Drug delivery systems for wound healing treatment of upper airway injury.

INTRODUCTION: Endotracheal intubation is a common procedure to maintain an open airway with risks for traumatic injury. Pathological changes resulting from intubation can cause upper airway complications, including vocal fold scarring, laryngotracheal stenosis, and granulomas and present with symptoms such as dysphonia, dysphagia, and dyspnea. Current intubation-related laryngotracheal injury treatment approaches lack standardized guidelines, relying on individual clinician experience, and surgical and medical interventions have limitations and carry risks. AREAS COVERED: The clinical and preclinical therapeutics for wound healing in the upper airway are described. This review discusses the current developments on local drug delivery systems in the upper airway utilizing particle-based delivery systems, including nanoparticles and microparticles, and bulk-based delivery systems, encompassing hydrogels and polymer-based approaches. EXPERT OPINION: Complex laryngotracheal diseases pose challenges for effective treatment, struggling due to the intricate anatomy, limited access, and recurrence. Symptomatic management often requires invasive surgical procedures or medications that are unable to achieve lasting effects. Recent advances in nanotechnology and biocompatible materials provide potential solutions, enabling precise drug delivery, personalization, and extended treatment efficacy. Combining these technologies could lead to groundbreaking treatments for upper airways diseases, significantly improving patients' quality of life. Research and innovation in this field are crucial for further advancements.

Identification of temporal shifts of oral bacteria in bone regeneration following mandibular bone defect injury and therapeutic surgery in a porcine model.

BACKGROUND: Considered the second largest and most diverse microbiome after the gut, the human oral ecosystem is complex with diverse and niche-specific microorganisms. Although evidence is growing for the importance of oral microbiome in supporting a healthy immune system and preventing local and systemic infections, the influence of craniomaxillofacial (CMF) trauma and routine reconstructive surgical treatments on community structure and function of oral resident microbes remains unknown. CMF injuries affect a large number of people, needing extensive rehabilitation with lasting morbidity and loss of human productivity. Treatment efficacy can be complicated by the overgrowth of opportunistic commensals or multidrug-resistant pathogens in the oral ecosystem due to weakened host immune function and reduced colonization resistance in a dysbiotic oral microbiome. AIMS: To understand the dynamics of microbiota's community structure during CMF injury and subsequent treatments, we induced supra-alveolar mandibular defect in Hanford miniature swine (n = 3) and compared therapeutic approaches of immediate mandibullar reconstructive (IMR) versus delayed mandibullar reconstructive (DMR) surgeries. METHODS: Using bacterial 16S ribosomal RNA gene marker sequencing, the composition and abundance of the bacterial community of the uninjured maxilla (control) and the injured left mandibula (lingual and buccal) treated by DMR were surveyed up to 70-day post-wounding. For the injured right mandibula receiving IMR treatment, the microbial composition and abundance were surveyed up to 14-day post-wounding. Moreover, we measured sera level of biochemical markers (e.g., osteocalcin) associated with bone regeneration and healing. Computed tomography was used to measure and compare mandibular bone characteristics such as trabecular thickness between sites receiving DMR and IMR therapeutic approaches until day 140, the end of study period. RESULTS: Independent of IMR versus DMR therapy, we observed similar dysbiosis and shifts of the mucosal bacteria residents after CMF injury and/or following treatment. There was an enrichment of Fusobacterium, Porphyromonadaceae, and Bacteroidales accompanied by a decline in Pasteurellaceae, Moraxella, and Neisseria relative abundance in days allotted for healing. We also observed a decline in species richness and abundance driven by reduction in temporal instability and inter-animal heterogeneity on days 0 and 56, with day 0 corresponding to injury in DMR group and day 56 corresponding to delayed treatment for DMR or injury and immediate treatment for the IMR group. Analysis of bone healing features showed comparable bone-healing profiles for IMR vs. DMR therapeutic approach.

Endotracheal tubes with dexamethasone eluting electrospun coating improve tissue mechanical function after upper airway injury.

Corticosteroid-eluting endotracheal tubes (ETTs) were developed and employed in a swine laryngotracheal injury model to maintain airway patency and provide localized drug delivery to inhibit fibrotic scarring. Polycaprolactone (PCL) fibers with or without dexamethasone were electrospun onto the ETT surface PCL-only coated ETTs and placed in native airways of 18 Yorkshire swine. Regular and dexamethasone-PCL coated ETTs were placed in airways of another 18 swine injured by inner laryngeal mucosal abrasion. All groups were evaluated after 3, 7 and 14 days (n = 3/treatment/time). Larynges were bisected and localized stiffness determined by normal indentation, then sequentially matched with histological assessment. In the native airway, tissue stiffness with PCL-only ETT placement increased significantly from 3 to 7 days (p = 0.0016) and 3 to 14 days (p < 0.0001) while dexamethasone-PCL ETT placement resulted in stiffness decreasing from 7 to 14 days (p = 0.031). In the injured airway, localized stiffness at 14 days was significantly greater after regular ETT placement (23.1 ± 0.725 N/m) versus dexamethasone-PCL ETTs (17.10 ± 0.930 N/m, p < 0.0001). Dexamethasone-loaded ETTs were found to reduce laryngotracheal tissue stiffening after simulated intubation injury compared to regular ETTs, supported by a trend of reduced collagen in the basement membrane in injured swine over time. Findings suggest localized corticosteroid delivery allows for tissue stiffness control and potential use as an approach for prevention and treatment of scarring caused by intubation injury.

A Large Cohort Analysis of Epiglottic Phenotypes and Pharyngeal Residue.

OBJECTIVE: To describe the phenotypic characteristics of the epiglottis at rest and their impact on vallecular residue. METHODS: Videofluoroscopic studies (VFSS) were pooled from 2 Laryngology practices, and Image J was used to measure epiglottic anatomic features at rest. Studies were rated by the MBSImp and presence of vallecular residue following swallow of thin and puree boluses. A conditional inference tree analysis was performed to isolate which epiglottic parameters were risk factors for presence of vallecular reside followed by logistic regression. RESULTS: The majority of patients had a normal shaped epiglottis, followed by omega shape. The mean angle of the epiglottis from the hyoid was approximately 90°. Only abnormal epiglottic movement was associated with increased risk of residue for thin boluses (OR 35.09, CI 10.93-158.66, P < .001). However, in those with normal epiglottic movement, age >70 years old was associated with increased risk of residue (OR 3.98, CI 1.73-9.23, P = .001). For puree boluses, a normal or omega shaped epiglottis was associated with residue (OR 5.19, CI 2.41-11.51, P < .001), and this relationship was further modulated by increased distance of the epiglottic tip from the posterior pharyngeal wall. No other anatomic features of the resting epiglottis were associated with residue. Comorbidities potentially affecting swallow were infrequent in the cohort and were not associated with residue. CONCLUSION: Abnormal epiglottic movement is associated with aspiration, and in this study we find that abnormal epiglottic movement increases the risk of vallecular residue and that older age is a risk factor for residue. The resting properties of the epiglottis do not appear to be associated with abnormal epiglottic movement or residue.

Surgical Outcomes in Zenker Diverticula: A Multicenter, Prospective, Longitudinal Study.

OBJECTIVE: To compare improvement in patient-reported outcomes (PROM) in persons undergoing endoscopic and open surgical management of Zenker diverticula (ZD). METHODOLOGY: Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgery for ZD. Patient survey, radiography reports, and the 10-item Eating Assessment Tool (EAT-10) pre- and post-procedure were abstracted from a REDCap database, which summarized means, medians, percentages, and frequencies of. Outcome based on operative intervention (endoscopic vs. open) was compared using t-test, Wilcoxon rank sum test or chi-square test, as appropriate. RESULTS: One hundred and forty-seven persons were prospectively followed. The mean age (SD) of the cohort was 68.7 (11.0). Overall, 66% of patients reported 100% improvement in EAT-10; 81% of patients had greater than 75% improvement; and 88% had greater than 50% improvement. Endoscopic was used for n = 109 patients, and open surgical intervention was used for n = 38. The median [interquartile range, IQR] EAT-10 percent improvement for endoscopic treatment was 93.3% [72, 100], and open was 100% [92.3, 100] (p = 0.05). The incidence of intraoperative complications was 3.7% for endoscopic and 7.9% for open surgical management. The median [IQR] in follow-up was 86 and 97.5 days, respectively. CONCLUSION: Both endoscopic and open surgical management of ZD provide significant improvement in patient-reported outcomes. The data suggest that open diverticulectomy may provide a modest advantage in symptomatic improvement compared to endoscopic management. The data suggest that the postoperative complication rate is higher in the open surgical group. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:97-102, 2024.

Changes in vocal fold gene expression and histology after injection augmentation in a recurrent laryngeal nerve injury model.

OBJECTIVE: To investigate changes in neuroregenerative pathways with vocal fold denervation in response to vocal fold augmentation. METHODS: Eighteen Yorkshire crossbreed swine underwent left recurrent laryngeal nerve transection, followed by observation or augmentation with carboxymethylcellulose or calcium hydroxyapatite at two weeks. Polymerase chain reaction expression of genes regulating muscle growth (MyoD1, MyoG and FoxO1) and atrophy (FBXO32) were analysed at 4 and 12 weeks post-injection. Thyroarytenoid neuromuscular junction density was quantified using immunohistochemistry. RESULTS: Denervated vocal folds demonstrated reduced expression of MyoD1, MyoG, FoxO1 and FBXO32, but overexpression after augmentation. Healthy vocal folds showed increased early and late MyoD1, MyoG, FoxO1 and FBXO32 expression in all animals. Neuromuscular junction density had a slower decline in augmented compared to untreated denervated vocal folds, and was significantly reduced in healthy vocal folds contralateral to augmentation. CONCLUSION: Injection augmentation may slow neuromuscular degeneration pathways in denervated vocal folds and reduce compensatory remodelling in contralateral healthy vocal folds.

Quantifying Intubation Forces on Incisors and Tongue Base Across Exposure Difficulty and Experience in a Simulator.

OBJECTIVE: Laryngoscopy simulators quantifying forces on critical structures in progressively challenging airways and operator expertise are lacking. We aimed to quantify laryngoscopy forces across expertise and exposure difficulty. STUDY DESIGN: Prospective observational study Setting: Tertiary care medical center Methods: Force gauges were affixed to a difficult airway mannequin to quantify teeth and tongue forces across increasingly challenging airway exposure. Medical students (n=10), residents (n=11), and otolaryngology staff (n=10) performed direct laryngoscopy using a Miller size 3 laryngoscope with 1) normal neck/jaw mobility, 2) restricted neck extension, 3) restricted jaw opening, and 4) restricted neck/jaw mobility. Incisor and tongue pounds of force (lbf) were continuously measured. RESULTS: As the difficulty setting increased, forces exerted by the students, residents, and staff on the incisors and tongue base increased (p=0.01). Between normal and maximally restricted settings, force delivered to the incisors increased by 6.95 lbf (standard error (SE) 1.29), 5.93 lbf (SE 0.98), and 5.94 lbf (SE 0.70) for the students, residents, and staff, respectively. At the tongue base, force increased by 0.37 lbf (SE 0.18), 0.46 lbf (SE 0.14), and 0.73 lbf (SE 0.15) for the students, residents, and staff, respectively. Esophageal intubations occurred in 50% of the students, 23% of the residents, and 45% of the otolaryngology staff at maximal difficulty, with none at the easiest setting (p=0.33). Compared to the residents, the staff applied significantly increased pressure on the tongue base during laryngoscopy (p=0.02). CONCLUSION: Forces exerted on the incisors and tongue base varied across exposure difficulty and expertise levels, suggesting that they may be useful markers for training and competence assessment.

Effect of continuous local dexamethasone on tissue biomechanics and histology after inhalational burn in a preclinical model.

Objective: Inhalational burns frequently lead to dysphonia and airway stenosis. We hypothesize local dexamethasone delivery via a novel drug-eluting electrospun polymer-mesh endotracheal tube (ETT) reduces biomechanical and histologic changes in the vocal folds in inhalational burn. Methods: Dexamethasone-loaded polymer mesh was electrospun onto ETTs trimmed to transglottic endolaryngeal segments and secured in nine Yorkshire Crossbreed swine with directed 150°C inhalation burns. Uncoated ETTs were implanted in nine additional swine with identical burns. ETT segments were maintained for 3 and 7 days. Vocal fold (VF) structural stiffness was measured using automated-indentation mapping and compared across groups and to four uninjured controls, and matched histologic assessment performed. Statistical analysis was conducted using two-way ANOVA with Tukey's post hoc test and Wilcoxon rank-sum test. Results: VF stiffness after burn decreased with longer intubation, from 19.4 (7.6) mN/mm at 3 days to 11.3 (5.2) mN/mm at 7 days (p < .0001). Stiffness similarly decreased with local dexamethasone, from 25.9 (17.2) mN/mm at 3 days to 18.1 (13.0) mN/mm at 7 days (p < .0001). VF stiffness in the dexamethasone group was increased compared to tissues without local dexamethasone (p = .0002), and all groups with ETT placement had higher tissue stiffness at 3 days (p < .001). No significant change in histologic evidence of epithelial ulceration or fibrosis was noted, while an increased degree of inflammation was noted in the dexamethasone group (p = .04). Conclusion: Local dexamethasone delivery increases VF stiffness and degree of inflammation compared to uncoated ETTs in an acute laryngeal burn model, reflected in early biomechanical and histologic changes in an inhalational burn model.

A Novel Instrument Holder to Improve Operative Efficiency in Endoscopic Laryngeal and Airway Surgery.

OBJECTIVE: Receiving instruments from surgical technicians during endoscopic laryngeal and airway microsurgery (ELAM) has challenges including repeated, expeditious handling of delicate instruments and passing them to the surgeon's hand opposite of where the surgical assistant is standing. Optimizing this interaction may reduce surgical errors and improve operative efficiency. METHODS: A proprietary ELAM instrument holder was attached to both sides of the operating room bed. The device consisted of an articulating arm with custom silicone inserts mounted on a tray (storing up to three endoscopic instruments). ELAM cases were randomized to be performed either with (device) or without the holder (control). Using custom software, instrument pass time (IPT), instrument drop rate (IDR), and communication errors (eg handing incorrect instruments) were manually recorded. Qualitative use metrics relating to overall device satisfaction were also obtained. RESULTS: Data were collected from 25 device and 23 control cases among three different laryngologists. Average IPT was nearly three times quicker for the device (0.80 s, n = 1175 passes) compared with controls (2.09 s, n = 1208 passes) [p < 0.001]. IPT interquartile range was five times higher for control (1.65 s) versus device cases (0.42 s). IDR was not significantly different [p = 0.48]; however, device cases had significantly lower communication errors compared to control cases [p = 0.01]. Surgeons and surgical assistants were similarly satisfied with the device on a 5-point Likert scale (mean: 4.2/5, standard deviation: 0.92). CONCLUSION: The proposed endoscopic instrument holder can improve ELAM operative workflow by reducing instrument passing time and variability without increasing IDR. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3492-3498, 2023.

Developing a Social Media Ontology Across Otolaryngology and its Subspecialties.

OBJECTIVE: To determine how social media is used in the dissemination of new information within otolaryngology, and to emphasize the importance of standardizing Twitter hashtag use. METHODS: Based on the 2019 SCImago journal rankings, the Twitter posts from the accounts of the top three journals covering each otolaryngology subspecialty were reviewed from August 1, 2020 to May 1, 2021. Twitter posts from the primary otolaryngology-related academic societies were also reviewed during this timeframe. A list of hashtags was generated based on a combination of the most common otolaryngologic procedures and most commonly used hashtags in the social media space. This list was then crowd-sourced with 10 fellowship-trained otolaryngologists for each subspecialty. RESULTS: Hashtag use among key stakeholders in the otolaryngology social media space varies considerably. For instance, #HNSCC, #HeadAndNeckSquamousCellCarcinoma, #HeadAndNeckCancer, #HeadAndNeckCancers, #OropharyngealCancer, #OropharynxCancer, #OralCancer, and #OPSCC were all commonly used hashtags to identify posts discussing oropharyngeal squamous cell carcinoma. #HeadAndNeckCancer and #HNSCC were most popular and used in a total of 85 and 65 tweets, respectively. #HeadAndNeckCancer was found alone in 32 out of 85 tweets (38%), whereas #HNSCC was found alone in 27 out of 65 tweets (42%). A standardized hashtag ontology covering all subspecialties within otolaryngology is proposed herein. CONCLUSIONS: Adoption of a standardized social media ontology within otolaryngology will improve information dissemination across all key stakeholders. Laryngoscope, 133:1595-1599, 2023.

Scalable and High-Throughput In Vitro Vibratory Platform for Vocal Fold Tissue Engineering Applications.

The vocal folds (VFs) are constantly exposed to mechanical stimulation leading to changes in biomechanical properties, structure, and composition. The development of long-term strategies for VF treatment depends on the characterization of related cells, biomaterials, or engineered tissues in a controlled mechanical environment. Our aim was to design, develop, and characterize a scalable and high-throughput platform that mimics the mechanical microenvironment of the VFs in vitro. The platform consists of a 24-well plate fitted with a flexible membrane atop a waveguide equipped with piezoelectric speakers which allows for cells to be exposed to various phonatory stimuli. The displacements of the flexible membrane were characterized via Laser Doppler Vibrometry (LDV). Human VF fibroblasts and mesenchymal stem cells were seeded, exposed to various vibratory regimes, and the expression of pro-fibrotic and pro-inflammatory genes was analyzed. Compared to current bioreactor designs, the platform developed in this study can incorporate commercial assay formats ranging from 6- to 96-well plates which represents a significant improvement in scalability. This platform is modular and allows for tunable frequency regimes.

Characterization of Vocal Fold Pathology in Military Drill Instructors.

OBJECTIVE: Military drill instructors have extreme vocal demands that place them at risk for phonotrauma. Characterization of laryngeal pathology and vibratory characteristics among drill instructors presenting for specialized voice care is lacking. METHODS: A retrospective review in a specialized voice clinic over a two-year period was conducted. Patients identified as current drill instructors between the ages of 28-43 with a diagnosis of dysphonia were included. Laryngeal pathology was diagnosed by a fellowship trained laryngologist and vibratory characteristics were evaluated utilizing the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) rating form. All patients were also evaluated by a speech-language pathologist. Patient reported outcome measures were collected along with perceptual voice evaluations utilizing the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V). RESULTS: Twelve current drill instructors were identified, and all had phonotraumatic lesions. Lesions were categorized as vocal fold hemorrhage (8%), ectasia (25%), unilateral epithelial thickening (33.3%), bilateral epithelial thickening (58.3%), ventricular cyst (8%), polyp (25%), and sulcus vocalis (25%). Vibratory abnormalities were assessed with the VALI rating scale and correlated to CAPE-V perceptual ratings with 83% having reduced mucosal wave, 75% reduced amplitude of lateral excursion, 50% aperiodic vibrations, 50% asymmetric or chasing wave, 58% glottal insufficiency, 100% supraglottic hyperfunction, and an average CAPE-V overall severity of 50% with severe perceptual dysphonia. The average Voice Handicap Index (VHI-10) and Reflux Symptom Index (RSI) score was 15.5 and 14.7, respectively. CONCLUSION: Phonotraumatic lesions were universally present in drill instructors complaining of hoarseness, suggesting early referral, and intervention may be warranted in this population. LEVEL OF EVIDENCE: 4.

Vocal Fold Thinning in Transgender Patients.

PURPOSE: Transgender individuals strive to match their voice and gender identity. An increased glottal gap is often noted on stroboscopy without a clear etiology. We hypothesize this gap can be quantified and results from hormone replacement therapy impacting laryngeal tissues. METHODS: Videostroboscopy exams were retrospectively collected for transgender patients from a tertiary care laryngology practice over two years. Data included hormone duration/type and voice therapy duration. Modal pitch videostroboscopy frame counts determined the open quotient in consecutive vocal fold cycles. Glottal opening was measured using the widest still frame gap during stroboscopy with fully adducted arytenoids. RESULTS: Sixteen transgender patients, along with male and female controls, were included, with 15 patients on hormone therapy (mean = 18 months). Voice therapy, employed in 9/16 patients, ranged from 0 to 23 months (mean = 10.67). One-way ANOVA testing revealed a difference between the open quotient in transgender individuals, males, and females.Tukey's post hoc test identified transgender patients as different from both male (P <0.001) and female (P = 0.037) controls. Length of hormone therapy did not correlate to glottal area measurement or open quotient. Conversely, voice therapy length correlated to increased glottal area (Kendall's Tau = 0.03). Mean phonation time, VHI-10, and mean pitch did not correlate to measured glottal area on stroboscopy. CONCLUSIONS: The increased glottal gap noted in many transgender patients, quantified via the open quotient, differs from male and female controls. Results suggest these findings may correlate to duration of voice therapy.

Longitudinal Effects of Base of Tongue Concurrent Chemoradiation Therapy in a Pre-Clinical Model.

BACKGROUND/OBJECTIVES: Base of tongue (BOT) dysfunction is common following oropharyngeal concurrent chemoradiation therapy (CCRT). We present a clinically relevant animal model quantifying the effects of CCRT on tongue strength and elasticity over time. METHODS: Fifty-three male and 53 female Sprague-Dawley rats were randomized to control or experimental groups. Experimental animals received cisplatin, 5-fluorouracil, and 5 fractions of 7 Gy directed to the BOT. Controls received no intervention. At 2 weeks, 5 months, or 10 months after CCRT, animals underwent non-survival surgery to measure twitch and tetanic tongue strength, which were analyzed using multivariate linear mixed effects models. Tongue displacement, a surrogate for tongue elasticity, was also determined via stress-strain testing and analyzed via a multivariate linear mixed effects model. RESULTS: Reporting the combined results of both sexes, the estimated experimental group mean peak twitch forces became more divergent over time compared to controls, being 8.3% lower than controls at 2 weeks post-CCRT, 15.7% lower at 5 months, and 31.6% lower at 10 months. Estimated experimental group mean peak tetanic forces followed a similar course and were 2.9% lower than controls at 2 weeks post CCRT, 20.7% lower at 5 months, and 27.0% lower at 10 months. Stress-strain testing did not find CCRT to have a significant effect on tongue displacement across experimental timepoints. CONCLUSIONS: This study demonstrates an increasing difference in tongue strength over time between controls and animals exposed to CCRT. Tongue elasticity was not significantly affected by CCRT, suggesting that changes in strength may not be caused by fibrosis. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1455-1461, 2023.

Augmentation and vocal fold biomechanics in a recurrent laryngeal nerve injury model.

Objectives/hypothesis: Composite vocal fold (VF) biomechanical data are lacking for augmentation after recurrent laryngeal nerve (RLN) injury. We hypothesize resulting atrophy decreases VF stiffness and augmentation restores native VF biomechanics. Methods: Sixteen Yorkshire Crossbreed swine underwent left RLN transection and were observed or underwent carboxymethylcellulose (CMC) or calcium hydroxyapatite (CaHa) augmentation at 2 weeks. Biomechanical measurements (structural stiffness, displacement, and maximum load) were measured at 4 or 12 weeks. Thyroarytenoid (TA) muscle cross-sectional area was quantified and compared with two-way ANOVA with Tukey's post hoc test. Results: After 4 weeks, right greater than left structural stiffness (mean ± SE) was observed (49.6 ± 0.003 vs. 28.4 ± 0.002 mN/mm), left greater than right displacement at 6.3 mN (0.54 ± 0.01 vs. 0.46 ± 0.01 mm, p < .01) was identified, and right greater than left maximum load (72.3 ± 0.005 vs. 40.8 ± 0.003 mN) was recorded. TA muscle atrophy in the injured group without augmentations was significant compared to the noninjured side, and muscle atrophy was seen at overall muscle area and individual muscle bundles. CMC augmentation appears to maintain TA muscle structure in the first 4 weeks with atrophy present at 12 weeks. Conclusions: VF biomechanical properties match TA muscle atrophy in this model, and both CMC and CaHa injection demonstrated improved biomechanical properties and slower TA atrophy compared to the uninjured side. Taken together, these data provide a quantifiable biomechanical basis for early injection laryngoplasty to improve dysphonia and potentially improve healing in reversible unilateral vocal fold atrophy. Level of evidence: N/A.

Laryngeal inhalational injuries: A systematic review.

Laryngeal inhalation injury carries a significant increase in mortality rate and often indicates immediate airway evaluation. This may be difficult in the setting of clinical deterioration necessitating immediate intubation, which itself can synergistically cause mucosal damage. Prior studies do not encompass predictive factors or long-term outcomes for the laryngotracheal complex. This systemic review of PubMed, Embase, and Cochrane identified studies investigating inhalational injuries of the upper airway. Demographic data as well as presentation, physical findings, and delayed sequelae were documented. Laryngotracheal burn patients were divided into two cohorts based on timing of laryngeal injury diagnosis (before- versus after-airway intervention). 1051 papers met initial search criteria and 43 studies were ultimately included. Airway stenosis was more common in patients that were intubated immediately (50.0%, n = 18 versus 5.2%, n = 13; p = 0.57). Posterior glottic involvement was only identified in patients intubated prior to airway evaluation (71.4%, n = 15). All studies reported a closed space setting for those patients in whom airway intervention preceded laryngeal evaluation. Laryngeal inhalational injuries are a distinct subset that can have a variety of minor to severe laryngotracheal delayed sequelae, particularly for thermal injuries occurring within enclosed spaces. Given these findings, early otolaryngology referral may mitigate or treat these effects.

In-Office Superior Laryngeal Nerve Block for Paralaryngeal Pain and Odynophonia.

OBJECTIVES: Pain localized to the thyrohyoid region may be due to neuralgia of the superior laryngeal nerve (SLN), inflammation of the thyrohyoid complex, or a voice disorder. We present outcomes of treatment of paralaryngeal pain and odynophonia with SLN block. STUDY DESIGN: Retrospective Review. METHODS: A retrospective chart review of patients undergoing in-office SLN block for paralaryngeal pain between 2015 and 2018 at two tertiary care centers was conducted. Patient demographics, indications, and response to treatment were analyzed. RESULTS: Thirty-eight patients underwent blockade of the internal branch of the SLN for paralaryngeal pain, with 10 excluded for incomplete medical records. Eighty-two percent (23/28) reported an improvement in their symptoms. Patients underwent an average of 2.5 blocks (SD = 1.88, range 1-8), with 10 patients (36%) undergoing a single procedure. Of the 18 patients who underwent multiple blocks, nine had eventual cessation of symptoms (50%) compared to resolution in 6/10 undergoing a single injection. Eleven patients (39%) noted odynophonia related to vocal effort, and all of these patients had improvement in or resolution of their symptoms and were more likely to improve compared to those without odynophonia (P = .006). Of the four patients who had a vocal process granuloma (VPG) at presentation, three had complete resolution of the lesion at follow-up. CONCLUSION: In-office SLN block is effective in the treatment of paralaryngeal pain. It may be used as an adjunct in the treatment of vocal process granulomas, as well as voice disorders where odynophonia is a prominent symptom. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:401-405, 2022.

Autologous Lipoaugmentation Long-Term Clinical Outcomes: A Systematic Review.

OBJECTIVES/HYPOTHESIS: Vocal fold (VF) lipoaugmentation can be employed to treat glottal insufficiency although variable data exist on its length of effectiveness. We aimed to review published long-term outcomes following lipoaugmentation across the literature and compile outcome data. STUDY DESIGN: Systematic review. METHODS: A systematic search in September 2020 of PubMed, MEDLINE, Cochrane Library, and Web of Science used the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify 128 relevant articles related to VF lipoaugmentation effectiveness duration. Primary search terms included the following: vocal cord, fat, lipo, and atrophy. Forty-eight full-text articles were reviewed and 31 were included in the final analysis. Primary endpoints included the following: duration of effectiveness per patient-reported outcome measures, objective findings, and additional procedures performed. In addition, fat harvest location and processing techniques were recorded. FINDINGS: Thirty-one studies totaling 764 patients were included in the review. Indications for augmentation were VF paralysis (N = 690) and atrophy (N = 74). Fat was harvested from the abdominal region in 21 studies (529 patients), the thigh/abdomen in 5 studies (91 patients), and buccal/submental region in 2 studies (33 patients). Processing techniques and injectable volume varied. Across included studies, only 11 of 764 patients (1.4%) reported no improvement in voice and/or swallowing. Within the first year, 71 of 608 patients (11.7%) reported a regression toward baseline. Beyond 1 year and up to 8 years, 27 of 214 patients (12.6%) reported regression from initial improvement. Thirty-three patients underwent additional procedures. CONCLUSION: Although improvements in voice and swallowing after lipoaugmentation taper over time, most patients experienced long-term benefit. Laryngoscope, 132:1042-1053, 2022.

State of the Science in Tracheal Stents: A Scoping Review.

OBJECTIVE: Recent material science advancements are driving tracheal stent innovation. We sought to assess the state of the science regarding materials and preclinical/clinical outcomes for tracheal stents in adults with benign tracheal disease. METHODS: A comprehensive literature search in April 2021 identified 556 articles related to tracheal stents. One-hundred and twenty-eight full-text articles were reviewed and 58 were included in the final analysis. Datapoints examined were stent materials, clinical applications and outcomes, and preclinical findings, including emerging technologies. RESULTS: In the 58 included studies, stent materials were metals (n = 28), polymers (n = 19), coated stents (n = 19), and drug-eluting (n = 5). Metals included nitinol, steel, magnesium alloys, and elgiloy. Studies utilized 10 different polymers, the most popular included polydioxanone, poly-l-lactic acid, poly(d,l-lactide-co-glycolide), and polycaprolactone. Coated stents employed a metal or polymer framework and were coated with polyurethane, silicone, polytetrafluoroethylene, or polyester, with some polymer coatings designed specifically for drug elution. Drug-eluting stents utilized mitomycin C, arsenic trioxide, paclitaxel, rapamycin, and doxycycline. Of the 58 studies, 18 were human and 40 were animal studies (leporine = 21, canine = 9, swine = 4, rat = 3, ovine/feline/murine = 1). Noted complications included granulation tissue and/or stenosis, stent migration, death, infection, and fragmentation. CONCLUSION: An increasing diversity of materials and coatings are employed for tracheal stents, growing more pronounced over the past decade. Though most studies are still preclinical, awareness of tracheal stent developments is important in contextualizing novel stent concepts and clinical trials. Laryngoscope, 132:2111-2123, 2022.