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Background Arteries, veins, and lymphatic vessels are distinguished by structural differences that correspond to their different functions. Each of these vessels is also defined by specific molecular markers that persist throughout adult life; these markers are some of the molecular determinants that control the differentiation of embryonic undifferentiated cells into arteries, veins, or lymphatics. Methods This is a review of experimental literature. Results The Eph-B4 receptor and its ligand, ephrin-B2, are critical molecular determinants of vessel identity, arising on endothelial cells early in embryonic development. Eph-B4 and ephrin-B2 continue to be expressed on adult vessels and mark vessel identity. However, after vascular surgery, vessel identity can change and is marked by altered Eph-B4 and ephrin-B2 expression. Vein grafts show loss of venous identity, with less Eph-B4 expression. Arteriovenous fistulas show gain of dual arterial-venous identity, with both Eph-B4 and ephrin-B2 expression, and manipulation of Eph-B4 improves arteriovenous fistula patency. Patches used to close arteries and veins exhibit context-dependent gain of identity, that is, patches in the arterial environment gain arterial identity, whereas patches in the venous environment gain venous identity; these results show the importance of the host infiltrating cells in determining vascular identity after vascular surgery. Conclusions Changes in the vessel's molecular identity after vascular surgery correspond to structural changes that depend on the host's postsurgical environment. Regulation of vascular identity and the underlying molecular mechanisms may allow new therapeutic approaches to improve vascular surgical procedures.

Despite scientific advances, vascular diseases are responsible for one third of deaths. Understanding the biology of stem cells and cell therapy can mean an important advance in reducing this mortality. Apesar dos avanços científicos, as doenças vasculares são responsáveis por um terço dos óbitos. Entender a biologia das células tronco e a terapia celular pode significar importante avanço na redução desta mortalidade.

Background: Arteriovenous fistulae (AVF) are the preferred access for hemodialysis but still have poor rates of maturation and patency limiting their clinical use. The underlying mechanisms of venous remodeling remain poorly understood, and only limited numbers of unbiased approaches have been reported. Methods: Biological Gene Ontology (GO) term enrichment analysis and differentially expressed genes (DEG) analysis were performed for three AVF datasets. A microRNA enrichment analysis and L1000CDS2 query were performed to identify factors predicting AVF patency. Results: The inflammatory and immune responses were activated during both early and late phases of AVF maturation, with upregulation of neutrophil and leukocyte regulation, cytokine production, and cytokine-mediated signaling. In men with failed AVF, negative regulation of myeloid-leukocyte differentiation and regulation of macrophage activation were significantly upregulated. Compared to non-diabetic patients, diabetic patients had significantly reduced immune response-related enrichment such as cell activation in immune response, regulation of immune-effector process, and positive regulation of defense response; in addition, diabetic patients showed no enrichment of the immune response-regulating signaling pathway. Conclusions: These data show coordinated, and differential regulation of genes associated with AVF maturation, and different patterns of several pathways are associated with sex differences in AVF failure. Inflammatory and immune responses are activated during AVF maturation and diabetes may impair AVF maturation by altering these responses. These findings suggest several novel molecular targets to improve sex specific AVF maturation.

Key points Patients with end-stage renal failure need arteriovenous fistulas (AVF) to undergo dialysis. However, AVFs present a high rate of failure as a result of excessive venous thickness. Excessive venous thickness may be a consequence of surgical dissection and change in oxygen concentration within the venous wall. We show that venous cells adapt their metabolism and growth depending on oxygen concentration, and drugs targeting the hypoxic response pathway modulate this response in vitro. We used the same drugs on a mouse model of AVF and show that direct or indirect inhibition of the hypoxia-inducible factors (HIFs) help decrease excessive venous thickness. Hypoxia and HIFs can be targets of therapeutic drugs to prevent excessive venous thickness in patients undergoing AVF surgical creation. Abstract Because the oxygen concentration changes in the venous wall, surrounding tissue and the blood during surgical creation of arteriovenous fistula (AVF), we hypothesized that hypoxia could contribute to AVF failure as a result of neointimal hyperplasia. We postulated that modulation of the hypoxia-inducible factors (HIF) with pharmacological compounds could promote AVF maturation. Fibroblasts [normal human fibroblasts (NHF)], smooth muscle cells [human umbilical vein smooth muscle cells (HUVSMC)] and endothelial cells [human umbilical vein endothelial cells (HUVEC)], representing the three layers of the venous wall, were tested in vitro for proliferation, cell death, metabolism, reactive oxygen species production and migration after silencing of HIF1/2-α or after treatment with deferioxamine (DFO), everolimus (Eve), metformin (Met), N-acetyl-l-cysteine (NAC) and topoisomerase I (TOPO), which modulate HIF-α stability or activity. Compounds that were considered to most probably modify intimal hyperplasia were applied locally to the vessels in a mouse model of aortocaval fistula. We showed, in vitro, that NHF and HUVSMC can adapt their metabolism and thus their growth depending on oxygen concentration, whereas HUVEC appears to be less flexible. siHIF1/2α, DFO, Eve, Met, NAC and TOPO can modulate metabolism and proliferation depending on the cell type and the oxygen concentration. In vivo, siHIF1/2α, Eve and TOPO decreased neointimal hyperplasia by 32%-50%, 7 days after treatment. Within the vascular wall, hypoxia and HIF-1/2 mediate early failure of AVF. Local delivery of drugs targeting HIF-1/2 could inhibit neointimal hyperplasia in a mouse model of AVF. Such compounds may be delivered during the surgical procedure for AVF creation to prevent early AVF failure.

Endovascular treatment of complex common iliac artery (CIA) and internal iliac artery (IIA) aneurysms using iliac branch endoprostheses (IBE) has proven safe and effective. Instructions for use (IFU) require deployment of current IBE technology with the corresponding manufacturer's modular bifurcated aortic endograft. Concomitant aortoiliac occlusive disease, inadequate renal artery-iliac bifurcation length, and unfavorable aortic anatomy preclude on-label IBE deployment. This study aimed to evaluate the technical feasibility and safety of Alternative Endograft Aortoiliac Reconstruction (AEGAR) for branched endovascular treatment of complex iliac artery aneurysms.In 7 consecutive patients with CIA or IIA aneurysms, computed tomography angiography (CTA) and center-line reconstruction revealed aortoiliac anatomy incompatible with the current IBE IFU due to inadequate proximal CIA landing zone (n = 7), inadequate renal artery to iliac bifurcation length (n = 2), compromised aortic anatomy (n = 3), or short infrarenal neck15 mm (n = 1), either alone or in combination. To overcome these restrictions and facilitate IBE deployment, aortoiliac reconstruction was performed using the Endologix AFX, Endologix Ovation limbs or the Medtronic Endurant II platforms (AEGAR technique). All internal iliac artery reconstructions and external iliac artery extensions were performed using the Gore VBX or Viabahn stent grafts. Technical success was defined as successful delivery of all endograft components without migration or endoleak.The mean patient age was 69 years (range 52-82 years; 6 male). Four patients had bilateral CIA aneurysms and 3 patients had unilateral CIA aneurysms (mean diameter 4.3cm; range 2.2-7 cm). There were 13 IIA VBX stent grafts used for a total of 9 IIAs treated with IBE (bilateral IBE = 2 patients). The mean fluoroscopy time was 38.8 min (range 21.3-64.3 min) and the mean contrast volume was 168.5 mL (range 122-226 mL). Technical success was achieved in all patients and there were no perioperative complications. Mean hospital-stay was 2.2 days (range 1-3 days). Follow-up ranged from 82-957 days (mean = 487 days). At last follow-up, all patients were alive without cardiovascular morbidity; and CTA revealed stable or decreased aneurysm size, patent endografts, and no evidence of endoleak or migration.The AEGAR technique can be used to safely and effectively overcome certain aortoiliac anatomic constraints that preclude use of current IBE technology. We encourage broader use of these alternative endografts in pertinent anatomic configurations.

Objective: Arteriovenous fistulae (AVF) are the preferred vascular access for hemodialysis, but the primary success rate of AVF remains poor. Successful AVF maturation requires vascular wall thickening and outward remodeling. A key factor determining successful AVF maturation is inflammation that is characterized by accumulation of both T-cells and macrophages. We have previously shown that anti-inflammatory (M2) macrophages are critically important for vascular wall thickening during venous remodeling; therefore, regulation of macrophage accumulation may be an important mechanism promoting AVF maturation. Since CD4+ T-cells such as T-helper type 1 cells, T-helper type 2 cells, and regulatory T-cells can induce macrophage migration, proliferation, and polarization, we hypothesized that CD4+ T-cells regulate macrophage accumulation to promote AVF maturation. Approach and Results: In a mouse aortocaval fistula model, T-cells temporally precede macrophages in the remodeling AVF wall. CsA (cyclosporine A; 5 mg/kg, sq, daily) or vehicle (5% dimethyl sulfoxide) was administered to inhibit T-cell function during venous remodeling. CsA reduced the numbers of T-helper type 1 cells, T-helper type 2, and regulatory T-cells, as well as M1- and M2-macrophage accumulation in the wall of the remodeling fistula; these effects were associated with reduced vascular wall thickening and increased outward remodeling in wild-type mice. However, these effects were eliminated in nude mice, showing that the effects of CsA on macrophage accumulation and adaptive venous remodeling are T-cell-dependent. Conclusions: T-cells regulate macrophage accumulation in the maturing venous wall to control adaptive remodeling. Regulation of T-cells during AVF maturation may be a strategy that can improve AVF maturation. Graphic Abstract: A graphic abstract is available for this article.

International audience; Arteriovenous fistulae (AVF) are the preferred mode of hemodialysis access, but 60% of conventional [vein-to-artery (V-A)] AVF fail to mature, and only 50% remain patent at 1 year. We previously showed improved maturation and patency in a pilot study of the radial artery deviation and reimplantation (RADAR) technique that uses an artery-to-vein (A-V) configuration. Here, we show that RADAR exhibits higher rates of maturation, as well as increased primary and secondary long-term patencies. RADAR is also protective in female patients, where it is associated with decreased reintervention rates and improved secondary patency. RADAR and conventional geometries were compared further in a rat bilateral carotid artery-internal jugular vein fistula model. There was decreased cell proliferation and neointimal hyperplasia in the A-V configuration in male and female animals, but no difference in hypoxia between the A-V and V-A configurations. Similar trends were seen in uremic male rats. The A-V configuration also associated with increased peak systolic velocity and expression of Kruppel-like factor 2 and phosphorylated endothelial nitric oxide synthase, consistent with improved hemodynamics. Computed tomography and ultrasound-informed computational modeling showed different hemodynamics in the A-V and V-A configurations, and improving the hemodynamics in the V-A configuration was protective against neointimal hyperplasia. These findings collectively demonstrate that RADAR is a durable surgical option for patients requiring radial-cephalic AVF for hemodialysis access.

Cardiovascular disease remains the leading cause of death worldwide, with sequelae of atherosclerosis contributing significantly to patient morbidity and mortality. A number of sex differences in the pathophysiology of atherosclerosis and in the outcomes after procedures performed for atherosclerotic complications have been documented in humans; however, despite women accounting for half the number of participants in clinical trials supported by the National Institutes of Health, there are very few preclinical studies that include female animals. Animal models of atherosclerosis, ischemia, angioplasty, aneurysms, and venous remodeling have focused on sex hormones as drivers of sex-specific disease outcomes. Estrogens appear to play a protective role in decreasing atherosclerosis, vessel response to injury, and aneurysm formation through modulation of the cellular response to hypoxia and injury, lipid metabolism, inflammatory responses, modulation of the extracellular matrix, and decreased oxidative stress. While androgens contribute to positive vessel remodeling, such as seen during arteriovenous fistula maturation, they are also responsible for increased proteolysis, leading to an increased rate of aneurysm formation.

Stem cell therapy is emerging as an exciting new strategy for the treatment of chronic wounds representing a promising approach of regenerative medicine. Induced pluripotent stem cells (iPSC) represent an innovative, adult-derived, stem cell source with enhanced therapeutic and translational potential. iPSC are pluripotent stem cells derived from somatic donor cells, harvested via noninvasive techniques from a limitless donor pool. The use of iPSC technologies allows for generation of autologous pluripotent stem cell populations with enhanced in vivo survival while obviating ethical issues surrounding destruction of embryos. Because of their ability to differentiate into and repopulate all cell types found in the skin, iPSC have the potential to enhance each phase of wound healing via paracrine and direct cellular effects. Current methods that generate iPSC are often inefficient, predispose cells to mutagenesis, and yield impure cellular populations. Because undifferentiated cells carry tumorigenic potential, selection of terminally differentiated cells and use of cell-free extracellular vesicles may improve iPSC safety profile. While the ideal delivery platform for improving cell function and survival is yet to be designed, advances in bioengineered materials to create next-generation delivery scaffolds have shown promising results. Thus, despite tremendous advantages and promise for tissue regeneration, further studies to improve iPSC safety profile and generation methods are urgently needed prior to widespread clinical adoption.

Objective We aimed to investigate whether a current commercially available high-intensity focused ultrasound (HIFU) probe can adequately image targeted vascular malformations (VMs) in anticipation of HIFU treatment planning and delivery. Methods We enrolled 10 consecutive patients who were scheduled to undergo treatment of symptomatic peripheral VMs confirmed by routine preoperative contrast-enhanced magnetic resonance imaging and soft tissue duplex ultrasound. The lesions were situated no more than 6 cm from the skin. After induction of general anesthesia and before surgical intervention, we prepared and positioned the Sonablate HIFU probe (SonaCare Medical, LLC, Charlotte, NC) to obtain multiple B-mode images of the targeted VM in the transverse and longitudinal dimensions. We then rated the quality of the images and the feasibility of the imaging process itself using a previously devised questionnaire aimed at evaluating the adequacy of the images for potential HIFU treatment planning and delivery. The patients subsequently underwent surgical intervention and clinical follow-up for their VM per the standard protocol. Results The study included 10 participants aged 21 to 67 years (mean ± standard deviation, 36.5 ± 16.5 years). Six patients (60%) identified as female. The VMs imaged consisted of eight venous (80%), one lymphatic (10%), and one combined lymphovenous (10%) malformation. The lesions were in the extremities only (50%), trunk only (20%), trunk and extremities (20%), or neck and extremities (10%). Pain related to the VM was present in all 10 patients (100%). In all 10 patients, the boundary and location of the VM could be visualized via the HIFU probe despite the diminished B-mode imaging resolution. The absence of Doppler functionality in the HIFU probe did not prevent the identification of the VMs in any patient up to a depth of 6 cm. The results from the postimaging survey showed that difficulty in preparing the study device for imaging was 1.1 ± 0.3 and difficulty in use was 1.1 ± 0.1, with a score of 1 equal to easy and 5 to difficult. The stability of the acoustic coupling to the patient was 1.3 ± 0.2, with a score of 1 representing very stable. Conclusions We were able to ultrasonically identify and outline all targeted peripheral VMs using a commercially available HIFU probe in anticipation of treatment planning and delivery. Baseline magnetic resonance imaging and soft tissue duplex ultrasound remain essential tools for guiding probe placement and HIFU imaging.

In the United States, a patient suffers from a myocardial infarction (MI) every 40 seconds, and heart disease remains the leading cause of death worldwide. Despite optimal medical and surgical care, one in every two patients who develops heart failure will die within 5 years. A series of pathological remodeling changes occur to compensate for the myocardium lost during an MI that lead to fibrosis, hypertrophy, and ventricular dilation, with the end-stage pathology often culminating in decreased ejection fraction (EF) and heart failure (HF). Post-MI myocardial recovery is worsened by the adult myocardium’s limited regenerative ability, particularly in an ischemic environment; accordingly, there is great interest in stem cell therapy to treat post-MI injury, and the field is rapidly evolving. Several endogenous and exogenous cellular sources have already been evaluated in clinical trials, with varied results and modest efficacy. Limitations surrounding stem cell treatment include lack of standardization across clinical trials, poor cellular retention and differentiation rates, suboptimal delivery methods, and limited source of candidate cells. In order to optimize stem cell efficacy, future work should focus on efficient generation of the optimal cellular source, development of delivery carriers capable of noninvasive delivery methods that improve cellular survival, and standardization of clinical trials to allow for meaningful comparisons.

Stem cells are a nascent therapy for vascular diseases such as stroke and peripheral artery disease. Cells, like any other pharmaceutic agent, need to be delivered to a target organ with an optimal dose and timing to achieve therapeutic effect. A number of techniques, grouped into local, regional, and systemic approaches, have been used in human trials to deliver a variety of stem cells in both stroke and peripheral artery disease. This chapter reviews stem cell therapy for these two diseases with a focus on delivery methods. Technical details as well as the impact of patient, disease, and cell factors for each approach are discussed. Each method’s merits and pitfalls are explored, highlighting the benefit of a diverse set of delivery options for a diverse population of patients.

Stem cell therapy has recently emerged as an innovative therapeutic strategy for various vascular diseases. Stem cell therapy comprises a spectrum of cell-based regenerative strategies characterized by three sets of variables: (1) stem cell intrinsic properties (origin, type, isolation/induction, culture, and priming features); (2) therapy protocol (dose, concentration, administration route, adjuvants); and (3) patient characteristics (medical history, immune reaction, disease of interest). In this chapter, we introduce basic concepts regarding stem cell therapy: stem cell types and origin, mechanisms of regeneration, isolation, cell culture and priming, administration routes, and therapeutic risks. We also discuss the effects and interactions between these variables as well as their impact in the treatment of vascular diseases.

Buerger’s disease or Thromboangiitis Obliterans (TAO) is a nonatherosclerotic segmental vascular disease which affects small and medium arteries and veins in the upper and lower extremities. Based on pathological findings, TAO can be considered as a distinct form of vasculitis that is most prevalent in young male smokers. There is no definitive cure for this disease as therapeutic modalities are limited in number and efficacy. Surgical bypass has limited utility and 24% of patients will ultimately require amputation. Recently, studies have shown that therapeutic angiogenesis and immunomodulatory approaches through the delivery of stem cells to target tissues are potential options for ischemic lesion treatment. In this review, we summarize the current knowledge of TAO treatment and provide an overview of stem cell-based treatment modalities.

Objective The COVID‐19 pandemic has led to significant changes in healthcare systems that impact the management of chronic diseases such as diabetic foot (DF). We hypothesized that lack of access to healthcare would increase the severity of disease and lead to worse outcomes. Methods The medical records of patients with DF were reviewed to determine demographic data and outcomes including wound healing, major amputation (MA), and death. Groups were divided into the pre–COVID-19 era (15 March 2019–15 March 2020) and the COVID-19 era (16 March 2020–16 March 2021); multivariable logistic analysis was performed to identify risk factors for MA. Results 261 patients with DF were included, 163 in the pre–COVID-19 era and 98 during the COVID-19 era. Patients in the COVID-19 presented with increased cardiovascular disease (19 vs 7%, p = 0.01), increased mean HbA1C (9.1 ± 2.1 vs 8.2 ± 2.1, p = 0.008) and higher WIFI-IV stage (78 vs 53%, p ≤ 0.0001). Patients with DF in the COVID-19 era were more likely to require MA (41 vs 21%, p ≤ 0.0001). Revascularization (OR = 0.12; 95% CI, 0.038–0.38) was a protective factor to reduce MA. Conclusions MA among DF patients increased two-fold during the COVID-19 era. Revascularization avoids MA in diabetic patients even during the COVID-19 pandemic, suggesting that revascularization should be performed when possible.

Objective The glucocorticoid receptor (GR) is a member of the nuclear receptor family that controls key biological processes in the cardiovascular system and has recently been shown to modulate Wnt signaling in endothelial cells. Wnt/β-catenin signaling has been demonstrated to be crucial in the process of angiogenesis. In the current study, we studied whether GR could regulate angiogenesis via the Wnt/β-catenin pathway. Approach and Resultsa Key components of the Wnt/β-catenin pathway were evaluated using quantitative PCR and Western blot in the presence or absence of GR. Enhanced angiogenesis was found in GR deficiency in vitro and confirmed with cell viability assays, proliferation assays and tube formation assays. Consistent with these in vitro findings, endothelial cell-specific GR loss GR in vivo promoted angiogenesis in both a hind limb ischemia model and sponge implantation assay. Results were further verified in a novel mouse model lacking endothelial LRP5/6, a key receptor in canonical Wnt signaling, and showed substantially suppressed angiogenesis using these same in vitro and in vivo assays. To further investigate the mechanism of GR regulation of Wnt signaling, autophagy flux was investigated in endothelial cells by visualizing auto phagolysosomes as well as by assessing P62 degradation and LC3B conversion. Results indicated that potentiated autophagy flux participated in GR-Wnt regulation. Conclusions Lack of endothelial GR triggers autophagy flux, leads to activation of Wnt/β-catenin signaling and promotes angiogenesis. There may also be a synergistic interaction between autophagy and Wnt/β-catenin signaling.

OBJECTIVE Magnetic resonance imaging (MRI) is used in patients with lower extremity venous disease to screen for iliac vein stenosis. The objective of the present study was to determine the prevalence of iliac vein stenosis and associated lower extremity venous symptoms in consecutive patients undergoing MRI of the pelvis. METHODS A retrospective study of all consecutive adult patients who had undergone MRI of the pelvis for various indications from March 2012 to June 2016 was performed. The electronic medical records (EMRs) were reviewed for patient characteristics and, specifically, for the presence and laterality of venous symptoms. All MRI scans were reviewed, and the maximal degree of iliac vein stenosis was recorded. All the patients also responded to a brief telephone survey inquiring about the presence of venous symptoms. Two thresholds of venous stenosis, ≥50% and ≥70%, were used to correlate its presence with the presence of venous symptoms determined from the EMR review and telephone survey results. RESULTS A total of 120 patients were included, with a mean age of 53 ± 14 years; 79% were women and 79% were white. The prevalence of iliac vein stenosis ≥50% was significantly greater on the left than on the right (34.2% vs 16.7%; P < .001). The survey demonstrated that 44 of the 120 patients (36.7%) had had venous symptoms compared with only 30 patients (25%) according to the EMR review (P = .001). No differences were found between patients with positive vs negative survey results for venous symptoms and the occurrence of iliac vein stenosis ≥50% on the right (17.2% vs 15.2%; P = .78) or the left (38% vs 26.8%; P = .22). We also found no differences when the occurrence of iliac vein stenosis ≥70% was used as threshold between the right (2.3% vs 3%; P = .99) and the left (10.1% vs 2.4%; P = .16). Analysis of the venous symptoms from the EMR review yielded similar results. CONCLUSIONS In our study, iliac vein stenosis was more common on the left and was encountered in up to one third of patients who had undergone MRI of the pelvis. No correlation was found in our study between the presence of iliac vein stenosis and the occurrence of ipsilateral venous symptoms. Venous symptoms were underreported in the EMRs. Further studies are necessary to identify the predictors of pathologic iliac vein stenosis.

Objective Peripheral artery disease (PAD) affects more than 200 million people worldwide, among whom more than two-thirds reside in low- and middle-income countries. China, as the largest low- and middle-income country, faces a challenge from the burden of PAD as the country undergoes economic expansion. We compared the patterns of PAD between China and Western countries to determine if there are differences in risk factors, awareness, or treatment of PAD. Methods Literature searches were performed both in English databases and Chinese databases covering January 1, 1995, to March 1, 2020. Both landmark and high-quality articles were evaluated. Results The prevalence of PAD in high-income countries increases linearly with age, whereas PAD increases slowly until the middle 60s and exponentially thereafter in China. In contrast with Western countries, the prevalence of PAD in China is reported to be higher in women than in men. There is a higher prevalence of risk factors in China, but the rates of awareness and treatment of these risk factors are low. Conclusions The lack of awareness and lower rates of treatment and control of PAD and its risk factors in China may be underlying the higher prevalence of PAD in women than in men as well as the steep increase in PAD after the middle 60s. In all countries, more attention should be paid to the planning and implementation of preventative strategies and clinical services. The societal and economic effects of PAD are considerable and ongoing studies are needed to help curtail the burden of this disease.

Varicose veins are commonly caused by valvular reflux in the saphenous vein. Most insurance companies will approve venous ablation (VA) for the treatment of junctional reflux only and will deny coverage for symptomatic patients with significant nonjunctional reflux of the saphenous vein at the deep system. The present study compared the outcomes of VA for patients with junctional reflux and patients with nonjunctional reflux.A retrospective, single-center review of consecutive patients who had undergone VA using radiofrequency in an outpatient office was performed from 2012 to 2016. The patients' electronic medical records were reviewed for the characteristics, imaging findings, and outcomes. A telephone survey inquiring about the intensity of symptoms using a numeric rating scale of 0 to 10 before and after treatment was also conducted, with higher number correlating with increasing symptom severity. Patients were grouped according to the location of reflux, either at the saphenofemoral-saphenopopliteal junction or below the junction (nonjunctional). The patient characteristics and outcomes were compared between the two groups. Clinical success was defined by symptom improvement or resolution. Technical success was defined by vein closure on duplex ultrasonography.A total of 265 patients (224 with junctional reflux [84.5%] and 41 with nonjunctional reflux [15.5%]) had undergone VA of 343 veins. The mean patient age was 58.8 ± 15 years. No differences in age, sex, or race were present between the two groups. Patients with junctional reflux were significantly more likely to have undergone bilateral treatment (33.3% vs 12.2%; P = .006). No difference was found in CEAP (clinical, etiologic, anatomic, pathophysiologic) class, laterality, or type of vein treated. On ultrasonography, the veins with junctional reflux had significantly larger diameters (5.8 ± 2.1 mm vs 4.8 ± 1.8 mm; P = .004). However, the veins with nonjunctional reflux had a longer reflux time (5.5 ± 0.6 seconds vs 4 ± 1.7 seconds; P .0001). The clinical success rates, technical success rates, and incidence of complications were not different between patients with junctional reflux and those with nonjunctional reflux. The telephone survey was completed by 217 patients after a mean follow-up of 24.9 ± 11.3 months. The survey results demonstrated no differences in improvement in pain or swelling or recurrence of pain or swelling after 2 years.Junctional reflux in the saphenous vein is more likely to be bilateral compared with nonjunctional reflux. The location of reflux did not affect patient presentation or outcomes after VA.

Objective: Arteriovenous fistulae (AVF) are the optimal conduit for hemodialysis access but have high rates of primary maturation failure. Successful AVF maturation requires wall thickening with deposition of ECM (extracellular matrix) including collagen and fibronectin, as well as lumen dilation. TAK1 (TGFβ [transforming growth factor-beta]–activated kinase 1) is a mediator of noncanonical TGFβ signaling and plays crucial roles in regulation of ECM production and deposition; therefore, we hypothesized that TAK1 regulates wall thickening and lumen dilation during AVF maturation. Approach and Results: In both human and mouse AVF, immunoreactivity of TAK1, JNK (c-Jun N-terminal kinase), p38, collagen 1, and fibronectin was significantly increased compared with control veins. Manipulation of TAK1 in vivo altered AVF wall thickening and luminal diameter; reduced TAK1 function was associated with reduced thickness and smaller diameter, whereas activation of TAK1 function was associated with increased thickness and larger diameter. Arterial magnitudes of laminar shear stress (20 dyne/cm 2 ) activated noncanonical TGFβ signaling including TAK1 phosphorylation in mouse endothelial cells. Conclusions: TAK1 is increased in AVF, and TAK1 manipulation in a mouse AVF model regulates AVF thickness and diameter. Targeting noncanonical TGFβ signaling such as TAK1 might be a novel therapeutic approach to improve AVF maturation.

Endothelial cells play a key role in the regulation of disease and other developmental processes. Defective regulation of endothelial cell homeostasis may cause mesenchymal activation of other endothelial cells by autocrine effects or of neighboring cell types by paracrine effects, and in both cases contribute to organ fibrosis. However, regulatory control of endothelial cell homeostasis, is not well studied. Diabetes induced renal fibrosis in endothelial GR knock out mice (GRfl/fl;Tie 1 Cre; GRECKO) but not in control mice (GRfl/fl); hypercholesterolemia further enhanced severe renal fibrosis in diabetic GRECKO; Apoe−/− (DKO) but not in diabetic littermates (GRfl/fl; Apoe−/−). The fibrogenic phenotype in the kidneys of diabetic GRECKO and diabetic DKO were associated with aberrant cytokine and chemokine reprogramming. Canonical Wnt signaling was identified as new target for the action of endothelial GR. Wnt inhibiton improved kidney fibrosis by mitigating endothelial-to-mesenchymal transition (EndMT) and epithelial-to-mesenchymal transitions (EMT). Similarly, activation of fatty acid oxidation also suppressed kidney fibrosis. Conditioned media from endothelial cells from diabetic GRECKO stimulated Wnt signaling-dependent epithelial-to-mesenchymal transition in tubular epithelial cells from diabetic controls. These data demonstrate that endothelial GR is an essential antifibrotic core molecule in diabetes.

Background The high rate of clinical failure of prosthetic arteriovenous grafts continues to suggest the need for novel tissue-engineered vascular grafts. We tested the hypothesis that the decellularized rat jugular vein could be successfully used as a conduit and that it would support reendothelialization as well as adaptation to the arterial environment. Materials and methods Autologous (control) or heterologous decellularized jugular vein (1 cm length, 1 mm diameter) was sewn between the inferior vena cava and aorta as an arteriovenous graft in Wistar rats. Rats were sacrificed on postoperative day 21 for examination. Results All rats survived, and grafts had 100% patency in both the control and decellularized groups. Both control and decellularized jugular vein grafts showed similar rates of reendothelialization, smooth muscle cell deposition, macrophage infiltration, and cell turnover. The outflow veins distal to the grafts showed similar adaptation to the arteriovenous flow. Both CD34, CD90 and nestin positive cells, as well as M1-type and M2-type macrophages accumulated around the graft. Conclusions This model shows that decellularized vein can be successfully used as an arteriovenous graft between the rat aorta and the inferior vena cava. Several types of cells, including progenitor cells and macrophages, are present in the host response to these grafts in this model. This model can be used to test the application of arteriovenous grafts before conducting large animal experiments.

The use of embolic protection device (EPD) during lower extremity peripheral vascular interventions (PVI) has been reported, but its impact on outcomes is unclear. The goal of this study was to assess the use and outcomes of EPDs during PVI.All PVI between 2010 and 2014 in the Vascular Study Group of New England (VSGNE) database were reviewed. The characteristics of patients and lesions treated with EPD were identified. A propensity-matched control group without EPD was selected. The outcomes of both groups were compared, and a multivariable analysis was performed.There were a total of 10,875 procedures. EPD was used in 2% of the procedures. From 2010 to 2014, EPD use significantly increased from 1.1 to 3.5% (P 0.001). Patients undergoing PVI with EPD were less likely to be white but more likely to have diabetes, chronic obstructive pulmonary disease, coronary artery disease, and history of prior PVI. After propensity matching, there were 182 procedures with EPD and 604 controls with no significant difference in risk factors. There was no difference in indication or anatomic level treated, with claudication (52.7% vs. 49.8%) being most common indication and the superficial femoral artery (65.4% vs. 62.1%), the most commonly treated artery. Patients undergoing PVI with EPD were more likely to be treated with excisional atherectomy (26.4% vs. 12.6%), whereas patients without EPD were more likely to be treated with orbital atherectomy (31.9% vs. 41.6%, P = 0.017). There was no significant difference in the incidence of minor distal embolization (DE) (1.1% vs. 1.5%) or DE requiring endovascular treatment (2.8% vs. 2.6%) between the two groups, but EPD use was significantly associated with increased fluoroscopy time (P 0.001). There was no difference in technical success, patency, amputation, or mortality between the two groups. On multivariable analysis, there was no significant association between the use of EPD and patency (incidence relative risk (IRR) [95% CI] = 1.1 [0.9-1.3]), amputation (IRR = 0.7 [0.2-2.1]), or mortality (IRR = 0.8 [0.6-1.2]). However, there was a significant difference in fluoroscopy time (mean ratio [95% CI] = 1.2 [1.1-1.3]). The analysis was repeated after eliminating all procedures with DE in the EPD group (assuming that EPD use is 100% effective in preventing DE), and the results were no different.EPD use during PVI has significantly increased. Despite EPDs increasing procedural complexity and time, they do not seem to have any impact on PVI outcomes. Additional studies are needed to characterize which patients would benefit from EPDs.

Thoracic endovascular aortic repair (TEVAR) has become the most common surgical procedure for treatment of descending thoracic aortic pathology. Cervical debranching in the form of carotid-subclavian bypass or transposition (CSBT) and carotid-carotid bypass (CCB) has enabled the use of TEVAR for the treatment of more complex anatomy involving the arch. The present study examined the effects of concomitant cervical bypass on the perioperative outcomes of TEVAR.The American College of Surgeons National Surgical Quality Improvement Program files (2005-2017) were reviewed. Using the Current Procedural Terminology codes, all patients who had undergone TEVAR were identified and were divided into three groups: TEVAR, TEVAR with one bypass (CSBT or CCB), and TEVAR with two bypasses (CSBT and CCB). The patient characteristics and perioperative outcomes of the three groups were compared. Multivariable analysis was performed to determine the factors associated with mortality.A total of 3281 patients had undergone TEVAR and 10% had also undergone one or more debranching procedure (one bypass, 9%; two bypasses, 1%). The frequency of debranching had increased from 3.4% to 10.9% (P = .01) during the study period. Significant differences were found among the three groups in age, sex, smoking history, urgency of surgery, and anesthesia technique. The patients who had undergone TEVAR with cervical debranching had had significantly greater morbidity, longer operating times, and longer hospital stays compared with those who had undergone TEVAR alone. The mortality of TEVAR with two bypasses (22.6%) was significantly greater than that of TEVAR alone (7.5%) and TEVAR with one bypass (6.8%; P .01). The total morbidity (30.9% vs 35.1% vs 67.7%; P .001) and stroke rate (3% vs 7.5% vs 12.9%; P .0001) increased with the increasing number of bypasses. A subgroup analysis of patients who had undergone TEVAR with one bypass showed no significant differences in mortality between TEVAR plus CSBT (6.6%) vs TEVAR plus CCB (8.8%; P = .63). Multivariable analysis showed that TEVAR with two bypasses was associated with significantly increased mortality compared with TEVAR alone (odds ratio [OR], 4.33; 95% confidence interval [CI], 1.75-10.73) and TEVAR with one bypass (OR, 3.44; 95% CI, 1.24-9.51). Older age (OR, 1.74; 95% CI, 1.42-2.13), dependent functional status (OR, 1.48; 1.00-2.19), dialysis (OR, 2.61; 95% CI, 1.57-4.33), and emergent status (OR, 3.66; 95% CI, 2.73-4.90) were also associated with mortality.TEVAR with concomitant cervical debranching has been increasingly used to treat complex aortic pathology but is associated with significantly worse outcomes than TEVAR alone. As advanced endovascular technology to treat the aortic arch emerges, the outcomes of open surgical debranching in the present study constitute an important benchmark for comparison.

The application of human-induced pluripotent stem cells (hiPSCs) to generate vascular smooth muscle cells (hiPSC-VSMCs) in abundance is a promising strategy for vascular regeneration. While hiPSC-VSMCs have already been utilized for tissue-engineered vascular grafts and disease modeling, there is a lack of investigations exploring their therapeutic secretory factors. The objective of this manuscript was to understand how the biophysical property of a collagen-based scaffold dictates changes in the secretory function of hiPSC-VSMCs while developing hiPSC-VSMC-based therapy for durable regenerative wound healing. We investigated the effect of collagen fibrillar density (CFD) on hiPSC-VSMC&rsquo, s paracrine secretion and cytokines via the construction of varying density of collagen scaffolds. Our study demonstrated that CFD is a key scaffold property that modulates the secretory function of hiPSC-VSMCs. This study lays the foundation for developing collagen-based scaffold materials for the delivery of hiPSC-VSMCs to promote regenerative healing through guiding paracrine signaling pathways.

Neointimal hyperplasia remains an obstacle after vascular interventions. Programmed death-1 (PD-1) antibody treatment decreases tumor cell proliferation and secretion of inflammatory factors, and several antineoplastic drugs show efficacy against neointimal hyperplasia. We hypothesized that inhibition of PD-1 inhibits neointimal hyperplasia in a rat patch angioplasty model. In a rat aorta patch angioplasty model, four groups were compared: the control group without treatment, a single dose of humanized PD-1 antibody (4 mg/kg) injected immediately after patch angioplasty, PD-1 antibody-coated patches, and BMS-1 (PD-1 inhibitor)-coated patches. Patches were harvested (Day 14) and analyzed. After patch angioplasty, PD-1-positive cells were present. Inhibition of PD-1 using both intraperitoneal injection of humanized PD1 antibody as well as using patches coated with humanized PD1 antibody significantly decreased neointimal thickness (p = 0.0199). There were significantly fewer PD-1 (p = 0.0148), CD3 (p = 0.0072), CD68 (p = 0.0001), CD45 (p = 0.001), and PCNA (p < 0.0001)-positive cells, and PCNA/α-actin dual positive cells (p = 0.0005), in the treated groups. Patches coated with BMS-1 showed similarly decreased neointimal thickness and accumulation of inflammatory cells. Inhibition of PD-1 using PD-1 antibody or its inhibitor BMS-1 can significantly decrease neointimal thickness in vascular patches. Inhibition of the PD-1 pathway may be a promising therapeutic strategy to inhibit neointimal hyperplasia.

BACKGROUND To quantitatively evaluate edema of the lower legs in patients with saphenous varicose veins, and to determine the association between leg edema and venous hemodynamics of the lower legs. METHODS The data of 140 patients with saphenous varicose veins in Eniwa Midorino Clinic from April 2018 to November 2019 were retrospectively analyzed. Body composition values, including Body Mass Index, extracellular water/total body water (ECW/TBW) ratio of each leg, and skeletal muscle mass of each leg, were measured by segmental multi-frequency bioelectrical impedance analyzer. Overall venous hemodynamics of the leg, including functional venous volume, venous filling index (VFI), and ejection fraction, were assessed using air-plethysmography. Saphenous and deep vein reflux were evaluated by duplex scan. RESULTS A total of 140 patients (58 men and 82 women) with a mean age of 66.0 years (range, 21 to 84 years) were analyzed. On visual inspection, 204 legs had saphenous-type varicose veins, while 76 legs did not. The legs were divided into two groups according to the presence or absence of leg edema, which was defined as ECW/TBW ≥0.390 and

Background: Autologous vein grafting remains the gold standard for surgical bypass grafts. However, vein bypasses still have significant incidence of failure. Ephrin type-B receptor 4 (EphB4), the embryonic venous determinant, may modulate vein graft adaptation. Although EphB4 is expressed in venous endothelial and smooth muscle cells (SMCs), it is not known whether EphB4 is functional in human SMCs. Materials and methods: Human adult venous SMCs were obtained from the inferior vena cava of an adult human liver donor. Primary SMCs were stimulated with EphrinB2/Fc or transfected with an EphB4-expression vector (GV219-EphB4). Expression of SMC phenotype markers, migration, and proliferation were evaluated. Results: Activation of EphB4 with EphrinB2/Fc increased the mRNA and protein expression of the venous SMC contractile markers alpha actin, calponin-1, SM22, and MYH11, while decreasing the expression of the synthetic marker osteopontin. EphrinB2/Fc treatment inhibited SMC migration, but not proliferation. In addition, overexpression of EphB4 increased mRNA expression of SMC contractile markers, while decreasing expression of the apoptosis marker caspase-9. Conclusions: EphB4 was present and functional in adult human venous SMCs. Stimulation of EphB4 increased expression of contractile SMC phenotypic markers and decreased SMC migration in vitro, functioning to retain the contractile phenotype of SMCs. EphB4 activation, therefore, recapitulates changes observed during vein graft adaptation to the arterial environment in vivo. EphB4 represents a new strategy to inhibit neointimal hyperplasia during vein graft adaption.

3D Printing has become a mainstay of industry, with several applications in the medical field. One area that could benefit from 3D printing is intestinal failure due to injury or genetic malformations. We bioprinted cylindrical tubes from rat vascular cells that were sized to form biopatches. 2 mm enterotomies were made in the small intestine of male Sprague-Dawley rats, and sealed with biopatches. These intestinal segments were connected to an ex vivo perfusion device that provided independent extraluminal and intraluminal perfusion. The fluorescence signal of fluorescein isothiocyanate (FITC)-inulin in the intraluminal perfusate, a non-absorbable fluorescent marker of intestinal integrity, was measured every 15 min over 90 min, and used to assess the integrity of the segments under both continuous perfusion and alternate-flow perfusion. Enterotomies were made an inch away from the ileocecal junction in male Wistar rats and sealed with biopatches. The animals were monitored daily and euthanized at post-operative days 7, 14, 21, and 30. Blinded histopathological analysis was conducted to compare the patch segments to native intestine. Biopatch-sealed intestinal segments withstood both continuous and pulsatile flow rates without leakage of FITC-inulin above the control baseline. 21 of 26 animals survived with normal activity, weight gain, and stool output. Histopathology of the explanted segments showed progressive villi and crypt formation over the enterotomies, with complete restoration of the epithelium by 30 days. This study presents a novel application of 3D bioprinting to develop a universal repair patch that can seal lesions in vivo, and fully integrate into the native intestine.

Octogenarians and nonagenarians are considered the “very old” and are often viewed as one group. Americans are aging, with the proportion of the very old expected to increase from 1.9 per cent of the population to 4.3 per cent in 2050. This study aimed to underscore the differences in surgical trends, demographics, and outcomes between octogenarians and nonagenarians. The ACS-NSQIP database (2007–2012) was used to derive the type of surgeries, demographics, and outcomes of octogenarian and nonagenarians undergoing nonemergent vascular, orthopedic, and general surgery procedures. Between 2007 and 2012, nonagenarians accounted for an increasing percentage of surgeries (85 to 121 per 10,000 surgeries, relative risk = 1.42; 95% CI: 1.30–1.54) across surgical specialties, including vascular, general, and orthopedic surgery, whereas the percentage of octogenarians undergoing surgery remained unchanged. Nonagenarians had a higher 30-day perioperative mortality and a longer hospital stay than octogenarians after vascular, orthopedic, and general surgery procedures. Nonagenarians are a rapidly growing group of surgical patients with significantly higher perioperative mortality and longer postoperative hospital stay. The impact of surgery on the quality of life of nonagenarians needs to be studied to justify the increasing healthcare costs.

Endothelial cells play a key role in the regulation of disease. Defective regulation of endothelial cell homeostasis may cause mesenchymal activation of other endothelial cells or neighboring cell types, and in both cases contributes to organ fibrosis. Regulatory control of endothelial cell homeostasis is not well studied. Diabetes accelerates renal fibrosis in mice lacking the endothelial glucocorticoid receptor (GR), compared to control mice. Hypercholesterolemia further enhances severe renal fibrosis. The fibrogenic phenotype in the kidneys of diabetic mice lacking endothelial GR is associated with aberrant cytokine and chemokine reprogramming, augmented Wnt signaling and suppression of fatty acid oxidation. Both neutralization of IL-6 and Wnt inhibition improve kidney fibrosis by mitigating mesenchymal transition. Conditioned media from endothelial cells from diabetic mice lacking endothelial GR stimulate Wnt signaling-dependent epithelial-to-mesenchymal transition in tubular epithelial cells from diabetic controls. These data demonstrate that endothelial GR is an essential antifibrotic molecule in diabetes., The endothelial glucocorticoid receptor plays a key role in the regulation of many diseases, including diabetes. Loss of this receptor results in accelerated renal fibrosis, a heightened inflammatory milieu, augmented Wnt signaling and suppression of fatty acid oxidation in diabetic kidneys.

International audience; Arteriovenous fistulas (AVFs) are the preferred vascular access for haemodialysis of patients suffering from end-stage renal disease, a worldwide public health problem. However, they are prone to a high rate of failure due to neointimal hyperplasia and stenosis. This study aimed to determine if osteopontin (OPN) was induced in hypoxia and if OPN could be responsible for driving AVF failure. Identification of new factors that participate in remodelling of AVFs is a challenge. Three cell lines representing the cells of the three layers of the walls of arteries and veins, fibroblasts, smooth muscle cells and endothelial cells, were tested in mono- and co-culture in vitro for OPN expression and secretion in normoxia compared to hypoxia after silencing the hypoxia-inducible factors (HIF-1α, HIF-2α and HIF-1/2α) with siRNA or after treatment with an inhibitor of NF-kB. None of the cells in mono-culture showed OPN induction in hypoxia, whereas cells in co-culture secreted OPN in hypoxia. The changes in oxygenation that occur during AVF maturation up-regulate secretion of OPN through cell-cell interactions between the different cell layers that form AVF, and in turn, these promote endothelial cell proliferation and could participate in neointimal hyperplasia.

The purpose of this study was to determine the trends in patient numbers, procedures numbers, amputation rate, length of stay (LOS) and hospitalization expenses in a National Clinical Research Center for Geriatric Disorders over 17 years (2002-2018).The data of inpatients with chronic lower extremity ischemia caused by atherosclerosis in Xuanwu Hospital from 2002 to 2018 was reviewed.5137 patients were reviewed, of whom 58% (2976/5137) were diabetic. The numbers of annual inpatients, endovascular treatment cases, and mean hospitalization expenses increased over time, and the mean LOS progressively decreased. The amputation rate decreased from 8.12% in 2002 to 2007 to 0.87% in 2008 to 2018 (P .0001). The mean LOS decreased from 28.20 days in 2002 to 2007 to 11.12 days in 2008 to 2018 (P .0001). The mean hospitalization expenses rose from 54,466.94 yuan in 2002 to 2007 to 76,469.40 yuan in 2008-2018 (p = .0013). There were no significant differences in mean LOS and mean hospitalization expenses between the diabetic and the non-diabetic groups. In the diabetic subgroup, the amputation rate decreased from 8.83% in 2002 to 2007 into 0.99% in 2008 to 2018 (P .0001).From 2002 to 2018, the number of inpatients with atherosclerotic chronic lower limb ischemia increased gradually, and the number of endovascular treatments increased significantly; concomitantly, the amputation rate and mean LOS decreased, and the mean hospitalization expenses increased. The decreased amputation rate may be related to increased implementation of endovascular treatment or angiogenesis therapy.

Patients with end-stage renal failure depend on hemodialysis indefinitely without renal transplantation, requiring a long-term patent vascular access. Although an arteriovenous fistula (AVF) remains the preferred vascular access for hemodialysis because of its longer patency and fewer complications compared with other vascular accesses, the primary patency of AVF is only 50% to 60%, presenting a clinical need for improvement. AVF mature by developing a thickened vascular wall and increased diameter to adapt to arterial blood pressure and flow volume. Inflammation plays a critical role during vascular remodeling and fistula maturation; increased shear stress triggers infiltration of T cells and macrophages that initiate inflammation, with involvement of several different subsets of T cells and macrophages. We review the literature describing distinct roles of the various subsets of T cells and macrophages during vascular remodeling. Immunosuppression with sirolimus or prednisolone decreases neointimal hyperplasia during AVF maturation, suggesting novel approaches to enhance vascular remodeling. However, M2 macrophages and CD4+ T cells play essential roles during AVF maturation, suggesting that total immunosuppression may suppress adaptive vascular remodeling. Therefore, it is likely that regulation of inflammation during fistula maturation will require a balanced approach to coordinate the various inflammatory cell subsets. Advances in immunosuppressive drug development and delivery systems may allow for more targeted regulation of inflammation to improve vascular remodeling and enhance AVF maturation. (JVS–Vascular Science 2020;1:207-18.) : Clinical Relevance: Patients with end-stage renal failure depend on successful AVF maturation to have a useful access. Inflammation occurs during fistula maturation and may be a therapeutic target to improve fistula maturation and utilization. Inflammation is mainly caused by T cells and macrophages, which have several subsets with distinct phenotypes and roles during vascular remodeling. Regulation of inflammation during fistula maturation requires a balanced approach to coordinate the various inflammatory cell subsets.

The purpose of this study was to describe the vascular surgeons' experience with an endovascular-first approach for critical limb ischemia (CLI) due to arteriosclerotic disease involving infrapopliteal vessels. From April 2006 to September 2013, 55 limbs with CLI in 45 consecutive patients who had undergone infrapopliteal percutaneous transluminal angioplasty (PTA) were evaluated. All limbs presented with ulcers or gangrenes (Rutherford 5 or 6), and were treated with infrapopliteal PTA as the initial treatment. Clinical outcomes of major adverse limb event (MALE) + perioperative death (POD), amputation-free survival (AFS), limb salvage, and survival were analyzed with the Kaplan–Meier method. Multivariable perioperative predictors of MALE + POD and AFS were identified using the stepwise Cox proportional hazards regression model. The technical success rate was 95% (52/55). Clinical success was attained in 37 of 55 limbs (67%). Freedom from MALE + POD, AFS, limb salvage, and survival were 89%, 84%, 92%, and 92% at 6 months, respectively, and 82%, 68%, 89%, and 78% at 12 months, respectively. Clinical success (HR, 0.06; 0.01–0.50; P = 0.009) was associated with freedom from MALE + POD. Rutherford 6 (HR, 3.0; 95% CI, 1.1–8.3; P < 0.004) and clinical success (HR, 0.19; 95% CI, 0.07–0.49; P < 0.0007) were associated with AFS. These results suggest that infrapopliteal PTA can be offered as a first therapeutic option for a significant proportion of patients with CLI. Vascular surgeons must embrace and validate endovascular technology if they are to remain competitive in treatment of peripheral artery disease.

Background An arteriovenous fistula (AVF) exposes the outflow vein to arterial magnitudes and frequencies of blood pressure and flow, triggering molecular pathways that result in venous remodeling and AVF maturation. It is unknown, however, how venous remodeling, that is lumen dilation and wall thickening, affects venous mechanical properties. We hypothesized that a fistula is more compliant compared with a vein because of altered contributions of collagen and elastin to the mechanical properties. Methods Ephb4+/− and littermate wild-type (WT) male mice were treated with sham surgery or needle puncture to create an abdominal aortocaval fistulae. The thoracic inferior vena cava was harvested 3 wk postoperatively for mechanical testing and histological analyses of collagen and elastin. Results Mechanical testing of the thoracic inferior vena cava from Ephb4+/− and WT mice showed increased distensibility and increased compliance of downstream veins after AVF compared with sham. Although Ephb4+/− veins were thicker than WT veins at the baseline, after AVF, both Ephb4+/− and WT veins showed similar wall thickness as well as similar collagen and elastin area fractions, but increased collagen undulation compared with sham. Conclusions Fistula-induced remodeling of the outflow vein results in circumferentially increased distensibility and compliance, likely due to post-translational modifications to collagen.

Background Multiple societal guidelines recommend medical optimization and exercise therapy for patients with claudication prior to lower extremity revascularization (LER). However, the application of those guidelines in practice remains unknown. Our hypothesis is that vascular surgeons (VS) are more adherent to guidelines compared to non-vascular surgeons treating claudication. Methods The records of patients undergoing LER for claudication in a single center were reviewed, and adherence to guidelines prior to LER was assessed. Patients received conservative therapy if the impact of claudication on quality of life (QOL) was documented, ankle brachial index (ABI) was obtained, and patients were treated with at least 3 months of walking exercise and smoking cessation when indicated. Results There were 187 patients treated for claudication (VS=65, non-vascular surgeons=122). There were 161 patients who underwent endovascular intervention, 19 patients had an open revascularization, and 7 patients had a hybrid procedure. Patients treated by VS were younger and more likely to be African American. Patients treated by non-vascular surgeons were more likely to have hyperlipidemia, coronary artery disease, smoke, and be on antiplatelet and statin medications. VS were more likely to assess pattern of symptoms with claudication and obtain ABIs compared to non-vascular surgeons, although the mean ABIs were no different. VS were more likely to use walking exercises and smoking cessation when indicated before LER. Even though 70.8% and 31.1% of patients treated by VS and non-vascular surgeons respectively were recommended walking exercises, only 33.8% and 18.0% were given a period of three months to benefit from it prior to LER. Conservative therapy was significantly higher among VS compared to non-vascular surgeons but was overall low (VS=12.3%, non-vascular surgeons=3.3%, p=.016). After a mean follow up of 3.1 ± 1.3 years, there was no difference in mortality or major amputation. Conclusions Although adherence to guidelines in the medical management of vascular claudication prior to LER was higher among VS compared with non-vascular surgeons, overall rates of adherence were low. Stricter institutional protocols and oversight across specialties are needed to reinforce the application of the established standards of care.

We identified changes in renal function in patients who underwent thoracic endovascular aortic repair (TEVAR) and the factors that may influence renal function. Information on 470 consecutive patients was collected. Kidney function and contrast volume were recorded. Unpaired t test, Spearman correlation, and logistic regression were used for statistical analysis. A Kaplan-Meier curve helped clarify our follow-up findings. Mean contrast volume was 90.5 ± 21.2 mL. The change in serum creatinine was significantly correlated with (1) preexisting renal pathology ( P = .033) and (2) aortic dissection (AD) involving the renal arteries ( P = .019). The change in serum urea nitrogen (ΔBUN) was only significantly correlated with AD involving the renal arteries ( P = .0348). Contrast volume ( P = .036, odds ratio = 1.010, 95% confidence interval: 1.001-1.019) was a risk factor for contrast-induced nephropathy (CIN) after TEVAR. Survival rates and renal failure rates among no CIN, CIN, and CIN–acute kidney injury groups at longest 27 months follow-up were significantly different. Creatinine and BUN were generally elevated post-TEVAR. Contrast-induced nephropathy post-TEVAR may correlate with renal comorbidities and renal artery involvement. Contrast volume is risk factor for CIN after TEVAR. More attention needs to be paid to patient renal function during follow-up.

Purpose: To investigate the utilization of local anesthesia or peripheral nerve block with monitored anesthesia care (LPMAC) and its impact on the perioperative outcomes of hybrid lower extremity revascularization (LER) compared with general anesthesia (GA). Materials and Methods: A search of the ACS-NSQIP database between 2005 and 2017 identified 9430 patients who underwent hybrid LER for peripheral artery disease. Excluding 449 ineligible cases left 8981 hybrid LER patients for analysis. The patients were dichotomized based on the anesthetic technique: 8631 (96.1%) GA and 350 (3.9%) LPMAC. The GA patients were matched 3:1 based on propensity scores to patients in the LPMAC group based on gender, age, race, functional status, transfer status, chronic obstructive pulmonary disease (COPD), dialysis status, American Society of Anesthesiologists (ASA) class, emergent surgery, preoperative sepsis, indication, and type of open and endovascular procedure. Outcomes including complications, mortality, procedure time, and hospital length of stay were compared between the matched groups (801 GA vs 267 LPMAC). Results: Comparing the unmatched groups, those treated under LPMAC were older (72.7±9 vs 68±8.4 years, p48 hours was less frequent (0.4% vs 2.6%) for LPMAC patients, though statistical significance was not reached. There was no difference in mortality or hospital length of stay. Conclusion: LPMAC is an infrequent anesthetic technique for hybrid LER and is primarily used for patients with a high burden of comorbidities. LPMAC is associated with reduced overall morbidity and operating time. Further studies are needed to identify which patients undergoing hybrid LER benefit most from LPMAC.

Background Patients presenting a carotid stenosis and contralateral carotid occlusion (CCO) have been historically considered at high risk of carotid surgical treatment, and there are few data regarding short-term recovery after stenting therapy in patients with CCO. The aim of this study is to evaluate the short-term recovery and safety of stenting for patients with CCO and different subgroup population. Methods We retrospectively reviewed the records of consecutive patients with CCO who were treated with stenting endovascular methods between 2008 and 2014. The postoperative outcomes were analyzed according to age, ischemic symptom, cerebral infarction history, and collateral situation subgroups, respectively. Results Fifty-eight consecutive patients with CCO were treated and 49 (84.5%) completed a 3-year follow-up. There were significant higher stroke, myocardial infarction, or death events in the aged (≥75 years old) group and poor collateral group (P = .007 and .0024, respectively). There was no difference in the 3-year primary endpoint incidence between the cerebral ischemia symptom subgroups and cerebral infarction history subgroups. Event-free survival, aged group, and poor collateral group were lower (P = .007 and P = .0024, respectively). Conclusions Carotid artery stenting (CAS) for patients with common carotid artery is a safe and effective therapy. Factors such as age 75 years or older and poor collateral are associated with a higher 3-year rate of postprocedural stroke, myocardial infarction and death, and lower event-free survival in patients with CCO treated by CAS. Meanwhile, our data do not show a significant impact of cerebral ischemic symptom and cerebral infarction history on clinical outcome of patients with CCO undergoing CAS.

OBJECTIVE: To compare the effectiveness of surgical bypass and endovascular therapy for juxtarenal abdominal aortic occlusion. METHODS: Data of 37 patients treated with open arterial bypass surgery or endovascular therapy for juxtarenal abdominal aortic occlusion in the last 10 years were retrospectively analyzed. RESULTS: Of the 37 cases, 32 were male and five were female; the mean age was 58.5 years; the mean disease history was 8.2 months. Open surgery was performed in 18 cases and endovascular treatment was done in 19 cases. No significant differences in either technical success rate or perioperative symptom improvement rate were found between the open surgery and endovascular therapy groups. There w as much more blood loss, hospital stay time, and fewer hospitalization expenses in the open group than the endo group. In the open group, the mean follow-up time was 60.5 months and graft patency rate was 94.4%; in the endo group, the mean follow-up was 52.5 months but the patency rate was 82.4% (P = 0.009). CONCLUSIONS: Both open surgery and endovascular treatment are effective for juxtarenal aortic occlusion. In comparison, open surgery has lower cost with better long-term eff icacy, while endovascular therapy has less invasiveness with faster postoperative recovery. O perative approach should be made according to the patient's clinical conditions.

Objective The Caprini model estimates patients' risk for venous thromboembolism by 30 different factors. Hemodynamically significant pulmonary embolism (PE), defined as high-risk (massive) or intermediate-risk (submassive) PE, has high morbidity and mortality rates. This study tests whether the Caprini model and deep venous thrombosis (DVT) characteristics correlate with the prevalence of PE and hemodynamically significant PE in patients with DVT. Methods A retrospective review of patients diagnosed with DVT between January 2013 and August 2014 in a tertiary care center was performed. Multivariable analysis was used to determine predictors of PE and hemodynamically significant PE. Results Of 838 consecutive patients with DVT, 217 (25.9%) had concomitant PE at presentation, of whom 135 had hemodynamically significant PE (101 submassive PE, 34 massive PE). The mean age was 65 years, and 51.0% were women. There was no significant relation between age or gender and the occurrence of PE or hemodynamically significant PE. Patients with PE were less likely to have undergone recent surgery (18.4% vs 30.3%; P = .001), to have sepsis (4.6% vs 11.8%; P = .002), and to have higher Caprini scores (6.1 vs 6.5; P = .047). Patients with DVT were less likely to have hemodynamically significant PE after recent surgery (13.3% vs 27.2%; P = .011) but more likely to have hemodynamically significant PE with proximal DVT (80.7% vs 64.2%). There was no association between Caprini score and hemodynamically significant PE (6.3 vs 5.7; P = .171). Conclusions The Caprini model has a poor association with PE or hemodynamically significant PE in patients with DVT. Among all patients with DVT, a concomitant diagnosis of PE or hemodynamically significant PE is less common in those with sepsis or undergoing recent surgery but more common in those with proximal DVT.