CLI

Casper O. da Costa-Luis

tqdm is intended to be used in frontends (giving end users a visual indication of progress of computations or data transfer). It is also useful for developers for debugging purposes, both as a profiling tool and also as a way of displaying logging information of an iterative task (such as error during training of machine learning algorithms). Due to its ease of use, the library is also an ideal candidate for inclusion in Python educational courses. For general (not necessarily Python) purposes, the command-line interface (CLI) mode further presents a useful tool for CLI users and system administrators monitoring data flow through pipes.

A. Farber, K. Rosenfield, Sandra Siami, Michael Strong, M. Menard

Abstract There is significant variability and equipoise in the management of critical limb ischemia (CLI). The Best Endovascular vs Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST‐CLI) trial, funded by the National Heart, Lung, and Blood Institute, is a prospective, open label, multicenter, multispecialty randomized controlled trial designed to compare treatment efficacy, functional outcomes, cost‐effectiveness, and quality of life for 2100 patients suffering from CLI. BEST‐CLI is enrolling those patients who are determined to be candidates for open surgical or endovascular revascularization and is designed to be comprehensive, pragmatic, and balanced. Enrollment is occurring at >130 sites across the world, and BEST‐CLI is nearing the finish line. Although the trial has encountered a number of obstacles, they are being successfully navigated. This trial promises to establish an evidence‐based standard of care in the management of this population of vulnerable patients.

M. Menard, M. Jaff, A. Farber, K. Rosenfield, M. Conte, C. White, J. Beckman, N. Choudhry, L. Clavijo, T. Huber, Katherine R. Tuttle, Taye H. Hamza, A. Schanzer, I. Laskowski, M. Cziraky, A. Drooz, Maxwell Van Over, M. Strong, I. Weinberg

OBJECTIVES The utilization of optimal medical therapy (OMT) in patients with chronic limb threatening ischemia (CLTI) has not been well studied. BEST-CLI is an NIH-sponsored multi-center randomized controlled trial comparing revascularization strategies in CLTI patients. We evaluated the utilization of guideline-based OMT among patients with CLTI at the time of their enrollment into the trial. METHODS A multidisciplinary committee defined OMT criteria related to blood pressure and diabetic management, lipid-lowering and anti-platelet medication use, and smoking status for patients enrolled in BEST-CLI. Status reports indicating adherence to OMT were provided to participating sites at regular intervals. Baseline demographic characteristics, comorbid medical conditions, and utilization of OMT at trial entry were evaluated for all randomized patients. A linear regression model was used to identify the relationship of predictors to utilization of OMT. RESULTS At time of randomization (n=1830 total enrolled), 87% of patients in BEST-CLI had hypertension, 69% had diabetes, 73% had hyperlipidemia, and 35% were currently smoking. Adherence to 4 OMT components (controlled blood pressure, not currently smoking, use of one lipid-lowering medication, and use of an antiplatelet agent) was modest. Only 25% of patients met all 4 OMT criteria; 38% met 3, 24% met 2, 11% met only 1 and 2% met none. Age ≥80 years, coronary artery disease, diabetes, and Hispanic ethnicity were positively associated, while Black race was negatively associated, with utilization of OMT. CONCLUSIONS A significant proportion of patients in BEST-CLI did not meet OMT guideline-based recommendations at time of entry. This data suggests a persistent major gap in the medical management of patients with advanced peripheral atherosclerosis and CLTI. Changes in OMT adherence over the course of the trial and their impact on clinical outcomes and quality of life will be assessed in future analyses.

Grazia Marsico, C. Jin, S. Abbah, E. Brauchle, Dilip Thomas, A. L. Rebelo, D. Orbanić, S. Chantepie, P. Contessotto, D. Papy-Garcia, C. Rodriguez-Cabello, M. Kilcoyne, K. Schenke-Layland, N. Karlsson, Karl J. A. McCullagh, A. Pandit

Critical limb ischemia (CLI) is characterized by the impairment of microcirculation, necrosis and inflammation of the muscular tissue. Although the role of glycans in mediating inflammation has been reported, changes in the glycosylation following muscle ischemia remains poorly understood. Here, a murine CLI model was used to show the increase of high mannose, α-(2, 6)-sialic acid and the decrease of hybrid and bisected N-glycans as glycosylation associated with the ischemic environment. Using this model, the efficacy of an elastin-like recombinamers (ELR) hydrogel was assessed. The hydrogel modulates key angiogenic signaling pathways, resulting in capillary formation, and ECM remodeling. Arterioles formation, reduction of fibrosis and anti-inflammatory macrophage polarization wa also induced by the hydrogel administration. Modulation of glycosylation was observed, suggesting, in particular, a role for mannosylation and sialylation in the mediation of tissue repair. Our study elucidates the angiogenic potential of the ELR hydrogel for CLI applications and identifies glycosylation alterations as potential new therapeutic targets.

Zeinab Shirbaghaee, Saeed Heidari Keshel, M. Rasouli, M. Valizadeh, S. H. Hashemi Nazari, Mohammad Hassani, M. Soleimani

Background Critical limb ischemia (CLI) is associated with increased risk of tissue loss, leading to significant morbidity and mortality. Therapeutic angiogenesis using cell-based treatments, notably mesenchymal stem cells (MSCs), is essential for enhancing blood flow to ischemic areas in subjects suffering from CLI. The objective of this study was to evaluate the feasibility of using placenta-derived mesenchymal stem cells (P-MSCs) in patients with CLI. Methods This phase I dose-escalation study investigated P-MSCs in nine CLI patients who were enrolled into each of the two dosage groups (20 × 10^6 and 60 × 10^6 cells), delivered intramuscularly twice, two months apart. The incidence of treatment-related adverse events was the primary endpoint. The decrease in inflammatory cytokines, improvement in the ankle-brachial pressure index (ABI), maximum walking distance, vascular collateralization, alleviation of rest pain, healing of ulceration, and avoidance of major amputation in the target leg were the efficacy outcomes. Results All dosages of P-MSCs, including the highest tested dose of 60 × 10^6 cells, were well tolerated. During the 6-month follow-up period, there was a statistically significant decrease in IL-1 and IFN-γ serum levels following P-MSC treatment. The blood lymphocyte profile of participants with CLI did not significantly differ, suggesting that the injection of allogeneic cells did not cause T-cell proliferation in vivo. We found clinically substantial improvement in rest pain, ulcer healing, and maximum walking distance after P-MSC implantation. In patients with CLI, we performed minor amputations rather than major amputations. Angiography was unable to demonstrate new small vessels formation significantly. Conclusion The observations from this phase I clinical study indicate that intramuscular administration of P-MSCs is considered safe and well tolerated and may dramatically improve physical performance and minimize inflammatory conditions in patients with CLI. Trial registration : IRCT, IRCT20210221050446N1. Registered May 09, 2021.