Lott, David G

Objective To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short‐term surgical complications requiring a return to the operating room and 30‐day mortality utilizing data from the Multi‐Institutional Study on Tracheotomy (MIST). Methods A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. Results Among the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy ( p = 0.001). Morbidly obese patients (BMI ≥35 kg/m 2 ) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%–75%]: 11.0 days [7–17 days] versus 9.0 days [5–14 days]; p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days ( p = 0.12) or mortality ( p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%–75%]: 10.0 days [6–15 days] versus 10.0 days [6–15 days]; p = 0.36). Conclusion BMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. Level of Evidence 3 Laryngoscope , 134:4674–4681, 2024

ObjectivesThere is an absence of data in the literature regarding methods to improve the patient experience during the performance of awake in‐office laryngeal injections. This study sought to evaluate whether the use of local anesthetic or a vibrating instrument decreased overall pain experienced by patients with laryngeal dystonia, frequently referred to as spasmodic dysphonia (SD), undergoing transcervical botulinum toxin injections.MethodsThis was an unblinded, prospective randomized control trial with a crossover design where each patient received transcutaneous transcricothyroid injection of botulinum toxin with alternating use of no anesthesia, local anesthesia (2% lidocaine in 1:100,000 epinephrine), and vibrating instrument in three consecutive laryngeal injections to treat adductor SD. Patients were randomized to the order they received these treatments. Patients measured pain on a 0–10 visual analogue scale (VAS) and selected their preferred technique after receiving all three analgesic modalities.ResultsThirty‐two patients completed the study. There was no statistically significant difference in pain between the three analgesic techniques (p = 0.38). The most preferred analgesic technique was the vibrating wand (44% (14/32)). Lidocaine was the second most preferred (37% (12/32)) and 19% (6/32) of patients preferred nothing. When combining the wand and nothing groups, 63% of patients preferred one of these two methods (95% exact CI: 44%–79%).ConclusionThere was no statistically significant difference in median pain experienced by patients during laryngeal botulinum toxin injection between these different analgesic modalities. More than half of the patients selected a preference for a technique that did not include lidocaine. This data supports individualization of analgesia during transcutaneous laryngeal injections.Level of Evidence2 Laryngoscope, 134:2277–2281, 2024

Objectives: Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between patients with iSGS and controls, and between tracheal and subglottic tissue within patients. Methods: RNA sequencing was conducted on biopsied mucosal samples collected from subglottic and tracheal (in-patient control) regions in iSGS patients, and from subglottis in controls. The gene expression differences were validated on a protein level by (1) staining the tissue samples obtained from a second cohort of patients and controls; and (2) in vitro functional assays using primary subglottic epithelial cells from both iSGS patients and healthy donors. Results: We found 7 upregulated genes in the subglottic region of iSGS patients relative to both the tracheal mucosa and subglottic region of controls. A gene ontology enrichment analysis found that the epithelial cell differentiation and cornification pathways are significant, involving specifically 3 of the genes: involucrin ( IVL), small proline rich protein 1B ( SPRR1B), and keratin 16 ( KRT16). Involvement of these pathways suggests squamous metaplasia of the epithelium. Histological analyses of epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of the samples from iSGS patients and in 25% from controls. Immunohistochemical evaluation of the samples presented with squamous epithelium revealed increased expression of the protein encoded by SPRR1B, hyperproliferative basal cells, shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. Cultured primary subglottic epithelial cells from iSGS patients had higher proliferation rates compared to healthy donors and squamous metaplastic differentiation formed thinner epithelia with increased expression proteins encoded by INV, SPRR1B, and KRT16, suggesting intrinsic dysfunction of basal cells in iSGS. Conclusions: Abnormal squamous differentiation of epithelial cells may contribute to the pathogenesis of iSGS. Patients having metaplastic epithelial phenotype may be sensitive to drugs that reverse it to a normal phenotype.

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

Objectives: To date, there are no specific guidelines on antithrombotic therapy (ATT) management, which includes both anticoagulation and antiplatelet medications, for open tracheostomy. The objective of this study was to evaluate whether the use of perioperative antithrombotic medication during open tracheostomy influences the incidence of perioperative or postoperative complications. Methods: A retrospective review was conducted of all patients who underwent open tracheostomies at a tertiary care medical center from January 2015 to December 2019. Charts were reviewed for demographics, comorbidities, indication for tracheostomy, ATT use, operative details, and complications. Results: A total of 217 tracheostomies were evaluated for this study, of which 148 (68.2%) were not on ATT and 69 (31.8%) were on ATT during surgery. No significant difference was observed based on ATT status in perioperative bleeding ( P = .983), postoperative bleeding ( P = .24), or median days to decannulation ( P = .5986). ATT patients were 2.67 times more likely to experience 30-day mortality than those non-ATT patients ( P = .035). There was only one death due to hemorrhage in the ATT group. This was unrelated to the tracheostomy. This compares to 2 hemorrhage-related deaths in those not on ATT. Conclusion: There was no significant difference in perioperative or postoperative bleeding based on ATT use. Patients on ATT were significantly more likely to experience 30-day mortality, however only one death was due to hemorrhage in the ATT group and was unrelated to tracheostomy. Therefore, continued perioperative ATT use appears to be safe when performing open tracheostomy. Level of Evidence: 4

ObjectivesTo evaluate the safety and clinical effectiveness of transoral laser microsurgery (TLM) with potassium‐titanyl‐phosphate (KTP) laser ablation for glottic neoplasms.Data SourceMEDLINE via PubMed, SCOPUS, Web of Science, and Cochrane Library.Review MethodsA systematic review and meta‐analysis of studies assessing the safety and efficacy of KTP laser therapy in patients with early‐stage glottic neoplasms.ResultsEight studies were included. After an average follow‐up of 3.3 years, the overall survival and disease‐free survival for patients who underwent KTP were 90.7% (95% CI 85%–96.5%) and 98.5% (95% CI 97.3%–99.8%), respectively. In the single‐arm meta‐analysis, the pooled estimate of recurrence was 7.7% (95% CI 3.4%–12%). The overall voice handicap index (VHI) estimate attributed to KTP in the single‐arm meta‐analysis was 6.76 (95% CI [3.05, 10.48]) and 5.21 (95% CI [2.86, 7.56]) within 6 months and after a one‐year follow‐up, respectively.ConclusionKTP laser ablation is a safe and effective method for treating patients with early glottic neoplasms. Laryngoscope, 133:1806–1814, 2023

Objectives: Bullous pemphigoid has previously been linked to radiotherapy, but here we report the first case of MMP suspected to be a consequence of RT. Methods: The patient described is an 85-year-old male who underwent RT to treat squamous cell carcinoma of the palatine tonsil. Shortly after therapy, the patient developed blisters with worsening dyspnea and dysphonia. Results: This patient was successfully treated with a combination of oral immunosuppressants and surgical intervention. Conclusion: This incident underscores that not all episodes of mucosal ulceration following radiation are a result of mucositis and MMP should be considered in the differential. Level of evidence: Level 4.

Objectives/HypothesisDevelop a patient‐specific tissue engineered construct for laryngeal reconstruction following a partial laryngectomy.Study DesignBench and animal research.MethodsA construct made from a porous polyethylene scaffold shaped in a canine‐specific configuration and seeded with autologous canine adipose‐derived stem cells in fibrin glue was implanted in a canine following a partial laryngectomy. After 1 year, the construct was first evaluated in vivo with high‐speed imaging and acoustic–aerodynamic measures. It was then explanted and evaluated histologically.ResultsThe canine study at 1 year revealed the construct provided voicing (barking) with acoustic and aerodynamic measures within normal ranges. The canine was able to eat and breathe normally without long‐term support. The construct was integrated with epithelialization of all areas except the medial portion of the vocal fold structure. No anti‐infective agents were needed after the standard perioperative medications were completed.ConclusionThis study provided a successful first step toward developing a patient‐specific composite construct for patients undergoing partial laryngectomies.Level of EvidenceNA Laryngoscope, 132:S1–S11, 2022

ObjectivesThis study was designed to evaluate significant differences in treatment and survival outcomes between patients with T1a and T1b glottic cancer.MethodsPatients within the SEER Research Plus, 18 Registries dataset who were diagnosed with Stage I T1a or T1b cancer of the glottis between 2004 and 2015 were included in this study. Data prior to 2004 could not be included, as the SEER database did not distinguish between T1a and T1b glottic cancer until that year.ResultsThe 5‐year disease‐specific survival for T1a patients was significantly better than that of patients diagnosed with T1b glottic cancer. Age and year of diagnosis were also independent factors that impacted mortality. More patients who were diagnosed with T1b glottic cancer underwent external beam radiation than those diagnosed with T1a glottic cancer.ConclusionOur data shows that there are several independent factors effecting mortality including T classification, age at time of diagnosis, and year of diagnosis. T1a glottic cancers also show a significantly better prognosis compared with T1b. T1b glottic cancers are much more likely to be treated with primary radiotherapy compared with surgery.Level of Evidence4 Laryngoscope, 132:2187–2193, 2022

Abstract Introduction Several independent studies report an alarming increase in patients younger than 40 being diagnosed with squamous cell carcinoma. There is currently a lack of available data clearly tracking changes in the age distribution of head and neck cancer (HNC) within the United States. This study attempts to elucidate any trends in oral cavity, oropharynx, larynx and hypopharynx cancer age distribution in the United States population from 1975 to 2016. Unlike previous studies, this paper does not track incidence but rather reports proportional changes of prevalence within age cohorts over time. Methods This is a retrospective chart review centred on data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). Each decade interval from 1975 to 2016 displays the proportion of HNC patients, classified by primary tumour subsite, within each age cohort. Results Mean age at diagnosis increased for all subsites except oropharynx. Oropharyngeal cancer was the only subsite to show a decrease in the mean age at diagnosis. In addition, oropharyngeal cancer was the only subsite to demonstrate an overall increase in proportional prevalence, largely due to increased incidence in middle‐age (40–59 years) patients. Cancers of the oral cavity were the only subset to show a true increase in the proportion of young (0–39 years) patients, but its mean age at diagnosis still increased. When stratifying by gender, the proportion of young patients in female HNC cases is higher than the young male proportion. Conclusion Overall, this study demonstrates an increased proportion of older HNC patients that is consistent with the ageing population. Oral cavity cancer demonstrated a true increase in the proportion of young patients, likely due to the increased incidence of young women diagnosed with this cancer. Oropharyngeal cancer was the only subsite to show a decrease in the mean age at diagnosis. The increased proportion of middle‐age patients with oropharyngeal cancer likely reflects the increase in HPV‐related cancers.