Jianming Guo

Future research directions to improve fistula maturation and reduce access failure

With the increasing prevalence of end-stage renal disease, there is a growing need for hemodialysis. Arteriovenous fistulae (AVF) are the preferred type of vascular access for hemodialysis, but maturation and failure continue to present significant barriers to successful fistula use. AVF maturation integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes in the setting of uremia, systemic inflammation, oxidative stress, and pre-existent vascular pathology. AVF can fail due to both failure to mature adequately to support hemodialysis and development of neointimal hyperplasia that narrows the AVF lumen, typically near the fistula anastomosis. Failure due to neointimal hyperplasia involves vascular cell activation and migration and extracellular matrix remodeling with complex interactions of growth factors, adhesion molecules, inflammatory mediators, and chemokines, all of which result in maladaptive remodeling. Different strategies have been proposed to prevent and treat AVF failure based on current understanding of the modes and pathology of access failure; these approaches range from appropriate patient selection and use of alternative surgical strategies for fistula creation, to the use of novel interventional techniques or drugs to treat failing fistulae. Effective treatments to prevent or treat AVF failure require a multidisciplinary approach involving nephrologists, vascular surgeons, and interventional radiologists, careful patient selection, and the use of tailored systemic or localized interventions to improve patient-specific outcomes. This review provides contemporary information on the underlying mechanisms of AVF maturation and failure and discusses the broad spectrum of options that can be tailored for specific therapy.

Polyester vascular patches acquire arterial or venous identity depending on their environment

Polyester is commonly used in vascular surgery for patch angioplasty and grafts. We hypothesized that polyester patches heal by infiltration of arterial or venous progenitor cells depending on the site of implantation. Polyester patches were implanted into the Wistar rat aorta or inferior vena cava and explanted on day 7 or 30. Neointima that formed on polyester patches was thicker in the venous environment compared to the amount that formed on patches in the arterial environment. Venous patches had more cell proliferation and greater numbers of VCAM-positive and CD68-positive cells, whereas arterial patches had greater numbers of vimentin-positive and alpha-actin-positive cells. Although there were similar numbers of endothelial progenitor cells in the neointimal endothelium, cells in the arterial patch were Ephrin-B2- and notch-4-positive while those in the venous patch were Eph-B4- and COUP-TFII-positive. Venous patches treated with an arteriovenous fistula had decreased neointimal thickness; neointimal endothelial cells expressed Ephrin-B2 and notch-4 in addition to Eph-B4 and COUP-TFII. Polyester patches in the venous environment acquire venous identity, whereas patches in the arterial environment acquire arterial identity; patches in the fistula environment acquire dual arterial-venous identity. These data suggest that synthetic patches heal by acquisition of identity of their environment.

Stem cell therapy for diabetic foot ulcers: a review of preclinical and clinical research

BackgroundDiabetic foot ulcer (DFU) is a severe complication of diabetes, preceding most diabetes-related amputations. DFUs require over US

Three-Year Clinical Results of Carotid Artery Stenting in Treating Patients with Contralateral Carotid Artery Occlusion

9 billion for yearly treatment and are now a global public health issue. DFU occurs in the setting of ischemia, infection, neuropathy, and metabolic disorders that result in poor wound healing and poor treatment options. Recently, stem cell therapy has emerged as a new interventional strategy to treat DFU and appears to be safe and effective in both preclinical and clinical trials. However, variability in the stem cell type and origin, route and protocol for administration, and concomitant use of angioplasty confound easy interpretation and generalization of the results.MethodsThe PubMed, Google Scholar, and EMBASE databases were searched and 89 preclinical and clinical studies were selected for analysis.ResultsThere was divergence between preclinical and clinical studies regarding stem cell type, origin, and delivery techniques. There was heterogeneous preclinical and clinical study design and few randomized clinical trials. Granulocyte-colony stimulating factor was employed in some studies but with differing protocols. Concomitant performance of angioplasty with stem cell therapy showed increased efficiency compared to either therapy alone.ConclusionsStem cell therapy is an effective treatment for diabetic foot ulcers and is currently used as an alternative to amputation for some patients without other options for revascularization. Concordance between preclinical and clinical studies may help design future randomized clinical trials.

Transforming Growth Factor-β1 Inhibits Pseudoaneurysm Formation After Aortic Patch Angioplasty

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

Angiojet rheolytic thrombectomy combined with catheter fragmentation in a patient presenting with massive pulmonary embolism and cardiogenic shock

Objective— Pseudoaneurysms remain a significant complication after vascular procedures. We hypothesized that TGF-&bgr; (transforming growth factor-&bgr;) signaling plays a mechanistic role in the development of pseudoaneurysms. Approach and Results— Rat aortic pericardial patch angioplasty was associated with a high incidence (88%) of pseudoaneurysms at 30 days, with increased smad2 phosphorylation in small pseudoaneurysms but not in large pseudoaneurysms; TGF-&bgr;1 receptors were increased in small pseudoaneurysms and preserved in large pseudoaneurysms. Delivery of TGF-&bgr;1 via nanoparticles covalently bonded to the patch stimulated smad2 phosphorylation both in vitro and in vivo and significantly decreased pseudoaneurysm formation (6.7%). Inhibition of TGF-&bgr;1 signaling with SB431542 decreased smad2 phosphorylation both in vitro and in vivo and significantly induced pseudoaneurysm formation by day 7 (66.7%). Conclusions— Normal healing after aortic patch angioplasty is associated with increased TGF-&bgr;1 signaling, and recruitment of smad2 signaling may limit pseudoaneurysm formation; loss of TGF-&bgr;1 signaling is associated with the formation of large pseudoaneurysms. Enhancement of TGF-&bgr;1 signaling may be a potential mechanism to limit pseudoaneurysm formation after vascular intervention.

A comparative study of percutaneous atherectomy for femoropopliteal arterial occlusive disease

Massive pulmonary embolism (MPE) is associated with a high rate of mortality, and chronic thromboembolic pulmonary hypertension leads to ongoing morbidity among many survivors. Here we report a case of a MPE successfully treated by Angiojet rheolytic thrombectomy combined with catheter fragmentation. This is the first report of the use of these two methods together for MPE treatment.

Meta-analysis on the treatment of diabetic foot ulcers with autologous stem cells

BACKGROUND SilverHawk™ directional atherectomy has been used to treat more than 300 thousand cases of lower extremity atherosclerotic occlusive disease in the world since it was approved by FDA in 2003. This study aimed to analyze the safety and effectiveness of symptomatic femoral popliteal atherosclerotic disease treated by directional atherectomy (DA). METHODS Clinical data of all consecutive patients treated with percutaneous atherectomy utilizing the SilverHawk™ plaque excision was retrospectively analyzed. The anatomic criteria of the atherosclerotic lesions were divided into four types: type I stenosis; type II occlusion; type III in-stent restenosis; type IV stent occlusion. RESULTS There were 160 patients treated during the study period. Intermittent claudication in 75 patients (47%), rest pain in 55 patients (34.5%) and tissue loss in 30 patients (18.5%). The number of patients was 72, 15, 49 and 24 in type I, II, III and IV lesions, respectively. Technical success rate was 98.6%, 93.3%, 97.9% and 91.7% in type I, II, III and IV lesions, respectively. Debris of intimal plaque was captured by protection device in 92 patients (71.3%). The mean follow-up period was 23.5±10.4 months. Restenosis rate of type I to IV lesions was 21%, 36%, 36% and 40% respectively. Restenosis rate in type I lesion was significantly lower than that in type III and IV lesions (P<0.05). Patients with tissue loss responded to revascularization as follow: type I, 11/13 healed or reduced (84.6%), type II, 3/3 patients improved (100%), type III, 5/6 patients improved (83.3%) and type IV 4/4 healed (100%). In type IV group, four patients had in-stent thrombosis found by postoperative Duplex ultrasonography. They all underwent DA after catheter-directed thrombolysis with good angiographic results. CONCLUSIONS Percutaneous DA is safe and effective for both de-novo atherosclerotic and in-stent stenotic or occlusive lesions. Thrombolysis before plaque excision is recommended in case of in-stenting thrombosis.