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Cannabis is one of the most commonly used substances in the United States, with national use on the rise. However, there is a paucity of data regarding the effects of cannabis and surgical outcomes. The aim of this study was to assess the association of cannabis use on postoperative outcomes after lower extremity bypass.We queried a large statewide registry from 2014 to 2021 to assess patients who underwent lower extremity bypass procedures. Data were gathered regarding cannabis use and the association with postoperative outcomes at 30 days and 1 year.A total of 11,013 patients were identified. Ninety-one percent of patients (10,024) reported no cannabis use, whereas 9.0% (989) reported cannabis use in the past month. Compared with noncannabis users, patients using cannabis had higher opioid use at discharge (odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.28-1.90), decreased bypass patency at 30 days (OR: 0.52, 95% CI: 0.36-0.78) and 1 year (OR: 0.64, 95% CI 0.47-0.86), and an increased amputation rate at 1 year (OR: 1.25, 95% CI: 1.02-1.52) after lower extremity bypass.This study shows that cannabis use in vascular surgical patients was associated with decreased graft patency, increased amputation, and increased opioid use after lower extremity bypass procedures. Although future studies are needed, the present study provides novel data that can be used to counsel patients undergoing vascular surgery.

Therapeutic anticoagulation with either a vitamin K antagonist (VKA) or direct anticoagulant (DOAC) is often newly prescribed to patients undergoing lower extremity bypass (LEB) to aid in graft patency when risk factors for thrombosis are present or to treat postoperative venous thromboembolism or atrial fibrillation. There is a gap in knowledge as to how DOAC usage impacts postoperative outcomes compared with the standard-of-care VKAs.To determine temporal trends in DOAC prescription after infrainguinal LEB, impact on length of stay (LOS), and associated bleeding and thrombotic complications, patients undergoing elective LEB were identified from the Vascular Quality Initiative between January 2013 and May 2019. Postoperative bleeding, LOS, and graft occlusion for patients receiving VKA compared with DOAC were evaluated.A total of 24,459 LEBs were performed during the study period. Among 2,656 patients newly prescribed an anticoagulant, 78.0% (n = 2,072) received VKA and 22.0% (n = 584) received a DOAC, with DOAC use increasing throughout the study period. There was no significant difference in postoperative bleeding (VKA 2.3%, DOAC 1.7%, p = 0.413) or graft occlusion (VKA 1.2%, DOAC 1.4%, p = 0.762) between the anticoagulant classes. LOS was shorter in the DOAC group than in the VKA group (5.7 vs 6.8 days; plt; 0.001).This analysis demonstrates that DOAC use is increasing with time in Vascular Quality Initiative centers. DOACs are a safe and comparable alternative to VKAs in the postoperative setting with similar rates of bleeding complications and early graft patency and are associated with a reduced postoperative LOS.

Patients with abdominal aortic aneurysm (AAA) can choose open repair or endovascular repair (EVAR). While EVAR is less invasive, it requires lifelong surveillance and more frequent aneurysm-related reinterventions than open repair. A decision aid may help patients receive their preferred type of AAA repair.To determine the effect of a decision aid on agreement between patient preference for AAA repair type and the repair type they receive.In this cluster randomized trial, 235 patients were randomized at 22 VA vascular surgery clinics. All patients had AAAs greater than 5.0 cm in diameter and were candidates for both open repair and EVAR. Data were collected from August 2017 to December 2020, and data were analyzed from December 2020 to June 2021.Presurgical consultation using a decision aid vs usual care.The primary outcome was the proportion of patients who had agreement between their preference and their repair type, measured using χ2 analyses, κ statistics, and adjusted odds ratios.Of 235 included patients, 234 (99.6%) were male, and the mean (SD) age was 73 (5.9) years. A total of 126 patients were enrolled in the decision aid group, and 109 were enrolled in the control group. Within 2 years after enrollment, 192 (81.7%) underwent repair. Patients were similar between the decision aid and control groups by age, sex, aneurysm size, iliac artery involvement, and Charlson Comorbidity Index score. Patients preferred EVAR over open repair in both groups (96 of 122 [79%] in the decision aid group; 81 of 106 [76%] in the control group; P = .60). Patients in the decision aid group were more likely to receive their preferred repair type than patients in the control group (95% agreement [93 of 98] vs 86% agreement [81 of 94]; P = .03), and κ statistics were higher in the decision aid group (κ = 0.78; 95% CI, 0.60-0.95) compared with the control group (κ = 0.53; 95% CI, 0.32-0.74). Adjusted models confirmed this association (odds ratio of agreement in the decision aid group relative to control group, 2.93; 95% CI, 1.10-7.70).Patients exposed to a decision aid were more likely to receive their preferred AAA repair type, suggesting that decision aids can help better align patient preferences and treatments in major cardiovascular procedures.ClinicalTrials.gov Identifier: NCT03115346.

OBJECTIVE: Opioid use is common among patients with peripheral arterial disease (PAD), given that pain is a defining symptom. Unfortunately, long-term opioid use places patients at dramatically increased risk of overdose and death. Although surgical revascularization is extremely effective in alleviating ischemic pain related to PAD, it is unclear whether this practice results in the discontinuation of opioids after surgery. Therefore, we conducted the following study to investigate trends in opioid use before and after surgical bypass in patients with PAD, as well as the risk factors for continued opioid use after surgery. METHODS: We conducted a retrospective analysis of patients undergoing open lower extremity bypass for claudication or rest pain between June 1, 2017, and March 31, 2021. Patients were grouped according to whether they reported preoperative opioid use at the time of surgery. The primary outcome was continued opioid use at 30-day follow-up after discharge. A multivariable logistic regression was conducted to estimate the association of continued opioid use with patient characteristics, preoperative opioid use, and receiving a postoperative opioid prescription. RESULTS: Among 3873 patients undergoing surgery, the mean age was 65.7 (10.2) years and 2650 (68.4%) patients were male. There were 913 patients (23.6%) who used opioids preoperatively and hydrocodone was the most common preoperative opioid (583 [63.9%]). At discharge, 2506 patients (64.7%) received a postoperative opioid prescription. Postoperative opioid prescriptions were significantly more common for preoperative opioid users than opioid-naïve patients (813 [89.0%] vs 1693 [57.2%]; P < .001) and were significantly larger in size (24.3 [21.1] pills vs 19.9 [10.5] pills; P < .001). On 30-day follow-up, 522 preoperative opioid users (61.3%) and 616 opioid-naïve patients (28.4%) reported that they were still using opioids (P < .001). Continued opioid use at follow-up was associated with preoperative opioid use (adjusted odds ratio, 3.23; 95% confidence interval, 2.70–3.89) and receiving a postoperative opioid prescription (adjusted odds ratio, 10.83; 95% confidence interval, 7.96–15.06). CONCLUSIONS: Most patients with PAD who use opioids preoperatively do not discontinue opioids after lower extremity bypass. Moreover, a significant proportion of previously opioid-naïve patients are still using opioids 1 month after surgery. In both cases, postoperative opioid prescriptions had the strongest association with continued opioid use. These findings underscore the need for improved prescribing practice and increased attentiveness to discontinuation of unnecessary medications after surgery. (J Vasc Surg 2022;75:998–1007.)

Objective Tobacco use is common among vascular surgery patients and negatively impacts outcomes and longevity. In the second quarter of 2018, a statewide vascular quality collaborative launched an initiative across its 35 participating hospitals to promote smoking cessation at the time of surgery. This intervention was based on the Vascular Physician Offer and Report (VAPOR) trial and consisted of 3 components: brief physician-delivered advice, referral to telephone-based counseling, and nicotine replacement therapy. The goal of this study is to evaluate the results of this intervention. Methods We performed a retrospective analysis of patients undergoing vascular surgery between 2018 and 2020. Procedures included open abdominal aortic aneurysm repair, endovascular aneurysm repair, open vascular bypass, open thrombectomy, carotid endarterectomy, and carotid stenting. The primary explanatory variables were receipt of tobacco cessation interventions as documented in the medical record. The primary outcome was tobacco cessation, captured during 30-day and 1-year chart review and/or patient follow-up. A multivariable logistic regression model was calculated to estimate the association of covariates with smoking cessation while adjusting for patient and clinical characteristics. Results A total of 13,890 patients underwent surgery during the study period. The mean age was 69.4 ± 10 years; 4687 patients (34%) were female, and 5158 patients (37%) were current smokers. At least one smoking cessation component was delivered to 2245 patients (44% of smokers). The quit rate was 35% among 4671 patients with 30-day follow-up and 43% among 2936 patients with 1-year follow up. On multivariable regression, at 30 days, receiving two intervention components was associated with 1.29 (95% confidence interval [CI], 1.07-1.55) higher odds of quitting. At both time points, smoking cessation was also associated with undergoing an emergent procedure (30-day odds ratio [OR], 1.52; 95% CI, 1.16-1.99; 1-year OR, 1.41; 95% CI, 1.01-1.97) and undergoing open abdominal aortic aneurysm repair (30-day OR, 1.71; 95% CI, 1.20-2.43; 1-year OR, 1.75; 95% CI, 1.11-2.78). Conclusions In a cohort of vascular surgical patients where tobacco use was common, nearly one-half of patients quit smoking 1 year after surgery. Receiving two smoking cessation intervention components was associated with quitting at 30 days. Overall, these results demonstrate encouraging quit rates and identify an opportunity for longer-term intervention to maintain even greater 1-year tobacco cessation.

Coronavirus-associated coagulopathy (CAC) is a morbid and lethal sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CAC results from a perturbed balance between coagulation and fibrinolysis and occurs in conjunction with exaggerated activation of monocytes/macrophages (MO/Mφs), and the mechanisms that collectively govern this phenotype seen in CAC remain unclear. Here, using experimental models that use the murine betacoronavirus MHVA59, a well-established model of SARS-CoV-2 infection, we identify that the histone methyltransferase mixed lineage leukemia 1 (MLL1/KMT2A) is an important regulator of MO/Mφ expression of procoagulant and profibrinolytic factors such as tissue factor (F3; TF), urokinase (PLAU), and urokinase receptor (PLAUR) (herein, “coagulopathy-related factors”) in noninfected and infected cells. We show that MLL1 concurrently promotes the expression of the proinflammatory cytokines while suppressing the expression of interferon alfa (IFN-α), a well-known inducer of TF and PLAUR. Using in vitro models, we identify MLL1-dependent NF-κB/RelA–mediated transcription of these coagulation-related factors and identify a context-dependent, MLL1-independent role for RelA in the expression of these factors in vivo. As functional correlates for these findings, we demonstrate that the inflammatory, procoagulant, and profibrinolytic phenotypes seen in vivo after coronavirus infection were MLL1-dependent despite blunted Ifna induction in MO/Mφs. Finally, in an analysis of SARS-CoV-2 positive human samples, we identify differential upregulation of MLL1 and coagulopathy-related factor expression and activity in CD14+ MO/Mφs relative to noninfected and healthy controls. We also observed elevated plasma PLAU and TF activity in COVID-positive samples. Collectively, these findings highlight an important role for MO/Mφ MLL1 in promoting CAC and inflammation.

Dialysis vascular access remains vitally important to maintain life and functional capacity with end stage renal disease. Angioplasty is an integral part of maintaining dialysis access function and patency. To understand the effect of angioplasty balloon dilation on vascular wall mechanics, we conducted a clinical study to evaluate the elastic modulus of the anastomosis in five subjects with anastomosis stenoses, before and after six angioplasty procedures, using B-mode ultrasound DICOM data. A novel and open source vascular ultrasound high-resolution speckle tracking software tool was used. The median lumen diameter increased from 3.4 to 5.5 mm after angioplasty. Meanwhile, the median elastic modulus of the 18 measurements at the anastomosis increased by 52.2%, from 2.24 × 103 to 3.41 × 103 mmHg. The results support our hypothesis that the structural changes induced in the vessel wall by balloon dilation lead to reduced vascular compliance and a higher elastic modulus of the vessel wall.

Maintaining dialysis vascular access is a source of considerable morbidity in patients with end-stage renal disease (ESRD). High-resolution radiofrequency (RF) ultrasound vascular strain imaging has been applied experimentally in the vascular access setting to assist in diagnosis and management. Unfortunately, high-resolution RF data are not routinely accessible to clinicians. In contrast, the standard DICOM formatted B-mode ultrasound data are widely accessible. However, B-mode, representing the envelope of the RF signal, is of much lower resolution. If strain imaging could use open-source B-mode data, these imaging techniques could be more broadly investigated. We conducted experiments to detect wall strain signals with submillimeter tracking resolutions ranging from 0.2 mm (3 pixels) to 0.65 mm (10 pixels) using DICOM B-mode data. We compared this submillimeter tracking to the overall vascular distensibility as the reference measurements to see if high-strain resolution strain could be detected using open-source B-Mode data. We measured the best-fit coefficient of determination between signals, expressed as the percentage of strain waveforms that exhibited a correlation with a p value of 0.05 or less. The lowest percentage was 86.7%, and most were 90% and higher. This indicates high-resolution strain signals can be detected within the vessel wall using B-mode DICOM data.

Background: Up to 50% of patients with proximal deep vein thrombosis (DVT) will develop the postthrombotic syndrome characterized by limb swelling and discomfort, hyperpigmentation, skin ulcers, and impaired quality of life. Although catheter-based interventions enabling the restoration of blood flow (RBF) have demonstrated little benefit on postthrombotic syndrome, the impact on the acuity of the thrombus and mechanisms underlying this finding remain obscure. In experimental and clinical studies, we examined whether RBF has a restricted time window for improving DVT resolution. Methods: First, experimental stasis DVT was generated in C57/BL6 mice (n=291) by inferior vena cava ligation. To promote RBF, mice underwent mechanical deligation with or without intravenous recombinant tissue plasminogen activator administered 2 days after deligation. RBF was assessed over time by ultrasonography and intravital microscopy. Resected thrombosed inferior vena cava specimens underwent thrombus and vein wall histological and gene expression assays. Next, in a clinical study, we conducted a post hoc analysis of the ATTRACT (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) pharmacomechanical catheter-directed thrombolysis (PCDT) trial (NCT00790335) to assess the effects of PCDT on Venous Insufficiency Epidemiological and Economic Study quality-of-life and Villalta scores for specific symptom-onset-to-randomization timeframes. Results: Mice that developed RBF by day 4, but not later, exhibited reduced day 8 thrombus burden parameters and reduced day 8 vein wall fibrosis and inflammation, compared with controls. In mice without RBF, recombinant tissue plasminogen activator administered at day 4, but not later, reduced day 8 thrombus burden and vein wall fibrosis. It is notable that, in mice already exhibiting RBF by day 4, recombinant tissue plasminogen activator administration did not further reduce thrombus burden or vein wall fibrosis. In the ATTRACT trial, patients receiving PCDT in an intermediate symptom-onset-to-randomization timeframe of 4 to 8 days demonstrated maximal benefits in Venous Insufficiency Epidemiological and Economic Study quality-of-life and Villalta scores (between-group difference=8.41 and 1.68, respectively, P 8 days. Conclusions: Taken together, these data illustrate that, within a restricted therapeutic window, RBF improves DVT resolution, and PCDT may improve clinical outcomes. Further studies are warranted to examine the value of time-restricted RBF strategies to reduce postthrombotic syndrome in patients with DVT.

Background Quantitative methods for evaluating microstructure of arterial specimens typically rely on histologic techniques that involve random sampling, which cannot account for the unique spatial distribution of features in three dimensions. Methods To overcome this limitation, we demonstrate a nondestructive method for three-dimensional imaging of intact human blood vessels using microcomputed tomography (microCT). Human artery segments were dehydrated and stained in an iodine solution then imaged with a standard laboratory microCT scanner. Image visualization and segmentation was performed using commercially available and open source software. Results Staining of cadaveric vessels with iodine enabled clear visualization of the arterial wall with microCT, preserved tissue morphology, and generated high-resolution images with a voxel size of 5.4 μm. Various components of the arterial wall were segmented using a combination of manual and automatic thresholding algorithms. Conclusions Our approach allows for spatial mapping of human artery tissue samples that can guide targeted histologic analysis of smaller tissue segments, provide geometric data to inform finite element models, quantify degree of atherosclerosis, and help to evaluate the foreign body response to intravascular medical implants. (JVS–Vascular Science 2020;2:13-19.) Clinical Relevance In this article, we describe a powerful technique for whole artery analysis of pathologic human tissue specimens that provides high-resolution spatial detail regarding composition of the blood vessel wall. The protocol described here is a valuable adjunct that can be used as a research tool to inform finite element modeling of arteries, quantify pathologic response (ie, neointimal hyperplasia and vascular calcification), and evaluate the tissue/device interface of implanted medical devices.

Objectives: Coronavirus associated coagulopathy (CAC) is postulated to be driven by systemic macrophage activation after SARS-CoV-2 infection and presents with elevated risk of thrombogenesis and hyperfibrinolysis. Previous work shows that the histone methyltransferase KMT2A/MLL1 is a key mediator of inflammatory signaling in monocytes and macrophages (Mo/Mϕs). In this study, we sought to identify the regulation of factors important in CAC by MLL1. Methods: Mice with myeloid specific knockout of MLL1 (Cre+) and littermate controls (Cre-) underwent intranasal inoculation of 2 x 10 5 pfu of the murine coronavirus MHVA59, an established model which phenocopies SARS-CoV-2 infection. Splenic Mϕs (surrogate for circulating Mo/Mϕs) were isolated and RNA and protein levels of urokinase (Plau; profibrinolytic), urokinase receptor (Plaur; profibrinolytic), and tissue factor (F3/TF; procoagulant) were analyzed using qRT-PCR and ELISA, respectively. Thromboelastography (TEG) on whole blood and urokinase activity assays from mouse plasma were performed. Urokinase and TF activity assays were performed on plasma from human samples. Results: RNA (top panel) and protein (bottom) levels of Plau, Plaur, and F3 were suppressed in the Splenic Mϕs harvested from sham (intranasal PBS) and infected Cre+ animals (white bars) compared to Splenic Mϕs harvested from Cre- animals (blue bars; Fig. 1A). Cre- mice displayed a shortened R-time (reaction time) as measured by TEG (Fig. 1B) and elevated plasma urokinase activity levels (not shown). Hospitalized COVID-positive patients (hCOV+) displayed elevated plasma urokinase and TF activity levels (Fig. 1C). Conclusions: We identify a role for MLL1 for basal expression and for coronavirus-mediated induction of factors important for fibrinolysis and coagulation in murine Mo/Mϕs and in driving coagulopathy. Our results suggest that MLL1 blockade may be an attractive strategy to combat coronavirus associated coagulopathy.

This retrospective cohort study analyzes venous thromboembolism (VTE) incidence, morbidity, and mortality amongst postsurgical patients with and without VTE chemoprophylaxis within a quality collaborative. Postoperative thromboprophylaxis was broadly applied, yet was associated with no decrease in VTE, without affecting transfusion or mortality. Predictors of breakthrough VTE development despite evidence-based thromboprophylaxis are identified.We hypothesized that a high rate of prescription of VTE chemoprophylaxis would be associated with decreased VTE incidence and mortality.Recommendations for VTE prevention in surgical patients include chemoprophylaxis based upon preoperative risk stratification.This retrospective cohort study analyzed VTE incidence, morbidity, and mortality amongst postsurgical patients with and without VTE chemoprophylaxis between April 2013 and September 2017 from 63 hospitals within the Michigan Surgical Quality Collaborative. A VTE risk assessment survey was distributed to providers. Bivariate and multivariate comparisons were made, as well as using propensity score matched cohorts to determine if VTE chemoprophylaxis was associated with decreased VTE events. Hospitals were compared using risk-reliability adjusted VTE prophylaxis and postoperative VTE event rates.Within the registry, 80% of practitioners reported performing formal VTE risk assessment. Amongst 32,856 operations, there were 480 (1.46%) postoperative VTE, and an overall mortality of 609 (1.85%) patients. Using a propensity matched cohort, we found that rates of VTE were similar in those receiving unfractionated heparin or low molecular weight heparin compared to those not receiving chemoprophylaxis (1.22 vs 1.13%, P = 0.57). When stratified further by VTE risk scoring, even the highest risk patients did not have an associated lower VTE rate (3.68 vs 4.22% P = 0.092). Postoperative transfusion (8.28 vs 7.50%, P = 0.057) and mortality (2.00% vs 1.62%, P = 0.064) rates were similar amongst those receiving and those not receiving chemoprophylaxis. No correlation was found between postoperative VTE chemoprophylaxis application and hospital specific risk adjusted postoperative VTE rates.In modern day postsurgical care, VTE remains a significant occurrence, despite wide adoption of VTE risk assessment. Although postoperative VTE chemoprophylaxis was broadly applied, after adjusting for confounders, no reduction in VTE was observed in at-risk surgical patients.

Post-thrombotic syndrome (PTS) is an end stage manifestation of deep vein thrombosis. This is an inherently inflammatory process, with consequent fibrosis. Multiple cellular types are involved, and are likely driven by leukocytes. Herein, we review the current gaps in therapy, and insights from rodent models of venous thrombosis that suggest possible targets to treat and prevent PTS.

Objective The objective of this study was to determine how electronic consults (eConsults) are used in vascular surgery in a veterans health care setting and whether their use is safe for patients. Methods A retrospective review was performed of all eConsults completed by the vascular surgery service at the Ann Arbor Veterans Affairs Healthcare System between October 10, 2012 and November 15, 2013. Patients' demographics and comorbidities were collected. eConsult recommendations and patient and provider compliance with recommendations were collected. Data on adverse outcomes up to 1 year after consultation and data on all-cause mortality at 1 year and 5 years were collected. Results Between October 10, 2012 and November 15, 2013, of 350 eConsults completed, 123 (35%) were for peripheral artery disease, 93 (27%) for carotid stenosis, and 57 (16%) for abdominal aortic aneurysm. Unique recommendations were made for 291 consults (83%). Medication recommendations were made in 140 consults (40%). The most commonly recommended medication was cilostazol. Compliance with medication recommendations ranged from 30% to 61%. Noninvasive imaging was recommended in 220 consults (60.3%). Procedures overall were recommended in only six consults (1.7%). Five-year all-cause mortality for categorized diagnoses ranged from 8.3% for nonabdominal aneurysm to 28.1% for abdominal aortic aneurysm. Conclusions Within the Veterans Affairs vascular surgery service, eConsults provide a safe and effective means of triaging and providing recommendations for patients with vascular disease. eConsults used to augment traditional consultations may provide an important means of reducing clinic congestion for providers and reducing time and cost for patients.

Objective Venous thromboembolism (VTE) is a common disease with potentially devastating and long-term sequelae, such as pulmonary embolism and post-thrombotic syndrome (PTS). Given the mortality risk, prevalence of VTE, and limited access to diagnostic imaging, clinically relevant biomarkers for diagnosis and prognostication are needed. Therefore, this review aimed to summarize the data on clinically applicable biomarkers that best indicate acute VTE and chronic PTS. Methods We reviewed the medical and scientific literature from 2001 to 2019 for VTE biomarkers. Randomized controlled trials, meta-analyses, and review articles were included. Primary basic research papers with no clinical applicability, opinion papers, institutional guidelines, and case reports were excluded. Results We highlight the diagnostic value of D-dimer alongside other promising biomarkers, including cellular adhesion molecules, P-selectin, cytokines (interleukins 6 and 10), fibrin monomer complexes, and coagulation factors (factor VIII). Conclusions High-sensitivity D-dimer remains the most clinically established VTE biomarker. Current research endeavors are under way to identify more precise biomarkers of VTE and PTS.

Volume-outcome relationships exist for many complex surgical procedures, prompting institutions to adopt surgical volume standards for credentialing. The current Leapfrog Group Hospital volume standard for open abdominal aortic aneurysm repair (OAR) is 15 per year. However, this is primarily based on data from the 1990s and may not be appropriate given the dramatic decline in OAR. We sought to quantify the proportion of hospitals meeting volume standards, the difference in perioperative outcomes between low-volume and high-volume hospitals, and the potential travel burden of volume credentialing on patients.We identified Medicare beneficiaries for individuals aged ≥65 years undergoing OAR in 2013-2014. Hospital "all-payer" annual volume was estimated based on the national proportion of patients undergoing OAR covered by Medicare in the Vascular Quality Initiative. Hospital annual OAR volume was characterized as5/year, 5-9/year, 10-14/year, and ≥15/year (high volume). Adjusted rates of postoperative morbidity, reoperation, failure to rescue, and mortality in 2014 were compared across volume cohorts. Distance between patients' home zip code and high-volume hospitals was calculated.A total of 21,191 OARs were performed at 1,445 hospitals between 2013 and 2014. The average hospital OAR annual volume was 7.8 (standard deviation [SD] ± 9.3) with a median of 4.5. Among the 1,445 hospitals, only 190 (13.1%) performed ≥15 OARs per year whereas 756 hospitals (53.3%) performed5 per year. Among patients who underwent OAR in 2014, 5,395 (53.3%) received care at a hospital that performed15 per year. There was no difference in complication, reoperation, or failure to rescue rates between high-volume and low-volume hospitals. Mortality did not significantly differ among OAR volume cohorts. Hospitals performing5 OARs per year had a mortality rate of 5.7% compared with 5.6% at high-volume hospitals (P = 0.817). One-quarter of patients who received care at a low-volume hospital would have had to travel more than 60 miles to reach a high-volume hospital.By conservative estimates, only 13% of hospitals performing OAR meet current volume standards. Triaging all patients to high-volume hospitals would require shifting over 5,000 patients annually with no associated improvement in perioperative outcomes. Implementation of the current OAR hospital volume standard may significantly burden patients and hospitals without improving surgical outcomes.

A ruptured abdominal aortic aneurysm (rAAA) is a life-threatening condition that carries a high mortality rate. Recent guidelines have recommended a goal "door-to-intervention" time of ≤90 minutes despite a paucity of evidence to support this goal. The aim of this study was to analyze recent trends in door-to-intervention time for rAAAs and determine the effect of the 90-minute door-to-intervention benchmark on postoperative complications.A retrospective analysis of all patients who underwent open aortic repair (OAR) or endovascular aneurysm repair (EVAR) of a rAAA in the Vascular Quality Initiative database (2003-2018) was performed. Variation in door-to-intervention time was analyzed at the patient and hospital level. Patients were dichotomized into ≤90 or90 minute door-to-intervention time cohorts. Hierarchical modeling controlling for the hospital random effect and multivariate logistic models was used to analyze the association on 30-day mortality and major in-hospital complications.A total of 3,630 operative cases for rAAA were identified (1696 OAR and 1934 EVAR). For the OAR cohort, 1035 patients (61%) had a door-to-intervention time of ≤90 minutes. However, at the hospital level, a minority of hospitals (49%) reliably achieved the OAR goal door-to-intervention time. For OARs, there was no difference in 30-day risk-adjusted major complications or mortality between the ≤90- and 90-minute cohorts. For EVAR, 1014 patients (53.8%) had a door-to-intervention time of ≤90 minutes and a minority of hospitals (40%) upheld the recommended ≤90 minute door-to-intervention threshold. In the EVAR group, patients with a ≤90 minute door-to-intervention time had higher rates of postoperative myocardial infarction (12.0% vs. 8.5%; P 0.05) but no difference in 30-day risk-adjusted mortality.A low percentage of rAAAs are being treated within the recommended door-to-intervention time. Despite this deficiency, the ≤90-minute benchmark has minimal impact on postoperative morbidity and mortality. Based on these findings, alternative quality metrics should be identified to improve the clinical care of patients with rAAA.

Objective: Prior research on median arcuate ligament syndrome has been limited to institutional case series, making the optimal approach to median arcuate ligament release (MALR) and resulting outcomes unclear. In the present study, we compared the outcomes of different approaches to MALR and determined the predictors of long-term treatment failure. Methods: The Vascular Low Frequency Disease Consortium is an international, multi-institutional research consortium. Data on open, laparoscopic, and robotic MALR performed from 2000 to 2020 were gathered. The primary outcome was treatment failure, defined as no improvement in median arcuate ligament syndrome symptoms after MALR or symptom recurrence between MALR and the last clinical follow-up. Results: For 516 patients treated at 24 institutions, open, laparoscopic, and robotic MALR had been performed in 227 (44.0%), 235 (45.5%), and 54 (10.5%) patients, respectively. Perioperative complications (ileus, cardiac, and wound complications; readmissions; unplanned procedures) occurred in 19.2% (open, 30.0%; laparoscopic, 8.9%; robotic, 18.5%; P < .001). The median follow-up was 1.59 years (interquartile range, 0.38-4.35 years). For the 488 patients with follow-up data available, 287 (58.8%) had had full relief, 119 (24.4%) had had partial relief, and 82 (16.8%) had derived no benefit from MALR. The 1- and 3-year freedom from treatment failure for the overall cohort was 63.8% (95% confidence interval [CI], 59.0%-68.3%) and 51.9% (95% CI, 46.1%-57.3%), respectively. The factors associated with an increased hazard of treatment failure on multivariable analysis included robotic MALR (hazard ratio [HR], 1.73; 95% CI, 1.16-2.59; P = .007), a history of gastroparesis (HR, 1.83; 95% CI, 1.09-3.09; P = .023), abdominal cancer (HR, 10.3; 95% CI, 3.06-34.6; P < .001), dysphagia and/or odynophagia (HR, 2.44; 95% CI, 1.27-4.69; P = .008), no relief from a celiac plexus block (HR, 2.18; 95% CI, 1.00-4.72; P = .049), and an increasing number of preoperative pain locations (HR, 1.12 per location; 95% CI, 1.00-1.25; P = .042). The factors associated with a lower hazard included increasing age (HR, 0.99 per increasing year; 95% CI, 0.98-1.0; P = .012) and an increasing number of preoperative diagnostic gastrointestinal studies (HR, 0.84 per study; 95% CI, 0.74-0.96; P = .012) Open and laparoscopic MALR resulted in similar long-term freedom from treatment failure. No radiographic parameters were associated with differences in treatment failure. Conclusions: No difference was found in long-term failure after open vs laparoscopic MALR; however, open release was associated with higher perioperative morbidity. These results support the use of a preoperative celiac plexus block to aid in patient selection. Operative candidates for MALR should be counseled regarding the factors associated with treatment failure and the relatively high overall rate of treatment failure.

Venous thromboembolism (VTE) is a significant cause of mortality1, yet its genetic determinants remain incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank testing ~13 million DNA sequence variants for association with VTE (26,066 cases; 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 VTE cases and 167,295 controls. We identified 22 novel loci, bringing the total number of VTE-associated loci to 33 and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for VTE that identifies 5% of the population at equivalent incident VTE risk to carriers of the established F5 Leiden (p.R506Q) and prothrombin G20210A mutations. Our data provide new mechanistic insights into the genetic epidemiology of VTE and suggest a greater overlap among venous and arterial cardiovascular disease than previously suggested., Editorial summary Genome-wide analysis of venous thromboembolism identifies 22 new risk loci and facilitates construction of a polygenic risk score. Comparison to arterial vascular disease highlights shared pathophysiology and potential therapeutic strategies.

Recent vascular societal guidelines have recommended an abdominal aortic aneurysm (AAA) size threshold for elective intervention; however, limited data have documented how well these AAA diameter benchmarks are being met. The objective of this study was to analyze variation in management of AAAs based on diameter and to determine the physician's rationale for intervention on small AAAs in relation to recommended treatment guidelines.A retrospective review of a statewide vascular surgery registry of all elective endovascular or open surgical AAA repairs from January 2012 to January 2016 was performed. Patients were dichotomized on the basis of aortic diameter at time of intervention into either guideline size AAAs or small AAAs, which were defined as 5.5 cm in men, 5.0 cm in women, or with growth 1.0 cm/y. An internal review was conducted of all small AAAs to determine the physician's rationale for intervention. The primary outcomes were variation in adherence to recommended treatment guidelines and the physician's rationale for treatment of small AAAs. Risk-adjusted major complication and mortality rates were calculated at 30 days and 1 year using a propensity score matching analysis.Among the 3932 patients who underwent an elective AAA repair, 485 (12.3%) were repaired at diameters smaller than recommended by guidelines. The median AAA size in the small AAA cohort was 5.1 cm (interquartile range, 4.7-5.3 cm) vs 5.6 cm (interquartile range, 5.2-6.1 cm) in the guideline-based group. Percentage of small AAA repairs varied widely between hospitals from 1.4% to 44.4%. The physician's rationale for the majority of early interventions included the patient's anxiety (12.0%), combined aortoiliac occlusive disease (14.8%), aneurysm anatomy (28.2%), and does not adhere to guidelines (30%). The small AAA cohort had no significant difference in the 30-day or 1-year risk-adjusted mortality in comparison to guideline size AAAs.Despite well-established aortic diameter threshold guidelines, marked variation exists both at the hospital level and in terms of the physician's rationale for the management of elective AAA repairs. These findings demonstrate the challenge of providing uniform care for patients with AAAs despite established guidelines.

Murine models are widely used valuable tools to study deep vein thrombosis. Leading experts in venous thrombosis research came together through the American Venous Forum to develop a consensus on maximizing the utility and application of available mouse models of venous thrombosis. In this work, we provide an algorithm for model selection, with discussion of the advantages, disadvantages, and applications of the main mouse models of venous thrombosis. Additionally, we provide a detailed surgical description of the models with guidelines to validate surgical technique.

Myeloid cells are critical for orchestrating regulated inflammation during wound healing. TLRs, particularly TLR4, and its downstream-signaling MyD88 pathway play an important role in regulating myeloid-mediated inflammation. Because an initial inflammatory phase is vital for tissue repair, we investigated the role of TLR4-regulated, myeloid-mediated inflammation in wound healing. In a cutaneous tissue injury murine model, we found that TLR4 expression is dynamic in wound myeloid cells during the course of normal wound healing. We identified that changes in myeloid TLR4 during tissue repair correlated with increased expression of the histone methyltransferase, mixed-lineage leukemia 1 (MLL1), which specifically trimethylates the histone 3 lysine 4 (H3K4me3) position of the TLR4 promoter. Furthermore, we used a myeloid-specific Mll1 knockout (Mll1f/fLyz2Cre+) to determine MLL1 drives Tlr4 expression during wound healing. To understand the critical role of myeloid-specific TLR4 signaling, we used mice deficient in Tlr4 (Tlr4−/−), Myd88 (Myd88−/−), and myeloid-specific Tlr4 (Tlr4f/fLyz2Cre+) to demonstrate delayed wound healing at early time points postinjury. Furthermore, in vivo wound myeloid cells isolated from Tlr4−/− and Myd88−/− wounds demonstrated decreased inflammatory cytokine production. Importantly, adoptive transfer of monocyte/macrophages from wild-type mice trafficked to wounds with restoration of normal healing and myeloid cell function in Tlr4-deficient mice. These results define a role for myeloid-specific, MyD88-dependent TLR4 signaling in the inflammatory response following cutaneous tissue injury and suggest that MLL1 regulates TLR4 expression in wound myeloid cells.

Background: Varicose veins are common in older adults, and associated with major clinical adverse outcomes such as deep venous thrombosis. Although there are a few established risk factors of varicose veins such as female sex, height, and obesity, some other risk factors demonstrated inconsistent results. Aim: To identify demographic and clinical risk factors of incident varicose veins Methods: Using data from the Atherosclerosis Risk in Communities (ARIC) Study over five clinic visits, we constructed a cohort of 6612 adults aged 65-70 years to be able to capture outpatient visits using Medicare data. For each participant, the first visit when meeting age range (65-70 years) was used as baseline. Varicose veins were defined as two outpatient encounters (at least a week apart) or inpatient diagnoses through 2015 (ICD9 codes:454.xx). Participants with clinically-recognized varicose veins prior to baseline were excluded. We explored demographic and clinical predictors routinely evaluated in ARIC visits using Cox regression. Results: During a median follow-up of 15 years, 348 (5%) of participants developed incident clinically-recognized varicose veins. We confirmed female sex, greater height, and higher body mass index were associated with varicose veins ( Table ). In addition, white race, loop diuretic use, prevalent heart failure were independently associated with incident varicosities. In subsample with relevant data, higher cardiac troponin T and natriuretic peptide were also independently associated with varicose veins. When we censored participants who left Medicare fee-for-service, results were largely consistent. Conclusions: In this community-based cohort study of older adults, in addition to established predictors, we found that white race and clinical and treatment factors related to cardiac function were associated with clinically-recognized varicose veins that may help identify those at high-risk of varicose veins.

Introduction Abdominal aortic aneurysm (AAA) repair may be performed through open or endovascular approaches, but the factors influencing a patient's repair-type preference are not well characterized. Here we performed a qualitative analysis to better understand factors influencing patient preference within the Preference for Open Versus Endovascular Repair of AAA Trial. Methods Open-ended responses regarding primary (n = 21) and secondary (n = 47) factors influencing patient preference underwent qualitative analysis using the constant comparative method with iterative reviews. Codes were used to generate themes and themes grouped into categories, with each step conducted via consensus agreement between three researchers. Relative prevalence of themes were compared to ascertain trends in patient preference. Results Patient responses regarding both primary and secondary factors fell into four categories: Short-term concerns, long-term concerns, advice & experience, and other. Patients most frequently described short-term concerns (23) as their primary influence, with themes including post-op complications, hospitalization & recovery, and intraoperative concerns. Long-term concerns were more prevalent (20) as secondary factors, which included themes such as survival, and chronic management. The average age of patients voicing only long-term concerns as a primary factor was 11 years younger than those listing only short-term concerns. Conclusion Short-term concerns relating to the procedure and recovery are more often the primary factor influencing patient preference, while long term concerns play a more secondary role. Long-term concerns are more often a primary factor in younger patients. Vascular surgeons should consider this information in shared decision making to reach an optimal outcome.

Background: The postthrombotic syndrome is a common, often morbid sequela of venous thrombosis (VT) that arises from thrombus persistence and inflammatory scarring of juxtaposed vein walls and valves. Noninvasive 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging can measure neutrophil inflammation in VT. Here, we hypothesized (1) early fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) VT inflammation can predict subsequent vein wall scarring (VWS) and (2) statin therapy can reduce FDG-PET VT inflammation and subsequent VWS. Methods: C57BL/6J mice (n=75) underwent induction of stasis-induced VT of the inferior vena cava or jugular vein. Inferior vena cava VT mice (n=44) were randomized to daily oral rosuvastatin 5 mg/kg or saline starting at day −1. Subgroups of mice then underwent FDG-PET/CT 2 days after VT induction. On day 14, a subset of mice was euthanized, and VWS was assessed via histology. In vitro studies were further performed on bone marrow-derived neutrophils. Results: Statin therapy reduced early day 2 FDG-PET VT inflammation, thrombus neutrophil influx, and plasma IL (interleukin)-6 levels. At day 14, statin therapy reduced VWS but did not affect day 2 thrombus mass, cholesterol, or white blood counts, nor reduce day 2 glucose transporter 1 or myeloperoxidase expression in thrombus or in isolated neutrophils. In survival studies, the day 2 FDG-PET VT inflammation signal as measured by mean and maximum standardized uptake values predicted the extent of day 14 VWS (area under the receiver operating characteristic curve =0.82) with a strong correlation coefficient ( r ) of r =0.73 and r =0.74, respectively. Mediation analyses revealed that 40% of the statin-induced VWS reduction was mediated by reductions in VT inflammation as quantified by FDG-PET. Conclusions: Early noninvasive FDG-PET/CT imaging of VT inflammation predicts the magnitude of subsequent VWS and may provide a new translatable approach to identify individuals at risk for postthrombotic syndrome and to assess anti-inflammatory postthrombotic syndrome therapies, such as statins.

To evaluate the association between gender and long-term clinician-reported and patient-reported outcomes after endovenous ablation procedures.This retrospective cohort study of prospectively collected data from the Vascular Quality Initiative's Varicose Vein Registry included patients undergoing endovenous ablation procedures on truncal veins with or without treatment of perforating veins between 2015 and 2019. A univariate analysis included comparisons of preprocedural, postprocedural, and periprocedural change in Venous Clinical Severity Score (VCSS) and total symptom score by gender. Rates of complications including deep vein thrombosis, endovenous heat-induced thrombosis, leg pigmentation, blistering, paresthesia, incisional infection, and any postprocedural complications were reported by gender. Multivariable analysis leveraged linear regression to examine how gender affected the relationships between patient characteristics, complication rates, and periprocedural change in VCSS score and total symptom score.Of 9743 patients who met the inclusion criteria, 3090 (31.7%) were men and 6653 (68.2%) were women. The perioperative change in VCSS score was greater for men than women (average -4.46 for men vs -4.13 for women; P .0001). Perioperative change in total symptom score was greater for women than for men (average -10.64 for women vs -9.64 for men; P .0001). Women had lower incidence of any leg complication (6.1% vs 8.6%; P = .001) endovenous heat-induced thrombosis (1.1% vs 2.2%; P = .002), and infection (0.4% vs 0.7%; P = .001). In multivariable analysis, among patients with a body mass index of more than 40, presence of deep reflux, and preoperative Clinical, Etiologic, Anatomic, and Physiologic classification of 2, women had a greater periprocedural change in VCSS score than men.Women benefited from endovenous ablation similarly as men, with a lower incidence of postprocedural complications. Gender may be useful for patient selection and counseling for endovenous ablation, with particular usefulness among patients with a high body mass index, presence of deep reflux, and preoperative Clinical, Etiologic, Anatomic, and Physiologic classification of 2.