Helper-dependent adenoviral vectors (HDAd) are devoid of all viral coding sequences and are thus an improvement over early generation Ad because they can provide long-term transgene expression in vivo without chronic toxicity. However, high vector doses are required to achieve efficient hepatic transduction by systemic intravenous injection, and this unfortunately results in dose-dependent acute toxicity. To overcome this important obstacle, we have developed a minimally invasive method to preferentially deliver HDAd into the liver of nonhuman primates. Briefly, a balloon occlusion catheter was percutaneously positioned in the inferior vena cava to occlude hepatic venous outflow. HDAd was injected directly into the occluded liver via a percutaneously placed hepatic artery catheter. Compared to systemic vector injection, this approach resulted in substantially higher hepatic transduction efficiency using clinically relevant low vector doses and was accompanied by mild-to-moderate acute but transient toxicities. Transgene expression was sustained for up to 964 days. These results suggest that our minimally invasive method of delivery can significantly improve the vector's therapeutic index and may be a first step toward clinical application of HDAd for liver-directed gene therapy.

Helper-dependent adenoviral vectors (HDAd) have been shown to mediate a considerably longer duration of transgene expression than first-generation adenoviral vectors. We have previously shown that transgene expression from HDAd-transduced hepatocytes can persist at high levels for up to 2.6 years in nonhuman primates following a single-vector administration. Because duration of transgene expression and long-term toxicity are critical for risk:benefit assessment, we have continued to monitor these animals. We report here that transgene expression has persisted for the entire observation period of up to 7 years for all animals without long-term adverse effects. However, in all cases, transgene expression level slowly declined over time to less than 10% of peak values by the end of the observation period but remained 2.3-111-fold above baseline values. These results will provide important information for a more informed risk:benefit assessment before clinical application of HDAd.

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Stents implants for PA stenoses provide effective improvement in vessel caliber in the long-term. Although repeat interventions are necessary, this procedure reduces RV pressure and provides an important alternative to surgery for residual PA obstruction.

BackgroundTranscatheter pulmonary valve implantation is approved for the treatment of dysfunctional right ventricle to pulmonary artery conduits. However, the literature is limited because of a small patient population, and it does not reflect changing procedural practice patterns over the last decade.Methods and ResultsA comprehensive search of Medline and Scopus databases from inception through August 31, 2016 was conducted using predefined criteria. We included studies reporting transcatheter pulmonary valve implantation in at least 5 patients with a follow‐up duration of 6 months or more. In 19 eligible studies, 1044 patients underwent transcatheter pulmonary valve implantation with a pooled follow‐up of 2271 person‐years. Procedural success rate was 96.2% (95% confidence intervals [CI], 94.6–97.4) with a conduit rupture rate of 4.1% (95% CI, 2.5–6.8) and coronary complication rate of 1.3% (95% CI, 0.7–2.3). Incidence of reintervention was 4.4 per 100 person‐years overall (95% CI, 3.0–5.9) with a marked reduction in studies reporting ≥75% prestenting (2.9 per 100 person‐years [95% CI, 1.5–4.3] versus 6.5/100 person‐years [95% CI, 4.6–8.5]; P<0.01). Pooled endocarditis rate was 1.4 per 100 person‐years (95% CI, 0.9–2.0).ConclusionsOur study provides favorable updated estimates of procedural and follow‐up outcomes after transcatheter pulmonary valve implantation. Widespread adoption of prestenting has improved longer‐term outcomes in these patients.

This novel long-axis real-time ultrasound technique facilitates placement of femoral vein central venous line in critically ill neonates with cardiac disease at a higher rate of success with fewer attempts and lower occurrence of complications when compared with the landmark technique.

Low-dose arginine vasopressin infusion initiated in the operating room after complex neonatal cardiac surgery was associated with decreased fluid resuscitation and catecholamine requirements in the first 24 postoperative hours.

With the exception of RV-PA conduit stents, fracture is rare and asymptomatic. PA stent fractures occurred in 2.5% and did not embolize, whereas RV-PA conduit stent fractures were significantly more common and may embolize.