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Objectives: To assess the efficacy of intralesional steroid treatment in preventing vocal fold scarring following vocal fold surgery using a rabbit model. Methods: The research involved 42 male New Zealand white rabbits. Fourteen rabbits underwent vocal fold scar surgery using a 532nm laser and served as controls (control group). The remaining rabbits were divided into two groups of 14: one group received vocal fold scar surgery followed by dexamethasone injection (Dexa group) and the other received the same surgery followed by triamcinolone injection (Triam group). Four weeks after surgery, histological examinations and high‐speed video analyses of vocal fold vibration were conducted. The maximum amplitude of vibration was the primary measure for assessing vocal fold function. In addition, real‐time polymerase chain reaction (PCR) studies were undertaken to analyze scar regeneration and remodeling. Results: The maximum amplitude differences were notably higher in the Dexa and Triam groups than in controls. Histologically, the collagen density (CD) ratios in both the Dexa and Triam groups were significantly reduced compared with controls. Real‐time PCR analysis indicated marked elevations of Has‐2 and Mmp‐9 in the Dexa and Triam groups relative to controls. Conclusions: Intralesional steroid injections after vocal fold surgery are effective for reducing vocal fold scarring in a rabbit model. Level of Evidence: NA Laryngoscope, 135:176–182, 2025 [ABSTRACT FROM AUTHOR]

ObjectiveNumerous 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.MethodsEighteen 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.ResultsAll 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.ConclusionCOVR implantation in both acutely injured and chronically scarred VF demonstrate persistence of implanted cells, restored tissue biomechanics, and increased hyaluronic acid content.Level of evidenceNA Laryngoscope, 134:764-772, 2024.

Objectives: Systemic dehydration may induce osmotic and oxidative stress in the vocal folds, but our knowledge of the biology and mitigation with rehydration is limited. The purpose of this experiment was to evaluate whether systemic dehydration induces vocal fold oxidative and osmotic stress and to compare the impact of rehydration by water intake versus electrolyte intake on osmotic and oxidative stress‐related gene expression. Methods: Four‐month‐old male Sprague–Dawley rats (N = 32) underwent water restriction. Rehydration was achieved with ad libitum access to water or electrolytes for 24 hours. Rats were divided into four groups: euhydration control, dehydration‐only, dehydration followed by either water or electrolyte rehydration (n = 8/group). Gene expression was assessed via RT2 Gene Expression Profiler arrays. Results: With respect to oxidative stress, 10 genes were upregulated and 2 were downregulated after vocal fold dehydration compared with the euhydrated control. Concerning osmotic stress, six genes were upregulated with dehydration only, six genes were upregulated following rehydration with water, whereas a single gene was upregulated with electrolyte rehydration. All genes with significantly different expression between the rehydration groups showed lower expression with electrolytes compared with water. Conclusions: The results support a potential role of oxidative and osmotic stresses in vocal folds related to systemic dehydration. The differences in stress‐related gene expression in vocal fold tissue between rehydration with electrolytes or water, albeit modest, suggest that both rehydration options offer clinical utility to subjects experiencing vocal fold dehydration with preliminary evidence that electrolytes may be more effective than water in resolving osmotic stress. Level of Evidence: NA (prospective animal study) Laryngoscope, 134:4636–4641, 2024 [ABSTRACT FROM AUTHOR]

Objectives: Vocal fold scar remains a therapeutic challenge. Vocal fold fibroblasts (VFFs) secrete extracellular matrix (ECM), and transforming growth factor‐beta 1 (TGF‐β1)‐mediated fibroblast to myofibroblast differentiation is central to the development of fibrosis. The transient receptor potential (TRP) channel superfamily is a group of nonselective cation channels, and activation of TRP ankyrin 1 (TRPA1) channel has been shown to have antifibrotic effects through TGF‐β1/Smad signaling in various organs. This study aimed to elucidate expression of TRPA1 and the impact of TRPA1 activation on TGF‐β1/Smad signaling in VFFs. Methods: Vocal folds were dissected from 10‐week‐old, male Sprague‐Dawley rats and primary VFFs were established. TRPA1 was examined in VFFs and lamina propria via immunostaining. VFFs were treated with allyl isothiocyanate (AITC, TRP channel agonist, 10−5 M) ± TGF‐β1 (10 ng/ml) ± A‐967079 (selective TRPA1 channel antagonist, 5.0 × 10−7 M) for 4 or 24 h. Trpa1, Smad3, Smad7, Col1a1, Acta2, and Has1 mRNA expression were quantified via qPCR. Results: TRPA1 was expressed in cultured VFFs and the lamina propria. TGF‐β1 administration significantly increased Trpa1 compared to control. AITC alone did not alter Smad3, Smad7, Acta2, or ECM related genes. However, the combination of AITC and TGF‐β1 significantly increased Smad3 and decreased Smad7 and Acta2 compared to TGF‐β1 alone; A‐967079 significantly reduced this response. Conclusions: VFFs expressed TRPA1, and the activation of TRPA1 regulated TGF‐β1/Smad signaling in VFFs. These findings provide preliminary insights into potential anti‐fibrotic mechanisms of TRPA1 activation through TGF‐β1/Smad signaling in VFFs. Level of Evidence: NA Laryngoscope, 134:4593–4598, 2024 [ABSTRACT FROM AUTHOR]

Purpose: There are few options for treatment of dysphonia secondary to vocal pathology related to lamina propria scar, atrophy, sulcus, or inflammatory disorders. Platelet rich plasma (PRP) may provide anti-inflammatory and regenerative properties seen with other tissue engineering therapies without the risks associated with these treatments. We evaluated vocal fold (VF) injection of PRP for feasibility, phonatory effects, patient satisfaction and durability. Methods: Patients with dysphonia secondary to vocal fold scar, atrophy, sulcus and inflammatory lesions were included. PRP injections were administered in office, to bilateral vocal folds. Patients were followed up at 1 week, 1 month, 3 months and 6 months to assess outcomes (GRBAS scale, maximum phonation time, vocal fatigue index (VFI), voice handicap index (VHI-10) and stroboscopy). Results: 75 intracordal PRP injections were administered to 48 patients. All injections were completed, and no adverse reactions were experienced. Improvements in VHI-10 scores at 1,3,6 months were seen (mean VHI 21.73 at baseline, 15.62 at six months, p < 0.001). 72.3% rated improvement at 7 or above on Likert scale. 95.7% of patients would consider a future PRP injection. Secondary outcomes VFI, MPT, and GRBAS also demonstrated significant improvements over time. Patients receiving a single PRP injection (n = 26) still demonstrated significant VHI-10 improvements at 1,3 and 6 months. Conclusions: VF office PRP injections are feasible and safe and can provide phonatory benefit and reduce vocal effort in benign VF disorders. A single PRP injection is sufficient to provide sustained benefit in some cases. Level of evidence: Level III: prospective cohort study. [ABSTRACT FROM AUTHOR]

Objective: Current laryngeal injection models rely on the transoral route and are suboptimal due to limited view, narrowed working space, and the need to sacrifice animals for investigation of the injectables. In the present study, a novel surgical model for laryngeal intervention therapy utilizing an ultra‐high frequency ultrasound imaging system was proposed. Based on this system, we developed a systemic evaluation approach, from guidance of the injection process, documentation of the injection site of the material, to in vivo longitudinal follow‐up on the augmentation and medialization effect by analyzing the ultrasonography data. Study Design: In vivo animal study. Setting: Academic institution. Methods: Injection laryngoplasty with hyaluronic acid under ultrasonography guidance was performed on Sprague‐Dawley rats one week after induced unilateral vocal paralysis. Ultrasonography was performed at preinjection, immediately postinjection, on Day 2, Day 7 and then weekly for 4 weeks to obtain measurements, including the glottic area, angle between bilateral folds, and vocal fold width ratio. Laryngoscopic and histologic studies were also performed. Results: Unilateral injections to the paralyzed fold were successfully performed as demonstrated by ultrasonographic, laryngoscopic, and histologic studies. The width ratio was significantly increased after injection for 4 weeks, while the glottic airway area was unchanged. Conclusion: Here, a novel surgical model for laryngeal injection utilizing ultrasonography in rats was established. In addition to providing visual guidance for precise localization of the injection, robust documentation of the treatment effect was also demonstrated. This methodology could be beneficial for screening therapeutic agents for treatment of glottic insufficiency. [ABSTRACT FROM AUTHOR]

Introduction: The function of the vocal folds (VFs) is determined by the phenotype, abundance, and distribution of differentiated cells within specific microenvironments. Identifying this histologic framework is crucial in understanding laryngeal disease. A paucity of studies investigating VF cellular heterogeneity has been undertaken. Here, we examined the cellular landscape of human VFs by utilizing single‐nuclei RNA‐sequencing. Methods: Normal true VF tissue was excised from five patients undergoing pitch elevation surgery. Tissue was snap frozen in liquid nitrogen and subjected to cellular digestion and nuclear extraction. Nuclei were processed for single‐nucleus sequencing using the 10X Genomics Chromium platform. Sequencing reads were assembled using cellranger and analyzed with the scanpy package in python. Results: RNA sequencing revealed 18 global cell clusters. While many were of epithelial origin, expected cell types, such as fibroblasts, immune cells, muscle cells, and endothelial cells were present. Subcluster analysis defined unique epithelial, immune, and fibroblast subpopulations. Conclusion: This study evaluated the cellular heterogeneity of normal human VFs by utilizing single‐nuclei RNA‐sequencing. With further confirmation through additional spatial sequencing and microscopic imaging, a novel cellular map of the VFs may provide insight into new cellular targets for VF disease. Level of Evidence: NA Laryngoscope, 134:3193–3200, 2024 [ABSTRACT FROM AUTHOR]

Objectives: Percutaneous Vocal Fold Lateralization (PVFL) consists of external fixation with non-absorbable percutaneous suture of the vocal fold in a lateral position, under direct glottic visualization. The objective of this study is to determine the effectiveness of PVFL in a university pediatric hospital, as well as to describe the potential risks and complications of the surgery. Methods: Retrospective cohort study, with data collected from electronic medical records. The study was approved by the Research Ethics Committee of the institution. Surgeries were performed with the modified Lichentenberg technique and data, and outcomes were analyzed. Results: Six patients with Bilateral Vocal Fold Paralysis who underwent Percutaneous Vocal Fold Lateralization were evaluated. Three patients were male. The age at diagnosis ranged from 2 to 132 days (mean 10.5 days). The reason for investigating the upper airway was the presence of increased work of breathing and stridor. Five patients had a favorable clinical evolution, with spontaneous ventilation in room air and absence of stridor or ventilatory effort, without the need for tracheostomy. Surgical results in this series corroborate the findings of other similar cohorts, which showed Percutaneous Vocal Fold Lateralization as a safe and effective procedure in avoiding tracheostomy or allowing decannulation in children with Bilateral Vocal Fold Paralysis. Conclusions: PVFL seems to be a safe and effective procedure, but it has morbidity, due to immediate, and probably late, non-serious complications. Studies with a larger number of patients, with longer follow-up and using a controlled and randomized clinical design are needed to establish the role of PVFL in the treatment of BVFP in newborns and infants. Levels of evidence: Level 4 (step 4).

ObjectivesVocal fold (VF) scarring, manifested by increased collagen, decreased glycosaminoglycans (GAGs), and disrupted elastic fibers, remains a negative consequence of VF injury or resection. The objective of this study is to compare four reconstructive options after Vf mucosal resection in rabbits. A Cell-Based Outer Vocal fold Replacement (COVR) using human adipose-derived mesenchymal stromal cells (hASCs) in fibrin scaffold is directly compared with a decellularized scaffold implant, hASC injection, and resection alone without reconstruction. The primary hypothesis is that the cells-in-scaffold construct better reconstitutes the VF structure than either cells or scaffold alone, or than healing by secondary intention.MethodsA total of49 rabbits received bilateral VF cordectomy, followed by either COVR implant, decellularized scaffold implant, hASC injection, or no reconstruction (injured control group). Larynges were harvested after 6 weeks.ResultsHistology demonstrated greater lamina propria thickness, less collagen deposition, and more GAGs in COVR animals versus all other treatment groups. Evidence of persistent human cells was found in about half of the cell-treated animals. RNA levels of fibrosis pathway and macrophage phenotype markers were statistically unchanged among treatment groups at 6 weeks.ConclusionThese data support the efficacy of COVR implantation in restoring VF microstructure in rabbits. The intact COVR was required; isolated components of decellularized scaffold or injected hASC still produced histologic scarring. We propose that the unique bilayered cell structure within fibrin enables controlled matrix remodeling to minimize wound contraction and fibrosis, and to promote GAG deposition.Level of evidenceBasic science study.

The larynx in cats presents many differences between the larynxes of other species of domestic animals. The objective of this work was to determine the structure, origin and insertion of the thyroarytenoid muscle and its relationship with the vestibular and vocal folds in the cat. Eight larynx from domestic cats were used. The larynxes were sectioned in the sagittal plane and then the mucosa was removed. Finally, the thyroarytenoid muscle was dissected from the side to expose its insertion. It was observed that the mucosa corresponding to the vocal fold covered the caudal part of the thyroarytenoid muscle. The muscle continued rostrally and was covered with mucosa. The laryngeal mucosa corresponding to the vestibular fold covered the most rostral part of the muscle. The thyroarytenoid muscle consisted of a single continuous mass, flattened lateromedially and he had a triangular shape. His belly did not present an homogeneous thickness. The thyroarytenoid muscle and the vestibular and vocal folds in the cat are structures closely related. The thyroarytenoid muscle is lateromedially flattened, triangular, and originating at the base of the epiglottic cartilage and the dorsal surface of the body of the thyroid cartilage, laterally to the midline. It inserts on the lateral surface of the arytenoid cartilage, in the vocal process, arched crest and muscular process. It has a base, two edges, a vertex, and two surfaces. It has three portions: rostral, middle, and caudal. The vestibular fold is an structure supported by the rostral border and the rostral portion of the thyroarytenoid muscle. The laryngeal cavity fossa is formed superficially by the laryngeal mucosa that lines the middle portion of the thyroarytenoid muscle. The vocal fold is supported by the caudal portion and the caudal edge of the thyroarytenoid muscle. [ABSTRACT FROM AUTHOR]

To evaluate the anatomical and voice results of conservative management of patients diagnosed with contralateral reactive lesions (CRL) in our voice unit. A retrospective chart review was conducted of all new adult patients with benign vocal fold lesions with or without CRL, treated in the voice unit at Universidad Católica Clinical Hospital between 2015 and 2019. Patients were divided into two groups, without CRL (group A) and with CRL (group B). Analysis of preoperative and 1 month after surgery videostroboscopy, GRBASI, Voice Handicap Index-10 (VHI-10), Voice Related Quality of Life (VRQOL) surveys and management of CRL was conducted. A total of 62 patients were included, 45 (72.6%) had CRL. When compared, bivariate and multivariate analysis revealed that age was significantly associated as a mild protective factor of presenting a CRL (P < 0.05). No significative differences were found between preoperative group A and B perceptual voice analysis or voice surveys. In terms of CRL management, 30 (66.6%) were injected, conservative management with observation was performed in 12 patients (26.7%) and, three (6.7%) were surgically resected. After 1 month follow-up, 32 (71.1%) had complete CRL resolution, eight (17.8%) had CRL persistence and, five (11.1%) had CRL recurrence. Postoperative vocal outcomes, GRBASI, VHI-10 and VRQOL showed significative improvement as compared with preoperative data for each group. No differences were seen between group A and B in terms of postoperative vocal outcomes. CRL are prevalent, and their management is controversial. On our study 72.6% of BFVL presented with CRL and 93.3% of them were conservatively managed. Improvement in perceptual voice analysis and quality of life surveys were similar in both groups. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effects of androgen therapy on the thyroarytenoid (TA) muscle, expression of androgen receptors (ARs) and hyaluronic acid (HA) concentration in the vocal folds (VFs) of adult female rats. Methods: Twenty‐one adult female Wistar rats were divided into experimental and control groups. The experimental group received weekly intramuscular injections of nandrolone decanoate for 9 weeks. Following euthanasia and dissection of the VFs, histomorphometric analysis of the TA muscle, immunohistochemical evaluation of ARs, and measurement of HA concentration using the ELISA‐like fluorimetric method were performed. Results: The experimental group exhibited a significantly larger mean fiber cross‐sectional area in the TA muscle compared to the control group (434.3 ± 68.6 μm2 versus 305.7 ± 110.1 μm2; p = 0.029), indicating muscle hypertrophy. There was no significant difference in the number of muscle fibers. The experimental group showed higher expression of ARs in the lamina propria (62.0% ± 30.3% versus 22.0% ± 22.8%; p = 0.046) and in the TA muscle (45.0% ± 22.6% versus 18.3% ± 9.8%; p = 0.024). There was no significant difference in the concentration of HA. Conclusion: Exposure of adult female rats to androgen therapy resulted in hypertrophy of the TA muscle and increased expression of ARs in the VFs. The TA muscle seems to be the primary target of testosterone action in the VF, and the up‐regulation of ARs might contribute to the persistent deepening of the voice. Level of Evidence: NA Laryngoscope, 134:2316–2321, 2024 [ABSTRACT FROM AUTHOR]

BACKGROUND: Dysphonia is a common symptom among ENT consultation, it can be caused by vocal fold paralysis. Ortner's or cardiovocal syndrome is a rare condition, accounting for less than 11% of all causes of recurrent laryngeal nerve paralysis. Aortic aneurysms are the most common cause of Ortner's syndrome, these can be fungal, atherosclerotic, traumatic and with or without aortic dissection. CLINICAL CASE: An 88-year-old male patient who reported dyspnea of small efforts of two weeks of evolution, vocal fatigue, pharyngeal globus and bloody expectorations. Diagnostic approach found an aortic aneurysm of 47.7 x 48.5 mm, mural thrombus in the brachiocephalic trunk, as well as paralysis of the left vocal fold. CONCLUSIONS: Aortic aneurysm is the most common cause of Ortner's syndrome. Even though Ortner's syndrome is rare, it is extremely important to consider it in the approach of a patient with unilateral paralysis of the vocal cords. [ABSTRACT FROM AUTHOR]

Objective: Paradoxical vocal fold motion (PVFM) is characterized by inappropriate adduction of vocal folds during inspiration causing dyspnea. While anxiety is suspected to be a predisposing factor, incidence has been understudied. Study Designs: Retrospective review. Setting: Multidisciplinary PVFM hospital clinic. Methods: We used patient‐reported outcome measures to examine anxiety and depression in consecutive patients aged 10 to 17 years using Pediatric SFv1.1 Anxiety 8b and Level 2‐Depression inventories (parents completed proxy forms). T‐scores were classified as normal (none to slight <55) or elevated (mild 55‐59.9, moderate 60‐69.9, severe >70). Results: Twenty‐three pediatric patients and 20 parents completed surveys. Mean age was 13.74 years. For anxiety, 69.6% of patients and 40% of parents identified elevated levels. For depression, 30.4% of patients and 15% of parents identified elevated levels. Therapy need for the sample was 65.2% (34.8% active in services and 30.4% referred). Child anxiety scores were significantly higher in the therapy need group, U = 17, P =.004. Conclusion: This study of adolescents with PVFM confirmed elevated anxiety and depression scores in 2/3 of the participants. Anxiety likely precedes diagnosis and is a predisposing factor. Referral for individualized intervention targeting anxiety and depression is indicated. [ABSTRACT FROM AUTHOR]

The vocal fold vibrates in high frequency to create voice sound. The vocal fold has a sophisticated histological "layered structure" that enables such vibration. As the vibration causes fricative damage to the mucosa, excessive voicing can cause inflammation or injury to the mucosa. Chronic inflammation or repeated injury to the vocal fold occasionally induces scar formation in the mucosa, which can result in severe dysphonia, which is difficult to treat. Oxidative stress has been proven to be an important factor in aggravating the injury, which can lead to scarring. It is important to avoid excessive oxidative stress during the wound healing period. Excessive accumulation of reactive oxygen species (ROS) has been found in the injured vocal folds of rats during the early phase of wound healing. Antioxidants proved to be useful in preventing the accumulation of ROS during the period with less scar formation in the long-term results. Oxidative stress is also revealed to contribute to aging of the vocal fold, in which the mucosa becomes thin and stiff with a reduction in vibratory capacity. The aged voice can be characterized as weak and breathy. It has been confirmed that ROS gradually increases in rat vocal fold mucosa with age, which may cause further damage to the vocal fold. Antioxidants have also proved effective in avoiding aging of the vocal fold in rat models. Recently, human trials have shown significant effects of the antioxidant Twendee X for maintaining the voice of professional opera singers. In conclusion, it is suggested that oxidative stress has a great impact on the damage or deterioration of the vocal folds, and the use of antioxidants is effective for preventing damage of the vocal fold and maintaining the voice. [ABSTRACT FROM AUTHOR]

Vocal fold paralysis (VFP) can happen in various conditions due to mediastinal LADs, however no study has proposed anthracosis as an etiology. Here we discussed the chest CT features of anthracosis related LADs causing VFP. Among 41 cases of pulmonary anthracosis, 10 had VFP that all were presented with hoarseness. The paralysis was unilateral (left side) in all cases. Extra-nodal infiltration and conglomeration of lymph nodes were significantly higher in patients with paralysis. Left paratracheal, pre-vascular, and aortopulmonary window lymph nodes were seen in all patients. We propose that mediastinal LADs secondary to anthracosis could be a reason for left side VFP. [ABSTRACT FROM AUTHOR]

Introduction: Electromyography (EMG) of the larynx provides information on the electrophysiological condition of laryngeal muscles and innervation. Integration of information obtained from the EMG exams with the clinical parameters as obtained by other methods for laryngeal assessment (endoscopy, perceptual and acoustic analysis, voice self-assessment) provides a multidimensional picture of dysphonia, which is of particular importance in patients with vocal fold (VF) mobility disorders accompanied by glottic insufficiency. Aim: The aim of this study was to evaluate laryngeal EMG records acquired in subjects with unilateral vocal fold immobilization with signs of atrophy and glottic insufficiency. Material and methods: From the available material of 74 EMG records of patients referred for the exam due to unilateral laryngeal paralysis, records of 17 patients with endoscopic features suggestive of complete laryngeal muscle denervation were selected. The EMG study of thyroarytenoid muscles of mobile and immobile VFs was evaluated qualitatively and quantitatively at rest and during volitional activity involving free phonation of vowel /e/ [ε]. Results: In all patients, the EMG records from mobile VFs were significantly different from those from immobile VFs. Despite endoscopic features of paralysis, no VF activity whatsoever was observed in as few as 2 patients so as to meet the neurophysiological definition of paralysis. In 88% of cases, electromyographic activity of the thyroarytenoid muscle was observed despite immobilization and atrophy of the vocal fold. In these patients, neurogenic type of record was observed with numerous high--amplitude mobility units. On the basis of the results, quantitative features of EMG records indicative of paralysis and residual activity of the thyroarytenoid muscle were determined. Conclusions: Qualitative and quantitative analysis of laryngeal EMG records provides detailed information on the condition of vocal fold muscles and innervation. EMG records of mobile vs immobile VFs differ significantly from each other. Endoscopic evaluation does not provide sufficient basis for the diagnosis of complete laryngeal muscle denervation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to classify the degree of edema in patients with Reinke’s edema (RE) and examine its impact on their voice parameters using both objective and subjective assessment methods. Methods: Objective and subjective voice data of 104 patients diagnosed with RE between 2018 and 2021 were evaluated retrospectively. RE is classified into 4 groups (types 1, 2, 3, and 4). The evaluation included videolaryngostroboscopic examination, acoustic voice analysis, and aerodynamic measurements, GRBAS, Voice Handicap Index-10 (VHI-10), Voice-Related Quality of Life Scale (V-RQOL), and Reflux Septum Index (RSI). Results: Patients with type 1 RE had a significantly lower mean age than those with types 3–4. Although there were no significant differences in acoustic and aerodynamic parameters between the groups, it was observed that F0 and the maximum phonation time decreased as the degree of edema increased. The GRBASTotal, G, and R scores of types 1 and 2 were significantly lower than those of types 3 and 4, as were the scores of type 1 S. There were no statistically significant differences between the RE groups in terms of VHI-10, V-RQOL, and RSI scores. Conclusion: It has been observed that as the severity of RE increases, voice perception and quality (especially types 3 and 4) are negatively affected. Determining the degree of edema will guide the clinician in both the planning of the intervention phase and the follow-up phase.

Purpose: This study prospectively assessed the efficacy and safety of 532-nm diode laser glottoplasty in patients with sulcus vocalis. Methods: A prospective human trial was performed from August 2016 to September 2021. 532-nm diode laser glottoplasty was performed in 30 consecutive patients with sulcus vocalis who suffered from voice problems. Patients underwent acoustic aerodynamic, perceptual, stroboscopic, and Voice Handicap Index-10 (VHI-10) evaluations before and 1, 6, and 12 months after laser glottoplasty. Results: Most subjective parameters showed significant improvement (P < 0.05) at 6 months after laser glottoplasty and remained stable at 12 months. Most objective parameters showed significant improvement (P < 0.05) at 12 months after laser glottoplasty. Complications during follow-up included mild vocal fold vibration reduction in 3.3% of patients (1/30) and persistent vocal fold edema in 3.3% of patients (1/30). Conclusions: Statistically significant voice improvement at 12 months after 532-nm diode laser glottoplasty was achieved without serious complications. [ABSTRACT FROM AUTHOR]

High-speed videolaryngoscopy and quantitative analysis of laryngeal images are relevant in accurately diagnosing vocal fold closure patterns. To analyze the parameters of digital videokymography obtained through high-speed videolaryngoscopy in women and men with complete and incomplete glottal closure, and posterior glottal chink. We conducted an observational, analytical, cross-sectional study with data from 65 adults, which we divided into groups according to sex and glottal closure. Digital videokymography parameters were analyzed using an image-processing program. The Anderson–Darling and Mann–Whitney U tests were used to verify sample normality and compare videokymography parameters between groups, respectively. The significance level was set at 5%. Among 65 laryngeal images, 20 each were from women with complete and incomplete glottal closure, and 20 and 5 were from men with complete and incomplete glottal closure, respectively. Considering the clinical relevance of the evaluated data, groups of 11 women and 4 men with posterior glottal chink were compared with sex-similar groups with complete glottal closure. Digital videokymography showed a lower maximum and mean vocal fold opening in women with incomplete glottal closure, and a lower dominant left vocal fold-opening amplitude and higher dominant frequency of bilateral vocal fold opening in men with incomplete glottal closure. It also showed a lower closed phase percentage in the posterior region for women and men, with higher closed phase percentage in the anterior and middle regions in women. Both groups with posterior glottal chink showed similar results. Incomplete glottal closure may interfere with the results of the digital videokymography parameters, with higher impact on the posterior vocal fold region in males and the middle and anterior vocal fold regions in females. [ABSTRACT FROM AUTHOR]

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Objective: This study aimed to classify the degree of edema in patients with Reinke's edema (RE) and examine its impact on their voice parameters using both objective and subjective assessment methods. Methods: Objective and subjective voice data of 104 patients diagnosed with RE between 2018 and 2021 were evaluated retrospectively. RE is classified into 4 groups (types 1, 2, 3, and 4). The evaluation included videolaryngostroboscopic examination, acoustic voice analysis, and aerodynamic measurements, GRBAS, Voice Handicap Index-10 (VHI-10), Voice-Related Quality of Life Scale (V-RQOL), and Reflux Septum Index (RSI). Results: Patients with type 1 RE had a significantly lower mean age than those with types 3-- Although there were no significant differences in acoustic and aerodynamic parameters between the groups, it was observed that F0 and the maximum phonation time decreased as the degree of edema increased. The GRBASTotal, G, and R scores of types 1 and 2 were significantly lower than those of types 3 and 4, as were the scores of type 1 S. There were no statistically significant differences between the RE groups in terms of VHI-10, V-RQOL, and RSI scores. Conclusion: It has been observed that as the severity of RE increases, voice perception and quality (especially types 3 and 4) are negatively affected. Determining the degree of edema will guide the clinician in both the planning of the intervention phase and the follow-up phase. [ABSTRACT FROM AUTHOR]

Objectives and hypothesis: Vocal dysfunction, including hypophonia, in Parkinson disease (PD) manifests in the prodromal period and significantly impacts an individual's quality of life. Data from human studies suggest that pathology leading to vocal deficits may be structurally related to the larynx and its function. The Pink1−/− rat is a translational model used to study pathogenesis in the context of early‐stage mitochondrial dysfunction. The primary objective of this work was to identify differentially expressed genes in the thyroarytenoid muscle and examine the dysregulated biological pathways in the female rat. Methods: RNA sequencing was used to determine thyroarytenoid (TA) muscle gene expression in adult female Pink1−/− rats compared with controls. A bioinformatic approach and the ENRICHR gene analysis tool were used to compare the sequencing dataset with biological pathways and processes, disease relationships, and drug‐repurposing compounds. Weighted Gene Co‐expression Network Analysis was used to construct biological network modules. The data were compared with a previously published dataset in male rats. Results: Significant upregulated pathways in female Pink1−/− rats included fatty acid oxidation and muscle contraction, synaptic transmission, and neuromuscular processes. Downregulated pathways included anterograde transsynaptic signaling, chemical synaptic transmission, and ion release. Several drug treatment options including cetuximab, fluoxetine, and resveratrol are hypothesized to reverse observed genetic dysregulation. Conclusions: Data presented here are useful for identifying biological pathways that may underlie the mechanisms of peripheral dysfunction including neuromuscular synaptic transmission to the TA muscle. These experimental biomarkers have the potential to be targeted as sites for improving the treatment for hypophonia in early‐stage PD. Level of Evidence: NA Laryngoscope, 133:3412–3421, 2023 [ABSTRACT FROM AUTHOR]

Objectives: The 2 µm-wavelength thulium laser is an effective cutter during partial arytenoidectomy, but thermal trauma can damage adjacent laryngeal tissue. Pulsing laser energy may reduce trauma when compared to continuous-wave cutting. This study measured temperature changes, thermal trauma, and time to complete partial arytenoidectomy, with and without pulsing, in an ex-vivo calf model. Methods: Tissue temperature and time to complete a trans-cartilaginous cut were measured during partial arytenoidectomy on ex-vivo calf vocal folds (N = 24) using a thulium laser in continuous-wave (CW, N = 12) and pulsed-wave (PW, N = 12) modes. Energy was 5 W for CW and PW cuts; pulse-widths were 250, 500, and 750 ms. Thermal damage was analyzed histologically by measuring the depth of lactate dehydrogenase (LDH) inactivation perpendicular to the laser-cut edge at the vocal process. Paired t-tests compared CW and PW modes. Results: Change in temperature was lower using CW (6.5°C) compared to PW modes (250 ms = 18°; 500 ms = 16°; 750 = 19°; P <.05). Trans-cartilaginous cuts were completed faster using CW (37 seconds) compared to PW (250 ms = 136 seconds; 500 ms = 61 seconds; 750 = 44 seconds; P <.05), and both modes delivered the same total Joules. The average depth of LDH depletion (thermal damage) was similar for all cuts. Conclusions: 1. Thulium laser cuts in continuous-mode unexpectedly produced less tissue heating yet created similar thermal damage than pulsed-mode cuts during simulated partial arytenoidectomy. 2. Trans-cartilaginous cuts were completed significantly faster in continuous-mode as compared to pulsed-mode cutting. 3. Pulsing the thulium laser does not minimize thermal damage compared to continuous wave cutting during thulium laser-assisted partial arytenoidectomy. [ABSTRACT FROM AUTHOR]

Objective: The diversity of glucocorticoid (GC) properties may underlie variability of clinical efficacy for vocal fold (VF) disease. Optimized therapeutic approaches must account for tissue complexity as well as interactions between cell types. We previously reported that reduced GC concentrations inhibited inflammation without eliciting fibrosis in mono‐cultured VF fibroblasts and macrophages. These data suggested that a refined approach to GC concentration may improve outcomes. In the current study, co‐culture of VF fibroblasts and macrophages was employed to investigate the effects of different concentrations of methylprednisolone on fibrotic and inflammatory response genes in VF fibroblasts to optimize management paradigms. Study Design: In vitro. Methods: THP‐1 monocyte‐derived macrophages were stimulated with interferon‐γ (IFN‐γ), lipopolysaccharide (LPS), or transforming growth factor‐β (TGF‐β) to induce inflammatory (M(IFN/LPS)) and fibrotic (M(TGF)) phenotypes. Macrophages were then co‐cultured with a human VF fibroblast cell line using a 0.4 μm pore membrane with or without 0.1–3000 nM methylprednisolone. Inflammatory (CXCL10, TNF, and PTGS2) and fibrotic (ACTA2, CCN2, and COL1A1) gene expression was quantified in fibroblasts. Results: Incubating VF fibroblasts with M(IFN/LPS) macrophages increased expression of TNF and PTGS2, and this effect was inhibited by methylprednisolone. Incubation of VF fibroblasts with M(TGF) macrophages increased expression of ACTA2, CCN2, and COL1A1, and this effect was enhanced by methylprednisolone. The concentration of methylprednisolone required to downregulate inflammatory genes (TNF and PTGS2) was lower than that to upregulate fibrotic genes (ACTA2, CCN2, and COL1A1). Conclusion: Reduced concentration of methylprednisolone effectively suppressed inflammatory genes without enhancing fibrotic genes, suggesting that a refined approach to GC concentration may improve clinical outcomes. Level of Evidence: N/A Laryngoscope, 133:3116–3122, 2023 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Myofiber culture has been employed to investigate muscle physiology in vitro and is well‐established in the rodent hind limb. Thyroarytenoid (TA) myofiber culture has not been described, providing an opportunity to employ this method to investigate distinct TA myofiber functions. The purpose of this study was to assess the feasibility of a TA myofiber culture model. Study Design: In vitro. Methods: TA muscles from five Sprague Dawley rats were independently isolated and digested for 90 min. A smooth‐tip, wide‐bored pipette dissociated TA myofibers from cartilage, and the fibers were distributed on collagen‐coated dishes and incubated at 37°C, 5% CO2 for 2 h. Myofiber specificity was determined via immunolabeling for desmin and myosin heavy chain (MHC). Myofibers viability was assessed over 7 days via esterase assay. Additional myofibers were immunolabeled for satellite cell marker Pax‐7. Glucocorticoid (GC) receptor (GR) was immunolabeled following GC treatment. Results: The harvest technique yielded ~120 myofibers per larynx. By day 7, ~60% of the fibers remained attached and were calcein AM‐positive/ethidium homodimer‐negative, indicating viability. Myofibers were positive for desmin and MHC, indicating muscle specificity. Cells surrounding myofibers were positive for Pax‐7, indicating the presence of myogenic satellite cells. Myofibers also responded to GC treatment as determined by GR nuclear translocation. Conclusion: TA myofibers remained viable in culture for at least 7 days with a predictable response to exogenous stimuli. This technique provides novel investigative opportunities regarding TA structure and function. Level of Evidence: N/A Laryngoscope, 133:3109–3115, 2023 [ABSTRACT FROM AUTHOR]

This study used a two-dimensional flow-structure-interaction computer model to investigate the effects of flow-separation-vortex-induced negative pressure on vocal fold vibration and flow dynamics during vocal fold vibration. The study found that negative pressure induced by flow separation vortices enhances vocal fold vibration by increasing aeroelastic energy transfer during vibration. The result showed that the intraglottal pressure was predominantly negative after flow separation before gradually recovering to zero at the glottis exit. When the negative pressure was removed, the vibration amplitude and flow rate were reduced by up to 20%, and the closing speed, flow skewness quotient, and maximum flow declination rate were reduced by up to 40%. The study provides insights into the complex interactions between flow dynamics, vocal fold vibration, and energy transfer during voice production. [ABSTRACT FROM AUTHOR]

Objective: Variable outcomes of glucocorticoid (GC) therapy for laryngeal disease are putatively due to diverse interactions of the GC receptor (GR) with cell signaling pathways, limited consideration regarding concentration‐dependent effects, and inconsistent selection of GCs. In the current study, we evaluated the concentration‐dependent effects of three frequently administered GCs on transcription factors with an emphasis on the phosphorylation of GR at Ser203 and Ser211 regulating the nuclear translocation of GR. This study provides foundational data regarding the diverse functions of GCs to optimize therapeutic approaches. Study design: In vitro. Methods: Human vocal fold fibroblasts and THP1‐derived macrophages were treated with different concentrations of dexamethasone, methylprednisolone, and triamcinolone in combination with IFN‐γ, TNF‐α, or IL4. Phosphorylated STAT1, NF‐κB family molecules, and phosphorylated STAT6 were analyzed by Western blotting. Ser211‐phosphorylated GR (S211‐pGR) levels relative to GAPDH and Ser203‐phosphorylated GR (S203‐pGR) were also analyzed. Results: GCs differentially altered phosphorylated STAT1 and NF‐κB family molecules in different cell types under IFN‐γ and TNF‐α stimuli. GCs did not alter phosphorylated STAT6 in IL4‐treated macrophages. The three GCs were nearly equivalent. A lower concentration of dexamethasone increased S211‐pGR/GAPDH ratios relative to increased S211‐pGR/S203‐pGR ratios regardless of cell type and treatment. Conclusion: The three GCs employed in two cell lines had nearly equivalent effects on transcription factor regulation. Relatively high levels of Ser203‐phosphorylation at low GC concentrations may be related to concentration‐dependent differential effects of GCs in the two cell lines. Level of Evidence: NA Laryngoscope, 133:2704–2711, 2023 [ABSTRACT FROM AUTHOR]

Objectives: Effective treatments for vocal fold fibrosis remain elusive. Tamoxifen (TAM) is a selective estrogen receptor modulator and was recently reported to have antifibrotic actions. We hypothesized that TAM inhibits vocal fold fibrosis via altered transforming growth factor beta 1 (TGF‐β1) signaling. Both in vitro and in vivo approaches were employed to address this hypothesis. Methods: In vitro, vocal fold fibroblasts were treated with TAM (10−8 or 10−9 M) ± TGF‐β1 (10 ng/ml) to quantify cell proliferation. The effects of TAM on genes related to fibrosis were quantified via quantitative real‐time polymerase chain reaction. In vivo, rat vocal folds were unilaterally injured, and TAM was administered by oral gavage from pre‐injury day 5 to post‐injury day 7. The rats were randomized into two groups: 0 mg/kg/day (sham) and 50 mg/kg/day (TAM). Histological changes were examined on day 56 to assess tissue architecture. Results: TAM (10−8 M) did not affect Smad3, Smad7, Acta2, or genes related to extracellular matrix metabolism. TAM (10−8 or 10−9 M) + TGF‐β1, however, significantly increased Smad7 and Has3 expression and decreased Col1a1 and Acta2 expression compared to TGF‐β1 alone. In vivo, TAM significantly increased lamina propria area, hyaluronic acid concentration, and reduced collagen deposition compared to sham treatment. Conclusions: TAM has antifibrotic potential via the regulation of TGF‐β1/Smad signaling in vocal fold injury. These findings provide foundational data to develop innovative therapeutic options for vocal fold fibrosis. Level of Evidence: NA Laryngoscope, 133:2248–2254, 2023 [ABSTRACT FROM AUTHOR]

Objectives/hypothesisTo assess the safety and efficacy of autologous cultured fibroblasts (ACFs) to treat dysphonia related to vocal fold scar and age-related vocal atrophy (ARVA).Study designRandomized, double-blinded, placebo-controlled, multi-institutional, phase II trial.MethodsACFs were expanded from punch biopsies of the postauricular skin in each subject; randomization was 2:1 (treatment vs. placebo). Three injections of 1-2 × 107 cells or placebo saline was performed at 4-week intervals for each vocal fold. Follow-up was performed at 4, 8, and 12 months. The primary outcome was improved mucosal waves. Secondary outcomes included Voice Handicap Index (VHI)-30, patient reported voice quality outcomes, and perceptual analysis of voice.ResultsFifteen subjects received ACF and six received saline injections. At 4, 8, and 12 months after ACF treatments, a significant improvement in mucosal wave grade relative to baseline was observed in both vocal scar and ARVA groups. Relative to control group, mucosal waves were significantly improved in the ARVA group at 4 and 8 months. Perceptual analysis significantly improved in the vocal scar group 12 months after ACF treatments compared to controls. Vocal scar group reported significantly improved vocal quality from baseline. VHI and expert rater voice grade improved in both groups, but did not achieve significance. No adverse events related to fibroblast injections were observed.ConclusionsIn this cohort, injection of ACFs into the vocal fold lamina propria (LP) was safe and significantly improved mucosal waves in patients with vocal scar and ARVA. ACF may hold promise to reconstruct the LP.Level of evidence1 Laryngoscope, 130:2650-2658, 2020.

Objectives: In order to examine each variety of khuumii used by Mongolians, this study compares the anatomical structures involved in the development of khuumii as well as the characteristics and patterns of their functioning. Methods: 50 people between the ages of 18 and 60 were chosen for the cross-sectional study, using a non-random sampling procedure. Statistical analysis was performed using SPSS23 software using questionnaires, X-ray, endoscopy, and acoustic analysis. Results: During the formation of khuumii sound, thoracic cavity, diaphragm, and lungs regulate the intensity of the air reaching the vocal folds, exert pressure on the airways and vibrate the sound waves through air flows passing through the larynx and vocal folds. The mouth-nose cavity as well as the pharynx are responsible for resonating the sound. Khuumii increases the workload of the cardiovascular system by 70-80%. Furthermore, the sound frequency is 2-4 times higher than that of normal speech, and sound volume is 0.5-1 times higher. 95.3% of throat singers do not have a sore throat, 88.4% do not experience heavy breathing, and 74.1% have no hoarseness. Conclusion: The Mongolian throat singing khuumii, including mixed voices and multivoice, iss related to the presence of dual vibration sound sources. Its high overtone form of singing (isgeree khuumii) is related to stenosis at the resonance chambers initiation site (ventricular folds level).

Abstract Objective The primary aim of this study was to identify expression of TRPV3 and TRPV4 chemoreceptors across perinatal and adult stages using a murine model with direct comparisons to human laryngeal mucosa. Our secondary aim was to establish novel cell expression patterns of mechanoreceptors PIEZO1 and PIEZO2 in human tissue samples. Study design In vivo. Methods We harvested murine laryngeal tissue to localize and describe TRPV3/4 endogenous protein expression patterns via immunofluorescence analyses across two developmental (E16.5, P0) and adult (6 weeks) timepoints. Additionally, we obtained a 60‐year‐old female larynx including the proximal trachea and esophagus to investigate TRPV3/4 and PIEZO1/2 protein expression patterns via immunofluorescence analyses for comparison to murine adult tissue. Results Murine TRPV3/4 expression was noted at E16.5 with epithelial cell colocalization to supraglottic regions of the arytenoids, aryepiglottic folds and epiglottis through to birth (P0), extending to the adult timepoint. Human TRPV3/4 protein expression was most evident to epithelium of the arytenoid region, with additional expression of TRPV3 and TRPV4 to proximal esophageal and tracheal epithelium, respectively. Human PIEZO1 expression was selective to differentiated, stratified squamous epithelia of the true vocal fold and esophagus, while PIEZO2 expression exhibited selectivity for intermediate and respiratory epithelia of the false vocal fold, ventricles, subglottis, arytenoid, and trachea. Conclusion Results exhibited expression of TRPV3/4 chemoreceptors in utero, suggesting their importance during fetal/neonatal stages. TRPV3/4 and PIEZO1/2 were noted to adult murine and human laryngeal epithelium. Data indicates conservation of chemosensory receptors across species given similar regional expression in both the murine and human larynx.

There is growing evidence that the maculae flavae of the human vocal fold are a stem cell niche, which is a microenvironment nurturing tissue stem cells. This study investigated the microenvironment, especially vascularity, in the maculae flavae of the human vocal fold. Three normal human adult, three normal newborn vocal folds obtained from autopsy cases and three surgical specimens of glottic carcinoma were investigated using light and electron microscopy. For scanning electron microscopy, a chemical digestion method (modified sodium hydroxide maceration method) was used to observe the inner 3-dimensional structure of the macula flava. Capillaries ran around the anterior and posterior maculae flavae in adults and newborns. However, there was no vascularity in the maculae flavae of the vocal fold. The inner 3-dimensional electron microscopic structure of the macula flava showed there were no blood vessels in the maculae flavae of the vocal fold. Glottic carcinoma (squamous cell carcinoma) surrounded and was in contact with the macula flava, however, the carcinoma did not invade the macula flava indicating there was no vascular supply into the macula flava from the surrounding tissue. There was no vascularity in the anterior and posterior maculae flavae in the human adult and newborn vocal folds. The present study is consistent with the hypothesis that the hypoxic microenvironment in the maculae flavae of the adult and newborn vocal fold as a stem cell niche is likely favorable to maintaining the stemness and undifferentiated states of the tissue stem cells in the stem cell system. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this investigation is to examine the prevalence of allergy in patients with primary dysphonia. Methods: The medical records of patients diagnosed with primary dysphonia and who underwent allergy testing during the period extending from June 2018–2020 were reviewed. Patients' demographics, laryngoscopic findings and allergy skin prick testing were analyzed. Results: A total of 22 patients were included. Eleven out of twenty-two patients (50%) tested positive to at least 2 allergens, and eight (36%) tested positive for at least 3 allergens. The most common allergens tested positive were D. Farinae for household inhalants, followed by Chenopodium, Russian thistle and weed mix for weeds. In patients with a positive allergy testing, the most common laryngeal findings included edema in 36%, followed by excess mucus and MTD in 18% of cases each. Conclusion: Allergy is common in patients presenting with primary dysphonia and non-specific laryngeal findings. Allergy testing should be part of the diagnostic work-up of affected patients. [ABSTRACT FROM AUTHOR]

Abstract Objectives Vocal fold (VF) scarring, manifested by increased collagen, decreased glycosaminoglycans (GAGs), and disrupted elastic fibers, remains a negative consequence of VF injury or resection. The objective of this study is to compare four reconstructive options after Vf mucosal resection in rabbits. A Cell‐Based Outer Vocal fold Replacement (COVR) using human adipose‐derived mesenchymal stromal cells (hASCs) in fibrin scaffold is directly compared with a decellularized scaffold implant, hASC injection, and resection alone without reconstruction. The primary hypothesis is that the cells‐in‐scaffold construct better reconstitutes the VF structure than either cells or scaffold alone, or than healing by secondary intention. Methods A total of49 rabbits received bilateral VF cordectomy, followed by either COVR implant, decellularized scaffold implant, hASC injection, or no reconstruction (injured control group). Larynges were harvested after 6 weeks. Results Histology demonstrated greater lamina propria thickness, less collagen deposition, and more GAGs in COVR animals versus all other treatment groups. Evidence of persistent human cells was found in about half of the cell‐treated animals. RNA levels of fibrosis pathway and macrophage phenotype markers were statistically unchanged among treatment groups at 6 weeks. Conclusion These data support the efficacy of COVR implantation in restoring VF microstructure in rabbits. The intact COVR was required; isolated components of decellularized scaffold or injected hASC still produced histologic scarring. We propose that the unique bilayered cell structure within fibrin enables controlled matrix remodeling to minimize wound contraction and fibrosis, and to promote GAG deposition. Level of Evidence Basic science study

The larynx is an organ of the upper airway that participates in breathing, glutition, voice production, and airway protection. These complex functions depend on vocal fold (VF) movement, facilitated in turn by the action of the intrinsic laryngeal muscles (ILM). The necessary precise and near-instantaneous modulation of each ILM contraction relies on proprioceptive innervation of the larynx. Dysfunctional laryngeal proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia, vocal fold paresis, and paralysis. While the proprioceptive system in skeletal muscle derived from somites is well described, the proprioceptive circuitry that governs head and neck structures such as VF has not been so well characterized. For over two centuries, researchers have investigated the question of whether canonical proprioceptive organs, muscle spindles, and Golgi tendon organs, exist in the ILM, with variable findings. The present work is a state-of-the-art review of the peripheral component of laryngeal proprioception, including current knowledge of canonical and possible alternative proprioceptive circuitry elements in the larynx. [ABSTRACT FROM AUTHOR]

The vocal folds (VFs) are constantly exposed to mechanical stimulation leading to changes in biomechanical properties, structure, and composition. The development of long-term strategies for VF treatment depends on the characterization of related cells, biomaterials, or engineered tissues in a controlled mechanical environment. Our aim was to design, develop, and characterize a scalable and high-throughput platform that mimics the mechanical microenvironment of the VFs in vitro. The platform consists of a 24-well plate fitted with a flexible membrane atop a waveguide equipped with piezoelectric speakers which allows for cells to be exposed to various phonatory stimuli. The displacements of the flexible membrane were characterized via Laser Doppler Vibrometry (LDV). Human VF fibroblasts and mesenchymal stem cells were seeded, exposed to various vibratory regimes, and the expression of pro-fibrotic and pro-inflammatory genes was analyzed. Compared to current bioreactor designs, the platform developed in this study can incorporate commercial assay formats ranging from 6- to 96-well plates which represents a significant improvement in scalability. This platform is modular and allows for tunable frequency regimes. [ABSTRACT FROM AUTHOR]

Objective: Glucocorticoids (GCs) modulate multiple cellular activities including inflammatory and fibrotic responses. Outcomes of GC treatment for laryngeal disease vary, affording opportunity to optimize treatment. In the current study, three clinically employed GCs were evaluated to identify optimal in vitro concentrations at which GCs mediate favorable anti‐inflammatory and fibrotic effects in multiple cell types. We hypothesize a therapeutic window will emerge as a foundation for optimized therapeutic strategies for patients with laryngeal disease. Study Design: In vitro. Methods: Human vocal fold fibroblasts and human macrophages derived from THP‐1 monocytes were treated with 0.03–1000 nM dexamethasone, 0.3–10,000 nM methylprednisolone, and 0.3–10,000 nM triamcinolone in combination with interferon‐γ, tumor necrosis factor‐α, or interleukin‐4. Real‐time polymerase chain reaction was performed to analyze inflammatory (CXCL10, CXCl11, PTGS2, TNF, IL1B) and fibrotic (CCN2, LOX, TGM2) genes, and TSC22D3, a target gene of GC signaling. EC50 and IC50 to alter inflammatory and fibrotic gene expression was calculated. Results: Interferon‐γ and tumor necrosis factor‐α increased inflammatory gene expression in both cell types; this response was reduced by GCs. Interleukin‐4 increased LOX and TGM2 expression in macrophages; this response was also reduced by GCs. GCs induced TSC22D3 and CCN2 expression independent of cytokine treatment. EC50 for each GC to upregulate CCN2 was higher than the IC50 to downregulate other genes. Conclusion: Lower concentrations of GCs repressed inflammatory gene expression and only moderately induced genes involved in fibrosis. These data warrant consideration as a foundation for optimized clinical care paradigms to reduce inflammation and mitigate fibrosis. Level of Evidence: NA Laryngoscope, 133:1169–1175, 2023 [ABSTRACT FROM AUTHOR]

Objective: To offer pragmatic, evidence‐informed guidance on the use of systemic corticosteroids (SCS) for common otolaryngologic disorders. Data Sources: PubMed, Cochrane Library, and American Academy of Otolaryngology–Head and Neck Surgery Foundation clinical practice guidelines. Review Methods: A comprehensive search of published literature through November 2021 was conducted on the efficacy of SCS, alone or in combination with other treatments, for managing disorders in otolaryngology and the subdisciplines. Clinical practice guidelines, systematic reviews, and randomized controlled trials, when available, were preferentially retrieved. Interventions and outcomes of SCS use were compiled to generate summary tables and narrative synthesis of findings. Conclusions: Evidence on the effectiveness of SCS varies widely across otolaryngology disorders. High‐level evidence supports SCS use for Bell's palsy, sinonasal polyposis, and lower airway disease. Conversely, evidence is weak or absent for upper respiratory tract infection, eustachian tube dysfunction, benign paroxysmal positional vertigo, adenotonsillar hypertrophy, or nonallergic rhinitis. Evidence is indeterminate for acute laryngitis, acute pharyngitis, acute sinusitis, angioedema, chronic rhinosinusitis without polyps, Ménière's disease, postviral olfactory loss, postoperative nerve paresis/paralysis, facial pain, and sudden sensorineural hearing loss. Implications for Practice: Clinicians should bring an evidence‐informed lens to SCS prescribing to best counsel patients regarding the risks, anticipated benefits, and limited data on long‐term effects. Alternate routes of corticosteroid administration—such as sprays, drops, inhalers, and intralesional injections—may be preferable for many disorders, particularly those that are self‐limited or require a prolonged duration of therapy. Prudent use of SCS reduces the risk of medication‐related adverse effects. Clinicians who are conversant with high‐level evidence can achieve optimal outcomes and stewardship when prescribing SCS. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify vocal fold leukoplakia (VFL) lesions on the inferior surface as a risk factor for recurrence. Methods: This was a retrospective study with data collected from 2001 to 2018. The study comprised 37 patients with VFL, divided into the nonrecurrent and recurrent groups. We examined the clinicopathological characteristics and the surgical procedures performed in each patient. Results: Among the 37 patients, 15 (40.5%) had residual (3) or recurrent (12) VFL. Of those patients with and without recurrence, 8 of 12 (66.7%) and 6 of 22 (27.3%), respectively, had inferior surface lesions of the vocal fold at the initial operation (P =.036). Recurrences were significantly higher in patients with inferior surface lesions. Other evaluated factors did not show significance for recurrence. Conclusion: The presence of VFL lesions on the inferior surface is a significant risk factor for recurrence. [ABSTRACT FROM AUTHOR]

To review the authors experience in un-sedated office-based biopsies of patients with vocal fold leukoplakia and to review the literature. A retrospective review of 29 patients was conducted. A total of 41 office-based procedures were performed (eight patients had bilateral vocal fold lesions and four patients had the procedure performed twice). In 26 out of the 41 biopsies, the pathology revealed benign lesion. In eight cases, the pathology showed dysplasia (four high-grade and four low-grade). Seven biopsies revealed squamous cell carcinoma. Five patients underwent suspension micro-laryngoscopy for definitive diagnosis. Four of whom had a change in their diagnosis. Un-sedated office-based biopsy of vocal fold leukoplakia is an alternative to suspension microlaryngoscopy in case of carcinoma or nonmalignant lesions. [ABSTRACT FROM AUTHOR]

Abstract Objectives The epithelial associated mucus layer of vocal fold (VF) mucosa, plays an essential role in protecting and lubricating the tissue, as well as promoting normal voice quality. Serving as a habitat for laryngeal microbiota involved in the regulation of host immunity, VF mucus contributes to laryngeal health and disease. However, its unstable structure renders its' investigation challenging. We aim to establish a reproducible histological protocol to recover the natural appearance of the VF mucus layer for investigation. Methods Using a murine model, we compared the suitability of multiple fixation methods—methacarn, formalin, and cryopreservation followed by post‐fixation with formalin, paraformaldehyde (PFA), acetone, and two staining methods—Alcian Blue (pH 2.5)/Periodic Acid Schiff (AB/PAS) or PAS. Fixation and staining outcomes were evaluated based on the preservation of tissue morphology and mucus layer integrity. Mucin proteins, Muc1 and Muc4, were stained to validate the presence of mucus layer overlaying the VF mucosa. Results Methacarn fixation followed by PAS staining was capable of preserving and displaying the smooth and continuous mucus layer, ensuring the determination of mucus thickness and mucin staining. Conclusions Our study if the first to establish a histological protocol for the visualization of the in situ VF mucus layer whereby facilitating the study of VF mucus biology including VF surface hydration, ion/nutrients transports, biomechanical properties that maintains normal voice quality as well as VF pathophysiology and host‐microbe interactions in the larynx. Level of Evidence N/A.

Objectives/hypothesisIn 1974, Minoru Hirano proposed his theory of voice production that is now known as the cover-body theory. He described the thyroarytenoid (TA) and cricothyroid (CT) muscles as the major determinants of vocal fold shape and stiffness, and theorized four typical laryngeal configurations resulting from unique TA/CT activations, with implications for the resulting voice quality. In this study, we directly observed the vocal fold medial surface shape under Hirano's unique TA/CT activation conditions to obtain a three-dimensional (3D) understanding of these laryngeal configurations during muscle activation.Study designIn vivo canine hemilarynx model.MethodsFlesh points were marked along the medial surface of the vocal fold. Selective TA and CT activation were performed via respective laryngeal nerves. 3D reconstructions of the vocal fold medial surface were derived using digital image correlation.ResultsLow level TA and CT activation yielded anteroposterior lengthening and vertical thinning of the vocal fold. When TA activation is far greater than CT, the vocal fold shortens and thickens. With slightly greater TA than CT, activation the vocal length is maintained on average, whereas its vertical thickness decreases. With CT far greater than TA activation, the vocal fold lengthens and thins. In all conditions, glottal contour changes remained minimal.ConclusionsAnalysis of the 3D geometry of the vocal fold medial surface under Hirano's four typical laryngeal configurations revealed that the key geometric changes during TA/CT interactions lie within the anteroposterior length and the vertical thickness of the vocal fold.Level of evidenceNA. Laryngoscope, 128:1412-1418, 2018.