Rationale and design of a single-center randomized trial to compare the graft patency between the radial artery and the no-touch saphenous vein in coronary artery bypass grafting surgery (GRAFT-CAB Study).

BACKGROUND: Previous studies suggested only the radial artery and the No-touch (NT) technique were effective in reducing graft occlusion after coronary artery bypass grafting (CABG) surgery. However, there is no randomized trial comparing these 2 graft conduits. The optimum second conduit for CABG remains undetermined. MATERIALS AND METHODS: This study is a prospective, single-center randomized clinical trial, aiming to compare the graft patency between the radial artery and the NT vein graft. All patients undergoing isolated CABG with left internal mammary artery (LIMA) plus at least 2 additional grafts will be considered eligible. About 774 cases (516 in the radial artery group and 258 in the NT vein group) will be enrolled in over 1 to 2 years. Participants will be randomized and allocated to two bypass strategies: the LIMA plus 1 radial artery and 1 conventional vein graft, or the LIMA plus 2 NT vein grafts. The primary outcome is graft occlusion at 1 year after CABG evaluated by CT angiography. The secondary outcomes include graft occlusion at 3 and 5 years and major adverse cardiac or cerebrovascular events at 1, 3, and 5 years follow-ups. DISCUSSION: This study will define whether or not the NT vein has a lower graft occlusion rate than the radial artery in short and mid-term follow-ups, and provide new evidence for the second conduit choice in CABG surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT06014047. Registered on October 15th, 2023.

Omentin reduces venous neointimal hyperplasia in arteriovenous fistula through hypoxia-inducible factor-1 alpha inhibition.

Arteriovenous fistula (AVF) failure often involves venous neointimal hyperplasia (VNH) driven by elevated hypoxia-inducible factor-1 alpha (HIF-1α) in the venous wall. Omentin, known for its anti-inflammatory and anti-hyperplasia properties, has an uncertain role in early AVF failure. This study investigates omentin's impact on VNH using a chronic renal failure (CRF) rabbit model. The CRF rabbit model of AVF received omentin-expressing adenoviral vector or control ß-gal vector to assess omentin's effects on VNH. Human vascular smooth muscle cells (HVSMCs), stimulated with tumor necrosis factor-α (TNF-α), were exposed to recombinant human omentin (Rh-OMT) to study its influence on cell proliferation and migration. The AMP-activated protein kinase (AMPK) inhibitor compound C and the mammalian target of rapamycin (mTOR) activator MHY1485 were employed to explore omentin's mechanisms in VNH reduction through HIF-1α inhibition. Omentin treatment reduced VNH in CRF rabbits, concomitant with HIF-1α down-regulation and the suppression of downstream factors, including vascular endothelial growth factor and matrix metalloproteinases. Rh-OMT inhibited TNF-α-induced HVSMC proliferation and migration by modulating both cell cycle and cell adhesion proteins. Additionally, omentin reduced HIF-1α expression through the AMPK/mTOR pathway activation. Notably, the blockade of AMPK/mTOR signaling reversed omentin-mediated inhibition of VNH, cell proliferation, and migration, both in vivo and in vitro. In conclusion, omentin mitigates VNH post-AVF creation by restraining HIF-1α via AMPK/mTOR signaling. Strategies boosting circulating omentin levels may offer promise in averting AVF failure.

The Effect of Angiotensin Receptor Blockers on In-Stent Restenosis After Stent Implantation: A Meta-Analysis.

AIM: Angiotensin receptor blockers (ARBs) have been shown to inhibit restenosis in vitro and in vivo, but the evidence found in humans is inconsistent. This study aimed to evaluate the effectiveness of ARBs in preventing in-stent restenosis after percutaneous coronary intervention (PCI). METHOD: Databases including the Cochrane Library, MEDLINE, Web of Science, EMBASE, and CNKI were searched to collect randomised controlled trials on ARBs inhibiting restenosis that were published before October 2022. A total of 1,056 patients enrolled in eight trials were included in the study. RESULTS: The ARBs group showed lower target lesion revascularisation than the control group (RR 0.54; 95% CI 0.34-0.86; p=0.01), but the restenosis incidence between these two groups was not statistically significant (RR 0.85; 95% CI 0.65-1.11; p>0.05). CONCLUSION: This study found that ARBs might have a potential effect on reducing target lesion revascularisation after PCI in coronary heart disease patients but has no impact on angiographic restenosis.

Ticagrelor versus aspirin and vein graft patency after coronary bypass: A randomized trial.

BACKGROUND: Antiplatelet therapy prevents saphenous vein graft (SVG) occlusion and improves outcomes after coronary artery bypass graft surgery (CABG). However, the optimal postoperative antiplatelet regimen remains unclear. The goal of the Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET) trial was to assess whether early postoperative ticagrelor reduces SVG occlusion compared to conventional aspirin therapy. METHODS: In this multi-center double-blind randomized trial, 250 patients who had CABG with SVG were randomized to receive either aspirin 81 mg twice daily or ticagrelor 90 mg twice daily. The primary outcome was SVG occlusion at 1 year. RESULTS: Altogether, 123 patients were randomized to aspirin and 127 received ticagrelor. One-year graft assessment was performed in 202 patients (80.8%), examining 588 grafts, yielding an overall graft occlusion rate of 10.9%. The primary outcome, SVG occlusion at 1 year, did not significantly differ between the two groups (17.4% vs. 13.2%, aspirin vs. ticagrelor, p = .30). The incidence of vein grafts with any disease (stenosis or occlusion) did not significantly differ between the groups (21.5% vs. 22.3%, aspirin vs. ticagrelor, p = .90), and the number of patients with vein graft disease did not significantly differ between the groups (29.4% vs. 28.0%, aspirin vs. ticagrelor, p = .88). Freedom from major adverse cardiovascular events at 1 year was similar between the groups (p = .60). CONCLUSIONS: Compared to conventional aspirin therapy, ticagrelor did not significantly reduce vein graft occlusion 1 year after CABG. Further study will assess the impact of ticagrelor on 2-year graft patency for this cohort.

Commentary: Prevention of saphenous vein graft disease remains elusive.

One-year outcomes of Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET), a randomized double-blinded clinical trial comparing post-coronary artery bypass surgery antiplatelet therapy with ticagrelor versus aspirin are published in this issue of the Journal. Although the authors did not detect statistically significant differences in their primary outcome (saphenous vein graft patency at 1 year) and major adverse cardiovascular events, their findings must be interpreted with caution given important limitations in the design and execution of the trial.

Ticagrelor versus aspirin 2 years after coronary bypass: Observational analysis from the TARGET trial.

BACKGROUND: Compared to conventional aspirin therapy, ticagrelor did not improve vein graft patency 1 year after coronary bypass surgery (CABG) in the ticagrelor antiplatelet therapy to reduce graft events and thrombosis (TARGET) trial. However, it is unknown whether ticagrelor may impact graft patency long-term following surgery. METHODS: In the TARGET multicenter trial, 250 CABG patients were randomized to aspirin 81 mg or ticagrelor 90 mg twice daily. In this observational analysis, 2 years after surgery, vein graft occlusion and clinical events were compared among subjects who agreed to a second year of double-blind study drug administration (N = 156). RESULTS: Two-year graft assessment was performed for 142 patients (80 aspirin patients, 62 ticagrelor patients, 425 total grafts), with an overall 2-year graft occlusion rate of 10.6%. Vein graft occlusion at 2 years, the primary outcome of this study, did not significantly differ between the two groups (15.7% vs. 13.2%, aspirin vs. ticagrelor, p = .71). The incidence of vein grafts with any disease (stenosis or occlusion) did not significantly differ between the groups (19.4% vs. 19.8%, aspirin vs. ticagrelor, p = 1.00), and the number of patients with vein graft disease did not significantly differ between the groups (30.0% vs. 29.0%, aspirin vs. ticagrelor, p = 1.00). Vein grafts developing new disease did not significantly differ between the two groups (1.5% vs. 3.8%, aspirin vs. ticagrelor, p = .41). Freedom from major adverse cardiovascular events at 2 years was similar between the groups (p = .75). CONCLUSION: Compared to conventional aspirin therapy, ticagrelor did not significantly reduce vein graft disease 2 years after CABG.

Predictors of vein graft disease progression between one week and one year after surgical coronary revascularization: Impact of secondary prevention medications.

OBJECTIVE: This study aimed to detect the predictors of vein graft disease (VGD) progression between 1 week and 1 year after surgery and to evaluate the impact of secondary prevention medications. METHODS: A total of 218 consecutive patients underwent surgical coronary revascularization were evaluated by coronary computed tomography angiography both at 1-week and 1-year follow-up. Logistic regression analyses were performed to investigate the predictors of VGD progression. A risk score (0-4) was set up to evaluate implementation result of secondary prevention measures according to 1-year follow-up result. Association between VGD progression and the risk score was assessed. RESULTS: VGD progression occurred in 11.3% of saphenous vein grafts (SVG) and 22.1% of patients. At the patient level, poor vein graft (odds ratio [OR] = 4.25), noncontrolled hyperlipidemia (OR = 3.01), and diabetes mellitus (DM) (OR = 2.96) were predictors, while diameter of SVG (mm, OR = 0.35) was protective factor. At the graft level, DM (OR = 3.52), noncontrolled hyperlipidemia (OR = 2.33), and peripheral artery disease (PAD) (OR = 2.20) were predictors, while number of SVGs (OR = 0.63), diameter of SVG (mm, OR = 0.39), and mean graft flow >25 ml/min (OR = 0.35) were protective factors. VGD progression was significantly associated with the risk score at both the patient (OR = 1.52) and the graft level (OR = 1.38). CONCLUSIONS: Poor vein graft, noncontrolled hyperlipidemia and DM were predictors of VGD progression between 1 week and 1 year after surgery at the patient level, while larger SVG diameter was a protective factor. DM, PAD and noncontrolled hyperlipidemia were predictors at the graft level, while a number of SVGs, larger SVG diameter, and mean graft flow >25 ml/min were protective factors. Implementation failure of secondary prevention medications was associated with VGD progression from as early as 1 year after surgery.

Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis.

Importance: The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear. Objective: To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery. Data Sources: MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction. Study Selection: Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure. Data Extraction and Synthesis: Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used. Main Outcomes and Measures: The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin. Results: A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, -8.7% [95% CI, -13.5% to -3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, -9.7% [95% CI, -14.9% to -4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, -1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, -2.6% [95% CI, -9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, -2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46). Conclusions and Relevance: Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.

Effect of Adding Ticagrelor to Standard Aspirin on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting (POPular CABG): A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Approximately 15% of saphenous vein grafts (SVGs) occlude during the first year after coronary artery bypass graft surgery (CABG) despite aspirin use. The POPular CABG trial (The Effect of Ticagrelor on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting Surgery) investigated whether ticagrelor added to standard aspirin improves SVG patency at 1 year after CABG. METHODS: In this investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial, patients with ≥1 SVGs were randomly assigned (1:1) after CABG to ticagrelor or placebo added to standard aspirin (80 mg or 100 mg). The primary outcome was SVG occlusion at 1 year, assessed with coronary computed tomography angiography, in all patients that had primary outcome imaging available. A generalized estimating equation model was used to perform the primary analysis per SVG. The secondary outcome was 1-year SVG failure, which was a composite of SVG occlusion, SVG revascularization, myocardial infarction in myocardial territory supplied by a SVG, or sudden death. RESULTS: Among 499 randomly assigned patients, the mean age was 67.9±8.3 years, 87.1% were male, the indication for CABG was acute coronary syndrome in 31.3%, and 95.2% of procedures used cardiopulmonary bypass. Primary outcome imaging was available in 220 patients in the ticagrelor group and 223 patients in the placebo group. The SVG occlusion rate in the ticagrelor group was 10.5% (51 of 484 SVGs) versus 9.1% in the placebo group (43 of 470 SVGs), odds ratio, 1.29 [95% CI, 0.73-2.30]; P=0.38. SVG failure occurred in 35 (14.2%) patients in the ticagrelor group versus 29 (11.6%) patients in the placebo group (odds ratio, 1.22 [95% CI, 0.72-2.05]). CONCLUSIONS: In this randomized, placebo-controlled trial, the addition of ticagrelor to standard aspirin did not reduce SVG occlusion at 1 year after CABG. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02352402.

External stenting and disease progression in vein grafts 1 year after open surgical repair of popliteal artery aneurysm.

OBJECTIVE: Open surgical repair remains the gold standard treatment for popliteal artery aneurysms (PAA). The objective of this study was to evaluate the safety of external stenting and its medium-term effect on vein graft disease after open PAA repair. METHODS: Between December 2017 and September 2019, 12 consecutive patients with PAA underwent open surgical repair with externally stented saphenous vein grafts. Duplex ultrasound scanning of the grafts was performed at discharge and at 3, 6, and 12 months after the procedure to evaluate graft patency, average lumen diameter and lumen uniformity. RESULTS: Eleven patients underwent aneurysm ligation and bypass grafting and one patient was treated with aneurysm exclusion and interposition of a venous segment. External stenting of the vein graft was successful in all patients. The mean follow-up time was 12 months (range, 7-17 months), with a primary patency rate of 100% and no graft revisions or reinterventions. The mean lumen diameters at 3, 6, and 12 months were 5.9 ± 1.2 mm, 5.7 ± 0.8 mm, and 5.7 ± 0.7 mm, respectively, with no significant changes between 3 and 6 (P = .34) and between 6 and 12 months (P = .34). The coefficient of variance at 3, 6, and 12 months was 8.2 ± 9.3, 9.4 ± 7.2, and 10.4 ± 8.9, respectively, with no significant change between 3 and 6 months (P = .78) or 6 and 12 months (P = .98). No mortality or amputations were recorded throughout the follow-up period. CONCLUSIONS: External stenting of vein grafts in open surgical repair of PAA is feasible and safe. This technique may potentially improve the outcomes of surgical repair in patients with PAA.

Effects of dual antiplatelet therapy on graft patency after lower extremity bypass.

OBJECTIVE: Current guidelines recommend single-agent antiplatelet therapy for patients with symptomatic peripheral artery disease and consideration of dual antiplatelet therapy (DAPT) after surgical revascularization. The objective of this study was both to explore prescribing patterns of single antiplatelet therapy vs DAPT after lower extremity bypass surgery and to investigate the effects of antiplatelet therapy on bypass graft patency. METHODS: A retrospective analysis of prospectively collected nonemergent infrainguinal lower extremity bypass operations entered in the national Vascular Quality Initiative (2003-2018) with captured long-term follow-up was performed. Patients discharged on aspirin monotherapy or DAPT were identified. Linear regression investigated temporal trends in antiplatelet use. Multivariable Cox regression investigated predictors of primary, primary assisted, and secondary patency. RESULTS: Of the 13,020 patients investigated, 52.2% were discharged on aspirin monotherapy and 47.8% on DAPT. The proportion of patients discharged on DAPT increased from 10.6% in 2003 to 60.6% in 2018 (P < .001). The DAPT cohort was younger, had higher rates of medical (hypertension, diabetes, congestive heart failure, chronic obstructive pulmonary disease) and atherosclerotic (coronary artery disease, prior coronary artery bypass graft or percutaneous coronary intervention, prior lower extremity intervention) comorbidities, and had higher risk bypass procedures (more distal targets, prior inflow bypass procedure, prosthetic conduit use). Multivariable Cox regression analysis did not show any difference between the DAPT and aspirin cohorts in primary patency (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.88-1.10; P = .78), primary assisted patency (HR, 0.93; 95% CI, 0.80-1.07; P = .30), or secondary patency (HR, 0.88; 95% CI, 0.74-1.06; P = .18). On subgroup analysis based on bypass conduit, DAPT was found to have a protective effect on patency only in the prosthetic bypass cohort (primary patency: HR, 0.81 [95% CI, 0.66-1.00; P = .05]; primary assisted patency: HR, 0.74 [95% CI, 0.58-0.94; P = .01]; and secondary patency: HR, 0.60 [95% CI, 0.44-0.82; P < .001]). No patency differences were observed on adjusted subgroup analysis for the other bypass conduits. CONCLUSIONS: A significant and increasing proportion of patients are discharged on DAPT after lower extremity bypass revascularization. These patients represent a higher risk cohort with more medical comorbidities and higher risk bypass features. After controlling for these differences, DAPT therapy had no beneficial effect on overall bypass graft patency or major adverse limb events. However, on subgroup analysis, DAPT was associated with improved bypass graft patency in patients receiving prosthetic bypass conduits. Further study is warranted to investigate optimal duration of DAPT therapy and its possible bleeding complications in prosthetic bypass patients.

Drug-coated balloon angioplasty for failing haemodialysis access: meta-analysis of randomized clinical trials.

BACKGROUND: Arteriovenous fistulas, a major treatment for end-stage kidney disease, frequently require endovascular reinterventions to maintain haemodialysis function. Drug-coated angioplasty balloons (DCBs) were developed with the intention of reducing reintervention rates. The aim of this study was to perform a systematic review and meta-analysis of DCBs in the treatment of failing haemodialysis access. METHODS: Electronic databases were searched systematically to identify all relevant RCTs and any follow-up studies from RCTs. Pooled estimates of dichotomous outcomes were calculated using the odds ratio (OR) and 95 per cent confidence interval. Effect data are presented as summary hazard ratio and 95 per cent confidence interval. RESULTS: Some 19 studies from 18 RCTs and comprising 1898 patients were included in the meta-analysis. Compared with plain balloon angioplasty (PBA), DCB use was associated with higher target-lesion primary patency (HR 0.60, 95 per cent c.i. 0.45 to 0.79), access-circuit primary patency (HR 0.67, 0.56 to 0.80), and less target-lesion revascularization (TLR) within 6 months (OR 0.33, 0.23 to 0.47). No difference was observed between DCB and PBA in 12-month TLR (OR 0.62, 0.28 to 1.37). Mortality after DCB use was similar to that associated with PBA use at 6 months (OR 1.20, 0.65 to 2.21) and 12 months (OR 0.99, 0.66 to 1.49), and was higher at 24 months (23.1 versus 16.6 per cent), although the difference was not statistically significant (OR 1.53, 0.92 to 2.53). CONCLUSION: Drug-coated balloon angioplasty of haemodialysis fistulas is associated with higher patency rates and lower rates of reintervention in the short to mid term. Although mortality rates appeared to be higher with drug-coated angioplasty at 24 months, this did not reach statistical significance.

The PROTAGORAS 2.0 Study to Identify Sizing and Planning Predictors for Optimal Outcomes in Abdominal Chimney Endovascular Procedures.

OBJECTIVE: The aim was to identify predictors of adequate pre-operative sizing and planning for chimney endovascular aortic repair (ChEVAR) in order to reduce the incidence of persistent type Ia endoleaks (IaELs) without influencing chimney graft (CG) patency. METHODS: Consecutive patients who underwent ChEVAR between January 2009 and December 2017 at a single centre were evaluated retrospectively. Included were patients treated with one device combination (Medtronic Endurant mated with Getinge Advanta V12/iCast) and placement of single or double CG. The freedom from IaEL related re-interventions and primary CG patency was estimated by measuring aortic stent graft oversizing (OS), total neck length (TNL), and a composite parameter (L-OS: TNL [mm] + OS [%]). RESULTS: Seventy-three patients who underwent placement of 101 CGs (45 single, 28 double) met the inclusion criteria. The median radiological follow up was 25.5 (interquartile range [IQR] 12-48) months. Freedom from IaEL related re-intervention was achieved in 94.6% with a median OS of 38.5% (IQR 30%-44%, p = .004), TNL 19 mm (16-25 mm, p = .62), and L-OS 59 (51-65, p = .018). Primary CG patency was achieved in 95% of the cases with a median OS of 36% (29%-42%, p = .008), TNL 19 mm (15.5-26 mm, p = .91), and L-OS 57 (50-64, p = .005). By using the receiver operating characteristic curve, an optimal cut off to prevent IaEL related re-interventions was identified by an OS of 30% (p < .001; L-OS 55, p = .006) and to avoid CG stenosis/occlusions by OS 42% (p < .001; L-OS 65, p < .001). In multivariable analysis, aortic endograft OS was the only independent parameter preventive for IaEL related re-intervention (odds ratio, 0.78; 95% confidence interval, 0.61-0.99). CONCLUSION: With the Endurant-Advanta V12/iCast combination, an aortic stent graft OS of at least 30% (range 30%-42%) should be used to avoid type Ia endoleaks and likewise to ensure CG patency.

Outflow vein venoplasty of left lateral section graft for living donor liver transplantation in infant recipients.

The orifice size of the LHV trunk in LLS grafts is often too small for direct anastomosis. Several methods were developed to enlarge the graft and recipient hepatic vein orifices. This study described our surgical techniques to secure hepatic vein reconstruction in infant recipients and analyzed the patency outcomes. Twelve infants undergoing pediatric LDLT were selected during 2-year study period between January 2018 and December 2019. Surgical techniques and vascular complications of graft hepatic vein outflow were analyzed. The mean recipient age was 12.5 ± 4.5 months; mean body weight was 9.4 ± 1.0 Kg; and mean graft-recipient weight ratio was 2.8 ± 0.6%. Primary diseases were biliary atresia in six patients, metabolic diseases in two, hepatoblastoma in two, and acute liver failure in two. Eight LLS grafts were recovered through an open method, and four LLS grafts were recovered through a laparoscopic method. A small superficial LHV branch was present in five of 12 LLS grafts, which was opened to widen the graft hepatic vein orifice. Incision-and-patch venoplasty was performed in 10, unification venoplasty in 1 and no venoplasty in 1. All four LLS grafts recovered through a laparoscopic approach required circumferential vein patch because of very short hepatic vein stump. No patient experienced graft hepatic vein-associated vascular complications during the follow-up period of 19.3 ± 9.3 months. Our surgical techniques with incision-and-patch venoplasty for LLS grafts is beneficial to reduce the risk of hepatic vein outflow obstruction in recipients receiving LLS grafts.

Revascularisation of type 2 diabetics with coronary artery disease: Insights and therapeutic targeting of O-GlcNAcylation.

AIM: Coronary artery bypass graft (CABG) using autologous saphenous vein continues to be a gold standard procedure to restore the supply of oxygen-rich blood to the heart muscles in coronary artery disease (CAD) patients with or without type 2 diabetes mellitus (T2DM). However, CAD patients with T2DM are at higher risk of graft failure. While failure rates have been reduced through improvements in procedure-related factors, much less is known about the molecular and cellular mechanisms by which T2DM initiates vein graft failure. This review gives novel insights into these cellular and molecular mechanisms and identifies potential therapeutic targets for development of new medicines to improve vein graft patency. DATA SYNTHESIS: One important cellular process that has been implicated in the pathogenesis of T2DM is protein O-GlcNAcylation, a dynamic, reversible post-translational modification of serine and threonine residues on target proteins that is controlled by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Protein O-GlcNAcylation impacts a range of cellular processes, including trafficking, metabolism, inflammation and cytoskeletal organisation. Altered O-GlcNAcylation homeostasis have, therefore, been linked to a range of human pathologies with a metabolic component, including T2DM. CONCLUSION: We propose that protein O-GlcNAcylation alters vascular smooth muscle and endothelial cell function through modification of specific protein targets which contribute to the vascular re-modelling responsible for saphenous vein graft failure in T2DM.

Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts.

BACKGROUND: People with end-stage renal disease (ESRD) often require either the formation of an arteriovenous fistula (AVF) or an interposition prosthetic arteriovenous graft (AVG) for haemodialysis. These access sites should ideally have a long life and a low rate of complications (e.g. thrombosis, infection, stenosis, aneurysm formation and distal limb ischaemia). Although some of the complications may be unavoidable, any adjuvant technique or medical treatment aimed at decreasing complications would be welcome. This is the fourth update of the review first published in 2003. OBJECTIVES: To assess the effects of adjuvant drug treatment in people with ESRD on haemodialysis via autologous AVFs or prosthetic interposition AVGs. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and ClinicalTrials.gov trials register to 6 August 2020. SELECTION CRITERIA: Randomised controlled trials of active drug versus placebo in people with ESRD undergoing haemodialysis via an AVF or prosthetic interposition AVG. DATA COLLECTION AND ANALYSIS: For this update, two review authors (IM, MFAK) independently selected trials for inclusion, extracted data, assessed risk of bias and assessed the certainty of the evidence according to GRADE. We resolved disagreements by discussion or consultation with another review author (ADS). The primary outcome was the long-term fistula or graft patency rate. Secondary outcomes included duration of hospital stay; complications such as infection, aneurysm formation, stenosis and distal limb ischaemia; and number of related surgical or radiological interventions. MAIN RESULTS: For this update, one additional study was suitable for inclusion, making a total of 13 trials with 2080 participants. Overall the certainty of the evidence was low or moderate due to short follow-up periods, heterogeneity between trials, small sample sizes, and risk of bias due to incomplete reporting. Medical adjuvant treatments used in the included trials were aspirin, ticlopidine, dipyridamole, dipyridamole plus aspirin, warfarin, fish oil, clopidogrel, sulphinpyrazone and glyceryl trinitrate (GTN) patch.  All included studies reported on graft patency by measuring graft thrombosis. There was insufficient evidence to determine if there was a difference in graft patency in studies comparing aspirin versus placebo (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.07 to 2.25; 3 studies, 175 participants; low-certainty evidence). The meta-analysis for graft patency comparing ticlopidine versus placebo favoured ticlopidine (OR 0.45, 95% CI 0.25 to 0.82; 3 studies, 339 participants; moderate-certainty evidence). There was insufficient evidence to determine if there was a difference in graft patency in studies comparing fish oil versus placebo (OR 0.24, 95% CI 0.03 to 1.95; 2 studies, 220 participants; low-certainty evidence); and studies comparing clopidogrel and placebo (OR 0.40, 95% CI 0.13 to 1.19; 2 studies, 959 participants; moderate-certainty evidence). Similarly, there was insufficient evidence to determine if there was a difference in graft patency comparing the effect of dipyridamole versus placebo (OR 0.46, 95% CI 0.11 to 1.94; 1 study, 42 participants, moderate-certainty evidence) and dipyridamole plus aspirin versus placebo (OR 0.64, CI 0.16 to 2.56; 1 study, 41 participants; moderate-certainty evidence); comparing low-intensity warfarin with placebo (OR 1.76, 95% CI 0.78 to 3.99; 1 study, 107 participants; low-certainty evidence); comparing sulphinpyrazone versus placebo (OR 0.43, 95% CI 0.03 to 5.98; 1 study, 16 participants; low-certainty evidence) and comparing GTN patch and placebo (OR 1.26, 95% CI 0.63 to 2.54; 1 study, 167 participants; moderate-certainty evidence). The single trial evaluating warfarin was terminated early because of major bleeding events in the warfarin group. Only two studies published data on the secondary outcome of related interventions (surgical or radiological); there was insufficient evidence to determine if there was a difference in related interventions between placebo and treatment groups. None of the included studies reported on the duration of hospital stay.  Most studies reported complications ranging from mortality to nausea. However, data on complications were limited and reporting varied between studies. AUTHORS' CONCLUSIONS: The meta-analyses of three studies for ticlopidine (an antiplatelet treatment), which all used the same dose of treatment but with a short follow-up of only one month, suggest ticlopidine may have a beneficial effect as an adjuvant treatment to increase the patency of AVFs and AVGs in the short term. There was insufficient evidence to determine if there was a difference in graft patency between placebo and other treatments such as aspirin, fish oil, clopidogrel, dipyridamole, dipyridamole plus aspirin, warfarin, sulphinpyrazone and GTN patch. The certainty of the evidence was low to moderate due to short follow-up periods, the small number of studies for each comparison, small sample sizes, heterogeneity between trials and risk of bias due to incomplete reporting. Therefore, it appears reasonable to suggest further prospective studies be undertaken to assess the use of these antiplatelet drugs in renal patients with an AVF or AVG.

Adjuvant heparinization before manipulation of artery reduces early failure in primary arteriovenous fistula for end-stage renal disease patients.

BACKGROUND: Arteriovenous fistula (AVF) is the most preferred vascular access for hemodialysis patients, and early failure of AVF is one of the most avoidable complications of this procedure. We retrospectively evaluated whether adjuvant systemic heparinization just before arterial manipulation could reduce early failure of primary AVF. METHODS: Three hundred and fifty-six patients with end-stage renal failure who underwent primary AVF surgery from April 2009 to September 2020 were enrolled in this study. The patients were divided into two groups based on whether they received adjuvant heparinization or not. Patient backgrounds, frequency of early AVF failure, and bleeding events were compared between the two groups. Multivariate Cox regression analysis identified risk factors for early AVF failure. RESULTS: Early failure of AVF was observed in only 2 of 157 patients (1.2%) in the adjuvant group, and the incident was significantly lower than observed in the non-adjuvant group, i.e., 17 of 199 patients (8.5%) (p = 0.002). Bleeding events were not significantly different between the two groups. Seven of 157 patients (4.5%) in the adjuvant group and 7 of 199 patients (3.5%) in the non-adjuvant group experienced bleeding events (p = 0.785). Female sex, use of steroids, hypoalbuminemia, venous stenosis in pre-surgical evaluation, arterial spasm in the perioperative period, new-onset venous stenosis after AVF anastomosis, technical failure of surgery, no early cannulation after surgery, and non-adjuvant heparinization were related to early AVF failure in the multivariate regression analysis. CONCLUSION: Adjuvant systemic heparinization therapy just before arterial manipulation reduced early failure of primary AVF without increasing bleeding events.

Statins Protect against Thrombosis of Cannulated Radiocephalic Fistulas in Diabetic Patients.

BACKGROUND: Radiocephalic arteriovenous fistula (RCAVF) creation is the preferred first line hemodialysis access procedure. Analysis of diabetic rat arteriovenous fistula model indicates improved vascular function with HMG-CoA-Reductase Inhibitor (statin) use. We predict similar outcomes in diabetic patients undergoing primary RCAVF placement. METHODS: A Veterans Administration Hospital dialysis access database over a 15-year period was queried identifying all RCAVF placements in diabetic patients. Patients were stratified into statin medication usage or not at RCAVF creation. Outcomes examined include rate of successful cannulation, functional patency duration, interventions per access, and rates of access thrombosis. Thrombosis-free survival of cannulated RCAVFs were compared using Kaplan-Meier method with log-rank analysis followed by univariate, stepwise logistic regression and ROC curve analysis. RESULTS: Total number of 123 RCAVF cases were performed in 122 diabetic male patients. At the time of RCAVF placement, 92 cases were performed on patients that were taking statin medication and 31 cases were performed on patients that were not taking statin medication. There was no difference in terms of rate of successful cannulation, functional patency duration, and number of interventions per access between the statin and non-statin groups. However, rate of RCAVF thrombosis once accessed was significantly lower in the statin group compared to the non-statin group (P = 0.0005). Kaplan-Meier survival curve for each group were compared using log-rank test to reveal that diabetic patients who were on statin therapy at the time of operation had significantly higher access survival over time against thrombosis once it was cannulated for dialysis treatment compared to those who were not on statin therapy (P = 0.0003). Univariate, stepwise logistic regression model indicated statin use as the only significant factor associated with lack of thrombosis (P = 0.05). CONCLUSIONS: Statins appear to have protective effects against RCAVF thrombosis as predicted in animal models for diabetic patients undergoing primary RCAVF placements. There were similar functional outcomes in terms of rate of successful cannulation, functional patency duration, and number of interventions per access. These data should encourage further investigation of statins and their role in hemodialysis access.

Effect of Hydraulic Expansion on Arteriovenous Fistula of Hemodialysis Patients.

BACKGROUND: Chronic kidney disease has become a serious public health problem in China. Our study is to explore effect of hydraulic expansion on arteriovenous fistula (AVF) of hemodialysis patients. METHODS: A total of 190 patients with end-stage renal disease (ESRD) were randomly divided into hydraulic expansion group (n = 117) and conventional surgery group (n = 73). Age, sex, the cause of ESRD, height, weight, body mass index (BMI), blood pressure, and diameter of artery and vein from ultrasonography before surgery from patients were recorded. Doppler ultrasonography of vessel was performed with a 12-MHz scanning probe for vascular measurements. The time of first cannulation was recorded. Primary and secondary patency rates were compared between the two groups. RESULTS: The mean arterial pressure for this cohort of patients was around 98.12 mm Hg. The mean diameters of artery and vein ready for anastomoses measured by ultrasonography before surgery were 1.96 and 2.04 mm, respectively. Age, weight, BMI, sex ratio, the cause of renal failure, history of catheter insertion, mean arterial pressure, frequency of hemodialysis, blood flow of hemodialysis, and the mode of anastomoses of AVF in conventional surgery group were similar to hydraulic expansion group. There were no differences in stroke volume of radius arterial and venous pressure before dilation between the two groups. The stroke volume of radius artery increased significantly after hydraulic expansion than before dilation and control group. The primary patency rates of AVF in patients with hydraulic expansion were higher significantly than conventional surgery group. The secondary patency rates in conventional surgery group were not different from hydraulic expansion group. CONCLUSION: Hydraulic expansion showed no difference from conventional surgery in complication after operation, and could decrease the time reliance on catheters and the risk of catheter-related infection, thrombosis, and decrease the related medical care costs.

Therapeutic Effect of Adipose Derived Mesenchymal Stem Cell Transplantation in Reducing Restenosis in a Murine Angioplasty Model.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) is the first line of treatment for stenosis in the arteriovenous fistula (AVF) created to provide access for hemodialysis, but resenosis still occurs. Transplants of adipose-derived mesenchymal stem cells (AMSCs) labeled with green fluorescent protein (GFP) to the adventitia could reduce pro-inflammatory gene expression, possibly restoring patency in a murine model of PTA for venous stenosis. METHODS: Partial nephrectomy of male C57BL/6J mice induced CKD. Placement of the AVF was 28 days later and, 14 days after that, PTA of the stenotic outflow vein was performed with delivery of either vehicle control or AMSCs (5×105) to the adventitia of the vein. Mice were euthanized 3 days later and gene expression for interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha TNF-α) analyzed, and histopathologic analysis performed on day 14 and 28. GFP (+) AMSCs were tracked after transplantation for up to 28 days and Doppler ultrasound performed weekly after AVF creation. RESULTS: Gene and protein expression of IL-1ß and TNF-α, fibrosis, proliferation, apoptosis and smooth muscle actin decreased, and the proportions of macrophage types (M2/M1) shifted in a manner consistent with less inflammation in AMSC-transplanted vessels compared to controls. After PTA, AMSC-treated vessels had significantly higher wall shear stress, average peak, and mean velocity, with increased lumen vessel area and decreased neointima/media area ratio compared to the control group. At 28 days after delivery, GFP (+) AMSC were present in the adventitia of the outflow vein. CONCLUSIONS: AMSC-treated vessels had improved vascular remodeling with decreased proinflammatory gene expression, inflammation, and fibrotic staining compared to untreated vessels.