Tissue-Engineered Implant for Hemilaryngectomy Reconstruction with Recurrent Laryngeal Nerve Injury.

OBJECTIVE: Laryngeal cancer resections often require excision of portions of the larynx along with sacrifice of the ipsilateral recurrent laryngeal nerve (RLN). In such cases, there are no reconstructive options that reliably restore laryngeal function, rendering patients with severe functional impairment. To address this unmet clinical need, we extend our evaluation of a 3-implant mucosal, muscle, cartilage reconstruction approach aimed at promoting functional laryngeal restoration in a porcine hemilaryngectomy model with ipsilateral RLN transection. METHODS: Six Yucatan mini-pigs underwent full-thickness hemilaryngectomies with RLN transection followed by transmural reconstruction using fabricated collagen polymeric mucosal, muscle, and cartilage replacements. To determine the effect of adding therapeutic cell populations, subsets of animals received collagen muscle implants containing motor-endplate-expressing muscle progenitor cells (MEEs) and/or collagen cartilage implants containing adipose stem cell (ASC)-derived chondrocyte-like cells. Acoustic vocalization and laryngeal electromyography (L-EMG) provided functional assessments and histopathological analysis with immunostaining was used to characterize the tissue response. RESULTS: Five of six animals survived the 4-week postoperative period with weight gain, airway maintenance, and audible phonation. No tracheostomy or feeding tube was required. Gross and histological assessments of all animals revealed implant integration and regenerative remodeling of airway mucosa epithelium, muscle, and cartilage in the absence of a material-mediated foreign body reaction or biodegradation. Early voice and L-EMG data were suggestive of positive functional outcomes. CONCLUSION: Laryngeal reconstruction with collagen polymeric mucosa, muscle, and cartilage replacements may provide effective restoration of function after hemilaryngectomy with RLN transection. Future preclinical studies should focus on long-term functional outcomes. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Outcome Reporting in Prospective Studies Evaluating Neurostimulation for Obstructive Sleep Apnea.

OBJECTIVE: Due to the controversy surrounding the appropriate outcomes in neurostimulation, we sought to systematically describe ways in which polysomnography and apnea-hypopnea index are reported in prospective studies involving unilateral hypoglossal nerve stimulation. DATA SOURCES: MEDLINE (Ovid), Embase (Ovid), Cochrane Library, and Scopus. REVIEW METHODS: Following the Preferred Reporting items of Systematic Reviews and Meta-analysis (PRISMA) Statement guidelines, a systematic two-reviewer system was used for study screening and quality assessment. Articles that met inclusion criteria were included. Quality was evaluated with either the Newcastle-Ottawa Quality Assessment Scale or the Covidence risk-of-bias tool. RESULTS: Fifteen studies met the inclusion criteria, which included 14 prospective cohort studies and one randomized controlled trial. Titration polysomnography was the primary sleep study used to acquire data in five of the studies compared to only three studies employing exclusively non-titration polysomnography to report outcomes. Three studies compiled data from two or more sleep studies to report a single apnea-hypopnea index. Within the 15 studies, non-titration apnea-hypopnea index was the most reported type (five studies). Titration apnea-hypopnea index was used to report outcomes in one study. Five studies did not specify what type of apnea-hypopnea index was employed to report treatment effectiveness. CONCLUSION: The reported sleep studies and corresponding apnea-hypopnea indices were highly variable across the studies. Because of the high degree of heterogeneity, future research would benefit from consistent use of a standardized apnea-hypopnea index to report outcomes related to hypoglossal nerve stimulation. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Scaffold-Forming Collagen and Motor-Endplate Expressing Muscle Cells for Porcine Laryngoplasty.

OBJECTIVE: Vocal fold paralysis impairs quality of life, and no curative injectable therapy exists. We evaluated injection of a novel in situ polymerizing (scaffold-forming) collagen in the presence and absence of muscle-derived motor-endplate expressing cells (MEEs) to promote medialization and recurrent laryngeal nerve (RLN) regeneration in a porcine model of unilateral vocal fold paralysis. METHODS: Twelve Yucatan minipigs underwent right RLN transection. Autologous muscle progenitor cells were isolated from muscle biopsies, differentiated, and induced to MEEs. Three weeks after RLN injury, animals received injections of collagen, collagen containing MEEs, or saline into the paralyzed right vocal fold. Stimulated laryngeal electromyography and acoustic vocalization were used for function assessments. Larynges were harvested and underwent histologic, gene expression, and further quantitative analyses. RESULTS: Injections were well-tolerated, with the collagen scaffold showing immunotolerance and collagen-encapsulated MEEs remaining viable. Collagen-treated paralyzed vocal folds showed increased laryngeal adductor muscle volumes relative to that of the uninjured side, with those receiving MEEs and collagen showing the highest volumes. Muscles injected with MEEs and collagen demonstrated increased expression of select neurotrophic (BDNF and NTN1), motor-endplate (DOK7, CHRNA1, and MUSK), and myogenic (MYOG and MYOD) related genes relative to saline controls. CONCLUSION: In a porcine model of unilateral vocal fold paralysis, injection of in situ polymerizing collagen in the absence and presence of MEEs enhanced laryngeal adductor muscle volume, modulated expression of neurotrophic and myogenic factors, and avoided adverse material-mediated immune responses. Further study is needed to determine long-term functional outcomes with this novel therapeutic approach. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

A Protocolized Approach to Awake Endoscopy With Advanced Programming to Optimize Hypoglossal Nerve Stimulation.

Hypoglossal nerve stimulation is a treatment option for patients with obstructive sleep apnea who are intolerant to positive airway pressure therapy. In the post-implant period, awake endoscopy with advanced programming (AEAP) can be employed to optimize apnea-hypopnea index reduction and/or patient comfort and usage. The report herein describes awake endoscopy with AEAP as a guide to providers involved in post-implant care. The first 5 consecutive patients were reviewed to provide general understanding of outcomes and safety when implementing such a protocolized approach.

Evolving microbial patterns of acute mastoiditis in pediatric patients undergoing mastoidectomy.

OBJECTIVE: To investigate the microbial patterns and clinical outcomes of pediatric patients undergoing mastoidectomy for acute coalescent mastoiditis and to identify factors associated with poor outcomes and/or prolonged treatment. STUDY DESIGN: Monocentric retrospective cohort study. SETTING: Tertiary referral pediatric hospital in Indiana. METHODS: By cross-referencing database data from the Pediatric Health Information System (PHIS) querying for all inpatient stays (patients younger than eighteen) with a diagnostic code of mastoiditis between January 1st, 2010 and August 31, 2019, and the electronic health record (Cerner) for Riley Hospital for Children, 46 patients with mastoidectomy were included. A two-tailed T-test was used to evaluate continuous parametric data. Statistical significance was determined as P < 0.05. For continuous variables, data was analyzed using continuous logistic regression. A criteria of p > 0.1 was used for inclusion in the multivariate regression. RESULTS: Inclusion criteria was met by 46 patients. From 2010 to 2019, S. pyogenes and S. pneumoniae were the most common bacteria, each isolated in 11 of 42 bacterial isolates (26.2%). There was no growth in 35.4% (17/48) of intra-operative wound cultures. On univariate analysis, patients with negative cultures had longer length of hospital stay (LOS) (7.7 days [6.5] vs. 4.3 [2.8]; p = 0.018) as well as higher rates of PICC (peripherally inserted central catheter) placement (53.3% vs. 19.4%; p = 0.021). There was a statistically significant difference in terms of gender (p = 0.021), with 15 males and 16 females in the positive culture cohort and 13 males and 2 females in the negative culture cohort. On multivariate analysis, which included gender, PICC placement, both intracranial and extracranial complications, duration of antibiotics, and LOS, female gender was the only significant predictor of positive culture status (p = 0.039). CONCLUSION: S. pyogenes and S. pneumoniae were the predominant etiologic agents in acute coalescent mastoiditis between 2010 and 2019, and negative wound cultures were associated with worse clinical outcomes.