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Updated: Jun 13, 2025

Predicting Amputation using Local Circulating Mononuclear Progenitor Cells in Angioplasty-treated Patients with Critical Limb Ischemia
Published on: September 22, 2020
Streamlined Clinical Management Pathways May Reduce Major Amputations in Patients with Chronic Limb Threatening
John S M Houghton1, Anna Meffen2, Laura J Gray3
1Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; Leicester Vascular Institute, University Hospitals of Leicester NHS Trust, Leicester, UK; National Institute for Health Research Leicester Biomedical Research Centre - The Glenfield Hospital, Leicester, UK.
Objective:
Patient characteristics and patterns of disease in chronic limb threatening ischaemia (CLTI) have markedly changed in recent years. Urgent specialist referral and timely revascularisation are recommended in international guidelines. UK guidelines now recommend revascularisation within five days of referral for inpatients and two weeks in outpatients. This study compared the contemporary one year major amputation incidence in patients with CLTI with a historical cohort at a single UK centre.
Methods:
This was a single centre, observational cohort study with historical controls. A prospective cohort was recruited between May 2019 and March 2022. A historical cohort presenting between 2013 and 2015 inclusive was retrospectively identified. Significant changes in management pathways, including establishing a rapid access limb salvage clinic, occurred between these periods, aiming to expedite time from referral to revascularisation. The one year primary outcome was major amputation, and the secondary outcome was death. Major amputation was analysed by Fine-Gray competing risks models (death as the competing risk), presented as subdistribution hazard ratios (SHRs). One year mortality was analysed by Cox regression, presented as hazard ratios. Analyses were adjusted for propensity score.
Results:
A total of 928 patients were included (432 prospective and 496 historical). Proportions of patients presenting with tissue loss (72.2% vs. 71.6%; p = .090) were similar in both cohorts. At one year, 48 patients (11.1%) in the prospective cohort and 124 patients (25.0%) in the historical cohort had undergone a major amputation (p < .001). Risk of major amputation was 57.0% lower in the prospective cohort compared with the historical cohort after adjustment for propensity score (SHR 0.43, 95% confidence interval 0.29 - 0.63; p < .001).
Conclusion:
An encouraging reduction in major amputation incidence was observed after improvements to CLTI management pathways, but residual confounding is likely. The generalisability of these results is uncertain.

