We hypothesized that adequately engineered attenuated Salmonella enterica serovar Typhi strains can serve as multivalent mucosal live vector vaccines to immunize against unrelated human pathogens. Toward this ultimate goal, we have developed a novel genetic stabilization system for antigen-expressing plasmids, engineered to encode the single-stranded binding protein (SSB), an essential protein involved in DNA metabolism which was deleted from the live vector chromosome. We utilized full-length protective antigen (PA83) of anthrax toxin from Bacillus anthracis as a foreign antigen and expressed PA83 as a fusion with the ClyA export protein, which allows export of ClyA-PA83 to the surface of S. Typhi live vectors. A series of SSB-encoding multicopy expression plasmids were introduced into reengineered S. Typhi strains previously tested in clinical trials, i.e., CVD 908-htrA and its less attenuated parent CVD 908. Immunogenicity was examined using a mouse model of intranasal immunization with live vector, followed by parenteral boosting with purified PA83. PA-specific antibody responses markedly improved as the copy number of the SSB-encoding plasmids decreased, and this effect was dramatically enhanced when the foreign antigen was delivered by the less attenuated live vector CVD 908ssb. These results suggest that antibody responses to antigens delivered by S. Typhi live vectors are inversely related to the metabolic burden imposed by expression of the foreign antigen and that these responses can be improved when antigens are expressed from low-copy-number plasmids and exported out of the cytoplasm of less attenuated live vectors.

Early free flap coverage in lower extremity trauma is a practice largely supported by research that may be outdated and is frequently impractical due to logistics, resuscitation efforts, and associated injuries. Our objective was to re-evaluate this paradigm to determine whether reconstructive timing impacts outcome in modern clinical practice. We reviewed 60 free flaps for traumatic lower extremity coverage from December 2005 to December 2010 by the plastic surgery service at an academic medical center. All reconstructions were >72-hours from injury, spanning from 3 days to 2.2 years. The overall failure rate was 13.3% (8/60). Statistical analysis yielded no significant associations between reconstructive timing and flap failure or morbidity, although there was a trend toward fewer failures among latest reconstructions (>91 days) compared to within 30 days (P = 0.053). These findings support that delays may be safely utilized to allow patient and wound optimization without negatively impacting outcomes in free tissue transfer.

The data demonstrated a successful outcome for latissimus dorsi and implant breast reconstruction for patients with a low or normal body mass index and a small (A to C cup) breast size. The aesthetic outcome of latissimus dorsi breast reconstruction has been improved over the past 15 years by the adoption of SSM and ASM techniques. Immediate nipple reconstruction and the placement of an adjustable saline implant potentially render this procedure a true single-stage reconstruction. Prepectoral implant position provides good aesthetics while preserving the subpectoral space for future management of capsular contracture if required.

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