The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes and a foot ulcer.

Diabetes related foot complications have become a major cause of morbidity and are implicated in most major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events. The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the management and prevention of diabetes related foot complications since 1999. This guideline is an update of the 2019 IWGDF guideline on the diagnosis, prognosis and management of peripheral artery disease in people with diabetes mellitus and a foot ulcer. For this guideline the IWGDF, the European Society for Vascular Surgery and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of recommendations relevant to clinicians in all countries. This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment, Development, and Evaluation framework clinically relevant questions were formulated, and the literature was systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability, equity, resources required, and when available, costs. Through this process five recommendations were developed for diagnosing PAD in a person with diabetes, with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing Committee has highlighted key research questions where current evidence is lacking. The Writing Committee believes that following these recommendations will help healthcare professionals to provide better care and will reduce the burden of diabetes related foot complications.

Endovascular revascularization of critical limb ischemia: the role of ultrasound-guided popliteal sciatic nerve block for the procedural pain management.

OBJECTIVES: To evaluate the impact of the ultrasound-guided popliteal sciatic nerve block (PSNB) for pain management during endovascular treatment of chronic limb-threatening ischemia (CLTI). MATERIAL AND METHODS: From November 2020 to January 2022, 111 CLTI patients that underwent endovascular procedures were prospectively enrolled in this prospective single-arm interventional study. Ultrasound-guided PSNB was used for procedural pain control. Pain intensity was evaluated throughout the procedure (baseline, 10 min after the block, pain peak, and at the end of the procedure) with the visual analog scale (VAS). RESULTS: Forty-six patients underwent above-the-knee revascularization (ATK), 20/111 below-the-knee (BTK) revascularization, 20/111 to both ATK and BTK revascularization. In 25 cases, no endovascular option was feasible at diagnostic angiography. The PSNB was effective in 96% of patients, with no need for further pain management with a statistically significant reduction (p < 0.0001) in the mean value of the VAS from 7.86 ± 1.81 (pre-procedural) to 2.04 ± 2.20 after 10 min from the block and up to 0.74 ± 1.43 at the end of the procedure (mean time 43 min). Only 1 complication related to the popliteal sciatic nerve block was registered (a temporary foot drop, completely resolved within 48 h). The time necessary to perform the block ranged between 4 and 10 min. CONCLUSION: Ultrasound-guided PSNB is a feasible and effective method to manage patients with rest pain and increase comfort and compliance during endovascular procedures. CLINICAL RELEVANCE STATEMENT: An ultrasound-guided popliteal sciatic nerve block is a safe, feasible, and effective technique to manage pain during endovascular treatment of chronic limb-threatening ischemia, especially in frail patients with multiple comorbidities who are poor candidates for deep sedoanalgesia or general anesthesia. KEY POINTS: Endovascular treatment of CTLI may require long revascularization sessions in patients with high levels of pain at rest, which could be exacerbated during the revascularization procedure. The PSNB is routinely used for anesthesia and analgesia during foot and ankle surgery, but the experience with lower limb revascularization procedures is very limited and not included in any international guideline. Ultrasound-guided PSNB is a feasible and effective regional anesthesia technique to relieve procedural and resting pain. Because of its safety and availability, every interventional radiologist should know how to perform this type of loco-regional anesthesia.

The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes mellitus and a foot ulcer.

Diabetes related foot complications have become a major cause of morbidity and are implicated in most major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events. The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the management and prevention of diabetes related foot complications since 1999. This guideline is an update of the 2019 IWGDF guideline on the diagnosis, prognosis, and management of peripheral artery disease in people with diabetes mellitus and a foot ulcer. For this updated guideline, the IWGDF, the European Society for Vascular Surgery, and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of recommendations relevant to clinicians in all countries. This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment, Development and Evaluation framework clinically relevant questions were formulated, and the literature was systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability, equity, resources required, and when available, costs. Through this process five recommendations were developed for diagnosing PAD in a person with diabetes, with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing Committee has highlighted key research questions where current evidence is lacking. The Writing Committee believes that following these recommendations will help healthcare professionals to provide better care and will reduce the burden of diabetes related foot complications.

The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot Ulcer.

Diabetes related foot complications have become a major cause of morbidity and are implicated in most major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events. The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the management and prevention of diabetes related foot complications since 1999. This guideline is an update of the 2019 IWGDF guideline on the diagnosis, prognosis, and management of peripheral artery disease in people with diabetes mellitus and a foot ulcer. For this updated guideline, the IWGDF, the European Society for Vascular Surgery, and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of recommendations relevant to clinicians in all countries. This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment, Development and Evaluation framework clinically relevant questions were formulated, and the literature was systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability, equity, resources required, and when available, costs. Through this process five recommendations were developed for diagnosing PAD in a person with diabetes, with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing Committee has highlighted key research questions where current evidence is lacking. The Writing Committee believes that following these recommendations will help healthcare professionals to provide better care and will reduce the burden of diabetes related foot complications.

Evaluation of the lower extremity blood supply in no-option critical limb ischemia patients with stem cell transplantation by time maximum intensity projection CT perfusion: A single-centre prospective study.

OBJECTIVES: Cell therapy has had satisfactory safety and efficacy outcomes for no-option critical limb ischaemia (NO-CLI) patients. In the current study, we aimed to compare the image quality of ischaemic lower limb blood vessels shown on volumetric CT-based time maximum intensity projection CT perfusion (t-MIP CTP) versus single-phase CTA (sCTA). We also tried to quantify the blood flow of the ischaemic lower extremity based on the t-MIP technique, not only to precisely show the dynamic change in blood flow from before to after cell therapy but also to detect any relationship between this change and patient prognosis. METHODS: A total of 31 patients with thromboangiitis obliterans (TAO)-induced NO-CLI who had been referred from the department of vascular surgery to undergo autologous stem cell transplantation into a single limb from January 2020 to March 2021 were prospectively enrolled in this study. Preoperative sCTA or t-MIP CTP and postoperative 1-month t-MIP CTP were performed in all patients. Clinical outcomes, including the 1-month ankle-brachial index (ABI) and 3-month CLI status, were also analysed. Image quality, including objective scores (attenuation, signal-to-noise ratio [SNR] and contrast-to-noise ratio [CNR]), subjective scores and collateral scores, was compared between preoperative sCTA and t-MIP CTP. Vascular volume was calculated as the total volume (mL) of lower limb arteries within the scanning range. All images and calculations were performed by 2 separate radiologists. Receiver operating characteristic curves were drawn to reveal the sensitivity and specificity of vascular volume and ABI in predicting prognosis. RESULTS: Both sCTA and t-MIP CTP images exhibited good quality for diagnosis. t-MIP CTP images showed significantly higher attenuation, SNR and CNR in all arterial segments (popliteal artery, anterior tibial artery, posterior tibial artery and peroneal artery). In subjective and collateral score evaluations, t-MIP CTP images were also significantly better than sCTA images (both p < .05). At 1 month after transplantation, both vascular volume and ABI showed significant improvement (both p < .01). At 3 months after transplantation, 38.71% of patients (12/31) achieved CLI relief (Rutherford class < 4). Through the receiver operating characteristic (ROC) curve, the 1-month vascular volume increase ratio showed better ability to predict the 3-month prognosis (radiologist 1: AUC, 0.757; sensitivity, 0.750; specificity, 0.840; radiologist 2: AUC, 0.803; sensitivity, 0.500; specificity, 1.000) than the 1-month ABI increase ratio (AUC, 0.607; sensitivity, 0.230; specificity, 0.820) or 1-month ABI (AUC, 0.410; sensitivity, 0.080; specificity, 0.580). CONCLUSION: t-MIP CTP showed significantly higher-quality images of ischaemic limb vascularity than sCTA. t-MIP CTP can reveal the anatomical information of collaterals more accurately, which is of great importance for NO-CLI patients undergoing cell transplantation. The 1-month vascular volume increase ratio can predict the 3-month prognosis more precisely on this basis.

Quality of Life in Chronic Limb Threatening Ischaemia: Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the comparative effectiveness and temporal changes in quality of life (QoL) outcomes after revascularisation, major lower extremity amputation (MLEA), and conservative management (CM) in chronic limb threatening ischaemia (CLTI). DATA SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. REVIEW METHODS: A systematic review and meta-analysis were performed on QoL measured by any QoL instrument in adult patients with CLTI after open surgery (OS), endovascular intervention (EVI), MLEA, or CM. Randomised controlled trials and prospective observational studies published in any language between 1 January 1990 and 21 May 2021 were included. There was a pre-specified measurement time point of six months. Random effects meta-analysis was conducted on total scores for each QoL instrument. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach (PROSPERO registration: CRD42021253953). RESULTS: Fifty-five studies with 8 909 patients were included. There was significant heterogeneity in the methods used to measure QoL, and the study characteristics. In particular, 14 different QoL instruments were used with various combinations of disease specific and generic instruments within each study. A narrative summary is therefore presented. Comparative effectiveness data showed there was reasonable certainty that QoL was similar between OS and EVI at six months. Temporal outcomes suggested small to moderate improvements in QOL six months after OS and EVI compared with baseline. Limited data indicated that QoL can be maintained or slightly improved after MLEA or CM. Treatment effects were overestimated owing to small study effects, selective non-reporting, attrition, and survivorship bias. CONCLUSION: QoL after OS and EVI appears to be similar. Revascularisation may provide modest QoL benefits, while MLEA or CM can maintain QoL. However, certainty of evidence is generally low or very low, and interpretation is hampered by significant heterogeneity. There is a need for a CLTI specific QoL instrument and methodological standardisation in QoL studies.

A Dose Response Association Between Body Mass Index and Mortality in Patients with Peripheral Artery Disease: A Meta-analysis Including 5 729 272 Individuals.

OBJECTIVE: Obesity is a significant risk factor for atherosclerotic cardiovascular disease; however, the "obesity paradox", in which obese patients enjoy superior survival, has been observed in various cardiovascular conditions. Whether this phenomenon exists for peripheral artery disease (PAD) remains uncertain. The goal of this study was to evaluate the relationship between body mass index (BMI) and mortality in patients with PAD. METHODS: A comprehensive literature search identified seven eligible cohort studies that reported the association between BMI and all cause mortality in patients with PAD. A dose response meta-analysis was done for all cause mortality, short term (30 day or in hospital) mortality and long term mortality. The dose response association between BMI and mortality was also assessed in patients who received endovascular therapy (EVT). RESULTS: The non-linear dose response analysis showed that higher BMI values were associated with a lower mortality risk from the range between 15 kg/m2 to approximately 33 - 34 kg/m2. The risk of mortality increased slightly thereafter. This relationship was consistent with that of long term mortality but was not apparent in short term mortality. A U shaped relationship was also observed between BMI and mortality in patients who received EVT with the lowest mortality observed at around 30 kg/m2. CONCLUSION: The obesity paradox was evident in the analysis of long term survival among patients with PAD, with the lowest mortality rates observed in obese patients. However, this association was not observed for short term or in hospital mortality.

Real Life Outcomes of Infrapopliteal Endovascular and Surgical Bypass Intervention for Chronic Limb Threatening Ischaemia in GLASS Stages II and III.

OBJECTIVE: Great efforts have been made to choose between bypass surgery and angioplasty as the first choice for revascularisation in chronic limb threatening ischaemia (CLTI). Endovascular therapy predominates despite limited evidence for its advantages. The purpose of this observational cohort study was to investigate outcomes after open and endovascular infrapopliteal revascularisation in extensive infrainguinal arterial disease. METHODS: The medical records of 1 427 patients who underwent infrainguinal revascularisation exclusively for CLTI in the period January 2014 to February 2019 were reviewed. After detailed analysis, only infrapopliteal revascularisations classified as GLASS stage II or III were considered, resulting in 326 procedures. In total, 127 patients underwent endovascular therapy and 199 patients underwent bypass graft surgery (BGS). The primary endpoints included amputation free survival (AFS) and overall survival (OS). Secondary endpoints included the analyses of multiple factors related to long term AFS. RESULTS: Regarding the primary endpoint, AFS was 75.2% and 65.2% at one and three years, respectively. OS at one and three years was 91.2% and 83.1%, respectively. In the univariable analysis, the hazard of the combined endpoint of major amputation or death was higher after bypass surgery than after endovascular therapy (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.13 - 2.89; p = .013). After either revascularisation method, TASC II femoropopliteal D was associated with a higher risk of amputation or death (HR 1.69, 95% CI 1.10 - 2.58; p = .015). Multivariable Cox regression analysis revealed no association between the variables analysed for AFS. CONCLUSION: Patients with CLTI submitted to infrapopliteal revascularisation and classified as GLASS II and III had satisfactory AFS and OS rates after an individualised team conference decision. Furthermore, the revascularisation modality (endovascular or open) did not influence the AFS results.

The use of fetal bovine acellular dermal matrix in severe diabetic foot ulceration and threatened limbs with tissue loss the use of FBADM as an adjunct for complex wounds.

OBJECTIVES: Foot ulceration associated with diabetic foot disease (DFD) and chronic limb-threatening ischaemia (CLTI) presents a complex clinical challenge and failure to heal the wound imposes a significant risk of major limb amputation (MLA). In attempt to accelerate wound healing rates and decrease MLA, tissue engineering research into bio-engineered scaffolds and skin substitutes has become a growing area of interest. Advanced wound therapies such as fetal bovine acellular dermal matrix (FBADM) may have success in the treatment of difficult to heal chronic foot ulcers. The FBADM traps and binds the patients' own epithelial cells to rebuild the dermis layer of the skin. Previous studies have suggested that wounds treated with FBADM had a faster healing rate than wounds managed with conventional dressings. However, these studies excluded foot wounds with chronic exposed bone or tendon, active infection, gangrene, or osteomyelitis and patients with uncontrolled blood glucose levels were excluded. The aim of this study was to assess the efficacy of FBADM for patients admitted to hospital acutely with severe foot ulceration secondary to DFD and CLTI. METHODS: Between February 2020 and December 2021, inpatients admitted acutely at a single tertiary centre with a severe non-healing foot ulcer and had a wound suitable for application of a FBADM after primary debridement were included in the study. A severe non-healing foot wound was defined as a Society for Vascular Surgery Wound, Ischaemia, and foot Infection (WIfI) stage of 3 or 4. Participants were prospectively followed up at regular intervals at a multidisciplinary high-risk diabetic foot clinic until June 2022. The primary endpoint was time to wound closure. The secondary endpoints were number of applications of FBADM, readmission rate and amputation-free survival. RESULTS: There were 22 patients included in the study with a median age of 71 (50-87) years and 15 were male. Five patients had a WIfI stage of 3 and 17 had a WIfI score of 4. Overall, 14 patients required revascularisation procedures (6 open surgery,8 endovascular intervention). A total of 18 patients achieved complete wound healing with a median time to wound healing of 178 (28-397) days. Two patients underwent a MLA and two patients died prior to complete wound healing. The median length of stay was 16.5 (5-115) days, and 4 patients were readmitted to hospital within 12 months. CONCLUSION: FBADM may be a useful adjunct in the acute setting of complex DFD and CLTI ulceration to assist with wound healing. Future comparative prospective studies are required to further validate these preliminary findings.

Bifurcated bypass in severe chronic limb threatening ischaemia.

OBJECTIVES: Revascularization according to the angiosome concept is of proven importance for limb salvage in chronic limb threatening ischaemia but it is not always practicable. Bifurcated bypasses could be considered as an option when an endovascular approach is not feasible or has already failed and a single bypass would not allow direct revascularization of the ischaemic area. Bifurcated bypasses are characterized by landing on two different arteries, the main artery (in direct continuity with the foot vessels) and the secondary one (perfusing the angiosome district). The aim of this study is to evaluate the safety and effectiveness of bifurcated bypass in chronic limb threatening ischaemia. METHODS: Thirty-five patients were consecutively treated with a bifurcated bypass for chronic limb threatening ischaemia from January 2014 to December 2019 in a single vascular surgery centre. Data from clinical records and operative registers were collected prospectively in an electronic database and retrospectively analysed. Primary and primary assisted bypass patency, amputation-free survival, morbidity and mortality rates at 12 and 24 months were analysed. RESULTS: Mean follow-up period was 25.1 months (range 2-72 months). Thirty-six bifurcated bypasses were performed on 35 patients (age 75.3 ± 7.2 years; 69.4% were male). According to Wound, Ischemia, foot Infection classification 22.2% belonged to stage 3 and 77.8% to stage 4 and the mean Rutherford's class was 5.1 ± 0.7. Immediate technical success was 100%. Early mortality and morbidity rates were respectively 5.5%, and 33.3%; foot surgery was performed in 50% of cases with wound healing in all patients. Primary patency and primary assisted bypass patency were 96.7% and 100% at 6 months; 85.2% and 92% at 12 months, 59.9% and 73.4% at 24 months, respectively. Amputation-free survival at 12 and 24 months was, respectively, 95.6% and 78.8%. Overall survival rates at 12 and 24 months were respectively 94.4% and 91.6%. CONCLUSIONS: Bifurcates bypass can provide good results in patients with chronic limb threatening ischaemia without endovascular option, especially in diabetic ones. Bifurcated bypass is a complex surgical solution, both to be planned and performed, and it is quite invasive for frail patients that should be accurately selected.

Systematic review of inframalleolar endovascular interventions and rates of limb salvage, wound healing, restenosis, rest pain, reintervention and complications.

OBJECTIVES: Peripheral artery disease is estimated to affect 237 million individuals worldwide. Critical limb ischaemia, also known as chronic limb threatening ischaemia is a consequence of the progression of peripheral artery disease which occurs in ∼21% of patients over a five-year period. The aim of this systematic review is to assess the use of additional below-the-ankle angioplasty in comparison to the use of above-the-ankle angioplasty alone, and the subsequent rates of amputation, wound healing, restenosis, rest pain, reintervention and complications. METHODS: This systematic review was undertaken in accordance with PRISMA guidelines following a registered protocol (CRD42019154893). Online databases were searched using a search strategy of 20 keywords. Included articles reported the outcome for inframalleolar (pedal artery, pedal arch, plantar arteries) angioplasty with additional proximal angioplasty in comparison to proximal angioplasty alone. GRADE assessment was applied to assess the quality of the evidence. RESULTS: After screening 1089 articles, 10 articles met the inclusion criteria. Comparative performance assessment of below-the-ankle with above-the-ankle versus above-the-ankle angioplasty alone was undertaken in 3 articles, with the remaining 7 articles reporting outcomes of below-the-ankle with above-the-ankle angioplasty with no distinct comparator group. Significant decrease in major lower limb amputation at the last follow-up in the below-the-ankle group when compared with the above-the-ankle angioplasty alone group was observed in a single study (3.45% vs. 14.9%, p < 0.05). Improved wound healing rate at follow-up in the below-the-ankle group versus above-the-ankle angioplasty alone group was also reported in a single study (59.3% vs. 38.1%, p < 0.05). Subsequent rate of amputation after below-the-ankle angioplasty has been estimated as 23.5%. CONCLUSION: To date, there is a lack of studies assessing inframalleolar interventions and their use in improving limb salvage, wound healing and symptomatology. Prospective RCTs should be undertaken with adequate participant numbers to be sufficiently powered and report clinically important end-points.

Patient Reported Outcome Measures for Major Lower Limb Amputation Caused by Peripheral Artery Disease or Diabetes: A Systematic Review.

OBJECTIVE: Most major lower limb amputations are related to peripheral artery disease (PAD) or diabetes. Just 40% of patients who undergo major lower limb amputation will use a prosthesis yet measures of surgical success commonly focus on prosthesis use. Patient reported outcome measures (PROMs) are valuable to comprehensively evaluate health related quality of life (HRQL) after surgery. This systematic review aimed to identify and describe PROMs available to assess HRQL in patients after amputation for PAD or diabetes. METHODS: A search was conducted based on the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) for systematic reviews of PROMs. Ovid MEDLINE, Ovid EMBASE, PsycINFO, CINAHL, and Cochrane CENTRAL were also searched from inception until August 2019. Included were articles describing the development, measurement properties, or evaluation of HRQL via a PROM in adult patients after amputation for PAD or diabetes. Studies of amputation exclusively for trauma or malignancy were excluded. Data were collected on study characteristics, PROM characteristics (generic/disease specific), and properties of amputation specific PROMs. RESULTS: Of 3 317 abstracts screened, 111 full text articles were assessed for eligibility and 64 included. Fifty-six studies evaluated HRQL, with 23 (46%) of these using an amputation specific PROM to do so. Eleven different amputation specific PROMs were identified, 10 (91%) of which were developed only for prosthesis users. One measure was suitable for use in all patients after amputation. This "Amputee single item mobility measure" includes a single item evaluating mobility. Nine studies reported some psychometric testing of an amputation specific PROM. CONCLUSION: A well tested, multidimensional PROM applicable to wheelchair and prosthetic users after amputation is lacking and urgently needed for studies in this field. Future work to develop an appropriate measure is required.

Technical Success and Complication Rates of Retrograde Arterial Access for Endovascular Therapy for Critical Limb Ischaemia: A Systematic Review and Meta-Analysis.

OBJECTIVE: Antegrade crossing techniques via transfemoral access are often challenging and may be associated with technical and clinical failure when treating patients with critical limb ischaemia (CLI). The objective of this study was to summarise all available literature regarding retrograde endovascular treatment of patients with CLI and to investigate the technical success and complication rate of retrograde access. METHODS: A systematic literature search was performed in PubMed, Scopus, and Cochrane Central until May 2020. A meta-analysis of 31 observational studies (29 retrospective and two prospective; 26 and five studies with low and moderate risk of bias, respectively) was conducted with random effects modelling. The incidence of adverse events peri-procedurally and during follow up were calculated. RESULTS: The 31 studies enrolled 1 910 patients who were treated endovascularly for femoropopliteal and/or infrapopliteal lesions causing CLI. Most of the patients had diabetes while more than half of the overall population had coronary artery disease and dyslipidaemia. All lesions were located in the infra-inguinal segment and most were chronic total occlusions (96%; 95% CI 85%-100%). Seven studies reported moderate or severe calcification in approximately half of the cases (45%; 95% CI 30%-60%). The overall technical success of the retrograde approach was 96% (18 studies; 95% CI 92%-100%). Perforation, flow limiting dissection, distal embolisation, and local haematoma at the retrograde access site were infrequent and observed in 2.1%, 0.6%, 0.1%, and 1.3% of the patients, respectively. The six month primary patency rate was 78% (five studies; 95% CI 46%-99%), the six month limb salvage rate was 77% (four studies; 95% CI 70%-84%). CONCLUSION: The results indicated that the retrograde or bidirectional antegrade/retrograde approach is safe and effective and facilitates angioplasty when antegrade treatment fails. However, prospective studies with standardised wound care and surveillance protocols are needed to investigate retrograde techniques in patients with CLI who failed antegrade revascularisation, to improve long term limb salvage and survival.

Intraprocedural Transcutaneous Oxygen Pressure and Systolic Toe Pressure Measurements During and After Endovascular Intervention in Patients with Chronic Limb Threatening Ischaemia.

OBJECTIVE: The aim of this study was to evaluate changes in transcutaneous oxygen pressure (tcpO2) and systolic toe pressure (TP) during endovascular intervention. METHODS: This was a single centre prospective, non-randomised, observational feasibility study. Patients with chronic limb threatening ischaemia (CLTI) due to infrainguinal disease scheduled for endovascular treatment were included between March 2018 and December 2019. TcpO2 was measured continuously bilaterally at foot level throughout the procedure and at follow up. Specific time points during the intervention were chosen for comparison to baseline (before arterial puncture): average tcpO2 level five minutes prior to percutaneous transluminal angioplasty (PTA); 10 minutes after PTA; and at completion. Bilateral TP was recorded using laser Doppler flowmetry before arterial puncture, at completion, and at clinical follow up. Angiograms were analysed for successful revascularisation and vascular lesions classified according to the Global Limb Anatomical Scoring System (GLASS). Rutherford and WIfI (Wound, Ischaemia, and foot Infection) classifications were registered, as well as clinical outcome. RESULTS: Twenty-one patients completed the study. Completion angiograms showed inline flow to the foot in all but two patients. Median time to follow up was 10 weeks (range 8 - 13 weeks) and all patients except one improved clinically. TcpO2 decreased during the initial stage of the intervention, from before arterial puncture to five minute average before PTA (p < .001) and did not recover to above baseline values at the end of intervention. TcpO2 increased significantly at follow up (p < .001). TP increased statistically significantly during intervention (p < .001) and at follow up (p < .001) compared with baseline. CONCLUSION: TcpO2 and TP measurements are safe and feasible non-invasive techniques for haemodynamic monitoring during endovascular revascularisation. TP increased significantly immediately after completion of the successful intervention, whereas tcpO2 did not. Both TP and tcpO2 demonstrated a significant increase at the 10 week follow up.

Associations of Clinical Frailty with Severity of Limb Threat and Outcomes in Chronic Limb-threatening Ischaemia.

OBJECTIVE: Investigate the relationship of frailty and severity of chronic limb-threatening ischaemia (CLTI), and their comparative associations with one-year outcomes, in patients presenting to a vascular limb salvage (VaLS) clinic. METHODS: This retrospective cohort study utilised data collected from a prospectively maintained VaLS clinic database. Patients aged ≥50 presenting to the VaLS clinic with CLTI between February 2018 and April 2019 were included. Frailty was measured using the Clinical Frailty Scale (CFS) and limb threat severity by the Wound, Ischaemia, and foot Infection (WIfI) score. Excessive polypharmacy was defined as ≥10 medications. Anticholinergic burden (ACB) score and Charlson comorbidity index (CCI) were calculated for all patients. The primary outcome measure was a composite endpoint of death or amputation at one-year. Associations with outcome were assessed using Cox regression and reported as hazards ratios (HR) with 95% confidence intervals (CI). RESULTS: A total of 198 patients were included, with CFS scores available for 190 patients. 98 patients (52%) were frail (CFS ≥5). 127 patients (67%) initially underwent endovascular revascularisation. Excessive polypharmacy was common (55 patients; 28%). Frailty was associated with increased WIfI stage (P = 0.025) as well as age, female sex, CCI score, number of medications, excessive polypharmacy but not ACB score. Frail patients were more frequently managed non-operatively (P = 0.017). Frailty (HR 1.91; 95% CI 1.09, 3.34; P = 0.024) and WIfI stage 4 (HR 3.29; 95%CI 1.23, 8.80; P = 0.018) were associated with death or amputation on univariable analysis. WIfI stage 4 (HR 2.80; 95%CI 1.04, 7.57; P = 0.042) and CCI score (HR 1.21; 95%CI 1.03, 1.41; P = 0.015), but not frailty (HR 1.25; 95%CI 0.67, 2.33; P = 0.474), were independently associated with death or amputation on multivariable analysis. CONCLUSIONS: Frailty is highly prevalent among CLTI patients and related to severity of limb threat. The CFS may be a useful adjunct to patient risk assessment in CLTI.

Peripheral blood mononuclear cell transplantation to treat no-option critical limb ischaemia: effectiveness and safety.

OBJECTIVE: Local intramuscular transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilised peripheral blood mononuclear cells (PB-MNC) has been shown to be effective for treating patients with no-option critical limb ischaemia (CLI) who are not considered suitable to undergo surgical bypass or percutaneous transluminal angioplasty. The aim of this study was to investigate the effectiveness and safety of PB-MNCs as a treatment for no-option CLI patients. METHOD: This prospective cohort study was conducted between April 2013 and December 2017. Patients with no-option CLI were treated with G-CSF 5-10 µg/kg/day for 3 days. PB-MNCs (7.1±2.2×1010) with CD34+ cells (2.1±1.2×108) were collected by blood cell separator and then injected into the calf or thigh of ischaemic limbs. Ankle-brachial index, toe-brachial index and transcutaneous oxygen tension were recorded at 1 and 3 months after injection. The amputation rate and the wound healing rate were also recorded. RESULTS: Eight patients took part in the study. Two patients experienced rest pain relief 1 month after PB-MNC therapy. Five patients had healed ulcer at 6 months after PB-MNC therapy. Limb ischaemia did not improve after PB-MNC therapy in one patient. Below-knee amputation was performed in that patient due to extension of gangrene. Two patients required reinjection of PB-MNCs because of recurrence of ischaemic ulcer. The limb salvage rate after 1 year was 87.5%. CONCLUSION: Local intramuscular transplantation of G-CSF-mobilised PB-MNCs might be a safe and effective treatment for no-option CLI patients.

Day case angioplasty in a secondary care setting - initial experience.

Background: Peripheral artery disease presents an increasing healthcare burden worldwide. Day-case angioplasty in a secondary care setting can be a safe and effective means of meeting the growing demand for lower limb revascularisation. We evaluated the safety and efficacy of a day-case-based angioplasty service in a UK district general hospital. Patients and methods: Consecutive patients undergoing endovascular revascularisation between August 2018-February 2020 were analysed retrospectively. All patients were discussed at a multi-disciplinary (diabetic foot) team meeting following a day case algorithm. Patient and procedural characteristics, technical success, peri-procedural complications, and 30-day outcome of day-case angioplasties were compared with those requiring overnight stay or were hospitalized. Results: Fifty-seven percent of 138 patients were diabetic, mean age 75 ± 12 years, 95% had critical limb ischaemia (Fontaine III 12%, IV 83%), and baseline ankle brachial pressure index [ABPI] 0.40 ± 0.30. Sixty-three patients (45%) were treated as planned day cases, 21 (15%) required overnight admission for social indications. Fifteen (11%) were planned admissions with the need for sequential debridement procedures, and 39 (28%) were already hospitalised at the time of referral to the vascular service. The overall technical success was 92% and not successful procedures mainly occurred in patients > 80 years. The ABPI increased at the initial follow-up to 0.84 ± 0.18. Fifty-three percent required treatment of > 1 level, 80% included recanalisations of chronic total occlusions, and average total lesion length was 133 ± 90 mm. Closure devices were employed in all cases. There were no major peri-procedural complications. A single minor access-site related bleeding episode (0.8%) occurred, requiring 24 h observation in hospital. While significantly more wounds had closed in out-patients, the mortality, major amputation and target lesion revascularization did not differ between groups. Conclusions: Safe and effective day-case-based angioplasty can be provided in a secondary care setting for patients with critical limb ischaemia needing complex multi-level procedures.

Frequency of limb salvage after infra-inguinal bypass for chronic limb-threatening ischaemia in diabetics: A retrospective study.

A study was conducted to assess the number of limbs salvaged among diabetic patients with chronic limb-threatening ischaemia after infra-inguinal bypass surgeries at a low- to middle-income country (LMIC) hospital. It was a retrospective chart review of diabetic patients who underwent infra-inguinal bypass for lower leg revascularisation for chronic limb-threatening ischaemia at the Section of Vascular Surgery, Aga Khan University Hospital, Karachi (Pakistan) from January 2008 till April 2019. Diabetic patients with chronic limb-threatening ischaemia had a salvage rate of 90.5%(29/32) after infra-inguinal bypass surgery in our set up which is comparable to those described in the literature.

Treatment of lower limb ischaemia in patients with diabetes.

Diabetic chronic limb-threatening ischaemia is a challenging clinical problem with patients at high risk of diabetic foot ulceration (DFU) and limb loss. Patients often remain asymptomatic even in the presence of severe pedal ischaemia until first presenting with tissue loss such as DFU or frank gangrene. Limb salvage units should have the facilities and expertise to provide multidisciplinary team-based holistic care through best medical therapy, rapid diagnosis, prompt revascularisation with endovascular or open surgical techniques and expert wound management. Endovascular revascularisation has become the first line strategy in contemporary clinical practice because of similar outcomes in wound healing and amputation rates in most patients when compared with open surgery. The primary goal is restoration of pulsatile in-line blood flow to the ankle or foot, with an angiosome-directed approach possibly achieving superior outcomes especially in diabetics with poor collaterals. A comprehensive overview of conventional endovascular techniques (such as antegrade true lumen and subintimal approaches), advanced techniques for complex disease (such as retrograde subintimal and pedal-plantar loop approaches or even deep venous arterialisation) and the various treatment options are described. Diabetic limb salvage rates can be excellent with suitable multidisciplinary expertise and care.

Incidence and Risk Factors for Delirium in Elderly Patients with Critical Limb Ischaemia.

OBJECTIVE: Delirium is associated with adverse outcomes, such as increased mortality and prolonged hospital stay. Information on the risk factors for delirium in elderly patients with critical limb ischaemia (CLI) is scarce. The aim of this study was to analyse the incidence of delirium and to identify risk factors for delirium in elderly patients undergoing surgical or endovascular treatment. METHODS: A retrospective cohort study was conducted including patients aged ≥ 65 years undergoing surgical or endovascular treatment for CLI between January 2013 and June 2018. Delirium was scored using the DOSS (Delirium Observation Screening Scale) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria. Risk factors for delirium were analysed using logistic regression. The discriminative ability of the model was calculated using the area under the receiver operating characteristics (AUROC) curve. RESULTS: In total, 392 patients were included, of which 70 (17.9%) developed delirium. Factors associated with an increased risk of delirium were: age, odds ratio (OR) 1.05 (95% confidence interval (CI) 1.0-1.1), history of femoral endarterectomy, OR 4.7 (95% CI 1.5-15), physical impairment, OR 2.2 (95% CI 1.1-4.5), history of delirium, OR 2.7 (95% CI 1.4-5.3), general anaesthesia, OR 2.6 (95% CI 1.2-5.7) and pre-operative anaemia, OR 5.9 (95% CI 2.3-15). The AUROC was .82 (95% CI 0.76-0.87, p < .001). Delirium was associated with more respiratory, renal and surgical complications, as well as a prolonged hospital stay and a more frequent discharge to a nursing home. CONCLUSION: Delirium occurs frequently in patients with critical limb ischaemia undergoing any type of invasive treatment. This study identified multiple risk factors for delirium that may be helpful to delineate patients susceptible to its development.