Phonomicrosurgery simulation: A low-cost teaching model using easily accessible materials.

OBJECTIVES/HYPOTHESIS: To introduce the use of a new phonomicrosurgical trainer using easily accessible materials, and to establish the effectiveness of the model. STUDY DESIGN: The model uses a grape imbedded in gelatin, a microscope, and microlaryngeal instruments. The study was designed to test baseline differences in training levels, as well as improvement in performance after training with the simulation model. METHODS: Thirty subjects enrolled in the Stanford University School of Medicine otolaryngology training program performed microlaryngeal surgery tasks on a grape. Tasks were designed to model both excision of a vocal fold lesion and vocal fold injection. Anonymized video recordings comparing presimulation and postsimulation training were collected and graded by an expert laryngologist. Both objective comparison of skills and subjective participant surveys were analyzed. RESULTS: Objectively, trainees in all groups made statistically significant improvements across all tested variables, including microscope positioning, creation of a linear incision, elevation of epithelial flaps, excision of a crescent of tissue, vocal fold injection, preservation of remaining tissue, and time to complete all tasks. Subjectively, 100% of participants felt that they had increased comfort with microlaryngeal instruments and decreased intimidation of microlaryngeal surgery after completing the simulation training. This appreciation of skills was most notable and statistically significant in the intern trainees. CONCLUSION: Microlaryngeal surgical simulation is a tool that can be used to train residents to prepare them for phonomicrosurgical procedures at all levels of training. Our low-cost model with accessible materials can be easily duplicated and used to introduce trainees to microlaryngeal surgery or improve skills of more senior trainees. LEVEL OF EVIDENCE: NA Laryngoscope, 126:2528-2533, 2016.

Cost-effectiveness landscape analysis of treatments addressing xerostomia in patients receiving head and neck radiation therapy.

Head and neck (H&N) radiation therapy (RT) can induce irreversible damage to the salivary glands thereby causing long-term xerostomia or dry mouth in 68%-85% of the patients. Not only does xerostomia significantly impair patients' quality-of-life (QOL) but it also has important medical sequelae, incurring high medical and dental costs. In this article, we review various measures to assess xerostomia and evaluate current and emerging solutions to address this condition in H&N cancer patients. These solutions typically seek to accomplish 1 of the 4 objectives: (1) to protect the salivary glands during RT, (2) to stimulate the remaining gland function, (3) to treat the symptoms of xerostomia, or (4) to regenerate the salivary glands. For each treatment, we assess its mechanisms of action, efficacy, safety, clinical utilization, and cost. We conclude that intensity-modulated radiation therapy is both the most widely used prevention approach and the most cost-effective existing solution and we highlight novel and promising techniques on the cost-effectiveness landscape.

Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells.

Based on their ability to control T-cell homeostasis, Foxp3(+)CD4(+)CD25(+) regulatory T cells (Tregs) are being considered for treatment of autoimmune disorders and acute graft-versus-host disease (aGVHD). When combining Tregs with the immunosuppressant rapamycin (RAPA), we observed reduced alloreactive conventional T-cell (Tconv) expansion and aGVHD lethality compared with each treatment alone. This synergistic in vivo protection was paralleled by intact expansion of polyclonal Tregs with conserved high FoxP3 expression. In contrast to Tconv, activation of Tregs with alloantigen and interleukin-2 preferentially led to signal transducer and activator of transcription 5 (STAT5) phosphorylation and not phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activity. Expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a negative regulator of the PI3K/Akt/mTOR pathway, remained high in Tregs but not Tconv during stimulation. Conversely, targeted deletion of PTEN increased susceptibility of Tregs to mTOR inhibition by RAPA. Differential impact of RAPA as a result of reduced usage of the mTOR pathway in Tregs compared with conventional T cells explains the synergistic effect of RAPA and Tregs in aGVHD protection, which has important implications for clinical trials using Tregs.

Host-derived interleukin-18 differentially impacts regulatory and conventional T cell expansion during acute graft-versus-host disease.

Interleukin (IL)-18 stimulates T helper 1 (Th1) and Th2-mediated immune responses, and has been shown to modulate acute graft-versus-host disease (aGVHD). It is still unknown whether increased IL-18 levels during aGVHD are of host or donor origin, and how the absence of IL-18 has an impact on migration and expansion of conventional CD4(+)CD25(-)(Tconv) and CD4(+)CD25(+) regulatory (Treg) T cells in vivo. By utilizing IL-18 gene-deficient donor versus recipient animals we found that the major cytokine production during the early phase of aGVHD induction was recipient derived, whereas donor hematopoietic cells contributed significantly less. By generating IL-18(-/-) luciferase transgenic mice we were able to investigate the impact of IL-18 on Tconv and Treg expansion and trafficking with in vivo bioluminescence imaging. Although migration to secondary lymphoid organs did not have a significantly impact from the absence of host IL-18, Tconv but not Treg expansion increased significantly. Absence of host IL-18 production translated into lower IFN-gamma levels in the early phase after transplantation. We conclude that host-derived IL-18 is a major factor for IFN-gamma production that may have a protective effect on CD4(+)-mediated aGVHD, but is nonessential for Treg expansion in an allogeneic environment.

Rat sex differences in anesthesia.

Studies involving substantially lengthy rat surgeries require extended anesthesia periods and often involve use of sodium pentobarbital (PENT). Results of previous experiments from our laboratory and elsewhere suggest that the duration of anesthesia and the need for anesthetic supplementation may differ between male and female rats. In the study reported here, we induced anesthesia in male and female Sprague Dawley rats (n = 10 for each sex), using a three-step procedure: brief induction with 5% isoflurane inhalation, PENT (50 mg/kg of body weight, i.p.), combined with 50 mg of PENT/kg given intragastrically. Adequate anesthesia depth was confirmed by absence of a response to a toe pinch. Plasma PENT concentration was measured at sequential 20-min periods and was found, on average, to be lower (P = 0.03) in male (13.28 +/- 1.13 microg/ml) than in female (20.27 +/- 0.66 microg/ml) rats, and decreased more rapidly (P = 0.003) in male rats. Distribution to a fractionally greater lean body mass and more rapid metabolism in males may account for these differences and explain the need for anesthetic supplementation in male, but not female rats.