Blood-Based Proteomics for Adult-Onset Focal Dystonias.

OBJECTIVES: The adult-onset focal dystonias are characterized by over-active muscles leading to abnormal movements. For most cases, the etiology and pathogenesis remain unknown. In the current study, unbiased proteomics methods were used to identify potential changes in blood plasma proteins. METHODS: A large-scale unbiased proteomics screen was used to compare proteins (N = 6,345) in blood plasma of normal healthy controls (N = 49) with adult-onset focal dystonia (N = 143) consisting of specific subpopulations of cervical dystonia (N = 45), laryngeal dystonia (N = 49), and blepharospasm (N = 49). Pathway analyses were conducted to identify relevant biological pathways. Finally, protein changes were used to build a prediction model for dystonia. RESULTS: After correction for multiple comparisons, 15 proteins were associated with adult-onset focal dystonia. Subgroup analyses revealed some proteins were shared across the dystonia subgroups while others were unique to 1 subgroup. The top biological pathways involved changes in the immune system, metal ion transport, and reactive oxygen species. A 4-protein model showed high accuracy in discriminating control individuals from dystonia cases [average area under the curve (AUC) = 0.89]. INTERPRETATION: These studies provide novel insights into the etiopathogenesis of dystonia, as well as novel potential biomarkers. ANN NEUROL 2024;96:110-120.

Bacterial Laryngotracheitis and Associated Upper Airway Obstruction: A Case Series.

BACKGROUND: Iatrogenic laryngotracheal stenosis (LTS) continues to be a known complication of indwelling endotracheal tubes (ETTs). It is well established that secondary scar formation caused by inflammation and mucosal injury are the main mechanisms by which stenosis occurs. Additionally, there are reports of bacterial colonization of ETTs and its potential association with tracheal scar formation. We describe 4 cases of patients with history of intubation and/or tracheostomy and presumed LTS that improved with the management of concurrent bacterial laryngotracheitis. METHODS: A retrospective case series of 4 subjects initially diagnosed at a tertiary care center with posterior glottic or subglottic stenosis and positive bacterial laryngotracheal cultures was performed. RESULTS: All 4 patients with presumed LTS had culture-proven bacterial growth isolated from the laryngotrachea and were treated with adjunct antibiotics. In the first 3 cases, complete resolution of upper airway obstruction was achieved. The fourth patient had notable improvement in her airway status without the need for additional surgical intervention. CONCLUSION: This case series suggests that bacterial growth within the airway may play a larger role in adult postintubation airway injury. Those patients presenting with concern for LTS and symptoms suspicious for an ongoing bacterial infection may benefit from adjunct antibiotic therapy.

Thoracic Duct Occlusion Leading to Intermittent Left Supraclavicular Swelling and Pancreatitis.

Intermittent left supraclavicular swelling is an uncommon and elusive condition that can lead to extensive diagnostic workups to determine the etiology and treatment. One potential cause is partial, intermittent, or complete thoracic duct occlusion (TDO). We report on a patient who presented with chronic, intermittent left supraclavicular swelling and abdominal pain that was relieved by thoracic duct angioplasty. Thoracic duct occlusion should be included in the differential diagnosis of left supraclavicular swelling. Lymphatic imaging can facilitate the diagnosis and allows for potential percutaneous treatment. Laryngoscope, 134:1313-1315, 2024.

Demographics and Clinical Characteristics Associated with the Spread of New-Onset Laryngeal Dystonia.

OBJECTIVES: Adult-onset idiopathic laryngeal dystonia (LD) can be associated with the risk of spread to muscles in the body. Subjects with extralaryngeal onset of dystonia have exhibited spread to the larynx. Previous studies analyze the spread of other dystonias but emphasis has not been placed on LD. The objective was to identify demographic and clinical factors contributing to the spread of dystonia to and from the larynx. METHODS: Data were obtained from the Dystonia Coalition (DC)-patients from 49 international clinical centers. Clinical and demographic data was taken from 143 out of 409 patients with diagnosed LD. Patient criteria included adult-onset LD diagnosed on exam with no co-morbid neurologic conditions and no dystonia in other locations. RESULTS: Among the 143 patients, 94 (65.7%) patients were diagnosed with focal laryngeal onset, with the remainder having extralaryngeal onset. Family history and age at study were statistically significant indicators of a patient developing laryngeal versus extralaryngeal onset of dystonia. Among the laryngeal onset group, 21 cases (22.3%) had an average time of 5.81 ± 5.79 years to spread from diagnosis, most commonly to neck (61.9%). Among extralaryngeal onset patients, mean time of larynx spread was 7.92 ± 7.737 years, most commonly to neck (22.7%). CONCLUSIONS: Our data indicates approximately a quarter of patients with laryngeal-onset dystonia will exhibit spread. There were no demographic or clinical factors that were statistically predictive of the likelihood of spread from larynx. Patients with dystonia elsewhere in the body should be counseled on the possibility of spread to larynx, and vice versa. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2295-2299, 2024.

Efficacy of Systemic Bevacizumab for Recurrent Respiratory Papillomatosis with Pulmonary Involvement.

OBJECTIVES: Pulmonary papillomatosis is a rare but severe manifestation of recurrent respiratory papillomatosis (RRP). Efficacy data of systemic bevacizumab for pulmonary RRP are limited. This study's objective was to characterize disease response of pulmonary RRP to systemic bevacizumab. METHODS: A retrospective review was performed to identify patients with pulmonary RRP seen at three medical institutions. Clinical symptoms, CT findings, and disease response were compared before and after initiation of systemic bevacizumab therapy. Disease response was categorized as complete response, partial response, stabilization, or progression for each subsite involved by papilloma. RESULTS: Of the 12 pulmonary RRP patients treated with systemic bevacizumab, 4 (33.3%) were male, and 11 (91.7%) were juvenile-onset RRP patients. All presented with laryngeal, tracheal, and pulmonary RRP. The median (range) age at first bevacizumab infusion was 48.1 (19.5-70.2) years. Progression to pulmonary malignancy was identified in 3 (25.0%) patients, 2 before initiation of and 1 after complete cessation of bevacizumab therapy. Clinical symptoms such as dyspnea (75.0% vs. 25.0%; p = 0.01) and dysphagia and/or odynophagia (33.3 vs. 0.0%; p = 0.03) were significantly decreased following bevacizumab therapy. Compared with pre-treatment baseline, 9 (75.0%) patients experienced a stable-to-partial response in the lungs to systemic bevacizumab, and 10 (83.3%) experienced partial-to-complete responses in the larynx and trachea. CONCLUSION: Systemic bevacizumab is effective in stabilizing progression in even the most severe cases of RRP, with both a dramatic reduction in laryngeal and tracheal disease as well as a stable-to-partial response of pulmonary involvement in a majority of patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:577-581, 2024.

Voice outcomes from subligamentous cordectomy for early glottic cancer.

OBJECTIVES: We evaluated the voice and vocal fold pliability outcomes of European Laryngological Society (ELS) deep type I (subepithelial) and type II (subligamentous) cordectomies for early glottic cancer. METHODS: We reviewed the medical records of patients with glottic carcinoma at a tertiary care medical center between 2005 and 2011. Their procedures were stratified into ELS type I and ELS type II cordectomies. The data recorded included age, gender, tumor stage, recurrence, patient-assessed voice-related quality of life, perceptual voice evaluation, and stroboscopy. RESULTS: Four patients were identified as having subepithelial cordectomy, and 13 as having subligamentous cordectomy. The average preoperative and postoperative voice-related quality of life scores were 65 and 74 for the ELS I cohort and 64 and 95 for the ELS II group. The preoperative and postoperative perceptual voice evaluation scores were 56 and 35 for the ELS I cohort and 45 and 21 for the ELS II cohort. The ELS I cohort had a moderately to severely reduced mucosal wave, with 75% of patients demonstrating glottic insufficiency, whereas the ELS II cohort had a mildly to moderately reduced mucosal wave, with 8% of patients demonstrating glottic insufficiency. The survival outcomes were the same. CONCLUSIONS: Patients who underwent subligamentous excision of early glottic cancer had significantly improved postoperative voice and stroboscopy scores. This finding suggests that if tumor resection reaches the vocal ligament, and minimal superficial lamina propria can be preserved, subligamentous cordectomy should be performed.

A Comparison of Voice Therapy Attendance Rates Between In-Person and Telepractice.

PURPOSE: This study sought to investigate whether a significant difference exists in attendance, cancellations, and no-shows between in-person therapy and telepractice. The authors hypothesized that telepractice no-show and cancellation rates would be less than in-person no-show and cancellation rates. METHOD: This retrospective study manually reviewed and analyzed attendance, no-show, and cancellation data over a 3-month span of in-person-only visits (September 2019-November 2019) and a 3-month span of telepractice visits (September 2020-November 2020) conducted at the Emory Voice Center, a tertiary care practice in urban Atlanta, Georgia. Additionally, data were collected for each patient's full course of therapy outside of the 3-month windows and analyzed for attendance, no-show, and cancellation patterns. RESULTS: Data from 521 patients were available for review from the selected time frame. In 2019 (in-person), 157 patients met inclusion criteria, and in 2020 (telepractice), 176 patients were included. Therapy initiation, therapy attendance, and no-show rates had significant increases in the telepractice year, and cancellations made greater than 24 hr before the appointments had a significant decrease in the telepractice year. Furthermore, the overall course of therapy showed significantly fewer missed appointments and more attended appointments in the telepractice year. CONCLUSIONS: Patients participating in voice therapy via telepractice are more likely to initiate treatment and attend treatment and less likely to cancel sessions compared with patients receiving treatment in person. These data combined with extant data on telepractice treatment efficacy indicate that telepractice should be considered standard of care and offered to all patients seeking treatment, as it removes many reported barriers to treatment.

Long-Term Follow-up of Parenteral Bevacizumab In Patients with Recurrent Respiratory Papillomatosis.

OBJECTIVE: The clinical course of recurrent respiratory papillomatosis (RRP) varies from spontaneous remission to severe airway obstruction with wide variability in recurrence. Standard treatment involves debulking to improve voice and/or breathing. Non-surgical therapies are emerging in hopes of non-operative disease control. This retrospective review analyzes long-term safety, efficacy, and durability of clinical control in the largest reported series of parenteral bevacizumab in adults with RRP. METHODS: Twenty-three patients with known RRP who have been receiving off-label systemic bevacizumab were included. Dosage, infusion interval, number of cycles, debulking requirements, subjective outcomes, adverse events, and reasons for treatment termination were investigated. RESULTS: Patients have been followed for an average of 791.43 (21-1468) days. The most common starting dosing regimen was 15 mg/kg at 3 weeks in 11 followed by 10 mg/kg at 6 weeks intervals in 6 individuals. Long-term maintenance dosage varied with the least intensive regimen being 10 mg/kg at 14-week intervals. Subjective improvement of voice and/or breathing was reported in 18/23 subjects. The median time for patients that needed a procedure after treatment was 634 days. Procedures after infusions decreased from 3.08 ± 2.48 procedures in the year prior to 0.52 ± 1.12 during systemic Bevacizumab, and to 0.86 ± 2.05 after stopping bevacizumab. Therapy termination occurred in 8 subjects where only 3 were due to adverse events. CONCLUSION: Parenteral bevacizumab remains a well-tolerated treatment for patients with recalcitrant RRP. There appears to be a durable reduction in the frequency of debulking surgery requirements although on a maintenance regimen. Laryngoscope, 133:2725-2733, 2023.

Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11-Associated Recurrent Respiratory Papillomatosis.

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

International consensus statement on allergy and rhinology: Allergic rhinitis - 2023.

BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Beauty and Attractiveness in the Human Voice.

OBJECTIVE: The objective of this study was to investigate the difference between vocal beauty and vocal attractiveness by determining whether perceptual ratings of vocal beauty and vocal attractiveness could be dissociated in a cohort of normal raters without a diagnosed sexual desire disorder. METHODS: Twenty five gay male participants were presented with randomly-chosen samples from the Geneva Voices and Faces Database, and were asked to rate each sample in terms of beauty, attractiveness for a relationship of short duration, and attractiveness for a relationship of long duration. Responses were recorded on a visual analog scale (0-100) using a touch-screen interface. The number of stimulus repetitions and the participant response times were also recorded. Statistical analyses were done using two-way Analysis of Variance tests and independent student's t tests. P values were considered statistically significant at the P < 0.05 level. RESULTS: Participants rated male voices significantly higher in terms of beauty, attractiveness for a relationship of long duration, and attractiveness for a relationship of short duration (P < 0.001). Participants rated female voices significantly higher for beauty than for attractiveness for relationship of long or short duration (P < 0.001). There was no significant difference in response time between male and female voices when rating vocal beauty (P = 0.5608). Response time was significantly longer for male voices than for female voices when assessing attractiveness for a relationship of short duration (P < 0.002) but not for long duration (P < 0.3496). Attractive voices (male and female) were repeated more often, and male voices were repeated more often than female voices for both long-term and short-term attractiveness. There was no difference in stimulus replay behavior as a function of the beauty ratings. CONCLUSION: In a cohort of gay male raters without a diagnosed sexual desire disorder, vocal beauty and vocal attractiveness ratings of male and female voices are two related but distinct perceptual constructs that can, under certain circumstances, be dissociated. In general, gay men rated male voices equivalently for beauty, short-term, and long-term attractiveness, while the same ratings for female voices showed a significant difference between ratings of beauty and ratings of short-term and long-term attractiveness.

Evaluating Safety of Awake, Bilateral Injection Laryngoplasty for Bilateral Vocal Fold Atrophy.

OBJECTIVE: Office-based injection laryngoplasty (IL) has emerged as a useful procedure for otolaryngologists to correct glottic insufficiency while avoiding the costs and risks of general anesthesia. This is the first study focused on addressing the safety of bilateral IL for bilateral vocal fold (VF) atrophy. METHODS: Patient records were reviewed from Emory University Hospital Midtown during the period of 2005 to 2017. Patients who underwent awake, bilateral transthyrohyoid, transoral, transcricothyroid, or transthyroid cartilage IL for bilateral VF atrophy were analyzed. All procedures, including repeat injections, were bilateral. Complication rate was used to evaluate safety. Patients with vocal cord paralysis, paresis, scar, and sulcus were excluded from the study. RESULTS: Total 174 procedures met inclusion criteria. There were four complications, yielding a complication rate of 2.3%. Complications included aborted cases for difficult anatomy or poor patient tolerance, injection material not resorbing, and a VF hematoma. No patients had any airway emergencies or required admission to the hospital or evaluation in the emergency room. CONCLUSIONS: This study illustrates a low complication rate for awake, bilateral IL in treating bilateral VF atrophy. This supports other studies that promote the safety of this procedure in the awake setting. Complications were associated with patient tolerance, unique anatomy, and in one case, anticoagulant medication. The low complication rate supports the conclusion that bilateral medialization IL is safe to perform in the office-based, awake setting.

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.

Parenteral Bevacizumab for the Treatment of Severe Respiratory Papillomatosis in an Adult Population.

OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a rare, potentially life-threatening, disease that impacts the voice, breathing, and quality of life of patients. Frequent surgical interventions may be needed to control symptoms. We examined the safety and efficacy of utilizing parenteral bevacizumab in the management of severe RRP in adults. STUDY DESIGN: This is a retrospective review of clinical management approaches in a group of patients with severe RRP defined as having a high disease burden, frequent need for debridement, and/or tracheobronchial disease. Patients were initially treated with 15 mg/kg of bevacizumab at 3-week intervals. Bevacizumab dosing and frequency was then individually titrated down. RESULTS: Fourteen adults received a median of 8.5 (range 2-17) bevacizumab infusions over approximately 24 months. All had a history of laryngeal RRP with 6/14 having additional tracheobronchial lesions. Patients required a median of 4 (range 2-11) procedures in the year prior to treatment. Only 3/10 (30%) patients who continued therapy required any additional procedures. Bevacizumab administration was generally well tolerated, with four patients discontinuing therapy. Medical reasons included severe epistaxis and hypertension and thrombocytopenia in an individual with systemic lupus erythematosus. Common side effects included hypertension (grade 2), headache (grades 1-2), elevated creatinine (grades 1-2), and epistaxis (grade 3). CONCLUSIONS: Intravenous bevacizumab for the primary treatment of severe RRP in adults appears clinically effective and safe. Expected and typically mild side effects related to bevacizumab were observed. Continued investigation of bevacizumab through a prospective clinical trial is warranted. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E921-E928, 2021.

Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality. STUDY DESIGN: Delphi method-based survey series. METHODS: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up. RESULTS: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18). CONCLUSION: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E1941-E1949, 2021.

Intubation Containment System for Improved Protection From Aerosolized Particles During Airway Management.

OBJECTIVES: Worldwide efforts to protect front line providers performing endotracheal intubation during the COVID-19 pandemic have led to innovative devices. Authors evaluated the aerosol containment effectiveness of a novel intubation aerosol containment system (IACS) compared with a recently promoted intubation box and no protective barrier. METHODS: In a simulation center at the authors' university, the IACS was compared to no protective barrier and an intubation box. Aerosolization was simulated using a commercial fog machine and leakage of aerosolize mist was visually assessed. RESULTS: The IACS appeared to contain the aerosolized mist, while the intubation box allowed for mist to contact the laryngoscopist and contaminate the clinical space through arm port holes and the open caudal end. Both devices protected the laryngoscopist better than no protective barrier. DISCUSSION: The IACS with integrated sleeves and plastic drape appears to offer superior protection for the laryngoscopist and assistant providers from aerosolized particles.

Phase Ib Study of Chemoprevention with Green Tea Polyphenon E and Erlotinib in Patients with Advanced Premalignant Lesions (APL) of the Head and Neck.

PURPOSE: On the basis of synergistic effects between green tea polyphenon E (PPE) and EGFR-tyrosine kinase inhibitor in preclinical studies, we conducted a phase Ib study of the PPE and erlotinib combination in patients with advanced premalignant lesions (APL) of the oral cavity and larynx. PATIENTS AND METHODS: Patients were treated with a fixed dose of PPE (200 mg three times a day) and dose escalation of erlotinib (50, 75, 100 mg daily) for 6 months with tissue biopsy at baseline and 6 months. Primary endpoints were safety and toxicity; secondary endpoints were evaluation of pathologic response, cancer-free survival (CFS), overall survival (OS), and biomarker modulation. RESULTS: Among 21 enrolled patients, 19 began treatment and 17 completed 6 months of treatment with PPE and erlotinib. Main characteristics of treated patients: 15 severe dysplasia or carcinoma in situ and 17 oral cavity. Only skin rash was associated with dose-limiting toxicity and MTD. Recommended doses for phase II studies are PPE 600 mg daily plus erlotinib 100 mg daily for 6 months. Pathologic responses in 17 evaluable patients: pathologic complete response (47%) and pathologic partial response (18%). The 5-year CFS and OS were 66.3% and 93%, respectively. Among tested biomarkers, only phosphorylated ERK was correlated with response to treatment. CONCLUSIONS: Treatment with PPE and erlotinib combination was well tolerated in patients with APLs of the head and neck, and showed a high rate of pathologic response with excellent CFS. This combination deserves further investigation for the chemoprevention and/or prevention of second primary tumors in early-stage head and neck cancer.

Comparison of an oropharyngeal pH probe and a standard dual pH probe for diagnosis of laryngopharyngeal reflux.

OBJECTIVES: We compared the ability of an oropharyngeal (OP) aerosol-detecting pH probe and a standard dual pH probe in measuring laryngopharyngeal reflux (LPR). METHODS: Fifteen subjects with LPR symptoms had 24-hour simultaneous placement of the OP probe and a standard dual pH probe. Acid exposure was defined as a 10% pH decrease below baseline for the OP probe or a pH of less than 4 at the upper esophageal sphincter (UES) probe of the dual pH probe. RESULTS: The mean duration of acid exposure was 650 seconds (SD, 619) or 0.75% of the total time for the OP probe and 438 seconds (SD, 511) or 0.51% of the total time for the UES probe. When we excluded meals and sleep, the mean duration of acid exposure was 271 seconds (SD, 356) or 0.31% of the total time for the OP probe and 271 seconds (SD, 359) or 0.31% of the total time for the UES probe. The correlation coefficient (R) between the two probes for measurement of the duration of acid exposure was 0.50 (p < 0.05). When we excluded meals and the supine position, the R was notably higher, at 0.95 (p < 0.0001). CONCLUSIONS: The OP probe reliably documented LPR events when meals and sleep were eliminated and was better tolerated than the standard dual probe.

Carcinoma presenting as idiopathic anterior glottic webs: A case series.

An anterior glottic web is an abnormal fusion of the anterior aspect of the membranous vocal folds. Noncongenital glottic webs are usually iatrogenic from intubation or laryngeal surgery. We present six adult patients whose initial in-office diagnoses were consistent with "idiopathic" benign anterior glottic webs as determined by three laryngologists (a.m.k., j.m.b., m.j.p.). Further evaluation revealed the diagnoses of laryngeal squamous cell carcinoma in all cases. The high risk of malignancy in cases of idiopathic anterior glottic web necessitates biopsy for tissue diagnosis of all such lesions. Laryngoscope, 129:2118-2120, 2019.

Vocal outcome measures after bilateral posterior cricoarytenoid muscle botulinum toxin injections for abductor spasmodic dysphonia.

OBJECTIVE: To review vocal outcome measures, using the Voice Related Quality of Life (VRQOL) index, after simultaneous bilateral posterior cricoarytenoid muscle botulinum toxin injections. STUDY DESIGN: Case series. SETTING: Tertiary care academic clinic. SUBJECTS AND METHODS: Fourteen subjects with abductor spasmodic dysphonia received 37 simultaneous bilateral posterior cricoarytenoid muscle botulinum toxin injections for isolated abductor spasmodic dysphonia (ABSD) over a 16-month period. MAIN OUTCOME MEASURES: VRQOL index. RESULTS: Of the 37 injections, 33 of 37 (89%) resulted in improvement. Three injections resulted in no improvement, and one injection resulted in a worse VRQOL. The overall VRQOL mean improvement was 19.8 (range 5-53), with an average pre/postinjection VRQOL interval of 36 days (range 21-45 days). CONCLUSIONS: Simultaneous bilateral posterior cricoarytenoid muscle botulinum injections result in a statistically significant improvement in VRQOL index scores for a high percentage of ABSD patients, thus improving patient quality of life.