Browsing by Subject "Peripheral Arterial Disease"

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    Contemporary Outcomes of Distal Lower Extremity Bypass for Chronic Limb Threatening Ischemia and a Model Based Comparison with Non-surgical Therapies
    (2021-03) Leckie, Katherin; Bakoyannis, Giorgos; Yiannoutsos, Constantin; Murphy, Michael
    Objective: Gold standard therapy for chronic limb threatening ischemia (CLTI) is revascularization but in patients in whom below-the-knee bypass is indicated autologous vein conduit may not be available. Contemporary outcomes of distal bypass with suboptimal conduits have not been well described and recent advances in non-surgical therapies raise the question of whether in some cases there is evidence that these should be considered. Methods: Data was obtained from the Vascular Quality Initiative (VQI) registry as well as from a multi-center, randomized clinical trial of cell therapy. Incidence of major amputation after distal bypass was estimated for the VQI cohort by conduit type using non-parametric survival analysis with death as a competing risk. A cox proportional hazards model was then fit to the pooled data in a stepwise fashion with death as a competing risk, including evaluations for appropriate transformation, time dependency and interactions for each included covariate, and hazard ratios were estimated for the risk of major amputation by treatment. Results: At 365 days, the estimated cumulative incidence of major amputation with death as a competing risk is 25% after distal bypass with non-autologous biologic conduit (0.2499, 95% CI 0.2242 - 0.2785), 13% for prosthetic (0.1276, 95% CI 0.1172 - 0.1389) and 9% for GSV (0.0900, 95% CI 0.0848 - 0.0956). The cox proportional hazards model found a significant interaction between age and treatment. Compared to bypass with non-autogenous biologic, the hazard ratios for bypass with GSV were 0.41 (p<0.0001), 0.41 (p<0.0001), 0.42 (p<0.0001) and 0.42 (p<0.0001) respectively at ages 55, 60, 65 and 70 and for bypass with prosthetic were 0.68 (p=0.0043), 0.67 (p=0.0004), 0.65 (p<0.0001) and 0.64 (p<0.0001) respectively and for autologous cell therapy 0.22 (p=0.0005), 0.34 (p=0.0011), 0.52 (p=0.0196) and 0.76 (p=0.3677) respectively. No significant differences were found between best medical management and distal bypass with non-autologous biologic. Conclusion: The risk of major amputation after distal bypass is lowest in patients with GSV conduit and highest following bypass with non-autologous biologic. Using a semi-parametric model, cell therapy was estimated to significantly decrease the risk of amputation compared to distal bypass with non-autologous biologic conduit in younger patients.
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    Rationale and design of the Clinical and Histologic Analysis of Mesenchymal Stromal Cells in AmPutations (CHAMP) trial investigating the therapeutic mechanism of mesenchymal stromal cells in the treatment of critical limb ischemia
    (Elsevier, 2018-07) Wang, S. Keisin; Green, Linden A.; Drucker, Natalie A.; Motaganahalli, Raghu L.; Fajardo, Andres; Murphy, Michael P.; Surgery, School of Medicine
    OBJECTIVE: Currently, there are no accepted nonsurgical therapies that improve the delivery of blood-derived nutrients to patients with critical limb ischemia. Here, we describe the ongoing phase 1/2 Clinical and Histologic Analysis of Mesenchymal Stromal Cells in AmPutations (CHAMP) trial, which will provide crucial evidence of the safety profile of mesenchymal stromal cells (MSCs) and explore their therapeutic mechanisms in the setting of critical limb ischemia requiring below-knee amputation (BKA). METHODS: In the CHAMP and the parallel marrowCHAMP trials (hereafter grouped together as CHAMP), a total of 32 extremities with rest pain or tissue loss requiring BKA will be enrolled to receive intramuscular injections of allogeneic MSCs (CHAMP; n = 16) or autogenous concentrated bone marrow aspirate (marrowCHAMP; n = 16) along the distribution of the BKA myocutaneous flap and proximal tibialis anterior. After treatment, subjects are randomized to BKA at four time points after injection (days 3, 7, 14, and 21). At the time of amputation, skeletal muscle is collected at 2-cm increments from the tibialis injection site and used to determine proangiogenic cytokine description, MSC retention, quantification of proangiogenic hematopoietic progenitor cells, and histologic description. Clinical limb perfusion before and after treatment will be quantified using transcutaneous oximetry, toe-brachial index, ankle-brachial index, and indocyanine angiography. Additional clinical end points include all-cause mortality, need for amputation revision, and gangrene incidence during the 6-month post-treatment follow-up. RESULTS: Enrollment is under way, with 10 patients treated per protocol thus far. We anticipate full conclusion of follow-up within the next 24 months. CONCLUSIONS: CHAMP will be pivotal in characterizing the safety, efficacy, and, most important, therapeutic mechanism of allogeneic MSCs and autogenous concentrated bone marrow aspirate in ischemic skeletal muscle.