Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity.

Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape1,2. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPR-Cas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH and KAP1 complexes as mediators of immune escape3-5. We also found that amplification of SETDB1 (1q21.3) in human tumours is associated with immune exclusion and resistance to immune checkpoint blockade. SETDB1 represses broad domains, primarily within the open genome compartment. These domains are enriched for transposable elements (TEs) and immune clusters associated with segmental duplication events, a central mechanism of genome evolution6. SETDB1 loss derepresses latent TE-derived regulatory elements, immunostimulatory genes, and TE-encoded retroviral antigens in these regions, and triggers TE-specific cytotoxic T cell responses in vivo. Our study establishes SETDB1 as an epigenetic checkpoint that suppresses tumour-intrinsic immunogenicity, and thus represents a candidate target for immunotherapy.

A Comparison of Venaseal Versus Radiofrequency Ablation Outcomes Within a Managed Care Organization.

BACKGROUND: Chronic venous insufficiency is a common medical condition that afflicts over 30 million adults in the United States. Treatment and management have changed dramatically over the past 20 years with the introduction of various endovenous therapies, including radiofrequency ablation (RFA) and cyanoacrylate closure using the Venaseal system. In this study, we explore a direct comparison of outcomes between RFA and VenaSeal conducted by a single surgeon within a managed care organization. METHODS: Between May 2020 and December 2021, there were 87 patients undergoing 97 total procedures who were treated with either VenaSeal (n = 55) or RFA (n = 42), conducted by a single surgeon within a managed care organization. Primary outcomes included successful greater saphenous vein (GSV) closure, postoperative deep vein thrombosis (DVT), embolization, saphenofemoral junction (SFJ) thrombosis, skin reaction (allergic or thrombophlebitis), or procedure-related emergency room (ER) and urgent care (UC) visits. Retrospective chart review was conducted to describe patient demographics, indications for treatment, treatment details (number of access sites and indication for treatment), as well as follow-up adjunctive vein procedures (sclerotherapy and stab phlebectomy). RESULTS: All patients had postprocedural ultrasound (US) performed within 7 days by the operating surgeon and mean overall patient follow-up from index procedure was 12 months; 2 patients were lost to follow-up due to death. All operations utilized intraoperative US, and SFJ thrombosis was not observed in any patient postprocedure. The average age of VenaSeal and RFA groups was 59.05 and 59.51 years, respectively. The average number of access sites during the procedure for VenaSeal and RFA was 1.56 and 1.20, respectively. Of the 55 VenaSeal treatments, 9.1% of patients reported postoperative skin reactions, and 9.1% of patients underwent subsequent stab phlebectomy (22 stabs on average). Of the 42 RFA treatments, 7.1% of RFA patients reported postoperative skin reactions, and 9.5% underwent subsequent stab phlebectomy (36 stabs on average). The percentage of patients who had postoperative UC or emergency department visits related to the procedure in the VenaSeal and RFA groups was 3.6% and 0%, respectively. CONCLUSIONS: Both VenaSeal and RFA demonstrated effective vein closure of the GSV at 12-month follow-up, with VenaSeal demonstrating continued noninferiority to RFA. Based on our data, postoperative skin reactions do not appear to be significantly higher with VenaSeal treatment, as previously reported.

The Use of Advanced Three-Dimensional Computed Tomography During Simple and Complex Endovascular Aortic Aneurysm Repairs.

BACKGROUND: Endovascular aneurysm repair (EVAR) success depends on imaging technology both in the planning and operative phases. Endovascular repair requires intravenous contrast and radiation exposure to the patient as well as radiation exposure to the operator. Recent developments in imaging technology attempt to merge preoperative imaging with intraoperative imaging to improve the efficiency and accuracy of EVAR. The Cydar 3-dimensional (3D) imaging system combines the preoperative and intraoperative imaging during the operation. We aim to investigate the use of the Cydar 3D imaging system during EVAR compared to conventional methods. METHODS: Retrospective review of all patients undergoing an EVAR at a single quaternary vascular center from 2019-2023 was collected. This cohort was divided into 2 groups: (1) repair using Cydar 3D imaging or (2) repair without Cydar 3D imaging. Overall, 138 unique patients were identified with 27 operations using Cydar 3D imaging and 111 operations without Cydar 3D imaging. We performed a 1-to-1 propensity score-matched analysis using nearest-neighbor matching for variables including age, case urgency, and if the case was performed in the operative room or interventional radiology room. A match occurred when a patient in the Cydar 3D imaging group had an estimated score within 0.01 standard deviations of a patient in the control group. From this, we paired 27 from each cohort for a total of 54 patients. Demographic data included length of stay in days, contrast volume (mL), fluoroscopy time (min), procedure length (mins), mortality, and blood loss (mL). Univariate analyses were performed and a P value less than 0.05 was considered statistically significant. RESULTS: A total of 54 vascular patients were analyzed: 27 without the Cydar 3D imaging and 27 with the Cydar 3D imaging. In the univariate analysis, there was no statistical difference in the average length of stay (6.4 days ± 11.76 vs. 4.1 ± 6.03, P = 0.372), aneurysm size (5.9 ± 1.4 vs. 5.9 ± 1.2, P = 0.88), contrast volume in mL (91.3 ± 47.0 vs. 91.1-33.49, P = 9.88), fluoroscopy time in mins (20.2 ± 17.2 vs. 19.5 ± 19.4, P = 0.89), procedure length (299.3 ± 177.9 vs. 353 ± 191.98, P = 0.279), and blood loss in mL (513.8 ± 791 vs. 353 ± 191.98, P = 0.594). There was an increase in reintervention for endoleaks in the group with use of Cydar 3D imaging (0 vs. 6, P = 0.043). A subanalysis of patients undergoing physician-modified EVARs did show a 15% reduction in the contrast volume used. CONCLUSIONS: The use of 3D imaging technology has the potential to increase the safety of EVAR to both patients and operators. In our study, we did not find any difference in standard EVARs; however, there was a contrast use decrease in physician-modified EVARs. Further studies will need to be performed to determine the realized benefit from performing EVARs using this new technology.

Energy-Based Devices for the Treatment of Cutaneous Verrucae: A Systematic Review.

BACKGROUND: Warts are one of the most common benign neoplasms caused by human papillomavirus infection and often pose a therapeutic challenge. OBJECTIVE: To summarize the current evidence on the safety and efficacy of laser and energy-based devices for the treatment of cutaneous verrucae. METHODS: A comprehensive systematic review of the literature on laser and energy-based devices for the treatment of cutaneous verrucae was performed. RESULTS: A total of 904 unique studies were identified, of which 109 were included in this review. The most commonly used lasers as a single treatment modality for verrucae included the long-pulsed Nd:Yag (n = 20) and pulsed dye (n = 18) lasers. Other modalities included the CO2 ablative laser (n = 10), photodynamic therapy (n = 11), local hyperthermia (n = 11), microwave therapy (n = 2), and nanopulse stimulation (n = 1). Other studies combined energy-based modalities with additional treatments, such as retinoids, imiquimod, and intralesional bleomycin. Overall, such devices were generally well-tolerated, with only a mild side effect profile. CONCLUSION: Overall, the use of laser and energy-based devices is a safe and well-tolerated option for cutaneous verrucae that is relatively less invasive than surgical interventions. Future studies using more consistent outcome assessment tools will be valuable to help clinicians develop device-specific protocols and treatment regimens to ensure replicable and effective outcomes.

Risk for surgical interventions following endovascular aneurysm repair with Endologix AFX or AFX2 Endovascular AAA Systems compared with other devices.

OBJECTIVE: To evaluate the risk for 90-day returns to care and long-term subsequent surgical interventions after primary endovascular aneurysm repair (EVAR) with an Endologix AFX Endovascular AAA System compared with three other high-volume endograft devices. METHODS: We conducted a matched cohort study using data from Kaiser Permanente's Endovascular Stent Graft Registry. Patients aged ≥18 years who underwent primary EVAR for AAA in the health care system from January 1, 2011, to December 31, 2017, comprised the eligible study sample. The treatment group included patients who received an Endologix AFX or AFX2 device (n = 470). Patients who received one of three other high-volume endograft devices used within the health care system comprised the eligible comparison group (n = 2122). These patients were 2:1 propensity score matched without replacement to patients who received an Endologix device based on a number of patient and procedural characteristics. After the application of matching, conditional logistic regression was used to evaluate the likelihood for 90-day emergency department visit and readmission. Cause-specific Cox regression was used to evaluate the long-term risk of endoleak, graft revision, secondary reintervention (not including revision), conversion to open repair, and rupture during follow-up. Cox proportional hazards regression was used to evaluate the risk of mortality (overall and aneurysm related). RESULTS: The final matched study sample included 470 patients who received an Endologix AFX or AFX2 device and 940 patients who received a different high-volume device. compared with the other devices, AFX/AFX2 had a higher risk for type III endoleak (hazard ratio [HR], 38.79; 95% confidence interval [CI], 14.51-103.67), revision surgery >1 year after the primary EVAR (HR, 4.50; 95% CI, 3.10-6.54), rupture (HR, 6.52; 95% CI, 1.73-24.63), and aneurysm-related mortality (HR, 2.43; 95% CI, 1.32-4.47) was observed with the use of AFX/AFX2. CONCLUSIONS: In our matched cohort study, patients who received an Endologix AFX System during their primary EVAR had a higher risk for several adverse longitudinal outcomes, as well as aneurysm-related mortality, when compared with patients who received other high-volume devices. Patients who have received these devices should be monitored closely after EVAR.

Regulation of cardiovascular calcification by lipids and lipoproteins.

PURPOSE OF REVIEW: Lipids and lipoproteins have long been known to contribute to atherosclerosis and cardiovascular calcification. One theme of recent work is the study of lipoprotein (a) [Lp(a)], a lipoprotein particle similar to LDL-cholesterol that carries a long apoprotein tail and most of the circulating oxidized phospholipids. RECENT FINDINGS: In-vitro studies show that Lp(a) stimulates osteoblastic differentiation and mineralization of vascular smooth muscle cells, while the association of Lp(a) with coronary artery calcification continues to have varying results, possibly because of the widely varying threshold levels of Lp(a) chosen for association analyses. Another emerging area in the field of cardiovascular calcification is pathological endothelial-to-mesenchymal transition (EndMT), the process whereby endothelial cell transition into multipotent mesenchymal cells, some of which differentiate into osteochondrogenic cells and mineralize. The effects of lipids and lipoproteins on EndMT suggest that they modulate cardiovascular calcification through multiple mechanisms. There are also emerging trends in imaging of calcific vasculopathy, including: intravascular optical coherence tomography for quantifying plaque characteristics, PET with a radiolabeled NaF tracer, with either CT or MRI to detect coronary plaque vulnerability. SUMMARY: Recent work in this field includes studies of Lp(a), EndMT, and new imaging techniques.

Early trends in cardiac allograft vasculopathy after implementation of the 2018 donor heart allocation policy in the United States.

STUDY OBJECTIVE: To evaluate the impact of the new donor heart allocation system implemented in the United States in October 2018 on development of early cardiac allograft vasculopathy (CAV). DESIGN: Retrospective cohort study. PARTICIPANTS: Adult (≥ 18 years) heart transplant recipients registered in the United Network for Organ Sharing database between October 18, 2015 and October 17, 2018 (old system) and October 18, 2018 and May 31, 2020 (new system). MAIN OUTCOME MEASURE: Incidence of angiographic CAV at 1 year (accelerated CAV) in the overall transplant population and among the highest acuity subgroup-Status 1A (old) and Status 1 or 2 (new). We included recipient and donor demographic, cardiovascular, and transplant factors in multivariable logistic regression models to identify predictors of accelerated CAV. RESULTS: Of 10,375 transplant recipients, 6,660 (64%) and 3,715 (36%) were listed in the old and new allocation cohorts, respectively. The incidence of accelerated CAV was 521 (8%) in the old period compared with 272 (7%) in the new period (P = .36). Similar incidence rates were observed in the highest acuity subgroup-363 (8%) compared with 143 (7%), respectively (P = .13). In adjusted analyses of the high-acuity cohort, the new allocation system was not associated with a higher likelihood of accelerated CAV (odds ratio = 0.87, 95% confidence interval: 0.70-1.08, P = .20). CONCLUSIONS: The new donor heart allocation system is not associated with development of accelerated angiographic CAV at 1 year, including among recipients requiring the most urgent transplants.

Decreasing trends in reintervention and readmission after endovascular aneurysm repair in a multiregional implant registry.

OBJECTIVE: As endovascular aortic aneurysm repair (EVAR) matures into its third decade, measures such as long-term reintervention and readmission have become a focus of quality improvement efforts. Within a large United States integrated health care system, we describe time trends in the rates of long-term reinterventions utilization measures. METHODS: Data from a United States multiregional EVAR registry was used to perform a descriptive study of 3891 adults who underwent conventional infrarenal EVAR for infrarenal abdominal aortic aneurysm between 2010 and 2019. Three-year follow-up was 96.7%. Outcomes included 1-, 3-, and 5-year graft revision (defined as a procedure involving placement of a new endograft component), secondary interventions (defined as a procedure necessary for maintenance of EVAR integrity [eg, coil embolization and balloon angioplasty/stenting]), conversion to open, interventions for type II endoleaks alone, and 90-day readmission. Crude cause-specific reintervention probabilities were calculated by operative year using the Aalen-Johansen estimator, with death as a competing risk and December 31, 2020 as the study end date. RESULTS: Excluding interventions for type II endoleak alone, 1-year secondary intervention incidence decreased from 5.9% for EVARs in 2010 to 2.0% in 2019 (P < .001) and 3-year incidence decreased from 7.2% to 3.6% from 2010 to 2017 (P = .03). The 3-year incidences of graft revision (mean incidence, 3.4%) and conversion to open remained fairly stable (mean incidence, 0.6%) over time. The 3-year incidence of interventions for type II endoleak alone also decreased from 3.4% in 2010 to 0.7% in 2017 (P = .01). Ninety-day readmission rates decreased from 19.3% for index EVAR in 2010 to 9.2% in 2019 (P = .03). CONCLUSIONS: Comprehensive data from a multiregional health care system demonstrates decreasing long-term secondary intervention and readmission rates over time in patients undergoing EVAR. These trends are not explained by evolving management of type II endoleaks and suggest improving graft durability, patient selection, or surgical technique. Further study is needed to define implant and anatomic predictors of different types of long-term reintervention.

Electrophysiological, structural, and functional disorders in patients with inflammatory cardiomyopathy secondary to inflammatory myopathy.

BACKGROUND: Inflammatory cardiomyopathy (IC) is a syndrome with chronic myocarditis and cardiac remodeling. This study aimed to explore predicting factors of adverse outcomes in patients with IC secondary to idiopathic inflammatory myopathy (IIM-IC). METHODS: By means of a single-center retrospective study, 52 patients with IIM-IC at Peking Union Medical College Hospital were identified from January 1999 to June 2019. Electrocardiogram and echocardiography data were analyzed for the primary outcome (defined as all-cause death) and secondary outcomes (defined as re-hospitalization of heart failure and all-cause death), using regression and survival analysis. RESULTS: The prevalence of atrial fibrillation, ventricular tachycardia, Q-wave abnormality, left ventricular conduction abnormalities, and reduced left ventricular ejection fraction (LVEF) (≤40%) were 65.4%, 67.3%, 67.3%, 61.6%, and 50.5%. After a median follow-up of 2 years (IQR 0.8-3.0), 26 cases were readmitted due to heart failure. Twenty-two deaths were recorded, including 20 cardiogenic deaths. Among the patients with adverse events, the incidence of poor R-wave progression, low-voltage of the limb leads, Q-wave abnormality, QRS duration >130 ms, left ventricular enlargement, and impaired systolic function were higher. Kaplan-Meier analysis showed that Q-wave abnormality, limb leads low-voltage, LVEF ≤40%, and left ventricular end-diastolic dimension >60 mm were correlated with shorter survival. However, multivariate Cox regression analysis revealed that only Q-wave abnormality (HR = 12.315) and LVEF ≤40% (HR = 5.616) were independent risk factors for all-cause death. CONCLUSION: Q-wave abnormality and reduced LVEF are predictive of poor prognosis in patients with IIM-IC.

COVID-19-related Peripheral Arterial Thrombosis Treated in a Large Health Maintenance Organization.

BACKGROUND: COVID-19 was initially identified as an acute respiratory disease, but it was quickly recognized that multiple organ systems could be affected. Venous thrombosis and pulmonary embolism have been well reported. However, there is a paucity of data on COVID-19-related arterial thrombosis. We examined the incidence, characteristics, treatment, and outcome in patients with acute COVID-19-related arterial thrombosis in a large health maintenance organization (HMO). METHODS: A retrospective multicenter case review was performed from March 2020 to March 2021. Cases were identified through a questionnaire sent to vascular surgeons. Patient characteristics, imaging, treatment, and outcome were reviewed. Successful revascularization was defined as restoration of blood flow with viability of the end organ and absence of death within 30 days. Limb salvage was defined as prevention of major amputation (transtibial or transfemoral) and absence of death in 30 days. RESULTS: There were 37,845 patients admitted with COVID-19 complications during this time. Among this group, 26 patients (0.07%) had COVID-19-related arterial thrombosis. The mean age was 61.7 years (range, 33-82 years) with 20 men (77%) and 6 women (23%). Ethnic minorities comprised 25 of 26 cases (96%). Peripheral arterial disease (PAD) was present in 4 of 26 (15%), active smoking in 1 of 26 (3.8%), and diabetes in 19 of 26 (73%) cases. Most patients developed acute arterial ischemia in the outpatient setting, 20 of 26 (77%). Of the outpatients, 6 of 20 (30%) had asymptomatic COVID-19 and 14 of 20 (70%) had only mild upper respiratory symptoms. Distribution of ischemia was as follows: 23 patients had at least one lower extremity ischemia, one patient had cerebral and lower extremity, one had mesenteric and lower extremity, and one had upper extremity ischemia. Revascularization was attempted in 21 patients, of which 12 of 21 (57%) were successful. Limb salvage was successful in 13 of 26 (50%) patients. The overall mortality was 31% (8/26). CONCLUSIONS: Our experience in a large HMO revealed that the incidence of COVID-19-related arterial thrombosis was low. The actual incidence is likely to be higher since our method of case collection was incomplete. The majority of arterial thrombosis occurred in the outpatient setting in patients with asymptomatic or mild/moderate COVID-19 respiratory disease. Acute ischemia was the inciting factor for hospitalization in these cases. Acute lower extremity ischemia was the most common presentation, and limb salvage rate was lower than that expected when compared to ischemia related to PAD. Arterial thrombosis associated with COVID-19 portends a significantly higher mortality. Education of primary care providers is paramount to prevent delayed diagnosis as most patients initially developed ischemia in the outpatient setting and did not have a high cardiovascular risk profile.

Percutaneous Axillary Artery Access for Peripheral and Complex Endovascular Interventions: Clinical Outcomes and Cost Benefits.

OBJECTIVES: The aim of this study was to determine the safety, efficacy, and applicability of percutaneous axillary artery (pAxA) access in patients requiring upper extremity large sheath access during complex aortic, cardiac, and peripheral endovascular procedures. We also take this opportunity to address the potential cost-benefits offered by pAxA access compared to open upper extremity access. METHODS: A total of 26 consecutive patients, between June 2018 and October 2020, underwent endovascular intervention, requiring upper extremity access (UEA). Ultrasound-guided, percutaneous access of the axillary artery was used in all 26 patients with off-label use of pre-close technique with Perclose ProGlide closure devices. Access sites accommodated sheath sizes that ranged from 6 to 14 French (F). End points were technical success and access site-related complications including isolated neuropathies, hematoma, distal embolization, access-site thrombosis, and post-operative bleeding requiring secondary interventions. Technical success was defined as successful arterial closure intraoperatively with no evidence of stenosis, occlusion, or persistent bleeding, requiring additional intervention. RESULTS: Of the 26 patients requiring pAxA access, 15 underwent complex endovascular aortic aneurysm repairs (EVAR) with branched, fenestrated, snorkel, or parallel endografts, 6 underwent peripheral vascular interventions, and 5 underwent cardiac interventions. Fifty-three percent accommodated sheath sizes of 12F or higher. Technical success was achieved in 100% of cases with no major perioperative access complications requiring additional open or endovascular procedures. In our series, we had one post-operative mortality secondary to myocardial infarction in a patient with significant coronary artery disease. CONCLUSIONS: Our data again demonstrated the proposed safety and efficacy attributable to pAxA access, while extending its application to wide spectrum of endovascular interventions which included peripheral or coronary vascular in addition to complex EVAR.

Cost-effectiveness of dehydrated human amnion/chorion membrane allografts in lower extremity diabetic ulcer treatment.

OBJECTIVE: To evaluate the cost-effectiveness and budget impact of using standard care (no advanced treatment, NAT) compared with an advanced treatment (AT), dehydrated human amnion/chorion membrane (DHACM), when following parameters for use (FPFU) in treating lower extremity diabetic ulcers (LEDUs). METHOD: We analysed a retrospective cohort of Medicare patients (2015-2019) to generate four propensity-matched cohorts of LEDU episodes. Outcomes for DHACM and NAT, such as amputations, and healthcare utilisation were tracked from claims codes, analysed and used to build a hybrid economic model, combining a one-year decision tree and a four-year Markov model. The budget impact was evaluated in the difference in per member per month spending following completion of the decision tree. Likewise, the cost-effectiveness was analysed before and after the Markov model at a willingness to pay (WTP) threshold of $100,000 per quality adjusted life year (QALY). The analysis was conducted from the healthcare sector perspective. RESULTS: There were 10,900,127 patients with a diagnosis of diabetes, of whom 1,213,614 had an LEDU. Propensity-matched Group 1 was generated from the 19,910 episodes that received AT. Only 9.2% of episodes were FPFU and DHACM was identified as the most widely used AT product among Medicare episodes. Propensity-matched Group 4 was limited by the 590 episodes that used DHACM FPFU. Episodes treated with DHACM FPFU had statistically fewer amputations and healthcare utilisation. In year one, DHACM FPFU provided an additional 0.013 QALYs, while saving $3,670 per patient. At a WTP of $100,000 per QALY, the five-year net monetary benefit was $5003. CONCLUSION: The findings of this study showed that DHACM FPFU reduced costs and improved clinical benefits compared with NAT for LEDU Medicare patients. DHACM FPFU provided better clinical outcomes than NAT by reducing major amputations, ED visits, inpatient admissions and readmissions. These clinical gains were achieved at a lower cost, in years 1-5, and were likely to be cost-effective at any WTP threshold. Adoption of best practices identified in this retrospective analysis is expected to generate clinically significant decreases in amputations and hospital utilisation while saving money.

Lipids and cardiovascular calcification: contributions to plaque vulnerability.

PURPOSE OF REVIEW: Cardiovascular calcification, a common feature of atherosclerotic lesions, has long been known to associate with cardiovascular risk. The roles of lipoproteins in atherosclerosis are also established, and lipid-modifying therapies have shown capacity for plaque regression. However, the association of lipid-modifying therapies with calcification is more complex, and currently no medical therapies have been found to reverse or attenuate calcification in patients. In this review, we summarize recent developments in our understanding of the interplay between lipids and cardiovascular calcification, as well as new imaging modalities for assessing calcified atherosclerotic plaque vulnerability. RECENT FINDINGS: Recent clinical studies have highlighted the associations of lipoprotein subtypes, such as low-density and high-density lipoprotein particles, as well as lipoprotein (a) [Lp(a)], with coronary calcification and calcific aortic valve disease. Further, evidence continues to emerge for the utility of fused 18F-sodium fluoride positron-emission tomographic and computed tomographic (18F-NaF PET/CT) imaging in characterizing the microarchitecture and vulnerability of atherosclerotic plaque, in both humans and animal models. SUMMARY: The relationship between lipids and cardiovascular calcification is complex, and new imaging techniques, such as 18F-NaF PET/CT imaging, may allow for better identification of disease-modifying therapies and prediction of calcified plaque progression and stability to help guide clinical management.

The value of the modern vascular surgeon to the health care system: A report from the Society for Vascular Surgery Valuation Work Group.

Vascular surgeons provide an important service to the health care system. They are capable of treating a wide range of disease processes that affect both the venous and arterial systems. Their presence broadens the complexity and diversity of services that a health care system can offer both in the outpatient setting and in the inpatient setting. Because of their ability to control hemorrhage, they are critical to a safe operating room environment. The vascular surgery service line has a positive impact on hospital margin through both the direct vascular profit and loss and the indirect result of assisting other surgical and medical services in providing care. The financial benefits of a vascular service line will hold true for a wide range of alternative payment models, such as bundled payments or capitation. To fully leverage a modern vascular surgeon's skill set, significant investment is required from the health care system that is, however, associated with substantial return on the investment.

Midterm outcomes for 605 patients receiving Endologix AFX or AFX2 Endovascular AAA Systems in an integrated healthcare system.

BACKGROUND: Endologix issued important safety updates for the AFX Endovascular AAA System in 2016 and 2018 owing to the risk of type III endoleaks. Outcomes with these devices are limited to small case series with short-term follow-up. We describe the midterm outcomes for a large cohort of patients who received an Endologix AFX or AFX2 device. STUDY DESIGN: Data from an integrated healthcare system's implant registry, which prospectively monitors all patients after endovascular aortic repair, was used for this descriptive study. Patients undergoing endovascular aortic repair with three AFX System variations (Strata [AFX-S], Duraply [AFX-D], and AFX2 with Duraply [AFX2]) were identified (2011-2017). Crude cumulative event probabilities for endoleak (types I and III), major reintervention, conversion to open, rupture, and mortality (aneurysm related and all cause) were estimated. RESULTS: Among 605 patients, 375 received AFX-S, 197 received AFX-D, and 33 received AFX2. Median follow-up for the cohort was 3.9 (interquartile range, 2.5-5.1) years. The crude 2-year incidence of overall endoleak, any subsequent reintervention or conversion, and mortality was 8.8% (95% confidence interval [CI], 6.3-12.3), 12.0% (95% CI, 9.1-15.9), and 8.8% (95% CI, 6.3-12.2) for AFX-S. Respective estimates for AFX-D were 7.9% (95% CI, 4.8-13.0), 10.6% (95% CI, 6.9-16.1), and 9.7% (95% CI, 6.3-14.7); for AFX2, they were 14.1% (95% CI, 4.7-38.2), 16.2% (95% CI, 6.4-37.7), and 21.2% (95% CI, 10.7-39.4). CONCLUSIONS: The midterm outcomes of a large U.S. patient cohort with an Endologix AFX or AFX2 System demonstrate a concerning rate of adverse postoperative events. Patients with these devices should receive close clinical surveillance to prevent device-related adverse events.

Changes in microarchitecture of atherosclerotic calcification assessed by 18F-NaF PET and CT after a progressive exercise regimen in hyperlipidemic mice.

BACKGROUND: Despite the association of physical activity with improved cardiovascular outcomes and the association of high coronary artery calcification (CAC) scores with poor prognosis, elite endurance athletes have increased CAC. Yet, they nevertheless have better cardiovascular survival. We hypothesized that exercise may transform vascular calcium deposits to a more stable morphology. METHODS: To test this, hyperlipidemic mice (Apoe-/-) with baseline aortic calcification were separated into 2 groups (n = 9/group) with control mice allowed to move ad-lib while the exercise group underwent a progressive treadmill regimen for 9 weeks. All mice underwent blood collections and in vivo 18F-NaF µPET/µCT imaging both at the start and end of the exercise regimen. At euthanasia, aortic root specimens were obtained for histomorphometry. RESULTS: Results showed that, while aortic calcification progressed similarly in both groups based on µCT, the fold change in 18F-NaF density was significantly less in the exercise group. Histomorphometric analysis of the aortic root calcium deposits showed that the exercised mice had a lower mineral surface area index than the control group. The exercise regimen also raised serum PTH levels twofold. CONCLUSION: These findings suggest that weeks-long progressive exercise alters the microarchitecture of atherosclerotic calcium deposits by reducing mineral surface growth, potentially favoring plaque stability.

Observed impact of skin substitutes in lower extremity diabetic ulcers: lessons from the Medicare Database (2015-2018).

OBJECTIVE: To evaluate large propensity-matched cohorts to assess outcomes in patients receiving advanced treatment (AT) with skin substitutes for lower extremity diabetic ulcers (LEDUs) versus no AT (NAT) for the management of LEDUs. METHOD: The Medicare Limited Dataset (1 October 2015 through 2 October 2018) were used to retrospectively analyse people receiving care for a LEDU treated with AT or NAT (propensity-matched Group 1). Analysis included major and minor amputations, emergency department (ED) visits and hospital readmissions. In addition, AT following parameters for use (FPFU) was compared with AT not FPFU (propensity-matched Group 2). A paired t-test was used for comparisons of the two groups. For comparisons of three groups, the Kruskal-Wallis test was used. A Bonferroni correction was performed when multiple comparisons were calculated. RESULTS: There were 9,738,760 patients with a diagnosis of diabetes, of whom 909,813 had a LEDU. In propensity-matched Group 1 (12,676 episodes per cohort), AT patients had statistically fewer minor amputations (p=0.0367), major amputations (p<0.0001), ED visits (p<0.0001), and readmissions (p<0.0001) compared with NAT patients. In propensity-matched Group 2 (1131 episodes per cohort), AT FPFU patients had fewer minor amputations (p=0.002) than those in the AT not FPFU group. CONCLUSION: AT for the management of LEDUs was associated with significant reductions in major and minor amputation, ED use, and hospital readmission compared with LEDUs managed with NAT. Clinics should implement AT in accordance with the highlighted parameters for use to improve outcomes and reduce costs.

COVID-19 in a high-risk dual heart and kidney transplant recipient.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly infecting people worldwide, resulting in the infectious disease coronavirus disease 19 (COVID-19) that has been declared a pandemic. Much remains unknown about COVID-19, including its effects on solid organ transplant (SOT) recipients. Given their immunosuppressed state, SOT recipients are presumed to be at high risk of complications with viral infections such as SARS-CoV-2. Limited case reports in single SOT recipients, however, have not suggested a particularly severe course in this population. In this report, we present a dual-organ (heart/kidney) transplant recipient who was found to have COVID-19 and, despite the presence of a number of risk factors for poor outcomes, had a relatively mild clinical course.

Asian-Americans and Pacific Islanders in COVID-19: Emerging Disparities Amid Discrimination.

Coronavirus disease 2019 (COVID-19) is a global pandemic. In the USA, the burden of mortality and morbidity has fallen on minority populations. The understanding of the impact of this pandemic has been limited in Asian-Americans and Pacific Islanders (AAPIs), though disaggregated data suggest disproportionately high mortality rates. AAPIs are at high risk for COVID-19 transmission, in part due to their over-representation in the essential workforce, but also due to cultural factors, such as intergenerational residency, and other social determinants of health, including poverty and lack of health insurance. Some AAPI subgroups also report a high comorbidity burden, which may increase their susceptibility to more severe COVID-19 infection. Furthermore, AAPIs have encountered rising xenophobia and racism across the country, and we fear such discrimination only serves to exacerbate these rapidly emerging disparities in this community. We recommend interventions including disaggregation of mortality and morbidity data, investment in community-based healthcare, advocacy against discrimination and the use of non-inflammatory language, and a continued emphasis on underlying comorbidities, to ensure the protection of vulnerable communities and the navigation of this current crisis.

Steroid Hormone Vitamin D: Implications for Cardiovascular Disease.

Understanding of vitamin D physiology is important because about half of the population is being diagnosed with deficiency and treated with supplements. Clinical guidelines were developed based on observational studies showing an association between low serum levels and increased cardiovascular risk. However, new randomized controlled trials have failed to confirm any cardiovascular benefit from supplementation in the general population. A major concern is that excess vitamin D is known to cause calcific vasculopathy and valvulopathy in animal models. For decades, administration of vitamin D has been used in rodents as a reliable experimental model of vascular calcification. Technically, vitamin D is a misnomer. It is not a true vitamin because it can be synthesized endogenously through ultraviolet exposure of the skin. It is a steroid hormone that comes in 3 forms that are sequential metabolites produced by hydroxylases. As a fat-soluble hormone, the vitamin D-hormone metabolites must have special mechanisms for delivery in the aqueous bloodstream. Importantly, endogenously synthesized forms are carried by a binding protein, whereas dietary forms are carried within lipoprotein particles. This may result in distinct biodistributions for sunlight-derived versus supplement-derived vitamin D hormones. Because the cardiovascular effects of vitamin D hormones are not straightforward, both toxic and beneficial effects may result from current recommendations.