Meeting Report of the 35th Annual Meeting of the Academy of Surgical Research: Summary of Presentations, Labs, and Workshops, Focusing on Experimental Surgery, Clearwater Beach, FL, 25-27 September 2019.

The 35th Annual Meeting of the Academy of Surgical Research took place in Clearwater Beach, Florida on 25-27 September 2019. This meeting brings together the experimental surgery community to share the latest in research and surgical techniques and fosters professional development through education, training, and certification. The Academy is made up of a diverse group of technicians, veterinarians, medical doctors, and biomedical researchers from industry, academia, and complimentary disciplines supporting discovery and translational research. Over 165 participants from 30 different states and 6 countries were in attendance for the scientific program and social events. Four keynotes were presented together with breakout and poster session tracks. Participants were able to work on applied skills in practical courses that included hands-on surgical technique wet-labs complimented with dry-lab suture technique and surgical anesthesia, plus workshops and roundtables focused on improving study design and publication best practices. Attendees were able to enjoy sun and fun while connecting with potential mentors and collaborators during the social program. We present the highlights from this meeting in this report together with selected abstracts that illustrate the diverse scientific expertise of the Academy and promising new surgical research.

Safety and Efficacy of a Novel, Self-Adhering Dural Substitute in a Canine Supratentorial Durotomy Model.

BACKGROUND: Cerebrospinal fluid (CSF) leaks increase postoperative risk for complication, likelihood of reoperation, and costs. OBJECTIVE: To investigate a novel, self-adhering polyethylene glycol-coated collagen pad (PCC) as a dural substitute relative to Duragen XS (DGX; Integra LifeSciences Corporation, Plainsboro, New Jersey) and as a dural sealant relative to Tachosil (Takeda Austria GmbH, Linz, Austria), a fibrinogen and thrombin-coated collagen pad (FTC). METHODS: A canine supratentorial durotomy surgical model was used to investigate the safety and efficacy of PCC. For safety, 4 animals were bilaterally treated with DGX or PCC and recovered for 1, 8, or 16 wk; total 24 animals. Each animal underwent physical and neurological examinations weekly and 16-wk animals underwent a magnetic resonance imaging (MRI) examination at each time point. For efficacy, 9 animals were unilaterally treated with FTC or PCC and underwent a burst pressure test intraoperatively or 14 d postoperatively; total 36 animals. RESULTS: In the safety study, no abnormal clinical signs or changes were noted on physical and neurological examinations, or in clinical pathology, CSF analysis or histopathology of DGX or PCC-treated animals. No consistent signs of cerebral compression, CSF leak, hemorrhage, or hydrocephalus were noted on MRI. In the efficacy study, no significant difference was found between FTC and PCC at each time point or overall (13.9 vs 12.3 mm Hg, n = 18 per group, P = .46). CONCLUSION: PCC is safe for use as a dural substitute and effective as a dural sealant. The novel, self-adhering combination of a polyethylene glycol-based sealant and a collagen pad may offer unique benefits to the advancement of duraplasty.

OTO-104: a sustained-release dexamethasone hydrogel for the treatment of otic disorders.

HYPOTHESIS: To investigate whether OTO-104, a poloxamer-based hydrogel containing micronized dexamethasone for intratympanic delivery, can provide long-lasting inner ear exposure and be well tolerated. METHODS: OTO-104 was administered intratympanically to guinea pigs and sheep, and its pharmacokinetic and toxicity profiles were examined. RESULTS: After a single intratympanic injection of OTO-104 (from 0.6% to 20%, w/w), significant and prolonged exposure to dexamethasone in the inner ear was observed. Increasing the concentration of OTO-104 resulted in higher perilymph drug levels as well as a more prolonged duration of exposure. At the highest dose, therapeutic perilymph levels of dexamethasone could be sustained over 3 months in guinea pigs and more than 1 month in sheep. A toxicologic evaluation was conducted, including assessments of middle and inner ear function and physiology, as well as appraisal of local and systemic toxicity. A small and transient shift in hearing threshold was observed, most probably conductive in nature. No significant histologic changes in middle or inner ear tissues were noted. Although macroscopically mild erythema/inflammation was documented in a subset of guinea pigs treated with 20% OTO-104, the nature and the severity of these changes were not different between the poloxamer vehicle, saline, and 20% OTO-104 groups. No evidence of acute dermal toxicity, delayed hypersensitivity, or systemic adverse effects was found. CONCLUSION: OTO-104 is a novel proprietary therapeutic delivery system that can achieve prolonged, sustained release of dexamethasone within the inner ear fluids. The administration of this clinical candidate formulation via intratympanic injection is expected to be well tolerated both locally and systemically.