Cost-Effectiveness of Depression Screening for Otolaryngology-Head and Neck Surgery Residents.

OBJECTIVES: This study aims to determine the cost-effectiveness of screening and treating otolaryngology-head and neck surgery residents for depression. METHODS: A Markov model was built using TreeAgePro, version 2019 (TreeAge Software Inc.; Williamstown, MA) to assess the cost-effectiveness of five potential treatment algorithms: 1) treat all residents with psychotherapy, 2) screen and treat depressed residents with psychotherapy, 3) screen and treat depressed residents with pharmacotherapy, 4) screen and treat depressed residents with combination psychotherapy/pharmacotherapy, and 5) no intervention. A Monte Carlo probabilistic sensitivity analysis (PSA), consisting of 1 thousand simulations over a cumulative 5-year period, was performed to evaluate both base case values and a range of values for model variables. RESULTS: Screening residents for depression and treating with combination psychotherapy/pharmacotherapy was cost-effective and the optimal strategy at a willingness-to-pay threshold of $50 thousand per quality-adjusted life year (QALY). This option demonstrated an incremental cost-effectiveness ratio of $27,578 per QALY for base case values. PSA confirmed these results and demonstrated that screening residents for depression and treating with either combination pharmacotherapy/psychotherapy, pharmacotherapy alone, or psychotherapy alone were cost-effective options in 94.9% of simulations. CONCLUSION: Depression and burnout remain crucial issues among resident physicians. This study demonstrates that actively screening residents for depression is cost-effective. Based on these results, residency programs may consider trialing standardized depression screening protocols. LEVEL OF EVIDENCE: I and II. Laryngoscope, 131:502-508, 2021.

Quantitative second harmonic generation imaging of leporine, canine, and porcine vocal fold collagen.

OBJECTIVES/HYPOTHESIS: Vocal fold collagen composition is an important determinant of material properties and mucosal wave propagation. Collagen alignment and straightness are quantitatively characterized by second harmonic generation (SHG) imaging. We examined leporine, canined and porcine vocal folds showing collagen composition variation that is species, location, and strain specific. STUDY DESIGN: Animal model. METHODS: Leporine (n = 5), canine (n = 5), and porcine (n = 5) larynges were harvested and fixed in situ. Samples were transversely sectioned, and SHG images were collected for two inferior-superior sections along five anterior-posterior locations. Additional porcine samples were fixed and imaged under tensile strain (0%, 5%, 10%, 15%, 20%, n = 5 per group). Two-way repeated measures (RM) analysis of variance (ANOVA) tested for section and location differences in each species. Multiway RM-ANOVA tested for section, location, and strain differences in porcine samples. RESULTS: Alignment and straightness were higher inferiorly in the porcine (P = .0047, P = .002) and canine (P = .0011, P < .001) vocal folds, but not in leporine samples (P = .67652, P = .4831). There were significant interactions between elongation and superior-inferior section for both alignment (P = .0047) and straightness (P = .0371). CONCLUSIONS: Our results correspond well to findings in the literature that the inferior vocal fold lip is stiffer in porcine and canine larynges. The absence of a collagen gradient in the leporine vocal fold is notable because rabbits are less vocal animals, indicating the collagen gradient may be a result of voice use and an important consideration in model selection when extracellular matrix is of interest. Strain results were also consistent with the role of collagen in strain stiffening behavior of vocal fold tissue. LEVEL OF EVIDENCE: NA Laryngoscope, 129:2549-2556, 2019.

Photodynamic therapy induces antifibrotic alterations in primary human vocal fold fibroblasts.

OBJECTIVES/HYPOTHESIS: Photodynamic therapy (PDT) is a promising treatment modality for laryngeal dysplasia, early-stage carcinoma, and papilloma, and was reported to have the ability to preserve laryngeal function and voice quality without clinical fibrotic response. We aimed to investigate the mechanism behind the antifibrotic effects of PDT on primary human vocal fold fibroblasts (VFFs) in vitro. STUDY DESIGN: In vitro analysis from one human donor. METHODS: Cell viability of VFFs in response to varying doses of PDT was investigated by the Cell Counting Kit-8 method. Sublethal-dose PDT (SL-PDT) was used for the following experiments. Expression of genes related to vocal fold extracellular matrix formation was analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. Effects of PDT on cell migration, collagen contraction, and transforming growth factor ß-1 (TGF-ß1)-induced myofibroblast differentiation were also analyzed. RESULTS: PDT affects the viability of VFFs in a dose-dependent manner. SL-PDT significantly changed the expression profile of VFFs with antifibrotic effects. It also inhibited cell migration, reduced collagen contraction, and reversed the fibroblast-myofibroblast differentiation induced by TGF-ß1. CONCLUSIONS: SL-PDT induces antifibrotic alterations in VFFs. This could explain the low incidence of vocal fold scar associated with PDT. Moreover, PDT may be useful in treating existing vocal fold scars. Further studies should focus on the in vivo effect of PDT on vocal fold wound healing and scar remodeling. LEVEL OF EVIDENCE: NA Laryngoscope, 128:E323-E331, 2018.

Excised larynx evaluation of subthyroid cartilage approach to medialization thyroplasty.

OBJECTIVES/HYPOTHESIS: To describe an alternative approach to medialization thyroplasty involving dissection underneath the thyroid cartilage with placement of a Gore-Tex implant, and to evaluate its effect on a range of phonatory measures using an excised canine larynx model. STUDY DESIGN: Animal model. METHODS: On each of eight excised canine larynges, the conditions of normal, paralysis, medialization thyroplasty by standard transthyroid cartilage approach, and medialization thyroplasty by experimental subthyroid cartilage approach were performed. Aerodynamic, acoustic, and mucosal wave parameters were measured for each condition. RESULTS: Compared to the vocal fold paralysis state, both the transthyroid and subthyroid approaches for Gore-Tex insertion resulted in significant decreases in phonation threshold pressure and phonation threshold flow. Both approaches also significantly decreased percent jitter, decreased percent shimmer, and improved signal-to-noise ratio. The mucosal wave was preserved after insertion of the Gore-Tex implant for both approaches. For all the phonatory measures except phonation threshold flow, there were no significant differences between the transthyroid and subthyroid approaches. CONCLUSIONS: Gore-Tex implantation via a subthyroid approach in an excised canine larynx model can produce effective medialization, preserve the mucosal wave, and significantly improve aerodynamic and acoustic parameters without meaningful difference compared to a traditional transthyroid approach. The subthyroid approach does not require creation of a thyroid cartilage window and could be a potentially valuable alternative method of performing medialization thyroplasty. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:675-681, 2018.

Oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States, 1973-2013.

OBJECTIVE: To analyze oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States for the years 1973 through 2013. STUDY DESIGN: Cross-sectional study using a large population-based cancer database. METHODS: Data on incidence and mortality rates were extracted from the Surveillance, Epidemiology, and End Results (SEER) 9 Database. Annual percentage change in rates was calculated using Joinpoint regression analysis (National Cancer Institute, Bethesda, MD). RESULTS: Incidence rates increased (annual percent change [APC]; 1.52, 95% confidence interval [CI] 0.17 to 2.88) from 1973 to 1983, remained stable (APC -0.52, 95% CI -1.30 to 0.26) from 1983 to 1997, and increased (APC 1.32, 95% CI 0.83 to 1.81) from 1997 to 2013. Overall, incidence rates increased for males (APC 0.73, 95% CI 0.22 to 1.25) but not females (APC -0.77, 95% CI -0.68 to 0.82). Incidence rates increased in the white population (APC 0.79, 95% CI 0.33 to 1.25) but decreased in the black population (APC -0.72, 95% CI -1.41 to -0.02). The incidence rates increased for tongue-base tumors (APC 1.17, 95% CI 0.42 to 1.92) and tonsil tumors (APC 0.47, 95% CI 1.10 to 4.96) but decreased for other sites. Incidence-based mortality decreased (APC -0.78, 95% CI -1.13 to -0.42) from 1993 to 2013. CONCLUSION: Oropharyngeal squamous cell carcinoma incidence rates increased in a nonlinear fashion from 1973 to 2013, whereas mortality rates declined. This, along with variation in trends by demographic and tumor factors, suggest that human papilloma virus is the main driver of the recent rise in incidence. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:1582-1588, 2018.

Purification and Characterization of RhoPDE, a Retinylidene/Phosphodiesterase Fusion Protein and Potential Optogenetic Tool from the Choanoflagellate Salpingoeca rosetta.

RhoPDE is a type I rhodopsin/phosphodiesterase gene fusion product from the choanoflagellate Salpingoeca rosetta. The gene was discovered around the time that a similar type I rhodopsin/guanylyl cyclase fusion protein, RhoGC, was shown to control phototaxis of an aquatic fungus through a cGMP signaling pathway. RhoPDE has potential as an optogenetic tool catalyzing the hydrolysis of cyclic nucleotides. Here we provide an expression and purification system for RhoPDE, as well as a crystal structure of the C-terminal phosphodiesterase catalytic domain. We show that RhoPDE contains an even number of transmembrane segments, with N- and C-termini both located on the cytoplasmic surface of the cell membrane. The purified protein exhibits an absorption maximum at 490 nm in the dark state, which shifts to 380 nm upon exposure to light. The protein acts as a cGMP-selective phosphodiesterase. However, the activity does not appear to be modulated by light. The protein is also active with cAMP as a substrate, but with a roughly 5-7-fold lower kcat. A truncation consisting solely of the phosphodiesterase domain is also active with a kcat for cGMP roughly 6-9-fold lower than that of the full-length protein. The isolated PDE domain was crystallized, and the X-ray structure showed the protein to be a dimer similar to human PDE9. We anticipate that the purification system introduced here will enable further structural and biochemical experiments to improve our understanding of the function and mechanism of this unique fusion protein.

Expression, purification, and spectral tuning of RhoGC, a retinylidene/guanylyl cyclase fusion protein and optogenetics tool from the aquatic fungus Blastocladiella emersonii.

RhoGC is a rhodopsin (Rho)-guanylyl cyclase (GC) gene fusion molecule that is central to zoospore phototaxis in the aquatic fungus Blastocladiella emersonii It has generated considerable excitement because of its demonstrated potential as a tool for optogenetic manipulation of cell-signaling pathways involving cyclic nucleotides. However, a reliable method for expressing and purifying RhoGC is currently lacking. We present here an expression and purification system for isolation of the full-length RhoGC protein expressed in HEK293 cells in detergent solution. The protein exhibits robust light-dependent guanylyl cyclase activity, whereas a truncated form lacking the 17- to 20-kDa N-terminal domain is completely inactive under identical conditions. Moreover, we designed several RhoGC mutants to increase the utility of the protein for optogenetic studies. The first class we generated has altered absorption spectra designed for selective activation by different wavelengths of light. Two mutants were created with blue-shifted (E254D, λmax = 390 nm; D380N, λmax = 506 nm) and one with red-shifted (D380E, λmax = 533 nm) absorption maxima relative to the wild-type protein (λmax = 527 nm). We also engineered a double mutant, E497K/C566D, that changes the enzyme to a specific, light-stimulated adenylyl cyclase that catalyzes the formation of cAMP from ATP. We anticipate that this expression/purification system and these RhoGC mutants will facilitate mechanistic and structural exploration of this important enzyme.

A Preliminary Case Report of a High-Quality Cost-effective Rigid Laryngoscopy Setup.

OBJECTIVE: To evaluate a cost-effective modified rigid laryngoscopy setup with a portable light source and high-resolution commercially available digital camera for use in smaller otolaryngology and family practice clinics. METHODS: The modified setup was used to obtain images of the larynx using both a traditional light source and a portable light source. Varying shutter speeds and ISOs were evaluated, and the optimal settings were determined for the modified setup. RESULTS: Picture quality was adequate, and the portable light source was bright enough. ISO from 640 to 1600 with shutter speeds ranging from 1/60 to 1/160 are ideal under the normal light source, while it is better to set the ISO between 4000 and 10 000 with shutter speeds from 1/60 to 1/100 under the portable light source. Picture quality was adequate with a resolution of 2768 pixels × 1848 pixels with 350 dpi × 350 dpi. CONCLUSIONS: Results show that the modified setup obtains images of adequate quality for use in the clinic. Additionally, since the larynx requires the most illumination for endoscopic imaging, a similar setup would work for imaging the ear and nose. This setup may make laryngoscopic exams more accessible to patients at smaller laryngoscopy clinics or family practice providers.

Parameters From the Complete Phonatory Range of an Excised Rabbit Larynx.

OBJECTIVE: This study aims to collect data throughout the complete phonatory range using rabbit larynges. STUDY DESIGN: This is a methodological excised rabbit larynx study. METHODS: Seven rabbit larynges were dissected and mounted on a modified excised laryngeal apparatus. Phonation was initiated at phonation threshold pressure (PTP) and airflow was increased by consistent increments until phonation instability pressure (PIP) was reached. At each airflow level, aerodynamic measurements, acoustic recordings, and high-speed videos were recorded. This procedure was repeated at multiple elongation conditions to further explore the parameters. Data were then compared across subjects and elongation conditions. RESULTS: At PTP, subglottal pressure, fundamental frequency, and sound pressure level were found to increase significantly as elongation was increased. As elongation was increased at PIP, airflow was found to significantly decrease, whereas fundamental frequency was found to significantly increase. Vibratory amplitude decreased at both PTP and PIP as elongation increased. Also, as elongation increased, the range of all parameters was found to decrease significantly. CONCLUSIONS: The results obtained, combined with the similarities of the histologic structure of the vocal fold lamina propria between rabbits and humans, validate the rabbit larynx as an effective and reliable model for tissue inflammation studies.

The Potential Role of Subglottal Convergence Angle and Measurement.

OBJECTIVE: This study aimed to explore subglottal convergence angle measurement. We hypothesize that the angle will change with glottis closure condition. Changes to the angle may alter vocal fold stress distribution, which could result in vocal fold pathologies. METHODS: Three vocal fold positions were evaluated by the degree of glottal closure and divided into three groups. Neck computed tomographic images of the subjects were gathered, and three-dimensional (3D) models of the vocal folds and the airway were reconstructed using Mimics software, through which the subglottal convergence angle was measured. Using one-way factor analysis of variance, we compared the angle among three groups. We explored the effect of the angle on vibration based on the material oblique section stress analysis. RESULTS: The subglottal convergence angle was effectively measured from 3D models. The angle changed with degree of glottal closure, with statistically significant differences among the three groups (P < 0.01). Changes to the angle alter subglottal stress distribution in the subglottal shear or normal direction by the material oblique section stress analysis theory. Larger subglottal convergence angle might reduce subglottal pressure in the shear direction below the vocal folds, which would make vibration and vocal fold mucosal wave generation more difficult. CONCLUSION: 3D model generation from computed tomographic data is an effective method of measuring the subglottal convergence angle, which changes with the degree of glottis closure, and may affect subglottal pressure distribution in the subglottal shear or normal direction and influence vocal fold vibration.

An Excised Canine Model of Anterior Glottic Web and Its Acoustic, Aerodynamic, and High-speed Measurements.

OBJECTIVES: This study aims to build an excised anterior glottic web (AGW) model and study the basic voice-related mechanisms of the AGW through investigating the acoustic, aerodynamic, and vibratory properties. STUDY DESIGN AND METHODS: Overall, four conditions were tested for each of the eight canine larynges used. At baseline, 10%, 20%, and 33% occlusion (as determined by the placement of the suture), acoustic, aerodynamic, and high-speed video data were collected while each larynx was phonated in a soundproof booth. RESULTS: The phonation threshold pressure (PTP) and the phonation threshold flow significantly increased as percent occlusion increased (P < 0.001). There were significant increases in jitter % and shimmer % from baseline group to AGW model groups at PTP, 1.25 PTP, and 1.5 PTP (P = 0.039, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.001, respectively). The fundamental frequency significantly increased as percent occlusion increased at all given pressures (P < 0.001). Correlation dimension (D2) was significantly higher in the AGW model groups than in the baseline group at PTP, 1.25 PTP, and 1.5 PTP (P = 0.002, P < 0.001, P = 0.01, respectively). High-speed videos revealed that, the left phase shift in the AGW model groups compared with the baseline at 1.25 PTP was significant (P = 0.027) and right phase shift at 1.5 PTP (P < 0.001). CONCLUSIONS: We presented an anatomically similar model of a type 1 AGW and confirmed its validity through aerodynamic, acoustic, and high-speed video analysis in our study. We observed and investigated the glottic web movement, which may be a new explanation for the pathologic voice-related mechanism of AGW.

Evaluation of type II thyroplasty on phonatory physiology in an excised canine larynx model.

OBJECTIVES/HYPOTHESIS: Type II thyroplasty is an alternative treatment for spasmodic dysphonia, addressing hyperadduction by incising and lateralizing the thyroid cartilage. We quantified the effect of lateralization width on phonatory physiology using excised canine larynges. METHODS: Normal closure, hyperadduction, and type II thyroplasty (lateralized up to 5 mm at 1-mm increments with hyperadducted arytenoids) were simulated in excised larynges (N = 7). Aerodynamic, acoustic, and videokymographic data were recorded at three subglottal pressures relative to phonation threshold pressure (PTP). One-way repeated measures analysis of variance assessed effect of condition on aerodynamic parameters. Random intercepts linear mixed effects models assessed effects of condition and subglottal pressure on acoustic and videokymographic parameters. RESULTS: PTP differed across conditions (P < .001). Condition affected percent shimmer (P < .005) but not percent jitter. Both pressure (P < .03) and condition (P < .001) affected fundamental frequency. Pressure affected vibratory amplitude (P < .05) and intrafold phase difference (P < .05). Condition affected phase difference between the vocal folds (P < .001). CONCLUSIONS: Hyperadduction increased PTP and worsened perturbation compared to normal, with near normal physiology restored with 1-mm lateralization. Further lateralization deteriorated voice quality and increased PTP. Acoustic and videokymographic results indicate that normal physiologic relationships between subglottal pressure and vibration are preserved at optimal lateralization width, but then degrade with further lateralization. The 1-mm optimal width observed here is due to the small canine larynx size. Future human trials would likely demonstrate a greater optimal width, with patient-specific value potentially determined based on larynx size and symptom severity. LEVEL OF EVIDENCE: NA Laryngoscope, 2016 127:396-404, 2017.

Over-vibration induced blood perfusion and vascular permeability changes may lead to vocal edema.

OBJECTIVES/HYPOTHESIS: To observe blood perfusion and vascular permeability changes under varying vibration frequency exposures. STUDY DESIGN: Animal model. METHODS: Blood perfusion was measured using laser Doppler flowmetry in eight rabbit auricular vessels (four rabbits) under nonvibration, and 62.5-Hz/1-mm, 125-Hz/1-mm, and 250-Hz/0.5-mm vibration frequency/amplitude exposures. Another 12 rabbits were randomly divided into vibration only and vibration with histamine groups. After 3 hours of continuous 125-Hz, 1-mm amplitude vibration of the auricle, vascular permeability was analyzed by absorbance of Evans blue-albumin complex. RESULTS: Significantly lower blood perfusion was observed in the vibration group, compared with no vibration exposure controls. Blood perfusion decreased 29 ± 16% as the vibration frequency was increased from 62.5 Hz to 125 Hz with the vibration amplitude constant at 1 mm. When the frequency was increased from 125 Hz to 250 Hz, while the amplitude was decreased from 1 mm to 0.5 mm, blood flow perfusion further decreased 29 ± 29%, and the decline tendency in blood perfusion showed no significant difference (P = .992). Meanwhile, in the vibration with histamine group, vascular permeability of the vibrated ears increased significantly compared to the nonvibrated ears (P = .005). CONCLUSIONS: Overvibration of the vocal folds due to voice overuse or abuse may significantly reduce blood perfusion, and increase vascular permeability in the vocal fold in inflammatory situations, which may lead to the formation of vocal edema. LEVEL OF EVIDENCE: NA Laryngoscope, 127:148-152, 2017.

Relocating the Active-Site Lysine in Rhodopsin: 2. Evolutionary Intermediates.

The visual pigment rhodopsin is a G protein-coupled receptor that covalently binds its retinal chromophore via a Schiff base linkage to an active-site Lys residue in the seventh transmembrane helix. Although this residue is strictly conserved among all type II retinylidene proteins, we found previously that the active-site Lys in bovine rhodopsin (Lys296) can be moved to three other locations (G90K, T94K, S186K) while retaining the ability to form a pigment with retinal and to activate transducin in a light-dependent manner [ Devine et al. ( 2013 ) Proc. Natl. Acad. Sci. USA 110 , 13351 - 13355 ]. Because the active-site Lys is not functionally constrained to be in helix seven, it is possible that it could relocate within the protein, most likely via an evolutionary intermediate with two active-site Lys. Therefore, in this study we characterized potential evolutionary intermediates with two Lys in the active site. Four mutant rhodopsins were prepared in which the original Lys296 was left untouched and a second Lys residue was substituted for G90K, T94K, S186K, or F293K. All four constructs covalently bind 11-cis-retinal, form a pigment, and activate transducin in a light-dependent manner. These results demonstrate that rhodopsin can tolerate a second Lys in the retinal binding pocket and suggest that an evolutionary intermediate with two Lys could allow migration of the Schiff base Lys to a position other than the observed, highly conserved location in the seventh TM helix. From sequence-based searches, we identified two groups of natural opsins, insect UV cones and neuropsins, that contain Lys residues at two positions in their active sites and also have intriguing spectral similarities to the mutant rhodopsins studied here.

Extension and Application of High-Speed Digital Imaging Analysis Via Spatiotemporal Correlation and Eigenmode Analysis of Vocal Fold Vibration Before and After Polyp Excision.

OBJECTIVES/HYPOTHESIS: To evaluate the spatiotemporal correlation of vocal fold vibration using eigenmode analysis before and after polyp removal and explore the potential clinical relevance of spatiotemporal analysis of correlation length and entropy as quantitative voice parameters. We hypothesized that increased order in the vibrating signal after surgical intervention would decrease the eigenmode-based entropy and increase correlation length. STUDY DESIGN: Prospective case series. METHODS: Forty subjects (23 males, 17 females) with unilateral (n = 24) or bilateral (n = 16) polyps underwent polyp removal. High-speed videoendoscopy was performed preoperatively and 2 weeks postoperatively. Spatiotemporal analysis was performed to determine entropy, quantification of signal disorder, correlation length, size, and spatially ordered structure of vocal fold vibration in comparison to full spatial consistency. The signal analyzed consists of the vibratory pattern in space and time derived from the high-speed video glottal area contour. RESULTS: Entropy decreased (Z = -3.871, P < .001) and correlation length increased (t = -8.913, P < .001) following polyp excision. The intraclass correlation coefficients (ICC) for correlation length and entropy were 0.84 and 0.93. CONCLUSION: Correlation length and entropy are sensitive to mass lesions. These parameters could potentially be used to augment subjective visualization after polyp excision when evaluating procedural efficacy.

Bioengineered vocal fold mucosa for voice restoration.

Patients with voice impairment caused by advanced vocal fold (VF) fibrosis or tissue loss have few treatment options. A transplantable, bioengineered VF mucosa would address the individual and societal costs of voice-related communication loss. Such a tissue must be biomechanically capable of aerodynamic-to-acoustic energy transfer and high-frequency vibration and physiologically capable of maintaining a barrier against the airway lumen. We isolated primary human VF fibroblasts and epithelial cells and cocultured them under organotypic conditions. The resulting engineered mucosae showed morphologic features of native tissue, proteome-level evidence of mucosal morphogenesis and emerging extracellular matrix complexity, and rudimentary barrier function in vitro. When grafted into canine larynges ex vivo, the mucosae generated vibratory behavior and acoustic output that were indistinguishable from those of native VF tissue. When grafted into humanized mice in vivo, the mucosae survived and were well tolerated by the human adaptive immune system. This tissue engineering approach has the potential to restore voice function in patients with otherwise untreatable VF mucosal disease.

Characterizing liquid redistribution in a biphasic vibrating vocal fold using finite element analysis.

OBJECTIVES: Vocal fold tissue is biphasic and consists of a solid extracellular matrix skeleton swelled with interstitial fluid. Interactions between the liquid and solid impact the material properties and stress response of the tissue. The objective of this study was to model the movement of liquid during vocal fold vibration and to estimate the volume of liquid accumulation and stress experienced by the tissue near the anterior-posterior midline, where benign lesions are observed to form. METHODS: A three-dimensional biphasic finite element model of a single vocal fold was built to solve for the liquid velocity, pore pressure, and von Mises stress during and just after vibration using the commercial finite element software COMSOL Multiphysics (Version 4.3a, 2013, Structural Mechanics and Subsurface Flow Modules). Vibration was induced by applying direct load pressures to the subglottal and intraglottal surfaces. Pressure ranges, frequency, and material parameters were chosen based on those reported in the literature. Postprocessing included liquid velocity, pore pressure, and von Mises stress calculations as well as the frequency-stress and amplitude-stress relationships. RESULTS: Resulting time-averaged velocity vectors during vibration indicated liquid movement toward the midline of the fold, as well as upward movement in the inferior-superior direction. Pore pressure and von Misses stresses were higher in this region just after vibration. A linear relationship was found between the amplitude and pore pressure, whereas a nonlinear relationship was found between the frequency and pore pressure. CONCLUSIONS: Although this study had certain computational simplifications, it is the first biphasic finite element model to use a realistic geometry and demonstrate the ability to characterize liquid movement due to vibration. Results indicate that there is a significant amount of liquid that accumulates at the midline; however, the role of this accumulation still requires investigation. Further investigation of these mechanical factors may lend insight into the mechanism of benign lesion formation.

Permeability of canine vocal fold lamina propria.

OBJECTIVES/HYPOTHESIS: Determine the permeability of excised canine vocal fold lamina propria. STUDY DESIGN: Basic science. METHODS: Vocal folds were excised from canine larynges and mounted within a device to measure the flow of 0.9% saline through the tissue over time. The resultant fluid volume displaced over time was then used in a variation of Darcy's law to calculate the permeability of the tissue. Permeability was found through each anatomical plane of the vocal fold, with five samples per plane. Permeability was also found for lamina propria stretched to 10%, 20%, and 30% of its initial length to determine the effects of tensile strain on permeability, with five samples per level of strain. RESULTS: Permeability was found to be 1.40 × 10(-13) m(3) s/kg through the sagittal plane, 1.00 × 10(-13) m(3) s/kg through the coronal plane, and 4.02 × 10(-13) m(3) s/kg through the axial plane. It was significantly greater through the axial plane than both the sagittal (P = .025) and coronal (P = .009) planes. Permeability under strain through the sagittal plane was found to be 1.94 × 10(-13) m(3) s/kg under 10% strain, 3.35 × 10(-13) m(3) s/kg under 20% strain, and 4.80 × 10(-13) m(3) s/kg under 30% strain. The permeability significantly increased after 20% strain (P < .05). CONCLUSIONS: Permeability in canine vocal fold lamina propria was found to be increased along the anterior-posterior axis, following the length of the vocal folds. This may influence fluid distribution within the lamina propria during and after vibration. Similarly, permeability increased after 20% strain was imposed on the lamina propria, and may influence vocal fold dynamics during certain phonation tasks. LEVEL OF EVIDENCE: NA Laryngoscope, 125:941-945, 2015.

Voice Outcome of Modified Frontolateral Partial Laryngectomy in Excised Canine Larynges and Finite Element Model.

OBJECTIVE: To evaluate vocal parameters after modified frontolateral partial laryngectomy (MFLPL) and frontolateral partial laryngectomy (FLPL) in both excised canine and finite element models. STUDY DESIGN: FLPL and MFLPL were compared, using a prospective paired case control laboratory study with excised canine larynx and computational modeling. SETTING: Basic science study conducted in university laboratory. METHODS: FLPL and MFLPL were performed serially on 9 excised canine larynges. The excised larynx bench apparatus was used to collect phonation threshold pressure (PTP) and high-speed video data. A finite element model was built to compare a normal vocal fold with applied tension, a cut fold with no applied tension (simulating FLPL), and a cut fold with applied tension (simulating MFLPL). Stress values and distributions across the 3 conditions were computed. RESULTS: The mean PTP increase after MFLPL (15.45-17.46 cmH2O) was not statistically significant. In the excised canine model, fundamental frequency (F0) showed a significant increase for the MFLPL (P = .039). Differences in vibration amplitudes were not statistically significant. Von Mises stress distribution was most similar between the MFLPL model and the normal fold. Maximum von Mises stresses at the midline were 17.56, 21.63, and 5.10 kPa for the normal, MFLPL, and FLPL, respectively, and 47.57, 63.98, and 101.97 kPa at the peripheries. CONCLUSIONS: From these results, we conclude that MFLPL has the potential to give a better voice outcome while avoiding tracheotomy in partial laryngectomy patients. In vivo study in canines to examine the healing process would lend further evidence-based support for this surgical method.