In the United States, >200 000 new patients are diagnosed with abdominal aortic aneurysm (AAA) each year. Consequently, >40 000 highly morbid aortic reconstructions are performed each year to prevent aneurysm rupture, a catastrophic event associated with near-certain mortality. No pharmaceutical currently exists to slow aneurysm growth, but a 50% reduction in diameter growth per annum could halve the number of aortic reconstructions required. Therefore, successful use of cell therapy to modulate chronic inflammation hallmark to AAA to slow diameter expansion represents a potentially paradigmaltering treatment.There continues to be no US Food and Drug-approved medication to slow or stop AAA growth. This deficit is certainly not because of a lack of effort over the previous decades. Initial investigations focused on the reduction of mechanical stress through decreasing blood pressure and sac pressurization cycles; however, clinical trials investigating drugs, such as, angiotensin II-converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers, all failed to demonstrate a therapeutic reduction of diameter growth compared with placebo. Next, the inhibition of matrix metalloproteinases was trialed with doxycycline, an antibiotic inhibitor of matrix metalloproteinases 2 and 9. Doxycycline also treats species of Chlamydia, which were isolated from the aortic walls of a minority of aneurysmal arteries. Although initial uncontrolled results were promising, therapeutic response was not replicated in large randomized studies. Last, aortic wall inflammation was targeted using statins, a ubiquitous anti-inflammatory, lipid-lowering drug to limited success. The discovery of a nonsurgical treatment for AAA is contingent on the robust understanding of disease pathogenesis, which continues to be nebulous at best.AAA risk factors, such as, tobacco abuse, advancing age, uncontrolled hypertension, male sex, and white ethnicity, have all been well described but fail to provide evidence elucidating pathogenesis. Regardless, existing evidence implicates that disease initiation is multifactorial with a strong genetic element.There has been a focus of late toward the role of autoimmune mechanisms in AAA formation. The characterization of aortic wall inflammation consisting of mononuclear infiltrates, immunoglobulins, cytokines, and proteases implicate both a host innate and adaptive response. Of note, concentrations of CD4 + T cells have been recently discovered in the periadventitial vascular-associated lymphatic tissue expressing identical T cell receptors, against a currently unknown antigen, and therefore clonally expanded, providing crucial evidence for AAA as an autoimmune disease.1 Moreover, interleukin (IL)-17, a cytokine elaborated from the antigen-specific Th17 lymphocyte and overexpressed in autoimmune disorders, is highly expressed in the AAA condition. Abrogation of this cytokine, in animal models, has demonstrated efficacy in decreasing aneurysm diameter growth.2 Although several putative autoantigens have b...

If successful, MOBILE could add definitive, high-quality evidence in support of cBMA for the treatment of poor-option CLI patients and provide an additional modality for patients who face amputation secondary to advanced limb ischemia.

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Objective: Previously published results of carotid revascularization with both transfemoral stenting and endarterectomy have demonstrated inferior outcomes in neurologically symptomatic patients. This study was completed to determine the real-world, symptom-based perioperative and 1-year outcomes for transcarotid artery revascularization (TCAR). Methods: An institutional retrospective review of all TCARs performed outside of clinical trial regulations from 2016 to 2019 was completed. Eligible patients were assigned as symptomatic or not on the basis of a history of a unilateral neurologic deficit attributable to a hemodynamically significant extracranial carotid artery lesion within the previous 180 days. Univariate analysis consisting of Fisher exact and Student t-tests, as appropriate, was performed between cohorts. Kaplan-Meier analysis was completed to estimate the stroke-free survival at 1 year postoperatively. Results: Within the investigational period, 167 patients (85 symptomatic) qualified for study inclusion. Baseline demographics were roughly equivalent, although symptomatic patients were more likely to be female (28.0% vs 9.4%; P < .01). Procedures in symptomatic patients were more difficult as measured by a composite of estimated blood loss (41 mL vs 58 mL; P ¼ .04) and operative time (67 minutes vs 75 minutes; P ¼ .06). We did not observe an increased incidence of macroscopic debris in the ENROUTE (Silk Road, Sunnyvale, Calif) neuroprotection filter in symptomatic patients after stent deployment. Within the 30-day perioperative period, we found no difference with respect to ipsilateral stroke (2.4% vs 1.2%; P > .99), myocardial infarction (0% vs 0%; P > .99), and Categorical variables are presented as percentage. Continuous variables are presented as mean 6 standard deviation.

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Introduction: Here we present a composite of proteomic, cellular, and radiological analyses that define the mechanisms by which autologous concentrated bone marrow mononuclear cells (cBMNC) promote limb preservation in patients with critical limb ischemia. Methods: CD45 + , CD34 + , CD105 + , and VEGFR-2 + cells were enumerated using fluorescent activated cell sorting (FACS) from aliquots of the cBMNC from each patient enrolled in the Phase III MOBILE TRIAL. Direct limb perfusion was measured with Positron Emission Tomography/Computed Tomography (PET/CT) with radiolabeled water ( 15 H20). Anterior tibialis muscle (ATM) into which cBMNC was injected prior to below knee amputation in the Phase I CHAMP trial were collected for capillary density and proteomic analyses. Results: There were no differences in the number of CD45 + (636 ± 388 vs. 868 ± 699 x 10 6 , p= 0.279), VEGFR-2 + (0.4 ± 0.8 vs. 0.3 ± 0.6 x10 6 , p=0.757) and CD34 + (21 ± 13 vs. 35 ± 30 x 10 6 , p= 0.156) cells in the cBMNC product injected in those patients undergoing amputation and those with a preserved limb (n=90). There was a significant association between CD105 + (7 ± 4 vs. 16 ± 13 x 10 6 , p= 0.05) cells in patients and freedom from amputation. A Blood Perfusion Index ( BPI ) was calculated by comparing the ratio of H2O 15 peak tracer uptake level of the untreated: treated leg with an increase from 0.38 at baseline to 0.54 (42%) at 12 weeks (n=4, p< 0.05). There was an increase in CD31 + capillaries in the ATM after injection of cBMNC. ATM specimen also showed increases in VEGF-A, angiopoietin-2, and MMP-9 compared to the untreated specimen. Conclusion: This first in man analyses provides conclusive evidence that cBMNC improves limb perfusion via capillary formation. This study suggests that bone marrow cell mediated angiogenesis may be dependent on CD105 + mesenchymal progenitor cells.