Identification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation.

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in Xenopus, we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC80 in microfluidic human organs-on-chips, as well as in explanted whole porcine hearts and limbs, demonstrating the cross-species relevance of this approach and potential clinical relevance for surgical transplantation. Pharmacological induction of physiological slowing in combination with organ perfusion transport systems may offer a new therapeutic approach for tissue and organ preservation for transplantation, trauma management, and enhancing patient survival in remote and low-resource locations.

Changes in Microwave Ablation Zone Dimensions after Transarterial Embolization in an Ex Vivo Human Kidney Perfusion Model.

PURPOSE: To utilize a novel ex vivo perfused human renal model and quantify microwave ablation (MWA) size differences in renal tissue when combining MWA with transarterial embolization (TAE). MATERIALS AND METHODS: Human kidneys (n = 5) declined for transplantation were obtained and connected to a fluoroscopy-compatible ex vivo perfusion system. Two ablations-1 standard MWA and 1 TAE-MWA-were performed in each kidney for 2 minutes at 100 W using a MWA system (Solero Angiodynamics). MWA alone was performed in the upper pole. In the lower pole, MWA was performed after TAE with 40-90 µm radiopaque microspheres to achieve angiographic stasis. Ablation zones of coagulative necrosis were sectioned along the long axis and segmented for maximal short-axis diameter (SAD) and long-axis diameter (LAD) measurements. RESULTS: A total of 10 ablations (5 MWAs and 5 TAE-MWAs) were performed in 5 human kidneys. TAE-MWA resulted in significantly increased SAD, LAD, volume, and sphericity compared with standard MWA ± SD, with mean measurements as follows (5 standard MWAs ± SD vs 5 TAE-MWAs ± SD, 2-tailed t-test): (a) SAD, 1.8 cm (SD ± 0.1) versus 2.5 cm (SD ± 0.1) (P < .001); (b) LAD, 2.9 cm (SD ± 0.3) versus 3.2 cm (SD ± 0.1) (P = .039); (c) volume, 5.0 mL (SD ± 0.5) versus 11.0 mL (SD ± 0.7) (P < .001); and (d) sphericity, 0.4 (SD ± 0.2) versus 0.6 (SD ± 0.1) (P = .049). Histology demonstrated no differences in TAE-MWA other than concentrated microspheres. CONCLUSIONS: This ex vivo human kidney perfusion model confirmed that combined MWA-TAE significantly increased ablation size and spherical shape compared with MWA alone.

Construct validity of a low-cost medium-fidelity endoscopic sinus surgery simulation model.

OBJECTIVE: Assess construct validity of a low-cost medium-fidelity silicone injection molded model task trainer for endoscopic sinus surgery (ESS) training. METHODS: Fellowship-trained rhinologists, otolaryngology attendings, and otolaryngology residents at various levels of training performed sinus endoscopy and seven procedures on the model. Construct validity was evaluated by comparing novice to various levels of experienced performance using a validated checklist. RESULTS: Thirty-two subjects participated in this study. Otolaryngology attendings and postgraduate year (PGY) 3 to 5 otolaryngology residents significantly outperformed PGY 1 to 2 otolaryngology residents on most tasks in the task-specific checklist. CONCLUSIONS: This study demonstrated the construct validity of the low-cost medium-fidelity ESS model. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1505-1509, 2019.

Fabrication and validation of a low-cost, medium-fidelity silicone injection molded endoscopic sinus surgery simulation model.

OBJECTIVES/HYPOTHESIS: Develop a low-cost, medium-fidelity model for education in endoscopic sinus surgery techniques. Establish face and content validity of the model based on the feedback of otolaryngology faculty including fellowship-trained rhinologists. STUDY DESIGN: Survey. METHODS: A novel silicone injection molded sinus model was constructed. Three fellowship-trained rhinologists and four general otolaryngologists were recruited to perform seven tasks and provide feedback of the model's performance via a 22-question Likert survey. RESULTS: Those surveyed strongly agreed the sinus model is useful for basic endoscopic skill acquisition such as camera skills (86%), hand-eye coordination (100%), nasal endoscopy skills (100%). Ratings of the model for training the specific tasks were consistently high. Neutral or lower were received for inferior turbinoplasty (14%), frontal balloon task (14%), understanding the ethmoid bulla (29%), and advanced sinus techniques (57%). All faculty strongly agreed they would be interested in using the model to train residents. CONCLUSIONS: Simulation models have proven efficacy in endoscopic skill and procedural training. The group developed a novel low-cost, medium-fidelity sinus training model utilizing three-dimensional modeling and printing. Testing of this model revealed high ratings for both face and construct validity for a range of endoscopic procedures. Strong interest in using this model for resident training was unanimous among all survey participants. LEVEL OF EVIDENCE: NA Laryngoscope, 127:781-786, 2017.

Failure pressures after repairs of 2-cm × 2.5-cm rhinologic dural defects in a porcine ex vivo model.

BACKGROUND: The objective of this study was to determine failure pressures of 6 rhinologic repair techniques of large skull base/dural defects in a controlled, ex vivo model. METHODS: Failure pressures of 6 dural repairs in a porcine model were studied using a closed testing apparatus; 24-mm × 19-mm dural defects were created; 40-mm × 34-mm grafts composed of porcine Duragen (Integra), fascia lata, and Biodesign (Cook) were used either with or without Tisseel (Baxter International Inc.) to create 6 repairs: Duragen/no glue (D/NG), Duragen/Tisseel (D/T), fascia lata/no glue (FL/NG), fascia lata/Tisseel (FL/T), Biodesign/no glue (B/NG), and Biodesign/Tisseel (B/T). Saline was infused at 30 mL/hour, applying even force to the underside of the graft until repair failure. Five trials were performed per repair type for a total of 30 repairs. RESULTS: Mean failure pressures were as follows: D/NG 1.361 ± 0.169 cmH2 O; D/T 9.127 ± 1.805 cmH2 O; FL/NG 0.200 ± 0.109 cmH2 O; FL/T 7.833 ± 2.657 cmH2 O; B/NG 0.299 ± 0.109 cmH2 O; and B/T 2.67 ± 0.619 cmH2 O. There were statistically significant differences between glued (Tisseel) and non-glued repairs for each repair category (p < 0.05). CONCLUSION: All glued repairs performed better than non-glued repairs. Both D/T and FL/T repairs performed better than B/T repairs. No repair tolerated pressures throughout the full range of adult supine intracranial pressure.

The validation of an endoscopic sinus surgery skills training model: a pilot study.

BACKGROUND: Performing functional endoscopic sinus surgery (FESS) requires a trainee surgeon to develop both thorough anatomic understanding and new manual dexterity skills. Traditionally, these skills were learned in the operating room setting. In an era of available surgical simulation, this practice introduces ethical concerns about exposing patients to unnecessary risks during surgical skills development. Additionally, cost-effective rhinologic training has become increasingly important. To address these problems, a low-cost, intermediate-fidelity FESS training model was developed, and both speed and accuracy of task completion were measured to assess both immediate and intermediate-term skills retention. METHODS: Preliminary data were collected on 12 medical students and 10 resident-level (PGY1, -2, and -3) learners. Distinct tasks were performed five times on the initial day of testing and repeated after 2 weeks. RESULTS: Both groups attained statistically significant improvement in time to complete both tasks by the second iteration of each task and retained this effect after 2 weeks. Similarly, statistically significant improvement was seen for accuracy relative to the initial attempt by the fifth iteration for residents. This effect was also seen by the third through fifth iterations and after 2 weeks for students. Additionally, when the 2-week follow-up testing was compared with the fifth attempt, the only skills that deteriorated significantly were the resident group with the complex task times and the students with measures of accuracy. However, in both cases a highly significant improvement from initial attempts was maintained (p = 0.02 and p = 0.005, respectively). Residents were significantly faster than medical students at both simple and complex tasks for attempts 1 through 4, but this difference was not significant for attempt 5 and after 2 weeks. Residents had significantly fewer errors for all but the 2-week data point. CONCLUSION: The data from this pilot study support improved FESS skills for both medical students and residents using this low-cost, intermediate-fidelity model.