Frenotomy Provides Improved Direct Laryngoscopy Exposure in Select Adult Patients With Ankyloglossia.

Objective: To analyze the effects of lingual frenotomy on adults with restrictive ankyloglossia and difficult direct laryngoscopy exposure. Methods: A case series study was conducted. Restriction of tongue protrusion due to ankyloglossia was identified in 2 patients who had a history of suboptimal true vocal fold (TVF) exposure on direct laryngoscopy for phonomicrosurgery. Inadequate exposure of the vocal folds was achieved on direct laryngoscopy attempts with manual tongue protrusion. Mandibular tori were not present in these patients. An intraoperative lingual frenotomy was performed in both patients. Results: After frenotomy and with manual tongue protrusion, direct laryngoscopy exposure was substantially improved allowing for considerably more visualization of the anterior TVFs. Conclusion: Lingual frenulum procedures with manual tongue protrusion should be considered in select adult patients with restrictive ankyloglossia affecting optimal direct laryngoscopy exposure.

Optimizing Botox regimens in patients with adductor spasmodic dysphonia and essential tremor of voice: A 31-year experience.

Objective: The purpose of this study was to quantitatively compare the effectiveness of unilateral and bilateral botulinum toxin A (BTX-A) injections for mitigating undesirable weak/breathy voice quality and dysphagia for patients with adductor spasmodic dysphonia and/or essential tremor of voice (ETV). Methods: Data were collected from the medical records of 319 patients, yielding three treatment cohorts: patients who received an equal dose bilateral injection regimen (BL=) throughout their course of treatment at VUMC, patients who switched to a unilateral injection regimen (UL), and patients who switched to an unequal dose bilateral injection regimen (BL≠). Changes in length of improvement, duration of weak/breathy voice, and dysphagia severity were compared. Results: The BL = treatment group reported the longest duration of improved voice. Shorter periods of improved voice were reported at baseline by patients who later switched to UL or BL ≠ injection regimens. Patients receiving UL injections reported significantly reduced weak/breathy voice and dysphagia. Patients receiving BL ≠ injections reported increased length of improved voice; however, dysphagia symptoms increased. Ninety-two percent of patients with ETV switched to a UL regimen, with 61% of patients transitioning within the first three injections. Conclusions: Patients with pronounced dysphagia and extended periods of weak/breathy voice may benefit from a UL injection approach to mitigate side effects from BTX-A without sacrificing improved voice outcomes. For patients seeking to extend their length of improved voice, a BL ≠ injection regimen may be effective provided the adverse side effects from BTX-A are minimal. Patients with ETV may benefit from a UL injection approach at the outset of their course of treatment with BTX-A. Level of evidence: III.

Spontaneous Regression of Laryngeal Squamous Cell Carcinoma After Biopsy.

Approximately 7 cases of spontaneous regression of adult laryngeal carcinoma have been published in the literature since 1900. This case presents a 62-year-old male with a 6-month history of hoarseness who was subsequently diagnosed with a T1aN0M0 left true vocal fold squamous cell carcinoma (SCC) after biopsy. One month following the initial biopsy, histopathological findings on repeat biopsy revealed absence of malignancy and regression of the tumor without radiation. There has been no evidence of tumor recurrence. This case exemplifies how innate immune modulation may play a role in the spontaneous regression of laryngeal SCC, although the mechanism remains unknown.

Twenty-One for 2021: The Most Influential Papers in Laryngology Since 2000.

OBJECTIVES/HYPOTHESIS: To identify the most influential publications in laryngology since 2000. STUDY DESIGN: Modified Delphi process. METHODS: Samples of laryngologists drawn from editors of leading journals, organization officers, and thought leaders were invited to participate in a modified Delphi identification of influential laryngology papers. Influential was defined as follows: yielding meaningful practice changes, catalyzing further work as a foundation for an important topic, altering traditional views, or demonstrating durability over time. Quality and validity were not among the selection criteria. Each participant nominated 5 to 10 papers in Round 1. These nominations, augmented with papers from bibliometric analysis, were narrowed further in Round 2 as participants identified their top 20. The 40 papers with the most Round 2 votes were discussed by video conference and then subjected to Round 3 voting, with each participant again selecting their top 20 most influential papers. Final results were collated by the number of Round 3 votes. RESULTS: Sixteen of 18 invited laryngologists participated overall (all 16 in Rounds 1 and 3; 14 in Round 2). Twenty-one papers were identified as most influential. One paper appeared on all 16 Round 3 lists; three papers with eight (50%) votes each were lasted to make the list. Eleven of these 21 focused on voice; three each related to cancer, airway, and swallowing; and one encompassed all of these clinical areas. CONCLUSIONS: This list of 21 influential laryngology papers serves to focus further research, provides perspective on recent advances within the field, and is an educational resource for trainees and practicing physicians. LEVEL OF EVIDENCE: NA Laryngoscope, 132:406-412, 2022.

Physical Therapy for Muscle Tension Dysphonia with Cervicalgia.

OBJECTIVES: This study investigated the effectiveness of a specialized manual physical therapy (PT) program at improving voice among patients diagnosed with concomitant muscle tension dysphonia (MTD) and cervicalgia at a tertiary care voice center. MATERIALS AND METHODS: Cervicalgia was determined by palpation of the anterior neck. Both voice therapy (VT) and PT was recommended for all patients diagnosed with MTD and cervicalgia. PT included full-body manual physical therapy with myofascial release. Patients underwent: 1) VT alone, 2) concurrent PT and VT (PT with VT), 3) PT alone, 4) VT, but did not have PT ordered by treating clinician (VT without PT order) or 5) VT followed by PT (VT then PT). The pairwise difference in post-Voice Handicap Index-10 (VHI-10) controlling for baseline variables was calculated with a linear regression model. RESULTS: 178 patients met criteria. All groups showed improvement with treatment. The covariate-adjusted differences in mean post-VHI-10 improvement comparing the VT alone group as a reference were as follows: PT with VT 9.95 (95% confidence interval 7.70, 12.20); PT alone 8.31 (6.16, 10.45); VT without PT order 8.51 (5.55, 11.47); VT then PT 5.47 (2.51, 8.42). CONCLUSION: Among patients diagnosed with MTD with cervicalgia, treatment with a specialized PT program was associated with improvement in VHI-10 scores regardless of whether they had VT. While VT is the standard of care for MTD, PT may also offer benefit for MTD patients with cervicalgia.

Association of Social Determinants of Health with Time to Diagnosis and Treatment Outcomes in Idiopathic Subglottic Stenosis.

OBJECTIVES: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients. METHODS: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence. RESULTS: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression. CONCLUSIONS: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.

Multi-Institutional Analysis of Outcomes in Supraglottic Jet Ventilation with a Team-Based Approach.

OBJECTIVES/HYPOTHESIS: To evaluate the safety and complications of endoscopic airway surgery using supraglottic jet ventilation with a team-based approach. STUDY DESIGN: Retrospective cohort study. METHODS: Subjects at two academic institutions diagnosed with laryngotracheal stenosis who underwent endoscopic airway surgery with jet ventilation between January 2008 and December 2018 were identified. Patient characteristics (age, gender, race, follow-up duration) and comorbidities were extracted from the electronic health record. Records were reviewed for treatment approach, intraoperative data, and complications (intraoperative, acute postoperative, and delayed postoperative). RESULTS: Eight hundred and ninety-four patient encounters from 371 patients were identified. Intraoperative complications (unplanned tracheotomy, profound or severe hypoxic events, barotrauma, laryngospasm) occurred in fewer than 1% of patient encounters. Acute postoperative complications (postoperative recovery unit [PACU] rapid response, PACU intubation, return to the emergency department [ED] within 24 hours of surgery) were rare, occurring in fewer than 3% of patient encounters. Delayed postoperative complications (return to the ED or admission for respiratory complaints within 30 days of surgery) occurred in fewer than 1% of patient encounters. Diabetes mellitus, active smoking, and history of previous tracheotomy were independently associated with intraoperative, acute, and delayed complications. CONCLUSIONS: Employing a team-based approach, jet ventilation during endoscopic airway surgery demonstrates a low rate of complications and provides for safe and successful surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2292-2297, 2021.

Validation of the Communicative Participation Item Bank as an Outcome Measure for Spasmodic Dysphonia.

OBJECTIVES: Current patient-reported outcome measures do not adequately capture the impact of spasmodic dysphonia (SD) on communication in daily life situations. The aim of this study was to validate the Communicative Participation Item Bank (CPIB), which specifically measures a disease's impact on daily conversational situations, as an outcome measure for SD. STUDY DESIGN: Multi-institutional prospective cohort study. METHODS: A prospective study was conducted with administration of the 46-question CPIB and the Voice Handicap Index-10 (VHI-10) to 190 participants with SD before (time 1) and 6 weeks after (time 2) botulinum toxin injection. Differential item function (DIF) analyses were performed to examine potential item bias. Paired t-tests were used to assess change in each of the CPIB and VHI-10 scores after treatment. Pearson correlations were calculated between the CPIB and VHI-10. RESULTS: DIF analyses revealed no clinically meaningful difference between the item parameters generated for this SD sample and the original CPIB calibration sample. There were statistically significant changes between the pre-treatment and post-treatment time points for both the CPIB and VHI-10. Correlations between the CPIB and VHI were moderate-high. CONCLUSIONS: The CPIB item bank, General Short Form, and scoring parameters can be used with people with SD for valid and reliable measurement of the impact of communication disorders on communication in everyday life. The CPIB is sensitive to changes with intervention, proving useful for clinical and research purposes to assess the efficacy and effectiveness of interventions. LEVEL OF EVIDENCE: Level 2, prospective observational research with an experimental design (ie, cohort study). Laryngoscope, 131:859-864, 2021.

Should I Buy This? A Decision-Making Tool for Surgical Value-Based Purchasing.

Many considerations affect the value that a new instrument or product may generate in a surgical practice. This review serves as a guide for surgeons considering new purchases and/or wishing to advocate for hospital acquisition of new items. A summary of data from academic and industry practices is presented, with pertinent examples using relevant surgical devices such as disposable devices, laparoscopic trocars, and otologic endoscopes. Surgeons considering incorporating a new instrument or technology within their practice should weigh the following factors before decision making: patient and clinical care factors, surgeon and care team factors, and hospital factors such as cost, revenue, and sourcing. A surgeon well-versed in stakeholder interests who is involved in the purchase of a new instrument may have significant influence in value-based decision making that not only affects his or her practice but ultimately maximizes value for the patient.

Unilateral and Bilateral Laryngeal Pacing for Bilateral Vocal Fold Paralysis.

PURPOSE OF REVIEW: Present the state-of-the-art overview of laryngeal pacing for treatment of bilateral vocal fold paralysis. A minimally invasive unilateral pacing system and a fully implantable bilateral pacing system are currently in clinical trials. The relative advantages and disadvantages of each are discussed. RECENT FINDINGS: Research in functional electrical stimulation for the reanimation of the posterior cricoarytenoid muscle has successfully translated from animal models to human clinical trials for unilateral pacing and bilateral pacing. Current findings suggest unilateral pacing in humans significantly improves ventilation but only marginally better than cordotomy. Bilateral pacing in canines increases glottal opening greater than 2-fold over unilateral pacing and restores exercise tolerance to normal. SUMMARY: Unilateral pacing can be considered a breathing assist device and may not be appropriate for active individuals. Bilateral pacing may be preferable for patients who wish to engage in strenuous exercise. Minimally invasive systems may be ideal for patients who prefer less invasive implantation and are not concerned with cosmesis. Fully implantable pacing systems offer greater electrode redundancy and stability, resulting in a system that is robust against electrode migration or damage.

Comparative Treatment Outcomes for Patients With Idiopathic Subglottic Stenosis.

Importance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research. Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease. Design, Setting, and Participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook. Main Outcomes and Measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications. Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk. Conclusions and Relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.

Incidence and Outcomes of Acute Laryngeal Injury After Prolonged Mechanical Ventilation.

OBJECTIVES: Upper airway injury is a recognized complication of prolonged endotracheal intubation, yet little attention has been paid to the consequences of laryngeal injury and functional impact. The purpose of our study was to prospectively define the incidence of acute laryngeal injury and investigate the impact of injury on breathing and voice outcomes. DESIGN: Prospective cohort study. SETTING: Tertiary referral critical care center. PATIENTS: Consecutive adult patients intubated greater than 12 hours in the medical ICU from August 2017 to May 2018 who underwent laryngoscopy within 36 hours of extubation. INTERVENTIONS: Laryngoscopy following endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: One hundred consecutive patients (62% male; median age, 58.5 yr) underwent endoscopic examination after extubation. Acute laryngeal injury (i.e., mucosal ulceration or granulation tissue in the larynx) was present in 57 patients (57%). Patients with laryngeal injury had significantly worse patient-reported breathing (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 1.05; interquartile range, 0.48-2.10) and vocal symptoms (Voice Handicap Index-10: median, 2; interquartile range, 0-6) compared with patients without injury (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 0.20; interquartile range, 0-0.80; p < 0.001; and Voice Handicap Index-10: median, 0; interquartile range, 0-1; p = 0.005). Multivariable logistic regression independently associated diabetes, body habitus, and endotracheal tube size greater than 7.0 with the development of laryngeal injury. CONCLUSIONS: Acute laryngeal injury occurs in more than half of patients who receive mechanical ventilation and is associated with significantly worse breathing and voicing 10 weeks after extubation. An endotracheal tube greater than size 7.0, diabetes, and larger body habitus may predispose to injury. Our results suggest that acute laryngeal injury impacts functional recovery from critical illness.

Decoding phonation with artificial intelligence (DeP AI): Proof of concept.

OBJECTIVE: Acoustic analysis of voice has the potential to expedite detection and diagnosis of voice disorders. Applying an image-based, neural-network approach to analyzing the acoustic signal may be an effective means for detecting and differentially diagnosing voice disorders. The purpose of this study is to provide a proof-of-concept that embedded data within human phonation can be accurately and efficiently decoded with deep learning neural network analysis to differentiate between normal and disordered voices. METHODS: Acoustic recordings from 10 vocally-healthy speakers, as well as 70 patients with one of seven voice disorders (n = 10 per diagnosis), were acquired from a clinical database. Acoustic signals were converted into spectrograms and used to train a convolutional neural network developed with the Keras library. The network architecture was trained separately for each of the seven diagnostic categories. Binary classification tasks (ie, to classify normal vs. disordered) were performed for each of the seven diagnostic categories. All models were validated using the 10-fold cross-validation technique. RESULTS: Binary classification averaged accuracies ranged from 58% to 90%. Models were most accurate in their classification of adductor spasmodic dysphonia, unilateral vocal fold paralysis, vocal fold polyp, polypoid corditis, and recurrent respiratory papillomatosis. Despite a small sample size, these findings are consistent with previously published data utilizing deep neural networks for classification of voice disorders. CONCLUSION: Promising preliminary results support further study of deep neural networks for clinical detection and diagnosis of human voice disorders. Current models should be optimized with a larger sample size. LEVELS OF EVIDENCE: Level III.

Association Between Red Blood Cell Distribution Width and Outcomes of Open Airway Reconstruction Surgery in Adults.

Importance: Airway reconstruction for adults with laryngotracheal stenosis (LTS) is directed toward improving airway caliber to mitigate the patient's dyspnea and achieve prosthesis-free breathing (ie, without tracheostomy, intraluminal stent, or T-tube). Despite the importance of preoperative risk stratification to minimize postoperative complications, consensus on an objective predictive algorithm for open airway reconstruction is lacking. Objective: To determine whether the ability to achieve a prosthesis-free airway in adults after open airway reconstruction is associated with red blood cell distribution width (RDW) at the time of surgery. Design, Setting, and Participants: Case series study investigating 92 consecutive patients 18 years and older with laryngotracheal stenosis who underwent open airway reconstruction at a US tertiary care hospital from January 1, 2006, to January 1, 2017. Main Outcomes and Measures: The main outcome was a prosthesis-free airway (absence of tracheostomy, intraluminal stent, or T-tubes) at last follow-up. Multivariate logistic regression modeling was used to identify independent factors associated with this outcome. Results: Of the 92 patients who met inclusion criteria, the median (interquartile range) age was 44 (33.0-60.3) years; 50 (53%) were female, and 82 (89%) were white. In all, 74 patients (80%) were prosthesis free at the last follow-up (mean, 833 days; 95% CI, 10-4229 days). In multivariate analyses, airway decannulation was significantly correlated with reduced RDW (odds ratio [OR], 0.40; 95% CI, 0.19-0.84) and the absence of posterior glottic stenosis (OR, 0.12; 95% CI, 0.04-0.37). Conclusions and Relevance: These data suggest that surgical success in open airway reconstruction is significantly associated with RDW and whether the patient had posterior glottic stenosis. The RDW is a routine laboratory parameter that may provide some insight to the preoperative probability of prosthesis removal, facilitate risk stratification, promote informed patient decision making, and optimize health care resource management.

Laryngeal temperature simulations during carbon dioxide laser irradiation delivered by a scanning micromanipulator.

We use scatter-limited phototherapy techniques to calculate the time-dependent temperature profiles of incisions made with a commercial carbon dioxide laser being used to make a 1-mm incision under computer control using the Digital Acublade™ and with incisions made with the same laser under manual control. The goal is to understand the differences in the amount of lateral thermal damage that is likely from the computer-controlled incisions versus the manually controlled incisions. The temperature profiles are calculated from the absorption and scatter of light in a homogeneous material. The resulting temperature profiles are presented as videos showing how the tissue heats up and cools down with the incident laser pulses. The time-dependent thermal distributions indicate that the computer-controlled laser incision could show as little as 210 µm of lateral thermal damage, whereas the manually controlled laser incisions could show as much as 375 µm of lateral thermal damage. The computer-controlled laser incision is able to control laser pulses fast enough that subsequent pulses can ablate away tissue with a significant amount of residual heat from the previous laser pulse. Using the scatter-limited phototherapy techniques, we can see how a computer-controlled laser can make incisions with less thermal damage by ablating away tissue holding a significant amount of heat from the previous pulse before it has time to diffuse through the tissue. This method of heat removal from laser incisions has not been previously described or demonstrated.

Defining differences in patient characteristics between spasmodic dysphonia and laryngeal tremor.

OBJECTIVE: To compare presenting characteristics of patients with adductor spasmodic dysphonia (ADSD), ADSD with laryngeal tremor (ADSD + LT), and laryngeal tremor without ADSD (LT). DESIGN: Cross-sectional analysis. METHODS: Patients treated for laryngeal movement disorders (1990-2016) were included. Analysis of variance and chi square tests measured differences in patient characteristics across the three disease groups. Using ADSD as the referent, multivariable logistic regression models were used to determine whether potential risk factors including patient demographics, family history, presence of potential inciting events prior to disease onset, and coprevalent movement disorders were associated with ADSD + LT or LT. RESULTS: In all, 652 patients with ADSD (n = 377), ADSD + LT (n = 98), and LT (n = 177) were included. ADSD patients were significantly younger than those with ADSD + LT and LT (52.5 ± 13.4, 63.9 ± 11.3, and 69.3 ± 10.5 years, respectively; P < 0.001). Coprevalent movement disorders were more common in ADSD + LT (38.7%) and LT (57.1%) groups than in the ADSD group (11.5%; P < 0.001). Compared to ADSD, patients with ADSD + LT and LT were more likely to develop an additional movement disorder during follow-up. In multivariable analyses, increasing age, female gender, and having a movement disorder at presentation were associated with significantly greater odds of having ADSD + LT or LT when compared to ADSD. CONCLUSION: ADSD + LT patients demonstrate intermediate gender composition and age distributions between those with ADSD and LT. These findings suggest that ADSD + LT may be a distinct phenotype in the spectrum of laryngeal movement disorders. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:170-176, 2019.

Pathologic Fibroblasts in Idiopathic Subglottic Stenosis Amplify Local Inflammatory Signals.

OBJECTIVE: To characterize the phenotype and function of fibroblasts derived from airway scar in idiopathic subglottic stenosis (iSGS) and to explore scar fibroblast response to interleukin 17A (IL-17A). STUDY DESIGN: Basic science. SETTING: Laboratory. SUBJECTS AND METHODS: Primary fibroblast cell lines from iSGS subjects, idiopathic pulmonary fibrosis subjects, and normal control airways were utilized for analysis. Protein, molecular, and flow cytometric techniques were applied in vitro to assess the phenotype and functional response of disease fibroblasts to IL-17A. RESULTS: Mechanistically, IL-17A drives iSGS scar fibroblast proliferation ( P < .01), synergizes with transforming growth factor ß1 to promote extracellular matrix production (collagen and fibronectin; P = .04), and directly stimulates scar fibroblasts to produce chemokines (chemokine ligand 2) and cytokines (IL-6 and granulocyte-macrophage colony-stimulating factor) critical to the recruitment and differentiation of myeloid cells ( P < .01). Glucocorticoids abrogated IL-17A-dependent iSGS scar fibroblast production of granulocyte-macrophage colony-stimulating factor ( P = .02). CONCLUSION: IL-17A directly drives iSGS scar fibroblast proliferation, synergizes with transforming growth factor ß1 to promote extracellular matrix production, and amplifies local inflammatory signaling. Glucocorticoids appear to partially abrogate fibroblast-dependent inflammatory signaling. These results offer mechanistic support for future translational study of clinical reagents for manipulation of the IL-17A pathway in iSGS patients.

Characterizing the Normative Voice Tremor Frequency in Essential Vocal Tremor.

Importance: Essential vocal tremor (EVT) is a neurologic voice disorder characterized by periodic fluctuations in pitch and loudness that can hinder intelligibility. Defining the normative range of vocal tremor frequency may assist in diagnosis and provide insight into disease mechanisms. Objective: To characterize the normative voice tremor frequency in EVT (in hertz). Design, Setting, and Participants: Cross-sectional observational study of 160 patients with EVT. The setting was a tertiary voice center. Participants were identified from a database of consecutive patients diagnosed as having laryngeal movement disorders between January 1, 1990, and April 1, 2017. Main Outcomes and Measures: The following 3 methods measured the frequency of tremor experienced by patients with EVT: perceptual method, computerized peak detection method, and laryngeal electromyography method. Within-person and population-level tremor frequencies were compared across modalities to assess measurement reliability and consistency and to characterize the normal distribution of tremor frequencies in this population. Results: Among 160 participants (median age, 70 years; interquartile range [IQR], 64-77 years; 90.6% female [n = 145]), the median frequency of EVT was consistently between 4 and 5 Hz across all 3 methods (perceptual, 4.8 Hz [IQR, 4.4-5.5 Hz]; computerized peak detection, 4.6 Hz [IQR, 4.2-5.0 Hz]; and laryngeal electromyography, 4.3 Hz [IQR, 3.8-5.0 Hz]). The mean in-person differences between each measurement method were not clinically meaningful (range, 0.1-0.5 Hz). Including all interquartile ranges across measurement modalities, the normative tremor frequency range for EVT was 3.8 to 5.5 Hz. Conclusions and Relevance: To our knowledge, this is the largest study to date to characterize the normal frequency of tremor in patients with EVT. The normative frequency of EVT (range, 3.8-5.5 Hz) falls within a much narrower range than previously reported. Those whose frequency is outside this range may still have EVT but should be carefully evaluated for potential other causes of vocal tremor. Defining characteristics of EVT may aid appropriate diagnosis and improve understanding of this disease.

Model to Select On-Therapy vs Off-Therapy Tests for Patients With Refractory Esophageal or Extraesophageal Symptoms.

BACKGROUND & AIMS: It is not clear whether we should test for reflux in patients with refractory heartburn or extraesophageal reflux (EER) symptoms, such as cough, hoarseness, or asthma. Guidelines recommend testing patients by pH monitoring when they are on or off acid-suppressive therapies based on pretest probability of reflux, determined by expert consensus. However, it is not clear what constitutes a low or high pretest probability of reflux in these patients. We aimed to develop a model that clinicians can use at bedside to estimate pretest probability of abnormal reflux. METHODS: We performed a prospective study of 471 adult patients with refractory heartburn (n = 214) or suspected EER symptoms (n = 257) who underwent endoscopy with wireless pH monitoring while they were off acid-suppressive treatment and assigned them to groups based on symptoms at presentation (discovery cohort). Using data from the discovery cohort, we performed proportional odds ordinal logistic regression to select factors (easy to obtain demographic criteria and clinical symptoms such as heartburn, regurgitation, asthma, cough, and hoarseness) associated with esophageal exposure to acid. We validated our findings in a cohort of 118 patients with the same features from 2 separate tertiary care centers (62% women; median age 59 years; 62% with cough as presenting symptom). RESULTS: Abnormal pH (>5.5% of time spent at pH <4) was found in 56% of patients with heartburn and 63% of patients with EER (P = .15). Within EER groups, abnormal pH was detected in a significantly larger proportion (80%) of patients with asthma compared with patients with cough (60%) or hoarseness (51%; P < .01). Factors significantly associated with abnormal pH in patients with heartburn were presence of hiatal hernia and body mass index >25 kg/m2. In patients with EER, the risk of reflux was independently associated with the presence of concomitant heartburn (odds ratio [OR] 2.0; 95% confidence interval [CI] 1.3-3.1), body mass index >25 kg/m2 (OR 2.1; 95% CI 1.5-3.1), asthma (OR 2.0; 95% CI 1.2-3.5), and presence of hiatal hernia (OR 1.9; 95% CI 1.2-3.1). When we used these factors to create a scoring system, we found that a score of ≤2 excluded patients with moderate to severe reflux, with a negative predictive value of 80% in the discovery cohort and a negative predictive value of 85% in the validation cohort. CONCLUSION: We developed a clinical model to estimate pretest probability of abnormal pH in patients who were failed by proton pump inhibitor therapy. This system can help guide clinicians at bedside in determining the most appropriate diagnostic test in this challenging group of patients.

Treatment options in idiopathic subglottic stenosis: protocol for a prospective international multicentre pragmatic trial.

INTRODUCTION: Idiopathic subglottic stenosis (iSGS) is an unexplained progressive obstruction of the upper airway that occurs almost exclusively in adult, Caucasian women. The disease is characterised by mucosal inflammation and localised fibrosis resulting in life-threatening blockage of the upper airway. Because of high recurrence rates, patients with iSGS will frequently require multiple procedures following their initial diagnosis. Both the disease and its therapies profoundly affect patients' ability to breathe, communicate and swallow. A variety of treatments have been advanced to manage this condition. However, comparative data on effectiveness and side effects of the unique approaches have never been systematically evaluated. This study will create an international, multi-institutional prospective cohort of patients with iSGS. It will compare three surgical approaches to determine how well the most commonly used treatments in iSGS 'work' and what quality of life (QOL) trade-offs are associated with each approach. METHODS AND ANALYSIS: A prospective pragmatic trial comparing the 'Standard of Care' for iSGS at multiple international institutions. Patients with a diagnosis of iSGS without clinical or laboratory evidence of vasculitis or a history of endotracheal intubation 2 years prior to symptom onset will be included in the study. Prospective evaluation of disease recurrence requiring operative intervention, validated patient-reported outcome (PRO) measures as well as patient-generated health data (mobile peak flow recordings and daily steps taken) will be longitudinally tracked for 36 months. The primary endpoint is treatment effectiveness defined as time to recurrent operative procedure. Secondary endpoints relate to treatment side effects and include PRO measures in voice, swallowing, breathing and global QOL as well as patient-generated health data. ETHICS AND DISSEMINATION: This protocol was approved by the local IRB Committee of the Vanderbilt University Medical Center in July 2015. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and directly to patient with iSGS via social media-based support groups. TRIAL REGISTRATION NUMBER: NCT02481817.