Summary Background For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. Methods We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. Findings Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47–72) of patients had primary patency, 73% (57–81) had primary assisted patency, and 97% (85–98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17–40) had primary patency, 38% (26–51) had primary assisted patency, and 89% (74–93) had secondary patency. Interpretation Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. Funding Humacyte and US National Institutes of Health.

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Abdominal aortic aneurysm (AAA) is an immune-mediated disease with a genetic component. The multifactorial pathophysiology is not clear and there is still no pharmacotherapy to slow the growth of aneurysms. The signal integration of cell-surface KIRs (killer cell immunoglobulin-like receptors) with HLA (ligands, human leukocyte class I antigen molecules) modulates the activity of natural killer immune cells. The genetic diversity of the KIR/HLA system is associated with the risk of immune disorders. This study was a multivariate analysis of the association between genetic variants of KIRs, HLA ligands, clinical data and AAA formation. Genotyping was performed by single polymerase chain reaction with sequence-specific primers using commercial assays. Patients with HLA-A-Bw4 have a larger aneurysm by an average of 4 mm (p = 0.008). We observed a relationship between aneurysm diameter and BMI in patients with AAA and co-existing CAD; its shape was determined by the presence of HLA-A-Bw4. There was also a nearly 10% difference in KIR3DL1 allele frequency between the study and control groups. High expression of the cell surface receptor KIR3DL1 may protect, to some extent, against AAA. The presence of HLA-A-Bw4 may affect the rate of aneurysm growth and represents a potential regional pathogenetic risk of autoimmune injury to the aneurysmal aorta.

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Objectives:We examined plasma concentrations of essential regulators of coagulation cascade, tissue factor (TF) and tissue factor inhibitor pathway (TFPI) in patients with abdominal aortic aneurysm (AAA) during two types of surgical repair , open (OAR) and endovascular repair (EVAR). Background:The interplay between TF and TFPI is important for the proper functioning of coagulation cascade. Although abnormal coagulation is known to contribute to the formation of AAA, little is known about the prognostic value of TF and TFPI levels in the perioperative stage of AAA repair. Methods:We have selected the reference group of 53 healthy, first-time blood donors and 66 patients scheduled for AAA repair using EVAR or OAR and measured TF and TFPI in their blood plasma using ELISA (enzyme-linked immunosorbent assay) before surgery, immediately after and 24 hours after surgery. Results:Patients with AAA had elevated levels of TF (219.242 pg/ml) compared to the reference group (149.170 pg/ml). TF levels were higher in AAA patients with limb ischemia (p=0.0026) and mural thrombi >30 mm (p=0.0015) but decreased in patient with BMI >25 (p=0.027). No differences were observed in TF and TFPI levels during EVAR and OAR or de-pending on the stent graft type. However, there was a correlation between the TF level and occurrence of post-surgical complications in OAR type of surgery Conclusions: Our results suggest that monitoring levels of TF and TFPI in perioperative period would be useful in risk assessment of surgery complications, especially in AAA patients with ischemic disorders undergoing OAR surgery.