Risk Of Major Amputation Research Articles

Effectiveness of most common adjuvant wound treatments (skin substitutes, negative pressure wound therapy, hyperbaric oxygen therapy, platelet-rich plasma/fibrin, and growth factors) for the management of hard-to-heal diabetic foot ulcers: a meta-analysis of randomized controlled trials for the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome.

To assess the effects of several adjuvant therapies (AT) commonly used in the treatment of diabetic foot ulcers (DFU). The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome. A Medline and Embase search were performed up to May 20th, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with DFU comparing AT with placebo/standard of care (SoC), with a duration of at least 12weeks. Prespecified endpoints were: ulcer healing (principal), time-to-healing, major and minor amputation, serious adverse events (SAE), and all-cause mortality. AT assessed were: growth factors (GF), Platelet-rich plasma and fibrin (PRP/F), skin substitutes (SS), negative pressure wound therapy (NPWT), and hyperbaric oxygen therapy (HBOT). Mantel-Haenzel Odds ratios and 95% confidence intervals (MH-OR, 95% CIs) were either calculated or extracted directly from the publications. Weighted mean differences and 95% CIs were calculated for continuous variables. Fifty-one studies fulfilled all inclusion criteria (3, 5, 27, 8, and 8 with GF, PRP/F, SS, NPWT, and HBOT, respectively). Participants treated with any of the explored AT had a significantly higher ulcer healing rate (MH-OR ranging from 2.17 to 4.18) and shorter time-to-healing in comparison with SoC/placebo. Only PRP/F and HBOT showed a significantly lower risk of major amputation (MH-OR: 0.32(0.11;0,93; p = 0.04 and 0.28(0.10;0,79; p = 0.02, respectively), despite a higher risk of SAE. No other significant effects on the above-reported prespecified endpoints were observed. For the primary endpoint, the quality of evidence was rated as "high" for all the AT, except for NPWT ("moderate"). In conclusion, AT can actively promote wound healing and shorten time-to-healing in patients with DFU. HBOT and PRP/F also showed a reduction of the risk of major amputation, despite a higher rate of SAE.

Comparison of safety and efficacy of femoropopliteal arterial disease using different dose drug-coated balloons: Systematic review and meta-analysis.

Endovascular therapy with balloon percutaneous angioplasty (PTA) in the femoro-popliteal segment is frequently performed, however, long-term favorable outcomes and patency remain challenging, with restenosis rates reaching 60% post-standard balloon angioplasty. Drug-coated balloons (DCBs) have shown promise in improving these outcomes; Paclitaxel, used in DCBs, inhibits hyperplasia and smooth muscle cell proliferation, reducing restenosis; however, the optimal dose of Paclitaxel remains unclear, with high-dose (HD-DCB [>3mg/mm2]) and low-dose (LD-DCB [<2.0mg/mm2]) options available. This meta-analysis aims to compare the efficacy and safety of HD-DCB and LD-DCB in treating femoropopliteal arterial disease. We followed PRISMA guidelines and conducted a comprehensive search of PubMed, EMBASE, Cochrane, Scopus, and Mendeley up to May 27, 2024. We included randomized controlled trials and cohort studies comparing HD-DCB and LD-DCB in patients with femoropopliteal arterial disease. Data were extracted on baseline characteristics, outcomes, and study quality. The Newcastle-Ottawa Scale and ROB2 tool were used for bias assessment. Outcomes included overall survival (OS), limb salvage (LS), freedom from clinically driven target lesion revascularization (CD-TLR), and major amputation. Six studies comprising 2563 patients were included. HD-DCB showed a significant benefit in limb salvage at 6 months (RR = 0.38, 95% CI = 0.18-0.78, p = .009) but not at 12 months (RR = 3.08, 95% CI = 0.14-67.13, p = .47). No significant difference was observed in overall survival between HD-DCB and LD-DCB at either 6 months (RR = 1.53, 95% CI = 0.25-9.57, p = .65) or 12 months (RR = 1.21, 95% CI = 0.17-8.84, p = .85). HD-DCB was associated with an increased risk of perioperative complications (RR = 1.90, 95% CI = 1.14-3.17, p = .01) and a higher, though not statistically significant, risk of major amputation (RR = 4.73, 95% CI = 0.54-41.52, p = .16). HD-DCB may offer advantages in limb salvage over LD-DCB in the short term, but this comes with an increased risk of perioperative complications. These findings underscore the need for careful patient selection when considering HD-DCB for femoropopliteal artery disease.

Advanced WIfI Stage is Associated with Poor Outcomes in the BEST-CLI Trial

Wound, ischemia, and foot infection (WIfI) staging was established to provide objective classification in patients with chronic limb threatening ischemia (CLTI) and to predict 1-year major amputation risk. Our goal was to validate WIfI staging using data from the Best Endovascular versus Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial. Data from the BEST-CLI Trial, a prospective randomized trial comparing surgical (OPEN) and endovascular (ENDO) revascularization, were used to assess the association of WIfI stage on long-term outcomes in an intention to treat analysis. Patients were prospectively allocated to two cohorts - cohort 1 and 2 - which included patients with and without adequate single segment greater saphenous vein (SSGSV), respectively. The primary outcome of this analysis was major amputation. There were 1,568 patients analyzed, representing 86% of the entire trial population; of these 35.5%, 29.6% and 34.9% were categorized as WIfI 4, WIfI 3, and WIfI 1/2, respectively. There were 1223 patients (606 OPEN, 617 ENDO) and 345 patients (OPEN 172, ENDO 173) in cohorts 1 and 2, respectively. On unadjusted Kaplan-Meier analysis, WIfI clinical stages 4 and 3, compared to WIfI 1/2, were associated with higher rates of major amputation (21.4%, 16.2% vs. 10.7%), death (33.5%, 35.7% vs. 24.6%), amputation/death (44.9%, 44.5% vs. 31.3%), MALE/death (34.4%, 33.9% vs. 29.5%), and reintervention/amputation/death (69.9% vs. 69% vs. 60.4%) (P<.05 for all) at 3 years. On risk adjusted analysis, compared to WIfI 1/2, major amputation was associated with WIfI 4 (HR 2.06, 95% CI 1.44 - 2.96, P<.001) and WIfI 3 (HR 1.62, 95% CI 1.1-2.37, P=.013) stages. Death was associated with both WIfI 4 (HR 1.3, 95% CI 1.03 - 1.63, P=.027) and WIfI 3 (HR 1.42, 95% CI 1.13-1.79, P=.003). MALE/death was associated with WIfI 4 (HR 1.29, 95% CI 1.02 - 1.63, P=.036. Reintervention amputation/death was associated with WIfI 4 (HR 1.28, 95% CI 1.09 - 1.50, P=.03) and WIfI 3 (HR 1.22, 99% CI 1.03 - 1.43), P=.018). When examining OPEN vs. ENDO revascularization by each WIfI stage, OPEN intervention was favored in cohort 1 for MALE/death for each stage. In BEST-CLI WIfI stage was strongly associated with major amputations, death, and MALE/death after revascularization for CLTI. Cohort 1 patients, with adequate preoperative SSGSV, had lower MALE/death with OPEN intervention across all WIfI stages. This validation of WIfI score in a prospective multicenter trial reinforces its importance in shared-decision making, informed consent, and prognostication.

Limb Preservation Program and Peripheral Arterial Disease

Limb – derived from the old English ‘Lim’. A paired parts (Arm, Leg and Wing) of human that stick out/extends from the trunk of a body. Limb preservation refers to the crucial steps taken in order to save a damaged limb from amputation. Amputation of a limb may be needed when there is serious infection a wound that won’t heal or poor circulation that causes tissue to die. Patients with vascular disease are at high risk for foot and leg wounds that do not heal and may ultimately require amputation to save their lives. Severe cases of Peripheral Artery Disease (PAD) can cause irreversible tissue damage and increase the risk for amputation if not treated. The Limb Preservative Program focuses on saving limbs and also on the overall health and well being of the patient. Limb-Preservation Program (LPP) requires coordinated effort by clinicians, nurses, allied health professionals and administrators dedicated to the cause of saving and maintaining functional limbs. This is a significant consideration because over 1.5 million people live after the loss of a limb; this number is expected to increase due to the aging of the population and the worldwide exponential rise in diabetes mellitus. Peripheral Arterial Disease (PAD) is one the important cause of limb amputation. The prevalence of PAD continues to increase worldwide. It is important to identify patients with PAD because of the increased risk of myocardial infarction, stroke and cardiovascular death and impaired quality of life because of a profound limitation in exercise performance. Lower extremity PAD affects approximately 10% of population, with 30% to 40% of these patients presenting with claudication symptoms. Peripheral arterial disease is common, but the diagnosis frequently is overlooked because of subtle physical findings and lack of classic symptoms. Screening based on the ankle brachial index using doppler ultrasonography may be more useful than physical examination alone. Noninvasive modalities to locate lesions include duplex scanning, computed tomography angiogram, magnetic resonance angiography and invasive modalities peripheral angiogram is the gold standard. Major risk factors for peripheral arterial disease are cigarette smoking, diabetes mellitus, older age (Older than 40 years) hypertension, hyperlipidemia and hyperhomocystinemia. Intermittent claudication may be improved by risk-factor modification, exercise and pharmacologic therapy. Based on available evidence, a supervised exercise program is the most effective treatment. Effective drug therapies for peripheral arterial disease include aspirin (With or without dipyridamole) clopidogrel, cilostazol, and pentoxifylline. By contrast, Critical Limb Ischemia (CLI) is considered the most severe pattern of peripheral artery disease. It is defined by the presence of chronic ischemic rest pain, ulceration or gangrene attributable to the occlusion of peripheral arterial vessels. It is associated with a high risk of major amputation, cardiovascular events and death. The management of CLI should include an exercise program, guideline-based medical therapy to lower the cardiovascular risk. Most of the cases, revascularization is indicated to save limbs, an “Endovascular First” approach and lastly surgical approach if all measures were failed. The choice of the intervention is dependent on the anatomy of the stenotic or occlusive lesion, percutaneous interventions are appropriate when the lesion is focal and short but longer lesions must be treated with surgical revascularization to achieve acceptable long-term outcome. A LPP should include a patient support group as there is a significant mental component to loss of limb or living with a foot ulcer. A patient support group can be very important both preoperatively and postoperatively in helping patients deal with the clinical situation in maintaining functionality and mentaloutlook. Education can be incorporated into the program in the form of seminars for patients and referring physicians. Education is critical to achieve the goal of limb preservation through the reduction of amputation and enhancement of the patient’s quality of life. The LPP also provides a format for research that is increasingly important to the healthcare system. Chatt Maa Shi Hosp Med Coll J; Vol.22 (2); July 2023; Page 1-2

Autologous cell therapy for ischemic diabetic foot: a meta-analysis of randomized controlled trials for the development of the Italian guidelines for the treatment of diabetic foot syndrome.

To assess the efficacy and safety of autologous cell therapy (ACT) in patients with ischemic diabetic foot ulcers (DFU). The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome (DFS). A Medline and Embase search were performed up to Feb 1st, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with ischemic foot ulcers comparing ACT with placebo/no therapy/standard of care (SoC), with a duration of at least 26 weeks. Prespecified endpoints were: major amputation (principal) and minor amputation, ulcer healing, time-to-healing, transcutaneous oxygen pressure (TcPO2), ankle-brachial index (ABI), pain, and all-cause mortality (secondary). Any ACT was allowed, irrespective of cell product type and route of administration (intra-arterial and intramuscular). Seven studies fulfilled all inclusion criteria, all using intramuscular transplantation as route of administration, but only 2 had a follow-up greater than 26 weeks. Participants treated with ACT had a significantly lower risk of major amputations in comparison with SoC/placebo (MH-OR 0.47 [0.24, 0.92], p = 0.03). ACT was also associated with a significantly higher rate of ulcer healing (MH-OR: 10.1 [3.5, 29.6], p < 0.001), greater increase of TcPO2 and ABI values (WMD: 17.57 [13.02, 22.12], p < 0.001), and reduction of pain (WMD: -1.83 [-2.32, -1.34], p = 0.003). ACT must be considered as a potential therapy for patients with ischemic diabetic foot ulcers. Further studies are needed to better clarify their role in the treatment and management of DFS.

Improved Diabetic Foot Ulcer Outcomes in Medicaid Beneficiaries with Podiatric Care Access.

This study aims to examine the association between state Medicaid coverage of podiatry services and the outcomes of beneficiaries with new diabetic foot ulcers (DFUs). Medicaid beneficiaries who developed a DFU between 2010 and 2015 were identified using the PearlDiver claims database. The states were categorized into covered states (CS) and non-covered states (NCS) based on podiatric coverage during the study period. The outcomes included major amputation, minor amputation, and hospitalization due to foot infection within 12 months of index diagnosis. Logistic regression was used to assess the association of state coverage type and outcomes, controlling for age, sex, and the Charlson Comorbidity Index (CCI). Our study included 16,905 Medicaid beneficiaries who developed new DFUs: 14,748 in CS and 2157 in NCS. The overall major amputation rate was 2.6%. The risk of major amputation was 48% lower among Medicaid beneficiaries in CS (OR 0.52, 95% CI 0.31-0.90) than in NCS. The Medicaid beneficiaries in CS had a 24% lower risk of hospitalization for foot infection (OR 0.76, 95% CI 0.67-0.85) but had a 58% higher risk of minor amputation (OR 1.58, 95% CI 1.22-2.07) than in NCS. Medicaid coverage of podiatry services might be associated with lower rates of major amputation and reduced risk of hospitalization for foot infection.

Competing risk analysis to estimate amputation incidence and risk in lower-extremity peripheral artery disease.

Background: Patients with peripheral artery disease face high amputation and mortality risk. When assessing vascular outcomes, consideration of mortality as a competing risk is not routine. We hypothesize standard time-to-event methods will overestimate major amputation risk in chronic limb-threatening ischemia (CLTI) and non-CLTI. Methods: Patients undergoing peripheral vascular intervention from 2017 to 2018 were abstracted from the Vascular Quality Initiative registry and stratified by mean age (⩾ 75 vs < 75 years). Mortality and amputation data were obtained from Medicare claims. The 2-year cumulative incidence function (CIF) and risk of major amputation from standard time-to-event analysis (1 - Kaplan-Meier and Cox regression) were compared with competing risk analysis (Aalen-Johansen and Fine-Gray model) in CLTI and non-CLTI. Results: A total of 7273 patients with CLTI and 5095 with non-CLTI were included. At 2-year follow up, 13.1% of patients underwent major amputation and 33.4% died without major amputation in the CLTI cohort; 1.3% and 10.7%, respectively, in the non-CLTI cohort. In CLTI, standard time-to-event analysis overestimated the 2-year CIF of major amputation by 20.5% and 13.7%, respectively, in patients ⩾ 75 and < 75 years old compared with competing risk analysis. The standard Cox regression overestimated adjusted 2-year major amputation risk in patients ⩾ 75 versus < 75 years old by 7.0%. In non-CLTI, the CIF was overestimated by 7.1% in patients ⩾ 75 years, and the adjusted risk was overestimated by 5.1% compared with competing risk analysis. Conclusions: Standard time-to-event analysis overestimates the incidence and risk of major amputation, especially in CLTI. Competing risk analyses are alternative approaches to estimate accurately amputation risk in vascular outcomes research.

Streamlined Clinical Management Pathways May Reduce Major Amputations in Patients with Chronic Limb Threatening Ischaemia: A Prospective Cohort Study with Historical Controls

Patient characteristics and patterns of disease in chronic limb threatening ischaemia (CLTI) have changed markedly in recent years. Urgent specialist referral and timely revascularisation are recommended in international guidelines. UK guidelines now recommend revascularisation within 5 days of referral for inpatients and 2 weeks in outpatients. This study compared the contemporary one year major amputation incidence in patients with CLTI with a historical cohort at a single UK centre. This was a single centre, observational cohort study with historical controls. A prospective cohort was recruited between May 2019 and March 2022. A historical cohort presenting between 2013 and 2015 inclusive was identified retrospectively. Significant changes in management pathways, including establishing a rapid access limb salvage clinic, occurred between these periods aiming to expedite time from referral to revascularisation. The one year primary outcome was major amputation, and the secondary outcome was death. Major amputation was analysed by Fine-Gray competing risks models (death as the competing risk), presented as subdistribution hazard ratios (SHRs). One year mortality was analysed by Cox regression, presented as hazard ratios. Analyses were adjusted for propensity score. A total of 928 patients were included (432 prospective and 496 historical). Proportions of patients presenting with tissue loss (72.2% vs. 71.6%; p = .090) were similar in both cohorts. At one year, 48 patients (11.1%) in the prospective cohort and 124 patients (25.0%) in the historical cohort had undergone a major amputation (p < .001). Risk of major amputation was 57.0% lower in the prospective cohort compared with the historical cohort after adjustment for propensity score (SHR 0.43, 95% confidence interval 0.29 - 0.63; p < .001). An encouraging reduction in major amputation incidence was observed after improvements to CLTI management pathways, but residual confounding is likely. The generalisability of these results is uncertain.

Early Tissue Resection Versus Watchful Waiting After Revascularization for Chronic Limb-Threatening Ischemia: A Meta-Analysis.

No consensus or guideline has been established regarding the optimal timing of tissue resection after revascularization in patients with chronic limb-threatening ischemia (CLTI). This study aimed to compare early tissue resection and watchful waiting after revascularization regarding the outcomes of patients with CLTI. We searched PubMed, the Cochrane Library, and EMBASE for relevant randomized trials and observational studies published from their inception to May 1, 2024. In total, five articles were analyzed. The results showed that the early tissue resection group had a higher wound healing rate than the watchful waiting group (I2 = 26%, odds ratio [OR] = 2.80, 95% confidence interval [CI] 1.32 to 5.92, P = 0.007). However, the rate of major amputation was significantly higher in the early tissue resection group than in the watchful waiting group (I2 = 5%, OR = 1.48, 95% CI 1.18 to 1.86, P < 0.001), and wound recurrence rate in the early tissue resection group was relatively higher than that in the watchful waiting group (I2 = 0%, OR = 2.42, 95% CI: 0.99 to 5.93, P = 0.05). No statistical significance was found in the rate of postoperative mortality (I2 = 2%, OR = 0.99, 95% CI: 0.69 to 1.41, P = 0.94) and wound healing time (I2 = 97%, standardized mean difference = -105.92, 95% CI -232.96 to 21.13, P = 0.10) between the early tissue resection and watchful waiting groups. For patients without signs of infection, a watchful waiting strategy could reduce the risk of major amputation.

Outcomes for Patients with Diabetic Foot Ulcers Following Transition from Medicaid to Commercial Insurance.

This study investigates the outcomes of Medicaid beneficiaries with diabetic foot ulcers (DFUs) who had transitioned to commercial insurance. We utilized the PearlDiver claims database to identify adult patients diagnosed with a new DFU between 2010 and 2019. The study cohort comprised 8856 Medicaid beneficiaries who had at least three years of continuous enrollment after DFU diagnosis. Medicaid beneficiaries who transitioned to Medicare during follow-up were excluded. Adjusted comparisons of outcomes were performed by propensity matching the two groups for age, gender, and Charlson Comorbidity Index (CCI) in a 1:1 ratio. We used logistic regression and Kaplan-Meier estimate to evaluate the association between insurance change (from Medicaid to commercial insurance) and major amputation. Among the 8856 Medicaid beneficiaries with DFUs, 66% (n = 5809) had transitioned to commercial insurance coverage during follow-up. The overall major amputation rate was 2.8% (n = 247), with a lower rate observed in patients who transitioned to commercial insurance compared to those with continuous Medicaid coverage (2.6% vs. 3.2%, p < 0.05). In multivariable analysis, Medicaid beneficiaries who transitioned to commercial insurance had a 27% lower risk of major amputation (study cohort: odds ratios [OR] 0.75, 95% CI 0.56-0.97, p = 0.03; matched cohort: OR 0.65, 95% 0.22, 0.55, p = 0.01) compared to those with continuous Medicaid coverage. Transitioning from Medicaid to commercial insurance may be associated with a lower risk of major amputation among Medicaid beneficiaries with DFUs.

Construction of a Prognostic Nomogram for Major Amputation Within 30 Days Postrevascularization in Patients With Acute Lower Limb Ischemia Based on 2D Perfusion Parameters.

The purpose of the study is to develop a prediction model for major amputation (MA) within 30 days after arterial revascularization in patients with acute lower limb ischemia (ALLI) using 2-dimensional (2D) perfusion imaging parameters. A retrospective study was performed in ALLI patients undergoing arterial revascularization between October 2015 and May 2022. Patients were randomly assigned into training and validation cohorts in a ratio of 7:3. Variables were selected using univariate and multivariate logistic regression. A nomogram for the MA risk within 30 days after arterial revascularization in ALLI patients was created. Its discrimination, calibration, and clinical effectiveness were reported. A total of 310 ALLI patients (326 limbs) were included. The MA rate within 30 days after arterial revascularization was 11.6%. Skin speckle, myoglobin, and time-to-peak were independent risk factors, while atrial fibrillation was a protective factor (all p<0.05). The nomogram predicted 30-day MA with satisfactory discriminative ability. The integrated discrimination improvement was 0.279 and 0.379 for the training and validation cohorts, respectively (both p<0.001). Calibration curves were close to the standard curve. The decision curve analysis demonstrated net benefits. This 2D perfusion imaging parameter-based nomogram could accurately predict the risk of MA within 30 days postrevascularization in ALLI patients. This study introduces a novel nomogram based on 2-dimensional (2D) perfusion imaging that can significantly advance the prognosis prediction in ALLI patients. By calculating the risk of major amputation within 30 days postrevascularization, this nomogram offers an accurate predictive tool and can lead to more informed decision-making on patient management. The innovative aspect of this research lies in its utilization of 2D perfusion parameters, a novel approach that enhances risk assessment accuracy in ALLI patients. This nomogram represents a significant step toward risk stratification and can guide future research for appropriate management on ALLI patients with different risk profiles.

Illness Trajectories After Revascularization in Patients With Peripheral Artery Disease: A Unified Approach to Understanding the Risk of Major Amputation and Death.

The aim of this study was to investigate the illness trajectories of patients with peripheral artery disease (PAD) after revascularization and estimate the independent risks of major amputation and death (from any cause) and their interaction. Data from Hospital Episode Statistics Admitted Patient Care were used to identify patients (≥50 years of age) who underwent lower limb revascularization for PAD in England from April 2013 to March 2020. A Markov illness-death model was developed to describe patterns of survival after the initial lower limb revascularization, if and when patients experienced major amputation, and survival after amputation. The model was also used to investigate the association between patient characteristics and these illness trajectories. We also analyzed the relative contribution of deaths after amputation to overall mortality and how the risk of mortality after amputation was related to the time from the index revascularization to amputation. The study analyzed 94 690 patients undergoing lower limb revascularization for PAD from 2013 to 2020. The majority were men (65.6%), and the median age was 72 years (interquartile range, 64-79). One-third (34.8%) of patients had nonelective revascularization, whereas others had elective procedures. For nonelective patients, the amputation rate was 15.2% (95% CI, 14.4-16.0) and 19.9% (19.0-20.8) at 1 and 5 years after revascularization, respectively. For elective patients, the corresponding amputation rate was 2.7% (95% CI, 2.4-3.1) and 5.3% (4.9-5.8). Overall, the risk of major amputation was higher among patients who were younger, had tissue loss, diabetes, greater frailty, nonelective revascularization, and more distal procedures. The mortality rate at 5 years after revascularization was 64.3% (95% CI, 63.2-65.5) for nonelective patients and 33.0% (32.0-34.1) for elective patients. After major amputation, patients were at an increased risk of mortality if they underwent major amputation within 6 months after the index revascularization. The illness-death model provides an integrated framework to understand patient outcomes after lower limb revascularization for PAD. Although mortality increased with age, the study highlights patients <60 years of age were at increased risk of major amputation, particularly after nonelective revascularization.

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

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. 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 ± 11.27years and average body mass index of 24.45 ± 3.56kg/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. 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. 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.

Presentation and patterns of reinterventions after revascularization in patients with premature peripheral arterial disease

ObjectivePremature peripheral arterial disease (PAD) (age ≤50 years) has been shown to negatively impact the outcomes of lower extremity revascularization (LER). Patients with premature PAD have an increased risk of major amputation compared with older patients. The primary goal of this study is to compare the frequency of reinterventions after LER in patients with premature PAD to their older counterparts with common age of presentation (ie, 60-80 years). MethodsA retrospective review of consecutive patients undergoing LER for PAD in a single center was performed. Clinical, procedural, and socioeconomic characteristics were compared between patients with premature PAD and the older group. Perioperative and long-term outcomes were captured and compared including mortality, major amputation, reintervention rate and frequency, as well as major adverse limb events. ResultsThere were 1274 patients who underwent LER (4.3% premature, 61.8% age 60-80). Patients with premature PAD were more likely to be females of racial minorities. Notably, the mean Distressed Communities Index score was significantly higher in the premature PAD group compared with the older patients. Patients with premature PAD were significantly more likely to have end-stage renal disease but less likely to have hypertension, hyperlipidemia, and coronary artery disease compared with older patients. There was no significant difference in perioperative complications. After a mean follow-up of 5 years, patients with premature PAD were significantly more likely to undergo more frequent reinterventions compared with older patients. Kaplan-Meier curves showed similar overall survival and major adverse limb event-free survival between the two groups. ConclusionsPatients with premature PAD are likely to undergo more frequent reinterventions after initial LER and have similar 5-year survival curves compared with patients at least 20 years older. Demographic and socioeconomic differences impacting patients with premature PAD, even in this relatively underpowered institutional experience, are striking and warrant further investigation.

Editor's Choice – Reduction of Major Amputations after Surgery versus Endovascular Intervention: The BEST-CLI Randomised Trial

BEST-CLI, an international randomised trial, compared an initial strategy of bypass surgery with endovascular treatment in chronic limb threatening ischaemia (CLTI). In this substudy, overall amputation rates and risk of major amputation as an initial or subsequent outcome were evaluated. A total of 1 830 patients were randomised to receive surgical or endovascular treatment in two parallel cohorts: patients with adequate single segment great saphenous vein (SSGSV) (n= 1 434) were assigned to cohort 1; and patients without adequate SSGSV (n= 396) were assigned to cohort 2. Differences in time to first event and number of amputations were evaluated. In cohort 1, there were 410 (45.6%) total amputation events in the surgical group vs. 490 (54.4%) in the endovascular group (p= .001) during a mean follow up of 2.7 years. Approximately one in three patients underwent minor amputation after index revascularisation: 31.5% of the surgical group vs. 34.9% in the endovascular group (p=.17). Subsequent major amputation was required significantly less often in the surgical group compared with the endovascular group (15.0% vs. 25.6%; p= .002). The first amputation was major in 5.6% of patients in the surgical group and 6.0% in the endovascular group (p= .72). Major amputation was required in 10.3% (74/718) of patients in the surgical group and 14.9% (107/716) in the endovascular group (p= .008). In cohort 2, there were 199 amputation events in 132 patients (33.3%) during a mean follow up of 1.6 years: 95 (47.7%) in the surgical group vs. 104 (52.3%) in the endovascular group (p= .49). Major amputation was required in 15.2% (30/197) of patients in the surgical group and 14.1% (28/199) in the endovascular group (p= .74). In patients with CLTI, surgical bypass with SSGSV was more effective than endovascular treatment in preventing major amputations, mainly due to a decrease in major amputations subsequent to minor amputations.

USE OF TAQMAN ARRAY TO INVESTIGATE INFECTION IN DIABETIC FOOT WOUNDS

IntroductionDiabetic foot disease is a major public health problem with an annual NHS expenditure in excess of £1 billion. Infection increases risk of major amputation fivefold. Due to the polymicrobial nature of diabetic foot infections, it is often difficult to isolate the correct organism with conventional culture techniques, to deliver appropriate narrow spectrum antibiotics. Rapid DNA-based technology using multi-channel arrays presents a quicker alternative and has previously been used effectively in intensive care and respiratory medicine.MethodsWe gained institutional and Local Ethics Committee approval for a prospective cohort study of patients with clinically infected diabetic foot wounds. They all had deep tissue samples taken in clinic processed with conventional culture and real-time PCR TaqMan array.Results50 samples were taken from 39 patients between October 2020 and March 2022. 84% of patient were male, 88% had type 2 diabetes. The ulcers were of variable chronicity prior to sampling (range 1–113 weeks) and mean HbA1c was 67.2mmol/mol. Ulcers were on the heel (3), midfoot (6) and forefoot (41). Minimum follow up was 3 months. 6 ulcers healed, 24 patients were admitted due to foot disease, there were 2 major amputations and 4 deaths. TaqMan array results were available a mean of 4.3 days earlier than culture results. 9 patients had negative conventional cultures and 8 were negative onarray testing. 17 patients had the same organisms detected on culture and array. 16 of these 17 had additional organisms detected by array. The most frequent organisms detected on array that were not detected by culture were Staphylococcus spp., Enterobacter, Pseudomonas and fungi.ConclusionTaqMan array shows promise in detecting infecting organisms from diabetic foot wounds and providing earlier results than standard culture, which may enable appropriate and timely antibiotic therapy.

Socioeconomic disadvantage is a leading variable in risk score for major amputation following emergent infrainguinal arterial bypass surgery

ObjectiveThe purpose of this study was to identify patients at particularly high risk for major amputation after emergent infrainguinal bypass to help tailor postoperative and long-term patient management. MethodsIn the Vascular Quality Initiative, we identified 2126 patients who underwent emergent infrainguinal artery bypass. Two primary outcomes were investigated: major ipsilateral amputation above the ankle level during the index hospitalization and major amputation above the ankle at any time after emergent infrainguinal bypass surgery (perioperative and postdischarge combined). Binary logistic regression analysis was performed for each outcome using variables that achieved a univariable P value of ≤.10. We then determined which variables have a multivariable association for the outcomes as defined by a regression P value of ≤.05. A risk score was then created for the outcome of amputation after emergent infrainguinal bypass using weighted beta-coefficient. Variables with a multivariable P value of ≤.05 were included in the risk score and weighted based on their respective regression beta-coefficient in a point scale. ResultsOverall, 17.1% of patients (368/2126) underwent major amputation at some point in follow-up after emergent infrainguinal artery bypass. The mean follow-up duration on the amputation variable was 261 days with the end point being time of amputation or time of last follow-up data on the amputation variable. Variables with a significant multivariable association (P < .05) with major amputation at any point after emergent infrainguinal arterial bypass were home status in top 10% (most deprived) of Area Deprivation Index, prior infrainguinal ipsilateral arterial bypass, prior ipsilateral endovascular arterial intervention, prosthetic bypass conduit, postoperative skin/soft tissue infection, and postoperative need to revise or thrombectomize bypass. Pertinent negatives on multivariable analysis included all baseline comorbidities, insurance status, race, and gender. There is steep progression in amputation rate ranging from 5% at scores of 0 and 1 to >60% for scores in of >10. Area under the curve analysis revealed a value of 0.706. ConclusionsPatients living in the most disadvantaged socioeconomic neighborhoods have an increased risk of amputation after emergent infrainguinal arterial bypass independent of baseline comorbidities and perioperative events. Baseline comorbidities are not impactful regarding amputation rates after emergent infrainguinal bypass surgery. The need for bypass revision or thrombectomy during the index hospitalization is the most impactful factor toward amputation after emergency bypass. A risk score with quality accuracy has been developed to help identify patients at particularly high likelihood of limb loss, which may aid in counseling regarding heightened vigilance in postoperative and long-term follow-up care.

Prognostic value of leukocyte-glycemic index in long-term evolution of diabetic patients with peripheral arterial disease following endovascular treatment

Abstract Objective: The aim of this article is to determine the predictive value of the leukocyte-glycemic index in the long-term evolution of diabetic patients with peripheral arterial disease following endovascular treatment. Methods: This retrospective observational study enrolled 127 diabetic patients diagnosed with peripheral arterial disease requiring endovascular treatment. Patients were categorized into two groups based on the severity of the infrapopliteal atherosclerotic lesions identified during the pre-operative Computer Tomography Angiography examination. Group 1 includes patients without severe damage to the infrapopliteal artery, while Group 2 includes patients with severe infrapopliteal artery damage, identified by stenosis greater than 70% on all infrapopliteal arteries. The primary outcome was to assess the association between leukocyte-glycemic index value at baseline and the severity of infrapopliteal atherosclerotic lesions and long-term major amputation after percutaneous transluminal angioplasty. Results: Patients in Group 2 had a higher incidence of cardiovascular events (p=0.009), stage IV Leriche-Fontaine (p=0.016), and incidence of major amputation (p&lt;0.001), as well as an increased value of leukocyte-glycemic index (p=0.004). During the follow-up, patients with above-median leukocyte-glycemic index value have a higher risk of major amputation (p=0.034), as seen in the Kaplan-Meier analysis. Moreover, at cox-regression, elevated biomarker values were associated with long-term risk of major amputation, independent of age, sex, cardiovascular risk factors, and below-the-knee arterial occlusion (HR:2.69, p=0.001). Conclusions: Elevated values of leukocyte-glycemic index are associated with the severity of infrapopliteal atherosclerotic lesions and major amputation in the long term.

Charcot Neuro-Osteoarthropathy With Superimposed Osteomyelitis in a Nondiabetic Patient, as a Consequence of Cancer Chemotherapy: A MR-Monitored Case Report.

Charcot neuro-osteoarthropathy (CNO) is a manifestation of peripheral neuropathy as a chronic complication of diabetes mellitus but, less frequently, can be associated to other conditions such as alcoholism or neurotoxic therapies. An increasingly emerging cause of CNO is the use of oncological drugs which can cause neuropathic damage. The use of these therapies dramatically increased in recent years. CNO leads to a progressive degeneration of the foot's joints and to bone destruction and resorption which ends in deformities. These alterations in the foot's anatomy determine a high risk of ulceration, infection, and osteomyelitis. The superimposition of osteomyelitis on CNO increases the risk of major amputation, already high in patients suffering either from only CNO or osteomyelitis alone. We report the case of a 61-year old nondiabetic woman affected by CNO as a consequence of antiblastic therapy for breast cancer and the subsequent overlap of osteomyelitis, confirmed by magnetic resonance imaging. This case underlines how it is necessary to consider CNO as a possible complication of antiblastic therapy in the view of the severe consequences of missing its diagnosis.

Association Between Diagnosis-to-Limb Revascularization Time and Clinical Outcomes in Outpatients With Chronic Limb-Threatening Ischemia: Insights From the CLIPPER Cohort.

The extent and consequences of ischemia in patients with chronic limb-threatening ischemia (CLTI) may change rapidly, and delays from diagnosis to revascularization may worsen outcomes. We sought to describe the association between time from diagnosis to endovascular lower extremity revascularization (diagnosis-to-limb revascularization [D2L] time) and clinical outcomes in outpatients with CLTI. In the CLIPPER cohort, comprising patients between 66 and 86 years old diagnosed with CLTI betweeen 2010 and 2019, we used Medicare claims data to identify patients who underwent outpatient endovascular revascularization within 180 days of diagnosis. We described the risk-adjusted association between D2L time and clinical outcomes. Among 1 130 065 patients aged between 66 and 86 years with CLTI, 99 221 (8.8%) underwent outpatient endovascular lower extremity revascularization within 180 days of their CLTI diagnosis. Among patients with D2L time <30 days, there was no association between D2L time and all-cause death or major lower extremity amputation. However, among patients with D2L time >30 days, each additional 10-day increase in D2L time was associated with a 2.5% greater risk of major amputation (hazard ratio, 1.025 [95% CI, 1.014-1.036]). There was no association between D2L time and all-cause death. A delay of >30 days from CLTI diagnosis to lower extremity endovascular revascularization was associated with an increased risk of major lower extremity amputation among patients undergoing outpatient endovascular revascularization. Improving systems of care to reduce D2L time could reduce amputations.