Background/Objectives: RNA interference (RNAi) is a promising strategy for mitigating diseases at the molecular level. However, RNAi is limited by its instability in biological fluids and impermeability to cellular membranes. In response, our lab has previously patented a non-ionizable lipid nanoparticle (LNP) platform (R8-PLP) for RNAi therapeutic delivery. This formulation incorporates 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve particle stability and drug retention. However, long-anchored PEGylated lipids like DSPE-PEG may impair internalization and stimulate immune responses. The literature suggests substituting short-anchored PEGylated-lipids like 1,2-dimyristoyl-rac-glycero-3-[methoxy(polyethylene glycol)-2000] (DMG-PEG) to attenuate these effects. Here, we evaluated whether substituting DMG-PEG for DSPE-PEG in our R8-PLP would improve in vitro cellular delivery and gene transfection without compromising in vitro critical quality attributes (CQAs) or increasing cytotoxicity. Methods: CQAs [encapsulation efficiency (EE%), particle size (nm), homogeneity (polydispersity index; PDI), and membrane zeta-potential] were assessed at assembly and after storage for up to 28 days at 4 °C. Additionally, in-serum stability at 4 °C and serum release kinetics at 37 °C were assessed. Human aortic smooth muscle cells (HASMCs) were treated with R8-PLPs and analyzed for cellular uptake (fluorometry), cytotoxicity (LIVE/DEAD stain), and gene modulation (qPCR). Results: DMG-PEG incorporation at variable mol% did not alter R8-PLP size, homogeneity, or siRNA EE% at assembly or after long-term storage, but did accelerate siRNA release kinetic profiles compared to DSPE-PEG controls. DMG-PEG substitution enhanced cellular uptake compared to DSPE-PEG R8-PLPs without increasing cytotoxicity. DMG-PEG incorporation also achieved significant silencing versus non-treated controls but did not improve gene silencing compared to DSPE-PEG R8-PLPs. Conclusions: Thus, DMG-PEG substitution did not enhance R8-PLP in vitro gene modulation efficacy despite improving cellular uptake and maintaining CQAs.

Trauma to the celiac artery may require ligation as a life-saving maneuver. Our patient sustained a gunshot wound resulting in celiac artery ligation during trauma laparotomy. Abdominal closure occurred the following day with drains placed owing to grade II pancreatic injury. Abdominal drainage was consistent with amylase-rich pancreatic fistula. Serial cross-sectional imaging demonstrated an enlarging celiac artery stump over 2 weeks. On day 15, a ruptured celiac artery pseudoaneurysm was found and treated with embolization and aortic stent graft cuff. This case highlights the importance of aggressive treatment for any enlarging artery in the setting of a pancreatic fistula.

This article presents the rationale, challenges, and adaptive strategies employed during the initiation and execution of the arteriovenous (AV) access trialda multicenter randomized controlled trial (RCT) comparing AV fistulas and AV grafts for hemodialysis in older adults with major comorbidities. Motivated by shifts in epidemiologic landscapes and evolving guidelines moving away from a fistula-first approach and to more patient-centric approaches, the objective of this randomized controlled trial was to fill critical knowledge gaps in determining the optimal vascular access for this complex patient population. We outline the challenges encountered in patient recruitment along with measures employed to overcome these obstacles in recruitment. We emphasize the pivotal role of continuous research in overcoming these challenges, underscoring its necessity to achieve a thorough comprehension of optimal vascular access strategies for this complex patient population. (JVS-Vascular Insights 2024;2:100108.)

This article presents the rationale, challenges, and adaptive strategies employed during the initiation and execution of the AV Access trial—a multicenter randomized controlled trial (RCT) comparing arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs) for hemodialysis in older adults with major comorbidities. Motivated by shifts in epidemiologic landscapes and evolving guidelines moving away from a Fistula First approach and to more patient-centric approaches, the objective of this RCT is to fill critical knowledge gaps in determining the optimal vascular access for this complex patient population. We outline the challenges encountered in patient recruitment along with measures employed to overcome these obstacles in recruitment. We emphasize the pivotal role of continuous research in overcoming these challenges, underscoring its necessity to achieve a thorough comprehension of optimal vascular access strategies for this complex patient population.

With the growing use of endovascular aortic repair for aortic aneurysm pathology, multiple cases have been reported of associated endovascular graft infections. Explantation of the infected endograft and the revascularization procedure performed should be individualized with attention to the offending organism. We present the cases of two patients who underwent endovascular aortic repair with the same endograft and developed a graft infection with Burkholderia cepacia, a gram-negative organism with low virulence. Both endografts cultured Burkholderia cepacia complex; however, the organisms were genetically tested and found to be separate, unrelated strains. Both patients underwent successful explantation and revascularization procedures without any surgical-related complications to date.

Carotid body paragangliomas are the most common extra-adrenal paraganglioma and arise from the carotid body at the bifurcation of the internal carotid artery and external carotid artery. The differential diagnosis for a cervical mass in this region includes vagal paraganglioma, jugulotympanic paraganglioma, middle ear adenoma, meningioma, schwannoma, and thyroid malignancy. This case describes an otherwise healthy 23 year old female who presented with right neck pain, swelling, difficulty swallowing, and intermittent left arm weakness and numbness. Multiple imaging studies demonstrated an 8 cm enhancing soft tissue mass encasing the internal carotid artery and extending from the carotid bifurcation to the skull base, with intracranial involvement of the posterior fossa. Due to the tumor location as well as involvement of the carotid artery, a multi-disciplinary team consisting of oral and maxillofacial surgery and vascular surgery performed resection of the tumor utilizing exposure of the skull base with a double mandibular osteotomy technique. Though the presumptive diagnosis of the tumor was paraganglioma, the pathology report revealed the tumor was a psammomatous meningioma. Extracranial meningioma is a rare disease process. In this case there were several findings atypical for carotid body tumor or paraganglioma. Despite the enhancing features of the tumor on CT scan there was no splaying of the internal and external carotid arteries that would be typical for a carotid body tumor. Moreover, though the majority of the tumor mass was extracranial, there was intracranial extension which is rare for cervical paragangliomas. With imaging showing tumor encasement of the carotid artery, preoperative planning was assisted by a ‘halo sign’ that demonstrated a tissue plane between the mass and the internal carotid artery (Figure). This case demonstrates the importance of establishing a wide differential diagnosis for a cervical mass and highlights that an extracranial meningioma can mimic a cervical paraganglioma. The creation of a multidisciplinary team proved essential for effective access to tumor removal and patient safety.

Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. Here, we present the progress in the development of targeted liposomal nanocarriers designed for preferential collagen IV binding under simulated static vascular flow conditions. PEGylated liposomes (PLPs), previously established as effective delivery systems in vascular cells types, served as non-targeting controls. Collagen-targeting liposomes (CT-PLPs) were formed by conjugating established collagen-binding peptides to modified lipid heads via click chemistry (CTL), and inserting them at varying mol% either at the time of PLP assembly or via micellar transfer. All groups included fluorescently labeled lipid species for imaging and quantification. Liposomes were exposed to collagen IV matrices statically or via hemodynamic flow, and binding was measured via fluorometric analyses. CT-PLPs formed with 5 mol% CTL at the time of assembly demonstrated the highest binding affinity to collagen IV under static conditions, while maintaining a nanoparticle characterization profile of ~50 nm size and a homogeneity polydispersity index (PDI) of ~0.2 favorable for clinical translation. When liposomes were exposed to collagen matrices within a pressurized flow system, empirically defined CT-PLPs demonstrated significant binding at shear stresses mimetic of physiological through pathological conditions in both the venous and arterial architectures. Furthermore, when human saphenous vein explants were perfused with liposomes within a closed bioreactor system, CT-PLPs demonstrated significant ex vivo binding to diseased vascular tissue. Ongoing studies aim to further develop CT-PLPs for controlled targeting in a rodent model of vascular injury. The CT-PLP nanocarriers established here show promise as the framework for a spatially controlled delivery platform for future application in targeted vascular therapeutics.

Lipid nanoparticles have become increasingly popular delivery platforms in the field of gene therapy, but bench-to-bedside success has been limited. Many liposomal gene vectors are comprised of synthetic cationic lipids, which are associated with lipid-induced cytotoxicity and immunogenicity. Natural, non-cationic PEGylated liposomes (PLPs) demonstrate favorable biocompatibility profiles but are not considered viable gene delivery vehicles due to inefficient nucleic acid loading and reduced cellular uptake. PLPs can be modified with cell-penetrating peptides (CPPs) to enhance the intracellular delivery of liposomal cargo but encapsulate leakage upon CPP-PLP assembly is problematic. Here, we aimed to identify parameters that overcome these performance barriers by incorporating nucleic acid condensers during CPP-PLP assembly and screening variable ethanol injection parameters for optimization. CPP-PLPs were formed with R8-amphiphiles via pre-insertion, post-insertion and post-conjugation techniques and liposomes were characterized for size, surface charge, homogeneity, siRNA encapsulation efficiency and retention and cell associative properties. Herein we demonstrate that pre-insertion of stearylated R8 into PLPs is an efficient method to produce non-cationic CPP-PLPs and we provide additional assembly parameter specifications for a modified ethanol injection technique that is optimized for siRNA encapsulation/retention and enhanced cell association. This assembly technique could provide improved clinical translation of liposomal based gene therapy applications.

Background: Intimal hyperplasia (IH) is the most common indicator for secondary intervention in peripheral vascular disease. Matrix metalloproteinases (MMPs) play a role in IH development due to their degradation of the extracellular matrix. Doxycycline (Doxy), a member of the tetracycline family of antibiotics, is a potent MMP inhibitor. We have previously shown that Doxy inhibits MMP activity and vascular smooth muscle cell migration in vitro. We hypothesized that Doxy would decrease MMP activity in vivo and inhibit the development of IH in a rodent model of vascular injury. Methods and Results: Doxy (400 mg/pellet) was delivered by a slow-release pellet implanted 3 days prior to or at the time of balloon angioplasty (BA) of the common carotid artery in female rats. At 14 days post-BA, intima-to-media (I:M) ratios were 0.77 +/- 0.21 and 1.04 +/- 0.32 in the Doxy treated groups, respectively, compared to 1.25 +/- 0.26 in the control group (P = not significant; n = 3). Additionally, the tested dose of Doxy in either group had no inhibitory effect on membrane type 1-MMP or MMP-2 tissue levels, as measured by immunohistochemistry, or on systemic levels of MMP, as measured by total MMP serum levels using enzyme-linked immunosorbent assay. At 14 days post-BA, VSMC proliferation in the injured artery was increased to Doxy treatment prior to and at the time of surgery (23.5 +/- 3.4 and 27.2 +/- 3.9%, respectively), compared to control (11.4 +/- 0.4%; n = 3), as measured by proliferating cellular nuclear antigen immunostaining. Conclusions: In our in vivo model of vascular injury, systemic Doxy administration prior to or at the time of vascular injury does not significantly hinder the progression of IH development. Additional doses and routes of administration could be examined in order to correlate therapeutic serum levels of Doxy with effective MMP inhibition in serum and arterial tissue. However, alternative drug delivery systems are needed in order to optimize therapeutic administration of targeted MMP inhibitors for the prevention of IH development.

BACKGROUND:Mycotic aortoiliac aneurysms in neonates are rare. Surgical treatment has traditionally been the standard of care, but recent case reports have suggested that endovascular management of mycotic iliac aneurysms may also be safe and effective. In this case, we describe successful management of a mycotic aortoiliac aneurysm in a neonate with exploratory laparotomy and ligation of the left common iliac artery. METHODS:A full-term infant boy of uncomplicated delivery was transferred to our institution on day 2 of life after a barium enema concerning for small left colon syndrome. An umbilical artery catheter had been placed for monitoring but was removed before transfer. During his hospital course, he developed left leg edema and fever. He was found to have a mycotic aneurysm of the left common and internal iliac arteries, causing common iliac venous compression. A repeat ultrasound revealed the aneurysm measured a maximum of 12 mm in diameter and 26 mm in length. RESULTS:Treatment was delayed until the patient was clinically stable. He was monitored with serial ultrasounds, which showed no significant increase in aneurysmal size. A review of the literature supported the perception the aneurysm posed an impending risk to the patient. On day 16 of life, the neonate underwent ligation and excision of the left common iliac artery aneurysm. CONCLUSION:Our experience found ligation of the common iliac artery to be safe and effective, establishing that surgical reconstruction is not required.

The "inside-out" technique eliminates the need for subclavian or femoral catheter placement by placing a supraclavicular catheter via a percutaneous femoral vein access. Few reports of its use in vascular surgery exist. The purpose of this article is to describe our version of the technique and report results. Between 2016 and 2017, the inside-out technique was performed on eight patients. All patients had more than four prior access sites and bilateral internal jugular vein occlusion. The technical success rates were 100% with no periprocedural complications and success in achieving dialysis access. One patient required catheter replacement within 48 hours, one catheter was used as a bridge to Hemodialysis Reliable Outflow (Hemosphere, a Cryolife Inc Company, Eden Prairie, Minn) graft placement, and one patient died of sepsis unrelated to their catheter. Our data show the inside-out technique to be safe and effective, removes the need for subclavian or femoral catheter placement, and should be a component of treatment algorithms for complex dialysis patients, which is consistent with National Kidney Foundation's Kidney Disease Outcomes Quality Initiative recommendations.

The polyherbal blend Zyflamend™ has been shown to have anti-inflammatory properties and attenuate inflammatory-modulated pathologies. Fish oils have also been shown to have cardioprotective properties. However, the beneficial effects of their combination have not been investigated. Intimal hyperplasia (IH), a pathological remodeling response of a vessel to injury, is heavily regulated by an immune-mediated reaction. The objective of this study was to determine if dietary supplementation with Zyflamend and/or Wholemega could affect inflammatory-dependent vascular remodeling mechanisms when provided at human equivalent doses. Based on their anti-inflammatory properties and protective benefits demonstrated in previous pre-clinical studies, we hypothesized administration of these supplements would prevent IH in an animal model of vascular injury. The diets of aged male rats were supplemented with human equivalent doses of Zyflamend (Zyf) and/or Wholemega (WMega) or placebo (Plac) for 1wk prior to balloon angioplasty (BA)-induced injury of the left carotid artery. At 28d post-injury morphometric analysis of carotid tissue revealed IH was decreased in Zyf + WMega animals compared to placebo, while Zyf or WMega independently had no significant effect. Serum cytokine screening indicated injury-induced interleukin family isoforms, interferon-γ, and macrophage inflammatory proteins were downregulated by Zyf + WMega. Immunohistochemical staining for monocyte/macrophage phenotypic markers revealed that while overall monocyte/macrophage vessel infiltration was not affected, Zyf + WMega limited the alternative differentiation of M2 macrophages and reduced the presence of myofibroblasts in the injured vessel wall. In summary, dietary supplementation with Zyf + WMega attenuated the acute inflammatory response following vascular injury and inhibited IH development in vivo.

Metformin, one of the most commonly used drugs for the treatment of type II diabetes, was recently found to exert its therapeutic effects, at least in part, by activating the AMP-activated protein kinase (AMPK). However, the site of its action, as well as the mechanism to activate AMPK, remains elusive. Here we report how metformin activates AMPK. In cultured bovine aortic endothelial cells, metformin dose-dependently activated AMPK in parallel with increased detection of reactive nitrogen species (RNS). Further, either depletion of mitochondria or adenoviral overexpression of superoxide dismutases, as well as inhibition of nitric-oxide synthase, abolished the metformin-enhanced phosphorylations and activities of AMPK, implicating that activation of AMPK by metformin might be mediated by the mitochondria-derived RNS. Furthermore, administration of metformin, which increased 3-nitrotyrosine staining in hearts of C57BL6, resulted in parallel activation of AMPK in the aorta and hearts of C57BL6 mice but not in those of endothelial nitric-oxide synthase (eNOS) knockout mice in which metformin had no effect on 3-nitrotyrosine staining. Because the eNOS knockout mice expressed normal levels of AMPK-alpha that was activated by 5-aminoimidazole-4-carboxamide riboside, an AMPK agonist, these data indicate that RNS generated by metformin is required for AMPK activation in vivo. In addition, metformin significantly increased the co-immunoprecipitation of AMPK and its upstream kinase, LKB1, in C57BL6 mice administered to metformin in vivo. Using pharmacological and genetic inhibitors, we found that inhibition of either c-Src or PI3K abolished AMPK that was enhanced by metformin. We conclude that activation of AMPK by metformin might be mediated by mitochondria-derived RNS, and activation of the c-Src/PI3K pathway might generate a metabolite or other molecule inside the cell to promote AMPK activation by the LKB1 complex.

BACKGROUND:Only 3 cases of aorto-cisterna chyli fistula have been described in the literature but none with a resulting pseudoaneurysm (PSA).METHODS:A 68-year-old man presented following a motor vehicle collision. Imaging revealed a retroperitoneal hematoma with enhancement of the cisterna chyli, representing an aortic to cisterna chyli fistula. Three days later, computed tomography angiography showed resolution of the fistula, but revealed a PSA. The patient underwent arteriography that confirmed the PSA, and then a computed tomography-guided thrombin injection was performed. Follow-up imaging showed resolution of the PSA.RESULTS:Only 3 cases of aorto-cisterna chyli fistula have been described. We hypothesize that this fistula was caused from his L2 vertebral body fracture, which avulsed the lumbar artery and injured the cisterna chyli. The cisterna chyli provided an outflow tract for the aortic injury. We believe this type of fistula follows a benign clinical course. Aorto-cisterna chyli fistula is rare, and reports point to spontaneous resolution. Our case is unique in that the patient progressed from a fistula to a PSA. Options for treatment of this PSA include covered stent graft, open repair, coil embolization, or thrombin injection.CONCLUSIONS:This case report describes an extremely rare diagnosis and the natural history of this aorto-cisterna chyli fistula. Furthermore, the resulting aortic PSA was successfully treated with computed tomography-guided thrombin injection, which in the appropriate setting, should be considered an acceptable option.

Objectives: Nanoparticles designed to localize to areas of vascular perturbations could provide a targeted delivery system for gene therapeutics aimed at improving intervention outcomes. PEGylated liposomes (PLPs) are potential delivery vectors, and PEG residues provide a scaffold for multifunctional surface modifications. We have previously developed PLPs functionalized with collagen targeting peptides (CTP-PLPs) that preferentially bind collagen IV, an abundant sub-endothelial matrix protein exposed during vascular intervention. Here we present dual ligand-modified liposomes with multifunctional potential, building on our CTP-PLP platform by simultaneously incorporating cell-penetrating peptides (R8) to enhance liposomal cell association and nucleic acid delivery. Methods: PLPs were formed with DOPC-PEG + 30mol% cholesterol + 0.1mol% Rhodamine-DOPE, and siRNA loaded via EtOH injection. CTP-PLPs were formed as PLPs + 5mol% CTP-modified-DSPE, as previously reported. Dual-ligand modified liposomes (R8-CTP-PLPs) incorporated CTP concurrently with 5-10mol% sterylated-R8. Vascular smooth muscle cells (VSMC) were treated for 24hr at 100uM lipid for cellular association, quantified via fluorimetry, or at 400nM siRNA encapsulate for gene silencing, quantified via qPCR. Results: While CTP-PLPs increased VSMC association by 1.6-fold compared to PLP, R8-CTP-PLPs increased association by 3.6-fold (5mol%R8) and 10.4-fold (10mol%R8; Fig1A). Likewise, siRNA delivery via R8-CTP-PLPs resulted in enhanced gene silencing compared to CTP-PLPs and non-treated controls (Fig1B). Conclusions: R8-CTP-PLP nanocarriers established here show promise as the framework for a spatially controlled drug delivery platform for targeted vascular therapeutics. Ongoing studies aim to elucidate R8-CTL-PLP vessel wall binding and targeted gene silencing in a dynamic living environment via ex vivo vessel perfusion and in vivo rodent models of vascular injury.

Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo: ROLE OF MITOCHONDRIAL REACTIVE NITROGEN SPECIESJournal of Biological ChemistryVol. 279Issue 42PreviewMetformin, one of the most commonly used drugs for the treatment of type II diabetes, was recently found to exert its therapeutic effects, at least in part, by activating the AMP-activated protein kinase (AMPK). However, the site of its action, as well as the mechanism to activate AMPK, remains elusive. Here we report how metformin activates AMPK. In cultured bovine aortic endothelial cells, metformin dose-dependently activated AMPK in parallel with increased detection of reactive nitrogen species (RNS). Full-Text PDF Open Access VOLUME 279 (2004) PAGES 43940–43951 This article has been withdrawn by the authors. The Journal raised questions that the AMPK immunoblot in Fig. 3C was reused in Fig. 4A as ACC, lanes 1 and 4 of the AMPK-P immunoblot in Fig. 4A were duplicated, and lanes 3 and 4 of the AMPK-P immunoblot in Fig. 4F were reused in Fig. 5A as ACC-P. Fifteen years after publication, the original data for these figures were not available for evaluation. The authors were able to provide to the Journal data from repeat experiments for Fig. 4A performed at the time of the original work, which they state confirm the results. The authors also provided the journal evidence that the duplications of Figs. 3C, 4F, and 5A occurred due to errors in the figure preparation. The authors offered to publish substitute figures based on the repeated experiments and corrected figures, alternatively, offered to repeat the experiments. However, the Journal declined both offers, a decision with which the authors respectfully disagree. Further, the authors state that the results of this article are confirmed by the results of complementary experiments presented in the article, and the principal conclusion was further confirmed in publications from other laboratories (Quintero, M. et al. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 5379–5384; Guilherme, L. et al. (2006) Diabetes Care 29, 1083–1089). The article, with confirmatory data supporting the results, can be obtained by contacting the authors. The authors stand by the experimental data and the conclusions of the article.

Vascular interventions inherently result in disruption of the tunica intima and exposure of subendothelial matrix proteins. Spatially controlled nanoparticles designed to colocalize to these exposed matrices could provide a targeted drug delivery system aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. We have previously reported the development of a surface-modified liposomal platform designed to preferentially bind collagen type IV, an abundant subendothelial matrix protein, in a static in vitro environment. Here we present our progress in this discovery-driven liposomal nanocarrier system by validating its collagen IV binding affinity under simulated physiological and pathologic vascular flow conditions. Nontargeting PEGylated liposomes (PLP) were formed with bulk DOPC-PEG + 30 mol% cholesterol + 0.1 mol% Rhodamine-DOPE. Collagen-targeting liposomes (CT-PLP) were formed by reacting DSPE-PEG-DBCO to previously established collagen binding peptides (CBP), via copper-free click chemistry, and inserting 5 mol% CBP-modified lipids to base PLPs at lipid hydration. Collagen IV matrices were dried at 3 μg/cm2, and hemodynamic liposome binding was assayed by live fluorescence microscopy over 60 minutes simulated flow at 5 to 115 dynes-s/cm2 using a closed parallel-plate flow chamber. Liposome binding was quantified by mean fluorescent intensity of bound Rhodamine-labeled lipid normalized to background. Under continuous flow, CT-PLPs demonstrated increased binding to collagen matrices over time at all tested sheer stress conditions (Fig, A). After 60 minutes of flow, CT-PLPs demonstrated remarkable binding under all conditions while nontargeted PLP control binding was negligible (Fig, B). CT-PLPs demonstrated an affinity for collagen IV binding under simulated hemodynamic flow at sheer stress conditions ranging from venous physiological to pathologic flow and arterial physiological to pathologic flow. CT-PLP nanocarriers established here show promise as the framework for a spatially controlled drug delivery platform for future application in targeted vascular therapeutics. Ongoing studies aim to demonstrate CT-PLP binding capacity in situ via ex vivo human saphenous vein and femoral artery perfusion under normal and elevated sheer stress.

Systematic literature reviews remain inconclusive on defining optimal thrombectomy methods to treat occluded hemodialysis access. Recent changes in Centers for Medicare and Medicaid Services bundling/reimbursement for endovascular thrombectomy procedures have led to renewed interest in delivering cost-effective care. Percutaneous mechanical rotational thrombectomy (RT) devices (Cleaner XT; Argon Medical Devices, Plano, Tex) have been developed to compete with traditional pharmacomechanical thrombectomy (PMT) devices (AngioJet with tissue plasminogen activator; Boston Scientific, Marlborough, Mass) for percutaneous thrombectomy procedures. The objective of this study was to evaluate clinical and economic factors of open surgical thrombectomy (OST) compared with contemporary percutaneous mechanical thrombectomy (PERC) devices for thrombosed hemodialysis vascular access. Data analysis was performed from a tertiary care hospital prospectively maintained hemodialysis database between 2012 and 2016. All patients undergoing outpatient thrombectomy for occluded hemodialysis access were captured. Clinical end points included arteriovenous access type, thrombectomy method, operative time, estimated blood loss, and intervention success rates. Financial end points included direct cost, total cost, operating margin, and total margin. Additional subgroup analysis of the percutaneous thrombectomy group was performed to compare pharmacomechanical with rotational techniques. Analysis using univariate and multivariate measures was performed with significance assigned as P < .05. Between 2012 and 2016, there were 1072 hemodialysis arteriovenous accesses (88.3% arteriovenous fistula [n = 947]; 11.7% arteriovenous graft [n = 125]) created; 391 patients required thrombectomy (OST, n = 64; PERC, n = 327), and 670 thrombectomy procedures were performed (OST, n = 71; PERC, n = 599). Arteriovenous graft was the predominant type of access requiring thrombectomy (77% arteriovenous graft [n = 506] vs 23% arteriovenous fistula [n = 151]; OST, 97.2%; PERC, 74.5%; P = NS). Most accesses were in the upper extremity (upper extremity, 90.7% [n = 592]; lower extremity, 9.3% [n = 60]; OST, 87.5%; PERC, 91.2%; P = NS). Despite that more diabetic patients were treated with PERC, no other statistical difference between groups was observed in gender or comorbidities, including hypertension, coronary artery disease, congestive heart failure, tobacco abuse, and hypercoagulable disorder. Concurrent intervention with outflow venous angioplasty was the most common single intervention (52.7%). Each thrombectomy method had high technical success rates (OST, 95.8%; PERC, 95.7%; P = NS). Subgroup analysis between percutaneous methods (42.7% RT [n = 256], 53.1% PMT [n = 318], 4.2% RT + PMT [n = 25]) showed that RT therapy had lower estimated blood loss (P < .001) and shorter operative time (RT, 48 minutes; PMT, 52 minutes; P < .03). The highest successful thrombectomy rate was RT (97.7% RT vs 94.7%; P < .07). Financially, all economic end points, specifically direct supply cost (OST, $3334; RT, $3241; PMT, $3529; RT + PMT, $4414; P < .001), total cost (OST, $7220; RT, $6291; PMT, $7317; RT + PMT, $9735; P = .001), operating margin (OST, $1331; RT, $−360; PMT, $−311; RT + PMT, $−1154; P < .001), and total margin (OST, $−894; RT, $−2200; PMT, $−2902; RT + PMT, $−4596; P < .001), favored OST therapy. With equal success rates between hemodialysis access thrombectomy methods, RT has the lowest operating and total cost, whereas OST has significantly better profit margins in a hospital-based setting. All thrombectomy procedure types had a negative profit margin in an outpatient hospital-based setting. PERC using RT decreases operative time, blood loss, and cost compared with PMT. Combination percutaneous thrombectomy leads to the greatest financial loss compared with any single therapy. With recent reimbursement/bundling changes for percutaneous hemodialysis thrombectomy, OST should be considered first-line treatment for occluded hemodialysis access in a hospital-based setting, whereas RT may be more cost-efficient in office-based settings as the cost profile is more favorable.