Evolving Endotracheal Tube Preferences and Practices: Intensivist Knowledge Gaps and Sex Disparities.

OBJECTIVES: The complex management of intubation-related laryngeal injury makes prevention vital. The purpose of this study is to assess endotracheal tube (ETT) practices and preferences among intensivists at our institution. METHODS: Chart review of intubated patients and intensivist survey were simultaneously performed in January 2016 and August 2022. A height-to-ETT size ratio (H:ETT) was calculated for each patient in the 2022 cohort. Intubated patients were followed until tracheostomy, extubation, or death occurred. Surveys assessed intensivist preferences for ETT size and management of intubated patients. RESULTS: 300 ICU patients were included. The mean ETT size for males decreased from 7.73 ± 0.30 in 2016 to 7.57 ± 0.25 in 2022 (p < 0.001). The average H:ETT of men was higher than females (p = 0.004), indicating that females in this population were intubated with larger ETTs relative to their height compared to males. Whereas the majority (66.7%) of intensivists endorse 7.0 ETTs as the standard for women, the majority (70%) of women at our institution are intubated with a 7.5 ETT or larger. Of intubated patients in the ICU, 23 (19.5%) were intubated for 11 days or longer. CONCLUSIONS: Compared to men, women are intubated with larger-than-preferred ETTs relative to height. Additionally, patients in our study were intubated for longer than preferred based on intensivist surveys, putting this population at higher risk for acute laryngeal injury (AlgI)-related laryngotracheal stenosis (LTS). Further studies should seek to identify similar trends and barriers to reducing ALgI-related LTS. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3080-3086, 2023.

Voice Outcomes Following Serial Office-Based Steroid Injections and Voice Therapy for Vocal Fold Scar.

OBJECTIVE: Previous studies indicate that certain voice outcomes can improve following a single office-based steroid injection with voice therapy for vocal fold scar. We evaluated voice outcomes after a series of three timed office-based steroid injections with voice therapy. STUDY DESIGN: Retrospective case series with chart review. SETTING: Academic medical center. METHODS: We evaluated pre-and postprocedural patient-reported, perceptual, acoustic, aerodynamic, and videostroboscopic parameters. We evaluated 23 patients who underwent three office-based dexamethasone injections into the superficial lamina propria one month apart. All patients pursued voice therapy. RESULTS: Voice Handicap Index (n = 19; P= .030) decreased after injection series. Total GRBAS score (grade, roughness, breathiness, asthenia, strain) decreased (n = 23; P = 0.001). Dysphonia severity index score improved (n = 20; P = 0.041). Phonation threshold pressure did not decrease significantly (n = 22; P = 0.536). Videostroboscopic parameters of vocal fold edge (P = 0.023), right mucosal wave (P = 0.023) improved or normalized after injection series. Glottic closure (P = 0.134) did not improve. CONCLUSIONS: Series of three office-based steroid injections combined with voice therapy for vocal fold scar does not appear to provide further benefit than one injection. Despite lack of improvements of PTP and other parameters, injection series is likewise unlikely to worsen dysphonia. A partially negative study provides value in investigation of less invasive treatment alternatives for a disorder that is challenging to treat. Future studies exploring effects of voice therapy alone without other intervention and consideration of sham injection versus steroid injection are warranted.

Long-Term Follow-up of 64 Patients With Idiopathic Subglottic Stenosis: Treatment Pathways, Outcomes, and Impact of Serial Intralesional Steroid Injections.

OBJECTIVE: To describe treatment pathways and long-term outcomes in 64 patients with idiopathic subglottic stenosis (iSGS), including the impact of serial intralesional steroid injection (SILSI) on degree of stenosis, need for subsequent operation, and patient-reported outcome measures. METHODS: Retrospective review of 64 female patients with iSGS undergoing varied management approaches, 57 of whom underwent SILSI as at least part of their care. Treatment pathways included SILSI only, endoscopic intervention followed by SILSI only, endoscopic interventions only, endoscopic intervention followed by SILSI followed by need for repeat endoscopic intervention, open surgery, and tracheotomy. Outcomes assessed included subjectively estimated percent airway stenosis, dyspnea index (DI), modified medical research council (MMRC) dyspnea scale, voice handicap index-10 (VHI-10), number of operative and office-based procedures performed, need for subsequent operative intervention, and inter-operative interval. RESULTS: Treatment pathways included SILSI alone (n = 6), endoscopic intervention(s) followed by SILSI only (n = 31), SILSI followed by additional endoscopic or office-based procedures (n = 16), open surgery (n = 3), and tracheostomy (n = 4). 57 of 64 patients underwent SILSI as at least part of their treatment. Inter-operative interval was increased after starting SILSI. Of patients undergoing SILSI, those with more procedures or shorter inter-operative interval prior to SILSI were more likely to return to the operating room. Estimated stenosis, DI, MMRC, and VHI-10 decreased with SILSI. Stenosis was not correlated with DI, MMRC, or VHI-10, though DI was correlated with both MMRC and VHI-10 score. CONCLUSION: Of 57 patients undergoing SILSI, 37 did not require further operative intervention. Improvements in inter-operative interval, dyspnea, and voice were observed across patients. Randomized trials to identify which patients may benefit most from SILSI are warranted.

Pain Experience and Tolerance of Awake In-Office Upper Airway Procedures: Influencing Factors.

OBJECTIVES/HYPOTHESIS: Awake, unsedated in-office upper airway procedures are performed frequently and have high completion rates, yet less is known about the patients' pain experience and potentially influencing factors. It is also unclear if patients' pain experiences become worse with repeated procedures. We identified procedure- and patient-related factors that might influence procedural completion and pain scores. STUDY DESIGN: Retrospective chart review. METHODS: Pre-, intra-, and post-procedure pain scores were collected prospectively for awake unsedated upper airway procedures performed at a single institution over a 5-year period. Patient factors reviewed were demographics, body mass index, psychiatric and/or pain diagnosis, and related medications. Procedure factors reviewed were procedure type, route, side, and performance of the same procedure multiple times. Patients reported their pain level before, during, and after the procedure using a standard 0 to 10 scale. Maximum pain score change (PΔmax), or the difference between highest and lowest reported pain levels, was calculated. Descriptive and multivariate analyses were performed. RESULTS: Procedure completion was 98.7% for 609 first time patients and 99.0% in 60 patients undergoing 292 repeat procedures. PΔmax did not covary with age, gender, or BMI. PΔmax covaried with pain and psychiatric conditions and associated medications. PΔmax was highest for injection medialization and lowest for tracheoscopy. PΔmax decreased over time for those undergoing multiple identical procedures. CONCLUSIONS: Procedures were performed with a very high completion rate and low pain scores. Age, sex, and BMI did not affect pain experience. A combination of pain and psychiatric conditions did. Injection medialization had the highest PΔmax and tracheoscopy the lowest. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1580-E1588, 2021.

Proteomic and Genomic Methylation Signatures of Idiopathic Subglottic Stenosis.

OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a chronic inflammatory condition that causes dyspnea and affects middle-aged women of White race and non-Latino or Hispanic ethnicity. To better characterize its phenotype and pathogenesis, we assessed the proteomic and genomic methylation signatures of subglottic tissue collected from iSGS patients compared to controls. STUDY DESIGN: Molecular analysis of clinical biospecimens. METHODS: We collected subglottic tissue biopsies from 12 patients during direct laryngoscopy, immediately prior to surgical treatment of iSGS; as well as from 4 age-, sex-, and race/ethnicity-matched control patients undergoing other direct laryngoscopic procedures. We isolated protein and genomic DNA, acquired proteomic data using label-free quantitative mass spectrometry techniques, and acquired genome-wide methylation data using bisulfite conversion and a microarray platform. We compared molecular profiles across the iSGS and control groups, and with respect to clinical course in the iSGS group. Eight of the 12 iSGS patients underwent subsequent blood collection and plasma isolation for further assessment. RESULTS: Proteomic analysis revealed 42 differentially abundant proteins in the iSGS biopsies compared to controls, inferring enrichment of biological pathways associated with early wound healing, innate immunity, matrix remodeling, and metabolism. Proteome-based hierarchical clustering organized patients into two iSGS and one control subgroups. Methylation analysis revealed five hypermethylated genes in the iSGS biopsies compared to controls, including the biotin recycling enzyme biotinidase (BTD). Follow-up analysis showed elevated plasma BTD activity in iSGS patients compared to both controls and published normative data. CONCLUSION: iSGS exhibits distinct proteomic and genomic methylation signatures. These signatures expand current understanding of the iSGS phenotype, support the possibility of disease subgroups, and should inform the direction of future experimental studies. LEVEL OF EVIDENCE: Not applicable Laryngoscope, 131:E540-E546, 2021.

Antitumor effect of insulin-like growth factor-1 receptor inhibition in head and neck squamous cell carcinoma.

OBJECTIVES: The insulin-like growth factor-1 receptor (IGF1R) has been implicated in therapeutic resistance in head and neck squamous cell carcinoma (HNSCC), and small molecule tyrosine kinase inhibitors (TKIs) of IGF1R activity may have anticancer activity. Therefore, the relationship between survival and IGF1R expression was assessed for oral cavity (OC) cancer, and the antitumor effects of two IGF1R-TKIs, OSI-906 and BMS-754807, were evaluated in HNSCC cell lines in vitro. METHODS: Clinical outcome data and tissue microarray immunohistochemistry were used to generate IGF1R expression-specific survival curves. Immunoblot, alamarBlue proliferation assay, trypan blue exclusion viability test, clonogenic assay, flow cytometry, and reverse phase protein array (RPPA) were used to evaluate in vitro responses to IGF1R-TKIs. RESULTS: For patients with stage III/IV OCSCC, higher IGF1R expression was associated with poorer overall 5-year survival (P = 0.029). Both BMS-754807 and OSI-906 caused dose-dependent inhibition of IGF1R and Akt phosphorylation and inhibited proliferation; BMS-754807 was more potent than OSI-906. Both drugs reduced HNSCC cell viability; only OSI-906 was able to eliminate all viable cells at 10 µM. The two drugs similarly inhibited clonogenic cell survival. At 1 µM, only BMS-754807 caused a fourfold increase in the basal apoptotic rate. RPPA demonstrated broad effects of both drugs on canonical IGF1R signaling pathways and also inhibition of human epidermal growth factor receptor-3 (HER3), Src, paxillin, and ezrin phosphorylation. CONCLUSION: OSI-906 and BMS-754807 inhibit IGF1R activity in HNSCC cell lines with reduction in prosurvival and proliferative signaling and with concomitant antiproliferative and proapoptotic effects. Such antagonists may have utility as adjuvants to existing therapies for HNSCC. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1470-1478, 2020.

Voice Outcomes in Surgical Repair of Zenker's Diverticulum.

The purpose of the study was to define the impact of Zenker's diverticula on voice and potential benefit from repair. Retrospective chart review of prospectively collected data from eleven patients with a Zenker's diverticulum treated surgically in a tertiary care center from November 2014 through January 2016. The voice handicap index-10 (VHI-10) and eating assessment tool-10 (EAT-10) questionnaires were collected as part of pre- and post-operative evaluation, with an average post-operative follow-up of 69 days. Surgical techniques included: trans-oral endoscopic diverticulotomy with laser assistance, or trans-cervical approach with diverticulopexy or diverticulectomy. The primary outcome was subjective voice improvement. Secondary outcome was swallowing function improvement. Statistical analysis was performed using Wilcoxon Signed-Ranks and Mann-Whitney U tests. In patients undergoing surgical treatment of Zenker's diverticula, there is a statistically significant improvement (p = 0.001) in patient-reported dysphagia symptoms measured by the EAT-10. There is also a clinically relevant improvement in subjective voice quality (average pre-operative total 6.55, post-operative 2.09, p = 0.022) as measured by the VHI-10. Many patients suffering from Zenker's diverticula experience subjective voice handicap. Most note improvement in voice quality post-operatively, which we were able to quantify using the voice handicap index. We consider this a relevant consideration in pre-operative evaluation.

Microvascular anastomosis simulation using a chicken thigh model: Interval versus massed training.

OBJECTIVES/HYPOTHESIS: To compare the effectiveness of massed versus interval training when teaching otolaryngology residents microvascular suturing on a validated microsurgical model. STUDY DESIGN: Otolaryngology residents were placed into interval (n = 7) or massed (n = 7) training groups. The interval group performed three separate 30-minute practice sessions separated by at least 1 week, and the massed group performed a single 90-minute practice session. Both groups viewed a video demonstration and recorded a pretest prior to the first training session. A post-test was administered following the last practice session. METHODS: At an academic medical center, 14 otolaryngology residents were assigned using stratified randomization to interval or massed training. Blinded evaluators graded performance using a validated microvascular Objective Structured Assessment of Technical Skill tool. The tool is comprised of two major components: task-specific score (TSS) and global rating scale (GRS). Participants also received pre- and poststudy surveys to compare subjective confidence in multiple aspects of microvascular skill acquisition. RESULTS: Overall, all residents showed increased TSS and GRS on post- versus pretest. After completion of training, the interval group had a statistically significant increase in both TSS and GRS, whereas the massed group's increase was not significant. Residents in both groups reported significantly increased levels of confidence after completion of the study. CONCLUSIONS: Self-directed learning using a chicken thigh artery model may benefit microsurgical skills, competence, and confidence for resident surgeons. Interval training results in significant improvement in early development of microvascular anastomosis skills, whereas massed training does not. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:2490-2494, 2017.

Use of the Teres Major Muscle in Chimeric Subscapular System Free Flaps for Head and Neck Reconstruction.

IMPORTANCE: We present what we believe to be the first case series in which the teres major muscle is used as a free flap in head and neck reconstruction. OBJECTIVES: To describe our experience with the teres major muscle in free flap reconstruction of head and neck defects and to identify advantages of this approach. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed at 2 tertiary care centers between February 1, 2007, and June 30, 2012. Data analysis was conducted from July 31, 2014, through December 1, 2014. INTERVENTION: Teres major muscle free flap for use in head and neck reconstruction. MAIN OUTCOMES AND MEASURES: Indications for use, complications, and outcomes including donor site morbidity. RESULTS: The teres major free flap was used in 11 patients as a component of chimeric subscapular system free flaps for a variety of complex head and neck defects. The teres major muscle was used to fill soft-tissue defects of the neck, face, and nasal cavity; it provided substantial soft-tissue volume but was less bulky than the latissimus dorsi muscle. The teres major muscle was also used to provide protection for vascular anastomoses and/or great vessels and to enhance soft-tissue coverage of the mandibular reconstruction plate. In addition, the muscle was selected as a substrate for skin grafting where inadequate neck skin remained. Flap survival occurred in 10 of 11 flaps (91%). Two flaps (18%) demonstrated venous congestion that was managed successfully. Two patients (18%) developed minor recipient-site complications (submental fistula and infection with recurrent wound dehiscence and plate exposure). All donor sites healed well, with chronic, mild shoulder pain noted in 2 patients (18%) and no postoperative seromas observed in any patient. CONCLUSIONS AND RELEVANCE: Addition of the teres major muscle to a subscapular system free flap is an option for reconstruction of a variety of complex head and neck defects, particularly when a moderate amount of soft tissue is required. In select cases, the teres major muscle may have advantages over the latissimus dorsi muscle.

Nanoimmunoassay to Detect Responses in Head and Neck Cancer: Feasibility in a Mouse Model.

OBJECTIVE: To demonstrate the feasibility of detecting and quantifying extracellular signal-related kinase (ERK) phosphorylation status using nanoimmunoassay (NIA). STUDY DESIGN: Analyses using Cal27, SCC25, and OSC19 head and neck squamous carcinoma cell lines in vitro and in a murine xenograft model. SUBJECTS AND METHODS: NIA and immunoblot were performed on whole-cell lysates, tumor lysates, and fine-needle aspirate biopsies to detect ERK phosphorylation states. RESULTS: Using NIA, all 6 isoforms of ERK1/2, including nonphosphorylated, monophosphorylated, and diphosphorylated species, could be reliably detected, distinguished, and quantified in a single assay using a single antibody. In vitro treatment of Cal27 cells with the epidermal growth factor receptor inhibitor gefitinib abolished phospho-ERK detection by immunoblot but resulted in residual detectable species by NIA. Residual phospho-ERK in gefitinib-treated cells could be further reduced by the addition of the insulin-like growth factor 1 receptor inhibitor OSI-906; this correlated with an additional decrease in proliferation over gefitinib alone. In a pilot study of 4 murine xenograft tumors, NIA performed on tumor lysates and fine-needle aspirate biopsies demonstrated altered ERK profiles after 2 days of gefitinib treatment compared with untreated mice. CONCLUSION: NIA offers a novel approach to quantitating the activation state of signaling molecules such as ERK in nanoscale in vitro and in vivo samples across a wide dynamic range. As such, it has potential to provide molecular diagnostic information before, during, and after treatment using a minimally invasive technique. Further study is warranted to determine its utility in assessing signaling proteins as biomolecular outcome predictors in clinical trials.

Imaging prevalence of sigmoid sinus dehiscence among patients with and without pulsatile tinnitus.

OBJECTIVE: Define the radiographic prevalence of sigmoid sinus diverticulum or dehiscence (SSDD) in patients with and without pulsatile tinnitus (PT). STUDY DESIGN: Case series with chart review. SETTING: Tertiary care university medical center. SUBJECTS: Patients imaged between January 1, 2003, and December 31, 2012. METHODS: Two groups were evaluated for SSDD. The first ("PT") included patients whose radiology report indicated a clinical history of PT (n = 37 symptomatic ears in 30 patients). The second ("non-PT") included all patients undergoing temporal bone high resolution CT (HRCT) between November 2011 and November 2012 (n = 308 ears in 164 patients) for reasons other than pulsatile tinnitus. Primary outcome measure was the radiographic presence of SSDD. Covariates including age, gender, body mass index (BMI), and audiometric data were analyzed by independent t tests and Fisher's exact test. RESULTS: Within the PT group, SSDD was identified in 24% of ears (9/37) and 23% of patients (7/30); all SSDD patients were female (P = .024). Patients with SSDD were significantly younger (P = .037). SSDD more frequently caused objective tinnitus (P = .016). There was no difference in average BMI between those with and those without SSDD. In the non-PT group, SSDD was identified in 2 (both female) of 164 patients (1.2%; 0.6% of ears). The difference in SSDD prevalence between groups was significant (P < .0001). CONCLUSIONS: The prevalence of SSDD in patients with PT was 23%. Among patients with PT, those with SSDD were younger, exclusively female, and presented with objective tinnitus. The prevalence of SSDD among asymptomatic patients in 1 year was 1.2%.

Utility of abdominal imaging to assess for liver metastasis in patients with head and neck cancer and abnormal liver function tests.

PURPOSE: To determine the utility of abdominal imaging to further evaluate abnormal pre-operative liver function tests (LFTs) in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Records of patients evaluated by the head and neck surgery service from January 2004 through December 2009 were reviewed. For patients with abnormal alkaline phosphatase, alanine transaminase, or aspartate transaminase, subsequent abdominal imaging was assessed. RESULTS: Of the 862 patients with HNSCC who had documented LFTs, 109 (12.6%) had one or more abnormal values. In the same time period, LFTs were also obtained on 361 patients with benign head and neck tumors; of these, 40 (11.1%) had abnormalities. Of the 109 patients with HNSCC and abnormal LFTs, 78 (71.6%) underwent abdominal imaging (ultrasound, CT, MRI, or PET/CT). Overall, liver metastasis was demonstrated in only 1 of 109 patients with abnormal LFTs (0.92%) and in only 1 of 862 patients with HNSCC (0.12%). CONCLUSIONS: While HNSCC patients rarely present with liver metastasis, they often have abnormal LFTs. Although the presence of liver metastasis can dramatically change patient management, the yield of follow-up liver imaging for all patients with elevated LFTs is exceedingly low. Thus, the use of risk-stratified abdominal imaging may be prudent and cost effective in a select group of patients in whom distant metastasis is more likely. However, characteristics of this group are difficult to define given the rarity of liver metastasis in HNSCC.