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Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly associated with an increased risk of MALE and MACE, independent of other risk factors. The ROC curve analysis identified a SIRT1 cutoff of 3.79 ng/mL for predicting the risk of MALE. Moreover, incorporating SIRT1 into predictive models significantly enhanced the accuracy of predicting adverse outcomes. Results suggest serum SIRT1 is a potential independent marker for predicting MALE and MACE in diabetic patients with CLTI undergoing LER. Further research is needed to clarify the mechanistic pathways in which SIRT1 may influence cardiovascular outcomes, and the role of this novel biomarker in the management of PAD and CLTI among patients with diabetes., (© 2024. The Author(s).)

Introduction: Arteriovenous fistulas (AVFs) and grafts are essential for long-term hemodialysis access in patients with end-stage renal disease. However, complications and access failure often necessitate re-intervention. In this study, we aim to delineate the factors associated with earlier failure of permanent hemodialysis access warranting revision procedures., Methods: This retrospective study aimed to identify factors associated with increased revision rates in AVFs and arteriovenous grafts, using multivariate survival analysis. A cohort of 136 patients who underwent initial arteriovenous access creation between 2005 and 2022 was analyzed. Patient characteristics, including age, comorbidities, access type, and vascular anatomy, were extracted, and hazard ratios (HR) were calculated to identify independent predictors of needing revision., Findings: A total of 119 patients were included in the final cohort, with a mean age of 55.2 years. Over 40% of patients had a previous central venous catheter placement, while 15% had a previous AVF. The majority of procedures were performed on the left side (74%), and brachiocephalic fistulas were most commonly created (41%). Univariate and multivariate Cox regression revealed that age (adjusted HR = 1.02, p = 0.01) and prior central venous catheter placement (adjusted HR = 1.77, p = 0.01) were independent predictors of earlier revision, while other variables such as sex, hypertension, and diabetes did not show significant associations. Patients with prior central venous catheter placement had a 77% increased risk of revision, even when adjusted for confounders., Discussion: Understanding predictors of successful long-term access outcomes can guide decision-making regarding access type and alternative strategies. In our cohort, increased age and prior central venous catheter placement are associated with a shorter time to failure of permanent hemodialysis access and an increased risk of needing revision., (© 2024 International Society for Hemodialysis.)

Background: We evaluated the impact of completion intraoperative venography on clinical outcomes for axillosubclavian vein (AxSCV) thrombosis owing to venous thoracic outlet syndrome (vTOS)., Methods: We performed a retrospective, single-center review of all patients with vTOS treated with first rib resection (FRR) and intraoperative venography from 2011 to 2023. We reviewed intraoperative venographic films to classify findings and collected demographics, clinical and perioperative variables, and clinical outcomes. Primary end points were symptomatic relief and primary patency at 3 months and 1 year. Secondary end points were time free from symptoms, reintervention rate, perioperative complications, and mortality., Results: Fifty-one AxSCVs (49 patients; mean age, 31.3 ± 12.6 years; 52.9% female) were treated for vTOS with FRR and external venolysis followed by completion intraoperative venography with a mean follow up of 15.5 ± 13.5 months. Before FRR, 32 underwent catheter-directed thrombolysis (62.7%). Completion intraoperative venography identified 16 patients with no stenosis (group 1, 31.3%), 17 with no stenosis after angioplasty (group 2, 33.3%), 10 with residual stenosis after angioplasty (group 3, 19.7%), and 8 with complete occlusion (group 4, 15.7%). The overall symptomatic relief was 44 of 51 (86.3%) and did not differ between venographic classifications (group 1, 14 of 16; group 2, 13 of 17; group 3, 10 of 10; and group 4, 7 of 8; log-rank test, P = .5). The overall 3-month and 1-year primary patency was 42 of 43 (97.7%) and 32 of 33 (97.0%), respectively (group 1, 16 of 16 and 9 of 9; group 2, 16 of 17 and 12 of 13; group 3, 10 of 10, 5 of 5; group 4, primary patency not obtained). There was one asymptomatic rethrombosis that resolved with anticoagulation, and three patients underwent reintervention with venous angioplasty for significant symptom recurrence an average 2.89 ± 1.7 months after FRR., Conclusions: Our single-center retrospective study demonstrates that FRR with completion intraoperative venography has excellent symptomatic relief and short- and mid-term patency despite residual venous stenosis and complete occlusion. Although completion intraoperative venographic classification did not correlate with adverse outcomes, this protocol yielded excellent results and provides important clinical data for postoperative management. Our results also support a conservative approach to AxSCV occlusion identified after FRR., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Peripheral artery disease (PAD), coronary artery disease (CAD), and cerebrovascular disease (CeVD) are characterized by atherosclerosis and inflammation as their underlying mechanisms. This paper aims to conduct a literature review on pharmacotherapy for PAD, specifically focusing on how different drug classes target pro-inflammatory pathways. The goal is to enhance the choice of therapeutic plans by considering their impact on the chronic subclinical inflammation that is associated with PAD development and progression. We conducted a comprehensive review of currently published original articles, narratives, systematic reviews, and meta-analyses. The aim was to explore the relationship between PAD and inflammation and evaluate the influence of current pharmacological and nonpharmacological interventions on the underlying chronic subclinical inflammation. Our findings indicate that the existing treatments have added anti-inflammatory properties that can potentially delay or prevent PAD progression and improve outcomes, independent of their effects on traditional risk factors. Although inflammation-targeted therapy in PAD shows promising potential, its benefits have not been definitively proven yet. However, it is crucial not to overlook the pleiotropic properties of the currently available treatments, as they may provide valuable insights for therapeutic strategies. Further studies focusing on the anti-inflammatory and immunomodulatory effects of these treatments could enhance our understanding of the mechanisms contributing to the residual risk in PAD and pave the way for the development of novel therapies.

Background: Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), High-Mobility Group Box-1 (HMGB-1), Osteoprotegerin (OPG), Sortilin and Omentin-1- at baseline, with cardiovascular outcomes (MACE and MALE) after LER in diabetic patients with CLTI., Methods: In this prospective non-randomized study, 264 diabetic patients with CLTI undergoing endovascular revascularization were enrolled. Serum levels of each biomarker were collected before revascularization and outcomes' incidence was evaluated after 1, 3, 6 and 12 months., Results: During the follow-up period, 42 cases of MACE and 81 cases of MALE occurred. There was a linear association for each biomarker at baseline and incident MACE and MALE, except Omentin-1 levels that were inversely related to the presence of MACE or MALE. After adjusting for traditional cardiovascular risk factors, the association between each biomarker baseline level and outcomes remained significant in multivariable analysis. Receiver operating characteristics (ROC) models were constructed using traditional clinical and laboratory risk factors and the inclusion of biomarkers significantly improved the prediction of incident events., Conclusions: Elevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG and Sortilin levels and low Omentin-1 levels at baseline correlate with worse vascular outcomes in diabetic patients with CLTI undergoing LER. Assessment of the inflammatory state with this panel of biomarkers may support physicians to identify a subset of patients more susceptible to the procedure failure and to develop cardiovascular adverse events after LER., (© 2023. The Author(s).)

Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER. A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs. 446.4 ± 171.7 pg/mL, p < 0.01), whereas increased serum levels FGF23 (75.0 ± 11.8 pg/mL vs. 53.2 ± 15.4 pg/mL, p < 0.01) were significantly associated with the development of MACE. Receiver operating characteristic (ROC) analysis confirmed the predictive power of Klotho and FGF23 baseline levels. Furthermore, decreased Klotho levels were associated with the occurrence of MALE after LER (329.1 ± 136.8 pg/mL vs 495.4 ± 183.9 pg/mL, p < 0.01). We found that Klotho and FGF23 baseline levels are a potential biomarker for increased cardiovascular risk after LER in diabetic patients with PAD and CLTI., (© 2023. The Author(s).)

Background: Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients. The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group of diabetic patients with chronic limb-threatening ischemia (CLTI)., Methods: We conducted a prospective observational study of 201 diabetic patients with PAD and CLTI requiring LER. Baseline serum HMGB-1 levels were determined before endovascular procedure. Data on cardiovascular and limb outcomes were collected in a 12-month follow-up., Results: During the follow-up period, 81 cases of MACE and 93 cases of MALE occurred. Patients who subsequently developed MACE and MALE had higher serum HMGB-1 levels. Specifically, 7.5 ng/mL vs 4.9 ng/mL (p < 0.01) for MACE and 7.2 ng/mL vs 4.8 ng/mL (p < 0.01) for MALE. After adjusting for traditional cardiovascular risk factors, the association between serum HMGB-1 levels and cardiovascular outcomes remained significant in multivariable analysis. In our receiver operating characteristic (ROC) curve analysis, serum HMGB-1 levels were a good predictor of MACE incidence (area under the curve [AUC] = 0.78) and MALE incidence (AUC = 0.75)., Conclusions: This study demonstrates that serum HMGB-1 levels are associated with the incidence of MACE and MALE after LER in diabetic populations with PAD and CLTI., (© 2022. The Author(s).)

Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE.

Placement of extracorporeal membrane oxygenation (ECMO) in obese patients has been challenging; however, cannulation risk in obese patients has not been clearly investigated. We therefore explored ECMO cannulation complications in this obese population. Data were reviewed from adult ECMO database from 2010 to 2019. Patients were stratified by body mass index (BMI) (normal weight [NW] [BMI 18.5-24.9], overweight [BMI 25-29.9], class I [BMI 30-34.9], class II [BMI 35-39.9], class III [BMI >40]). Patients with central cannulation were excluded from this study. Combined ECMO cannulation complications and survival data were retrospectively analyzed. There were 233 patients, 156 venoarterial (VA) ECMO patients (45 [28%] NW, 51 [33%] overweight, 37 [24%] class I, 12 [8%] class II, and 11 [7.0%] class III) and 77 venovenous (VV) ECMO patients (14 [18%] NW, 13 [17%] overweight, 17 [22%] class I, 11 [14%] class II, and 22 [29%] class III). There were significantly more cannulation site bleeds in VA class III (55%) patients compared with VA NW patients (22%), p = 0.006. There was no significant difference in cannulation site bleeding between BMI groups for VV ECMO. There was no difference in 30 day mortality, ECMO survival for all BMI groups in both VA and VV ECMO. There is significant increased risk of bleeding with peripheral VA cannulation of obese patients with BMI > 35. Cannulating surgeon should be aware of this bleeding risk in morbidly obese patient who undergo VA ECMO., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Objective: Venoarterial extracorporeal membrane oxygenation (ECMO) is a salvage therapy in patients with severe cardiopulmonary failure. Owing to the large size of the cannulas inserted via the femoral vessels (≤24-F) required for adequate oxygenation, this procedure could result in significant limb ischemic complications (10%-70%). This study evaluates the results of a distal limb perfusion arterial protocol designed to reduce associated complications., Methods: We conducted a retrospective institutional review board-approved review of consecutive patients requiring ECMO via femoral cannulation (July 2010-January 2015). To prevent arterial ischemia, a distal perfusion catheter (DPC) was placed antegrade into the superficial femoral artery and connected to the ECMO circuit. Limb perfusion was monitored via near-infrared spectroscopy (NIRS) placed on both calves. Decannulation involved open repair, patch angioplasty, and femoral thrombectomy as needed., Results: A total of 91 patients were placed on ECMO via femoral arterial cannula (16-F to 24-F) for a mean duration of 9 days (range, 1-40 days). A percutaneous DPC was inserted prophylactically at the time of cannulation in 55 of 91 patients, without subsequent ischemia. Of the remaining 36 patients without initial DPC placement, 12 (33% without DPC) developed ipsilateral limb ischemia related to arterial insufficiency, as detected by NIRS and clinical findings. In these patients, the placement of a DPC (n = 7) with or without a fasciotomy, or with a fasciotomy alone (n = 4), resulted in limb salvage; only one patient required subsequent amputation. After decannulation (n = 7), no patients had further evidence of limb ischemia. Risk factors for the development of limb ischemia identified by categorical analysis included lack of DPC at time of cannulation and ECMO cannula size of less than 20-Fr. There was a trend toward younger patient age. Overall ECMO survival rate was 42%, whereas survival in patients with limb ischemia was only 25%., Conclusions: Limb ischemia complications from ECMO may be decreased by prophylactic placement of an antegrade DPC. Without DPC, continuous monitoring using NIRS may identify limb ischemia, which can be treated subsequently with DPC and or fasciotomy., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Mycotic aortic aneurysms are rare occurrences and such aneurysms associated with Streptococcus pneumoniae are seldom seen in the current antibiotic era. We present the unusual case of a 68-year-old healthy female with a Streptococcal mycotic abdominal aortic aneurysm of unknown etiology treated with antibiotics and open surgical intervention. Postoperative imaging revealed multiple new thoracic mycotic aortic aneurysms for which she was treated with thoracic endovascular aortic repair. Sequential abdominal and thoracic Streptococcal mycotic aortic aneurysms treated with a combination of open and endovascular surgery demonstrate a unique and rare case., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Mycotic rupture of the arteries is a rare but deadly disorder. Current management typically involves open surgical repair. However, endovascular repair is a potential treatment that can be used to delay open repair, especially in acutely unstable patients. A case report and review of the literature was conducted to determine whether endovascular therapy could be a destination therapy for patients with arterial rupture secondary to infection., Methods: We present the case of a 72-year-old man with a left common iliac artery aneurysm rupture secondary to Salmonella infection treated with endovascular therapy upon initial presentation. A literature review of PubMed yielded 29 patients with ruptured aortic and iliac infected aneurysms that were initially treated with endovascular repair., Results: Majority of the patients (76.7%, 23 of 30) were successfully treated with the endovascular treatment and did not require open revision. These patients were often placed on long-term antibiotics., Conclusion: The literature review supports endovascular repair with a stent graft as a temporizing measure for infected ruptured arteries in an emergent setting and, in select cases, as a destination therapy., (© The Author(s) 2016.)

Importance: Median arcuate ligament (MAL) syndrome is a rare disease resulting from compression of the celiac axis by fibrous attachments of the diaphragmatic crura, the median arcuate ligament. Diagnostic workup and therapeutic intervention can be challenging., Objective: To review the literature to define an algorithm for accurate diagnosis and successful treatment for patients with MAL syndrome., Evidence Review: A search of PubMed (1995-September 28, 2015) was conducted, using the key terms median arcuate ligament syndrome and celiac artery compression syndrome., Findings: Typically a diagnosis of exclusion, MAL syndrome involves a vague constellation of symptoms including epigastric pain, postprandial pain, nausea, vomiting, and weight loss. Extrinsic compression of the vasculature and surrounding neural ganglion has been implicated as the cause of these symptoms. Multiple imaging techniques can be used to demonstrate celiac artery compression by the MAL including mesenteric duplex ultrasonography, computed tomography angiography, magnetic resonance angiography, gastric tonometry, and mesenteric arteriography. Surgical intervention involves open, laparoscopic, or robotic ligament release; celiac ganglionectomy; and celiac artery revascularization. There remains a limited role for angioplasty because this intervention does not address the underlying extrinsic compression resulting in symptoms, although angioplasty with stenting may be used in recalcitrant cases., Conclusions and Relevance: Median arcuate ligament syndrome is rare, and as a diagnosis of exclusion, diagnosis and treatment paradigms can be unclear. Based on previously published studies, symptom relief can be achieved with a variety of interventions including celiac ganglionectomy as well as open, laparoscopic, or robotic intervention.

Tarsal tunnel syndrome is a compressive neuropathy of the posterior tibial nerve within the tarsal tunnel. Its etiology varies, including space occupying lesions, trauma, inflammation, anatomic deformity, iatrogenic injury, and idiopathic and systemic causes. Herein, we describe a 46-year-old man who presented with left foot pain. Work up revealed a venous aneurysm impinging on the posterior tibial nerve. Following resection of the aneurysm and lysis of the nerve, his symptoms were alleviated. Review of the literature reveals an association between venous disease and tarsal tunnel syndrome; however, this report represents the first case of venous aneurysm causing symptomatic compression of the nerve., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Middle aortic coarctation (MAC), a variant of middle aortic syndrome, is a rare entity with only ∼200 cases described in the literature. It classically presents with early onset and refractory hypertension, abdominal angina, and lower extremity claudication. Although endovascular repair has been described for focal stenoses, open bypass remains the standard to restore abdominal inflow and correct renovascular hypertension., Methods: We describe an unusually late presentation of MAC in a 52-year-old man from El Salvador with refractory hypertension since age 8 requiring 5 antihypertensive medications. He presented with acute chest pain and severe hypertension. He denied mesenteric and peripheral vascular symptoms. Distal pulses were not palpable. Creatinine was 1.9 mg/dL (peak 4.0 mg/dL). Computed tomography angiography demonstrated coarctation of the descending thoracic aorta with extensive collateralization., Results: After control of blood pressure, the patient's singular anatomy dictated a descending thoracic aorta-infrarenal aortic bypass using a 16-mm woven Hemashield tube graft via a left fifth-interspace anterolateral thoracotomy and left retroperitoneal incision. The graft was tunneled through the posterior left hemidiaphragm. Patient had excellent recovery, with decrease in antihypertensive medications (5 to 2), restoration of all distal pulses, and no neurologic complications. Postoperative creatinine was 0.9 mg/dL., Conclusions: MACs are rare entities with presentation usually in youth or adolescence, comprising only 0.5-2% of all aortic coarctation cases. Etiologies include congenital, acquired, inflammatory, and infectious causes. If untreated, most patients do not survive past the fourth decade because of the sequelae of renovascular hypertension including myocardial infarction, heart failure, intracranial hemorrhage, and aortic rupture. Depending on technical considerations, open surgical bypass remains the standard repair for MAC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Smith-Lemli-Opitz syndrome (SLOS) is a congenital, autosomal recessive metabolic and developmental disorder caused by mutations in the enzyme which catalyzes the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. Herein we show that dermal fibroblasts obtained from SLOS children display increased basal levels of LC3B-II, the hallmark protein signifying increased autophagy. The elevated LC3B-II is accompanied by increased beclin-1 and cellular autophagosome content. We also show that the LC3B-II concentration in SLOS cells is directly proportional to the cellular concentration of 7DHC, suggesting that the increased autophagy is caused by 7DHC accumulation secondary to defective DHCR7. Further, the increased basal LC3B-II levels were decreased significantly by pretreating the cells with antioxidants implicating a role for oxidative stress in elevating autophagy in SLOS cells. Considering the possible source of oxidative stress, we examined mitochondrial function in the SLOS cells using JC-1 assay and found significant mitochondrial dysfunction compared to mitochondria in control cells. In addition, the levels of PINK1 which targets dysfunctional mitochondria for removal by the autophagic pathway are elevated in SLOS cells, consistent with mitochondrial dysfunction as a stimulant of mitophagy in SLOS. This suggests the increase in autophagic activity may be protective, i.e., to remove dysfunctional mitochondria. Taken together, these studies are consistent with a role for mitochondrial dysfunction leading to increased autophagy in SLOS pathophysiology.

The Jarvik 2000 left ventricular assist device is inserted via a left thoracotomy with the outflow graft anastomosed to the descending thoracic aorta. Removal of the device during heart transplantation involves division of the outflow graft, resulting in a retained remnant. We describe the first reported case of a mycotic pseudoaneurysm of the descending thoracic aorta related to the remnant of a left ventricular assist device outflow graft in an immunosuppressed heart recipient complicated with systemic Pseudomonas infection. The pseudoaneurysm was temporarily treated with endovascular stent grafting followed by delayed thoracotomy, pseudoaneurysm excision, and placement of an aortic interposition graft using an aortic allograft., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Inferior vena cava (IVC) filters have been reported to have complication rates up to 35%. Penetration of surrounding retroperitoneal structures is an uncommon, but potentially serious, complication, with several reports in the literature. We present a unique case of a 34-year-old intravenous drug user with infected IVC filter struts penetrating multiple structures simultaneously. Definitive operative management was necessary for removal of filter struts from the aorta, the second part of the duodenum and the iliopsoas muscle. Drainage and debridement of an associated iliopsoas abscess was performed, followed by aortic and caval reconstruction.

Background: Herein we evaluate the potential of adipose-derived stem cells (ASC) to differentiate into smooth muscle cells (SMC) and their potential for use in a tissue-engineered vascular graft., Materials and Methods: We isolated ASC (CD13+29+90+) from the peri-umbilical adipose tissue of patients undergoing vascular surgery, and cultured them in media containing angiotensin II (AngII), sphingosylphosphorylcholine (SPC), or transforming growth factor-beta 1 (TGFβ1) for up to 3 weeks. SMC differentiation was assessed by (1) expression of early (calponin, caldesmon) and late (myosin heavy chain, MHC) SMC markers by RT-PCR, qPCR and Western blot, and (2) contraction upon plating on collagen gel. Differentiated ASCs were seeded onto a vascular graft (decellularized saphenous vein) within a bioreactor, and cell attachment was determined using confocal microscopy., Results: Prior to differentiation, ASC expressed low levels of all three molecular markers. After culture in each differentiating medium, the extent of up-regulation of calponin, caldesmon, and MHC was variable across all cell lines. After seeding onto collagen gel, ASCs differentiated in SPC and TGFβ1 exhibit contractile properties, similar to smooth muscle cell controls. Differentiated stem cells adhered and proliferated on the vascular graft., Conclusion: These data suggest that human adipose-derived stem cells (1) exhibit variable expression of SMC molecular markers after differentiation, (2) exhibit a contractile phenotype after differentiation with SPC and TGFβ1, and (3) proliferate on a vascular graft scaffold. Thus, ASCs are potentially useful in the construction of autologous arteries., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Adipose-derived stem cells (ASCs) possess significant therapeutic potential for tissue engineering and regeneration. This study investigates the endothelial differentiation and functional capacity of ASCs isolated from elderly patients. Isolation of ASCs from 53 patients (50-89 years) revealed that advanced age or comorbidity did not negatively impact stem cell harvest; rather, higher numbers were observed in older donors (>70 years) than in younger. ASCs cultured in endothelial growth medium-2 for up to 3 weeks formed cords upon Matrigel and demonstrated acetylated-low-density lipoprotein and lectin uptake. Further stimulation with vascular endothelial growth factor and shear stress upregulated endothelial cell-specific markers (CD31, von Willebrand factor, endothelial nitric oxide synthase, and VE-cadherin). Inhibition of the PI(3)K but not mitogen-activated protein kinase pathway blocked the observed endothelial differentiation. Shear stress promoted an anti-thrombogenic phenotype as demonstrated by production of tissue-plasminogen activator and nitric oxide, and inhibition of plasminogen activator inhibitor-1. Shear stress augmented integrin α(5)β(1) expression and subsequently increased attachment of differentiated ASCs to basement membrane components. Finally, ASCs seeded onto a decellularized vein graft resisted detachment despite application of shear force up to 9 dynes. These results suggest that (1) advanced age and comorbidity do not negatively impact isolation of ASCs, and (2) these stem cells retain significant capacity to acquire key endothelial cell traits throughout life. As such, adipose tissue is a practical source of autologous stem cells for vascular tissue engineering.

Stem cells differentiate into a variety of cell lines, making them attractive for tissue engineering and regenerative medicine. Specific microenvironmental cues regulate self-renewal and differentiation capabilities. Oxygen is an important component of the cellular microenvironment, serving as both metabolic substrate and signaling molecule. Oxygen has been shown to have a variety of effects on embryonic and adult stem cells. This review examines the role of hypoxia in regulating stem cell biology, specifically focusing on growth, maintenance of pluripotency, differentiation, and production of growth factors. Particular attention is paid to hypoxia and stem cells in relation to therapeutic angiogenesis. We conclude that further study is needed to optimize the use of hypoxia as a stimulus for various stem cell functions, including its potential role in therapeutic angiogenesis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Most research evaluating adipose-derived stem cells (ASC) uses tissue obtained from young, healthy patients undergoing plastic surgical procedures. Given the propensity of other adult stem cell lines to diminish with increasing patient age and co-morbidities, we assess the availability of ASC in elderly patients undergoing vascular surgical procedures, and evaluate their acquisition of endothelial cell (EC) traits to define their potential use in vascular tissue engineering., Methods and Methods: Adipose tissue obtained by liposuction from patients undergoing vascular procedures (n = 50) was digested with collagenase and centrifuged to remove mature adipocytes. The resultant number of cells, defined as the stromal-vascular (SV) pellet, was quantified. Following a 7-d culture period and negative selection for CD31 and CD45, the resultant number of ASC was quantified. After culture in differentiating media (EMG-2), ASCs were tested for the acquisition of endothelial-specific traits (expression of CD31, realignment in shear, cord formation on Matrigel)., Results: The SV pellet contained 2.87 ± 0.34 × 10(5) cells/g fat, and the resultant number of ASCs obtained was 1.41 ± 0.18 × 10(5) cells/g fat. Flow cytometry revealed a homogeneous ASC population (>98% positive for CD13, 29, 90). Advanced age or co-morbidity (obesity, diabetes, renal or peripheral vascular disease) did not significantly alter yield of ASC. After culture in differentiating media (EMG-2), ASCs acquired each of the endothelial-specific traits., Conclusion: ASC isolation appears independent of age and co-morbidities, and ASCs harvested from patients with vascular disease retain their ability to differentiate into endothelial-like cells. Adipose tissue, therefore, is a practical source of autologous, adult stem cells for vascular tissue engineering., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Use of adult adipose-derived stem cells (ASCs) as endothelial cell substitutes in vascular tissue engineering is attractive because of their availability. However, when seeded onto decellularized vascular scaffolding and exposed to physiological fluid shear force, ASCs are physically separated from the graft lumen. Herein we have investigated methods of increasing initial ASC attachment using luminal precoats and a novel protocol for the gradual introduction of shear stress to optimize ASC retention. Fibronectin coating of the graft lumen increased ASC attachment by nearly sixfold compared with negative controls. Gradual introduction of near physiological fluid shear stress using a novel bioreactor whereby flow rate was increased every second at a rate of 1.5 dynes/cm(2) per day resulted in complete luminal coverage compared with near complete cell loss following conventional daily abrupt increases. An upregulation of the alpha(5)beta(1) integrin was evinced following exposure to shear stress, which accounts for the observed increase in ASC retention on the graft lumen. These results indicated a novel method for seeding, conditioning, and retaining of adult stem cells on a decellularized vein scaffold within a high-shear stress microenvironment.

Background: Adipose tissue is a readily available source of multipotent adult stem cells for use in tissue engineering/regenerative medicine. Various growth factors have been used to stimulate acquisition of endothelial characteristics by adipose-derived stem cells (ASC). Herein we study the effects of endothelial cell growth supplement (ECGS) and physiological shear force on the differentiation of ASC into endothelial cells., Materials and Methods: Human ASC (CD13(+)29(+)90(+)31(-)45(-)) were isolated from periumbilical fat, cultured in ECGS media (for up to 3 wk), and exposed to physiological shear force (12 dynes for up to 8 d) in vitro. Endothelial phenotype was defined by cord formation on Matrigel, acetylated-low density lipoprotein (acLDL) uptake, and expression of nitric oxide synthase (eNOS), von Willebrand factor (vWF), and CD31 (platelet endothelial cell adhesion molecule, PECAM). Additionally, cell thrombogenicity was evaluated by seeding canine autologous ASC onto vascular grafts implanted within the canine arterial circulation for 2 wk., Results: We found that undifferentiated ASC did not display any of the noted endothelial characteristics. After culture in ECGS, ASC formed cords in Matrigel but failed to take up acLDL or express the molecular markers. Subsequent exposure to shear resulted in stem cell realignment, acLDL uptake, and expression of CD31; eNOS and vWF expression was still not observed. Grafts seeded with cells grown in ECGS (+/- shear) remained patent (six of seven) at 2 wk but had a thin coat of fibrin along the luminal surfaces., Conclusions: This study suggests that (1) ECGS and shear promote the expression of several endothelial characteristics in human adipose-derived stem cells, but not eNOS or vWF; (2) their combined effects appear synergistic; and (3) stem cells differentiated in ECGS appear mildly thrombogenic in vitro, possibly related, in part, to insufficient eNOS expression. Thus, while the acquisition of several endothelial characteristics by adult stem cells derived from adipose tissue suggests these cells are a viable source of autologous cells for cardiovascular regeneration, further stimulation/modifications are necessary prior to using them as a true endothelial cell replacement.

Objective: Technological advances in vascular surgery have changed the field dramatically over the past 10 years. Herein, we evaluate the impact of endovascular procedures on general surgery training., Methods: National operative data from the Residency Review Committee for Surgery were examined from 1997 through 2006. Total major vascular operations, traditional open vascular operations and endovascular procedures were evaluated for mean number of cases per graduating chief general surgery resident (GSR) and vascular surgery fellow (VSF)., Results: As endovascular surgical therapies became widespread, GSR vascular case volume decreased 34% over 10 years, but VSF total cases increased 78%. GSR experience in open vascular operations decreased significantly, as evidenced by a 52% decrease (P < 0.0001) in elective open AAA repair. VSFs have also seen significant decreases in open vascular procedures. Experience in endovascular procedures has increased for both general surgery and vascular residents, but the increase has been much larger in absolute number for VSFs., Conclusions: GSR experience in open vascular procedures has significantly decreased as technology has advanced within the field. Unlike VSFs, this loss has not been replaced by direct experience with endovascular training. These data demonstrate the impact technology can have on how we currently train general surgeons. New educational paradigms may be necessary in which either vascular surgery as an essential component is abandoned or training in catheter-based interventions becomes required.

Infrainguinal occlusive disease is a complex problem necessitating the cooperation of both medical and surgical therapies to aid limb salvage and alleviate symptoms. Endovascular therapies are varied, with no treatment clearly outweighing the other in terms of efficacy and durability. Angioplasty for focal stenosis has gained ground as the treatment of choice when indicated. There has also been a rapid evolution in stent technology, from early stainless steel wall stents to today's drug eluting nitinol stents. In this article, we examine the literature on these new technologies and treatment options and make recommendations based on the best data available.

The treatment of external carotid artery stenosis has been described with a variety of operative interventions. We present a patient who presented with amaurosis fugax and a critical left external carotid artery stenosis with known left internal carotid artery occlusion. We treated this stenosis with angioplasty and stenting rather than endarterectomy. Our patient did well and had no complications from the procedure. Endovascular repair of symptomatic external carotid artery stenosis provides an alternative treatment method to conventional endarterectomy for patients with high surgical risk.

Background: We are investigating decellularized vein allograft as a scaffold to engineer a non-synthetic, small-diameter vascular graft. This study examines the in vivo behavior of this scaffolding after implantation into the arterial circulation., Materials and Methods: Canine animals underwent bilateral carotid interposition grafting using jugular vein implanted as either: 1) fresh autograft, 2) fresh allograft, or 3) decellularized allograft. Decellularization was achieved using sodium dodecyl sulfate. Grafts were examined with duplex ultrasound biweekly to determine luminal diameter, thrombosis, stenosis, or anastomotic breakdown. After perfusion fixation at 2 or 8 weeks, grafts underwent histological, morphometric, and immunohistochemical examination., Results: All animals survived without neurological or hemorrhagic complication. No deterioration of graft integrity (rupture, aneurysm) was observed in any group. Luminal narrowing was observed in both allograft groups, but secondary to different pathology. Fresh allografts had significant mononuclear cell infiltrate, intimal hyperplasia, and intramural hemorrhage consistent with rejection. Conversely, decellularized allografts had minimal evidence of rejection but instead had a compact fibrin layer formed along their lumen. This fibrin layer was absent in the peri-anastomotic regions where endothelium had migrated from the native artery. By 8 weeks, decellularized grafts had repopulated with cells staining positive for smooth muscle alpha-actin., Conclusions: After 8 weeks of arterial flow, decellularized vein allograft exhibits satisfactory strength, reduced antigenicity compared to fresh allograft, and supports cellular repopulation. These characteristics make it satisfactory for further tissue engineering; combined with luminal vascular cell seeding, it may prove useful as a small-diameter arterial bypass graft.

Objective: Residual subclavian vein stenosis after thoracic outlet decompression in patients with venous thoracic outlet syndrome is often treated with postoperative percutaneous angioplasty (PTA). However, interval recurrent thrombosis before postoperative angioplasty is performed can be a vexing problem. Therefore we initiated a prospective trial at 2 referral institutions to evaluate the safety and efficacy of combined thoracic outlet decompression with intraoperative PTA performed in 1 stage., Methods: Over 3 years 25 consecutive patients (16 women, 9 men; median age, 30 years) underwent treatment for venous thoracic outlet syndrome with a standard protocol at 2 institutions. Twenty-one patients (84%) underwent preoperative thrombolysis to treat axillosubclavian vein thrombosis. First-rib resection was performed through combined supraclavicular and infraclavicular incisions. Intraoperative venography and subclavian vein PTA were performed through a percutaneous basilic vein approach. Postoperative anticoagulation therapy was not used routinely. Venous duplex ultrasound scanning was performed postoperatively and at 1, 6, and 12 months., Results: Intraoperative venography enabled identification of residual subclavian vein stenosis in 16 patients (64%), and all underwent intraoperative PTA with 100% technical success. Postoperative duplex scans documented subclavian vein patency in 23 patients (92%). Complications included subclavian vein recurrent thrombosis in 2 patients (8%), and both underwent percutaneous mechanical thrombectomy, with restoration of patency in 1 patient. One-year primary and secondary patency rates were 92% and 96%, respectively, at life-table analysis., Conclusions: Residual subclavian vein stenosis after operative thoracic outlet decompression is common in patients with venous thoracic outlet syndrome. Combination treatment with surgical thoracic outlet decompression and intraoperative PTA is a safe and effective means for identifying and treating residual subclavian vein stenosis. Moreover, intraoperative PTA may reduce the incidence of postoperative recurrent thrombosis and eliminate the need for venous stent placement or open venous repair.

Purpose: Current strategies to create small-diameter vascular grafts involve seeding biocompatible, compliant scaffolds with autologous vascular cells. Our purpose was to study the composition and strength of decellularized vein to determine its potential as a vascular tissue-engineering scaffold., Methods: Intact human greater saphenous vein specimens were decellularized by using sodium dodecyl sulfate (SDS). Residual cellular and extracellular matrix composition was studied with light and electron microscopy as well as immunohistochemistry. Burst and suture-holding strength was measured in vitro by insufflation and pull-through techniques. To assess initial handling and durability of decellularized vein in vivo, a canine model was developed wherein decellularized canine jugular veins were implanted as carotid interposition grafts in recipient animals. After two weeks of arterial perfusion, these grafts were studied with duplex imaging and histologic methods., Results: Human saphenous vein decellularized by using SDS was devoid of endothelial cells and >94% of the cells resident within the vein wall. Collagen morphology appeared unchanged, and elastin staining decreased only slightly. Basement membrane collagen type IV remained intact. Compared with fresh vein, decellularized vein had similar in vitro burst (2480 +/- 460 mm Hg vs 2380 +/- 620 mm Hg; P >.05) and suture-holding (185 +/- 30 gm vs 178 +/- 66 gm; P >.05) strength. Decellularized canine vein functioned well in vivo without dilation, anastomotic complication, or rupture over 2 weeks of arterial perfusion., Conclusions: Vein rendered acellular with SDS has well-preserved extracellular matrix, basement membrane structure, and strength sufficient for vascular grafting. These properties suggest proof of concept for its use as a scaffold for further vascular tissue engineering., Clinical Relevance: The following research examines the creation of a new small-diameter bypass graft. It is clinically relevant to patients who need distal arterial bypass, coronary artery bypass, or hemodialysis access, but who do not have adequate autologous vein for their surgeries. Future investigations will involve further tissue engineering of this vascular scaffold (eg, autologous endothelial seeding of its lumen) and testing the clinical usefulness of the completed graft.

Objective: Aortic clamping proximal to the renal arteries is sometimes necessitated during infrarenal and juxtarenal aortic surgery and may be associated with an increased risk of renal ischemia and its consequences. The aim of the study was to estimate this risk and possibly identify a "safe" duration of renal ischemia., Methods: Medical records were retrospectively reviewed for 60 consecutive patients (from 1987 to 1994) with abdominal aortic aneurysm (n = 43) and occlusive disease (n = 17) confined to the infrarenal or juxtarenal aorta who underwent infrarenal aortic reconstruction with temporary suprarenal clamping. The data obtained included risk factors, preoperative and postoperative serum creatinine level, blood urea nitrogen (BUN) value, proteinuria before surgery, and suprarenal clamping times., Results: The mean age of the patients was 64.4 years (+/- 11.4 years), and 74% were men. Concomitant cardiac disease was present in 41% of the patients, and 9% had diabetes. The preoperative creatinine level was 1.21 mg/dL (+/- 0.54 mg/dL), and the BUN value was 16.6 mg/dL (+/- 7.8 mg/dL). During surgery, blood flow to the renal arteries was interrupted for 32.0 minutes (+/- 17 minutes). None of the surviving patients needed dialysis or had signs of acute renal failure after the operations, but transient azotemia (rise in creatinine level) occurred in 23% of the patients. Risk factors for this condition were high preoperative creatinine values and hypotension during surgery, but the main determinant was total renal ischemia time. Odds ratios for such transient renal dysfunction showed as much as a 10-fold risk when suprarenal aortic clamping was greater than 50 minutes as compared with 30 minutes or less., Conclusion: Postoperative renal function impairment is rare in this group of patients. If suprarenal clamp duration (renal ischemia time) is brief, patients with normal preoperative creatinine levels exhibit no increase or a marginal increase in BUN or creatinine levels after surgery. Accordingly, suprarenal aortic clamping less than 50 minutes in this patient group appears safe and well tolerated.

Endograft repair has rapidly become an alternative to conventional open repair of abdominal aortic aneurysms. Various trials continue to show decreased morbidity when compared to open repair. However, as with any new procedure, complications specifically related to this technique are being described. Herein, we report a case of an isolated ischemic jejunal stricture presenting as a small-bowel obstruction secondary to cholesterol emboli following endograft repair of an abdominal aortic aneurysms.

The lateral approach to the distal peroneal artery has been used by vascular surgeons for 25 years. No complications specifically related to this approach have previously been reported. We reviewed 18 cases of peroneal bypass for limb salvage using the lateral approach with fibula resection and found that two of these cases had ipsilateral tibia fractures within 1 year of the bypass. Eight out of 18 cases were women, and two of these eight had tibia fracture. Both women suffered from osteoporosis. We conclude that tibia fracture is a possible complication of this approach, especially in elderly women with osteoporosis.

Vertebral osteomyelitis may occur with mycotic aneurysms or infected aortic grafts. A high index of suspicion for these concurrent processes as well as appropriate preoperative evaluation and interspecialty communication is critical for appropriate diagnosis and treatment. Extraanatomic bypass, wide debridement of necrotic soft tissue and bony structures, and concurrent bony stabilization are important aspects of treatment.

Clostridial infection of the aorta is a rare and life-threatening condition. The management of a mycotic aneurysm involving the thoracoabdominal aorta due to Clostridium septicum infection is presented. Successful surgical management of the aortic infection involved arterial resection, wide debridement of the surrounding tissues, and in situ graft replacement. Sixteen additional cases of clostridial infection of the aortoiliac segment reported in the literature are also summarized. In ten of these 17 cases, an associated colonic adenocarcinoma was documented.

Background: We examined our long-term results of carotid reoperation to identify risk factors for morbidity and secondary recurrence., Methods: Medical record review revealed 27 patients had reoperative surgery for recurrent stenosis. Demographics, operative details, pathology, clinical outcome, and follow-up imaging results were reviewed., Results: No neurologic deficits and no mortalities were noted perioperatively. Long-term follow-up (average 54 months) revealed an 85% 5-year and 29% 10-year estimated survival. The 5- and 10-year estimated neurologic event rates were 15% and 35%, respectively. These included 3 ipsilateral strokes and 1 ipsilateral TIA; only the TIA involved secondary restenosis. Follow-up imaging revealed a 21% incidence of secondary restenosis, occurring more frequently in patients with hyperlipidemia (P < 0.05) and previous contralateral endarterectomy (P < 0.05)., Conclusions: (1) Reoperation provides long-term protection from stroke due to recurrent stenosis. (2) Secondary restenosis rates appear higher than those for primary surgery. (3) Hyperlipidemia and contralateral endarterectomy are risk factors for secondary restenosis.

Purpose: This study was performed to determine the indications, operative strategy, and hemodynamic benefit of redo aortic grafting procedures after earlier excision of an infected aortic graft., Methods: Among 164 patients treated for aortic graft infection, 15 later underwent redo aortic grafting procedures an average of 18 months (range, 1 to 59 months) after removal of an infected aortic graft. Redo grafting procedures were performed for leg ischemia (n = 11) or infection (proven, n = 3; suspected, n = 1). The new aortic graft originated either from the distal thoracic aorta (n = 5) or from the juxtarenal aortic stump (n = 10). Follow-up averaged 56 months (range, 7 to 110 months)., Results: All patients survived the redo grafting procedure. In the eleven patients who had ischemic symptoms, redo grafting procedures uniformly resulted in symptomatic improvement with an increase in ankle-brachial indexes (0.78 +/- 0.34 vs 0.50 +/- 0.29; p = 0.02). A graft limb occlusion developed in two of these patients (3 and 6 months), but no limbs were amputated. In the four patients who had proven or suspected extraanatomic bypass graft infection, there was one graft limb occlusion (29 months) and one amputation (17 months). Overall, recurrent graft infection occurred in three of 15 patients and may be more frequent in patients who have a proven extraanatomic bypass graft infection (2 of 3 vs 1 of 12; p = 0.08). Infection accounted for two of the three graft limb occlusions and two of the three late deaths. Recurrent infection was not associated with early (< 1 year) regrafting procedures, and culture results did not correlate with the microbiologic features of the primary infection., Conclusions: Redo aortic grafting procedures can be performed safely and at relatively early intervals (6 to 12 months) after removal of the infected aortic graft. The procedure reliably relieves ischemic symptoms of the hemodynamically inadequate extraanatomic bypass graft. Reinfection remains a risk after redo aortic grafting procedures, particularly when treating established extraanatomic bypass graft infection.

Purpose: We examined the effect of thrombin on human iliac artery endothelial cell monolayer repair and proliferation after denuding vascular injury., Methods: Human iliac artery endothelial cell monolayer repair was determined by scrape wounding confluent monolayers and measuring the advancement of the cells into the wounded area for 3 days. Proliferation studies involved plating human iliac artery endothelial cells at one tenth confluence and counting the increase in cell number every 2 days for a 2-week period. Proliferation during monolayer repair was examined by determining bromodeoxyuridine uptake in cells located at the leading edge of a scrape-wounded monolayer., Results: Thrombin (1 to 8 U/ml) inhibited human iliac artery endothelial cell monolayer repair in a concentration-related, reversible manner. The effect was augmented by decreasing serum concentration and was independent of the presence of endothelial cell growth supplement. Inactivation of thrombin's proteolytic site with diisopropylfluorophosphate eliminated its effect on monolayer repair. Thrombin (0.5 to 8 U/ml) inhibited human iliac artery endothelial cell proliferation in a dose-related manner. This effect was augmented by decreasing serum concentration. Finally, thrombin (4 U/ml) inhibited the proliferative response of cells located at the leading edge of wounded monolayers compared with control groups., Conclusion: Thrombin inhibits human arterial endothelial cell monolayer repair and proliferation after denuding vascular injury.