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Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV). INO-3107, DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11, was evaluated in a 52-week Phase 1/2 study for efficacy, safety, and immunogenicity (NCT04398433). Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP, requiring ≥2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation. The primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included surgical intervention frequency and change in RRP Severity Score (modified) post-INO-3107 and assessment of immune responses. 81% (26/32) of patients experienced surgery reduction following INO-3107 compared with the year prior to treatment. Blood assessments revealed HPV-6 and HPV-11 antigen-specific T-cell induction. RNA sequencing identified an inflammatory response in papillomas, inclusive of cytolytic CD8 + T-cell signatures. T-cell receptor sequencing revealed emergent T-cell clones in blood and confirmed trafficking to papillomas. Treatment-related adverse events (AEs) were reported in 13/32 (41%) patients, all low-grade. INO-3107 provides clinical benefit to HPV-6 and/or HPV-11-associated RRP adults and is well-tolerated. Importantly, treatment-induced peripheral T-cell responses traffic to airway tissue and are associated with clinical response. In this phase 1/2 trial, the authors show that INO-3107, a DNA immunotherapy designed to elicit an immune response against HPV-6 and -11 recurrent respiratory papillomatosis, is well-tolerated and demonstrates an antigen specific immune response resulting in surgical reduction in 81% of trial participants. [ABSTRACT FROM AUTHOR]

Objectives: The paralaryngeal muscles are thought to be hyperfunctional with phonation in patients with primary muscle tension dysphonia (pMTD). However, objective, quantitative tools to assess paralaryngeal movement patterns lack. The objectives of this study were to (1) validate the use of optical flow to characterize paralaryngeal movement patterns with phonation, (2) characterize phonatory optical flow velocities and variability of the paralaryngeal muscles before and after a vocal load challenge, and (3) compare phonatory optical flow measures to standard laryngoscopic, acoustic, and self‐perceptual assessments. Methods: Phonatory movement velocities and variability of the paralaryngeal muscles at vocal onsets and offsets were quantified from ultrasound videos and optical flow methods across 42 subjects with and without a diagnosis of pMTD, before and after a vocal load challenge. Severity of laryngoscopic mediolateral supraglottic compression, acoustic perturbation, and ratings of vocal effort and discomfort were also obtained at both time points. Results: There were no significant differences in optical flow measures of the paralaryngeal muscles with phonation between patients with pMTD and controls. Patients with pMTD had significantly more supraglottic compression, higher acoustic perturbations, and higher vocal effort and vocal tract discomfort ratings. Vocal load had a significant effect on vocal effort and discomfort but not on supraglottic compression, acoustics, or optical flow measures of the paralaryngeal muscles. Conclusion: Optical flow methods can be used to study paralaryngeal muscle movement velocity and variability patterns during vocal productions, although the role of the paralaryngeal in pMTD diagnostics (e.g., vocal hyperfunction) remains suspect. Level of Evidence: 2 Laryngoscope, 134:1792–1801, 2024 [ABSTRACT FROM AUTHOR]

Objective: To review the current literature about epidemiology, etiologies and surgical management of bilateral vocal fold paralysis (BVFP). Data Sources: PubMED, Scopus, and Cochrane Library. Review Methods: A systematic review of the literature on epidemiology, etiologies, and management of adult patients with BVFP was conducted through preferred reporting items for systematic reviews and meta‐analyses statements by 2 investigators. Results: Of the 360 identified papers, 245 were screened, and of these 55 were considered for review. The majority (76.6%) of BVFP cases are iatrogenic. BVFP requires immediate tracheotomy in 36.2% of cases. Laterofixation of the vocal fold was described in 9 studies and is a cost‐effective alternative procedure to tracheotomy while awaiting potential recovery. Unilateral and bilateral posterior transverse cordotomy outcomes were reported in 9 and 7 studies, respectively. Both approaches are associated with a 95.1% decannulation rate, adequate airway volume, but voice quality worsening. Unilateral/bilateral partial arytenoidectomy data were described in 4 studies, which reported lower decannulation rate (83%) and better voice quality outcome than cordotomy. Revision rates and complications vary across studies, with complications mainly involving edema, granuloma, fibrosis, and scarring. Selective posterior cricoarytenoid reinnervation is being performed by more surgeons and should be a promising addition to the BVFP surgical armamentarium. Conclusion: Depending on techniques, the management of BVFP may be associated with several degrees of airway improvements while worsened or unchanged voice quality. The heterogeneity between studies, the lack of large‐cohort controlled randomized studies and the confusion with posterior glottic stenosis limit the draw of clear conclusion about the superiority of some techniques over others. [ABSTRACT FROM AUTHOR]

Objectives: It has been assumed that patients with primary muscle tension dysphonia (pMTD) have more extrinsic laryngeal muscle (ELM) tension, but tools to study this phenomenon lack. Shear wave elastography (SWE) is a potential method to address these shortcomings. The objectives of this study were to apply SWE to the ELMs, compare SWE measures to standard clinical metrics, and determine group differences in pMTD and typical voice users before and after vocal load. Methods: SWE measurements of the ELMs from ultrasound examinations of the anterior neck, supraglottic compression severities from laryngoscopic images, cepstral peak prominences (CPP) from voice recordings, and self‐perceptual ratings of vocal effort and discomfort were obtained in voice users with (N = 30) and without (N = 35) pMTD, before and after a vocal load challenge. Results: ELM tension significantly increased from rest‐to‐voiced conditions in both groups. However, the groups were similar in their ELM stiffness levels at SWE at baseline, during vocalization, and post‐vocal load. Levels of vocal effort and discomfort and supraglottic compression were significantly higher and CPP was significantly lower in the pMTD group. Vocal load had a significant effect on vocal effort and discomfort but not on laryngeal or acoustic patterns. Conclusion: SWE can be used to quantify ELM tension with voicing. Although the pMTD group reported significantly higher levels of vocal effort and vocal tract discomfort and, on average, exhibited significantly more severe supraglottic compression and lower CPP values, there were no group differences in levels of ELM tension using SWE. Level of Evidence: 2 Laryngoscope, 133:3482–3491, 2023 [ABSTRACT FROM AUTHOR]

Background/Objectives: False vocal fold (FVF) hyperfunction during phonation is thought to be a diagnostic sign of primary muscle tension dysphonia (pMTD). However, hyperfunctional patterns with phonation are also observed in typical speakers. This study tested the hypothesis that FVF posturing during quiet breathing, as measured by the curvature of FVF, could differentiate patients with pMTD from typical speakers. Methods: Laryngoscopic images were collected prospectively in 30 subjects with pMTD and 33 typical speakers. Images were acquired at the end of expiration and maximal inspiration during quiet breathing, during sustained /i/, and during loud phonation before and after a 30‐min vocal loading task. The FVF curvature (degree of concavity/convexity) was quantified using a novel curvature index (CI, >0 for hyperfunctional/convex, <0 for "relaxed"/concave) and compared between the two groups. Results: At end‐expiration, the pMTD group adopted a convex FVF contour, whereas the control group adopted a concave FVF contour (mean CI 0.123 [SEM 0.046] vs. −0.093 [SEM 0.030], p = 0.0002) before vocal loading. At maximal inspiration, the pMTD group had a neutral/straight FVF contour, whereas the control group had a concave FVF contour (mean CI 0.012 [SEM 0.038] vs. −0.155 [SEM 0.018], p = 0.0002). There were no statistically significant differences in FVF curvature between groups in either the sustained voiced or loud conditions. Vocal loading did not change any of these relationships. Conclusions: A hyperfunctional posture of the FVFs during quiet breathing especially at end‐expiration may be more indicative of a hyperfunctional voice disorder than supraglottic constriction during voicing. Level of Evidence: 3 Laryngoscope, 133:3449–3454, 2023 [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety, immunogenicity, and efficacy of INO‐3107, a DNA immunotherapy designed to elicit targeted T‐cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433). Methods: Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO‐3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9. Patients underwent surgical debulking within 14 days prior to first dose, with office laryngoscopy and staging at screening and weeks 6, 11, 26, and 52. Primary endpoint was safety and tolerability, as assessed by treatment‐emergent adverse events (TEAEs). Secondary endpoints included frequency of surgical interventions post‐INO‐3107 and cellular immune responses. Results: An initial cohort of 21 patients was enrolled between October 2020 and August 2021. Fifteen (71.4%) patients had ≥1 TEAE; 11 (52.4%) were Grade 1, and 3 (14.3%) were Grade 3 (none treatment related). The most frequently reported TEAE was injection site or procedural pain (n = 8; 38.1%). Sixteen (76.2%) patients had fewer surgical interventions in the year following INO‐3107 administration, with a median decrease of 3 interventions versus the preceding year. The RRP severity score, modified by Pransky, showed improvement from baseline to week 52. INO‐3107 induced durable cellular responses against HPV‐6 and HPV‐11, with an increase in activated CD4 and CD8 T cells and CD8 cells with lytic potential. Conclusion: The data suggest that INO‐3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP. Level of Evidence: 3 Laryngoscope, 133:3087–3093, 2023 [ABSTRACT FROM AUTHOR]

Objective: To compare characteristics of patients ≥65 years presenting with idiopathic subglottic stenosis (iSGS) to patients diagnosed at <65 years. We hypothesize that the groups have similar comorbidities and disease courses. Data Sources: Medical records of patients treated for iSGS at a tertiary care institution from January 2005–September 2022. Review Methods: Patient demographics, time from symptom onset to diagnosis, medical history and comorbidities, and treatment modalities/intervals were recorded and analyzed. Characteristics of patients ≥65 and <65 years at presentation were compared using Chi‐square analysis for non‐numeric values and the Mann–Whitney U‐test for numeric values. Results: One hundred seven patients with iSGS were identified and 16 (15%) were aged ≥65 years (mean age 72.6, 15 female) at presentation. These patients were compared to 91 patients aged <65 years (mean age = 47.6, 90 female). Patients ≥65 years had higher rates of type 2 diabetes mellitus (T2DM) (p = 0.004) and tobacco use (p = 0.004). There were no significant differences in body mass index, gastroesophageal reflux disease, hormone replacement therapy, time from symptom onset to presentation, or length of operative treatment intervals. Conclusion: Patients ≥65 years with iSGS have higher rates of tobacco use, suggesting that alterations in wound healing may play a role in the development of iSGS in this age group. Although rates of T2DM were higher in the elderly group, clinical significance may be limited given the overall higher rate of diabetes mellitus in the elderly population. Level of Evidence: 4 Laryngoscope, 133:3075–3079, 2023 [ABSTRACT FROM AUTHOR]

Background/Objectives: Tightly‐focused ultrafast laser pulses (pulse widths of 100 fs–10 ps) provide high peak intensities to produce a spatially confined tissue ablation effect. The creation of sub‐epithelial voids within scarred vocal folds (VFs) via ultrafast laser ablation may help to localize injectable biomaterials to treat VF scarring. Here, we demonstrate the feasibility of this technique in an animal model using a custom‐designed endolaryngeal laser surgery probe. Methods: Unilateral VF mucosal injuries were created in two canines. Four months later, ultrashort laser pulses (5 ps pulses at 500 kHz) were delivered via the custom laser probe to create sub‐epithelial voids of ~3 × 3‐mm2 in both healthy and scarred VFs. PEG‐rhodamine was injected into these voids. Ex vivo optical imaging and histology were used to assess void morphology and biomaterial localization. Results: Large sub‐epithelial voids were observed in both healthy and scarred VFs immediately following in vivo laser treatment. Two‐photon imaging and histology confirmed ~3‐mm wide subsurface voids in healthy and scarred VFs of canine #2. Biomaterial localization within a void created in the scarred VF of canine #2 was confirmed with fluorescence imaging but was not visualized during follow‐up two‐photon imaging. As an alternative, the biomaterial was injected into the excised VF and could be observed to localize within the void. Conclusions: We demonstrated sub‐epithelial void formation and the ability to inject biomaterials into voids in a chronic VF scarring model. This proof‐of‐concept study provides preliminary evidence towards the clinical feasibility of such an approach to treating VF scarring using injectable biomaterials. Level of Evidences: N/A Laryngoscope, 133:3042–3048, 2023 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To determine if (1) the likelihood of presenting with phonotraumatic lesions differs by singing genre in treatment‐seeking singers and (2) if the distribution of phonotraumatic lesion types differs by singing genre. Study Type: Retrospective. Methods: Records of singers who presented with a voice complaint over the course of 2.5 years (June 2017–December 2019) were reviewed to determine the proportion of those with phonotraumatic lesions as a function of genre (Study 1). Separately, the lesion types and genres of singers diagnosed with phonotraumatic lesions over a 9‐year period (July 2011–March 2020) were determined (Study 2). Results: In Study 1, 191 of 712 (26.8%) dysphonic singers were diagnosed with phonotraumatic lesions. Country/folk, gospel/jazz, and musical theater singers were more likely to present with phonotraumatic lesions. In Study 2, in 443 singers with phonotraumatic lesions, polyps and pseudocysts, but not nodules, were found to be distributed unequally across genres (χ2p = 0.006, p < 0.0001, p = 0.064, respectively). Praise/worship singers had significantly higher proportions of polyps compared to choral singers (OR 4.8 [95% CI 1.9–12.5]) or compared to musical theater singers (OR 7.2 [95% CI 2.5–20.8]). Opera singers had significantly higher proportions of pseudocysts than choral singers (OR 3.1 [95% CI 1.5–6.1]) or musical theater singers (OR 3.7 [95% CI 1.8–7.6]). Conclusions: The higher incidence of polyps in praise/worship singers likely reflects the more emphatic nature of singing and the tendency for acute injury. The higher incidence of pseudocysts in opera singers may reflect a more chronic nature of injury. Level of Evidence: 4 Laryngoscope, 133:1683–1689, 2023 [ABSTRACT FROM AUTHOR]

Objectives: The clinical determination of vocal fold (VF) hypomobility based on laryngoscopy is subjective. Previous studies point to VF motion anomaly as the most commonly reported factor in the diagnosis of hypomobility. This study tested the hypotheses that VF angular velocities and angular range of motion (ROM) differ between the two VFs in cases of unilateral VF hypomobility. Study Design: Retrospective. Methods: Semi‐automated analysis of laryngoscopic videos of 18 subjects diagnosed with unilateral VF hypomobility and 13 subjects with normal VF mobility was performed to quantify/compare the VF angular velocity and ROM between the two VFs during /i/−sniff and laugh. Results: In the hypomobile VF group, 7 out of 15 (47%) videos with /i/−sniff and 5 out of 8 (63%) with laugh had a statistically significant difference in the angular velocities between the VFs in either abduction or adduction. For VF ROM, 8 out of 15 (53%) /i/−sniff videos and 4 out of 8 (50%) with laughter had a statistically significant difference between VFs. In the group without the diagnosis of VF hypomobility, 9 out of 13 subjects (69%) had no difference in VF angular velocity and ROM during either /i/−sniff or laugh. Conclusions: Differences in VF angular velocity or ROM are measurable in a substantial subset of subjects diagnosed with unilateral VF hypomobility. Clinicians' ability to gauge VF motion goes beyond what can be extracted from frame‐by‐frame analysis. Other visual cues, in addition to VF angular velocity and ROM, likely contribute to the perception of unilateral VF hypomobility. Level of Evidence: 3 Laryngoscope, 133:866–874, 2023 [ABSTRACT FROM AUTHOR]

Creation of sub-epithelial voids within scarred vocal folds via ultrafast laser ablation may help in localization of injectable therapeutic biomaterials towards an improved treatment for vocal fold scarring. Several ultrafast laser surgery probes have been developed for precise ablation of surface tissues; however, these probes lack the tight beam focusing required for sub-surface ablation in highly scattering tissues such as vocal folds. Here, we present a miniaturized ultrafast laser surgery probe designed to perform sub-epithelial ablation in vocal folds. The requirement of high numerical aperture for sub-surface ablation, in addition to the small form factor and side-firing architecture required for clinical use, made for a challenging optical design. An Inhibited Coupling guiding Kagome hollow core photonic crystal fiber delivered micro-Joule level ultrashort pulses from a high repetition rate fiber laser towards a custom-built miniaturized objective, producing a 1/e2 focal beam radius of 1.12 ± 0.10 μm and covering a 46 × 46 μm2 scan area. The probe could deliver up to 3.8 μJ pulses to the tissue surface at 40% transmission efficiency through the entire system, providing significantly higher fluences at the focal plane than were required for sub-epithelial ablation. To assess surgical performance, we performed ablation studies on freshly excised porcine hemi-larynges and found that large area sub-epithelial voids could be created within vocal folds by mechanically translating the probe tip across the tissue surface using external stages. Finally, injection of a model biomaterial into a 1 × 2 mm2 void created 114 ± 30 μm beneath the vocal fold epithelium surface indicated improved localization when compared to direct injection into the tissue without a void, suggesting that our probe may be useful for pre-clinical evaluation of injectable therapeutic biomaterials for vocal fold scarring therapy. With future developments, the surgical system presented here may enable treatment of vocal fold scarring in a clinical setting. [ABSTRACT FROM AUTHOR]

Objectives: To discover patterns of phonotraumatic lesions in singers and investigate factors that differentiate those who underwent surgery from those who did not. We hypothesized that 1) lesion type distribution differs by age, sex, singer classification (professional/amateur), and history of formal voice training; 2) the likelihood of surgery is associated with singer classification and voice training. Study Design: Retrospective. Methods: Retrospective review of 438 singers with phonotraumatic lesions over a 9‐year period. Lesion type distribution was analyzed with respect to sex, age, singer classification, and voice training. The association of eventual surgery with these factors was also analyzed. Results: Nodules accounted for over half of the cohort (58%), followed by pseudocysts (20%), polyps (14%), and cysts (4%). Nearly two of every three injured female singers, but fewer than one out of every three injured male singers, had nodules. In contrast, over half of the injured males had polyps, whereas only 6% of injured females had polyps. In females, polyps occurred at a later age, and in males, nodules occurred at a younger age compared to other lesion types. Only 14% of the total cohort eventually underwent surgery. Professional singers without formal voice training were almost eight times more likely to have undergone surgery than amateur singers with voice training. Conclusions: Professional singers were more likely to undergo surgery than amateurs, and formal voice training was associated with a lower likelihood of surgery. The observation that polyps tended to occur in older women may have implications for the pathogenesis of vocal fold polyps. Level of Evidence: 4 Laryngoscope, 132:2180–2186, 2022 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To examine patterns of recurrence of benign phonotraumatic vocal fold lesions over time for insights into pathophysiology. Study Design: Case series with mathematical modeling. Methods: Medical records and stroboscopic exams of adults who underwent microlaryngoscopic resection of phonotraumatic vocal fold lesions over a 13‐year period were reviewed for time to recurrence after surgery. Uniform and log‐normal probability distributions were fitted to the time to recurrence curves for vocal fold polyps, midfold masses, and pseudocysts. Model fits were compared using the Akaike information criterion corrected, a standard measure of the goodness of fit. Stochastic simulations were used to verify that the mechanistic hypotheses were concordant with the selected probability distributions and empiric data. Results: Of 567 patients who underwent microlaryngoscopic resection, 65 had a recurrence (16 polyps, 14 midfold masses, and 35 pseudocysts). Midfold mass and pseudocyst recurrences were predominantly seen in younger women. Polyps were best fit by a uniform distribution rather than log‐normal, whereas midfold masses and pseudocysts were better fit by log‐normal rather than uniform. Stochastic simulations suggest that polyps recur sporadically according to a paroxysmal‐developmental model, whereas midfold mass and pseudocyst recurrences follow a force‐multiplication, damage‐accumulation process. Conclusions: Vocal fold polyps are acute lesions evenly distributed by age and gender that recur uniformly over time, suggesting they arise from sudden tissue reactions to phonotraumatic stress. Pseudocysts and midfold fibrous masses are chronic lesions predominantly found in young women that recur with log‐normal distribution over time, suggesting gradual damage accumulation in larynges predisposed to enhanced phonotrauma. Level of Evidence: 4 Laryngoscope, 131:2523–2529, 2021 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Anterior (Wendler) glottoplasty has become a popular surgery for voice feminization. However, there has been some discrepancy between its theoretical pitch‐raising potential and what is actually achievable, and downsides to shortening the glottis have not been fully explored. In addition, descriptions of the surgery are inconsistent in their treatment of the vocal ligament. This study aimed to determine 1) how fundamental frequency (fo) is expected to vary with length of anterior glottic fixation, 2) the impact of glottic shortening on sound pressure level (SPL), and 3) the effect of including the ligament in fixation. Study Design: Computational simulation. Methods: Voice production was simulated in a fiber‐gel finite element computational model using canonical male vocal fold geometry incorporating a three‐layer vocal fold composition (superficial lamina propria, vocal ligament, and thyroarytenoid muscle). Progressive anterior glottic fixation (0, 1/8, 2/8, 3/8, etc. up to 7/8 of membranous vocal fold length) was simulated. Outcome measures were fo, SPL, and glottal flow waveforms. Results: fo increased from 110 Hz to 164 Hz when the anterior one‐half vocal fold was fixed and continued to progressively rise with further fixation. SPL progressively decreased beyond 1/8 to 1/4 fixation. Inclusion of the vocal ligament in fixation did not further increase fo. Any fixation increased aperiodicity in the acoustic signal. Conclusions: The optimal length of fixation is a compromise between pitch elevation and reduction in output acoustic power. The simulation also provided a potential explanation for vocal roughness that is sometimes noted after anterior glottoplasty. Level of Evidence: NA Laryngoscope, 131:1081–1087, 2021 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Carbon dioxide laser transverse posterior cordotomy (TPC) aims to improve airway aperture in patients with glottic obstruction. Postoperative complications may worsen airway compromise and necessitate additional interventions. We sought to identify factors impacting outcomes after TPC. Study Design: Retrospective chart review. Methods: Medical records of patients who underwent TPC for glottic airway obstruction at a tertiary‐care medical center between 2008 and 2018 were reviewed. Demographics, comorbidities, and intra‐ and postoperative management strategies were analyzed. Results: Twenty patients who underwent TPC for glottic airway obstruction met inclusion criteria. The mean age was 57 years, and 13 patients were female. Mean follow‐up time was 442 days. Seven patients had posterior glottic stenosis, and 13 had bilateral vocal fold paralysis. Twelve patients developed postoperative complications including granuloma formation (four patients), hospital readmission for dyspnea due to glottic edema (five patients), need for revision surgery (nine patients), or failure to decannulate tracheotomy (five patients). Eight patients had an uncomplicated recovery with improved dyspnea, with two patients with tracheotomies decannulated. Patients with a history of smoking tobacco were more likely to experience complications (P =.035). There were no significant differences in outcomes with respect to history of head and neck radiation or gastroesophageal reflux disease. Steroid injection at the surgical site and postoperative medications did not significantly impact outcomes. With respect to granuloma formation, none of the variables analyzed reached significance. Conclusions: History of tobacco use increases complication rates after TPC. Other patient comorbidities and intra‐ and postoperative management strategies do not impact outcomes. Level of Evidence: 4 Laryngoscope, 131:1066–1070, 2021 [ABSTRACT FROM AUTHOR]

Objective: Most type 1 thyroplasty implants and some common injectable materials are mechanically stiff. Placing them close to the supple vocal fold mucosa can potentially dampen vibration and adversely impact phonation, yet this effect has not been systematically investigated. This study aims to examine the effect of implant depth on vocal fold vibration and vocal output.Study Design: Computational simulation.Methods: Voice production was simulated with a fiber-gel finite element computational model that incorporates a three-layer vocal fold composition (superficial lamina propria, vocal ligament, thyroarytenoid muscle). Implants of various depths were simulated, with a "deeper" or more medial implant positioned closer to the vocal fold mucosa and replacing more muscle elements. Trajectories of surface and within-tissue nodal points during vibration were produced. Outcome measures were the trajectory radii, fundamental frequency (F0 ), sound pressure level (SPL), and smoothed cepstral peak prominence (CPPS) as a function of implant depth.Results: Amplitude of vibration at the vocal fold medial surface was reduced by an implant depth of as little as 14% of the total transverse vocal fold depth. Increase in F0 and decrease in CPPS were noted beyond 30% to 40% implant depth, and SPL decreased beyond 40% to 60% implant depth.Conclusions: Commonly used implants can dampen vibration "from a distance," ie, even without being immediately adjacent to vocal fold mucosa. Since implants are typically placed at depths examined in this study, stiff implants likely have a negative vocal impact in a subset of patients. Softer materials may be preferable, especially in bilateral medialization procedures.Level Of Evidence: N/A Laryngoscope, 130:2192-2198, 2020. [ABSTRACT FROM AUTHOR]

Objective: Spontaneous vocal recovery from idiopathic vocal fold paralysis (VFP) appears to differ in time course from recovery in iatrogenic VFP. This study aimed to determine if this difference could be explained by differing mechanisms causing recurrent laryngeal nerve (RLN) dysfunction, specifically whether idiopathic VFP is consistent with a focal RLN axonal lesion.Study Design: Case series with mathematical modeling.Methods: A review of 1267 cases of unilateral VFP over a 10-year period yielded 114 subjects (35 idiopathic, 79 iatrogenic) with a discrete onset of spontaneous vocal recovery. The time-to-recovery data were fit to a previously described two-phase model that incorporates the Seddon classification of neuropraxia and higher grades of axonal injury. Alternatively, the data were fit to a single phase model that does not assume a focal axonal lesion.Results: Time to vocal recovery in iatrogenic VFP can be reliably modeled by the assumption of a focal axonal lesion, with an early recovery group corresponding to neuropraxia and a late recovery group with more severe nerve damage. Time to recovery in idiopathic VFP can be more simply modeled in a single phase, with a time course that mirrors those in diverse biological processes such as transcription and microtubule growth.Conclusion: Idiopathic VFP may not be caused by a focal axonal lesion. Neuritis may be a compatible mechanism. The iatrogenic VFP data lend further support to the concept that the severity of RLN injury, not the length of axon to regenerate, is the chief determinant of recovery time after iatrogenic injury.Level Of Evidence: 4 Laryngoscope, 130:1520-1524, 2020. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Odynophonia is generally regarded as a symptom of a voice disorder. However, a subset of patients with odynophonia have debilitating pain out of proportion to the relatively mild degree of dysphonia and are not responsive to voice therapy. The goals of this study were to 1) describe the symptomatology of this subset of patients and differentiate it from typical odynophonia, 2) propose alternate models to explain this phenomenon of primary odynophonia, and 3) present a new treatment paradigm based on the proposed models.Study Design: Case series.Methods: Inclusion criteria were complaint of persistent pain associated with voicing, normal vocal fold mobility, complete glottic closure, and limited or lack of response of pain to voice therapy. Presenting symptoms, voice evaluation, and treatment outcomes were reviewed.Results: Eleven patients fit the inclusion criteria. The degree of pain did not follow the trajectory of vocal improvement with therapy. The pain was stagnant or worsened with voice exercises. The most dramatic improvement came about in one patient who received false vocal fold Botox injections, and another who received thyrohyoid lidocaine/triamcinolone injection. We propose that these patients had developed primary odynophonia, in which the pain had become self-sustaining and no longer responded to correction of hyperfunctional vocal behavior. The mechanism of pain persistence may involve superior laryngeal neuralgia, cartilaginous or ligamentous inflammation, and/or central sensitization.Conclusions: A minority of patients have primary odynophonia distinct from typical odynophonia. Direct treatment of pain may be advisable prior to or in conjunction with voice therapy.Level Of Evidence: 4 Laryngoscope, 130:E183-E189, 2020. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to test the hypothesis that stretch-and-flow voice therapy (SnF) is noninferior to resonant voice therapy (RVT) for speakers with muscle tension dysphonia. Method: Participants with primary muscle tension dysphonia were randomly assigned to 1 of 2 treatment groups. Participants received 6 sessions of either SnF or RVT for 6 weeks (1 session per week). Pretreatment and posttreatment audio recordings of sustained vowels and connected speech were acquired. Response to treatment was assessed using the voice handicap index (VHI) as the primary outcome measure. Secondary outcome measures included the acoustic voice quality index, the smoothed cepstral peak prominence, and scales from the Consensus Auditory-Perceptual Evaluation of Voice instrument. Data were analyzed for 21 participants who completed the study (12 in the SnF group, 9 in the RVT group). Results: Direction of change for the primary outcome measure and all 3 secondary outcome measures at posttreatment was in the direction of improvement for both SnF and RVT. Confidence intervals for VHI measures did not cross the null effect line on forest plots, suggesting significant effects for both treatments on the primary outcome measure. The effect sizes for pretreatment to posttreatment changes in VHI were large for both treatment groups. Similar results were found for the secondary acoustic outcome measures. There were statistically significant pretreatment to posttreatment changes in the primary and secondary outcome measures for patients receiving both treatments, indicating significant improvement in response to both RVT and SnF. There were no statistically significant differences in pretreatment to posttreatment changes in the primary outcome measure or any secondary outcome measure between the two groups. The within-group pretreatment to posttreatment changes in Consensus Auditory-Perceptual Evaluation of Voice scales did not reach statistical significance for either RVT or SnF. Conclusions: Both SnF and RVT produced positive treatment response in speakers with muscle tension dysphonia, with no statistically significant difference in the outcome measures between the two treatments. This suggests that SnF is noninferior to RVT and that both are effective options for treating vocal hyperfunction. Results from this study also support previous findings documenting the sensitivity of multidimensional acoustic measurements to treatment response. [ABSTRACT FROM AUTHOR]

The effective depth of vocal fold vibration is self-regulated and generally not known a priori in vocalization. In this study, the effective depth was quantified systematically under various phonatory conditions using a fiber-gel finite element vocal fold model. The horizontal and vertical excursions of each finite element nodal point trajectory were recorded to compute trajectory areas. The extent of vibration was then studied based on the variation of trajectory radii as a function of depth in several coronal sections along the anterior-posterior direction. The results suggested that the vocal fold nodal trajectory excursions decrease systematically as a function of depth but are affected by the layered structure of the vocal folds. The effective depth of vibration was found to range between 15 and 55% of the total anatomical depth across all phonatory conditions. The nodal trajectories from the current study were compared qualitatively with the results from excised human hemi-larynx experiments published in Döllinger and Berry [(2006). J. Voice. 20(3), 401–413]. An estimate of the effective mass of a one-mass vocal fold model was also computed based on the effective depth of vibration observed in this study under various phonatory conditions. [ABSTRACT FROM AUTHOR]

Objective: To determine the extent to which a sequential anesthetic technique 1) shortens time under sedation for thyroplasty with arytenoid adduction (TP-AA), 2) affects the total operative time, and 3) changes the voice outcome compared to TP-AA performed entirely under sedation/analgesia.Study Design: Case-control study.Methods: A new sequential anesthetic technique of performing most of the TP-AA surgery under general anesthesia (GA), followed by transition to sedation/analgesia (SA) for voice assessment, was developed to achieve smooth emergence from GA. Twenty-five TP-AA cases performed with the sequential GA-SA technique were compared with 25 TP-AA controls performed completely under sedation/analgesia. The primary outcome measure was the time under sedation. Voice improvement, as assessed by Consensus Auditory-Perceptual Evaluation of Voice, and total operative time were secondary outcome measures.Results: With the conventional all-SA anesthetic, the duration of SA was 209 ± 26.3 minutes. With the sequential GA-SA technique, the duration of SA was 79.0 ± 18.9 minutes, a 62.3% reduction (P < 0.0001). There was no significant difference in the total operative time (209.5 vs. 200.9 minutes; P = 0.42) or in voice outcome. This sequential anesthetic technique has been easily adopted by multiple anesthesiologists and nurse anesthetists at our institution.Conclusion: TP-AA is effectively performed under sequential GA-SA technique with a significant reduction in the duration of time under sedation. This allows the surgeon to perform the technically more challenging part of the surgery under GA, without having to contend with variability in patient tolerance for laryngeal manipulation under sedation.Level Of Evidence: 3b. Laryngoscope, 127:2813-2817, 2017. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Patients with unilateral vocal fold paralysis (UVFP) are commonly told to wait 12 months for spontaneous recovery. This study aims to 1) determine the time to vocal recovery in UVFP, 2) use that data to develop a neurophysiologically plausible model for recovery, and 3) use the model to generate meaningful predictions for patient counseling.Study Design: Case series with de novo mathematical modeling.Methods: Patients with UVFP who could pinpoint a discrete onset of vocal improvement were identified. The time-to-recovery data were modeled by assuming an "early" recovery group with neuropraxia and a "late" recovery group with more severe nerve injury. For the late group, a two-stage model was developed to explain the time to recovery: regenerating axons must cross the site of injury in stage 1 (probabilistic), followed by unimpeded regrowth to the larynx in stage 2 (deterministic).Results: Of 727 cases of UVFP over a 7-year period, 44 reported spontaneous recovery with a discrete onset of vocal improvement. A hybrid distribution incorporating the two stages (exponentially modified Gaussian) accurately modeled the time-to-recovery data (R2 = 0.918). The model predicts 86% of patients with recoverable UVFP will recover within 6 months, with 96% recovering within 9 months. Earlier vocal recovery is associated with recovery of vocal fold motion and younger age.Conclusions: Waiting 12 months for spontaneous recovery is probably too conservative. Repair across the site of injury, and not regrowth to larynx, is likely the rate-determining step in reinnervation, consistent with other works on peripheral nerve regeneration.Level Of Evidence: 4. Laryngoscope, 127:2585-2590, 2017. [ABSTRACT FROM AUTHOR]

Objective To identify factors associated with the likelihood of attending voice therapy among patients referred for it in the CHEER (Creating Healthcare Excellence through Education and Research) practice-based research network infrastructure. Study Design Prospectively enrolled cross-sectional study. Setting CHEER network of community and academic sites. Methods Data were collected on patient-reported demographics, voice-related diagnoses, voice-related handicap (Voice Handicap Index-10), likelihood of attending voice therapy (VT), and opinions on factors influencing likelihood of attending VT. The relationships between patient characteristics/opinions and likelihood of attending VT were investigated. Results A total of 170 patients with various voice-related diagnoses reported receiving a recommendation for VT. Of those, 85% indicated that they were likely to attend it, regardless of voice-related handicap severity. The most common factors influencing likelihood of VT attendance were insurance/copay, relief that it was not cancer, and travel. Those who were not likely to attend VT identified, as important factors, unclear potential improvement, not understanding the purpose of therapy, and concern that it would be too hard. In multivariate analysis, factors associated with greater likelihood of attending VT included shorter travel distance, age (40-59 years), and being seen in an academic practice. Conclusions Most patients reported plans to attend VT as recommended. Patients who intended to attend VT reported different considerations in their decision making from those who did not plan to attend. These findings may inform patient counseling and efforts to increase access to voice care. [ABSTRACT FROM AUTHOR]

Thyroplasty with arytenoid adduction, a combined procedure for treatment of unilateral vocal fold paralysis, is typically performed under local anesthesia with sedation to allow for intraoperative voice assessment. However, the need for patient immobility and suppression of laryngeal responses to surgical manipulation can make sedation-analgesia challenging. We describe our first 26 consecutive cases undergoing thyroplasty and arytenoid adduction with a standardized technique consisting of a combination of general anesthesia with tracheal intubation followed by sedation-analgesia. Most patients (69 %) were women, with age of 53 ± 15 years (mean ± SD). Neck surgery was the cause of vocal fold paralysis in 50 % of patients. Initially, general anesthesia was maintained with desflurane and remifentanil with dexmedetomidine added just before tracheal extubation. During the sedation-analgesia phase, patients received infusions of remifentanil and dexmedetomidine. Duration of general anesthesia and sedation-analgesia phases was 162 ± 68.2 and 79 ± 18.3 min, respectively. Mean (SD) wake-up time was 8.0 ± 4.0 min after desflurane discontinuation. Extubation occurred without coughing, bucking, or agitation in 96 % of patients. All the patients were able to phonate appropriately and remained comfortable after emergence. This technique allowed improved surgical conditions with reduced patient discomfort and may be advantageous for other laryngeal and neck surgeries in which intraoperative patient feedback is required. [ABSTRACT FROM AUTHOR]

The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold impairment. Overarching terms of vocal fold immobility and hypomobility are rigorously defined. This includes assessment techniques and inclusion and exclusion criteria for determining vocal fold immobility and hypomobility. In addition, criteria for use of the following terms have been outlined in detail: vocal fold paralysis, vocal fold paresis, vocal fold immobility/hypomobility associated with mechanical impairment of the crico-arytenoid joint and vocal fold immobility/hypomobility related to laryngeal malignant disease. This represents the first rigorously defined vocal fold motion impairment nomenclature system. This provides detailed definitions to the terms vocal fold paralysis and vocal fold paresis. [ABSTRACT FROM AUTHOR]

Objectives: To assess perspectives of patients with voice problems and identify factors associated with the likelihood of referral to voice therapy via the CHEER (Creating Healthcare Excellence through Education and Research) practice-based research network infrastructure.Study Design: Prospectively enrolled cross-sectional study of CHEER patients seen for a voice problem (dysphonia).Setting: The CHEER network of community and academic sites.Methods: Patient-reported demographic information, nature and severity of voice problems, clinical diagnoses, and proposed treatment plans were collected. The relationship between patient factors and voice therapy referral was investigated.Results: Patients (N = 249) were identified over 12 months from 10 sites comprising 30 otolaryngology physicians. The majority were women (68%) and white (82%). Most patients reported a recurrent voice problem (72%) and symptom duration >4 weeks (89%). The most commonly reported voice-related diagnoses were vocal strain, reflux, and benign vocal fold lesions. Sixty-seven percent of enrolled patients reported receiving a recommendation for voice therapy. After adjusting for sociodemographic and other factors, diagnoses including vocal strain/excessive tension and vocal fold paralysis and academic practice type were associated with increased likelihood of reporting a referral for voice therapy.Conclusions: The CHEER network successfully enrolled a representative sample of patients with dysphonia. Common diagnoses were vocal strain, reflux, and benign vocal fold lesions; commonly reported treatment recommendations included speech/voice therapy and antireflux medication. Recommendation for speech/voice therapy was associated with academic practice type. [ABSTRACT FROM AUTHOR]

Vocal folds are used as sound sources in various species, but it is unknown how vocal fold morphologies are optimized for different acoustic objectives. Here we identify two main variables affecting range of vocal fold vibration frequency, namely vocal fold elongation and tissue fiber stress. A simple vibrating string model is used to predict fundamental frequency ranges across species of different vocal fold sizes. While average fundamental frequency is predominantly determined by vocal fold length (larynx size), range of fundamental frequency is facilitated by (1) laryngeal muscles that control elongation and by (2) nonlinearity in tissue fiber tension. One adaptation that would increase fundamental frequency range is greater freedom in joint rotation or gliding of two cartilages (thyroid and cricoid), so that vocal fold length change is maximized. Alternatively, tissue layers can develop to bear a disproportionate fiber tension (i.e., a ligament with high density collagen fibers), increasing the fundamental frequency range and thereby vocal versatility. The range of fundamental frequency across species is thus not simply one-dimensional, but can be conceptualized as the dependent variable in a multi-dimensional morphospace. In humans, this could allow for variations that could be clinically important for voice therapy and vocal fold repair. Alternative solutions could also have importance in vocal training for singing and other highly-skilled vocalizations. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis To test the hypothesis that subligamental cordectomy produces superior acoustic outcome than subepithelial cordectomy for early (T1-2) glottic cancer that requires complete removal of the superficial lamina propria but does not involve the vocal ligament. Study Design Computer simulation. Methods A computational tool for vocal fold surgical planning and simulation (the National Center for Voice and Speech Phonosurgery Optimizer-Simulator) was used to evaluate the acoustic output of alternative vocal fold morphologies. Four morphologies were simulated: normal, subepithelial cordectomy, subligamental cordectomy, and transligamental cordectomy (partial ligament resection). The primary outcome measure was the range of fundamental frequency (F0) and sound pressure level (SPL). A more restricted F0-SPL range was considered less favorable because of reduced acoustic possibilities given the same range of driving subglottic pressure and identical vocal fold posturing. Results Subligamental cordectomy generated solutions covering an F0-SPL range 82% of normal for a rectangular vocal fold. In contrast, transligamental and subepithelial cordectomies produced significantly smaller F0-SPL ranges, 57% and 19% of normal, respectively. Conclusion This study illustrates the use of the Phonosurgery Optimizer-Simulator to test a specific hypothesis regarding the merits of two surgical alternatives. These simulation results provide theoretical support for vocal ligament excision with maximum muscle preservation when superficial lamina propria resection is necessary but the vocal ligament can be spared on oncological grounds. The resection of more tissue may paradoxically allow the eventual recovery of a better speaking voice, assuming glottal width is restored. Application of this conclusion to surgical practice will require confirmatory clinical data. Level of Evidence N/A. Laryngoscope, 125:1892-1899, 2015 [ABSTRACT FROM AUTHOR]

Objectives To investigate the effect of stretch-and-flow voice therapy on vocal function and handicap. Study Design Randomized controlled trial. Methods Participants with primary muscle tension dysphonia were randomly assigned to experimental or control groups. Experimental participants received vocal hygiene education followed by 6 weeks of stretch-and-flow voice therapy. Control participants received vocal hygiene education only. Outcome variables consisted of a measure of vocal handicap (Voice Handicap Index [VHI]), maximum phonation time, s/z ratio, and acoustic measures. All measures were obtained at baseline prior to treatment and within 2 weeks posttreatment or at the end of the control period. The pre- to posttreatment measurement change (delta Δ) was applied to statistical analyses. Results A multivariate analysis of variance revealed significant group differences in pre-to-post changes on measures of VHI, maximum phonation time, and cepstral peak prominence (CPP) in connected speech and vowels ( P = 0.003, 0.013, 0.025, and 0.017 respectively), with a significant reduction of VHI (Cohen's d = 1.6), increase in maximum phonation time (Cohen's d = 1.2), increase of CPP in connected speech (Cohen's d = 1.2), and increase of CPP in vowels (Cohen's d = 1.1) in the experimental group compared to the control group. Conclusions This preliminary small sample randomized controlled trial found significantly greater improvement in vocal handicap, maximum phonation time, and acoustic measures of vocal function after participants received stretch-and-flow voice therapy compared to participants receiving vocal hygiene education alone. Additional research incorporating larger samples will be needed to confirm and further investigate these findings. Level of Evidence 1b. Laryngoscope, 125:1420-1425, 2015 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis The relationship between patient-reported vocal handicap and clinician-rated measures of vocal dysfunction is not understood. This study aimed to determine if a correlation exists between the Voice Handicap Index-10 (VHI-10) and the Voice Functional Communication Measure rating in the National Outcomes Measurement System (NOMS). Study Design Retrospective case series. Methods Four hundred and nine voice evaluations over 12 months at a tertiary voice center were reviewed. The VHI-10 and NOMS scores, diagnoses, and potential comorbid factors were collected and analyzed. Results For the study population as a whole, there was a moderate negative correlation between the NOMS rating and the VHI-10 (Pearson r = −0.57). However, for a given NOMS level, there could be considerable spread in the VHI-10. In addition, as the NOMS decreased stepwise below level 4, there was a corresponding increase in the VHI-10. However, a similar trend in VHI-10 was not observed for NOMS above level 4, indicating the NOMS versus VHI-10 correlation was not linear. Among diagnostic groups, the strongest correlation was found for subjects with functional dysphonia. The NOMS versus VHI-10 correlation was not affected by gender or the coexistence of a psychiatric diagnosis. Conclusions A simple relationship between VHI-10 and NOMS rating does not exist. Patients with mild vocal dysfunction have a less direct relationship between their NOMS ratings and the VHI-10. These findings provide insight into the interpretation of patient-perceived and clinician-rated measures of vocal function and may allow for better management of expectations and patient counseling in the treatment of voice disorders. Level of Evidence 4 Laryngoscope, 125:180-185, 2015 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis To develop a vocal fold scarring model using an ablative laser in the rabbit as a platform for testing bioengineered therapies for missing or damaged lamina propria. Study Design Prospective controlled animal study. Methods An optimal laser energy level was first determined by assessing the depths of vocal fold injury created by a Holmium:YAG laser at various energy levels on fresh cadaveric rabbit larynges. The selected energy level was then used to create controlled unilateral injuries in vocal folds of New Zealand white rabbits, with the contralateral folds serving as uninjured controls. After 4 weeks, the larynges were harvested and subjected to excised-larynx phonation with high-speed imaging and immunohistochemical staining for collagen types I and III, elastin, and hyaluronic acid (HA) with quantitative histological analysis. Results A total of 1.8 joules produced full-thickness injury of the lamina propria without extensive muscle injury. After 4 weeks, the injured vocal folds vibrated with reduced amplitude ( P = 0.036) in excised-larynx phonation compared to normal vocal folds. The injured vocal folds contained a higher relative density of collagen type I ( P = 0.004), higher elastin ( P = 0.022), and lower HA ( P = 0.030) compared to normal controls. Collagen type III was unchanged. Conclusions With its potential for higher precision of injury, this laser vocal fold scarring model may serve as an alternative to scarring produced by cold instruments for studying the effects of vocal fold lamina propria bioengineered therapies. Level of Evidence N/A. Laryngoscope 124:2321-2326, 2014 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: 1) To test whether alteration of the vocal fold medial surface contour can improve phonation and 2) to demonstrate that implant material properties affect vibration even when implantation is deep to the vocal fold lamina propria. Study Design: Induced phonation of excised human larynges. Methods: Thirteen larynges were harvested within 24 hours postmortem. Phonation threshold pressure (PTP) and flow (PTF) were measured before and after vocal fold injections using either calcium hydroxylapatite (CaHA) or hyaluronic acid (HA). Small-volume injections (median, 0.0625 mL) were targeted to the inferomedial aspect of the thyroarytenoid muscle. Implant locations were assessed histologically. Results: The effect of implantation on PTP was material dependent. CaHA tended to increase PTP, whereas HA tended to decrease PTP (Wilcoxon test, P = .00013 for onset). In contrast, the effect of implantation on PTF was similar, with both materials tending to decrease PTF ( P = .16 for onset). Histology confirmed implant presence in the inferior half of the vocal fold vertical thickness. Conclusions: Taken together, these data suggested the implants may have altered the vocal fold medial surface contour, potentially resulting in a less convergent or more rectangular glottal geometry as a means to improve phonation. An implant with a closer viscoelastic match to vocal fold cover is desirable for this purpose, as material properties can affect vibration even when the implant is not placed within the lamina propria. This result is consistent with theoretical predictions and implies greater need for surgical precision in implant placement and care in material selection. Laryngoscope, 2012 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To determine the phonation threshold pressure (PTP) and phonation threshold flow (PTF) in excised human larynges; determine the effects of posterior glottal width, glottal area, and gender on PTP and PTF; test the hypothesis that hysteresis is present in excised human laryngeal phonation; and compare these results to those from canine experiments and human subject measurements. Study Design: Induced phonation of excised human larynges in the laboratory. Methods: Nine human larynges were harvested within 24 hours postmortem. PTP and PTF at phonation onset and offset were measured on a bench apparatus. The effects of posterior glottal width, glottal area, and gender were examined. Results: Large intersubject variability was observed in PTP and PTF. PTP was comparable to those measured in vivo, whereas PTF was substantially higher. One-way ANOVA showed no significant dependence of PTP and PTF on posterior glottal width. Hysteresis was observed, with offset PTP and PTF lower than onset values. Offset measurements had significantly less variability than onset measurements ( P = .012 for PTP, P = .0001 for PTF). Conclusions: This study is one of the first to report onset and offset PTP and PTF in fresh excised human larynges. The high PTF observed likely reflects a large direct current flow component due to vocal fold bowing. Offset PTP and PTF values may be intrinsically more reliably measured than onset values. The large intersubject variability in PTP and PTF may have implication for the clinical application of these aerodynamic parameters of phonation. [ABSTRACT FROM AUTHOR]

Objective. To determine the 3-dimensional (3D) conformation of the injected bolus in the larynx in vocal fold injections, to understand how the bolus interacts spatially with elements of the laryngeal framework, and to relate the above to clinical observations in performing vocal fold injections.Study Design. Excised cadaveric larynx study.Setting. Laboratory.Subjects and Methods. Vocal folds of 12 human excised cadaveric larynges were injected with calcium hydroxylapatite. High-resolution computed tomography scans were obtained of the injected larynges. Densities corresponding to the injected bolus and the laryngeal framework were extracted and processed with MATLAB routines to generate selective 3D reconstructions of the injected bolus within the laryngeal framework. Histology analysis was also performed to correlate with observations from the 3D reconstructions.Results. Boluses injected into the lateral aspect of the thyroarytenoid muscle tended to be irregularly shaped, appeared to fill up the paraglottic space, and were associated with significant muscle compression. The vertical thickness of the injected boluses averaged 9.5 mm for lateral boluses and 7.6 mm for medial boluses, which were comparable to the vertical thickness of uninjected vocal folds.Conclusion. Laterally injected boluses are shaped by spatial constraints imposed by elements of the laryngeal framework. Compression of vocal fold muscle may be a mechanism accounting for stiffness from overinjection. The irregular shapes of some boluses may affect the outcome of subsequent medialization attempts. Injections may enhance the vocal fold contact height as a favorable effect beyond simple medialization. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To quantitatively characterize arytenoid movement induced by vocal fold injection augmentation in an excised larynx model. Study Design: Laboratory and computational. Methods: Vocal folds of human cadaveric larynges were injected with calcium hydroxylapatite. High-resolution computed tomography scans were obtained before and after injection. Densities corresponding to the arytenoid and cricoid cartilages were extracted and processed with custom MATLAB routines to generate selective three-dimensional reconstructions of the larynx. Pre- and postinjection positions of the arytenoid were compared. Results: Vocal fold injections resulted in predominantly small-magnitude medial rotation and medial translation of the arytenoid. Movements in other directions as would be expected in physiologic adduction were not observed. Conclusions: Vocal fold injection augmentation induced passive movement of the arytenoid that has not been described previously. This movement does not reproduce the trajectory of physiologic adduction. This finding has implications for the treatment of unilateral vocal fold paralysis without arytenoid repositioning maneuvers. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Age, vocal fold atrophy, glottic closure pattern, and the burden of medical problems are associated with voice therapy outcomes for presbyphonia. Study Design: Retrospective. Methods: Records of patients seen over a 3-year period at a voice center were screened. Inclusion criteria consisted of age over 55 years, primary complaint of hoarseness, presence of vocal fold atrophy on examination, and absence of laryngeal or neurological pathology. Videostroboscopic examinations on initial presentation were reviewed. Voice therapy outcomes were assessed with the American Speech-Language-Hearing Association National Outcomes Measurement System scale. Statistical analysis was performed with Spearman rank correlation and χ2 tests. Results: Sixty-seven patients were included in the study. Of the patients, 85% demonstrated improvement with voice therapy. The most common type of glottic closure consisted of a slit gap. Gender or age had no effect on voice therapy outcomes. Larger glottic gaps on initial stroboscopy examination and more pronounced vocal fold atrophy were weakly correlated with less improvement from voice therapy. A weak correlation was also found between the number of chronic medical conditions and poorer outcomes from voice therapy. Conclusions: The degree of clinician-determined improvement in vocal function from voice therapy is independent of patient age but is influenced by the degree of vocal fold atrophy, glottic closure pattern, and the patient's burden of medical problems. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The purpose of this study was to examine the functional biomechanical properties of several injectable biomaterials currently or potentially used for vocal fold augmentation. Study Design: Rheometric investigation of phonosurgical materials in vitro. Methods: Linear viscoelastic shear properties of 3% bovine collagen (atelocollagen), micronized AlloDerm (Cymetra; LifeCell Corp., Branchburg, NJ), calcium hydroxylapatite (CaHA) (Radiesse; BioForm Medical, San Mateo, CA), and 2.4% cross-linked hyaluronic acid (HA) gel (Juvéderm; Allergan, Inc., Irvine, CA) were quantified as functions of frequency covering the phonatory range, and compared to those of the human vocal fold cover. Measurements of elastic shear modulus ( G′) and dynamic viscosity (η′) were made at up to 250 Hz with a controlled-strain simple-shear rheometer. Linear least-squares regression was conducted to curve-fit log G′ and log η′ versus log frequency, and statistical analysis was performed with one-way analysis of variance. Results: Radiesse and Cymetra were found to be the stiffest and the most viscous materials, followed by Juvéderm and atelocollagen. There were significant differences in the magnitudes of G′ and η′ among the phonosurgical materials and the normal human vocal fold cover ( p < .001), whereas there was no significant difference in the frequency dependence of G′ and η′ among the materials. Post hoc Tukey tests revealed significant differences ( p < .05) in pairwise comparisons of the magnitudes of G′ and η′ among all materials and the vocal fold cover. Conclusions: These findings suggested that although these biomaterials may be injected lateral to the lamina propria for the treatment of glottic insufficiency, none of them are rheologically optimal for the functional reconstruction of the vocal fold lamina propria. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]

Objective: To determine the influence of gender and injection site on the amount of injectate needed to medialize an immobile vocal fold, and to describe the distribution patterns of the injected bolus. Study Design: Surgical intervention in human cadaveric larynges in experimental setting. Subjects and Methods: Cadaveric larynges were injected with calcium hydroxylapatite into the lateral or medial aspect of the vocal fold. High-resolution CT scans were obtained before and after injection. Results: Males required 50% to 60% more material than females (P = 0.03). For both genders, lateral injections required more than medial injections (P < 0.001). Laterally injected boluses tended to distribute toward the cricothyroid space, with frank extrusions more common in females. Conclusion: The amount of injectate required to medialize male and female vocal folds is significantly different. The smaller size of the female larynx likely accounts for a higher incidence of extrusion through the cricothyroid space. These gender differences should be taken into consideration when performing injection laryngoplasty. [Copyright &y& Elsevier]

Objectives: To identify patterns of failure of the L-strut, to identify elements of the nasal framework that support the L-strut, and to investigate the effect of altering L-strut design on its stability. Study Design: Laboratory study with human cadaveric heads and computational modeling. Methods: Directional forces were applied to cadaveric L-struts and patterns of failure with incremental force were noted. Computational modeling using the finite element method (FEM) was employed to determine quantitatively the effect of various modifications on the stability of the L-strut. Results: The L-strut was found to respond to frontal force initially by buckling. This buckling was reversible until the force exceeded a certain threshold when the L-strut broke at the bony-cartilaginous junction. The threshold force varied depending on the length of the overlap with the bony vault. Intact mucoperichondrium provided significant stability. Modeling with FEM showed that the preservation of a triangular piece of cartilage at the dorsal anchor of a narrowed L-strut can offset some of the loss in mechanical stability. Conclusions: Intrinsic elasticity of the septal cartilage, the mucoperichondrial flap, and overlap with the bony vault all contribute to the stability of the L-strut, which is enhanced by preserving a small segment of cartilage at the bony-cartilaginous junction of the dorsal L-strut. [ABSTRACT FROM AUTHOR]

Objective To assess the value of planned neck dissection in patients with a complete response to definitive radiotherapy for squamous cell carcinoma of the tonsillar fossa with advanced nodal disease. Design Case series. Setting Academic tertiary care medical center. Patients A consecutive series of 36 patients with squamous cell carcinoma of the tonsillar fossa with N2 or N3 nodal disease treated with primary radiation therapy with or without concurrent chemotherapy between January 1, 1992, and April 1, 2003, at the University of California, San Francisco, Comprehensive Cancer Center. Patients treated with primary surgery, those treated with palliative intent, or those with preexisting malignancies were excluded. Main Outcome Measures Regional control and overall survival. Results Of the study group, 15 patients (42%) achieved a complete response, 17 (47%) achieved a partial response, and 1 (3%) was a nonresponder. The response in 3 patients (8%) could not be assessed. Of the 15 patients with a complete response, only 2 (13%) later developed regional recurrences, 1 of which was an isolated recurrence in the neck. Regional control and overall survival at 3 years were 78% and 48%, respectively. Conclusions The rate of regional recurrence after a complete response to radiation therapy with or without concurrent chemotherapy for tonsillar squamous cell carcinoma with advanced cervical metastases is low. Our results support close surveillance of the neck in those who have achieved a complete response after radiation therapy with or without chemotherapy. [ABSTRACT FROM AUTHOR]

While the majority of proteins fold rapidly and spontaneously to their native states, the extracellular bacterial protease α-lytic protease (αLP) has a t1/2 for folding of ~2,000 years, corresponding to a folding barrier of 30 kcal mol?1. αLP is synthesized as a pro-enzyme where its pro region (Pro) acts as a foldase to stabilize the transition state for the folding reaction. Pro also functions as a potent folding catalyst when supplied as a separate polypeptide chain, accelerating the rate of αLP folding by a factor of 3 × 109. In the absence of Pro, αLP folds only partially to a stable molten globule-like intermediate state. Addition of Pro to this intermediate leads to rapid formation of native αLP. Here we report the crystal structures of Pro and of the non-covalent inhibitory complex between Pro and native αLP. The C-shaped Pro surrounds the C-terminal ß-barrel domain of the folded protease, forming a large complementary interface. Regions of extensive hydration in the interface explain how Pro binds tightly to the native state, yet even more tightly to the folding transition state. Based on structural and functional data we propose that a specific structural element in αLP is largely responsible for the folding barrier and suggest how Pro can overcome this barrier. [ABSTRACT FROM AUTHOR]

We would like to thank Dr. Karkos and colleagues for their comments and sharing their experience. Some of the factors they noted were not included in our analysis and could very well play roles in the outcomes after transverse posterior cordotomy. The authors have no funding, financial relationships, or conflicts of interest to disclose. [Extracted from the article]

Objective: Determine the functional biomechanical properties of the human false vocal fold mucosa at phonatory frequencies, in comparison with those of the true vocal fold cover; and to quantify the vibration patterns of ventricular fold phonation with HSDI (high speed digital imaging). Method: Viscoelastic shear properties of false fold specimens were quantified as functions of frequency, with measurements of elastic shear modulus (G′) and dynamic viscosity (h′) at up to 250 Hz using a simple‐shear rheometer. Ventricular fold phonation of three subjects was analyzed by HSDI (high speed digital imaging) through kymography and laryngotopography. Results: All specimens showed similar frequency dependence of their viscoelastic properties, with G′ gradually increasing with frequency and h′ monotonically decreasing with frequency. G′ and h′ of the false fold mucosa were generally higher than those of the true vocal fold cover, although the differences did not reach statistical significance. Kymographic and laryngotopographic analysis of high speed digital images revealed vibration of the false fold mucosa for subjects undergoing ventricular fold phonation. The vibratory frequencies were lower than typical fundamental frequencies for phonation. Conclusion: These findings showed false folds could function as a secondary sound source. These preliminary data suggested that the false fold mucosa could serve as replacement material for patients with unrepairable vocal fold cover damage. [ABSTRACT FROM AUTHOR]

Educational Objective: At the conclusion of this presentation, the participants should be able to discuss the advantages of using 3D reconstruction of CT images to analyze laryngeal fractures for surgical planning. Study Design: Case report and development of image processing algorithm. Methods: A 30 year old man sustained blunt trauma to the neck. Axial CT images showed a significantly displaced posterolateral cricoid fracture. The images were imported into Adobe Photoshop to separate the densities corresponding to the cricoid and thyroid cartilages. The separated images were processed with custom routines written in MATLAB. 3D reconstructions of the laryngeal framework were generated for surgical planning. Results: Image processing algorithms were developed using MATLAB to allow versatile 3D reconstruction of the laryngeal framework. Independent renderings of the cricoid and the thyroid with different opacities allowed viewing of the cricoid fracture through the thyroid cartilage, which facilitated surgical planning. The 3D reconstructions suggested an open, lateral approach to the fracture line and also pointed to the necessity of a second approach to apply force in the appropriate direction to reduce the fracture. The surgery was carried out using a combined lateral approach and temporary cricothyrotomy. A thyrotomy or laryngeal stent was not necessary. Postoperative CT images were reconstructed in a similar manner and demonstrated successful reduction of the cricoid fracture. Conclusions: The use of 3D reconstructions from routinely obtained axial CT images can facilitate the appreciation of the 3D anatomy of laryngeal fractures and potentially improve surgical planning. [ABSTRACT FROM AUTHOR]