Gelbard, Alexander

ABSTRACT Objective Idiopathic subglottic stenosis (iSGS) is a rare, fibroinflammatory airway disorder with non‐standardized management. This study aimed to quantify the global clinical variation in surgical strategies for iSGS and identify barriers and facilitators to the adoption of both established and novel techniques. Methods An international cross‐sectional online survey was responded to by 193 clinicians (otolaryngologists, thoracic surgeons, and interventional pulmonologists) across 42 countries. Data on demographics, technique execution, treatment algorithms, clinician satisfaction (7‐point Likert scale), and adoption barriers were collected. Both statistical analysis and thematic analysis were performed. Results Otolaryngologists constituted the majority of respondents (84%), predominantly from Europe (52%) and North America (28%). Endoscopic dilation was nearly universal (95%), but execution was heterogeneous (85% used occlusive balloons, 56% used CO 2 laser). Newer techniques showed varied adoption: In‐office serial intralesional steroid injections were used by 57% of clinicians and the Maddern procedure by 17%. Overall satisfaction with current treatment strategies was moderate (mean Likert score: 5.07; SD = 1.15). Significant variation was found in the definition of treatment failure. Fellowship‐trained surgeons managed higher case volumes and were more likely to perform complex open surgery ( p = 0.019). Key barriers to adoption included lack of experience and insufficient supporting evidence. Conclusion Significant global clinical variation exists in the management of iSGS, affecting surgical technique, adjuvant therapy, and the definition of treatment failure. Standardization of clinical outcomes, continued large‐scale comparative effectiveness trials, and newer efforts aimed at implementing emerging evidence are needed to reduce variability, establish evidence‐based guidelines, and improve global patient care for this complex disease. Level of Evidence 5.

Summary Functional ex vivo assays using live tumor tissues have demonstrated strong predictive accuracy for response to immune checkpoint inhibitors (ICIs) but are not scalable, requiring manual processing of large resections collected at academic centers. Here, an ex vivo live tumor fragment (LTF) platform was developed using standard-of-care biopsies from 228 patients with suspected malignancy collected across prospective, multicenter observational trials and biobanks. Hierarchical clustering of ICI-mediated changes in cytokine production identified two groups: responders and nonresponders. A binary classifier (elive index) using 8 cytokines achieved an AUC of 0.99 for cluster prediction. elive index correctly predicted clinical benefit in 93% (26/28) of patients ( P = 3.2x10 -5 ) and accurately identified 83% (10/12) of objective responders. Critically, elive responders were identified among biomarker-negative patients, highlighting the platform as a scalable approach that complements existing companion diagnostics and expands the population of patients identified to benefit from ICI therapy.

The 2025 Voice AI Symposium represented a transition from conceptual research to clinical implementation in vocal biomarker science. Hosted by the NIH-funded Bridge2AI-Voice consortium, the meeting convened global experts to address the methodological, ethical, and translational challenges of integrating voice-based artificial intelligence (AI) into healthcare. This mini-review synthesizes symposium insights across six domains: multimodal integration, FAIR (Findable, Accessible, Interoperable, Reusable) and CARE (Collective Benefit, Authority to Control, Responsibility, Ethics) data governance, clinical translation, interdisciplinary training, and cross-sector innovation. Research presented demonstrated voice as a latent, multimodal biomarker reflecting neurological, cardiopulmonary, and psychological states, while discussions emphasized ethical data practices and human-centered design. The implementation-focused panels underscored the importance of workflow alignment and usability for adoption in real-world care. Collectively, the symposium reflects a field advancing toward translational readiness and ethical accountability, positioning voice AI as a scalable, inclusive tool for next-generation healthcare.

Abstract The North American Airway Collaborative (NoAAC) previously published a 3‐year multi‐institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re‐enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision‐making. Level of evidence: 2—prospective cohort study.

Objectives: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients. Methods: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence. Results: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression. Conclusions: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.

ObjectivesIdiopathic subglottic stenosis (iSGS) is an inflammatory process leading to fibrosis and narrowing of the laryngotracheal airway. There is variability in patient response to surgical intervention, but the mechanisms underlying this variability are unknown. In this pilot study, we measure expression of candidate targets at the mucosal surface of the subglottis in iSGS patients. We aim to identify putative biomarkers for iSGS that provide insights into the molecular basis of disease progression, yield a gene signature for the disease, and/or predict a response to therapy.Study DesignIn vitro comparative study of human cells.MethodsLevels of candidate transcripts and proteins were measured in healthy and stenotic laryngotracheal tissue specimens taken from the mucosal surface in 16 iSGS patients undergoing endoscopic balloon dilation. Pre‐ and post‐operative pulmonary function test and patient reported voice and breathing outcomes were also assessed. Unsupervised clustering was used to define patient subgroups based on expression profile.ResultsPulmonary function and voice and breathing outcome metrics demonstrated significant post‐operative improvement. Transcript levels of αSMA, CCL2, COL1A1, COL3A1, FN1, IFNG, and TGFB1 and protein levels of CCL2, IFNG, and IL‐6 were significantly upregulated in stenotic as compared to healthy tissues. Marked heterogeneity was observed in the patterns of expression of candidate markers across individuals and tissue types. Patient subgroups defined by expression profile did not show a statistically significant difference in dilation interval.ConclusionPro‐inflammatory and pro‐fibrotic pathways are significantly upregulated along the mucosal surface of stenotic laryngotracheal tissues, and CCL2 and IFNG merit further investigation as potential iSGS biomarkers.Level of Evidence4 Laryngoscope, 131:342–349, 2021

Abstract Objectives To describe tracheobronchial disease in patients with granulomatosis with polyangiitis (GPA) and evaluate the utility of dynamic expiratory CT to detect large-airway disease. Methods Demographic and clinical features associated with the presence of subglottic stenosis (SGS) or endobronchial involvement were assessed in a multicentre, observational cohort of patients with GPA. A subset of patients with GPA from a single-centre cohort underwent dynamic chest CT to evaluate the airways. Results Among 962 patients with GPA, SGS and endobronchial disease were identified in 95 (10%) and 59 (6%) patients, respectively. Patients with SGS were more likely to be female (72% vs 53%, P < 0.01), younger at time of diagnosis (36 vs 49 years, P < 0.01), and have saddle-nose deformities (28% vs 10%, P < 0.01), but were less likely to have renal involvement (39% vs 62%, P < 0.01). Patients with endobronchial disease were more likely to be PR3-ANCA positive (85% vs 66%, P < 0.01), with more ENT involvement (97% vs 77%, P < 0.01) and less renal involvement (42% vs 62%, P < 0.01). Disease activity in patients with large-airway disease was commonly isolated to the subglottis/upper airway (57%) or bronchi (32%). Seven of 23 patients screened by dynamic chest CT had large-airway pathology, including four patients with chronic, unexplained cough, discovered to have tracheobronchomalacia. Conclusion SGS and endobronchial disease occur in 10% and 6% of patients with GPA, respectively, and may occur without disease activity in other organs. Dynamic expiratory chest CT is a potential non-invasive screening test for large-airway involvement in GPA.

ObjectiveLaryngotracheal stenosis (LTS) is resource‐intensive disease. The cost‐effectiveness of LTS treatments has not been adequately explored. We aimed to conduct a cost‐effectiveness analysis comparing open reconstruction (cricotracheal/tracheal resection [CTR/TR]) with endoscopic dilation in the treatment of LTS.Study DesignRetrospective cohort.SettingTertiary referral center (2013‐2017).Subjects and MethodsThirty‐four LTS patients were recruited. Annual costs were derived from the Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University. Cost‐effectiveness analysis compared CTR/TR versus endoscopic dilation at a willingness‐to‐pay threshold of $50,000 per quality‐adjusted life year (QALY) over 5‐ and 10‐year time horizons. The incremental cost‐effectiveness ratio (ICER) was calculated with deterministic analysis and tested for sensitivity with univariate and probabilistic sensitivity analysis.ResultsMean LTS costs were $4080.09 (SE, $569.29) annually for related health care visits. The major risk factor for increased cost was etiology of stenosis. As compared with idiopathic patients, patients with intubation‐related stenosis had significantly higher annual costs ($5286.56 vs $2873.62, P =. 03). The cost of CTR/TR was $8583.91 (SE, $2263.22). Over a 5‐year time horizon, CTR/TR gained $896 per QALY over serial dilations and was cost‐effective. Over a 10‐year time horizon, CTR/TR dominated dilations with a lower cost and higher QALY.ConclusionThe cost of treatment for LTS is significant. Patients with intubation‐related stenosis have significantly higher annual costs than do idiopathic patients. CTR/TR contributes significantly to cost in LTS but is cost‐effective versus endoscopic dilations for appropriately selected patients over a 5‐ and 10‐year horizon.