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.

The incidence of early onset oral tongue squamous cell carcinoma (OTC) has been increasing in the United States, and no clear etiology has been identified. Studies on this topic have generally been small and presented varied results. The goal of this review is to analyze and synthesize the literature regarding early onset OTC risk factors, outcomes, and molecular analyses within the US. To date, studies suggest that early onset OTC patients tend to have less heavy cigarette use than typical onset patients, but there may be an association between early onset OTC and smokeless tobacco (chewing tobacco and snuff) use. Early onset OTC is associated with similar or possibly improved survival compared to typical onset OTC. There has been no evidence to support a significant role for human papillomavirus in development of early onset OTC. Further research with larger cohorts of these patients is needed to better characterize this disease entity.

Objectives The social determinants of health affect a wide range of health outcomes and risks. To date, there have been no studies evaluating the impact of social determinants of health on laryngotracheal stenosis (LTS). We sought to describe the social determinants in a cohort of LTS patients and explore their association with treatment outcome. Methods Subjects diagnosed with LTS undergoing surgical procedures between 2013 and 2018 were identified. Matched controls were identified from intensive care unit (ICU) patients who underwent intubation for greater than 24 hours. Medical comorbidities, stenosis characteristics, and patient demographics were abstracted from the clinical record. Tracheostomy at last follow‐up was recorded from the medical record and phone calls. Socioeconomic data was obtained from the American Community Survey. Results One hundred twenty‐two cases met inclusion criteria. Cases had significantly lower education compared to Tennessee (P = .009) but similar education rates as ICU controls. Cases had significantly higher body mass index (odds ratio [OR]: 1.04, P = .035), duration of intubation (OR: 1.21, P < .001), and tobacco use (OR: 1.21, P = .006) in adjusted analysis when compared to controls. Tracheostomy dependence within the case cohort was significantly associated with public insurance (OR: 1.33, P = .016) and chronic obstructive pulmonary disease (OR: 1.34, P = .018) in adjusted analysis. Conclusion Intubation practices, medical comorbidities and social determinants of health may influence the development of LTS and tracheostomy dependence after treatment. Identification of at‐risk populations in ICUs may allow for prevention of tracheostomy dependence through the use of early tracheostomy and specialized follow‐up. Level of Evidence Level 3, retrospective review comparing cases and controls Laryngoscope, 130:1000–1006, 2020

Background Incidence of oral tongue squamous cell carcinoma (OTC) is rising among those under age 50 years. The etiology is unknown. Methods A total of 395 cases of OTC diagnosed and/or treated at Vanderbilt University Medical Center between 2000 and 2017 were identified. Of those, 113 (28.6%) were early onset (age < 50 years). Logistic regression was used to identify factors associated with early onset OTC. Cox proportional hazards models evaluated survival and recurrence. Results Compared to typical onset patients, patients with early onset OTC were more likely to receive multimodality treatment (surgery and radiation; adjusted odds ratio [aOR], 2.7; 95% confidence interval [CI], 1.2‐6.3) and report a history of snuff use (aOR, 5.4; 95% CI, 1.8‐15.8) and were less likely to report a history of cigarette use (aOR, 0.5; 95% CI, 0.2‐0.9). Early onset patients had better overall survival (adjusted hazard ratio, 0.6). Conclusions This is the largest study to evaluate factors associated with early onset OTC and the first to report an association with snuff.

Background The incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing among younger birth cohorts. The etiology of early‐onset OTSCC (diagnosed before the age of 50 years) and cancer driver genes remain largely unknown. Methods The Sequencing Consortium of Oral Tongue Cancer was established through the pooling of somatic mutation data of oral tongue cancer specimens (n = 227 [107 early‐onset cases]) from 7 studies and The Cancer Genome Atlas. Somatic mutations at microsatellite loci and Catalog of Somatic Mutations in Cancer mutation signatures were identified. Cancer driver genes were identified with the MutSigCV and WITER algorithms. Mutation comparisons between early‐ and typical‐onset OTSCC were evaluated via linear regression with adjustments for patient‐related factors. Results Two novel driver genes (ATXN1 and CDC42EP1) and 5 previously reported driver genes (TP53, CDKN2A, CASP8, NOTCH1, and FAT1) were identified. Six recurrent mutations were identified, with 4 occurring in TP53. Early‐onset OTSCC had significantly fewer nonsilent mutations even after adjustments for tobacco use. No associations of microsatellite locus mutations and mutation signatures with the age of OTSCC onset were observed. Conclusions This international, multicenter consortium is the largest study to characterize the somatic mutational landscape of OTSCC and the first to suggest differences by age of onset. This study validates multiple previously identified OTSCC driver genes and proposes 2 novel cancer driver genes. In analyses by age, early‐onset OTSCC had a significantly smaller somatic mutational burden that was not explained by differences in tobacco use. Lay Summary This study identifies 7 specific areas in the human genetic code that could be responsible for promoting the development of tongue cancer. Tongue cancer in young patients (under the age of 50 years) has fewer overall changes to the genetic code in comparison with tongue cancer in older patients, but the authors do not think that this is due to differences in smoking rates between the 2 groups. The cause of increasing cases of tongue cancer in young patients remains unclear.

Objectives To measure disease-free, disease-specific, and overall survival among patients with T4aN0M0 mandibular gingival squamous cell carcinoma who were treated with surgery alone. Study Design Case series with chart review. Setting Tertiary care center. Subjects and Methods A retrospective chart review was performed of all adult patients treated surgically with an oral cavity composite resection between January 2005 and March 2017. Among other data, patient preoperative characteristics were recorded (eg, age, sex, smoking history, alcohol use, and clinical stage); operative notes were reviewed to determine tumor subsite involvement, reconstruction method, and intraoperative surgical complications; and pathology reports were evaluated for various pathologic findings. Survival outcomes were determined with Kaplan-Meier analysis. Results The mean follow-up was 18.5 months (range, 0.1-100). The 1- and 5-year disease-free survival rates were 90.5% and 84.5%, respectively, while the 1- and 5-year disease-specific survival rates were 87.8% and 81.9%. The 1- and 5-year overall survival rates were 86.4% and 80.6%. Conclusions Patients with T4aN0M0 squamous cell carcinoma of the mandibular gingiva treated with surgery alone have a 5-year overall survival of 80.6%. Treatment with surgery alone obviates morbidities associated with adjuvant therapy while upholding survival outcomes.

To determine if smaller endotracheal tubes are noninferior to larger endotracheal tubes with respect to critical illness outcomes. DESIGN, SETTING, AND PARTICIPANTSThis propensity score-matched retrospective cohort study included all adult patients who underwent endotracheal intubation in the emergency department or intensive care unit and received mechanical ventilation for at least 12 hours from June 2020 to November 2020 at a single tertiary referral academic medical center. EXPOSURES Endotracheal intubation.MAIN OUTCOMES AND MEASURES Propensity score-matched analyses were performed with respect to the primary end point of 30-day all-cause in-hospital survival as well as the secondary end points of duration of invasive mechanical ventilation, length of hospital stay, mean peak inspiratory pressure, 30-day readmission, need for reintubation, and need for tracheostomy or gastrostomy tube placement.RESULTS Overall, 523 participants (64%) were men and 291 (36%) were women. Of these, 814 patients were categorized into 3 endotracheal tube groups: small for height (n = 182), appropriate for height (n = 408), and large for height (n = 224). There was not a significant difference in 30-day all-cause in-hospital survival between groups ([HR, 1.1; 95% CI, 0.7-1.7] for small vs appropriate; [HR, 1.1; 95% CI, 0.7-1.6] for large vs appropriate). Patients with small-for-height endotracheal tubes had longer intubation durations (mean difference, 32.5 hrs [95% CI, 6.4-58.6 hrs]) compared with patients with appropriate-for-height tubes.CONCLUSIONS AND RELEVANCE Despite differences in intubation duration, the results of this cohort study suggest that smaller endotracheal tube sizes are not associated with impaired survival or recovery from critical illness. They support future prospective exploration of the association of smaller endotracheal tube sizes with recovery from critical illness.

and mechanical ventilation are life-saving treatments for acute respiratory failure but are complicated by significant rates of dyspnea and dysphonia after extubation. Unilateral vocal fold immobility (UVFI) after extubation can alter respiration and phonation, but its incidence, risk factors, and pathophysiology remain unclear.OBJECTIVES To determine the incidence of UVFI after prolonged (>12 hours) mechanical ventilation in a medical intensive care unit and investigate associated clinical risk factors for UVFI after prolonged mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTSThis subgroup analysis of a prospective cohort study was conducted in a single-center medical intensive care unit from August 17, 2017, through May 31, 2018, among 100 consecutive adult patients who were intubated for more than 12 hours. Patients were identified within 36 hours of extubation and recruited for study enrollment. Those with an established tracheostomy prior to mechanical ventilation, known laryngeal or tracheal pathologic characteristics, or a history of head and neck radiotherapy were excluded.EXPOSURE Invasive mechanical ventilation via an endotracheal tube. MAIN OUTCOMES AND MEASURESThe incidence of UVFI as determined by flexible nasolaryngoscopy.RESULTS One hundred patients (62 men [62%]; median age, 58.5 years [range, 19.0-87.0 years]) underwent endoscopic evaluation after extubation. Seven patients had UVFI, of which 6 cases (86%) were left sided. Patients with hypotension while intubated (odds ratio [OR], 10.8; 95% CI, 1.6 to ϱ), patients requiring vasopressors while intubated (OR, 16.7; 95% CI, 2.4 to ϱ), and patients with a preadmission diagnosis of peripheral vascular disease (OR, 6.2; 95% CI, 1.2-31.9) or coronary artery disease (OR, 5.1; 95% CI, 1.0-25.5) were more likely to develop UVFI.CONCLUSIONS AND RELEVANCE Unilateral vocal fold immobility occurred in 7 of 100 patients in the medical intensive care unit who were intubated for more than 12 hours. Unilateral vocal fold immobility was associated with inpatient hypotension and preadmission vascular disease, suggesting that ischemia of the recurrent laryngeal nerve may play a role in disease pathogenesis.