Citations

The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The Ad5 virus was superior to the species D viruses in BALB/c mice when delivered intramuscularly. However, the inverse was true when the viruses were delivered mucosally via the intranasal epithelia. Intramuscular transduction was restored in mice that ubiquitously expressed human CD46, the primary receptor for species D viruses. We analyzed both species C and D Ads for their ability to induce prophylactic immunity against influenza in the CD46 transgenic mouse model. Surprisingly, the species D vaccines again failed to induce greater levels of protective immunity as compared with the species C Ad5 when delivered intramuscularly. However, the species D Ad vaccine vector, Ad48, induced significantly greater protection as compared with Ad5 when delivered mucosally via the intranasal route in CD46 transgenic mice. These data shed light on the complexities between the species and types of Ad. Our findings indicate that more research will be required to identify the mechanisms that play a key role in the induction of protective immunity induced by species D Ad vaccines.

Objectives: We report the clinical findings, surgical management, and outcomes for lingual thyroidectomy. Methods: We performed a retrospective case review of lingual thyroidectomy performed at 3 tertiary-care academic referral centers between 1994 and 2012. Results: Nine patients underwent lingual thyroidectomy for symptoms including globus sensation (6 patients), dysphagia (5 patients), and airway obstruction (5 patients). Before surgery, 3 patients had attempted medical suppressive therapy. Lingual thyroidectomy was performed by transoral laser microsurgery in 4 patients, transoral robotic surgery in 3 patients, transoral surgery without microscopic assistance in 1 patient, and an open approach with a modified Sistrunk procedure in 1 patient. Total thyroidectomy was attained in 7 patients, and subtotal resection in 2. The follow-up averaged 8 months, and all patients reported significant improvement in their symptoms. One patient had a recurrence. Complications included postoperative bleeding and epiglottic perforation in 1 patient and airway obstruction secondary to angioedema in another patient. There was no significant difference in operative times between transoral laser microsurgery (91 ± 16 minutes) and transoral robotic surgery (109 ± 35 minutes). Transoral surgery without microscopic assistance and open resection had longer operative times (206 and 246 minutes, respectively). Conclusions: Surgical resection of lingual thyroid glands achieves significant improvement in patient symptoms, with low rates of recurrence. We favor a total lingual thyroidectomy approach with use of either a microscope or a robotic endoscope for optical assistance.

Key Points Zebrafish flt3 plays an important role in the initiation of definitive hematopoietic stem cells. Expression of human FLT3-ITD activates endogenous flt3 signaling and induces myeloid expansion.