Ischemic Tissue Loss Research Articles

Vein bypass first vs. best endovascular treatment first revascularisation strategy for chronic limb-threatening ischaemia due to infra-popliteal disease: the BASIL-2 RCT.

Chronic limb-threatening ischaemia with ischaemic pain and/or tissue loss. To examine the clinical and cost-effectiveness of a vein bypass-first compared to a best endovascular treatment-first revascularisation strategy in preventing major amputation or death. Superiority, open, pragmatic, multicentre, phase III randomised trial. Thirty-nine vascular surgery units in the United Kingdom, and one each in Sweden and Denmark. Patients with chronic limb-threatening ischaemia due to atherosclerotic peripheral arterial disease who required an infra-popliteal revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion. A vein bypass-first or a best endovascular treatment-first infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation strategy. The primary outcome was amputation-free survival. Secondary outcomes included overall survival, major amputation, further revascularisation interventions, major adverse limb event, health-related quality of life and serious adverse events. Participants were randomised to a vein bypass-first or a best endovascular treatment-first revascularisation strategy. The original sample size of 600 participants (247 events) was based on a hazard ratio of 0.66 with amputation-free survival rates of 0.72, 0.62, 0.53, 0.47 and 0.35 in years 1-5 in the best endovascular treatment-first group with 90% power and alpha at p = 0.05. The sample size was revised to an event-based approach as a result of increased follow-up time due to slower than anticipated recruitment rates. Participants were followed up for a minimum of 2 years. A cost-effectiveness analysis was employed to estimate differences in total hospital costs and amputation-free survival between the groups. Additionally, a cost-utility analysis was carried out and the total cost and quality-adjusted life-years, 2 and 3 years after randomisation were used. Between 22 July 2014 and 30 November 2020, 345 participants were randomised, 172 to vein bypass-first and 173 to best endovascular treatment-first. Non-amputation-free survival occurred in 108 (63%) of 172 patients in the vein bypass-first group and 92 (53%) of 173 patients in the best endovascular treatment-first group [adjusted hazard ratio 1.35 (95% confidence interval 1.02 to 1.80); p = 0.037]. Ninety-one (53%) of 172 patients in the vein bypass-first group and 77 (45%) of 173 patients in the best endovascular treatment-first group died [adjusted hazard ratio 1.37 (95% confidence interval 1.00 to 1.87)]. Over follow-up, the economic evaluation discounted results showed that best endovascular treatment-first was associated with £1690 less hospital costs compared to vein bypass-first. The cost utility analysis showed that compared to vein bypass-first, best endovascular treatment-first was associated with £224 and £2233 less discounted hospital costs and 0.016 and 0.085 discounted quality-adjusted life-year gain after 2 and 3 years from randomisation. Recruiting patients to the Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 trial was difficult and the target number of events was not achieved. A best endovascular treatment-first revascularisation strategy was associated with better amputation-free survival, which was largely driven by fewer deaths. Overall, the economic evaluation results suggest that best endovascular treatment-first dominates vein bypass-first in the cost-effectiveness analysis and cost-utility analysis as it was less costly and more effective than a vein bypass-first strategy. The Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 investigators have a data sharing agreement with the BEst Surgical Therapy in patients with Chronic Limb threatening Ischaemia investigators. One output of this collaboration will be an individual patient data meta-analysis. Current Controlled Trials ISRCTN27728689. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/35/45) and is published in full in Health Technology Assessment; Vol. 28, No. 65. See the NIHR Funding and Awards website for further award information.

Role of intravascular ultrasound for the technical assessment of endovascular reconstruction of the aortic bifurcation

ObjectiveThe aim of this study was to evaluate the role of intravascular ultrasound (IVUS) for the technical assessment of kissing stents (KSs) and covered endovascular reconstruction of the aortic bifurcation (CERAB) in the treatment of aortoiliac obstructive disease involving the aortic bifurcation. MethodsWe conducted a single-center retrospective review of patients undergoing endovascular treatment of severe aorto-iliac obstructive disease (2019-2023). IVUS was performed in patients treated by KSs or CERAB according to preoperative indications, in cases of moderate/severe calcifications, mural thrombus, total occlusions, and lesion extension towards the proximity of renal or hypogastric arteries. Indications for IVUS-guided intraoperative revisions were residual stenosis or compression >30%, incomplete stent-to-wall apposition, or flow-limiting dissection at the landing site. Follow-up assessment was performed at 6 and 12 months, and then yearly. Thirty-day outcomes and 2-year patency rates were evaluated. Logistic regression was used to identify factors associated with significant technical defects detected by IVUS needing intraoperative revision. ResultsIVUS was used for the technical assessment of 102 patients treated by KSs (n = 57; 56%) or CERAB (n = 45; 44%) presenting with severe intermittent claudication (39%), rest pain (39%), or ischemic tissue loss (25%). Twenty-nine significant technical defects were identified by IVUS in 25 patients (25%) who then had successful intraoperative correction by additional ballooning (n = 23; 80%) or stenting (n = 6; 20%). Patients with a severely calcified chronic total occlusion (odds ratio, 1.85; 95% confidence interval, 1.01-5.27; P = .044) or severely calcified narrow aortic bifurcation with <12 mm diameter (odds ratio, 2.34; 95% confidence interval, 1.10-8.64; P = .032) were at increased risk for IVUS-guided intraoperative revision. There were no postoperative deaths and no major adverse events. Two-year primary patency was 100%. ConclusionsIVUS was used for the technical assessment of KSs/CERAB in a selected cohort of patients with severe aorto-iliac obstructive disease. This allowed the identification and intraoperative correction of a significant technical defect not detected by completion angiogram in one-quarter of patients, achieving optimal 2-year results. IVUS assessment of KSs/CERAB may be considered especially in patients with a calcified total occlusion or narrow aortic bifurcation.

TO PREDICT THE NEED FOR AMPUTATION IN DIABETIC FOOT ULCER USING SVS - WIFI SCORING SYSTEM

Analysis of svs wifi scoring as a predictor for amputation in diabetic foot ulcer dr. Shibani chandiramani, dr lisha suraj department of general surgery mahatma gandhi medical college, navi mumbai introduction : Critical limb ishchemia in diabetic patients is defined as a clinical syndrome of ischemic pain at rest and/or ischemic tissue loss such as non healing ulcers or gangrene for more than 2 weeks with ankle pressure of &lt; 40mmhg. It differs from acute limb ischemia which is sudden loss of perfusion typically due to embolus or in situ thrombus. The svs wifi scoring system stratifies cli on the basis of perfusion , extent of wound and superadded infection to provide a composite score wich guides further management and predicts final prognosis. Aim:- to predict the need for amputation in diabetic foot ulcer using svs wifi scoring. Objectives:- To study the predictive role of svs wifi scoring system in diabetic foot ulcers undergoing amputation material and methods :- the subjects were 30 patients with diabetic foot ulcers, gangrene, wound presenting to general surgery, diabetic clinic or vascular surgery at mgm medical college , navi mumbai. Wifi scring of diabetic foot ulcers were done at the time of presentation after obtaining consent from the patient/ relatives.the wifi categories according to risk of limb loss were identified with endpoint being major/ minor amputations. Result:- The composite wifi score (a summmation of wound , infection and ischemia sub-scores) was a good predictor of need for amputation in diabetic ulcer patients.

Wound, Ischemia, Foot Infection (Wifi) Classification System And Its Predictive Ability Concerning Amputation-Free Survival, Mortality And Major Limb Amputation In A Portuguese Population: A Single Center Experience.

Commonly used chronic limb-threatening ischemia (CLTI) classifications lack granularity and detail to precisely stratify patients according to risk of limb loss, expected revascularization benefit and mortality. The aim of this study is to evaluate in a Portuguese population the prognostic value of an updated CLTI classification based on Wound, Ischemia, and foot Infection (WIfI) proposed by the Society for Vascular Surgery. Single-center retrospective evaluation of prospectively collected data of consecutive patients with CLTI submitted to lower limb revascularization from January to December of 2017. All consecutive patients with chronic peripheral artery disease with ischemic rest pain or tissue loss were included. The exclusion criteria were patients with intermittent claudication, vascular trauma, acute ischemia, non-atherosclerotic arterial disease and isolated iliac intervention. The primary end-point was major limb amputation, mortality and amputation-free survival (AFS) at 30 days, 1 year and 2 year follow-up. Secondary end-points were minor amputation, wound healing time (WHT) and rate (WHR). A total of 111 patients with CLTI were submitted to infra-inguinal revascularization: 91 endovascular and 20 open surgery. After categorizing them according to the WIfI: 20 had stage 1 (18.52%), 29 stage 2 (26.85%), 38 stage 3 (35.19%) and 21 stage 4 (19.44%). Overall mortality rate was 1.8%, 17% and 22.3% at 30 days, 1 year and 2 years follow-up. Major amputation rate was 0.9%, 2.7% and 2.7% at 30 days, 1 year and 2 years follow-up. AFS rate was 97.3%, 82.1%, and 76.8% at 30 days, 1 year, 2 years follow-up. In multi-variable analysis, higher WIfI score was the only predictive factor for mortality and AFS. WIfI 3 and 4 were also associated with increased risk of non-healing ulcer. This study proved the prognostic value of the WIfI classification in a Portuguese population by showing an association between higher scores and increased mortality, lower AFS and non-healing ulcer.

Single Center Outcomes of Percutaneous Deep Vein Arterialization in Patients with End-Stage Peripheral Artery Disease.

Background: Peripheral artery disease (PAD) can present as chronic limb threatening ischemia (CLTI) with ischemic pain and tissue loss. Progression of distal disease can lead to a "no option" or end-stage disease without traditional open or endovascular revascularization due to lack of pedal targets. Innovations in endovascular technology allow for the use of percutaneous deep vein arterialization (pDVA) to treat patients with CLTI. Purpose: We describe our experience and technique for treating four patients with end-stage PAD with pDVA. Research Design: Four patients with end-stage PAD were followed during and after pDVA creation. Technical success, complications, wound healing, and freedom from major amputation were analyzed. Data Collection and Analysis: Patient data and outcomes were collected via chart review and at time of follow up appointments in vascular surgery clinic. Results: Technical success was 100%, without post-procedural complications, and patients were continued on antiplatelet and anticoagulation. Three patients (75%) had successful wound healing, with 2 patients healing after transmetatarsal amputation (TMA), and 1 healing a distal foot ulceration that did not require surgery. One patient had worsening ischemic breakdown of a TMA, despite re-intervention on the pDVA, which required a below knee amputation (BKA). Freedom from major amputation was 75% overall, with an average follow-up time of 410 days post-procedure (Range: 113-563 days). Conclusions: Percutaneous deep vein arterialization attempts to provide blood flow to the preserved venous bed in patients with end-stage PAD. Exploration and utilization of this technique continues to expand in the modern vascular era. This case series highlights 4 patients with end-stage PVD who underwent pDVA, with 100% procedural success, and 75% limb salvage rate.

Predictors of Ambulatory Status at 1 Year Following Major Lower Extremity Amputation

Nearly 60,000 major lower extremity amputations (AKA/BKA) are performed annually in the United States. We created a simple risk score for predicting ambulation at 1 year following AKA/BKA. We queried the Vascular Quality Initiative amputation database for patients who underwent above-knee (AKA) or below-knee (BKA) amputation (2013-2018). The primary endpoint was ambulation at 1 year either independently or with assistance. The cohort was divided into 80% derivation and 20% validation. Using the derivation set, a multivariable model identified preoperatively available independent predictors of 1 year ambulation and an integer-based risk-score was created. Scores were calculated to assign patients to risk groups-low, medium, or high chance of being ambulatory at 1 year. Internal validation was performed by applying the risk score to the validation set. Of 8725 AKA/BKA, 2055 met inclusion criteria-excluded: 2644 nonambulatory prior to amputation, 3753 missing 1-year follow-up ambulatory status. The majority-n=1366, 66% were BKAs. The indications were CLTI; 47%, ischemic tissue loss; 9%, ischemic rest pain; 35%, infection/neuropathic; 9%, acute limb ischemia. Ambulation at 1 year was higher for BKA than AKA: 67%, versus 50%, p < .0001. In the final prediction model, contralateral BKA/AKA was the strongest predictor of nonambulation. The score provided reasonable discrimination (C-statistic=0.65) and was well calibrated (Hosmer-Lemeshow p=.24). Sixty-two percent of patients who were ambulatory preoperatively remained ambulatory at 1 year. An integer-based risk score can stratify patients according to chance of ambulation at 1 year after major amputation and may be useful for preoperative patient counseling and selection.

Evaluation of an Infrapopliteal Drug-Eluting Resorbable Scaffold: Design Methodology for the LIFE-BTK Randomized Controlled Trial.

Criticallimb-threatening ischemia (CLTI) is a severe condition characterized by rest pain and ischemic tissue loss that affects 5% to 10% of people with peripheral artery disease. In the United States, there are few Food and Drug Administration-approved devices for the primary treatment of arteries below-the-knee (BTK). Unfortunately, all suffer from high restenosis rates due to intimal hyperplasia, elastic recoil, and untreated dissection because of a lack of scaffolding. The Esprit BTK system is a resorbable, drug-eluting scaffold device with the potential to address an unmet need in people suffering from CLTI because of infrapopliteal atherosclerosis. The LIFE-BTK (pivotaL Investigation of saFety and Efficacy of drug-eluting resorbable scaffold treatment-Below The Knee) randomized controlled trial (RCT) is a prospectively designed premarket evaluation of the Esprit BTK drug-eluting resorbable scaffold used in the treatment of those patients. The LIFE-BTK trial enrolled 261 subjects with CLTI for the RCT and a further 7 subjects for a pharmacokinetic substudy. The objective of the RCT was to evaluate the safety and efficacy of the Esprit BTK scaffold compared to percutaneous transluminal angioplasty. The primary efficacy end point was a composite of limb salvage and primary patency at 12 months. The primary safety end point is freedom from major adverse limb events and peri-operative death at 6 months and 30 days, respectively. Clinical follow-up care is planned for 5 years. Novel devices must be tested in RCTs to evaluate their safety and efficacy compared to the standard of care if we are to improve outcomes for this challenging group of patients.

A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial

Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-2 was an open-label, pragmatic, multicentre, phase 3, randomised trial done at 41 vascular surgery units in the UK (n=39), Sweden (n=1), and Denmark (n=1). Eligible patients were those who presented to hospital-based vascular surgery units with chronic limb-threatening ischaemia due to atherosclerotic disease and who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Participants were randomly assigned (1:1) to receive either vein bypass (vein bypass group) or best endovascular treatment (best endovascular treatment group) as their first revascularisation procedure through a secure online randomisation system. Participants were excluded if they had ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease. Most vein bypasses used the great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug eluting stents. Participants were followed up for a minimum of 2 years. Data were collected locally at participating centres. In England, Wales, and Sweden, centralised databases were used to collect information on amputations and deaths. Data were analysed centrally at the Birmingham Clinical Trials Unit. The primary outcome was amputation-free survival defined as time to first major (above the ankle) amputation or death from any cause measured in the intention-to-treat population. Safety was assessed by monitoring serious adverse events up to 30-days after first revascularisation. The trial is registered with the ISRCTN registry, ISRCTN27728689. Between July 22, 2014, and Nov 30, 2020, 345 participants (65 [19%] women and 280 [81%] men; median age 72·5 years [62·7-79·3]) with chronic limb-threatening ischaemia were enrolled in the trial and randomly assigned: 172 (50%) to the vein bypass group and 173 (50%) to the best endovascular treatment group. Major amputation or death occurred in 108 (63%) of 172 patients in the vein bypass group and 92 (53%) of 173 patients in the best endovascular treatment group (adjusted hazard ratio [HR] 1·35 [95% CI 1·02-1·80]; p=0·037). 91 (53%) of 172 patients in the vein bypass group and 77 (45%) of 173 patients in the best endovascular treatment group died (adjusted HR 1·37 [95% CI 1·00-1·87]). In both groups the most common causes of morbidity and death, including that occurring within 30 days of their first revascularisation, were cardiovascular (61 deaths in the vein bypass group and 49 in the best endovascular treatment group) and respiratory events (25 deaths in the vein bypass group and 23 in the best endovascular treatment group; number of cardiovascular and respiratory deaths were not mutually exclusive). In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy. UK National Institute of Health Research Health Technology Programme.

The Feasibility and Applicability of Percutaneous Deep Vein Arterialization in Peripheral Artery Disease.

Peripheral artery disease (PAD) can often present with chronic limb threatening ischemia (CLTI), including ischemic rest pain and severe tissue loss. Progression of PAD can lead to "no option" or end-stage disease in which there are no traditional open or endovascular interventions available for revascularization. This cohort of patients have a poor prognosis, with a major amputation rate of 40% and mortality of up to 20% at six months. For this patient population, surgical deep vein arterialization (DVA) is offered as an attempt to provide blood flow to the distal preserved venous bed and reverse the ischemic process. Surgical DVA has traditionally been offered as an option and was pioneered by Herb Dardik. The evolution of endovascular technology has allowed for percutaneous DVA (pDVA). Using ultrasound and fluoroscopic guidance, an arteriovenous channel is created between a tibial artery and vein and reinforced with covered stent grafts to increase distal limb perfusion with the goals of improving wound healing and amputation-free survival. Lysis of venous valves with a valvulotome also aids with reversal of flow into the distal venous system. Investigations of percutaneous deep vein arterialization are underway with one device, the LimFlow System (LimFlow SA, Paris, France), which is undergoing feasibility trials. Here we present the current clinical indications, feasibility, results, and our institutional experience with the use of percutaneous deep vein arterialization.

Analysis of a Machine Learning–Based Risk Stratification Scheme for Chronic Limb-Threatening Ischemia

Valid risk stratification schemes are key to performing comparative effectiveness research; however, for chronic limb-threatening ischemia (CLTI), risk stratification schemes have limited efficacy. Improved, accurate, comprehensive, and reproducible risk stratification models for CLTI are needed. To evaluate the use of topic model cluster analysis to generate an accurate risk prediction model for CLTI. This multicenter, nested cohort study of existing Project of Ex Vivo Vein Graft Engineering via Transfection (PREVENT) III clinical trial data assessed data from patients undergoing infrainguinal vein bypass for the treatment of ischemic rest pain or ischemic tissue loss. Original data were collected from January 1, 2001, to December 31, 2003, and were analyzed in September 2021. All patients had 1 year of follow-up. Supervised topic model cluster analysis was applied to nested cohort data from the PREVENT III randomized clinical trial. Given a fixed number of clusters, the data were used to examine the probability that a patient belonged to each of the clusters and the distribution of the features within each cluster. The primary outcome was 1-year CLTI-free survival, a composite of survival with remission of ischemic rest pain, wound healing, and freedom from major lower-extremity amputation without recurrent CLTI. Of the original 1404 patients, 166 were excluded because of a lack of sufficient feature and/or outcome data, leaving 1238 patients for analysis (mean [SD] age, 68.4 [11.2] years; 800 [64.6%] male; 894 [72.2%] White). The Society for Vascular Surgery Wound, Ischemia, and Foot Infection grade 2 wounds were present in 543 patients (43.8%), with rest pain present in 645 (52.1%). Three distinct clusters were identified within the cohort (130 patients in stage 1, 578 in stage 2, and 530 in stage 3), with 1-year CLTI-free survival rates of 82.3% (107 of 130 patients) for stage 1, 61.1% (353 of 578 patients) for stage 2, and 53.4% (283 of 530 patients) for stage 3. Stratified by stage, 1-year mortality was 10.0% (13 of 130 observed deaths in stage 1) for stage 1, 13.5% (78 of 578 patients) for stage 2, and 20.2% (105 of 521 patients) for stage 3. Similarly, stratifying by stage revealed major limb amputation rates of 4.2% (5 of 119 observed major limb amputations in stage 1) for stage 1, 10.8% (55 of 509 patients) for stage 2, and 18.4% (81 of 440 patients) for stage 3. Among survivors without a major amputation, the rates of CLTI recurrence were 9.2% (11 of 119 observed recurrences in stage 1) for stage 1, 24.9% (130 of 523 patients) for stage 2, and 29.6% (132 of 446 patients) for stage 3. The topic model cluster analysis in this cohort study identified 3 distinct stages within CLTI. Findings suggest that CLTI-free survival is an end point that can be accurately and reproducibly quantified and may be used as a patient-centric outcome.

Distal venous arterialisation for ‘no-option’ chronic limb-threatening ischaemia

Chronic limb-threatening ischaemia (CLTI), defined as significant peripheral arterial disease causing ischaemic rest pain and/or tissue loss, is associated with a high amputation and mortality rate. Avoiding amputation in CLTI is crucial and restoration of blood flow is usually achieved using endovascular or open surgical revascularisation. However, significant occlusion of the distal limb vasculature may result in ‘no option’ CLTI, where there are no available target vessels for angioplasty or bypass. An emerging procedure to treat patients with ‘no option’ CLTI is distal venous arterialisation (DVA). This involves using the distal venous system as a conduit for arterial blood to revascularise the lower limb. This report describes a patient presenting with ‘no option’ CLTI who underwent limb-saving treatment with DVA. The case highlights how worsening clinical outcomes may occur despite technical success of DVA. It also emphasises complications of the procedure. Finally, the evidence base surrounding DVA for CLTI is examined.

Conservative Management of Non-Infected Diabetic Foot Ulcers Achieves Reliable Wound Healing and Limb Salvage in the Setting of Mild-Moderate Ischemia

The Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system has been validated to predict wound healing among patients with critical limb threatening ischemia (CLTI). Our goal was to analyze the use of a previously reported conservative wound care approach to non-infected (foot infection score of zero), diabetic foot ulcers with mild-moderate peripheral arterial disease enrolled in a conservative tier of a multidisciplinary limb preservation program. Veterans with CLTI and tissue loss were prospectively enrolled into our Prevention of Amputation in Veterans Everywhere (PAVE) program. All patients with wounds were stratified to a conservative approach based on perfusion evaluation and a validated pathway of care. Retrospective analysis of a prospectively maintained database was performed to evaluate all conservatively managed patients presenting without foot infection for the primary outcome of wound healing as well as secondary outcomes of time to wound healing, delayed revascularization, wound recurrence, and limb loss. Between January 2006 and December 2019, 1113 patients were prospectively enrolled into the PAVE program. A total of 241 limbs with 281 wounds (217 patients) were stratified to the conservative approach. Of these, 122 limbs (89 patients) met criteria of having diabetic foot wounds without infection at the time of enrollment and are analyzed in this report. Of the 122 limbs, 97 (79.5%) healed their index wound with a mean time to healing of 4.6 months (0.5-20 months). Wound recurrence ensued in 44 (45.4%) limbs, 93.2% of which healed again after recurrence. There were three (3.1%) limbs requiring major amputation in this group (one due to uncontrolled infection and two due to ischemic tissue loss). Of the 25 (20.5%) limbs that did not heal initially, four (16%) required amputation due to progressive symptoms of CLTI. In patients with diabetes and lower extremity wounds without infection in the setting of mild to moderate peripheral arterial disease, there appears to be an acceptable rate of index wound healing, and appropriate rate of recurrent wound healing with a low risk of limb loss. While wound recurrence is frequent, this can be successfully treated without the need for revascularization.

Mortality, Cardiovascular and Limb Events in Patients With Symptomatic Lower Extremity Artery Disease and Diabetes.

The aim of this study was to compare the prognosis of patients according to diabetes status, during a 1-year follow-up after hospital admission for lower extremity artery disease, in the prospective COPART (COhorte de Patients ARTériopathes) registry. Inclusion criteria were intermittent claudication, ischemic rest pain, tissue loss, or acute limb ischemia, with radiological and hemodynamic confirmation. Among 2494 patients, 1235 (49.5%) had diabetes. Incidence rates for major adverse cardiovascular events (MACE) were 18.0/100 person-years (95% confidence interval [CI], 15.4-21.0) for the diabetes group and 11.1/100 person-years (95% CI, 9.2-13.4) for the non-diabetes group. Incidence rates of all-cause mortality were 29.8/100 person-years (95% CI, 26.5-33.4) for the diabetes group and 19.7/100 person-years (95% CI, 17.2-22.7) for the non-diabetes group. Incidence rates of major limb amputation were 24.2/100 person-years (95% CI, 21.1-27.8) for the diabetes group and 11.6/100 person-years (95% CI, 9.6-14.0) for the non-diabetes group. Diabetes was associated with MACE, adjusted hazard ratio 1.60 (95% CI, 1.16-2.22), and all-cause mortality, unadjusted HR 1.49 (95% CI, 1.24-1.78). In the multivariate analysis, diabetes was no longer associated with major amputation, adjusted HR 1.15 (95% CI, .87-1.51). Patients hospitalized for LEAD with diabetes had a higher risk of MACE than those without diabetes.

Severe protein C deficiency in a newborn caused by a homozygous pathogenic variant in the PROC gene: a case report

BackgroundSevere protein C deficiency is a rare and inherited cause of thrombophilia in neonates. Protein C acts as an anticoagulant, and its deficiency results in vascular thrombosis. Herein, we report a case of protein C deficiency with a homozygous pathogenic variant in a term neonate, with good outcomes after proper treatment.Case presentationA four-day-old male newborn was transferred to the Seoul National University Hospital on account of dark red to black skin lesions. He was born full-term with an average birth weight without perinatal problems. There were no abnormal findings in the prenatal tests, including intrauterine sonography. The first skin lesion was observed on his right toes and rapidly progressed to proximal areas, such as the lower legs, left arm, and buttock. Under the impression of thromboembolism or vasculitis, we performed a coagulopathy workup, which revealed a high D-dimer level of 23.05 μg/ml. A skin biopsy showed fibrin clots in most capillaries, and his protein C activity level was below 10%, from which we diagnosed protein C deficiency. On postnatal day 6, he experienced an apnea event with desaturation and an abnormal right pupillary light reflex. Brain computed tomography showed multifocal patchy intracranial hemorrhage and intraventricular hemorrhage with an old ischemic lesion. Ophthalmic examination revealed bilateral retinal traction detachments with retinal folds. Protein C concentrate replacement therapy was added to previous treatments including steroids, prostaglandin E1, and anticoagulation. After replacement therapy, there were no new skin lesions, and the previous lesions recovered with scarring. Although there were no new brain hemorrhagic infarctions, there was ongoing ischemic tissue loss, which required further rehabilitation. Ophthalmic surgical interventions were performed to treat the bilateral retinal traction detachments with retinal folds. Molecular analysis revealed a homozygous pathogenic variant in the PROC gene.ConclusionSevere protein C deficiency can manifest as a fatal coagulopathy in any organ. Early diagnosis and proper treatment, including protein C concentrate replacement, may improve outcomes without serious sequelae.

Long Term Survival and Limb Salvage in Patients With Non-Revascularisable Chronic Limb Threatening Ischaemia

The aim of this study was to provide long term survival and limb salvage rates for patients with non-revascularisable (NR) chronic limb threatening ischaemia (CLTI). This was a retrospective review of prospectively collected data, derived from a randomised controlled trial (JUVENTAS) investigating the use of a regenerative cell therapy. Survival and limb salvage of the index limb in CLTI patients without viable options for revascularisation at inclusion were analysed retrospectively. The primary outcome was amputation free survival, a composite of survival and limb salvage, at five years after inclusion in the original trial. In 150 patients with NR-CLTI, amputation free survival was 43% five years after inclusion. This outcome was driven by an equal rate of all cause mortality (35%) and amputation (33%). Amputation occurred predominantly in the first year. Furthermore, 33% of those with amputation subsequently died within the investigated period, with a median interval of 291 days. Five years after the initial need for revascularisation, about half of the CLTI patients who were deemed non-revascularisable survived with salvage of the index limb. Although the prospects for these high risk patients are still poor, under optimal medical care, amputation free survival seems comparable with that of revascularisable CLTI patients, while the major amputation rate within one year, especially among NR-CLTI patients with ischaemic tissue loss, is very high.

Demographic, clinical, and anthropometric profiles and postoperative outcomes in patients with chronic limb threatening ischemia: A prospective descriptive study.

Chronic limb-threatening ischemia (CLTI) is a complex disease caused by peripheral artery disease. It is associated with ischemic foot pain (rest pain) and tissue loss in the form of chronic nonhealing foot ulcers or gangrene. CLTI has a high short-term risk of limb amputations, postoperative sepsis, and cardiovascular-related events. The present study was conducted to assess the demographic and anthropometric profile of patients with CLTI and their postoperative outcomes after 2-year follow-up at Groote Schuur Hospital, Cape Town, South Africa. This prospective descriptive pilot study, nested in a prospective cohort study, included adult patients with CLTI admitted to Groote Schuur Hospital from 1st January 2015 to 31st December 2016. Demographic data, anthropometric markers of CLTI, and the postoperative outcomes were documented using piloted and pretested vascular questionnaire. Descriptive statistics were used for baseline data, and postoperative outcomes were presented using actuarial life-table method (Kaplan-Meier analysis). Odds ratio, 95% confidence interval, and P value < 0.05 were used to test the hypothesis. Thirty-seven (50.6%) patients had a BMI >25.0. The mean waist: hip ratio was 0.96. Prevalence of smoking was 86%. Limb salvage and ambulation at 1 year were 79% and 67%, respectively. Majority of the patients who were ambulant preoperatively remained ambulant postoperatively. Most patients had truncal obesity with a high prevalence of smoking. High postoperative ambulatory recovery among ambulant preoperative patients was a significant outcome observed in our study.

Medical therapy for cardiovascular and limb-related risk reduction in critical limb ischemia.

Critical limb ischemia (CLI) constitutes the most advanced form of peripheral artery disease (PAD) and is characterized by ischemic rest pain, tissue loss and/or gangrene. Optimized medical care and risk factor modification in addition to revascularization could reduce the incidence of cardiovascular events and major adverse limb events, improving patients' quality of life and promising higher survival rates. Adequate adherence to cardioprotective medications, including antithrombotic therapy (e.g., antiplatelets, anticoagulants), cholesterol-lowering agents (e.g., statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors), angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and smoking cessation should be strongly encouraged for patients with CLI. This review examines these guideline-recommended therapies in terms of cardiovascular and limb-related risk reduction in patients with CLI.

Impact of Longer Hemodialysis Vintage with Higher Serum Phosphorus Level on Clinical Outcomes in Patients with Chronic Limb-Threatening Ischemia Presenting Tissue Loss after Endovascular Therapy.

Aims: Hemodialysis vintage and serum phosphorus levels adversely affect outcomes in patients on hemodialysis. Whether these factors have a similar prognostic impact on patients who are on hemodialysis and have chronic limb-threatening ischemia (CLTI) has not been systematically studied. We aimed to explore the risk factors, including hemodialysis vintage and serum phosphorus levels, on clinical outcomes after endovascular therapy (EVT) in hemodialysis patients with CLTI. Methods: The current study rerospectively analyzed 374 hemodialysis patients with CLTI presenting with ischemic tissue loss (age: 72.3±9.0 years, male: 73.3%, diabetes mellitus: 68.2%, Rutherford 5: 75.9%, 6: 24.1%, WIfI stage 4: 50.0%) primarily treated with EVT between April 2007 and December 2016. The primary outcome measure was 1-year amputation-free survival (AFS), while the secondary outcome measure was 1-year wound healing. Predictors for each outcome were evaluated by Cox proportional hazards model. Results: Multivariate analysis significantly associated longer hemodialysis vintages with higher serum phosphorus levels (hazard ratio [HR], 0.599; 95% confidence interval [CI], 0.394-0.910; p =0.016) with 1-year AFS. Longer vintages for hemodialysis with higher serum phosphorus levels were marginally, but not significantly, associated with 1-year wound healing. (HR, 0.684; 95% CI, 0.467–1.000; p =0.050). Conclusion: Longer hemodialysis vintages with higher serum phosphorus levels adversely affect outcomes after EVT for hemodialysis patients with CLTI presenting with ischemic tissue loss.

Wound outcomes and factors associated with wound healing after first-time femoropopliteal artery intervention in patients with ischemic tissue loss

Background/objectiveThis study’s goal is to describe wound outcomes at 2 years following intervention for atherosclerotic femoropopliteal lesions in patients with ischemic tissue loss. MethodsA retrospective review of 135 first-time endovascular procedures for chronic femoropopliteal atherosclerotic lesions related to ischemic tissue loss was performed. The final wound outcomes were categorized according to the initial wound healing, recurrence and the need of major/minor amputation. ResultsAt 2-years of follow up, 76 limbs (56.3%) showed complete wound healing without recurrence, however, wound development occurred at other sites on the same foot following complete primary healing in 11 limbs (8.1%). Tolerable wounds persisted or wounds recurred at the same site in 30 limbs (22.2%), and 18 limbs (13.3%) needed major amputations. Independent factors that prevented wound healing without recurrence at 2 years were renal insufficiency (HR = 0.225, 95% C.I. = 0.091–0.556, p = 0.001), ankle pressure < 50 mmHg or flat forefoot PVR (HR = 0.328, 95% C.I. = 0.124–0.867, p = 0.025) and functional performance < 4 metabolic equivalents (MET) (HR = 0.150, 95% C.I. = 0.063–0.360, p < 0.001). ConclusionWound outcome classifications showed detailed information regarding clinical outcomes in patients with ischemic tissue loss. Renal insufficiency, ischemia grade 3 and poor functional performance were independent risk factors that prevented wound healing.

Abstract 13331: Impact of Longer Hemodialysis Vintage With Higher Serum Phosphorus Level on Clinical Outcomes in Patients With Chronic Limb-threatening Ischemia

Background: Although hemodialysis vintage and serum phosphorus level adversely impact on outcomes in the field of general population on hemodialysis, it has not systematically studied whether these have similar prognostic impacts on clinical outcomes in population with chronic limb-threatening ischemia (CLTI). Methods: The current study retrospectively analyzed 374 hemodialysis patients with CLTI presenting ischemic tissue loss (age: 72.3±9.0 years, male: 73.3%, diabetes mellitus: 39.6%, Rutherford 5: 75.9%, 6: 24.1%, WIFI stage 4: 50.0%) primarily treated with endovascular therapy (EVT) between April 2007 and December 2016. Primary outcome measure was 1-year amputation-free survival (AFS), while secondary outcome measure was 1-year wound healing. Predictors for each outcome were evaluated by Cox proportional hazards model. Result: One-year rate of AFS and wound healing rate were 70.5±2.5%, and 57.1±3.0%, respectively. Multivariate analysis demonstrated that body mass index (hazard ratio [HR], 0.918; 95% confidence interval [CI], 0.859-0.981; p=0.012), non-ambulatory status (HR, 1.887; 95% CI, 1.222-2.913; p=0.004), lower serum albumin level (HR, 0.591; 95% CI, 0.414-0.844; p=0.004), WIfI stage 4 (HR, 1.782; 95% CI, 1.156-2.748; p=0.009) and longer vintages for hemodialysis with higher serum phosphorus levels (HR, 1.670; 95% CI, 1.099-2.537; p=0.016) were significantly associated with 1-year AFS (Figure), while WIfI stage 4 (HR, 0.713; 95% CI, 0.519-0.979; p=0.037) was associated and longer vintages for hemodialysis with higher serum phosphorus levels was close to significant association (HR, 0.684; 95% CI, 0.467-1.000; p=0.050) with 1-year wound healing. Conclusion: Longer hemodialysis vintage with higher serum phosphorus level would adversely affect clinical outcomes after EVT for hemodialysis patients with CLTI presenting ischemic tissue loss.