The two-stage brachial artery–brachial vein autogenous fistula for hemodialysis: An alternative autogenous option for hemodialysis access

The optimal dialysis access for the patient with chronic renal failure is considered to be an autogenous fistula; this is reflected in the recommendations of the National Kidney Foundation–Disease Outcomes Quality Initiatives (NKF-DOQI). If adequate superficial veins at the wrist or the forearm are not available, the next option is usually a prosthetic arteriovenous graft. In this case series, we describe our experience with an autogenous fistula constructed using the brachial vein. There were 20 patients over a 14-month period who were operated on for dialysis access. In these patients, no adequate superficial veins were found at operation. Instead of using a prosthetic graft, we performed a brachial artery–brachial vein fistula in two stages. The first stage involved a forearm anastomosis and then subsequently, weeks later, this fistula was “superficialized.” Twenty patients underwent a brachial artery–brachial vein fistula. Of these patients, all had successful maturation of their fistula and after a minimum waiting period of 12 weeks for maturation; all but one were able to be successfully dialyzed through their fistula. One patient developed arm swelling due to previously placed subclavian vein pacemaker wires. None of the other patients developed arm swelling or vascular steal. The brachial artery–brachial vein fistula is a feasible option for hemodialysis access and we suggest that this option be considered before a prosthetic arteriovenous graft is inserted. Arm swelling and steal have not been a problem, and all patients have been able to have full dialysis through the fistula after appropriate maturation times

Allogeneic endometrial regenerative cells: An "Off the shelf solution" for critical limb ischemia?

Critical limb ischemia (CLI) is an advanced form of peripheral artery disease which is responsible for approximately 100,000 amputations per year in the US. Trials to date have reported clinical improvement and reduced need for amputation in CLI patients receiving autologous bone marrow or mobilized peripheral blood stem cells for stimulation of angiogenesis. While such treatments are currently entering Phase III trials, practical and scientific pitfalls will limit widespread implementation if efficacy is proven. Hurdles to be overcome include: a) reduced angiogenic potential of autologous cells in aged patients with cardiovascular risk factors; b) invasiveness/adverse effects of bone marrow extraction and G-CSF mobilization, respectively; and c) need for on-site cellular manipulation. The Endometrial Regenerative Cell (ERC) is a mesenchymal-like stem cell derived from the menstrual blood that is believed to be associated with endometrial angiogenesis. We discuss the possibility of using allogeneic ERCs as an "off the shelf" treatment for CLI based on the following properties: a) High levels of growth factors and matrix metalloprotease production; b) Ability to inhibits inflammatory responses and lack of immunogenicity; and c) Expandability to great quantities without loss of differentiation ability or karyotypic abnormalities

A role for VEGF as a negative regulator of pericyte function and vessel maturation.

Angiogenesis does not only depend on endothelial cell invasion and proliferation: it also requires pericyte coverage of vascular sprouts for vessel stabilization. These processes are coordinated by vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) through their cognate receptors on endothelial cells and vascular smooth muscle cells (VSMCs), respectively. PDGF induces neovascularization by priming VSMCs/pericytes to release pro-angiogenic mediators. Although VEGF directly stimulates endothelial cell proliferation and migration, its role in pericyte biology is less clear. Here we define a role for VEGF as an inhibitor of neovascularization on the basis of its capacity to disrupt VSMC function. Specifically, under conditions of PDGF-mediated angiogenesis, VEGF ablates pericyte coverage of nascent vascular sprouts, leading to vessel destabilization. At the molecular level, VEGF-mediated activation of VEGF-R2 suppresses PDGF-Rbeta signalling in VSMCs through the assembly of a previously undescribed receptor complex consisting of PDGF-Rbeta and VEGF-R2. Inhibition of VEGF-R2 not only prevents assembly of this receptor complex but also restores angiogenesis in tissues exposed to both VEGF and PDGF. Finally, genetic deletion of tumour cell VEGF disrupts PDGF-Rbeta/VEGF-R2 complex formation and increases tumour vessel maturation. These findings underscore the importance of VSMCs/pericytes in neovascularization and reveal a dichotomous role for VEGF and VEGF-R2 signalling as both a promoter of endothelial cell function and a negative regulator of VSMCs and vessel maturation

A role for VEGF as a negative regulator of pericyte function and vessel maturation.

Angiogenesis does not only depend on endothelial cell invasion and proliferation: it also requires pericyte coverage of vascular sprouts for vessel stabilization. These processes are coordinated by vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) through their cognate receptors on endothelial cells and vascular smooth muscle cells (VSMCs), respectively. PDGF induces neovascularization by priming VSMCs/pericytes to release pro-angiogenic mediators. Although VEGF directly stimulates endothelial cell proliferation and migration, its role in pericyte biology is less clear. Here we define a role for VEGF as an inhibitor of neovascularization on the basis of its capacity to disrupt VSMC function. Specifically, under conditions of PDGF-mediated angiogenesis, VEGF ablates pericyte coverage of nascent vascular sprouts, leading to vessel destabilization. At the molecular level, VEGF-mediated activation of VEGF-R2 suppresses PDGF-Rbeta signalling in VSMCs through the assembly of a previously undescribed receptor complex consisting of PDGF-Rbeta and VEGF-R2. Inhibition of VEGF-R2 not only prevents assembly of this receptor complex but also restores angiogenesis in tissues exposed to both VEGF and PDGF. Finally, genetic deletion of tumour cell VEGF disrupts PDGF-Rbeta/VEGF-R2 complex formation and increases tumour vessel maturation. These findings underscore the importance of VSMCs/pericytes in neovascularization and reveal a dichotomous role for VEGF and VEGF-R2 signalling as both a promoter of endothelial cell function and a negative regulator of VSMCs and vessel maturation

Percutaneous intervention for infrainguinal occlusive disease in women: equivalent outcomes despite increased severity of disease compared with men

Experience with open surgical bypass suggests similar overall outcomes in women compared with men, but significantly increased risk of wound complications. Percutaneous treatment of lower extremity occlusive disease is therefore an attractive alternative in women, although it is not clear whether there is a difference in outcomes between women and men treated with this technique. We sought to determine the results and predictors of failure in women treated by percutaneous intervention. Percutaneous infrainguinal revascularization was performed on 309 women between 2001 and 2006. Procedures, complications, demographics, comorbidities, and follow-up data were entered into a prospective database for review. Patency was assessed primarily by duplex ultrasonography. Outcomes were expressed by Kaplan-Meier curves and compared by log-rank analysis. A total of 447 percutaneous interventions performed in 309 women were analyzed and compared with 553 interventions in men. Mean age in women was 73.2 years; comorbidities included hypertension (HTN) (86%), diabetes melitus (DM) (58%), chronic renal insufficiency (CRI) (15%), hemodialysis (7%), hypercholesterolemia (52%), coronary artery disease (CAD) (42%), and tobacco use (47%). Indications in women included claudication (38.0%), rest pain (18.8%), and tissue loss (43.2%). Overall primary & secondary patency and limb-salvage rates for women were 38% +/- 4%, 66% +/- 3%, and 80% +/- 4% at 24 months. In this patient sample, women were significantly more likely than men to present with limb-threatening ischemia (61.6% vs 47.3%, P < 0.001) and have lesions of TASC C and D severity (71.4% vs 61.7%, P < .005). However, there were no significant differences in primary and secondary patency rates or limb-salvage rates between genders. Furthermore, while women with limb-threat, diabetes, and advanced TASC severity lesions were at increased risk of failure overall, there were no differences between women and men with these characteristics. Percutaneous infrainguinal revascularization is a very effective modality in women with lower extremity occlusive disease. Although women in this sample were more likely to present with limb-threat than men, patency and limb-salvage rates were equivalent between genders, even in high-risk subsets such as diabetics or those with lesions of increased TASC severity

The Society for Vascular Surgery clinical practice guidelines on popliteal artery aneurysms

The Society for Vascular Surgery clinical practice guidelines on popliteal artery aneurysms (PAAs) leverage the work of a panel of experts chosen by the Society for Vascular Surgery to review the current world literature as it applies to PAAs to extract the most salient, evidence-based recommendations for the treatment of these patients. These guidelines focus on PAA screening, indications for intervention, choice of repair strategy, management of asymptomatic and symptomatic PAAs (including those presenting with acute limb ischemia), and follow-up of both untreated and treated PAAs. They offer long-awaited evidence-based recommendations for physicians taking care of these patients