.365 g/dL, 3.368 for C-reactive protein (CRP) >2.185 mg/L, 2.067 for presence of gangrenous Wagner stage, 1.931 for smoking tobacco >30 pack/year, and 1.790 for hematocrit (HCT) <31.5%. Most patients with major amputation presented with a neuroischemic foot (58%). Gender and age were not found to be risk factors for major amputation. Having less than 7% of hemoglobin A1c (HbA1c) levels had a direct proportion with major amputation numbers. The mortality rates in one year, two and three years after the major amputation operations were 24.6%, 30%, and 35.9%, respectively. Conclusion. Being familiar with these risk factors for major amputation is crucial for multi-disciplinary teams to take good care of patients with diabetic foot ulcers and to lower the need for major amputations.

Revascularization prevents amputation among patients with diabetic foot during the COVID-19 era.

OBJECTIVE: The COVID-19 pandemic has led to significant changes in healthcare systems that impact the management of chronic diseases such as diabetic foot (DF). We hypothesized that lack of access to healthcare would increase the severity of disease and lead to worse outcomes. METHODS: The medical records of patients with DF were reviewed to determine demographic data and outcomes including wound healing, major amputation (MA), and death. Groups were divided into the pre-COVID-19 era (15 March 2019-15 March 2020) and the COVID-19 era (16 March 2020-16 March 2021); multivariable logistic analysis was performed to identify risk factors for MA. RESULTS: 261 patients with DF were included, 163 in the pre-COVID-19 era and 98 during the COVID-19 era. Patients in the COVID-19 presented with increased cardiovascular disease (19 vs 7%, p = 0.01), increased mean HbA1C (9.1 ± 2.1 vs 8.2 ± 2.1, p = 0.008) and higher WIFI-IV stage (78 vs 53%, p ≤ 0.0001). Patients with DF in the COVID-19 era were more likely to require MA (41 vs 21%, p ≤ 0.0001). Revascularization (OR = 0.12; 95% CI, 0.038-0.38) was a protective factor to reduce MA. CONCLUSIONS: MA among DF patients increased two-fold during the COVID-19 era. Revascularization avoids MA in diabetic patients even during the COVID-19 pandemic, suggesting that revascularization should be performed when possible.

The relationship between hyperpolypharmacy and one-year outcomes in patients with critical limb ischemia undergoing below-knee endovascular therapy.

BACKGROUND: Critical limb ischemia (CLI) patients take too many medications because they are elderly and frail patients with multiple comorbidities. Polypharmacy is associated with frailty, although its prognostic significance in CLI patients is unknown. In this study, we aimed to determine the prevalence of hyperpolypharmacy among adults with CLI and its effect on 1-year amputation and mortality. METHODS: A total of 200 patients with CLI who underwent endovascular therapy (EVT) for below-knee (CTC) lesions were included in this study. Hyperpolypharmacy was defined as using ≥10 drugs. Patients were divided into two groups according to the presence of hyperpolypharmacy. RESULTS: We detected hyperpolypharmacy in 66 patients. The incidence of 1-year amputation [24 (36.4) versus 12 (9), p<.001] and mortality [28 (42.4) versus 12 (9), p<.001] were higher in patients with hyperpolypharmacy. Univariate and multivariate cox regression analyses were used to determine the independent predictors of amputation and mortality. In the receiver operating characteristic curve analysis, the cut-off value was defined as 10 or more drug use was able to detect the presence of 1-year mortality with 67.5% sensitivity and 79.4% specificity. The Kaplan-Meier method showed a significant difference (rank p <.001 between log groups), and hyperpolypharmacy was associated with 1-year amputation and mortality. CONCLUSION: Hyperpolypharmacy was significantly associated with 1-year mortality and major amputation in CLI patients. Hyperpolypharmacy can be a valuable aid in patient risk assessment in the CLI.

Evaluation of three nutritional indices as predictors of 2-year mortality and major amputation in patients with chronic limb-threatening ischemia.

OBJECTIVE: The present study aimed to examine which nutritional index, such as the controlling nutritional status (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), is better for predicting prognosis in patients with chronic limb-threatening ischemia (CLTI) following revascularization. METHOD: We retrospectively analyzed data of patients who underwent revascularization for CLTI between 2008 and 2020. The endpoints were 2-year overall survival and limb salvage. The optimal cutoff values of 2-year overall survival and major amputation were determined by receiver operating characteristic curve analyses. RESULT: A total of 238 patients with CLTI and 289 limbs were analyzed. The 2-year overall survival rates were 48.9%, 54.6%, and 53.5% in patients with CONUT score ≥4, PNI score <42.6, and GNRI <98.4 compared with 80.0%, 80.0%, and 78.4% in patients with CONUT score <4, PNI score ≥42.6, and GNRI ≥98.4 (p < 0.01). Age, non-ambulatory status, hemodialysis, and nutritional indices were independent risk factors for 2-year mortality in the multivariate analyses. The 2-year limb salvage rates were 70.1%, 82.2%, and 81.9% in patients with CONUT score ≥7, PNI score <41.9, and GNRI <95.3 compared with 92.8%, 98.3%, and 94.2% in patients with CONUT score <7, PNI score ≥41.9, and GNRI ≥95.3 (p < 0.01). Wound, ischemia, and foot infection stage and each nutritional index (CONUT and PNI) were independent risk factors for major amputation in multivariate analyses. The overall survival and limb salvage rates of patients with malnutrition diagnosed by CONUT score were poor compared with those of normal nutrition or malnutrition diagnosed by PNI and/or GNRI scores. CONCLUSION: The CONUT, PNI, and GNRI scores can predict the 2-year overall survival in patients with CLTI after revascularization. The CONUT and PNI scores were associated with major amputation.

Salami-Tactics: when is it time for a major cut after multiple minor amputations?

INTRODUCTION: Repetitive minor amputations carry the concomitant risks of multiple surgical procedures, major amputations have physical and economical major drawbacks. The aim of this study was to evaluate whether there is a distinct number of minor amputations predicting a major amputation in the same leg and to determine risk factors for major amputation in multiple minor amputations. MATERIALS AND METHODS: A retrospective chart review including 429 patients with 534 index minor amputations between 07/1984 and 06/2019 was conducted. Patient demographics and clinical data including number and level of re-amputations were extracted from medical records and statistically analyzed. RESULTS: 290 legs (54.3%) had one or multiple re-amputations after index minor amputation. 89 (16.7%) legs needed major amputation during follow up. Major amputation was performed at a mean of 32.5 (range 0 - 275.2) months after index minor amputation. No particular re-amputation demonstrated statistically significant elevated odds ratio (a.) to be a major amputation compared to the preceding amputation and (b.) to lead to a major amputation at any point during follow up. Stepwise multivariate Cox regression analysis revealed minor re-amputation within 90 days (HR 3.8, 95% CI 2.0-7.3, p <0.001) as the only risk factor for major amputation if at least one re-amputation had to be performed. CONCLUSIONS: There is no distinct number of prior minor amputations in one leg that would justify a major amputation on its own. If a re-amputation has to be done, the timepoint needs to be considered as re-amputations within 90 days carry a fourfold risk for major amputation. LEVEL OF EVIDENCE: Retrospective comparative study (Level III).

Demographics and Etiology for Lower Extremity Amputations-Experiences of an University Orthopaedic Center in Germany.

Background and Objectives: Currently, the worldwide incidence of major amputations in the general population is decreasing whereas the incidence of minor amputations is increasing. The purpose of our study was to analyze whether this trend is reflected among orthopaedic patients treated with lower extremity amputation in our orthopaedic university institution. Materials and Methods: We conducted a single-center retrospective study and included patients referred to our orthopaedic department for lower extremity amputation (LEA) between January 2007 and December 2019. Acquired data were the year of amputation, age, sex, level of amputation and cause of amputation. T test and Chi² test were performed to compare age and amputation rates between males and females; significance was defined as p < 0.05. Linear regression and multivariate logistic regression models were used to test time trends and to calculate probabilities for LEA. Results: A total of 114 amputations of the lower extremity were performed, of which 60.5% were major amputations. The number of major amputations increased over time with a rate of 0.6 amputation/year. Men were significantly more often affected by LEA than women. Age of LEA for men was significantly below the age of LEA for women (men: 54.8 ± 2.8 years, women: 64.9 ± 3.2 years, p = 0.021). Main causes leading to LEA were tumors (28.9%) and implant-associated complications (25.4%). Implant-associated complications and age raised the probability for major amputation, whereas malformation, angiopathies and infections were more likely to cause a minor amputation. Conclusions: Among patients in our orthopaedic institution, etiology of amputations of the lower extremity is multifactorial and differs from other surgical specialties. The number of major amputations has increased continuously over the past years. Age and sex, as well as diagnosis, influence the type and level of amputation.

Scoring Model to Predict Major Amputation in Patients With Chronic Limb-Threatening Ischemia at Wound, Ischemia, and Foot Infection Clinical Stage 4 After Endovascular Therapy.

PURPOSE: We investigated the predictors of major amputation (MA) at 1 year and prepared a scoring model to stratify the clinical outcomes of chronic limb-threatening ischemia (CLTI) patients at wound, ischemia, and foot infection (WIfI) clinical stage 4 after endovascular therapy (EVT). MATERIALS AND METHODS: This study was a retrospective, observational study performed at a single center. A total of 353 CLTI patients (390 limbs) were treated with EVT between April 2007 and December 2016. Among these, limbs at WIfI clinical stages 1, 2, and 3 were excluded, and 194 limbs at WIfI clinical stage 4 (49.7%) were enrolled. The primary endpoint was major amputation (MA) free rate at 1 year. Predictors of MA at 1 year was evaluated by Cox proportional hazard analysis. RESULTS: At 1 year, the incidence of MA was 18.0% (35 limbs). Cox proportional hazard analysis revealed that hemodialysis (hazard ratio [HR] 2.63; 95% confidence interval [CI], 1.24-5.58; p=0.012), fI3 (HR 2.54; 95% CI, 1.28-5.06; p=0.008), toe wounds (HR 0.29; 95% CI, 0.094-0.88; p=0.029), and visible blood flow to the wound (HR 0.43; 95% CI, 0.21-0.89; p=0.023) were associated with MA. We assigned 1 point for positive predictors of MA, hemodialysis, and fI3; 1 point was deducted for negative predictors of MA, toe wounds, and visible blood flow to the wound. A score of -2 or -1, was defined as the low-risk group, 0 was defined as the intermediate-risk group, and +1 or +2 were defined as the high-risk group. At 1 year, MA free rate, wound healing rate, and amputation-free survival rate were stratified according to a scoring model. MA free rate was 96.6% in low-risk, 72.4% in intermediate-risk, and 67.3% in high-risk (p<0.001); wound healing rate was 67.8% in low-risk, 27.6% in intermediate-risk, and 4.1% in high-risk (p<0.001); amputation-free survival rate was 65.3% in low-risk, 44.8% in intermediate-risk, and 18.4% in high-risk (p<0.001). CONCLUSIONS: The scoring model based on the predictors of MA stratified clinical outcomes in CLTI patients at WIfI clinical stage 4.

Epidemiology and Prognostic Factors in Acute Lower Limb Ischaemia: A Population Based Study.

OBJECTIVE: The aim of this study was to evaluate the contemporary population based incidence of acute lower limb ischaemia (ALI) and factors associated with major amputation/death at one year. METHODS: In this retrospective observational study, in hospital, operation, radiological, and autopsy registries were scrutinised to capture 161 citizens of Malmö, Sweden, with ALI between 2015 and 2018. Age and sex specific incidence rates were calculated in the population of Malmö between 2015 and 2018, expressed as number of patients per 100 000 person years (PY). Independent risk factors for major amputation/death at one year were identified by multivariable logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: One hundred and sixty-one patients with ALI gave an overall incidence of 12.2/100 000 PY (95% CI 10.3 - 14.1), with no sex related differences. Embolism (42.2%) was the most common cause of ALI. Among 52 patients with atrial fibrillation, 38.5% were on anticoagulant medication. Endovascular or open vascular revascularisation was performed in 54.7% of patients. The total cause specific mortality ratio was 2.63 (95% CI 1.66 - 3.61)/1 000 deaths, without no sex related differences. The combined major amputation/mortality rate at one year for the whole cohort was 46.6%. Rutherford ≥ IIb ALI (OR 4.19, 95% CI 1.94 - 9.02; p < .001), age (OR 1.03/year, 95% CI 1.00 - 1.06; p = .036), female sex (OR 2.37, 95% 1.07 - 5.26; p = .034), and anaemia (OR 2.46, 95% CI 1.08 - 5.62; p = .033) were associated with an increased risk of major amputation/death at one year. The major amputation/mortality rate at one year was 100% (n = 14/14) for patients living in a nursing home on admission. CONCLUSION: The incidence of ALI appears to be unchanged, and major amputation and mortality at one year remain high. It is necessary to include the substantial proportion of patients with ALI that do not undergo revascularisation in epidemiological studies. There is room for improvement in anticoagulation therapy in patients with atrial fibrillation to prevent ALI due to embolism. Research on gender inequalities in patients with ALI is warranted.

Cohort Study Examining the Association of Immunosuppressant Drug Prescription With Major Adverse Cardiovascular and Limb Events in Patients With Peripheral Artery Disease.

AIM: Immune activation is strongly implicated in atherosclerotic plaque instability, however, the effect of immunosuppressant drugs on cardiovascular events in patients with peripheral artery disease (PAD) is not known. The aim of this study was to assess whether prescription of one or more immune suppressant drugs was associated with a lower risk of major adverse cardiovascular (MACE; i.e. myocardial infarction, stroke or cardiovascular events) or limb events (MALE; i.e. major amputation or requirement for peripheral revascularization) in patients with PAD. METHODS: A total of 1506 participants with intermittent claudication (n = 872) or chronic limb threatening ischemia (CLTI; n = 634) of whom 53 (3.5%) were prescribed one or more immunosuppressant drugs (prednisolone 41; methotrexate 17; leflunomide 5; hydroxychloroquine 3; azathioprine 2; tocilizumab 2; mycophenolate 1; sulfasalazine 1; adalimumab 1) were recruited from 3 Australian hospitals. Participants were followed for a median of 3.9 (inter-quartile range 1.2, 7.3) years. The association of immunosuppressant drug prescription with MACE or MALE was examined using Cox proportional hazard analyses. RESULTS: After adjusting for other risk factors, prescription of an immunosuppressant drug was associated with a significantly greater risk of MACE (Hazard ratio, HR, 1.83, 95% confidence intervals, CI, 1.11, 3.01; P = 0.017) but not MALE (HR 1.32, 95% CI 0.90, 1.92; P = 0.153). In a sub-analysis restricted to participants with CLTI findings were similar: MACE (HR 2.44, 95% CI 1.32, 4.51; P = 0.005); MALE (HR 1.38, 95% CI 0.87, 2.19; P = 0.175); major amputation (HR 1.37, 95% CI 0.49, 3.86; P = 0.547). CONCLUSIONS: This cohort study suggested that immunosuppressant drug therapy is associated with a greater risk of MACE amongst patients with PAD.

Pneumatic tourniquet versus no tourniquet in transfemoral amputation - a study protocol for a randomized controlled trial.

BACKGROUND: Lower extremity amputation patients represent a frail group with extensive comorbidity. Transfemoral amputation is a high-risk procedure with 37-50% risk of mortality in the first year. Substantial blood loss during surgery increases the risk of anemic complications and death for these already weakened patients. The use of tourniquet during surgery may reduce blood loss, the need for blood transfusions, the related complications as well as the length of the surgery. However the use of tourniquet may be related to impaired wound healing and hence the use should be investigated in a randomized controlled trial. The primary aim of this study is to investigate the total blood loss and secondary to investigate differences in complications after transfemoral amputation between patients operated with or without tourniquet. METHODS: The total blood loss is calculated using Nadlers approach. Based on data from a pilot series, the sample size was calculated to 124, allocated 1:1 in two groups of 62 participants to ensure detection of at least 200 mL difference in the total blood loss. The primary outcome is the total blood loss. Secondary outcomes are blood transfusions, duration of surgery, length of hospital stay and risk of complications within 90 days (re-admissions, re-operations and mortality). Explorative outcomes are 1 year mortality and re-operation risk. Further explorative outcomes are postoperative quality of life (questionnaire EQ-5D-5L) and evaluation of number of prosthesis users including evaluation of prosthesis-specific function measured 3, 6, and 12 months postoperatively. DISCUSSION: The possibility to enhance patient safety is highly relevant and this trial will provide data for evidence based recommendations of best practice in amputation surgery. TRIAL REGISTRATION: The trial is registered on ClinicalTrials.gov with ID: NCT05550623. Initial release: 13/09 2022.

Endovascular treatment of calcific lesions of the common femoral artery using atherectomy device associated with scoring balloon angioplasty in diabetic patients with high "major amputation" risk.

OBJECTIVES: To investigate the outcomes of patients with calcific lesions in the common femoral artery undergoing endovascular procedures with atherectomy device and scoring balloon angioplasty combined with treatment of steno-occlusive disease of the remaining arterial districts of the lower limb. METHODS: Between January 2015 and December 2018, 11 diabetic patients at high risk for "major amputation", with calcific lesions of the common femoral artery and ischemic ulcers requiring endovascular treatment were retrospectively evaluated. Technical success was defined as revascularization of the common femoral artery with a residual stenosis lower than 30%. Primary endpoints were an immediate increase of perilesional transcutaneous oxygen pressure (TCPO2) > 40 mmHg, ulcerative lesions improvement up to healing or skin flaps re-epithelialization after minor amputation, limb rescue with rejected major amputation, and resolution of rest pain if present. RESULTS: The success rate of the revascularization procedures was 100%. No patient underwent surgical conversion. One case of peri-operative bleeding at the brachial access site was observed. There were no cases of arterial dissection or undesired distal embolization. The average baseline value of perilesional TCPO2 was 21.8 ± 9.2 mmHg. The mean TCPO2 value was 57.4 ± 7.2 mmHg three days after the procedure (P < 0.05), and 51.2 ± 9.8 mmHg 15 days after (P < 0.05). Minor amputations were performed in five patients with advanced ulcerative lesions. No major amputations were performed in the follow-up period. At 14 months follow-up, one patient developed new occlusion of the CFA for extension from the external iliac artery and underwent a new endovascular procedure. We observed an overall primary patency rate of 91% and a primary assisted patency rate of 100% in our 18-month follow-up. CONCLUSIONS: Endovascular approach for severely calcified atherosclerotic lesions of the common femoral artery seems to represent a valid therapeutic option associated with promising results in terms of clinical outcome and low complication rates.

The impact of an angiosome-targeted revascularization on healing rate, limb salvage and survival in critical limb threatening ischemia.

OBJECTIVE: According to the angiosome concept ulcer healing and limb salvage should be superior if direct arterial flow to the source vessel of an affected angiosome is established compared to indirect flow where the angiosome is perfused by means of collaterals. The objective of this study was to evaluate the impact of direct versus indirect revascularization (DR/IR) in endovascular versus bypass surgery on ulcer healing, limb salvage and mortality. MATERIALS AND METHODS: A retrospective analysis of both endovascular and bypass distal (below the knee) lower limb revascularizations for chronic limb-threatening ischemia (CLTI) between 1993 and 2014 was performed. RESULTS: The study population consisted of 126 endovascular and 198 bypass procedures. DR and IR were achieved in 57.4% and 42.6% limbs respectively. DR was not superior to IR regarding all three major endpoints when endovascular and bypass procedures were analyzed separately. Endovascular and bypass procedures resulted in comparable healing rates. All patients who did not achieve wound healing (HR 7.49; 95% CI 4.25-13.20, p = .0001) or needed to be treated with a bypass (HR 1.79; 95% CI 1.05-3.05, p = .034) were at an increased risk for major amputation. Increased mortality rate was noted after endovascular procedures (HR 1.45; 95% CI 1.04-2.00, p = .026). CONCLUSION: This retrospective study with comparable results for DR and IR did not support the angiosome concept. Achieving wound healing remains critical in patients with CLTI to reduce major amputation rates. Overall the implications of the angiosome concept seem to be limited due to its feasibility in patients with CLTI.

Outcomes in patients with chronic leg wounds in Denmark: A nationwide register-based cohort study.

This study aimed to investigate incidence and predictors of wound healing, relapse, major amputation, and/or death among patients with chronic leg wounds who were referred to specialist treatment at hospital for their condition. A nationwide register-based cohort study design was applied with 5 years of follow-up. All patients with diagnoses of chronic leg wounds in Denmark between 2007 and 2012 were included (n = 8394). Clinical, social, and demographic individual-level linked data from several Danish national registries were retrieved. Incidence rate per 1000 person-years (PY) was calculated. Predictors were investigated using Cox proportional hazards regression analysis. Incidence rates of having a healed wound was 236 per 1000 PY. For relapse, the incidence rate was 75 per 1000 PY, for amputation 16 per 1000 PY, and for death 100 per 1000 PY. Diabetes, peripheral arteria disease, or other comorbidities were associated with decreased chance of wound healing and increased risk of relapse, major amputation, and death. Regional differences in all four outcomes were detected. Basic or vocational education independently predicted risk of amputation and death. This study provides epidemiological data that may help identify patients at particular risk of poor outcomes. It also elucidates social inequality in outcomes.

The perioperative and long-term fates of patients with chronic limb-threatening ischaemia who underwent secondary major amputations.

This study investigated the perioperative and long-term fates of patients with chronic limb-threatening ischemia (CLTI) who underwent secondary major amputations. From April 2010 to December 2018, 1653 CLTI patients primarily underwent endovascular therapy (EVT). Of these patients, 138 who underwent secondary major amputations were included in this study. The primary outcome measure was the mortality. Prognostic factors associated with perioperative (30-day) and late mortality (after 30 days) were assessed. The 30-day mortality was 9.6%. Patients who died during the perioperative period had lower ejection fractions on echocardiography than those in the perioperative survivors (49.5 ± 14.9% vs 58.6 ± 12.4%, P = .018). None of the other clinical characteristics were significantly associated with perioperative death. Two-years postoperatively, 49.6%, 12.2%, and 4.3% of the patients had died, had contralateral amputations, and had additional above-knee amputations, respectively. In the alive patients who had not undergone additional amputation at 2 years, only 25.9% were ambulatory, whereas 51.7% and 22.4% were in wheelchairs and bedridden, respectively. An age ≥80 years and serum albumin <3.0 g/dL were significantly associated with late mortality (P = .032 and P = .042, respectively). In conclusion, the perioperative and long-term fates after secondary major amputation in CLTI patients who underwent EVT were considerably poor.