Long-Term Results from the Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula Creation for Hemodialysis Access

PurposeTo report the 5-year results from the Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula (pAVF) Creation for Hemodialysis Access.Materials and MethodsThe retrospective review of 107 intent-to-treat (ITT) patients from the pivotal trial provided a long-term follow-up population (LTP) of 85 patients with a median follow-up duration of 50 months (range, 12–60 months). Data evaluated in the LTP group were fistula maturation and usage, secondary procedures, and complications. The Kaplan-Meier analysis of primary patency, assisted primary patency, cumulative patency, and functional patency (time from 2-needle cannulation to abandonment) were performed for the ITT population.ResultsIn the LTP, 99% (84 of 85) of fistulae were mature, with 99% (78 of 79) of patients requiring hemodialysis using their pAVF. Sustained fistula use (2-needle cannulation at the prescribed rate, 2 of 3 sessions) was achieved in 92% (78 of 85) of patients, with 7 patients not using their pAVF because they were not on dialysis (n = 4), were on peritoneal dialysis (n = 2), and refused to use fistula (n = 1). Fistula maintenance was required in 31.8% (27 of 85) of patients and included fistula dysfunction (21.2%), thrombosis (5.9%), cannulation injury (12.9%), and arm swelling (4.7%). The number of procedures performed per patient per year to maintain function and patency was 0.32 (91 of 288) for years 2–5. The cumulative patency rates were 89.5%, 88.4%, 88.4%, 85.6%, and 82.0% for years 1, 2, 3, 4, and 5, respectively. The functional patency was 91.8% at the end of the study. There were no major complications related to pAVF during the long-term follow-up.ConclusionsPercutaneous fistulae have provided clinically effective and durable access for hemodialysis with low complications. The continued use and evaluation of pAVF are warranted.     

Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.     

Clinical Outcomes at 1 Year Following Transcatheter Left Atrial Appendage Occlusion in the United States

ObjectivesThe aim of this study was to report 1-year clinical outcomes following commercial transcatheter left atrial appendage occlusion (LAAO) in the United States.BackgroundThe National Cardiovascular Data Registry LAAO Registry was initiated to meet a condition of Medicare coverage and allow the assessment of clinical outcomes. The 1-year rates of thromboembolic events after transcatheter LAAO in such a large cohort of “real-world” patients have not been previously reported.MethodsPatients entered into the National Cardiovascular Data Registry LAAO Registry for a Watchman procedure between January 1, 2016, and December 31, 2018, were included. The primary endpoint was ischemic stroke. Key secondary endpoints included the rate of ischemic stroke or systemic embolism, mortality, and major bleeding. Major bleeding was defined as any bleeding requiring hospitalization, and/or causing a decrease in hemoglobin level > 2g/dL, and/or requiring blood transfusion that was not hemorrhagic stroke. The Kaplan-Meier method was used for 1-year estimates of cumulative event rates.ResultsThe study population consisted of 36,681 patients. The mean age was 76.0 ± 8.1 years, the mean CHA₂DS₂-VASc score was 4.8 ± 1.5, and the mean HAS-BLED score was 3.0 ± 1.1. Prior stroke was present in 25.5%, clinically relevant bleeding in 69.5%, and intracranial bleeding in 11.9%. Median follow-up was 374 days (IQR: 212-425 days). The Kaplan-Meier–estimated 1-year rate of ischemic stroke was 1.53% (95% CI: 1.39%-1.69%), the rate of ischemic stroke or systemic embolism was 2.19% (95% CI: 2.01%-2.38%), and the rate of mortality was 8.52% (95% CI: 8.19%-8.87%). The 1-year estimated rate of major bleeding was 6.93% (95% CI: 6.65%-7.21%). Most bleeding events occurred between discharge and 45 days following the procedure.ConclusionsThis study characterizes important outcomes in a national cohort of patients undergoing transcatheter LAAO in the United States. Clinicians and patients can integrate these data in shared decision making when considering this therapy.