Multi-institutional patterns of clopidogrel response among patients undergoing transcarotid artery revascularization.

OBJECTIVE: Current guidelines recommend dual antiplatelet therapy (DAPT) in patients undergoing carotid artery stenting. The most common DAPT regimen is aspirin and clopidogrel, a P2Y12 receptor antagonist; however, the prevalence of clopidogrel resistance (CR) in patients undergoing percutaneous coronary interventions may exceed 60%. Few studies have investigated the prevalence and impact of CR in patients undergoing extracranial carotid artery stenting, particularly transcarotid artery revascularization (TCAR). METHODS: Consecutive high-risk patients ≥ 18 years who underwent TCAR for high grade (≥70%) and/or symptomatic (≥50%) carotid stenosis with preoperative P2Y12 testing between August 2019 and December 2021 were identified across five institutions. Preoperative platelet reactivity was measured with the VerifyNow P2Y12 Reaction Unit (PRU) Test (Instrumentation Laboratory, Bedford, MA), with CR defined as PRU ≥ 194 and hyper-response as PRU <70. Patients without preoperative P2Y12 testing within 30 days prior to TCAR or those on a non-clopidogrel P2Y12 inhibitor preoperatively were excluded. The primary outcome of interest was prevalence of CR. Secondary outcomes of interest included the incidence of ischemic and hemorrhagic complications. RESULTS: Of 92 patients identified, the majority were male (59%) and Caucasian (75%) with a mean age of 75 years (±8, range 56-92). Preoperatively, 93% of patients were on aspirin, 100% on clopidogrel, and 13% on therapeutic anticoagulation. At presentation, 36% were symptomatic. The mean preoperative P2Y12 was 156 PRU (±76, range 6-349). In total, 30 (33%) patients met criteria for CR (mean PRU 240 ± 37; range 197-349), and 15 (16%) met criteria for hyper-responder (mean PRU 38 ± 20; range 6-68). There was no significant difference by clopidogrel response phenotype in terms of sex (p = 0.246), race (p = 0.384), or symptomatic presentation (p = 0.956). Postoperatively, the cumulative incidence of stroke and MI was 2.1%, with no statistically significant difference in the incidence of in-hospital stroke (PRU 238, p = 0.489) or MI (PRU 168, p = 1) between clopidogrel phenotypes. Three (3.3%) patients, one CR (PRU 240) and two responders (PRU 119 and PRU 189), experienced postoperative access site hematomas that required no subsequent intervention. No other index hospitalization hemorrhagic complications occurred. CONCLUSIONS: Using preoperative P2Y12 testing with a threshold PRU ≥ 194 to define CR, we identified a high prevalence of CR in patients undergoing TCAR similar to that in the pre-existing coronary literature. We found no significant differences in postoperative ischemic or hemorrhagic complications by clopidogrel response phenotype, although complication rates in the overall study cohort were low. CR may be a spectrum from responder to partial responder to complete non-responder, and this may account for the differences in our CR cohort compared to the ROADSTER 2 protocol deviation cohort. Further investigation is warranted to determine if a quantitative assessment of CR is sufficient to identify patients at risk of developing secondary cerebrovascular ischemic events in this patient population.

Regional Variation in Usage of Ultrasound-Guided Femoral Access in the Vascular Quality Initiative.

BACKGROUND: Access site complications are among the most common complications following peripheral vascular interventions. Previous studies have demonstrated a reduced rate of complications with ultrasound-guided vascular access (UGVA). The objective of this study is to evaluate the regional use of UGVA within the Vascular Quality Initiative (VQI). METHODS: The VQI peripheral intervention module between 2010 and 2018 was evaluated. Regional ID was used to compare distribution of ultrasound usage. Regions were grouped into terciles based on the rate of ultrasound use. Patients were categorized based on type of access. Primary outcome was use of ultrasound across regions. Secondary outcomes were access site complications. RESULTS: Over 43,000 cases across the 18 VQI regions were evaluated. The average rate of ultrasound usage was 71% across the regions with a wide variation (range 38-97%). There is a significant difference in utilization among the top third (87%), middle third (79%), and bottom third (58%) (P < 0.001). Average sheath size was similar across all 3 groups. A higher use of ultrasound-guided access was associated with significantly fewer access site complications (top third 1.96% vs. bottom third 3.04%, P < 0.001), the most significant of which was a decreased rate of access site hematoma (top third 1.37% vs. bottom third 2.35%, P < 0.001). CONCLUSIONS: This is the first study to evaluate ultrasound-guided access across VQI regions. Our results demonstrate that despite strong evidence supporting the utilization of UGVA, there remains a wide variation in ultrasound usage across VQI regions. This is also the first study to show that the prevalence of ultrasound use in peripheral vascular interventions (PVI) is inversely related to access site complications. Given all of the data supporting the usage of UGVA across numerous specialties, our findings encourage the consideration of an ultrasound-first approach for vascular access in PVI and the implementation of targeted strategies and evidence-based guidelines to enhance UGVA utilization in PVI.

The role of the inferior mesenteric artery in predicting secondary intervention for type II endoleak following endovascular aneurysm repair.

OBJECTIVE: Endovascular aneurysm repair (EVAR) is associated with a greater risk of graft-related complications and need for secondary interventions compared with open repair. Type II endoleak (EL-2) is the most common complication. We examined the hypothesis that a functionally occluded inferior mesenteric artery (IMA) before EVAR was associated with fewer secondary interventions for EL-2. METHODS: All nonruptured abdominal aortic aneurysms (AAA) treated by EVAR using U.S. Food and Drug Administration-approved endografts from January 2005 to December 2017 were retrospectively reviewed, including computed tomography angiograms. Preoperative patency of the IMA and any secondary interventions performed after the index EVAR procedure were recorded. A functionally occluded IMA was defined as one that was (1) chronically occluded or severely stenosed on preoperative imaging or (2) coil embolized before EVAR. Secondary interventions for persistent EL-2 were indicated when AAA sac diameter increased by more than 5 mm. RESULTS: The study cohort comprised 490 patients (84 women) with a mean age of 74.8 ± 8.2 years. The mean preoperative AAA diameter was 5.6 ± 0.9 cm. One hundred twenty-nine patients (26.3%) died during follow-up. The mean follow-up of survivors was 38 months. Types (prevalence) of endoleak were I (2.4%), II (18.9%), III (0.7%), IV (0.5%), and V (0.2%). Patients with a functionally occluded IMA underwent significantly fewer secondary interventions for EL-2 compared with patients with a patent IMA (2.6% vs 7.1%; P = .020). All secondary interventions in the functionally occluded IMA group involved the lumbar arteries (LA). When the IMA was patent, secondary interventions were equally distributed between the LA and IMA. Logistic regression confirmed that a functionally patent IMA was associated with a greater number of secondary interventions for EL-2 (odds ratio, 3.0; 95% confidence interval, 1.2-7.5; P = .025). CONCLUSIONS: Patients with a functionally occluded IMA required significantly fewer secondary interventions for EL-2 after EVAR. In addition, the type of vessels intervened on were primarily LA. Among patients with a patent IMA, preoperative coil embolization may decrease secondary interventions and improve the long-term durability of EVAR.

TREO Aortic Endograft Demonstrates Significant Aneurysmal Sac Shrinkage.

BACKGROUND: Aneurysmal sac shrinkage is associated with successful aneurysm repair after endovascular aortic repair (EVAR). There are a variety of approved aortic endografts, with a recent study demonstrating increased sac shrinkage in certain endografts compared with others. The TREO endograft (Terumo Aortic Ltd, Renfrewshire, Scotland, UK) is being evaluated for use in EVAR, with preliminary data demonstrating high rates of success. The objective of this study is to evaluate sac shrinkage of the TREO endograft. METHODS: This is a retrospective analysis of EVARs at a single institution by a high-volume surgeon over a 1-year period in which the TREO graft was used. The change in sac size and rate of sac shrinkage (mm/mo) were evaluated between TREO and non-TREO grafts. All TREO grafts were included in the analysis. Non-TREO grafts were matched a priori for TREO indications for use anatomic specifications. Non-TREO grafts were also excluded for traumatic or emergent cases. The primary outcome was sac shrinkage, and secondary outcomes were composite complication profile within 30 d of operation. RESULTS: Six TREO grafts and 16 non-TREO grafts were included for analysis. The groups were similar in age, gender, and race. The groups were also similar in aortic anatomy before EVAR. The aneurysm sac shrinkage rate (mm/mo) is significantly greater in the TREO group than in the non-TREO group (0.484 ± 0.107 versus 0.018 ± 0.112, P = 0.033). The total average size of sac shrinkage was also greater for the TREO group (-0.688 ± 2.262 versus 12.00 ± 2.78, P < 0.001). The composite complication profile of stroke, myocardial infarction, death, and respiratory complications was not different between groups. CONCLUSIONS: TREO aortic endografts for aneurysm repair are being used in Europe. However, their application in the United States is limited. Our data demonstrate the significant advantage the TREO graft has with increased sac shrinkage and minimal complications, compared with other grafts. This study adds to the growing body of literature supporting TREO graft use for EVAR.

Technical tips for success in transcarotid artery revascularization.

Transcarotid artery revascularization is a minimally invasive technique performed by vascular surgeons for the management of carotid artery stenosis via direct access of the common carotid artery and stenting of the common and internal carotid artery atherosclerotic stenosis. Unlike the transfemoral approach for carotid artery stent angioplasty, the transcarotid artery revascularization procedure allows cerebral protection from embolization without manipulation of the internal carotid artery stenotic lesion via the ENROUTE Transcarotid Neuroprotection System (Silk Road Medical, Sunnyvale, CA). The ENROUTE reverse flow cerebral protection affords the opportunity to predilate carotid artery lesions with relative impunity before stent deployment. Our technique of transcarotid artery revascularization is detailed in this report of 70 patients (112 procedures) with <1% perioperative neurologic morbidity and documents clinical and hemodynamic (duplex ultrasound testing) success at more than 6 months' follow-up.

A Potential Role for Green Tea as a Radiation Sensitizer for Prostate Cancer.

Prostate cancer (PCa) is the most common non-cutaneous cancer in the United States. There is currently a lack of safe and effective radiosensitizers that can enhance the effectiveness of radiation treatment (RT) for Pca. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase-3 activity assay were used to assess proliferation and apoptosis in DU145 Pca cells. RT-PCR/IHC were used to investigate the mechanisms. We found that the percentage of colonies, PCNA staining intensity, and the optical density value of DU145 cells were decreased (RT/GT vs. RT). TUNEL + cells and the relative caspase-3 activity were increased (RT/GT vs. RT). Compared to RT, the anti-proliferative effect of RT/GT correlated with increased expression of the anti-proliferative molecule p16. Compared to RT, the pro-apoptotic effect of RT/GT correlated with decreased expression of the anti-apoptotic molecule Bcl-2. GT enhances RT sensitivity of DU145 by inhibiting proliferation and promoting apoptosis.

SIV Infection-Mediated Changes in Gastrointestinal Bacterial Microbiome and Virome Are Associated with Immunodeficiency and Prevented by Vaccination.

AIDS caused by simian immunodeficiency virus (SIV) infection is associated with gastrointestinal disease, systemic immune activation, and, in cross-sectional studies, changes in the enteric virome. Here we performed a longitudinal study of a vaccine cohort to define the natural history of changes in the fecal metagenome in SIV-infected monkeys. Matched rhesus macaques were either uninfected or intrarectally challenged with SIV, with a subset receiving the Ad26 vaccine, an adenovirus vector expressing the viral Env/Gag/Pol antigens. Progression of SIV infection to AIDS was associated with increased detection of potentially pathogenic viruses and bacterial enteropathogens. Specifically, adenoviruses were associated with an increased incidence of gastrointestinal disease and AIDS-related mortality. Viral and bacterial enteropathogens were largely absent from animals protected by the vaccine. These data suggest that the SIV-associated gastrointestinal disease is associated with the presence of both viral and bacterial enteropathogens and that protection against SIV infection by vaccination prevents enteropathogen emergence.