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ObjectiveTo evaluate new medical devices and drugs pertinent to otolaryngology-head and neck surgery that were approved by the Food and Drug Administration (FDA) in 2021.Data sourcesPublicly available FDA device and drug approvals from ENT (ear, nose, and throat), anesthesia, neurosurgery, plastic surgery, and general surgery FDA committees.Review methodsFDA device and therapeutic approvals were identified and reviewed by members of the American Academy of Otolaryngology-Head and Neck Surgery's Medical Devices and Drugs Committee. Two independent reviewers assessed the relevance of devices and drugs to otolaryngologists. Medical devices and drugs were then allocated to their respective subspecialty fields for critical review based on available scientific literature.ConclusionsThe Medical Devices and Drugs Committee reviewed 1153 devices and 52 novel drugs that received FDA approval in 2021 (67 ENT, 106 anesthesia, 618 general surgery and plastic surgery, 362 neurosurgery). Twenty-three devices and 1 therapeutic agent relevant to otolaryngology were included in the state of the art review. Advances spanned all subspecialties, including over-the-counter hearing aid options in otology, expanding treatment options for rhinitis in rhinology, innovative laser-safe endotracheal tubes in laryngology, novel facial rejuvenation and implant technology in facial plastic surgery, and advances in noninvasive and surgical treatment options for obstructive sleep apnea.Implications for practiceFDA approvals for new technology and pharmaceuticals present new opportunities across subspecialties in otolaryngology. Clinicians' nuanced understanding of the safety, advantages, and limitations of these innovations ensures ongoing progress in patient care.

Objectives: Retrograde cricopharyngeal dysfunction (RCPD) is a newly described condition resulting from failure of cricopharyngeal sphincter relaxation during periods of esophageal distension that results in the inability to burp. Patients' perspectives on symptom experiences, barriers to care, and treatment benefits were investigated. Study Design: Qualitative semi‐structured interviews were conducted with patients diagnosed with RCPD who had been treated with botulinum toxin injection into the cricopharyngeus muscle. Interview questions centered on their experience living with RCPD. Conventional content analysis was performed on interview transcripts. Results: Thematic saturation was reached with 13 participants. All participants were diagnosed with RCPD by an otolaryngologist and underwent botulinum toxin injection into the cricopharyngeus muscle with or without dilation of the upper esophageal sphincter in the operating room. Participants described having no memories of ever being able to burp, and all started experiencing RCPD symptoms during adolescence. Patients with RCPD experienced increased social isolation, lost productivity, and worsened mental health. Unanimously, participants first learned about RCPD on social media. All patients were seen by physicians in non‐otolaryngology specialties regarding their symptoms prior to learning about their RCPD diagnosis and undergoing treatment by an otolaryngologist. Dilation and chemodenervation resulted in complete resolution of RCPD symptoms for 84.6% of participants. Participants emphasized a desire for more health providers to learn about RCPD and the impact it has on quality‐of‐life. Conclusion(s): The lived experience of patients with RCPD significantly impacts quality of life and is often met with diagnostic barriers in the medical community. Although social media plays a significant role in increasing awareness of RCPD, physician education about the impact of RCPD is essential to improve diagnosis and treatment. Level of Evidence: 4 Laryngoscope, 134:2136–2143, 2024 [ABSTRACT FROM AUTHOR]

Retrograde cricopharyngeal dysfunction (RCPD), also referred to as retrograde cricopharyngeus dysfunction, is a condition characterized by the inability to burp. The pathophysiology of this condition is thought to result from failure of cricopharyngeal sphincter relaxation during periods of esophageal distension, which leads to patients' bothersome symptoms. RCPD negatively impacts patients' quality of life and is associated with bloating, gurgling, avoidance of carbonation, self-imposed dietary and lifestyle changes designed to minimize discomfort, and flatulence. Complaints often start during adolescence, and many patients search for a diagnosis for years before obtaining treatment. A recent increase in awareness through patient-led social media discussion boards describing the 'no burp' syndrome is leading to an increasing incidence of presentations, often with patients making a self-diagnosis. The increased incidence of RCPD is fueling a larger case series investigating treatment options and outcomes. In this review, we discuss what is known about the pathophysiology of this condition, the otolaryngologic perspective on diagnosis and treatment, the patients' lived experience of this condition, and the influence of social media on RCPD. [ABSTRACT FROM AUTHOR]

Objectives: To aim of the study was to characterize the molecular profile and functional phenotype of idiopathic subglottic stenosis (iSGS)‐scar epithelium. Methods: Human tracheal biopsies from iSGS scar (n = 6) and matched non‐scar (n = 6) regions were analyzed using single‐cell RNA sequencing (scRNA‐seq). Separate specimens were used for epithelial cell expansion in vitro to assess average growth rate and functional capabilities using transepithelial‐electrical resistance (TEER), fluorescein isothiocyanate‐dextran flux permeability assay, ciliary coverage, and cilia beating frequency (CBF). Finally, epithelial tight junction protein expression of cultured cells was quantified using immunoblot assay (n = 4) and immunofluorescence (n = 6). Results: scRNA‐seq analysis revealed a decrease in goblet, ciliated, and basal epithelial cells in the scar iSGS cohort. Furthermore, mRNA expression of proteins E‐cadherin, claudin‐3, claudin‐10, occludin, TJP1, and TJP2 was also reduced (p < 0.001) in scar epithelium. Functional assays demonstrated a decrease in TEER (paired 95% confidence interval [CI], 195.68–890.83 Ω × cm2, p < 0.05), an increase in permeability (paired 95% CI, −6116.00 to −1401.99 RFU, p < 0.05), and reduced epithelial coverage (paired 95% CI, 0.1814–1.766, fold change p < 0.05) in iSGS‐scar epithelium relative to normal controls. No difference in growth rate (p < 0.05) or CBF was found (paired 95% CI, −2.118 to 3.820 Hz, p > 0.05). Immunoblot assay (paired 95% CI, 0.0367–0.605, p < 0.05) and immunofluorescence (paired 95% CI, 13.748–59.191 mean grey value, p < 0.05) revealed E‐cadherin reduction in iSGS‐scar epithelium. Conclusion: iSGS‐scar epithelium has a dysfunctional barrier and reduced structural protein expression. These results are consistent with dysfunctional epithelium seen in other airway pathology. Further studies are warranted to delineate the causality of epithelial dysfunction on the downstream fibroinflammatory cascade in iSGS. Level of Evidence: NA Laryngoscope, 134:374–381, 2024 [ABSTRACT FROM AUTHOR]

Objectives: Idiopathic subglottic stenosis (iSGS) is characterized by progressive fibrosis and subglottic luminal narrowing. Currently, immune characterization has focused on T‐cells; however, macrophages remain largely unexplored. The goals of this study are to characterize the transcriptome of iSGS macrophages and the fibrogenic nature of identifed biomarkers. Study Design: Bioinformatics and in vitro. Methods: Human tracheal biopsies from iSGS scar (n = 4), and matched non‐scar (n = 4) regions were analyzed using single‐cell RNA‐seq (scRNA‐seq). Immunofluorescence (IF) was performed on rapidly processed autopsies (RPA) and iSGS tracheal resections (n = 4) to co‐localize S100A8/9 and CD11b. Collagen gene/protein expression was assessed in iSGS fibroblasts (n = 4) treated with protein S100A8/9 (1000 ng/ml). Macrophages were subclustered to identify distinct subpopulations. Results: scRNA‐seq analysis revealed S100A8/S100A9 (fold change (FC) = 4.1/1.88, p < 0.001) as top differentially expressed genes in iSGS macrophages. IF exhibited increased CD11b+/S100A8/9+ cells in tracheal samples of iSGS versus RPA (26.75% ± 7.08 vs. 0.594% ± 0.974, n = 4, p = 0.029). iSGS fibroblasts treated with S100A8/9 demonstrated increased gene expression of COL1A1 (FC = 2.30 ± 0.45, p = 0.03, n = 4) and COL3A1 (FC = 2.44 ± 0.40, p = 0.03, n = 4). COL1A1 protein assays revealed an increase in the experimental group, albeit not significant, (p = 0.12, n = 4). Finally, macrophage sub clustering revealed one subpopulation as a predominant source of S100A8/S100A9 expression (FC = 7.94/5.47, p < 0.001). Conclusions: S100A8/9 is a key biomarker in iSGS macrophages. Although S100A8/9 demonstrates profibrotic nature in vitro, the role of S100A8/9+ macrophages in vivo warrants further investigation. Level of Evidence: NA Laryngoscope, 133:2308–2316, 2023 [ABSTRACT FROM AUTHOR]

Objective: To describe technical aspects and surgical outcomes of endoscopic resection and mucosal reconstitution with epidermal grafting (ie, the Maddern procedure) in the treatment of idiopathic subglottic stenosis. Study Design: Medical record abstraction. Setting: Johns Hopkins Hospital. Methods: Retrospective series of 9 adults with idiopathic subglottic stenosis who underwent the Maddern procedure by a single surgeon over a 5-year period. Prespecified outcomes included (1) perioperative outcomes (Clavien-Dindo grade 4/5 complications, need for staged tracheostomy, hospital length of stay), (2) postoperative outcomes (peak expiratory flow rate [PEFR], need for subsequent airway surgery, tracheostomy at follow-up), and (3) patient-reported quality-of-life outcomes (Clinical COPD Questionnaire, Voice Handicap Index–10, Eating Assessment Tool–10, and 12-Item Short Form Version 2). Wilcoxon matched-pairs signed rank test and Kaplan-Meier analysis were performed. Results: There were no Clavien-Dindo grade 4/5 complications; 2 patients required unplanned staged tracheostomy; and the median length of stay was 3 days. Following endoscopic resection and stent removal, a median of 2 laser resurfacing procedures were required. Two patients developed recurrent stenosis requiring cricotracheal resection (CTR). There were significant improvements in PEFR, Clinical COPD Questionnaire, and Voice Handicap Index–10, without significant difference in Eating Assessment Tool–10. The 12-Item Short Form Version 2 approximated the population norm. Kaplan-Meier analysis demonstrated significant improvement in time to surgery after the final laser resurfacing. Conclusion: The Maddern procedure has a low complication rate and offers durable physiologic improvement in PEFR, limiting need for additional procedures. Risks included need for CTR salvage, temporary tracheostomy, phlegm accumulation, and laryngospasm. It is a surgical option for patients with short dilation intervals who prefer to avoid the risks of CTR. [ABSTRACT FROM AUTHOR]

Objective: Iatrogenic laryngotracheal stenosis (iLTS) is the pathologic narrowing of the glottis, subglottis, and/or trachea secondary to intubation or tracheostomy related injury. Patients with type 2 diabetes mellitus (T2DM) are more likely to develop iLTS. To date, the metabolomics and phenotypic expression of cell markers in fibroblasts derived from patients with T2DM and iLTS are largely unknown. Study Design: Controlled in vitro cohort study. Setting: Tertiary referral center (2017-2020). Methods: This in vitro study assessed samples from 6 patients with iLTS who underwent surgery at a single institution. Fibroblasts were isolated from biopsy specimens of laryngotracheal scar and normal-appearing trachea and compared with controls obtained from the trachea of rapid autopsy specimens. Patients with iLTS were subcategorized into those with and without T2DM. Metabolic substrates were identified by mass spectrometry, and cell protein expression was measured by flow cytometry. Results: T2DM iLTS-scar fibroblasts had a metabolically distinct profile and clustered tightly on a Pearson correlation heat map as compared with non-T2DM iLTS-scar fibroblasts. Levels of itaconate were elevated in T2DM iLTS-scar fibroblasts. Flow cytometry demonstrated that T2DM iLTS-scar fibroblasts were associated with higher CD90 expression (Thy-1; mean, 95%) when compared with non-T2DM iLTS-scar (mean, 83.6%; P =.0109) or normal tracheal fibroblasts (mean, 81.1%; P =.0042). Conclusions: Scar-derived fibroblasts from patients with T2DM and iLTS have a metabolically distinct profile. These fibroblasts are characterized by an increase in itaconate, a metabolite related to immune-induced scar remodeling, and can be identified by elevated expression of CD90 (Thy-1) in vitro. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic subglottic stenosis (iSGS) is a rare disease, causing life‐threatening dyspnea secondary to scarring. Perhaps because it is rarely encountered, there is often a delay in diagnosing iSGS. The objective of this study is to characterize diagnostic delay of iSGS, factors that prolong delay, and its impact on iSGS patients. Study Design: Retrospective chart review. Methods: A retrospective chart review of 124 iSGS patients was performed. Times of symptom onset, presentation to otolaryngologist, diagnosis, imaging, pulmonary function testing (PFTs), surgeries, emergency department (ED) visits, and hospitalizations were recorded and univariate analyses were used to identify risk factors for delay. Results: The median total time to diagnosis from symptom onset was 24.5 months, with time to first presentation of 6.3 months and healthcare delay of 17.8 months. 54.8% of patients were diagnosed with asthma. Earlier presentation to otolaryngologist was associated with shorter healthcare delay and total time to diagnosis (rho = 0.75, rho = 0.99, P <.0001). Earlier CT imaging was correlated to shorter healthcare delay (rho = 0.84, P <.0001) and total time to diagnosis (rho = 0.74, P <.001), while earlier PFTs were correlated to shorter total time to diagnosis alone (rho = 0.71, P =.01). During evaluation, 10.5% (n = 17/124) of patients had ED visits and 13.7% (n = 13/124) patients were hospitalized. Before diagnosis, 7% (9/124) of patients underwent surgeries (including 3% (n = 4) undergoing tracheostomy) and 8% (n = 10) of patients required unplanned urgent endoscopic surgery that may have been avoided with earlier diagnosis. Conclusion: iSGS diagnosis is frequently delayed, resulting in additional surgeries (including tracheostomy), ED visits, and hospitalizations. Further, patients' symptoms are commonly attributed to asthma. Earlier otolaryngologist evaluation, PFTs, and CT imaging may expedite iSGS diagnosis. Level of Evidence: 4 Laryngoscope, 132:413–418, 2022 [ABSTRACT FROM AUTHOR]

Objectives: Iatrogenic laryngotracheal stenosis (iLTS) is the pathological narrowing of the glottis, subglottis, and/or trachea due to scar tissue. Patients with type 2 diabetes mellitus (T2DM) are over 8 times more likely to develop iLTS and represent 26% to 53% of all iLTS patients. In this investigation, we compared iLTS scar‐derived fibroblasts in patients with and without T2DM. Study Design: Controlled ex vivo study. Methods: iLTS scar fibroblasts were isolated and cultured from subglottic scar biopsies in iLTS patients diagnosed with or without type 2 diabetes (non‐T2DM). Fibroblast proliferation, fibrosis‐related gene expression, and metabolic utilization of oxidative phosphorylation (OXPHOS) and glycolysis were assessed. Contractility was measured using a collagen‐based assay. Metabolically targeted drugs (metformin, phenformin, amobarbital) were tested, and changes in fibrosis‐related gene expression, collagen protein, and contractility were evaluated. Results: Compared to non‐T2DM, T2DM iLTS scar fibroblasts had increased α‐smooth muscle actin (αSMA) expression (8.2× increased, P =.020), increased contractility (mean 71.4 ± 4.3% vs. 51.7 ± 16% Δ area × 90 minute−1, P =.016), and reduced proliferation (1.9× reduction at 5 days, P <.01). Collagen 1 (COL1) protein was significantly higher in the T2DM group (mean 2.06 ± 0.19 vs. 0.74 ±.44 COL1/total protein [pg/μg], P =.036). T2DM iLTS scar fibroblasts had increased measures of OXPHOS, including basal respiration (mean 86.7 vs. 31.5 pmol/minute/10 μg protein, P =.016) and adenosine triphosphate (ATP) generation (mean 97.5 vs. 25.7 pmol/minute/10 μg protein, P =.047) compared to non‐T2DM fibroblasts. Amobarbital reduced cellular contractility; decreased collagen protein; and decreased expression of αSMA, COL1, and fibronectin. Metformin and phenformin did not significantly affect fibrosis‐related gene expression. Conclusion: T2DM iLTS scar fibroblasts demonstrate a myofibroblast phenotype and greater contractility compared to non‐T2DM. Their bioenergetic preference for OXPHOS drives their increased contractility, which is selectively targeted by amobarbital. Level of Evidence: NA Laryngoscope, 131:1570–1577, 2021 [ABSTRACT FROM AUTHOR]

Objective: Iatrogenic laryngotracheal stenosis (iLTS) is characterized by fibroinflammatory narrowing of the upper airway and is most commonly caused by intubation injury. Evidence suggests a key role for CD4 T cells in its pathogenesis. The objective of this study is to validate emerging multiplex immunofluorescence (mIF) technology for use in the larynx and trachea while quantitatively characterizing the immune cell infiltrate in iLTS. In addition to analyzing previously unstudied immune cell subsets, this study aims to validate previously observed elevations in the immune checkpoint PD-1 and its ligand PD-L1 while exploring their spatial and cellular distributions in the iLTS microenvironment. Study Design: Controlled ex vivo cohort study. Setting: Tertiary care center. Methods: mIF staining was performed with formalin-fixed, paraffin-embedded slides from 10 patients with iLTS who underwent cricotracheal resection and 10 control specimens derived from rapid autopsy for CD4, CD8, CD20, FoxP3, PD-1, PD-L1, and cytokeratin. Results: There was greater infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, FoxP3+CD4+ Tregs, and FoxP3+CD8+ early effector T cells in the submucosa of iLTS specimens as compared with controls (P <.05 for all). PD-1 was primarily expressed on T cells and PD-L1 predominantly on CD4+ cells and "other" cells. Conclusion: This study leverages the power of mIF to quantify the iLTS immune infiltrate in greater detail. It confirms the highly inflammatory nature of iLTS, with CD4+ cells dominating the immune cell infiltrate; it further characterizes the cellular and spatial distribution of PD-1 and PD-L1; and it identifies novel immunologic targets in iLTS. [ABSTRACT FROM AUTHOR]

Objectives: Laryngotracheal stenosis (LTS) is a fibrotic condition of the upper airway. Recent evidence suggests dysregulated host immunity plays a role in LTS development and progression. The programmed death‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) axis, targeted by paradigm‐shifting immunotherapies for cancer treatment, has also recently been implicated in the pathogenesis of fibrotic pulmonary disease. However, a role for the PD‐1/PD‐L1 axis in the proximal airway fibrosis seen in LTS patients has not been explored. Study Design: Controlled ex vivo study. Methods: Expression of PD‐1, PD‐L1, CD4, and CD8 were evaluated using immunohistochemical staining of cricotracheal resection specimens from postintubation iatrogenic laryngotracheal stenosis (iLTS), idiopathic subglottic stenosis (iSGS) patients, and normal controls derived from rapid autopsy (n = 8 per group). Fibroblasts derived from iLTS scar were also treated with transforming growth factor beta 1 (TGFβ1) and analyzed for PD‐L1 expression by quantitative real‐time polymerase chain reaction (n = 6). Results: iLTS specimens exhibited increased expression of PD‐1, PD‐L1, and CD4 (all P <.0167) compared to controls, whereas iSGS specimens exhibited increased expression of PD‐1 and CD4 (P <.0167) compared to controls. PD‐1, PD‐L1, and CD4 showed periepithelial patterns of expression in both disease cohorts. TGFβ1 treatment of iLTS fibroblasts increased expression of PD‐L1 (the cognate ligand for PD‐1). Conclusion: Expression of both PD‐1 and its ligand PD‐L1 are significantly greater in patients with iLTS compared to controls, and PD‐1 expression is also elevated in patients with iSGS. Given published evidence implicating the PD‐1/PD‐L1 axis in pulmonary fibrosis, this suggests a possible role for checkpoint inhibitors targeting the PD‐1/PD‐L1 axis for the treatment of LTS. Level of Evidence: N/A Laryngoscope, 131:967–974, 2021 [ABSTRACT FROM AUTHOR]

Objective: Macrophages exhibit distinct phenotypes and are dysregulated in a model of iatrogenic laryngotracheal stenosis (iLTS). Increased populations of alternatively activated or M2 macrophages have been demonstrated. However, the role of these macrophages is unknown. The aims of this study are: 1) define the macrophage population in iLTS in the context of classically activated or M1 and M2 macrophage phenotypes, and 2) characterize the effect of monocyte‐derived M1 and M2 macrophages on normal airway and LTS‐derived fibroblasts (FBs) in vitro. Study Design: Comparative analysis; in vitro controlled study. Methods: Immunohistochemical analysis of human iLTS and control specimens was performed to define the macrophage population. In vitro, M1, and M2 macrophages were polarized using M‐CSF + Interferon‐gamma and lipopolysaccharide or Interleukin‐4, respectively. FBs isolated from laryngotracheal scar (LTS‐FBs) and normal tracheal airway (NA‐FBs) in eight patients with iLTS were cocultured with polarized macrophages. Fibrosis gene expression, soluble collagen production, and proliferation were assessed. Results: Immunohistochemical analysis revealed increased CD11b + cells (macrophage marker) in laryngotracheal scar specimens (18.3% vs. 8.5%, P =.03) and predominant CD206 (M2) costaining versus CD86 (M1) (51.5% vs. 9.8%, n = 10, P =.001). In vitro, NA‐FBs cultured with M2 macrophages demonstrated a 2.41‐fold increase in collagen‐1 expression (P =.05, n = 8) and an increase in soluble collagen (9.98 vs. 8.875, mean difference: 1.11 95%, confidence interval 0.024–2.192, n = 8, P =.015). Conclusion: Increased populations of CD11b cells are present in iLTS specimens and are predominantly CD206+, indicating an M2 phenotype. In vitro, M2 macrophages promoted collagen expression in airway FBs. Targeting macrophages may represent a therapeutic strategy for attenuating fibrosis in iLTS. Level of Evidence: NA Laryngoscope, 131:E346–E353, 2021 [ABSTRACT FROM AUTHOR]