Outcomes of Planned Two-Stage Hybrid Aortic Repair With Dacron-Replaced Proximal Landing Zone.

BACKGROUND: Results of hybrid arch repair (HAR) using the native zone 0 proximal landing zone (PLZ) have been unsatisfactory in many series, especially in the setting of ascending aortic dilation (>4.0 cm). This study reports early and late outcomes of planned two-stage HAR with open first-stage proximal aortic replacement, followed by second-stage thoracic endovascular aortic repair (TEVAR) with PLZ within the Dacron-replaced zone 0. METHODS: Between January 2006 and August 2017, 34 patients underwent planned two-stage HAR. The first-stage proximal aortic replacement included ascending aorta (with or without valve, with or without root) and total arch replacement, which was performed with creation of an elephant trunk in 22 patients (65%) and without an elephant trunk in 12 (35%). Primary outcomes included 30-day/in-hospital results and Kaplan-Meier estimates of overall/aorta-specific survival and freedom from reintervention. RESULTS: Mean age was 59 ± 12 years. Both stages of repair were completed in a single hospitalization in 53% of patients, including operations done since January 2012. The 30-day/in-hospital rates of mortality, stroke, permanent paraparesis/plegia, and new dialysis were 6%, 3%, 0%, and 0%, respectively. Kaplan-Meier overall and aorta-specific survivals at 5 years were 63% and 94%, respectively, with 5-year freedom from reintervention of 78%. CONCLUSIONS: Planned two-stage HAR with open first-stage proximal aortic replacement, followed by second-stage TEVAR with Dacron-replaced PLZ yields excellent short-term and long-term results, including low rates of reintervention likely due to the long-segment PLZ within the Dacron-replaced aorta. The technique should be considered in patients with even mild (>4.0 cm) ascending aortic dilation in whom HAR is otherwise the preferred treatment option.

Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens.

Protection against mucosally transmitted infections probably requires immunity at the site of pathogen entry, yet there are no mucosal adjuvant formulations licensed for human use. Polyethyleneimine (PEI) represents a family of organic polycations used as nucleic acid transfection reagents in vitro and DNA vaccine delivery vehicles in vivo. Here we show that diverse PEI forms have potent mucosal adjuvant activity for viral subunit glycoprotein antigens. A single intranasal administration of influenza hemagglutinin or herpes simplex virus type-2 (HSV-2) glycoprotein D with PEI elicited robust antibody-mediated protection from an otherwise lethal infection, and was superior to existing experimental mucosal adjuvants. PEI formed nanoscale complexes with antigen, which were taken up by antigen-presenting cells in vitro and in vivo, promoted dendritic cell trafficking to draining lymph nodes and induced non-proinflammatory cytokine responses. PEI adjuvanticity required release of host double-stranded DNA that triggered Irf3-dependent signaling. PEI therefore merits further investigation as a mucosal adjuvant for human use.