An audit of secondary prevention for peripheral arterial disease in primary care - scope for improved collaboration between vascular surgery and general practitioners.

BACKGROUND: Symptomatic peripheral arterial disease (PAD) is a common cause for referral from primary care to vascular surgery. Best medical therapy (BMT), encompassing anti-platelets, statins, smoking cessation, blood pressure and glycaemic control, is a cornerstone of PAD management. However, these easily modifiable risk factors are often left unaddressed between referral and clinic review. METHODS: A prospective audit of electronic 'Healthlink' referrals by GPs to the vascular department for symptomatic PAD between July 2021 and June 2022 was performed. Referrals were individually reviewed for demographics, symptoms, medical history, smoking status and medications. An information leaflet on BMT was posted to all GP practices in the Soalta region as part of an educational intervention, with plans to re-audit after 6 months. RESULTS: One-hundred-and-seventy referrals were analysed. The median age was 68.5 years (range 33-94) and 69% (n = 117) were male. The typical vasculopath comorbidity profile was noted. Fifty-two percent (n = 88) were referred with claudication-type pain and 25% (n = 43) with critical limb ischaemia (CLI). Twenty-eight percent (n = 33) were active smokers and 31% (n = 36) had no smoking status documented. Regarding BMT, only 34.5% (n = 40) and 52% (n = 60) were on anti-platelets and statins, respectively. Suspected CLI was not significantly associated with BMT prescription at referral (p = 0.664). Only eleven referral letters mentioned risk factor optimisation. CONCLUSIONS: Our first-cycle results identified significant scope for improvement in community-based risk factor modification for PAD referrals. We aim to continue supporting and educating our colleagues that effective medical management can start safely in primary care and further explore the barriers preventing this.

Acute limb ischaemia due to thrombosed persistent sciatic artery aneurysm presents a surgical challenge in a frail octogenarian.

OBJECTIVES: Persistent sciatic artery (PSA) is a rare congenital anomaly, whereby the embryonic sciatic artery remains patent with associated degrees of femoral axis hypoplasia. Aneurysmal degeneration and distal ischaemia from thromboembolic complications are common. Revascularisation strategies include embolectomy, bypass or interposition grafting and catheter-directed thrombolysis. METHODS: We describe a sedentary 88-year-old woman with right acute limb ischaemia secondary to a thrombosed PSA aneurysm and concurrent occlusive thrombus at the femoral bifurcation. RESULTS: The patient presented with a 3-day history of a cold, painful right foot. Examination revealed Rutherford IIb ischaemia. CT-angiography demonstrated no continuity between the hypoplastic superficial femoral and popliteal arteries, complete occlusion of the right PSA distal to the thrombosed aneurysm and occlusive thrombus in the right profunda. As she was too frail for femoral-distal bypass, we restored femoral axis inflow via profunda embolectomy. Her prognosis remained guarded as we deliberately did not reconstruct the PSA. However, she was discharged pain-free and mobilising with aids 2 weeks later. CONCLUSION: Limb ischaemia in frail, high-risk patients is an ever-increasing challenge for vascular surgeons and requires complex decision-making, balancing comorbidities against desired outcomes. This case illustrates that a selective approach can be sufficient to maintain function despite complex anatomy.

Marrow changes and reduced proliferative capacity of mesenchymal stromal cells from patients with "no-option" critical limb ischemia; observations on feasibility of the autologous approach from a clinical trial.

BACKGROUND AIMS: Approximately 1 in 3 patients with critical limb ischemia (CLI) are not suitable for surgical or endovascular revascularization. Those "no-option" patients are at high risk of amputation and death. Autologous bone marrow mesenchymal stromal cells (MSCs) may provide a limb salvage option. In this study, bone marrow characteristics and expansion potentials of CLI-derived MSCs produced during a phase 1b clinical trial were compared with young healthy donor MSCs to determine the feasibility of an autologous approach. Cells were produced under Good Manufacturing Practice conditions and underwent appropriate release testing. METHODS: Five bone marrow aspirates derived from patients with CLI were compared with six young healthy donor marrows in terms of number of colony-forming units-fibroblast (CFUF) and mononuclear cells. The mean population doubling times and final cell yields were used to evaluate expansion potential. The effect of increasing the volume of marrow on the CFUF count and final cell yield was evaluated by comparing 5 CLI-derived MSCs batches produced from a targeted 30 mL of marrow aspirate to five batches produced from a targeted 100 mL of marrow. RESULTS: CLI-derived marrow aspirate showed significantly lower numbers of mononuclear cells with no difference in the number of CFUFs when compared with healthy donors' marrow aspirate. CLI-derived MSCs showed a significantly longer population doubling time and reduced final cell yield compared with young healthy donors' MSCs. The poor growth kinetics of CLI MSCs were not mitigated by increasing the bone marrow aspirate from 30 to 100 mL. CONCLUSIONS: In addition to the previously reported karyotype abnormalities in MSCs isolated from patients with CLI, but not in cells from healthy donors, the feasibility of autologous transplantation of bone marrow MSCs for patients with no-option CLI is further limited by the increased expansion time and the reduced cell yield.

Diagnostic Performance of Ankle-Brachial Pressure Index in Lower Extremity Arterial Disease.

Introduction Ankle-brachial pressure indices (ABIs) continue to form the basis of diagnostics for lower extremity arterial disease (LEAD). However, there remains a paucity of data to support its accuracy. This study aims to evaluate its diagnostic sensitivity and specificity using established arterial-imaging modalities as a benchmark. Methods In this retrospective study, a regional, prospectively maintained, vascular laboratory database was interrogated to identify referred patients with arterial disease who underwent concomitant assessment with ABI and lower limb arterial duplex ultrasound (DUS). Duplex acted as the reference standard. Those who had peripheral computed tomography angiogram (CTA) within 3 months of initial assessment were included in a subgroup analysis to correlate ABI with CTA. The primary end point was the sensitivity and specificity of ABI compared with DUS as the reference standard. Results Concomitant assessment was performed in 438 limbs (250 patients) over a 27-month period. The ABI was normal (0.9 to 1.4) in 196 limbs (44.9%) and abnormal in the remaining 241 limbs (55.1%). False-positive results occurred in 83 out of 241 limbs (34.4%), and false-negative results occurred in 54 limbs out of 196 (27.5%). True-positive results were 158 out of 241 limbs (65.6%), whereas true-negative results were 142 out of 196 limbs (72.4%). ABI using DUS as a benchmark identified a sensitivity for peripheral artery disease of 72.3% and a specificity of 69.3%. Concomitant CTA imaging was available in 200 limbs. The sensitivity and specificity of ABI correlated with CTA were 65.5 and 68.8%, respectively. Conclusion ABIs have a moderate predictive value in the diagnosis of LEAD. Normal range outcomes cannot be taken to infer the absence of LEAD and, as such, further arterial imaging in the form of DUS or angiography should be strongly considered in those with suspected underlying disease requiring intervention. Further noninvasive tests such as exercise studies or pulse volume waveforms should be considered, if diagnostic uncertainty exists, in those requiring nonoperative intervention and risk factor control.

Validation of ERICVA Risk Score as a Predictor of One Year Amputation-Free Survival of Patients with Critical Limb Ischemia.

BACKGROUND: The ERICVA score was derived to predict amputation-free survival in patients with critical limb ischemia (CLI). It may be a useful tool to stratify patients in trials of novel interventions to treat CLI but, as yet, it has not been externally validated. METHODS: A prospective database of CLI patients was developed during prescreening of patients for a phase 1 stem cell therapy clinical trial. The primary outcome was amputation free survival (AFS) at 1 year. Both the full ERICVA scale (11 parameters) and simplified ERICVA scale (5 parameters) were validated. Data analysis was performed by calculation of the area under the receiver operating characteristic (ROC) curve examining the predictive value of the scores. The Chi-square test was used to examine the association between risk group and one-year AFS and the cumulative survival of the three risk groups was compared using Kaplan Meier survival curves. RESULTS: A series of 179 CLI patients were included in the analysis. The Chi-square test of independence showed a significant association between the risk group (high, medium and low) and one-year AFS outcome (P = 0.0007). Kaplan-Meier survival curve showed significant difference in one-year AFS between the three risk groups (log-rank P < 0.001). The area under the curve (AUC) was found to be 0.63 and 0.61 for the full and simplified score, respectively. The sensitivity of the full score was 0.44 with specificity of 0.84. The simplified score had a sensitivity of 0.28 and specificity of 0.92. CONCLUSION: The ERICVA risk score system was found to have a fair validity but cannot be considered reliable as a single predictor of one year AFS of CLI patients. The simplified score had an AUC almost identical to the full score and can accordingly replace the full score.

Concomitant vs. Staged Treatment of Varicose Tributaries as an Adjunct to Endovenous Ablation: A Systematic Review and Meta-Analysis.

OBJECTIVE: This review compares the outcomes of both concomitant and staged superficial varicose tributary (SVT) interventions as an adjunct to endovenous truncal ablation. METHODS: A systematic search of Medline through Pubmed, Embase, and the Cochrane Central Register of Controlled Trials was last performed in November 2019. All studies comparing the outcomes of both concomitant and staged treatments for SVT as an adjunct to endovenous truncal ablation were included. Each included study was subject to an evaluation of methodological quality using the Downs and Black assessment tool. Outcomes assessed included rates of re-intervention, complications, and thrombotic events. Quality of life (QOL) and disease severity were also analysed. Data were pooled with a random effects model. RESULTS: Fifteen studies (6 915 limbs) were included for analysis. Included studies were of reasonable methodological quality. Re-intervention rates were significantly lower in the concomitant group (6.3% vs. 36.1%) when compared with staged intervention (relative risk [RR] 0.21 [95% CI 0.07-0.62], p = .004, I2 = 90%, p ≤ .001). Reported complications (RR 1.14 [95% CI 0.67-1.93], p = .64) and rates of deep venous thrombosis (RR 1.41 [95% CI 0.72-2.77] p = .31) were similar in each group. Overall disease severity (Venous Clinical Severity Score) was lower in the concomitant group (-1.16 [95% CI, -1.97- -0.35] p = .005), while QOL, assessed using the Aberdeen Varicose Vein Questionnaire, favoured concomitant treatment when measured at less than three months (weighted mean difference [WMD] -3.6 [95% CI, -7.17- -0.03] p = .050) and between three and 12 months (WMD -1.61 [95% CI, -2.99- -0.23] p = .020). CONCLUSION: Concomitant and staged treatments are safe and effective. Improvements in early disease severity and QOL scores were better in the concomitant group. While meta-analysis suggests that concomitant intervention offers significantly lower rates of re-intervention, studies assessing its merits are subject to some biases. This benefit was not reflected by the randomised trial subgroup analysis, which identified no difference in re-intervention.

Determination of optimal implantation site in central venous system for wireless hemodynamic monitoring.

BACKGROUND/PURPOSE: In recent years, treatment of heart failure patients has proved to benefit from implantation of pressure sensors in the pulmonary artery. Despite this, pulmonary artery pressure is related to the left ventricle, and cannot provide information on the right side of the heart. By contrast, pressure in the central venous system is directly connected to the right atrium and could potentially predict a wider range of heart failure conditions. The purpose of this work is to find an optimal site for implantation in the central venous system of a hemodynamic wireless sensor for heart failure monitoring. Since all previous hemodynamic sensors were located in the pulmonary artery, there is no existing information about an optimal site in the central venous system. METHODS: This study analysed data obtained from CT scans of most relevant anatomical features in the inferior vena cava. The most important parameters of the sites of interest were extracted, analysed statistically and compared, with the purpose to select an optimal site of implantation. RESULTS: The results obtained show that the area comprised between the iliac bifurcation and the lower renal vein (and between the second and third lumbar veins) is the most suitable site of implantation for a hemodynamic sensor. Parameters such as its straight anatomy, diameter (21 mm) and link distance (106 mm) present it as a convenient location for implantation. Its procedure appears relatively easy, as access from the femoral vein is close to the site of interest. In addition, there are not major delicate structure in its surroundings that may pose a risk to the patient. CONCLUSION: This study concludes that the area between the iliac join and the lower renal vein (and the 2nd and 3rd lumbar veins) is an optimal site for the accommodation of a hemodynamic sensor.

Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities.

BACKGROUND: Critical limb ischemia (CLI) is the most severe manifestation of peripheral vascular disease. Revascularization is the preferred therapy, but it is not achievable in 25%-40% of patients due to diffuse anatomic distribution of the disease or medical comorbidities. No-option CLI represents an unmet medical need. Mesenchymal stromal cells (MSCs) may provide salvage therapy through their angiogenic and tissue-trophic properties. This article reports a phase 1b clinical study examining the safety and feasibility of intramuscular transplantation of autologous bone-marrow MSCs for patients with no-option CLI. METHODS: Twelve patients were enrolled in the clinical trial, and nine proceeded to bone marrow aspiration and culture expansion of MSCs. RESULTS: A high rate of karyotype abnormality (>30%) was detected in the produced cell batches, resulting in failure of release for clinical administration. Four patients were treated with the investigational medicinal product (IMP), three with a low dose of 20 × 106 MSCs and one with a mid-dose of 40 × 106 MSCs. There were no serious adverse events related to trial interventions, including bone marrow aspiration, IMP injection or therapy. CONCLUSIONS: The results of this trial conclude that an autologous cell therapy approach with MSCs for critical limb ischemia is limited by the high rate of karyotype abnormalities.