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The primary acoustic signal of the voice is generated by the complex oscillation of the vocal folds (VFs), whereby physicians can barely examine the medial VF surface due to its anatomical inaccessibility. In this study, we investigated possibilities to infer medial surface dynamics by analyzing correlations in the oscillatory behavior of the superior and medial VF surfaces of four human hemilarynges, each in 24 different combinations of flow rate, VF adduction, and elongation. The two surfaces were recorded synchronously during sustained phonation using two high-speed camera setups and were subsequently 3D-reconstructed. The 3D surface parameters of mean and maximum velocities and displacements and general phonation parameters were calculated. The VF oscillations were also analyzed using empirical eigenfunctions (EEFs) and mucosal wave propagation, calculated from medial surface trajectories. Strong linear correlations were found between the 3D parameters of the superior and medial VF surfaces, ranging from 0.8 to 0.95. The linear regressions showed similar values for the maximum velocities at all hemilarynges (0.69–0.9), indicating the most promising parameter for predicting the medial surface. Since excessive VF velocities are suspected to cause phono-trauma and VF polyps, this parameter could provide added value to laryngeal diagnostics in the future. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the vocal fold histological characteristics during different postnatal periods in rats, especially older rats. Methods: Sprague–Dawley rats aged 4 days, 4 and 12 weeks, and 12 and 24 months were used for the experiment. Five larynges were obtained for each age and cut into 5‐μm consecutive sections. The expression of Ki‐67 was assessed using immunohistochemistry to examine cell proliferation. Elastic van Gieson staining was used to detect the collagen and elastin concentrations. The cell type was determined using multicolor immunofluorescence. Results: Ki‐67 was not expressed in the macula flava (MF) of 12‐week‐, 12‐month‐, and 24‐month‐old adults. Collagen fibers in the lamina propria (LP) increased with age. The elastic fiber concentrations in the LP decreased significantly at 24 months (p <.01) but remained stable in the MF. All posterior MF cells showed strong glial fibrillary acidic protein and vimentin‐positive reactions with weaker expressions of CD68 and α‐smooth muscle actin (α‐SMA). The myofibroblasts (α‐SMA‐positive) and macrophages (CD68‐positive) in the LP of the 24‐month‐old rats were significantly the highest (p <.01). Conclusion: The extracellular matrix in the LP increases with age, presenting as an increase in collagen with the loss of elastin, which may be due to myofibroblast proliferation. Moreover, the cellular properties or extracellular matrix components of the mature MF in rats are comparable to those in humans. [ABSTRACT FROM AUTHOR]

Introduction Benign vocal fold lesions (BVFLs) disrupt the superficial lamina propria, impacting vocal fold pliability. Investigating the diagnostic competency of ear, nose, and throat (ENT) residents in identifying BVFLs, we hypothesize that factors such as residency year, subspecialty focus, and training center influence diagnostic accuracy. Objectives To assess the accuracy of diagnosis of BVFLs among ENT residents and to correlate diagnostic accuracy with the year of residency. Methods An observational cross-sectional study included all ENT residents in Saudi Arabia. It was performed in August and September 2021 using a self-administered online questionnaire that assessed demographic variables and included three images with open-ended questions on diagnosing vocal fold lesions. Results A total of 61 ENT residents (62.3% male) were included in this study. The images of vocal fold cyst, vocal fold polyp, and vocal fold nodule were correctly diagnosed by 60.7%, 88.5%, and 91.8% of residents, respectively. There was a correlation between the year of residency and the accuracy of diagnosing a vocal fold cyst (p = 0.029). Residents interested in laryngology correctly diagnosed all three lesions more frequently than other residents. Conclusion The ability of residents to diagnose vocal fold cysts was moderate. In particular, the senior residents were able to diagnose polyps and nodules with excellent accuracy. [ABSTRACT FROM AUTHOR]

Phonation onset is characterized by the unstable growth of vocal fold (VF) vibrations that ultimately results in self-sustained oscillation and the production of modal voice. Motivated by histological studies, much research has focused on the role of the layered structure of the vocal folds in influencing phonation onset, wherein the outer “cover” layer is relatively soft and the inner “body” layer is relatively stiff. Recent research, however, suggests that the body-cover (BC) structure over-simplifies actual stiffness distributions by neglecting important spatial variations, such as inferior–superior (IS) and anterior–posterior gradients and smooth transitions in stiffness from one histological layer to another. Herein, we explore sensitivity of phonation onset to stiffness gradients and smoothness. By assuming no a priori stiffness distribution and considering a second-order Taylor series sensitivity analysis of phonation onset pressure with respect to stiffness, we find two general smooth stiffness distributions most strongly influence onset pressure: a smooth stiffness containing aspects of BC differences and IS gradients in the cover, which plays a role in minimizing onset pressure, and uniform increases in stiffness, which raise onset pressure and frequency. While the smooth stiffness change contains aspects qualitatively similar to layered BC distributions used in computational studies, smooth transitions in stiffness result in higher sensitivity of onset pressure than discrete layering. These two general stiffness distributions also provide a simple, low-dimensional, interpretation of how complex variations in VF stiffness affect onset pressure, enabling refined exploration of the effects of stiffness distributions on phonation onset. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate the vocal fold histological characteristics during different postnatal periods in rats, especially older rats. Methods Sprague–Dawley rats aged 4 days, 4 and 12 weeks, and 12 and 24 months were used for the experiment. Five larynges were obtained for each age and cut into 5‐μm consecutive sections. The expression of Ki‐67 was assessed using immunohistochemistry to examine cell proliferation. Elastic van Gieson staining was used to detect the collagen and elastin concentrations. The cell type was determined using multicolor immunofluorescence. Results Ki‐67 was not expressed in the macula flava (MF) of 12‐week‐, 12‐month‐, and 24‐month‐old adults. Collagen fibers in the lamina propria (LP) increased with age. The elastic fiber concentrations in the LP decreased significantly at 24 months (p

Introduction Benign vocal fold lesions (BVFLs) disrupt the superficial lamina propria, impacting vocal fold pliability. Investigating the diagnostic competency of ear, nose, and throat (ENT) residents in identifying BVFLs, we hypothesize that factors such as residency year, subspecialty focus, and training center influence diagnostic accuracy.

The ventricular folds, located superiorly to the vocal folds, do not usually vibrate during normal phonations. It has been shown, however, that they do vibrate together with the vocal folds under special circumstances such as voice pathology and singing voice. Towards understanding the effect of the ventricular fold oscillations on the vocal fold oscillations, the present study developed a synthetic model that takes into account anatomical features of the human ventricular folds. The synthetic model is made of flexible silicone compounds with material properties comparable to those of human ventricular fold tissues. In our experiment, an air-flow was injected into the vocal and ventricular fold models. As the distance between the left and right ventricular folds was reduced, the ventricular folds started to co-vibrate with the vocal folds. Depending upon the distance, various oscillation patterns of the vocal-ventricular folds were observed, e.g. , synchronized dynamics with 1 : 1 or 1 : 2 frequency ratio and desynchronized chaotic dynamics. The observed chaotic dynamics might be related to voice pathology induced by the ventricular phonation. A computational model was further presented to elucidate the experimental findings. [ABSTRACT FROM AUTHOR]

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Objective: To investigate the sensitivity of laryngeal findings in predicting high‐grade dysplasia/carcinoma in situ (CIS) and squamous cell carcinoma (SCC) in patients with vocal fold leukoplakia. Methods: A retrospective review of the medical records and video recordings of the laryngeal examination of patients with vocal fold leukoplakia who underwent un‐sedated office‐based laryngeal biopsy in a tertiary referral center between January 2022 and August 2023 was conducted. Laryngeal findings included the size, surface, projection, and edges of the lesion. Vocal fold leukoplakia was classified according to the WHO as benign, low‐grade dysplasia, high‐grade dysplasia/CIS, and squamous cell carcinoma. Results: Seventy patients with 100 vocal fold leukoplakia were included. Size was found to have the highest sensitivity with an AUC of 0.730 (95% CI [0.618–0.842], p = 0.002) followed by surface and projection with AUCs of 0.672 (95% CI [0.548–0.795], p = 0.019) and 0.675 (95% CI [0.546–0.804], p = 0.017), respectively. Furthermore, the odds of diagnosing high‐risk lesions (high‐grade dysplasia/CIS and SCC) were the greatest when the lesion was large and rough (OR = 10.28; 95% CI [3.08–34.36]). Conclusion: The morphological features of vocal fold leukoplakia may assist the physician in predicting the risk of malignancy. Large and rough lesions were more likely to harbor high‐grade dysplasia/CIS and SCC compared to small and smooth lesions. [ABSTRACT FROM AUTHOR]

Objective: De novo occurrence of granuloma (granulation tissue) on the membranous vocal fold is not readily explained by usual causes of granuloma at the vocal process. We describe a series of patients. Study Design: Case series. Setting: Single academic institution. Methods: Cases were identified over a 16‐year period. All patients exhibited granulation tissue on pathology. Demographic details, presentation, treatment, histology, and clinical outcomes were recorded. Results: Five patients (mean age: 74.0 ± 6.1 years, 40.0% male, 40.0% former smokers) underwent a biopsy. Persistent or recurrent granulation led to a second biopsy in 4 patients an average of 1423.5 days later, revealing a new diagnosis of squamous cell carcinoma (SCC) in situ in one and mild dysplasia in another. Further persistence or recurrence led to a third biopsy or excision an average of 302.3 days later in 3 patients, demonstrating SCC in situ in 1. An average of 2.5 biopsies were required with a mean time to SCC in situ diagnosis of 919.5 days from presentation. Two patients continued to demonstrate persistent granulation tissue on histology. Conclusion: The membranous vocal fold is an atypical location for granuloma and portends a risk of occult malignancy. The occurrence of de novo granuloma at this site should prompt close long‐term clinical surveillance with a low threshold for biopsy. Consideration should be given to tissue collection in the operating room to adequately sample the lesion's base. Concern should persist even after a negative biopsy, and serial observation with repeat biopsy as needed should be pursued. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Systemic glucocorticoids (GC)s are employed to treat various voice disorders. However, GCs have varying pharmacodynamic properties with adverse effects ranging from changes in epithelial integrity, skeletal muscle catabolism, and altered body weight. We sought to characterize the acute temporal effects of systemic dexamethasone and methylprednisolone on vocal fold (VF) epithelial glucocorticoid receptor (GR) nuclear translocation, epithelial tight junction (ZO-1) expression, thyroarytenoid (TA) muscle fiber morphology, and body weight using an established pre-clinical model. We hypothesized dexamethasone and methylprednisolone will elicit changes in VF epithelial GR nuclear translocation, epithelial ZO-1 expression, TA muscle morphology, and body weight compared to placebo-treated controls. Methods: Forty-five New Zealand white rabbits received intramuscular injections of methylprednisolone (4.5 mg; n = 15), dexamethasone (450 µg; n = 15), or volume matched saline (n = 15) into the iliocostalis/longissimus muscle for 6 consecutive days. Vocal folds from 5 rabbits from each treatment group were harvested at 1-, 3-, or 7 days following the final injection and subjected to immunohistochemistry for ZO-1 and GR as well as TA muscle fiber cross-sectional area (CSA) measures. Results: Dexamethasone increased epithelial GR nuclear translocation and ZO-1 expression 1-day following injections compared to methylprednisolone (P =.024; P =.012). Dexamethasone and methylprednisolone increased TA CSA 1-day following injections (P =.011). Methylprednisolone decreased body weight 7 days following injections compared to controls (P =.004). Conclusions: Systemic dexamethasone may more efficiently activate GR in the VF epithelium with a lower risk of body weight loss, suggesting a role for more refined approaches to GC selection for laryngeal pathology. [ABSTRACT FROM AUTHOR]

Despite many attempts, we do not yet know how to answer the question exhaustively and adequately: What is common Danish stød phonetically? Specifically, is there an underlying physiological constancy behind the considerable acoustic variability? And is there a common denominator to the different acoustic manifestations that might explain their perceptual equivalence? Systematic acoustic, physiological, and perceptual investigations of common Danish stød now span (a little more than) three quarters of a century. This is a review of that research, to determine what may be considered established phonetic facts about common Danish stød and the open questions that remain for future research. [ABSTRACT FROM AUTHOR]

Swelling in the vocal folds is caused by the local accumulation of fluid, and has been implicated as a phase in the development of phonotraumatic vocal hyperfunction and related structural pathologies, such as vocal fold nodules. It has been posited that small degrees of swelling may be protective, but large amounts may lead to a vicious cycle wherein the engorged folds lead to conditions that promote further swelling, leading to pathologies. As a first effort to explore the mechanics of vocal fold swelling and its potential role in the etiology of voice disorders, this study employs a finite-element model with swelling confined to the superficial lamina propria, which changes the volume, mass, and stiffness of the cover layer. The impacts of swelling on a number of vocal fold kinematic and damage measures, including von Mises stress, internal viscous dissipation, and collision pressure, are presented. Swelling has small but consistent effects on voice outputs, including a reduction in fundamental frequency with increasing swelling (10 Hz at 30 % swelling). Average von Mises stress decreases slightly for small degrees of swelling but increases at large magnitudes, consistent with expectations for a vicious cycle. Both viscous dissipation and collision pressure consistently increase with the magnitude of swelling. This first effort at modeling the impact of swelling on vocal fold kinematics, kinetics, and damage measures highlights the complexity with which phonotrauma can influence performance metrics. Further identification and exploration of salient candidate measures of damage and refined studies coupling swelling with local phonotrauma are expected to shed further light on the etiological pathways of phonotraumatic vocal hyperfunction. [ABSTRACT FROM AUTHOR]

Human vocal folds are remarkable soft laryngeal structures that enable phonation due to their unique vibro-mechanical performances. These properties are tied to their specific fibrous architecture, especially in the upper layers, which comprise a gel-like composite called lamina propria. The lamina propria can withstand large and reversible deformations under various multiaxial loadings. Despite their importance, the relationships between the microstructure of vocal folds and their resulting macroscopic properties remain poorly understood. There is a need for versatile models that encompass their structural complexity while mimicking their mechanical features. In this study, we present a candidate model inspired by histological measurements of the upper layers of human vocal folds. Bi-photonic observations were used to quantify the distribution, orientation, width, and volume fraction of collagen and elastin fibers between histological layers. Using established biomaterials, polymer fiber-reinforced hydrogels were developed to replicate the fibrillar network and ground substance of native vocal fold tissue. To achieve this, jet-sprayed poly(ε-caprolactone) fibrillar mats were successfully impregnated with poly(L-lysine) dendrimers/polyethylene glycol hydrogels. The resulting composites exhibited versatile structural, physical and mechanical properties that could be customized through variations in the chemical formulation of their hydrogel matrix, the microstructural architecture of their fibrous networks (i.e. , fiber diameter, orientation and volume fraction) and their assembly process. By mimicking the collagen network of the lamina propria with polymer fibers and the elastin/ground substance with the hydrogel composition, we successfully replicated the non-linear, anisotropic, and viscoelastic mechanical behavior of the vocal-fold upper layers, accounting for inter/intra-individual variations. The development of this mimetic model offers promising avenues for a better understanding of the complex mechanisms involved in voice production. Human vocal folds are outstanding vibrating soft living tissues allowing phonation. Simple physical models that take into account the histological structure of the vocal fold and recapitulate its mechanical features are scarce. As a result, the relations between tissue components, organisation and vibro-mechanical performances still remain an open question. We describe here the development and the characterization of fiber-reinforced hydrogels inspired from the vocal-fold microstructure. These systems are able to reproduce the mechanics of vocal-fold tissues upon realistic cyclic and large strains under various multi-axial loadings, thus providing a mimetic model to further understand the impact of the fibrous network microstructure in phonation. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Biological data on the beneficial effects of vocal fold rehydration are lacking. This study aimed to examine the effects of acute systemic dehydration on vocal fold gene expression and determine whether rehydration would reverse these changes. Methods: Male New Zealand White rabbits (N = 24, n = 8/group) provided the animal model. Systemic dehydration was induced by 5 days of water volume restriction. Rehydration was provided by ad‐lib water for 3 days following dehydration. Euhydrated rabbits were used as the control group. Vocal fold tissue was dissected. Seventeen genes were selected based on physiological function and role in supporting vocal fold structure, oxidative stress, hemodynamics, and extracellular matrix turnover. Relative gene expression was assessed by RT‐qPCR. Results: Rehydration following systemic dehydration can modulate gene expression, with expression patterns suggesting that rehydration reverses dehydration‐induced changes in over half of the tested genes. CLIC5 (chloride intracellular channel 5) and EFEMP1 (EGF containing fibulin extracellular matrix protein 1) genes were significantly upregulated in the dehydration group compared with the euhydrated control. A1BG (alpha‐1B‐glycoprotein) and IL1RAP (interleukin 1 receptor accessory protein) were downregulated by rehydration compared with the dehydration group. Conclusion: This study provides molecular evidence for a transcriptional response to rehydration following acute systemic dehydration in the vocal folds. These data are the first to study gene expression following realistic dehydration and rehydration paradigms and provide biological data to support clinical recommendations to increase water intake after acute dehydration. Level of Evidence: NA Laryngoscope, 133:3499–3505, 2023 [ABSTRACT FROM AUTHOR]

Abstract Background There is growing interest to application of regenerative medicine approaches in otorhinolaryngological practice, especially in the framework of the therapy of vocal fold (VF) scar lesions. The used conservative and surgical methods, despite the achieved positive outcomes, are frequently unpredictable and do not result in the restoration of the VF’s lamina propria’s structure, which provides the mechanical properties necessary for vibration. In this connection, the aim of this study was to ascertain the safety and efficacy of a bioequivalent in the treatment of VF scars using a rabbit model of chronic damage. Methods The bioequivalent consisted of a hydrogel system based on a PEG-fibrin conjugate and human bone marrow-derived MSC. It was characterized and implanted heterotopically into rats and orthotopically into rabbits after VF scar excision. Results We showed that the fabricated bioequivalent consisted of viable cells retaining their metabolic and proliferative activity. While being implanted heterotopically, it had induced the low inflammatory reaction in 7 days and was well tolerated. The orthotopic implantation showed that the gel application was characterized by a lower hemorrhage intensity (p = 0.03945). The intensity of stridor and respiratory rate between the groups in total and between separate groups had no statistically significant difference (p = 0.96 and p = 1; p = 0.9593 and p = 0.97…1, respectively). In 3 days post-implantation, MSC were detected only in the tissues closely surrounding the VF defect. The bioequivalent injection caused that the scar collagen fibers were packed looser and more frequently mutually parallel that is inherent in the native tissue (p = 0.018). In all experimental groups, the fibrous tissue’s ingrowth in the adjacent exterior muscle tissue was observed; however, in Group 4 (PEG-Fibrin + MSC), it was much less pronounced than it was in Group 1 (normal saline) (p = 0.008). The difference between the thicknesses of the lamina propria in the control group and in Group 4 was not revealed to be statistically significant (p = 0.995). The Young’s modulus of the VF after the bioequivalent implantation (1.15 ± 0.25 kPa) did not statistically significantly differ from the intact VF modulus (1.17 ± 0.45 kPa); therefore, the tissue properties in this group more closely resembled the intact VF. Conclusions The developed bioequivalent showed to be biocompatible and highly efficient in the restoration of VF’s tissue.

Objective:Vocal fold nodules (VFNs) are among the most common causes of dysphonia. Phono-laryngeal microsurgery, pharmacological treatments, and voice therapy (VT) have been used for treating VFNs. VT has been advocated as the primary treatment of choice. This study investigated the efficacy of the DoctorVox Voice therapy technique (DVT) for treating VFNs.Methods:A total of 38 patients with VFNs and 40 individuals without any voice problem (control group) were included. All patients received the DVT program. Otorhinolaryngology examination, videolaryngostroboscopy (VLS), and acoustic analysis (SPL, mean F0, jitter %, shimmer %, NHR) were performed at pretreatment, one and six months after the end of treatment. The voice handicap index-10 (VHI-10) and the GRB scales were used for perceptual voice evaluation. GRB and VLS scorings were done blindly.Results:Compared with the pretreatment values, the first- and the sixth-month values after treatment demonstrated a significant decrease in VHI-10 (19.5 vs. 5.1), GRB (2.3 vs 0.68 for G value) and VLS scores, SPL (54.4 vs 66.1 dB), F0 (201 vs. 227 Hz), jitter % (1.46 vs 0.85), shimmer % (3.27 vs 2.51), NHR (1.15 vs. 0.46) values among patients. Most of the voice parameters in the sixth month after the DVT program did not differ significantly from those of the control group.Conclusion:The DVT was found to be an effective method in VFN treatment.

Abstract Objective To investigate the sensitivity of laryngeal findings in predicting high‐grade dysplasia/carcinoma in situ (CIS) and squamous cell carcinoma (SCC) in patients with vocal fold leukoplakia. Methods A retrospective review of the medical records and video recordings of the laryngeal examination of patients with vocal fold leukoplakia who underwent un‐sedated office‐based laryngeal biopsy in a tertiary referral center between January 2022 and August 2023 was conducted. Laryngeal findings included the size, surface, projection, and edges of the lesion. Vocal fold leukoplakia was classified according to the WHO as benign, low‐grade dysplasia, high‐grade dysplasia/CIS, and squamous cell carcinoma. Results Seventy patients with 100 vocal fold leukoplakia were included. Size was found to have the highest sensitivity with an AUC of 0.730 (95% CI [0.618–0.842], p = 0.002) followed by surface and projection with AUCs of 0.672 (95% CI [0.548–0.795], p = 0.019) and 0.675 (95% CI [0.546–0.804], p = 0.017), respectively. Furthermore, the odds of diagnosing high‐risk lesions (high‐grade dysplasia/CIS and SCC) were the greatest when the lesion was large and rough (OR = 10.28; 95% CI [3.08–34.36]). Conclusion The morphological features of vocal fold leukoplakia may assist the physician in predicting the risk of malignancy. Large and rough lesions were more likely to harbor high‐grade dysplasia/CIS and SCC compared to small and smooth lesions.

Vocal Cord Ulcer (VCU) is a contact ulcer that decreases the musculoskeletal laryngeal tension when speaking. With the advanced technology, including high-decision cameras and computational energy, it appears to be easy to construct. However, identifying laryngeal variation caused by VCU in CT images is still problematic. The paper aims to use image processing techniques to quantify the laryngeal variation caused by VCU, determine, and analyze its severity. The proposed 3D Swin Transforms Volumetric Segmentation Network (STVSNet) reduces the entanglement and improves the segmentation accuracy. Volumetric quantification on Contrast-Enhanced computed tomography (CECT) uses 3D STVSNet to extract shapes feature to evaluate the VCU severity. Evaluation results were 96.20% sensitivity, 97.15% accuracy, and 96.16% specificity. Concomitantly compared different prevail methods show better results for quantitative data. Experimental results show that 3D STVSNet indicates precise segmentation results for detecting VCU in any image type. [ABSTRACT FROM AUTHOR]

Background: There is growing interest to application of regenerative medicine approaches in otorhinolaryngological practice, especially in the framework of the therapy of vocal fold (VF) scar lesions. The used conservative and surgical methods, despite the achieved positive outcomes, are frequently unpredictable and do not result in the restoration of the VF's lamina propria's structure, which provides the mechanical properties necessary for vibration. In this connection, the aim of this study was to ascertain the safety and efficacy of a bioequivalent in the treatment of VF scars using a rabbit model of chronic damage. Methods: The bioequivalent consisted of a hydrogel system based on a PEG-fibrin conjugate and human bone marrow-derived MSC. It was characterized and implanted heterotopically into rats and orthotopically into rabbits after VF scar excision. Results: We showed that the fabricated bioequivalent consisted of viable cells retaining their metabolic and proliferative activity. While being implanted heterotopically, it had induced the low inflammatory reaction in 7 days and was well tolerated. The orthotopic implantation showed that the gel application was characterized by a lower hemorrhage intensity (p = 0.03945). The intensity of stridor and respiratory rate between the groups in total and between separate groups had no statistically significant difference (p = 0.96 and p = 1; p = 0.9593 and p = 0.97...1, respectively). In 3 days post-implantation, MSC were detected only in the tissues closely surrounding the VF defect. The bioequivalent injection caused that the scar collagen fibers were packed looser and more frequently mutually parallel that is inherent in the native tissue (p = 0.018). In all experimental groups, the fibrous tissue's ingrowth in the adjacent exterior muscle tissue was observed; however, in Group 4 (PEG-Fibrin + MSC), it was much less pronounced than it was in Group 1 (normal saline) (p = 0.008). The difference between the thicknesses of the lamina propria in the control group and in Group 4 was not revealed to be statistically significant (p = 0.995). The Young's modulus of the VF after the bioequivalent implantation (1.15 ± 0.25 kPa) did not statistically significantly differ from the intact VF modulus (1.17 ± 0.45 kPa); therefore, the tissue properties in this group more closely resembled the intact VF. Conclusions: The developed bioequivalent showed to be biocompatible and highly efficient in the restoration of VF's tissue. [ABSTRACT FROM AUTHOR]

Objective: Fat injection laryngoplasty (FIL) is a common procedure used to correct glottic insufficiency. Nevertheless, few studies have discussed potential treatments for cases with poor voice recovery after FIL. Methods: Eighteen patients with unfavorable vocal outcomes from FIL were analyzed. Each of these patients presented persistent dysphonia for more than 2 months following FIL, together with bulging vocal folds and poor mucosal wave. We applied microsurgery as the standard treatment to remove excessive fat. Vocal fold steroid injection (VFSI) was administered to patients that were hesitant or declined to undergo microsurgery. Voice outcomes were evaluated using the Voice Handicap Index-10 (VHI-10), grade-roughness-breathiness (GRB) scores, and smoothed cepstral peak prominence (CPPs). Results: Six patients underwent microsurgery directly, 6 patients received only VFSIs as a salvage treatment, and the remaining 6 patients received 1 to 3 courses of VFSIs before the decision to undergo microsurgery. Pathology reports were available for 10 patients, and contained 5 instances of adipose tissues, 3 of fat necrosis, 1 of chronic inflammation, and 1 of fibrosis. Seventeen patients reported satisfactory or improved outcomes. We found remarkable improvements in VHI-10, GRB, and CPPs (all P <.05) after salvage treatments for FIL. Subgroup analyses showed comparable voice outcomes for patients undergoing direct microsurgery, VFSI alone, and VFSI followed by microsurgery (P >.05). Conclusions: This study demonstrated that fat overinjection and/or fibrotic change in the injected vocal folds may cause poor voice outcomes after FIL. Both microsurgery and VFSI could be applied as salvage treatments with good voice recovery profiles. Level of evidence: Level 4. [ABSTRACT FROM AUTHOR]

Introduction: This study identifies the most suitable syllable for laryngeal diadochokinesis (LDDK) in Mandarin speakers. Methods: One hundred and ten Mandarin speakers aged 18–83 years were used in the study. LDDK was assessed using quick repetitions of /ʔe/, /ʔi/, /ʔa/, /he/, /ha/, and /hi/. The observation index included the average rate (syllable/s) and regularity (%). Results: In the various age groups, there was no significant difference in LDDK rate and regularity of adducted syllables (p > 0.05), and only the regularity of /ʔi/ is significantly different between aged 18–40 and 41–64 years (p = 0.040). When vocal fold adduction was compared between various syllables, there was no significant difference in LDDK rate and regularity (p > 0.05). In various age groups, the LDDK rate of abduction syllables is different (p < 0.05) compared with the LDDK regularity of abduction syllables (p > 0.05). In various abduction syllables, there is no difference in LDDK rate (p > 0.05); however, /ha/ and /hi/ have significant differences in LDDK regularity (p = 0.007). Conclusion: According to the preliminary data, /ʔa/ and /ha/ can be used as suitable indicators to analyse the coordination ability of the laryngeal movement of Mandarin speakers. [ABSTRACT FROM AUTHOR]

Nonlinear phenomena (NLP) in animal vocalizations arise from irregularities in the oscillation of the vocal folds. Various non-mutually exclusive hypotheses have been put forward to explain the occurrence of NLP, from adaptive to physiological ones. Non-human primates often display NLP in their vocalizations, yet the communicative role of these features, if any, is still unclear. We here investigate the occurrence of NLP in the song of a singing primate, the indri (Indri indri), testing for the effect of sex, age, season, and duration of the vocal display on their emission. Our results show that NLP occurrence in indri depends on phonation, i.e., the cumulative duration of all the units emitted by an individual, and that NLP have higher probability to be emitted in the later stages of the song, probably due to the fatigue indris may experience while singing. Furthermore, NLP happen earlier in the vocal display of adult females than in that of the adult males, and this is probably due to the fact that fatigue occurs earlier in the former because of a greater contribution within the song. Our findings suggest, therefore, that indris may be subjected to physiological constraints during the singing process which may impair the production of harmonic sounds. However, indris may still benefit from emitting NLP by strengthening the loudness of their signals for better advertising their presence to the neighboring conspecific groups. [ABSTRACT FROM AUTHOR]

Objectives: Pediatric bilateral vocal cord immobility (BVCI) represents a severe life‐threatening condition that often causes severe dyspnea. Endoscopic arytenoid lateral abduction (EALA) is a relatively new, secure, minimal‐invasive surgical technique. The present prospective observational study aims to evaluate the effects of EALA in terms of respiratory function, voice quality, and swallowing capabilities. Methods: Twenty‐one pediatric patients with BVCI underwent EALA. Eleven out of 21 patients had tracheostomy at the time of surgery. Pre and postoperative functional assessments included endoscopic evaluation, maximum phonation time, pediatric Voice Handicap Index (pVHI), GIRBAS Scale criteria, and Montreal Children's Hospital Feeding scale (MCH‐Feeding scale). peak tidal inspiratory flow or peak inspiratory flow (PIF) and number of desaturations/hour (ODI/h) were evaluated in patients without tracheostomy. Results: Postoperative endoscopy showed glottic airway improvement in all patients. Average time for decannulation was 4.6 weeks. One patient has not yet been decannulated. No major complications occurred. In patients without tracheostomy, we observed a significant improvement of ODI/h and PIF after surgery (p < 0.05) as expected. PVHI, MCH‐Feeding scale, and GIRBAS score significantly worsened 1 month after surgical intervention (p < 0.05). One year after surgery, however, all values, except for B and A parameters of the GIRBAS score, returned to levels comparable to those preoperative. Conclusions: EALA represents a simple, safe and effective solution in pediatric patients with BVCI, avoiding tracheostomy, allowing early decannulation, preserving swallowing function, and maintaining good quality voice. Level of Evidence: 4 Laryngoscope, 133:2325–2332, 2023 [ABSTRACT FROM AUTHOR]

Pigs have become important animal models in voice research. Several objective parameters exist to characterize the pig voice, but it is not clear which of them are sensitive to the impaired voice quality after laryngeal injury or surgery. In order to conduct meaningful voice research in pigs, it is critical to have standard functional voice outcome measures that can distinguish between normal and impaired voices. For this reason, we investigated 17 acoustic parameters before and early after surgery in three Yucatan mini pigs. Four parameters showed consistent changes between pre- and post-surgery recordings, mostly related to decreased spectral energy in higher frequencies after surgery. We recommend two of these, 50% spectral energy quartile (Q50) and Flux, for objective functional voice assessment of pigs undergoing laryngeal surgery. The long-term goal of this process is to enable quantitative voice outcome tracking of laryngeal surgical interventions in porcine models.

Mucus consistency affects voice physiology and is connected to voice disorders. Nevertheless, the rheological characteristics of human laryngeal mucus from the vocal folds remain unknown. Knowledge about mucus viscoelasticity enables fabrication of artificial mucus with natural properties, more realistic ex-vivo experiments and promotes a better understanding and improved treatment of dysphonia with regard to mucus consistency. We studied human laryngeal mucus samples from the vocal folds with two complementary approaches: 19 samples were successfully applied to particle tracking microrheology (PTM) and five additional samples to oscillatory shear rheology (OSR). Mucus was collected by experienced laryngologists from patients together with demographic data. The analysis of the viscoelasticity revealed diversity among the investigated mucus samples according to their rigidity (absolute G' and G″). Moreover some samples revealed throughout solid-like character (G' > G″), whereas some underwent a change from solid-like to liquid-like (G' < G″). This led to a subdivision into three groups. We assume that the reason for the differences is a variation in the hydration level of the mucus, which affects the mucin concentration and network formation factors of the mucin mesh. The demographic data could not be correlated to the differences, except for the smoking behavior. Mucus of predominant liquid-like character was associated with current smokers.

Abstract Objectives The compound betamethasone is widely used to prevent scarring in dermatology. This study aims to explore the effects of compound betamethasone on vocal fold (VF) wound healing. Study design Prospective animal study in rabbits. Methods Eighteen rabbits underwent bilateral VF stripping and three rabbits served as controls. 0.1 mL of compound betamethasone (1 mL: betamethasone sodium phosphate 5 mg and betamethasone dipropionate 2 mg) was injected into the right VF of each rabbit, and 0.1 mL 0.9% saline was injected into the contralateral VF. Endoscopy was performed for morphologic observation. Six larynges were harvested for histological analysis at 3 days, 7 days, and 1 month. The VFs were stained with hematoxylin and eosin (H&E), Alcian blue, and Masson' trichrome staining. Results In morphological analysis, there was no visible difference between betamethasone‐treated and saline‐treated VFs at 3 and 7 days. After 1 month, more VF scars appeared on the saline‐treated VFs than the VFs treated with betamethasone. Inflammatory cell number showed significant difference between both VFs at 3 days (p = .037) and 7 days (p = .045). No significant different was found in epithelial thickness at 1 month between the betamethasone and saline groups. The collagen in the saline‐treated VFs was significantly denser than that of the betamethasone‐treated group (p = .037). There was also a significant increase in the level of hyaluronic acid (HA) in betamethasone‐injected VFs in comparison to the saline‐injected VFs (p = .006). Conclusions Based on this study, compound betamethasone can improve VF healing. Our findings suggest that VF injection with compound betamethasone helps to minimize scarring by increasing HA level and decreasing collagen density.

Key clinical message Voice deepening surgery has en increasing interest among laryngologist worldwide and a case of surprising foreign body in the thyroid cartilage awakes alert thoughts of awareness to certain patient group.

Laryngoscopy images play a vital role in merging computer vision and otorhinolaryngology research. However, limited studies offer laryngeal datasets for comparative evaluation. Hence, this study introduces a novel dataset focusing on vocal fold images. Additionally, we propose a lightweight network utilizing knowledge distillation, with our student model achieving around 98.4% accuracy-comparable to the original EfficientNetB1 while reducing model weights by up to 88%. We also present an AI-assisted smartphone solution, enabling a portable and intelligent laryngoscopy system that aids laryngoscopists in efficiently targeting vocal fold areas for observation and diagnosis. To sum up, our contribution includes a laryngeal image dataset and a compressed version of the efficient model, suitable for handheld laryngoscopy devices. [ABSTRACT FROM AUTHOR]

Objective: Vocal fold nodules (VFNs) are among the most common causes of dysphonia. Phonolaryngeal microsurgery, pharmacological treatments, and voice therapy (VT) have been used for treating VFNs. VT has been advocated as the primary treatment of choice. This study investigated the efficacy of the DoctorVox Voice therapy technique (DVT) for treating VFNs. Methods: A total of 38 patients with VFNs and 40 individuals without any voice problem (control group) were included. All patients received the DVT program. Otorhinolaryngology examination, videolaryngostroboscopy (VLS), and acoustic analysis (SPL, mean F0, jitter %, shimmer %, NHR) were performed at pretreatment, one and six months after the end of treatment. The voice handicap index-10 (VHI-10) and the GRB scales were used for perceptual voice evaluation. GRB and VLS scorings were done blindly. Results: Compared with the pretreatment values, the first- and the sixth-month values after treatment demonstrated a significant decrease in VHI-10 (19.5 vs. 5.1), GRB (2.3 vs 0.68 for G value) and VLS scores, SPL (54.4 vs 66.1 dB), F0 (201 vs. 227 Hz), jitter % (1.46 vs 0.85), shimmer % (3.27 vs 2.51), NHR (1.15 vs. 0.46) values among patients. Most of the voice parameters in the sixth month after the DVT program did not differ significantly from those of the control group. Conclusion: The DVT was found to be an effective method in VFN treatment. [ABSTRACT FROM AUTHOR]

Videolaryngostroboscopy (VLS) is considered gold standard method for assessing voice disorders. But patients with irregular waveform of vocal folds cannot benefit from the VLS. Videokymography [VKG] is a single line real time, high speed imaging technique. It detects voice disorders based on vocal fold vibration characteristics whether the vibrations are regular or irregular. There is no standard clinical protocol or evidence on the clinical relevance of VKG for functional assessment of voice disorders. Since mechanism of voice production depends on vibration characteristics, VKG imaging leads to new possibilities for diagnosis, objective documentation and monitoring of vocal fold behavior in clinical practice in case of voice disorders. This study aims to evaluate clinical value of VKG in addition to VLS as a complementary tool for the assessment of voice disorder. [ABSTRACT FROM AUTHOR]

Objective: Vocal fold nodules (VFNs) are among the most common causes of dysphonia. Phonolaryngeal microsurgery, pharmacological treatments, and voice therapy (VT) have been used for treating VFNs. VT has been advocated as the primary treatment of choice. This study investigated the efficacy of the DoctorVox Voice therapy technique (DVT) for treating VFNs. Methods: A total of 38 patients with VFNs and 40 individuals without any voice problem (control group) were included. All patients received the DVT program. Otorhinolaryngology examination, videolaryngostroboscopy (VLS), and acoustic analysis (SPL, mean F0, jitter %, shimmer %, NHR) were performed at pretreatment, one and six months after the end of treatment. The voice handicap index-10 (VHI-10) and the GRB scales were used for perceptual voice evaluation. GRB and VLS scorings were done blindly. Results: Compared with the pretreatment values, the first- and the sixth-month values after treatment demonstrated a significant decrease in VHI-10 (19.5 vs. 5.1), GRB (2.3 vs 0.68 for G value) and VLS scores, SPL (54.4 vs 66.1 dB), F0 (201 vs. 227 Hz), jitter % (1.46 vs 0.85), shimmer % (3.27 vs 2.51), NHR (1.15 vs. 0.46) values among patients. Most of the voice parameters in the sixth month after the DVT program did not differ significantly from those of the control group. Conclusion: The DVT was found to be an effective method in VFN treatment. [ABSTRACT FROM AUTHOR]

Objective: To present and validate a new simulation model for endoscopic phonomicrosurgery training as an improved teaching method. Methods: A low-cost artificial model was assembled using 3D printing, silicone, and gelatin. The study was designed to test the model's ability to carry out training and teaching of endoscopic phonomicrosurgery. The synthetic model was built to simulate normal and pathological vocal folds such as polyps, intracordal cysts and keratoses, made of silicone and gelatin and embedded in a larynx framework made by 3D printing. Simulations of endoscopic surgical procedures were performed and documented through photographs and videos and the images were submitted to the evaluation of a group of 17 otorhinolaryngologists who used a Likert scale questionnaire. The responses were submitted to an agreement analysis using the sum of the scores obtained for the responses as an appropriate level of validation. Cronbach's alpha index was calculated to measure the degree of the questionnaire internal consistency. Result: The evaluations indicated maximum approval for the model adequacy for use in practical classes and for the teaching of the procedures, as well as in the overall satisfaction with the model in the use of surgical training. Conclusion: The present proposal for training laryngeal endoscopic surgery in a 3D synthetic model is a viable option according to the validation methodology used in the present study.

Abstract Rationale Systemic dehydration negatively alters the expression of vocal fold inflammatory and cell junction markers. These biological changes can have downstream effects on the healing processes of injured vocal folds. In the dermis, reduced hydration prolongs inflammation and delays healing. It is unknown whether this biological effect is observed in vocal fold tissue. Objective To investigate the effects of systemic dehydration on vocal fold healing outcomes following acute, bilateral vocal fold injury in a rodent model. Methods Eighteen systemic dehydrated and 18 euhydrated adult male Sprague Dawley rats experienced bilateral vocal fold injuries or no injury (N = 9/group). Vocal fold gene expression levels of inflammatory mediators and epithelial cell junction markers were measured 24 h post‐injury. Results Pro‐inflammatory gene markers (IL‐1β; TNF‐α) were differentially expressed in response to systemic dehydration with vocal fold injury compared to non‐injury. Epithelial cell junction markers (Cadherin‐3, Desmoglein‐1) also exhibited divergent trends following systemic dehydration, but these data were not statistically significant. Conclusions Systemic dehydration may affect cellular vocal fold healing processes within 24 h. These findings lay the groundwork for further investigation of how hydration status can affect vocal fold tissue recovery and influence clinical care.

Abstract Background Older adults are more prone to develop systemic dehydration. Systemic dehydration has implications for vocal fold biology by affecting gene and protein expression. The objective of this study was to quantify vocal fold protein changes between two age groups and hydration status, and to investigate the interaction of age and hydration status on protein expression, which has not been investigated in the context of vocal folds before. Comparative proteomics was used to analyze the vocal fold proteome of 6.5-month-old and > 3-year-old rabbits subjected to water ad libitum or water volume restriction protocol. Results Young and older adult rabbits (n = 22) were either euhydrated (water ad libitum) or dehydrated by water volume restriction. Dehydration was confirmed by body weight loss of − 5.4% and − 4.6% in young and older groups, respectively, and a 1.7-fold increase of kidney renin gene expression in the young rabbits. LC-MS/MS identified 2286 proteins in the rabbit vocal folds of young and older adult rabbits combined. Of these, 177, 169, and 81 proteins were significantly (p ≤ 0.05) affected by age, hydration status, or the interaction of both factors, respectively. Analysis of the interaction effect revealed 32 proteins with opposite change patterns after dehydration between older and young rabbit vocal folds, while 31 proteins were differentially regulated only in the older adult rabbits and ten only in the young rabbits in response to systemic dehydration. The magnitude of changes for either up or downregulated proteins was higher in the older rabbits. These proteins are predominantly related to structural components of the extracellular matrix and muscle layer, suggesting a disturbance in the viscoelastic properties of aging vocal fold tissue, especially when subjected to systemic dehydration. Conclusions Water restriction is a laboratory protocol to assess systemic dehydration-related changes in the vocal fold tissue that is translatable to human subjects. Our findings showed a higher number of proteins differentially regulated with a greater magnitude of change in the vocal folds of older adult rabbits in the presence of systemic dehydration compared to younger rabbits. The association of these proteins with vocal fold structure and biomechanical properties suggests that older human subjects may be more vulnerable to the effects of systemic dehydration on vocal function. The clinical implications of these protein changes warrant more investigation, but age should be taken into consideration when evaluating vocal treatment recommendations that interfere with body fluid balance.

The understanding of vocal fold hydration state, including dehydrated, euhydrated, rehydrated tissue, and how hydration affects vocal fold biomechanical properties is still evolving. Although clinical observations support the benefits of increasing vocal fold hydration after dehydrating events, more mechanistic information on the effects of vocal fold dehydration and the beneficial effects of rehydration are needed. Alterations to hyaluronic acid (HA), an important component of the vocal fold extracellular matrix, are likely to influence the biomechanical properties of vocal folds. In this study, we investigated the influence of hydration state and HA on vocal fold tissue stiffness via biomechanical testing. Prospective, ex vivo study design. Fresh porcine vocal folds (N = 18) were examined following sequential immersion in hypertonic (dehydration) and isotonic solutions (rehydration). In a separate experiment, vocal folds were incubated in hyaluronidase (Hyal) to remove HA. Control tissues were not exposed to any challenges. A custom micromechanical system with a microforce sensing probe was used to measure the force-displacement response. Optical strain was calculated, and ultrasound imaging was used to measure tissue cross-sectional area to obtain stress-strain curves. Significant increases (P ≤ 0.05) were found in tangent moduli between dehydrated and rehydrated vocal folds at strains of ε = 0.15. The tangent moduli of Hyal-digested tissues significantly increased at both ε = 0.15 and 0.3 (P ≤ 0.05). Vocal fold dehydration increased tissue stiffness and rehydration reduced the stiffness. Loss of HA increased vocal fold stiffness, suggesting a potential mechanical role for HA in euhydrated vocal folds. [ABSTRACT FROM AUTHOR]

Grouping the thin epithelium and thicker superficial lamina propria layers into a single cover layer has been widely adopted in finite element vocal fold models. Recent silicone vocal fold studies have suggested, however, that inclusion of a distinct epithelial layer leads to more physiologically representative motion. This study systematically explores the ramifications of incorporating an epithelial layer into a cover grouping for finite element vocal fold modeling. A membrane model for the epithelium is introduced to facilitate parametric investigation by reducing the mesh density requirement of the epithelium into a single infinitesimally thin layer. Excluding the epithelium entirely leads to increased energy in higher order modes and larger inferior-superior excursion of the folds. Integrating the epithelium into a cover layer with volume-weighted average stiffness results in similar kinematics to that of a model treating the epithelium as a distinct layer. However, the internal stress/strain and contact pressure during collision are higher, and viscous dissipation is lower, when the epithelium is integrated into the cover. Thus, careful treatment of the epithelium is recommended for finite element studies, particularly when employing the models for estimating measures dependent upon internal stress/strain and/or collision pressure, such as vocal dose. [ABSTRACT FROM AUTHOR]

Objectives: The compound betamethasone is widely used to prevent scarring in dermatology. This study aims to explore the effects of compound betamethasone on vocal fold (VF) wound healing. Study design: Prospective animal study in rabbits. Methods: Eighteen rabbits underwent bilateral VF stripping and three rabbits served as controls. 0.1 mL of compound betamethasone (1 mL: betamethasone sodium phosphate 5 mg and betamethasone dipropionate 2 mg) was injected into the right VF of each rabbit, and 0.1 mL 0.9% saline was injected into the contralateral VF. Endoscopy was performed for morphologic observation. Six larynges were harvested for histological analysis at 3 days, 7 days, and 1 month. The VFs were stained with hematoxylin and eosin (H&E), Alcian blue, and Masson' trichrome staining. Results: In morphological analysis, there was no visible difference between betamethasone‐treated and saline‐treated VFs at 3 and 7 days. After 1 month, more VF scars appeared on the saline‐treated VFs than the VFs treated with betamethasone. Inflammatory cell number showed significant difference between both VFs at 3 days (p =.037) and 7 days (p =.045). No significant different was found in epithelial thickness at 1 month between the betamethasone and saline groups. The collagen in the saline‐treated VFs was significantly denser than that of the betamethasone‐treated group (p =.037). There was also a significant increase in the level of hyaluronic acid (HA) in betamethasone‐injected VFs in comparison to the saline‐injected VFs (p =.006). Conclusions: Based on this study, compound betamethasone can improve VF healing. Our findings suggest that VF injection with compound betamethasone helps to minimize scarring by increasing HA level and decreasing collagen density. [ABSTRACT FROM AUTHOR]

Since Keratosis may be accompanied with severe dysplasia or malignancy; early management of this condition is of essence. However, since this condition has a high rate of recurrence the surgical dilemma remains as to how frequently the surgeries should be performed and what should be the factors to guide this decision. The objectives of our study are to attempt to understand the demographics of laryngeal keratosis and its behaviour pattern including the potential to recur, disease upstaging and malignant transformation. This is a 6-year retrospective study of patients presenting to a Voice and Swallowing Centre. All patients had been operated upon and confirmed to have keratosis with or without cancer. The medical records and stroboscopy videos were reviewed for details such as age, gender, history of smoking, laterality of lesion, location of lesion on the vocal fold, recurrence with any disease upstaging or malignant transformation. In the case of recurrence of lesion the histopathology of the recurrence was compared with the primary histopathology. Chi square test & Fisher's exact test was used for comparison of proportions between two groups. A total of 71 patients were included in the study, 88% were males. Recurrence was seen in 20 patients (28%), 14 with benign recurrence and 6 with malignant. Rate of recurrence when the primary keratosis had been benign was 30.7 and 20.6% when the primary keratosis had been associated with malignancy. A majority of patients with glottic keratosis were males and all that underwent malignant transformation were males. The rate of postoperative recurrence when the primary keratosis had been benign was higher than when it had been keratosis associated with malignancy. This may indicate the need for aggressive surgical management for benign keratosis. [ABSTRACT FROM AUTHOR]

ObjectivesThere have been many advancements in laryngeal imaging using optical coherence tomography (OCT), with varying system design and probes for use in research, office, and operating room settings. We evaluated the performance of six distinct OCT systems in imaging porcine vocal folds (cords) using computational image processing and segmentation.MethodsPorcine vocal folds were scanned using six OCT systems. Imaging system and probe performance were quantitatively assessed for signal penetration, layer differentiation, and epithelium (EP) measurement. Fitted exponential decay curves with corresponding α constant and intensity thresholding segmentation were utilized to quantify the aforementioned parameters.ResultsThe smallest average α constant and deepest signal penetration was of the SS-OCT 1700 nm 90 kHz microscope system (α = -1.74), followed by the SS-OCT 1310 nm 200 kHz VCSEL microscope system (α = -1.99), and SS-OCT 1310 nm 50 kHz rigid forward viewing endoscope system (α = -2.23). The EP was not readily visualized for three out of six systems, but was detected using automated segmentation. Average EP thickness (mean ± SD) was calculated as 55.79 ± 31.86 μm which agrees favorably with previous literature.ConclusionComparisons of OCT systems are challenging, as they encompass different probe design, optical path, and lasers, depending on application. Practical evaluation of different systems using computer based quantitative image processing and segmentation revealed basic, constructive information, such as EP measurements. To further validate the comparisons of system performance with clinical usability, in vivo human laryngeal imaging will be conducted. Further development of automated image processing and segmentation can be useful in rapid analysis of information. Lasers Surg. Med. 51:412-422, 2019. © 2019 Wiley Periodicals, Inc.

Vocal fold scarring is the fibrotic manifestation of a variety of voice disorders, and is difficult to treat. Tissue engineering therapies provide a potential strategy to regenerate the native tissue microenvironment in order to restore vocal fold functionality. However, major challenges remain in capturing the complexity of the native tissue and sustaining regeneration. We hypothesized that hydrogels with tunable viscoelastic properties that present relevant biological cues to cells might be better suited as therapeutics. Herein, we characterized the response of human vocal fold fibroblasts to four different biomimetic hydrogels: thiolated hyaluronan (HA) crosslinked with poly(ethylene glycol) diacrylate (PEGDA), HA-PEGDA with type I collagen (HA-Col I), HA-PEGDA with type III collagen (HA-Col III) and HA-PEGDA with type I and III collagen (HA-Col I-Col III). Collagen incorporation allowed for interpenetrating fibrils of collagen within the non-fibrillar HA network, which increased the mechanical properties of the hydrogels. The addition of collagen fibrils also reduced hyaluronidase degradation of HA and hydrogel swelling ratio. Fibroblasts encapsulated in the HA-Col gels adopted a spindle shaped fibroblastic morphology by day 7 and exhibited extensive cytoskeletal networks by day 21, suggesting that the incorporation of collagen was essential for cell adhesion and spreading. Cells remained viable and synthesized new DNA throughout 21 days of culture. Gene expression levels significantly differed between the cells encapsulated in the different hydrogels. Relative fold changes in gene expression of MMP1, COL1A1, fibronectin and decorin suggest higher degrees of remodeling in HA-Col I-Col III gels in comparison to HA-Col I or HA-Col III hydrogels, suggesting that the former may better serve as a natural biomimetic hydrogel for tissue engineering applications. STATEMENT OF SIGNIFICANCE: Voice disorders affect about 1/3rd of the US population and significantly reduce quality of life. Patients with vocal fold fibrosis have few treatment options. Tissue engineering therapies provide a potential strategy to regenerate the native tissue microenvironment in order to restore vocal fold functionality. Various studies have used collagen or thiolated hyaluronan (HA) with gelatin as potential tissue engineering therapies. However, there is room for improvement in providing cells with more relevant biological cues that mimic the native tissue microenvironment and sustain regeneration. The present study introduces the use of type I collagen and type III collagen along with thiolated HA as a natural biomimetic hydrogel for vocal fold tissue engineering applications.

Decellularized extracellular matrix (dECM) is a promising material for tissue engineering applications. Tissue‐specific dECM is seen as a favorable material that recapitulates a native‐like microenvironment for cellular remodeling. However, the minute quantity of dECM derivable from small organs like the vocal fold (VF) hampers manufacturing scalability. Small intestinal submucosa (SIS), a commercial product with proven regenerative capacity, may be a viable option for VF applications. This study aims to compare SIS and VF dECM hydrogels with respect to protein content and functionality using mass spectrometry‐based proteomics and in vitro studies. Proteomic analysis reveals that VF and SIS dECM share 75% of core matrisome proteins. Although VF dECM proteins have greater overlap with native VF, SIS dECM shows less cross‐sample variability. Following decellularization, significant reductions of soluble collagen (61%), elastin (81%), and hyaluronan (44%) are noted in VF dECM. SIS dECM contains comparable elastin and hyaluronan but 67% greater soluble collagen than VF dECM. Cells deposit more neo‐collagen on SIS than VF‐dECM hydrogels, but comparable neo‐elastin (≈50 μg scaffold−1) and neo‐hyaluronan (≈6 μg scaffold−1). Overall, SIS dECM possesses a reasonably similar proteomic profile and regenerative capacity to VF dECM. SIS dECM is a promising alternative for dECM‐derived biomaterials for VF regeneration.

Fundamental frequency patterns during phonation onset have received renewed interest due to their promising application in objective classification of normal and pathological voices. However, the associated underlying mechanisms producing the wide array of patterns observed in different phonetic contexts are not yet fully understood. Herein, we employ theoretical and numerical analyses in an effort to elucidate the potential mechanisms driving opposing frequency patterns for initial/isolated vowels versus vowels preceded by voiceless consonants. Utilizing deterministic lumped-mass oscillator models of the vocal folds, we systematically explore the roles of collision and muscle activation in the dynamics of phonation onset. We find that an increasing trend in fundamental frequency, as observed for initial/isolated vowels, arises naturally through a progressive increase in system stiffness as collision intensifies as onset progresses, without the need for time-varying vocal fold tension or changes in aerodynamic loading. In contrast, reduction in cricothyroid muscle activation during onset is required to generate the decrease in fundamental frequency observed for vowels preceded by voiceless consonants. For such phonetic contexts, our analysis shows that the magnitude of reduction in the cricothyroid muscle activation and the activation level of the thyroarytenoid muscle are potential factors underlying observed differences in (relative) fundamental frequency between speakers with healthy and hyperfunctional voices. This work highlights the roles of sometimes competing laryngeal factors in producing the complex array of observed fundamental frequency patterns during phonation onset. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare a self-reported satisfaction questionnaire with the first two botulinum toxin injections in patients with adductor spasmodic dysphonia. MATERIALS AND METHODS: A comparative retrospective study was done in a laryngology private center of Mexico City from March 2011 to July 2021. Patients with spasmodic dysphonia were included and received treatment based on bilateral botulinum toxin vocal fold injections through cricothyroid membrane with electromyography guidance. RESULTS: Thirty-five subjects were enrolled. Average of units per vocal fold was 2.8 ± 2.1 and 3.4 ± 2.7 in the first and second injections, respectively (p = 0.01). Less patients asked for dosage modification (increased or decreased) in the second injection (23/35) compared to the first (25/35) and an increase in the number of patients that wanted to maintain the same units of botulinum toxin after the first and second injection, 10 to 12, respectively, was also seen. CONCLUSIONS: There was a tendency toward a greater percentage of subjects wanting to maintain their previous botulinum toxin dosage, suggesting greater satisfaction between dosages. [ABSTRACT FROM AUTHOR]

Introduction Laryngeal leukoplakia corresponds to a white lesion in the mucosa developed by the deposit of keratin in the epithelium, potentiated by chronic smoking. It is considered a preneoplastic lesion. Surgery is the most adopted treatment; however, non-surgical treatment is advocated by some authors. Objective To evaluate the effectiveness of vitamin A in the management of vocal fold leukoplakia. Methods Patients with videolaryngoscopy diagnosis of vocal fold leukoplakia were selected. The endoscopic images were photographed and with the aid of the ImageJ software (National Institutes of Health, Bethesda, MD, USA), the proportion of the size of the leukoplakia was calculated. Eligible patients were prescribed 50,000U of vitamin A, twice daily for 2 months, at which point videolaryngostroboscopy was repeated for comparative analysis between pre and posttreatment. The efficacy of the treatment was classified as: outcome I - complete improvement of the lesion, outcome II - partial improvement, and outcome III - no difference or increased lesion size. Results Fifteen patients (eight women, seven men) were included, six of whom had bilateral lesions. Smoking was reported in 86.8% of patients. Complete improvement of the lesion was found in 7 cases (33.4%, outcome I), partial improvement in 6 (28.6%, outcome II), and worsening of the injury in 8 (38.1%, outcome III). Of the latter, 6 underwent microsurgery; histopathology indicated absence of dysplasia in 3, and mild dysplasia in 3. Conclusions In this study, the treatment with vitamin A at a dose of 100,000 IU daily for 2 months was effective in reducing the laryngeal leukoplakia size in 62% of cases. [ABSTRACT FROM AUTHOR]