Long-term stimulation by implanted pacemaker enables non-atrophic treatment of bilateral vocal fold paresis in a human-like animal model.

A wide variety of treatments have been developed to improve respiratory function and quality of life in patients with bilateral vocal fold paresis (BVFP). One experimental method is the electrical activation of the posterior cricoarytenoid (PCA) muscle with a laryngeal pacemaker (LP) to open the vocal folds. We used an ovine (sheep) model of unilateral VFP to study the long-term effects of functional electrical stimulation on the PCA muscles. The left recurrent laryngeal nerve was cryo-damaged in all animals and an LP was implanted except for the controls. After a reinnervation phase of six months, animals were pooled into groups that received either no treatment, implantation of an LP only, or implantation of an LP and six months of stimulation with different duty cycles. Automated image analysis of fluorescently stained PCA cross-sections was performed to assess relevant muscle characteristics. We observed a fast-to-slow fibre type shift in response to nerve damage and stimulation, but no complete conversion to a slow-twitch-muscle. Fibre size, proportion of hybrid fibres, and intramuscular collagen content were not substantially altered by the stimulation. These results demonstrate that 30 Hz burst stimulation with duty cycles of 40% and 70% did not induce PCA atrophy or fibrosis. Thus, long-term stimulation with an LP is a promising approach for treating BVFP in humans without compromising muscle conditions.

[Clinical characteristics and efficacy of vocal fold epidermoid cysts coexisting with sulcus vocalis].

Objective: To investigate the clinical characteristics and voice outcomes after laryngeal microsurgery for vocal fold epidermoid cysts coexisting with sulcus vocalis. Methods: The clinical data of 115 vocal fold epidermoid cysts coexisting with sulcus vocalis patients in Shandong provincial ENT hospital, were retrospectively analyzed, including 49 males and 66 females, aged 17-70 years old, and the duration of hoarseness ranged from 6 months to 30 years. All patients underwent surgery through suspension laryngoscope and microscope under general anestgesia. Ninety-four patients were treated with microflap excision of sulcus vocalis, cyst wall, and contents.And 21 patients that occulted with mucosal bridges were applied mucosal bridges resection (2 cases) and mucosal bridges reconstruction (19 cases) respectively. Videolaryngoscopy, subjective voice evaluation (GRBAS), objective voice evaluation, and Voice Handicap Index(VHI) were performed before and after surgery. All patients underwent histopathologic examination and follow-up after the procedure. The preoperative acoustic parameters of patients with vocal fold epidermoid cysts coexisting with sulcus vocalis were compared with those of vocal fold mucus retention cysts and simple vocal fold epidermoid cysts by independent samples t-test. The patients were compared by paired t-test for preoperative and postoperative parameters. Results: Significant reduction or lack of mucosal waves were shown via videolaryngostroboscopy in all 115 cases.In addition, vascular changes including dilation, tortuousness, increased branches, and abrupt direction change were shown on the cystic area. Eighty-one patients were detected cysts and/or sulcus vocalis by preoperative laryngoscopy, and intraoperative microscopic findings in the remaining 34 patients. The intraoperative microscopic examination revealed a focal pouch-like deficit plunging into the vocal ligament or muscle. The deep surface of the mucosal bridges was sulcus vocalis, and that in 89 cysts was lined with caseous content. Histopathology demonstrated a cystic cavity structure lined with squamous epithelium and caseous keratin desquamation inside the cystic cavity. Four of 115 patients were lost at follow-up and excluded from the analysis of voice outcomes after surgery. There was no significant mucosal wave and the voice quality in all but 14 patients 1month after surgery. Except for the fundamental frequency and noise harmonic ratio, all other voice parameters[ G, R, B, A, VHI-10, jitter, shimmer, maximum phonatory time (MPT) ]showed a significant improvement 3 months after surgery(t=15.82, 20.82, 17.61, 7.30, 38.88, 7.84, 5.88, -6.26, respectively, P<0.05). Then mucosal waves and the voice quality were gradually improved and became steady in 6 months after surgery. The subjective and objective voice parameters[G, R, B, A, VHI-10, jitter, shimmer, noise to harmonic ratio(NHR), MPT], except for the fundamental frequency, were all significantly improved(t=23.47, 25.79, 18.37, 9.84, 54.45, 10.68, 8.07, 3.24, -9.08, respectively, P<0.05). In addition, there were 2 patients with no significant improvement after the operation. Steady function with no complications was observed during the 12 months (up to 3 years in 34 patients) follow-up period in 111 patients. Conclusion: Ruptured vocal fold epidermoid cysts can result in sulcus vocalis and mucosal bridges. Characteristics changes in preoperative videolaryngoscopy are effective diagnostic tools. The complete excision of the cyst wall and repair of the lamina propria can lead to satisfactory long-term effects.

Classification of laryngeal diseases including laryngeal cancer, benign mucosal disease, and vocal cord paralysis by artificial intelligence using voice analysis.

Voice change is often the first sign of laryngeal cancer, leading to diagnosis through hospital laryngoscopy. Screening for laryngeal cancer solely based on voice could enhance early detection. However, identifying voice indicators specific to laryngeal cancer is challenging, especially when differentiating it from other laryngeal ailments. This study presents an artificial intelligence model designed to distinguish between healthy voices, laryngeal cancer voices, and those of the other laryngeal conditions. We gathered voice samples of individuals with laryngeal cancer, vocal cord paralysis, benign mucosal diseases, and healthy participants. Comprehensive testing was conducted to determine the best mel-frequency cepstral coefficient conversion and machine learning techniques, with results analyzed in-depth. In our tests, laryngeal diseases distinguishing from healthy voices achieved an accuracy of 0.85-0.97. However, when multiclass classification, accuracy ranged from 0.75 to 0.83. These findings highlight the challenges of artificial intelligence-driven voice-based diagnosis due to overlaps with benign conditions but also underscore its potential.

Significance of Contusion at the Vocal Cord and Perivocal Cord Area in Cases of Non-intubated Death.

Every finding during a neck autopsy may be essential for accurately diagnosing and explaining the mechanism of death. In this prospective study in the Department of Forensic Medicine and Toxicology of Jordan University Hospital, 17 out of 95 neck autopsies revealed contusions of the laryngeal mucosa in the vocal or perivocal area. These contusions were found to be associated with various causes of death, including mechanical asphyxia (such as throttling, ligature strangulation, hanging, smothering, choking, plastic bag asphyxia, gagging, and inhalation of blood) and other causes (such as atypical drowning, carbon monoxide poisoning, head injury due to a road traffic accident, burns, electrocution, and brain edema). This study provides insight into the mechanisms of this important lesion and may contribute to a better understanding of the cause of death.

Discrimination of vocal folds lesions by multiclass classification using autofluorescence spectroscopy: An ex vivo study.

BACKGROUND: Autofluorescence spectroscopy is effective for noninvasive detection but underutilized in tissue with various pathology analyses. This study evaluates whether AFS can be used to discriminate between different types of laryngeal lesions in view of assisting in vocal fold surgery and preoperative investigations. METHODS: A total of 1308 spectra were recorded from 29 vocal fold samples obtained from 23 patients. Multiclass analysis was performed on the spectral data, categorizing lesions into normal, benign, dysplastic, or carcinoma. RESULTS: Through an appropriate selection of spectral components and a cascading classification approach based on artificial neural networks, a classification rate of 97% was achieved for each lesion class, compared to 52% using autofluorescence intensity. CONCLUSIONS: The ex vivo study demonstrates the effectiveness of AFS combined with multivariate analysis for accurate classification of vocal fold lesions. Comprehensive analysis of spectral data significantly improves classification accuracy, such as distinguishing malignant from precancerous or benign lesions.

Office-based blue laser therapy for vocal fold polyps and Reinke's edema: a case study and review of the literature.

PURPOSE: To report the efficacy of blue laser in the treatment of vocal fold polyps and Reinke's edema in an office setting. METHODS: The medical records and video-recordings of patients who underwent office-based blue laser therapy in a tertiary referral center for vocal fold polyps and/or Reinke's edema were reviewed. The primary outcome measures were the Voice Handicap Index-10 (VHI-10) score and disease regression. Acoustic and aerodynamic parameters were also analyzed. RESULTS: Thirty-five patients (21 with vocal fold polyps and 14 with Reinke's edema) were included and a total of 47 lesions were treated. Out of the 35 patients, 7 patients were lost for follow-up. The mean VHI-10 score dropped significantly after surgery by 17.41 ± 8.67 points (p < 0.001). The endoscopic examinations of 38 lesions were reviewed (17 vocal fold polyps and 21 Reinke's edema) before and up to 6 months after laser therapy. In the subgroup with vocal fold polyps (N = 17), there was complete disease regression in 13 and partial in 4. In the subgroup with Reinke's edema (N = 21), there was complete disease regression in 7 and partial disease regression in 14. For patients with vocal fold polyp, there was a significant decrease in shimmer and a significant increase in maximum phonation time postoperatively. For patients with Reinke's edema, there was a significant decrease in shimmer and noise-to-harmonic ratio following treatment. CONCLUSION: Office-based blue laser therapy is an effective treatment for vocal fold polyps and Reinke's edema leading to complete or partial disease regression. All patients had improvement in voice quality.

Vocal fold leukoplakia recurrence risk model.

The paper aims to define the variables that elevate the risk of VFL recurrence after adequate primary treatment, and to present the Recurrence Risk Model with practical conclusions to handle pVFL and rVFL. Out of 207 patients with primary vocal fold leukoplakia (pVFL), in 41 (19.8%) recurrent VFL (rVFL) was diagnosed. All patients were assessed by using a trans-nasal flexible video-endoscope using white light, and NBI. The primary measure of our study was to investigate whether morphological features of pVFL in WL, vascular pattern in NBI, and primary histological findings could predict VFL recurrence. To create a model of risk factors, two methods were used: logistic regression and a conditional inference decision tree. The study showed smoking was the factor that significantly and most strongly increased the likelihood of rVFL, as well as the older age groups have a greater odds of rVFL. Types IV, V and VI, according to Ni 2019 classification, were associated with a significantly higher risk of rVFL. The algorithm combining patients' dependent variables and the combination of two classifications improves the predictive value of the presented VFL Recurrence Risk Model.

Value of high-speed videoendoscopy as an auxiliary tool in differentiation of benign and malignant unilateral vocal lesions.

PURPOSE: The study aimed to assess the relevance of objective vibratory parameters derived from high-speed videolaryngoscopy (HSV) as a supporting tool, to assist clinicians in establishing the initial diagnosis of benign and malignant glottal organic lesions. METHODS: The HSV examinations were conducted in 175 subjects: 50 normophonic, 85 subjects with benign vocal fold lesions, and 40 with early glottic cancer; organic lesions were confirmed by histopathologic examination. The parameters, derived from HSV kymography: amplitude, symmetry, and glottal dynamic characteristics, were compared statistically between the groups with the following ROC analysis. RESULTS: Among 14 calculated parameters, 10 differed significantly between the groups. Four of them, the average resultant amplitude of the involved vocal fold (AmpInvolvedAvg), average amplitude asymmetry for the whole glottis and its middle third part (AmplAsymAvg; AmplAsymAvg_2/3), and absolute average phase difference (AbsPhaseDiffAvg), showed significant differences between benign and malignant lesions. Amplitude values were decreasing, while asymmetry and phase difference values were increasing with the risk of malignancy. In ROC analysis, the highest AUC was observed for AmpAsymAvg (0.719; p < 0.0001), and next in order was AmpInvolvedAvg (0.70; p = 0.0002). CONCLUSION: The golden standard in the diagnosis of organic lesions of glottis remains clinical examination with videolaryngoscopy, confirmed by histopathological examination. Our results showed that measurements of amplitude, asymmetry, and phase of vibrations in malignant vocal fold masses deteriorate significantly in comparison to benign vocal lesions. High-speed videolaryngoscopy could aid their preliminary differentiation noninvasively before histopathological examination; however, further research on larger groups is needed.

Identification and analysis of Nonlinear behaviors of vocal fold biomechanics during phonation to assess efficacy of surgery for benign laryngeal Diseases.

BACKGROUND: Current voice assessments focus on perceptive evaluation and acoustic analysis. The interaction of vocal tract pressure (PVT) and vocal fold (VF) vibrations are important for volume and pitch control. However, there are currently little non-invasive ways to measure PVT. Limited information has been provided by previous human trials, and interactions between PVT and VF vibrations and the potential clinical application remain unclear. Here, we propose a non-invasive method for monitoring the nonlinear characteristics of PVT and VF vibrations, analyze voices from pathological and healthy individuals, and evaluate treatment efficacy. METHOD: Healthy volunteers and patients with benign laryngeal lesions were recruited for this study. PVT was estimated using an airflow interruption method, VF vibrational frequency was calculated from accelerometer signals, and nonlinear relationships between PVT and VF vibrations were analyzed. Results from healthy volunteers and patients, as well as pre- and post-operation for the patients, were compared. RESULTS: For healthy volunteers, nonlinearity was exhibited as an initial increase and then prompt decrease in vibrational frequency at the end of phonation, coinciding with PVT equilibrating with the subglottal pressure upon airflow interruption. For patients, nonlinearity was present throughout the phonation period pre-operatively, but showed a similar trend to healthy volunteers post-operatively. CONCLUSION: This novel method simultaneously monitors PVT and VF vibration and helps clarify the role of PVT. The results demonstrate differences in nonlinear characteristics between healthy volunteers and patients, and pre-/post-operation in patients. The method may serve as an analysis tool for clinicians to assess pathological phonation and treatment efficacy.

What Are Vocal Cord Nodules?

This Patient Page describes the symptoms, diagnosis, and treatment of vocal cord nodules.

Deep learning in voice analysis for diagnosing vocal cord pathologies: a systematic review.

OBJECTIVES: With smartphones and wearable devices becoming ubiquitous, they offer an opportunity for large-scale voice sampling. This systematic review explores the application of deep learning models for the automated analysis of voice samples to detect vocal cord pathologies. METHODS: We conducted a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. We searched MEDLINE and Embase databases for original publications on deep learning applications for diagnosing vocal cord pathologies between 2002 and 2022. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). RESULTS: Out of the 14 studies that met the inclusion criteria, data from a total of 3037 patients were analyzed. All studies were retrospective. Deep learning applications targeted Reinke's edema, nodules, polyps, cysts, unilateral cord paralysis, and vocal fold cancer detection. Most pathologies had detection accuracy above 90%. Thirteen studies (93%) exhibited a high risk of bias and concerns about applicability. CONCLUSIONS: Technology holds promise for enhancing the screening and diagnosis of vocal cord pathologies. While current research is limited, the presented studies offer proof of concept for developing larger-scale solutions.

Changes in vocal fold gene expression and histology after injection augmentation in a recurrent laryngeal nerve injury model.

OBJECTIVE: To investigate changes in neuroregenerative pathways with vocal fold denervation in response to vocal fold augmentation. METHODS: Eighteen Yorkshire crossbreed swine underwent left recurrent laryngeal nerve transection, followed by observation or augmentation with carboxymethylcellulose or calcium hydroxyapatite at two weeks. Polymerase chain reaction expression of genes regulating muscle growth (MyoD1, MyoG and FoxO1) and atrophy (FBXO32) were analysed at 4 and 12 weeks post-injection. Thyroarytenoid neuromuscular junction density was quantified using immunohistochemistry. RESULTS: Denervated vocal folds demonstrated reduced expression of MyoD1, MyoG, FoxO1 and FBXO32, but overexpression after augmentation. Healthy vocal folds showed increased early and late MyoD1, MyoG, FoxO1 and FBXO32 expression in all animals. Neuromuscular junction density had a slower decline in augmented compared to untreated denervated vocal folds, and was significantly reduced in healthy vocal folds contralateral to augmentation. CONCLUSION: Injection augmentation may slow neuromuscular degeneration pathways in denervated vocal folds and reduce compensatory remodelling in contralateral healthy vocal folds.

Visual Gaze Patterns in the Analysis of Glottic Lesions: Does Experience Increase Diagnostic Accuracy?

OBJECTIVES: The purpose of this study was to evaluate visual gaze patterns and the ability to correctly identify cancer among participants of different experience levels when viewing benign and malignant vocal cord lesions. METHODS: Thirty-one participants were divided into groups based on level of experience. These included novice (medical students, PGY1-2 otolaryngology residents), intermediate (PGY3-5 otolaryngology residents, gastroenterology fellow), advanced practice providers (physician assistants, nurse practitioners, and speech language pathologists), and experts (board-certified otolaryngologists). Each participant was shown 7 images of vocal cord pathology including glottic cancer, infectious laryngitis, and granuloma and asked to determine the likelihood of cancer on a scale of certain, probable, possible, and unlikely. Eye tracking data were collected and used to identify the area of interest (AOI) that each participant fixated on first, fixated on the longest, and had the greatest number of fixations. RESULTS: No significant differences were seen among groups when comparing AOI with first fixation, AOI with longest fixation, or AOI with most fixations. Novices were significantly more likely to rate a low likelihood of cancer when viewing infectious laryngitis compared to more experienced groups (P < .001). There was no difference in likelihood of cancer rating among groups for the remaining images. CONCLUSIONS: There was no significant difference in gaze targets among participants of different experience levels evaluating vocal cord pathology. Symmetric appearance of vocal cord lesions may explain differences seen in likelihood of cancer rating among groups. Future studies with larger sample sizes will better elucidate gaze targets that lead to accurate diagnosis of vocal cord pathology.

Acute Effects of Systemic Glucocorticoids on the Vocal Folds in a Pre-Clinical Model.

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.

Determining the Efficacy of Surgical Versus Non-Surgical Management in T3M0 Laryngeal Cancer With Cord Fixation.

OBJECTIVE: Survival of laryngeal cancer is decreasing; thus, optimal treatment selection is paramount. Specifically, T3 disease survival appears similar with surgical or non-surgical management; however, the implications of vocal cord fixation on treatment selection and survival are unknown. This study seeks to determine if surgical treatment of patients with T3M0 laryngeal cancer with vocal cord fixation is associated with superior survival compared to non-surgical treatment. METHODS: The National Cancer Database (NCDB) was queried for all T3M0 laryngeal carcinoma cases from 2004 to 2015, whose treatment included surgery or radiation therapy. Cases were stratified by cord fixation status and overall survival was compared using multivariable methods based on surgical versus non-surgical management. RESULTS: Non-surgical management was more common, regardless of cord fixation status (84% in fixed and 79% in mobile). Cord fixation itself did not influence survival; however, surgical management had a significant survival benefit in the fixed cohort (HR = 0.843; 95% CI: 0.738, 0.962). CONCLUSION: In this large observational cohort study of T3M0 laryngeal cancer, those with fixed cords had superior survival when managed surgically.

Quantitative Evaluation of Vocal Bowing Following Bilateral Thyroplasty in Age-Related Vocal Atrophy.

OBJECTIVE: Age-related vocal atrophy (ARVA) is associated with vocal fold bowing, persistent glottal gap during phonation, and dysphonia. Bilateral medialization thyroplasty is sometimes performed in patients with ARVA to improve vocal fold closure and voice. We set out to quantify stroboscopic changes in vocal fold bowing, glottal closure, and abduction angle following bilateral thyroplasty and determine how these changes affect voice quality among patients with ARVA. METHODS: Fifteen individuals with ARVA who underwent bilateral medialization thyroplasty were included in this study. Two independent investigators calculated bowing index (BI), normalized glottal gap area (NGGA), and maximum abduction angle from laryngostroboscopic exams using ImageJ™. Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) and patient-reported measures were collected before and after thyroplasty. RESULTS: Thyroplasty resulted in a 10-point improvement in overall CAPE-V (Mean dif -10; 95% CI -17, -3.3, p < 0.01) and VHI-10 (mean dif -3.8; 95% CI -9.8, 2.3, p = 0.19, n = 8). NGGA and BI significantly decreased following surgery (mean dif -78; 95% CI -155, -1.5, p = 0.05; and mean dif -2.1; 95% CI -2.4, -0.84, p < 0.01, respectively). BI correlated with CAPE-V scores (r = 0.66, 95% CI 0.22, 0.87, p < 0.01). When considering the normalized combined contributions of both NGGA and BI, there was a stronger correlation in CAPE-V scores (r = 0.87, 95% CI 0.50, 0.97, p < 0.01) compared with either measure alone. CONCLUSIONS: Thyroplasty resulted in a decrease in vocal fold bowing, glottal gap area, and CAPE-V scores in patients with ARVA. Correction of vocal bowing and glottal gap, following bilateral thyroplasty, improved voice measures following surgery. Quantitative evaluation of vocal fold morphology may be valuable when assessing the severity and treatment-response in patients with ARVA following bilateral thyroplasty. Laryngoscope, 134:835-841, 2024.

Pathogenesis of Reinke's Edema of the Vocal Fold.

OBJECTIVES: The most frequent etiologic factor of Reinke's edema (RE) is considered to be smoking. However, the mechanism for the onset and development of the disease remains unclear. Hypoxia-inducible factor-1α (HIF-1α) is an oxygen-dependent transcriptional activator which plays crucial roles in angiogenesis in hypoxic microenvironments. HIF-1α induces the expression of vascular endothelial growth factor (VEGF) which involves angiogenesis and enhances vascular permeability. This study investigated the roles of HIF-1α in the pathogenesis of RE. METHODS: Surgical specimens of RE from patients who underwent endolaryngeal microsurgery were used. Normal vocal folds were used as a control group. Expression of HIF-1α and VEGF was analyzed by immunohistochemistry. Three-dimensional fine structures of the vessels in RE were investigated using correlative light and electron microscopy (CLEM) technique. RESULTS: HIF-1α and VEGF were broadly expressed in the stromal, inflammatory, and endothelial cells in the lamina propria of the vocal fold of RE. The expression of HIF-1α and VEGF of RE were significantly higher than in the lamina propria of the normal vocal fold mucosa. CLEM showed vascularization and telangiectasia and there were many dilated capillaries with thin endothelium not covered with pericytes indicating the vessels were fragile. CONCLUSION: Transcription factor HIF-1α and induced VEGF likely play roles in the pathogenesis of RE. And increased vascular permeability with fragile vessels in angiogenesis is likely to be an etiology of RE. Transcription factor HIF-1α and induced VEGF are potential therapeutic targets for RE. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1785-1791, 2024.

The Use of a Dehydrated Cellularized Collagen Matrix to Replace Fibrotic Vocal Fold Mucosa.

OBJECTIVES: Fibrosis of the vocal fold lamina propria reduces vocal cord vibration resulting in a chronically hoarse voice. We describe a novel approach using umbilical cord-derived mesenchymal stem cells in a dehydrated collagen matrix (cellogen) to reconstruct the delicate balance of extracellular matrix within the vocal fold lamina propria whilst limiting the host inflammatory response to the implant. METHODS: Human umbilical cord-derived mesenchymal stem-cells were embedded in bovine type I collagen hydrogel and dehydrated using the RAFT™ 3D culture system. The extracellular matrix, cellular viability and composition, paracrine profile, and genomic profile were assessed and the scaffold engrafted onto the hind muscle of NUDE mice. RESULTS: The cells retained stem-cell markers following fabrication and secreted collagen III, fibronectin, and glycosaminoglycans within the scaffold. Electron microscopy showed the scaffold consisted of single strands of protein with interspersed bundles of a similar size to native vocal fold lamina propria. The use of the dehydration step improved cell viability and upregulated the expression of genes important in wound healing and matrix organization compared with unmodified collagen hydrogel carriers. The cells were shown to secrete exosomes and cytokines and, following engraftment within an immunocompromised mouse model, appeared to modulate the host inflammatory response compared with controls. CONCLUSION: This article provides a scalable cell-protein scaffold that with further modifications could provide a replacement for lost or damaged vocal fold mucosa. Further investigations are required to assess the mechanical properties of the scaffold and inhibit the differentiation of the umbilical cord-derived stem-cells following implantation. Laryngoscope, 134:882-893, 2024.

Return to Vocal Performance Following Microlaryngoscopy in Singers.

INTRODUCTION: Although microlaryngoscopy has been recognized to be effective in addressing lesions in vocal performers, no detailed information regarding return to performance (RTP) following surgery exists. We describe our experience and offer proposals to establish standardized criteria for RTP among vocal performers. METHODS: Records for adult vocalists who underwent microlaryngoscopy for benign vocal fold (VF) lesions and had a clearly documented RTP date between 2006 and 2022 were reviewed. Patient demographics, diagnoses, interventions, and postsurgical care before and after RTP were described. The need for medical and procedural interventions and rate of reinjury were used to determine the success of RTP. RESULTS: Sixty-nine vocal performers (average age: 32.8 years, 41 [59.4%] female, 61 [88.4%] musical theater) underwent surgery for 37 (53.6%) pseudocysts, 25 (36.2%) polyps, 5 (7.2%) cysts, 1 (1.4%) varix, and 1 (1.4%) mucosal bridge. Fifty-seven (82.6%) underwent voice therapy. The average time to RTP was 65.0 ± 29.8 days. Prior to RTP, six (8.7%) experienced VF edema requiring oral steroids and one (1.4%) underwent a VF steroid injection. Within 6 months following RTP, eight (11.6%) received oral steroids for edema and three underwent procedural interventions (two steroid injections for edema/stiffness, one injection augmentation for paresis). One patient experienced pseudocyst recurrence. CONCLUSIONS: Return to vocal performance at an average of 2 months following microlaryngoscopy for benign lesions appears overwhelmingly successful, with low rates of need for additional intervention. There is a need for validated instruments to better measure performance fitness to refine and possibly accelerate RTP. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:329-334, 2024.

Cell-Based Outer Vocal Fold Replacement Both Treats and Prevents Vocal Fold Scarring in Rabbits.

OBJECTIVE: Numerous pharmacological and cell-based treatments have shown promise in preventing vocal fold (VF) scarring when applied at the time of injury. A common clinical scenario, however, is the finding of mature scar impeding voicing. Many treatments are less effective in remodeling existing scar tissue. This objective of this study is to determine if a cell-based outer vocal fold replacement (COVR) effectively restores VF function when applied to existing scar. METHODS: Eighteen rabbits were allocated to three groups: unilateral COVR implant at the time of cordectomy (acute COVR); unilateral cordectomy followed by COVR implant 2 months later (chronic COVR); and unilateral cordectomy followed by sham implant surgery 2 months later (chronic scar). Larynges were harvested 2 months after implant or sham surgery. RESULTS: All larynges in the COVR groups demonstrated human leukocyte antigen labeling on immunohistochemistry (IHC). COVR groups had increased hyaluronic acid content compared with normal. VF stiffness as measured by elastic moduli in acute COVR and chronic COVR were similar to their contralateral unoperated VF. CONCLUSION: COVR implantation in both acutely injured and chronically scarred VF demonstrate persistence of implanted cells, restored tissue biomechanics, and increased hyaluronic acid content. LEVEL OF EVIDENCE: NA Laryngoscope, 134:764-772, 2024.