Cytomegalovirus Infection Facilitates the Costimulation of CD57+CD28- CD8 T Cells in HIV Infection and Atherosclerosis via the CD2-LFA-3 Axis.

CD8 T cells are emerging as important mediators in atherosclerosis and cardiovascular disease (CVD). Immune activation may play a particular role in people with HIV (PWH) who are at an increased risk of CVD, even after controlling for known CVD risk factors. Latent CMV infection is associated with increased CVD risk for both PWH and people without HIV, and human CMV-specific CD4 and CD8 T cells are enriched for an immunosenescent phenotype. We previously showed that CMV coinfection in PWH promotes vascular homing and activation of inflammatory CD4 T cells through the CD2-LFA-3 axis. However, the role of CD2/LFA3 costimulation of CD8 T cells in PWH with CMV has yet to be described. In the present study, we demonstrate that CD2 expression on CX3CR1+CD57+CD28- inflammescent CD8 T cells is increased on cells from CMV-seropositive PWH. In vitro CD2/LFA-3 costimulation enhances TCR-mediated activation of these inflammatory CD8 memory T cells. Finally, we show that LFA-3 is highly expressed in aortas of SIV-infected rhesus macaques and in atherosclerotic plaques of people without HIV. Our findings are consistent with a model in which CMV infection enhances CD2 expression on highly proinflammatory CD8 T cells that can then be stimulated by LFA-3 expressed in the vasculature, even in the absence of CD28 costimulation. This model, in which CMV infection exacerbates toxic cytokine and granzyme production by CD8 T cells within the vasculature, highlights a potential therapeutic target in atherosclerosis development and progression, especially for PWH.

Trends and outcomes associated with intravascular ultrasound use during femoropopliteal revascularization in the Vascular Quality Initiative.

OBJECTIVE: Intravascular ultrasound (IVUS) use in lower extremity interventions is growing in popularity owing to its imaging in the axial plane, superior detail in imaging lesion characteristics, and its enhanced ability to delineate lesion severity and extent compared with catheter angiograms. However, there are conflicting data regarding whether IVUS affects outcomes. The purpose of this study was to assess the effect associated with IVUS implementation in femoropopliteal interventions. METHODS: This retrospective cohort study used Vascular Quality Initiative data. Patients undergoing an index endovascular femoropopliteal revascularization from 2016 to 2021 were included. Patients were differentiated by whether or not IVUS was used to assess the femoropopliteal segment during intervention (no IVUS, IVUS). Propensity score matching, based on preoperative demographics and measures of disease severity was used. Primary outcomes were major amputation-free survival (AFS), femoropopliteal reintervention-free survival (RFS), and primarily patent survival (PPS) at 12 months. RESULTS: IVUS use grew steadily throughout the study period, comprising 0.6% of interventions in 2016 and increasing to 8.2% of interventions by 2021; growth was most dramatic in ambulatory surgical center or office-based laboratory settings where IVUS use grew from 4.4% to 43% to 47% of interventions. In unmatched cohorts, patients receiving interventions using IVUS tended to have lower prevalence of multiple cardiovascular comorbidities (eg, congestive heart failure, hypertension, diabetes, and dialysis dependence) and presented more often with claudication and less often with chronic limb-threatening ischemia (CLTI). Intraoperatively, IVUS was used more often in complex femoropopliteal lesions (Transatlantic Intersociety grade D vs A), and more often in conjunction with stenting and/or atherectomy. IVUS use was associated with improved AFS, but similar RFS and PPS at 12 months. However, in multivariable analysis IVUS was not associated with any of the primary outcomes independently; rather, all outcomes were influenced primarily by CLTI, dialysis dependence, and prior major amputation status; technical outcomes (ie, RFS and PPS loss) were further driven by complexity of lesion (worse in Transatlantic Intersociety grade D vs A lesions) and treatment setting (ie, ambulatory surgical center or office-based laboratory setting associated with increased hazard for RFS and PPS loss). CONCLUSIONS: IVUS implementation in femoropopliteal interventions is growing, with rapid adoption among interventions in ambulatory surgical centers and office-based laboratories. IVUS was not associated with an effect on technical outcomes at 12 months; improvement in major AFS was observed; however, multivariable analysis suggests this finding may be an effect of confounding by multiple factors highly associated with IVUS use, namely, in patients with lower prevalence of CLTI, dialysis dependence, and prior major amputations, thus conveying baseline lower risk for major amputation and death.

CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis.

Atherosclerotic cardiovascular disease (ASCVD) remains an important cause of morbidity in the general population and risk for ASCVD is increased approximately 2-fold in persons living with HIV infection (PLWH). This risk is linked to elevated CD8 T cell counts that are abundant in atherosclerotic plaques and have been implicated in disease pathogenesis yet the mechanisms driving T cell recruitment to and activation within plaques are poorly defined. Here we investigated the role of CD8 T cells in atherosclerosis in a non-human primate model of HIV infection and in the HIV-uninfected elderly; we sought to identify factors that promote the activation, function, and recruitment to endothelium of CX3CR1+ CD8 T cells. We measured elevated expression of CX3CL1 and IL-15, and increased CD8 T cell numbers in the aortas of rhesus macaques infected with SIV or SHIV, and demonstrated similar findings in atherosclerotic vessels of HIV-uninfected humans. We found that recombinant TNF enhanced the production and release of CX3CL1 and bioactive IL-15 from aortic endothelial cells, but not from aortic smooth muscle cells. IL-15 in turn promoted CX3CR1 surface expression on and TNF synthesis by CD8 T cells, and IL-15-treated CD8 T cells exhibited enhanced CX3CL1-dependent chemoattraction toward endothelial cells in vitro. Finally, we show that CD8 T cells in human atherosclerotic plaques have an activated, resident phenotype consistent with in vivo IL-15 and CX3CL1 exposure. In this report, we define a novel model of CD8 T cell involvement in atherosclerosis whereby CX3CL1 and IL-15 operate in tandem within the vascular endothelium to promote infiltration by activated CX3CR1+ memory CD8 T cells that drive further endothelial activation via TNF. We propose that these interactions are prevalent in aging and in PLWH, populations where circulating activated CX3CR1+ CD8 T cell numbers are often expanded.

Physician-modified endografts are associated with a survival benefit over parallel grafting in thoracoabdominal aneurysms.

OBJECTIVE: Physician-modified endografts (PMEG) and parallel grafting (PG) are important techniques for endovascular repair of complex aortic aneurysms using off-the-shelf devices. However, there are few data regarding the relative efficacy and outcomes of these techniques in thoracoabdominal extent aneurysms. This study sought to compare the outcomes of PG and PMEG across different extents of thoracoabdominal aneurysms (TAAAs) for which they can be used. METHODS: The Society for Vascular Surgery Vascular Quality Initiative thoracic endovascular aortic repair/complex endovascular aortic repair module was queried for all patients undergoing repair of an unruptured, TAAA (extents I-IV) from 2012 to 2020; aneurysm types were defined by repair extent as determined by proximal and distal seal zones. Patients were differentiated based on whether they underwent repair with a PMEG or PG. The primary outcomes for this study were overall survival and freedom from aneurysm- or procedure-related mortality at 1 year determined via Kaplan-Meier analysis, with a Cox hazard regression analysis conducted to examine the independent association of repair modality with primary outcomes. RESULTS: There were 813 patients who met the inclusion criteria (TAAA I-III, n = 362; TAAA IV, n = 451; PG, n = 426; PMEG, n = 387). PMEG repairs were performed at centers with a nearly two- to three-fold higher annual volume of endovascular TAAA repairs. Type Ia endoleaks were reduced with PMEG repair, most significantly in TAAA IV (TAAA I-III, 2.2% PMEG vs 10% PG [P = .2]; TAAA IV, 1.2% PMEG vs 21.6% PG [P < .001]). Thoracoabdominal repairs demonstrated improved survival at 1 year with PMEG devices, significant for TAAA I to III repairs (TAAA I-III, PMEG 85% vs PG 74% [P = .01]; TAAA IV, 84% PMEG vs PG 78% [P = .08]). Freedom from aneurysm- or procedure-related mortality was also improved with PMEG repairs, remaining significant at 1 year in the case of TAAA IV (TAAA I-III:, PMEG 94% vs PG 86% [P = .06]; TAAA IV, PMEG 94% vs PG 88% [P = .02]). PMEG demonstrated decreases in several measures of postoperative morbidity, including stroke, death, major adverse cardiovascular events, and postoperative complications. In the multivariate analysis, repair modality was not associated with either primary outcome; rather, several perioperative complications conveyed the greatest hazard for both primary outcomes across repair extents. CONCLUSIONS: Survival after endovascular TAAA repair is improved with the use of PMEG compared with PG. Several key factors of this study demonstrate the shortcomings of PG in complex aneurysm repair, namely, high rates of critical endoleaks, the need for adjunctive access sites, and an increase in perioperative complications that influence longer term outcomes.

Cytomegalovirus Coinfection Is Associated with Increased Vascular-Homing CD57+ CD4 T Cells in HIV Infection.

Cytotoxic CD4 T cells are linked to cardiovascular morbidities and accumulate in both HIV and CMV infections, both of which are associated with increased risk of cardiovascular disease (CVD). In this study, we identify CMV coinfection as a major driver of the cytotoxic phenotype, characterized by elevated CD57 expression and reduced CD28 expression, in circulating CD4 T cells from people living with HIV infection, and investigate potential mechanisms linking this cell population to CVD. We find that human CD57+ CD4 T cells express high levels of the costimulatory receptor CD2 and that CD2/LFA-3 costimulation results in a more robust and polyfunctional effector response to TCR signals, compared with CD28-mediated costimulation. CD57+ CD4 T cells also express the vascular endothelium-homing receptor CX3CR1 and migrate toward CX3CL1-expressing endothelial cells in vitro. IL-15 promotes the cytotoxic phenotype, elevates CX3CR1 expression, and enhances the trafficking of CD57+ CD4 T cells to endothelium and may therefore be important in linking these cells to cardiovascular complications. Finally, we demonstrate the presence of activated CD57+ CD4 T cells and expression of CX3CL1 and LFA-3 in atherosclerotic plaque tissues from HIV-uninfected donors. Our findings are consistent with a model in which cytotoxic CD4 T cells contribute to CVD in HIV/CMV coinfection and in atherosclerosis via CX3CR1-mediated trafficking and CD2/LFA-3-mediated costimulation. This study identifies several targets for therapeutic interventions and may help bridge the gap in understanding how CMV infection and immunity are linked to increased cardiovascular risk in people living with HIV infection.

Systematic review of hemostatic agents used in vascular surgery.

BACKGROUND: Hemostatic agents are routinely used in vascular surgery to complement proper suture techniques and decrease the risk of perioperative bleeding. A relative lack of comparative research studies have left surgeons with the option of choosing hemostatic agents based on their personal experience. The present review has highlighted the efficacy and safety of hemostatic agents and categorized them according to their primary mechanism of action and cost. METHODS: A systematic search strategy encompassing hemostatic agent products was deployed in the PubMed database. Single-center and multicenter, randomized, controlled trials with >10 patients were included in the present study. RESULTS: We reviewed 12 studies on the efficacy and safety of hemostatic agents compared with manual compression or other hemostatic agents. Using the time to hemostasis as the primary end point, all studies had found hemostatic agents to be significantly more efficient than manual compression. Likewise, adhesives (high pressure sealants) and dual agents (containing biologically active and absorbable components) were found to be more efficient, but costlier, than agents with either biologically active or absorbable components only. Agents with porcine or bovine constituents were found to trigger anaphylactic reactions in rare cases. Additionally, the absence of fibrin stabilizing factor XIII in a brand of fibrin sealant was speculated to reduce the affinity of the fibrin sealant for the expanded polytetrafluoroethylene graft. The cost of agents varied greatly depending on their active ingredient. CONCLUSIONS: Hemostatic agents appear to be highly effective at decreasing the risk of bleeding during surgical procedures. Although some hemostatic agents were demonstrated to achieve hemostasis faster than others, most are able to control bleeding within <10 minutes. Based on the limited data, the least expensive agents might suffice for limited suture lines used in routine procedures.

Paclitaxel-coated peripheral arterial devices are associated with improved overall survival and limb salvage in patients with chronic limb-threatening ischemia.

OBJECTIVE: Paclitaxel (PTX)-coated peripheral arterial devices have been shown to decrease femoropopliteal artery restenosis and the need for reintervention compared with non-PTX-coated devices. The data regarding PTX efficacy and safety come from randomized controlled trials that almost exclusively enrolled patients with claudication. The outcomes of PTX treatment in patients who present with chronic limb-threatening ischemia (CLTI) are unknown. This study compares long-term outcomes in patients with CLTI treated with and without PTX. METHODS: We retrospectively reviewed 983 patients with CLTI treated with femoropopliteal artery angioplasty, atherectomy, stent, or combination between 2011 and 2019. Procedures were performed with additional proximal or distal tibial interventions as needed. Kaplan-Meier survival analysis and multivariable Cox-regression analysis compared overall survival (OS), amputation-free survival (AFS), freedom from major amputation (ff-MA), and freedom from target vessel revascularization (ff-TVR) between patients treated with and without PTX. RESULTS: Demographics, comorbidities, and Rutherford class were similar between 574 PTX (58.5%) and 409 non-PTX (41.6%) patients except that non-PTX patients were more likely to be male (56.2% vs 49.7%), dialysis dependent (19.6% vs 14.3%), and have higher average creatinine (2.3 vs 1.8 mg/dL). Through 4-year follow-up, the PTX group demonstrated a significant increase in OS (56.2% vs 43.9%, P = .013), AFS (52.6% vs 36.1%, P < .0001), ff-MA (87.4% vs 78.7%, P = .0007), and ff-TVR (77.6% vs 70.6%, P = .012). Multivariable Cox-regression analysis demonstrated that PTX treatment was associated with improved OS, AFS, ff-MA, and ff-TVR. CONCLUSIONS: In patients with CLTI, treatment with a PTX-coated device is associated with improved OS, AFS, ff-MA, and ff-TVR through 4-year follow-up. PTX-coated devices may be especially beneficial in patients who present with CLTI.

Paclitaxel-Coated Peripheral Arterial Devices are Associated with Reduced Mortality in Younger Patients.

BACKGROUND: Paclitaxel-coated devices have been shown to decrease restenosis when used in the femoropopliteal artery. Recent reports have suggested a possible risk of increased late mortality in patients treated with paclitaxel. It has been suggested that younger patients and those with limited comorbidities may be at higher risk. Our objective was to analyze long-term mortality based on patient age comparing treatment with paclitaxel to uncoated devices. METHODS: We performed a retrospective review of 1,170 consecutive patients who underwent femoropopliteal percutaneous intervention by angioplasty, atherectomy, stent placement, or combination between 2011 and 2018. Patients were grouped by age at the time of procedure: <60 years old (n = 244, 20.9%), 60-80 years old (n = 635, 54.3%), and >80 years old (n = 291, 24.9%). Within each group, patients were further divided by use of paclitaxel. The primary outcome measure was survival assessed by Kaplan-Meier analysis. Differences between the groups were analyzed with analysis of variance. Multivariable analysis was performed using Cox proportional hazard models. RESULTS: Of the 1,170 patients who underwent femoropopliteal percutaneous intervention, 654 (55.9%) received a paclitaxel-coated device during treatment and 516 (44.1%) did not. Mean age of the overall patient cohort was 70.4 ± 12.6 years and 663 (56.7%) were male. When comparing the groups by age we found an increase in age but a decrease in the proportion of patients who smoke. The use of paclitaxel-coated devices was similar across the groups (<60 years old, 56.2%; 60-80 years old, 57.0%; >80 years old, 52.6%; P = 0.45). Demographics and comorbidities were similar between the patients treated with and without paclitaxel within each age group except more males in the <60-year-old group treated without paclitaxel and more patients with chronic limb threatening ischemia in the >80-year-old group treated with paclitaxel. In patients <60 and 60-80 years old paclitaxel use was associated with increased survival at 4 years: <60 (80.7% vs. 64.4%; P = 0.04); 60-80 (63.2% vs. 55.1%; P = 0.04). Survival was similar in the >80-year-old group (46.6% vs. 32.8%; P = 0.65). CONCLUSIONS: Our data suggest that the use of paclitaxel-coated arterial devices is not associated with increased mortality. On the contrary, our data show that younger patients treated with paclitaxel show improved survival compared with those treated without paclitaxel. Paclitaxel-coated devices may be used with continued caution especially in patients at high risk for restenosis.

Elevated Neutrophil to Lymphocyte Ratio is Associated with Worse Outcomes after Carotid Endarterectomy in Asymptomatic Patients.

OBJECTIVE: Management of carotid artery stenosis (CAS) remains controversial and proper patient selection critical. Elevated neutrophil to lymphocyte ratio (NLR) has been associated with poor outcomes after vascular procedures. The effect of NLR on outcomes after carotid endarterectomy (CEA) in asymptomatic and symptomatic patients is assessed. MATERIALS AND METHODS: A retrospective review was conducted of all patients between 2010 and 2018 with carotid stenosis >70% as defined by CREST 2 criteria. A total of 922 patients were identified, of whom 806 were treated with CEA and 116 non-operatively with best medical therapy (BMT). Of patients undergoing CEA, 401 patients (290 asymptomatic [aCEA], 111 symptomatic [sCEA]) also had an available NLR calculated from a complete blood count with differential. All patients treated with BMT were asymptomatic and had a baseline NLR available. Kaplan-Meier analysis assessed composite ipsilateral stroke or death over 3 years. RESULTS: In sCEA group, the 3-year composite stroke/death rates did not differ between NLR < 3.0 (22.9%) vs NLR > 3.0 (38.1%) (P=.10). In aCEA group, patients with a baseline NLR >3.0 had an increased risk of 3-year stroke/death (42.6%) compared to both those with NLR <3.0 (9.3%, P<.0001) and those treated with BMT (23.6%, P=.003). In patients with NLR <3.0, aCEA showed a superior benefit over BMT with regard to stroke or death (9.3% vs. 26.2%, P=.02). However, in patients with NLR >3.0, there was no longer a benefit to prophylactic CEA compared to BMT (42.6% vs. 22.2%, P=.05). Multivariable analysis identified NLR >3.0 (HR, 3.23; 95% CI, 1.93-5.42; P<.001) and congestive heart failure (HR, 2.18; 95% CI, 1.33-3.58; P=.002) as independent risk factors for stroke/death in patients with asymptomatic carotid artery stenosis. CONCLUSIONS: NLR >3.0 is associated with an increased risk of late stroke/death after prophylactic CEA for asymptomatic carotid artery stenosis, with benefits not superior to BMT. NLR may be used to help with selecting asymptomatic patients for CEA. The effect of NLR and outcomes in symptomatic patients requires further study. Better understanding of the mechanism(s) for NLR elevation and medical intervention strategies are needed to modulate outcome risk in these patients.

Anatomic criteria in the selection of treatment modality for atherosclerotic carotid artery disease.

OBJECTIVE: Three procedures are currently available to treat atherosclerotic carotid artery stenosis: carotid endarterectomy (CEA), transfemoral carotid artery stenting (TF-CAS), and transcarotid artery revascularization (TCAR). Although there is considerable debate evaluating each of these in a head-to-head comparison to determine superiority, little has been mentioned concerning the specific anatomic criteria that make one more appropriate. We conducted a study to define anatomic criteria in relation to inclusion and exclusion criteria and relative contraindications. METHODS: A retrospective review was conducted of 448 carotid arteries from 224 consecutive patients who underwent a neck and head computed tomography arteriography (CTA) scan before carotid intervention for significant carotid artery stenosis. Occlusion of the internal carotid artery (ICA) occurred in 15, yielding 433 arteries for analysis. Anatomic data were collected from CTA images and demographic and comorbidities from chart review. Eligibility for CEA, TF-CAS, and TCAR was defined on the basis of anatomy, not by comorbidity. RESULTS: CTA analysis revealed that 92 of 433 arteries (21%) were ineligible for CEA because of carotid lesions extending cephalad to the second cervical vertebra. Overall, 26 arteries (6.0%) were not eligible for any type of carotid artery stent because of small ICA diameter (n = 11), heavy circumferential calcium (n = 14), or combination (n = 1). An additional 126 arteries were ineligible for TF-CAS on the basis of a hostile aortic arch (n = 115) or severe distal ICA tortuosity (n = 11), yielding 281 arteries (64.9%) that were eligible. In addition to the 26 arteries ineligible for any carotid stent, TCAR was contraindicated in 39 because of a clavicle to bifurcation distance <5 cm (n = 17), common carotid artery diameter <6 mm (n = 3), or significant plaque at the TCAR sheath access site (n = 20), yielding 368 arteries (85.0%) that were eligible for TCAR. CONCLUSIONS: A significant proportion of patients who present with carotid artery stenosis have anatomy that makes one or more carotid interventions contraindicated or less desirable. Anatomic factors should play a key role in selecting the most appropriate procedure to treat carotid artery stenosis. Determination of superiority for one procedure over another should be tempered until anatomic criteria have been assessed to select the best procedural options for each patient.

Elevated neutrophil-lymphocyte ratio predicts mortality following elective endovascular aneurysm repair.

OBJECTIVE: The neutrophil-lymphocyte ratio (NLR) is an inexpensive and useful inflammatory marker that incorporates the balance of the innate (neutrophil) and adaptive (lymphocyte) immune responses. Data exist on the association between NLR and mortality in various coronary diseases and in cancer surgery, but there is a paucity of data on the impact of preoperative NLR on vascular surgical outcomes. The aim of this study was to evaluate the relationship between preoperative NLR and elective endovascular aortic aneurysm repair (EVAR) outcome. METHODS: A retrospective review of all patients who underwent elective EVAR at a single institution between 2010 and 2018 was conducted (n = 373). Only patients who had a preoperative complete blood count with differential within 30 days of their operation were included. The NLR was computed by dividing the absolute neutrophil count by the absolute lymphocyte count. A receiver operating characteristic curve was used to determine the optimal cutoff value of NLR with the strongest association with mortality. NLR was dichotomized so that patients with NLR above the threshold were at increased risk of mortality compared with those below it. Continuous variables were analyzed using Wilcoxon nonparametric signed-rank test and categorical variables with the Fisher exact test. A comparison of NLR and mortality was completed using Kaplan-Meier survival analysis. Cox regression analysis was used to evaluate factors associated with mortality through 5-year follow-up. RESULTS: Overall, 108 patients were included in this study. An NLR ≥ 4.0 was found to be associated with mortality (P < .0001). Thirty-two patients composed the High-NLR (NLR ≥ 4.0) group and the remaining 76 patients formed the Low-NLR (NLR < 4.0) group. Baseline characteristics were similar between groups, except that the High-NLR group was older (77.9 vs 74.4; P = .047). At a mean of 36.4 months follow-up, the overall mortality rate was 32.4%. Although there were no differences in the perioperative period, the Kaplan-Meier estimates of mortality were significantly greater in the High-NLR group at 1, 2, and 5 years postoperatively (P < .0001). The mean preoperative NLR of the deceased was higher (5.94 ± 5.20; median, 4.75; interquartile range, 3.17-7.83) than those who survived (2.87 ± 1.61; median, 2.53; interquartile range, 1.97-3.49) (P < .0001). Secondary interventions and sac enlargement rates were similar between groups. On univariable analysis, NLR (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.10-1.23; P < .0001), age (HR, 1.06; 95% CI, 1.02-1.11; P = .004), and aneurysm diameter (HR, 1.04; 95% CI, 1.01-1.07; P = .003) were associated with mortality. On multivariable analysis, NLR (HR, 1.19; 95% CI, 1.12-1.27; P < .0001), age (HR, 1.06; 95% CI, 1.01-1.11; P = .026), and aneurysm diameter (HR, 1.04; 95% CI, 1.02-1.07; P = .003) were associated with mortality. CONCLUSIONS: Patients with an elevated preoperative NLR, irrespective of other comorbidities, may represent a previously unrecognized subset of patients who are at heightened risk of mortality after elective EVAR. A complete blood count with differential is an inexpensive test that may be used as a prognostic indicator for outcome after EVAR. Further research is warranted to identify clinical, pathological, or anatomical factors associated with an elevated NLR and to determine modifiable factors, which may help improve long-term survival.

Frequency of perigraft hygroma after open aortic reconstruction.

OBJECTIVE: The incidence of perigraft hygroma (PGH) development after aortic reconstruction remains poorly defined and its clinical relevance is questionable. This study was designed to establish the incidence of and determine the risk factors associated with PGH formation and its outcomes. METHODS: Patients who underwent open aortic reconstruction for either aneurysmal or occlusive disease with an expanded polytetrafluoroethylene (ePTFE) or polyester graft from 2004 to 2018 were retrospectively reviewed (n = 262). Only those who had follow-up imaging 3 or more months after repair were included. Patients with mixed graft types were excluded. PGH was defined as a perigraft fluid collection of 30 mm or greater in diameter with a radiodensity of 30 or fewer Hounsfield units on computed tomography at a minimum of 3 postoperative months. Analysis was conducted between patients with and without PGH. RESULTS: One hundred forty patients met the inclusion criteria: 88 were treated with ePTFE and 52 with polyester grafts. Twenty-three patients (16.4%) were found to have radiologic evidence of PGH. PGH developed more frequently in patients with ePTFE (21/88 [23.9%]) compared with those with polyester grafts (2/52 [3.8%]) (P = .002). Mean PGH size was 63.5 ± 36.4 mm (range, 33-153 mm) and the average time to PGH detection 27.7 months (range, 3-112 months). Baseline characteristics were similar between the groups. Patients who developed PGH had larger aneurysms, more often received ePTFE grafts, had larger graft diameters, and had bifurcated grafts. The overall mortality was 32.1% at a mean follow-up of 5.2 years. The 5-year mortality rates were similar between patients with and without PGH (26.1% vs 18.8%; P = .41). Of the 23 patients with PGH, 4 (all with ePTFE) presented with symptoms related to the PGH. The average size of symptomatic and asymptomatic PGH were 11.5 and 4.8 cm, respectively. Mortality rates overall were similar between those with and without symptoms (50.0% vs 36.8%; P = .99). CONCLUSIONS: Nearly one-quarter of aortic reconstructions with ePTFE are associated with PGH formation compared with 4% with polyester. Clinically significant PGH-related symptom development occurs in 20%. Patient education and close surveillance are warranted. Manufacturer's device modification is needed.

Paclitaxel-coated peripheral artery devices are not associated with increased mortality.

OBJECTIVE: Long-term safety concerns have been raised that the use of paclitaxel-coated balloons and stents is linked to excess mortality. Our objective was to compare outcomes in patients treated with paclitaxel vs uncoated devices and to analyze long-term mortality. METHODS: We conducted a retrospective single-institution review of 1170 consecutive patients who underwent femoropopliteal percutaneous revascularization by angioplasty, atherectomy, stent placement, or combination between 2011 and 2018. The primary outcome measure was all-cause mortality. Groups were divided into patients who received paclitaxel (n = 652) and those who did not (n = 518). Categorical variables were assessed using χ2 analysis and continuous variables with the Wilcoxon signed rank test. A multivariable analysis was performed using multivariable logistic regression models. Mortality was compared using Kaplan-Meier survival analysis. RESULTS: Demographics, risk factors, and Rutherford class were similar between the groups, except that the paclitaxel group was more likely to have diabetes (60.9% vs 55.0%; P = .04), was less likely to be on dialysis (10.7% vs 14.9%; P = .04), and had lower average creatinine concentration (1.6 ± 1.8 mg/dL vs 2.0 ± 2.3 mg/dL; P = .003). There were no differences in all-cause mortality through 2 years between paclitaxel and no-paclitaxel cohorts (25.5% vs 30.3%; log-rank, P = .098). At 3 years and 3.5 years, mortality was significantly lower in the paclitaxel group: year 3, 32.1% vs 39.4% (log-rank, P = .041); year 3.5, 35.2% vs 43.9% (log-rank, P = .027). Survival rates were not significantly different in examining subgroups by diabetes, chronic kidney disease, presence of chronic limb-threatening ischemia, or paclitaxel-coated balloon manufacturer. Multivariable analysis demonstrated that age, dialysis, chronic limb-threatening ischemia, chronic kidney disease, and congestive heart failure were independent risk factors for mortality, whereas paclitaxel use was associated with lower mortality. CONCLUSIONS: The use of paclitaxel-coated balloons and stents does not increase mortality compared with uncoated devices out to 3.5 years. Paclitaxel-coated devices can be used with continued caution, especially in patients at increased risk of restenosis. Further long-term studies are needed to determine the risk of late mortality.

A systematic review of the efficacy of aspirin monotherapy versus other antiplatelet therapy regimens in peripheral arterial disease.

BACKGROUND: Dual antiplatelet therapy (DAPT) usually refers to the administration of aspirin plus a platelet P2Y12 receptor blocker. This combination is commonly prescribed after revascularization procedures in patients with peripheral arterial disease (PAD) to prevent failure of the intervention. However, there is not a consensus among peripheral vascular specialists regarding whether the optimal treatment regimen for their patients is mono antiplatelet therapy (MAPT) or DAPT. Furthermore, there is no consensus regarding the optimal duration of DAPT. This study was undertaken to systematically and critically review the evidence for the use of DAPT after revascularization in PAD, hypothesizing that longer durations of DAPT will result in decreased rates of major adverse cardiac events, major adverse limb events, and mortality, without a significant increase in severe bleeding episodes compared with MAPT or shorter durations of DAPT. METHODS: A systematic search strategy encompassing DAPT and PAD was deployed in two databases. Studies including arterial bypasses using venous or prosthetic conduits, endovascular procedures, diagnostic angiography of lower extremity arteries, and patients with high risk factors were included. RESULTS: We included 14 studies, 10 of which were randomized controlled trials (RCTs). The overall risk of bias for the RCTs ranged from low to moderate, whereas nonrandomized studies had moderate to high risk of bias. The results of this review suggest that use of DAPT in patients with PAD reduces rates of major adverse cardiac events (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.68-0.91; P = .002), major adverse cardiac and cerebrovascular events, and mortality (RR, 0.57; 95% CI, 0.45-0.72; P < .00,001) compared with those of patients treated with MAPT. Lower extremity-specific end points, such as major adverse limb events and target lesion revascularization (RR, 0.70; 95% CI, 0.49-1.01; P = .06) were also decreased in the DAPT cohort. Rates of moderate bleeding, however, were increased in those treated with DAPT, whereas rates of major bleeding (RR, 0.98; 95% CI, 0.68-1.41; P = .92) remained similar in both treatment groups. The effects of DAPT duration on outcomes of revascularization in patients with PAD have yet to be studied in an RCT. CONCLUSIONS: DAPT appears to be beneficial for preventing complications after revascularization in PAD, including thrombotic failure of the intervention. However, the durations of DAPT use in these studies are heterogeneous, suggesting that additional data are needed to determine the optimal use of DAPT in PAD patients.

Characterizing tissue perfusion after lower extremity intervention using two-dimensional color-coded digital subtraction angiography.

OBJECTIVE: Digital subtraction angiography (DSA) of the peripheral arterial vasculature provides lumenographic information but only a qualitative assessment of blood flow. The ability to quantify adequate tissue perfusion of the lower extremities would enable real-time perfusion assessment during DSA of patients with peripheral arterial disease (PAD). In this study, we used a novel real-time imaging software to delineate tissue perfusion parameters in the foot in PAD patients. METHODS: Between March 2015 and June 2016, patients (N = 31) underwent lower extremity angiography using a two-dimensional perfusion (2DP) imaging protocol (Philips Healthcare, Andover, Mass). Of the 31 enrolled patients, 16 patients received preintervention and postintervention DSA images (18 angiograms), while contrast agent injection settings and the position of the foot, catheter, and C-arm were kept constant. The region of interest for perfusion measurements was taken at the level of the medial malleolus. Perfusion parameters included arrival time (AT) of contrast material, wash-in rate (WIR), time to peak (TTP) contrast intensity, and area under the curve (AUC). RESULTS: Patients (mean age, 67 years; male, 61%) undergoing 2DP had limbs classified as Rutherford class 3 (n = 9 limbs), class 4 (n = 11), and class 5 (n = 14) ischemia with a mean ankle-brachial index of 0.63. For the whole cohort, median (interquartile range) AT measured 5.20 (3.10-7.25) seconds; WIR, 61.95 (43.53-86.43) signal intensity (SI)/s; TTP, 3.80 (2.88-4.50) seconds; peak intensity, 725.00 (613.75-1138.00) SI; and AUC, 12,084.00 (6742.80-17,059.70) SI*s. A subset of patients had 2DP performed before and after intervention (n = 18 cases). A detectable improvement in SI and two-dimensional flow parameters was seen after intervention. Average AT of contrast material to the region of interest shortened after intervention with percentage decrease of 30.1% ± 49.1%, corresponding decrease in TTP of 17.6% ± 24.7%, increase in WIR of 68.8% ± 94.2% and in AUC of 10.5% ± 37.6%, decrease in mean transit time of 18.7% ± 28.1%, and increase in peak of 34.4% ± 42.2%. CONCLUSIONS: The 2DP imaging allows measurement of blood flow in real time as an adjunct to DSA. The AT may be the most sensitive marker of perfusion change in the lower extremity. Quantitative thresholds based on 2DP hold promise for immediate treatment effectiveness assessment in patients with PAD.

Multidisciplinary Approach to Venous Disease: Enhancing Patient Care and Trainee Education Through Collaboration.

The full spectrum of venous disease poses a significant burden on individuals and health-care systems globally. Venous disease can lead to a wide range of symptoms based on the level of disease and underlying pathology. In general, underlying pathologies are due to nonthrombotic (reflux/obstructive) and thrombotic causes. Most conditions are a sequela of the long-term effects of chronic venous insufficiency, deep vein thrombosis (DVT), or nonthrombotic deep vein obstruction. The prevalence of venous disease is substantial, impacting the quality of life of a considerable proportion of the adult population. Untreated and progressive lower extremity venous disease can lead to venous ulceration and other complications. Additionally, poorly recognized and poorly understood venous conditions of the abdomen and pelvis leave many patients "orphaned" in health-care systems that lack expertise in complex venous conditions. Addressing the burden and breadth of venous disease requires comprehensive management approaches, early diagnosis, appropriate treatment interventions, and provider and patient education. Multidisciplinary collaborations and further research are essential to enhance our understanding, develop innovative therapies, and improve patient outcomes in the field of venous disease. In this paper, we highlight the importance of multidisciplinary collaboration and our journey to building an institutional venous team, as well as lessons learned.

Evaluation of fibrin sealant for biologic mesh fixation at the hiatus in a porcine model.

BACKGROUND: The ideal method to secure biologic mesh during laparoscopic hiatal hernia repair remains uncertain. Suture or tack fixation can be technically difficult, and serious cardiovascular complications have been reported. Fibrin sealant (FS) offers a potential solution to this problem. We hypothesized that FS provides comparable mesh fixation to suture repair during laparoscopic mesh hiatoplasty. STUDY DESIGN: Using a porcine model, laparoscopic hiatal hernia repair was performed with suture reapproximation of the crura and reinforcement with an acellular porcine dermal matrix. Prior to repair, animals were randomized to mesh fixation with sutures (S) or FS. After 30-day survival, an esophagram was performed, the diaphragm harvested, and mesh position, fixation, and incorporation were evaluated histologically and biomechanically using a T-peel test. RESULTS: Twenty (10 S and 10 FS) laparoscopic hiatal hernia repairs were performed. Total operative time was significantly less in the FS group (74.7 versus 127.0 min, p < 0.01). There were no instances of mesh migration in any animal. Mean peel force did not differ significantly between the S and FS groups (0.21 vs. 0.18 N/mm, respectively; p = 0.49). There was no significant difference in cellular repopularization or inflammatory changes around the mesh. CONCLUSIONS: Fibrin sealant offers a reasonable alternative to suturing biologic mesh during laparoscopic hiatal hernia repair with equivalent mesh fixation. At 30 days it provides adhesive strength similar to suture fixation, while significantly reducing operative time.

Thirty-day readmission after ventral hernia repair: predictable or preventable?

INTRODUCTION: Thirty-day readmission has become an increasingly scrutinized event in the field of surgery, especially in light of projected cuts in reimbursement. Although studies have evaluated large populations, little work has been done on procedure-specific populations. Our objective is to determine if any factors are predictive of 30-day readmission in patients undergoing ventral hernia repair. METHODS: We retrospectively reviewed the charts of all patients who underwent laparoscopic or open ventral hernia repair over a 4-year period. We evaluated patients based on demographic, preoperative, and operative variables. The primary outcome measure was all-cause 30-day readmission. RESULTS: There were 420 patients identified for evaluation. Fifty-one (12%) patients required readmission to the hospital within 30 days. The most common indications for readmission were wound infection (57%; n=29) and gastrointestinal (GI) complication (19%; n=10). On analysis, demographic variables were similar between the two groups. However, patients who were readmitted were more likely to have had more prior abdominal surgeries (4 vs. 2; p<0.0001), more previous hernia repairs (2 vs. 1; p=0.006), open repair (76% vs. 46%; p<0.0001), and active abdominal infection (37% vs. 12%; p<0.0001). In addition, patients also had longer procedures (235 vs. 150 min; p<0.0001) and larger defects (350 vs. 96 cm2; p<0.0001). On multivariate analysis, independent predictors of readmission included presence of fistula [odds ratio (OR)=8.55; 95% confidence interval (CI) 3.21-22.72], defect size>300 cm2 (OR=5.35; 95% CI 2.59-11.05), active abdominal infection (OR=4.37; 95% CI 2.28-8.37), and open repair (OR=4.27; 95% CI 2.17-8.42). CONCLUSIONS: Patients undergoing ventral hernia repair can represent a complex group. In our practice, enterocutaneous fistula, defect size>300 cm2, active abdominal infection, and open repair were all independent risk factors (OR>4) for 30-day readmission after ventral hernia repair. Recognition of these high-risk patients can help focus resources to increase surveillance and possible early intervention to reduce readmissions.

Open versus endoscopic component separation: a cost comparison.

BACKGROUND: The components separation technique (CST) is performed through an open or endoscopic approach. It is unclear whether the costs associated with the endoscopic instruments outweigh any clinical benefit derived from their use and the avoidance of lipocutaneous flaps. This study aimed to compare the direct costs associated with each approach. METHODS: A retrospective review of patients undergoing open or endoscopic CST between 2005 and 2009 was performed. The review compared patient-related variables, length of hospital stay, wound morbidity, and costs associated with the index operation and encounters within a 6-month period. RESULTS: Of the 54 patients identified, 59% underwent endoscopic repair, and 41% had an open CST repair. The patients were similar in age, American Society of Anesthesiology (ASA) score, gender, body mass index (BMI), number of prior surgeries, active abdominal infection, defect size, operating room time, and length of hospital stay. The overall median direct costs were similar between endoscopic and open CST ($9,942 vs. $17,701; p = 0.09). No difference was detected in median operating room costs, but an approximate $7,000 difference was noted between endoscopic and open CST ($1,871 vs. $8,705; p = 0.96). The median mesh costs differed significantly between endoscopic and open CST ($733 vs. $8,415; p = 0.05) as did stapler use costs ($35 vs. $190; p = 0.002). The median cost of endoscopic instruments was $848. Open CST had a 41% major wound morbidity rate compared with 19% in the endoscopic group (p = 0.07). Most of the encounters in the 6-month follow-up period (85%) were related to wound morbidity. The median cumulative direct costs differed between endoscopic and open CST at 3 and 6 months ($12,528 vs. $20,326; p = 0.05). CONCLUSIONS: In a similarly complex group of patients, the total direct costs associated with endoscopic and open CST were similar. Endoscopic instruments made a marginal contribution to the total overall costs, but significant cost contributors were the use of biologic grafts and wound morbidity.

Elevated neutrophil to lymphocyte ratio is associated with decreased amputation-free survival after femoropopliteal percutaneous revascularization.

BACKGROUND: An elevated neutrophil-lymphocyte ratio (NLR) is a biomarker associated with adverse outcomes after cardiovascular surgery. This study evaluates the association of preoperative NLR with clinical outcomes after peripheral vascular intervention (PVI) of the femoropopliteal segments. METHODS: A retrospective review identified 488 patients who underwent percutaneous interventions of femoropopliteal arteries between 2011 and 2018 and had a pre-procedural complete blood count with differential with normal white blood cell count within 30 days prior to intervention. Amputation-free survival (AFS), survival, and freedom from major amputation were assessed using Kaplan-Meier methods. Cohorts of patients with NLR <3 (Low), 3-4 (Mid), and >4 (High) were compared using univariate and multivariable statistical models. In these analyses NLR was analyzed as a continuous variable to correlate with clinical outcomes. RESULTS: Mean age was 71.7±12.8 years and males constituted 55.5%. The majority of patients presented with chronic limb threatening ischemia (CLTI, 78.5%). Increasing NLR was correlated with increasing rates of comorbidities, except for smoking history. The 30-day mortality rates increased with increasing NLR: 1.4%, 4.3%, and 7.0% for low (<3), mid (3-4) and high (>4) NLR groups, respectively (P=0.005). Patients with a lower pre-operative NLR achieved significantly greater amputation-free survival at 4-year follow-up: low NLR, 65.5%; mid NLR, 37.5%; and high NLR, 17.6% (P<0.0001). By multivariable analysis, increasing NLR, advanced age, CLTI, and dialysis-dependent renal failure reduced AFS. CONCLUSIONS: Elevated NLR is an independent predictor of decreased AFS following percutaneous interventions of femoropopliteal segments. Further research on identification and modulation of risk factors for high NLR are warranted.