Lott, David G.

ABSTRACT Objective To compare antigen removal processing with conventional sodium dodecyl sulfate decellularization for generating laryngotracheoesophageal scaffolds, focusing on preservation of extracellular matrix integrity and removal of immunogenic material. Methods Laryngotracheoesophageal complexes were harvested from C57BL/6 mice and processed using either antigen removal or sodium dodecyl sulfate‐based protocols. Scaffolds were analyzed for residual double‐stranded DNA content, collagen preservation, glycosaminoglycan retention, and ultrastructural integrity via histology, quantitative image analysis, and scanning electron microscopy. Results Both antigen removal and sodium dodecyl sulfate protocols achieved effective decellularization, with comparable dsDNA removal relative to native controls ( p = 0.001; p < 0.001). Antigen removal scaffolds demonstrated better collagen preservation compared to sodium dodecyl scaffolds, which exhibited marked collagen depletion (Muscle: Collagen I, p < 0.001; Collagen III, p < 0.01; Cartilage: Collagen I, p < 0.05; Collagen III, p < 0.01). Both antigen removal and sodium dodecyl sulfate groups showed significant glycosaminoglycan depletion compared with controls ( p < 0.001). Scanning electron microscopy confirmed superior ultrastructural preservation in antigen removal‐treated scaffolds, characterized by intact fibrillar architecture and lacunar morphology, while sodium dodecyl sulfate scaffolds demonstrated collapsed lacunae and irregular extracellular matrix organization. Conclusion Antigen removal processing generates laryngotracheoesophageal scaffolds with enhanced extracellular matrix preservation compared with conventional sodium dodecyl sulfate decellularization, while maintaining equivalent levels of antigen elimination. Retention of collagen and ultrastructure suggests antigen removal scaffolds may provide superior biomechanical and biologic performance for laryngeal tissue engineering. Although glycosaminoglycan depletion remains a limitation in both approaches, antigen removal scaffolds represent a promising pathway toward clinically translatable alternatives to immunosuppression‐dependent laryngotracheoesophageal repair. Level of Evidence Preclinical.

Objectives To compare patients’ perception of their degree of subglottic stenosis to their endoscopic exam findings, Clinical Dyspnea Questionnaire, and peak flow results. Study Design Prospective Multi-Institutional. Setting Tertiary Care Clinic. Methods A study of 50 patients comparing patients’ perception of their degree of subglottic stenosis to their endoscopic exam findings. All patients filled out a Clinical Dyspnea Questionnaire and a 10-point scale reflecting their perceived degree of stenosis in 10% intervals. Surgeons filled out the same scale based on measurements from the patients’ exam. Accuracy was defined as +/-1 on a 10-point scale. Pulmonary function testing, number of dilation procedures undergone, cause of stenosis, and demographic information were collected. Results Data complete for 49/50 patients. 48 (98%) were female, 47 (97.9%) Caucasian, 44 (89.8%) had idiopathic subglottic stenosis, and 28 (58.3%) had Grade I subglottic stenosis on the Cotton-Meyer scale. Spearman correlation coefficient was 0.67 indicating moderate correlation overall but 0.88, or high correlation, for those with normal Body Mass Index. Increased Dyspnea Index scores and higher Body Mass Index were correlated with decreased accuracy. Number of previous procedures was not correlated with accuracy. Higher Body Mass Index was correlated with increased dyspnea and lower peak flow volume. Conclusion Patients with normal Body Mass Index have strong predictive accuracy regarding their degree of subglottic stenosis. Better dyspnea scores were correlated with improved accuracy. There is no standard consensus on subglottic stenosis patient follow up. Prior studies have looked at using peak flow meters and validated questionnaires to monitor symptoms.

ABSTRACT Objectives Laryngeal chondrosarcoma (LC) is a rare tumor accounting for less than 1% of all laryngeal cancers. While surgery is the primary treatment, national trends in management and outcomes remain poorly defined. This study aimed to analyze incidence, survival, and treatment strategies for LC using the Surveillance, Epidemiology, and End Results (SEER) database. Methods Patients with LC diagnosed between 2000 and 2021 were identified from SEER. Demographic, treatment, and survival data were analyzed. Kaplan–Meier analysis and multivariate Cox regression were used to analyze survival outcomes. Results In total, 351 patients with LC were identified, representing 0.3% of all laryngeal malignancies. Among patients with treatment data, 53.3% underwent local excision or partial laryngectomy, 27.5% underwent total laryngectomy (TL), and 19.2% received no surgery. Ten‐year disease‐specific survival was 84.8%. Patients undergoing partial resection demonstrated significantly improved survival compared with TL ( p < 0.05), although this finding is likely confounded by tumor size and stage. On multivariate analysis, advanced stage (HR 2.59, 95% CI 1.68–3.97), older age (HR 1.66, 95% CI 1.36–1.99), and TL (HR 2.95, 95% CI 1.88–4.62) were associated with worse survival. Conclusion LC remains rare but carries favorable long‐term survival. National trends demonstrate a shift toward organ‐preserving surgery, with partial resections increasingly favored over TL. Prognosis is most strongly influenced by age and stage, while radiation therapy appears to play a little role. These findings support organ preservation in appropriately selected patients and highlight the need for prospective studies integrating oncologic and functional outcomes. Level of Evidence 4

ABSTRACT Objective With regulatory approval of HPV‐specific immunotherapy for recurrent respiratory papillomatosis (RRP) and growing experience with systemic bevacizumab, a management algorithm incorporating these medical treatments is warranted. Data Sources and Methods RRP Foundation (RRPF) Key Opinion Leaders offer a proposed management algorithm for adults with RRP considering published literature and commercial drug availability. Results Preventative HPV vaccination should be considered for all patients. Determination of HPV type and pulmonary imaging are important for contemporary RRP patient care and assist in decision making. Risks and benefits of papilloma debulking as needed versus medical management of RRP must be deliberated on a patient case‐by‐case basis. HPV ‐specific immunotherapy that induces an HPV ‐specific T cell response to target the underlying HPV infection that is the cause of RRP is safe, offers the possibility of durable disease control following a short treatment course and is the recommended first‐line medical treatment for patients who wish to avoid the risks of repeat procedural management. Papilloma disease control with systemic bevacizumab, which carries defined risks and must be continued for clinical benefit is the recommended second‐line medical treatment for patients who do not achieve a complete response with immunotherapy and wish to continue medical management. For patients who elect to be treated with debulking procedures as needed, use of locally‐administered adjuvant should be considered. Conclusion This proposed management algorithm from the RRPF serves as a contemporary resource and information guide for adult patients with RRP and their physicians considering treatment options. Level of Evidence 5

Additive manufacturing (AM) of polyetheretherketone (PEEK) offers a promising route for producing lightweight, biocompatible, and patient-specific medical implants with complex geometries. This study investigates and optimizes fused deposition modeling (FDM) parameters for fabricating small-scale PEEK medical components with improved dimensional accuracy and surface quality. PEEK’s high processing temperature and thermal contraction make precision printing of fine features challenging. A Taguchi design of experiments (L9 orthogonal array) was employed to assess the effects of nozzle temperature, layer height, printing speed, and extrusion width on dimensional deviation and surface roughness using 5 × 5 × 5 mm cube specimens. Dimensional accuracy was quantified along the horizontal and vertical axes, and surface roughness was measured using a stylus profilometer. Statistical analysis showed layer height was the most significant factor affecting horizontal accuracy (p = 0.0225), while printing speed most strongly influenced vertical deviation. The optimal parameters, 450 °C nozzle temperature, 0.06 mm layer height, 7.5 mm/s printing speed, and 0.4 mm extrusion width, achieved mean deviations of 0.013 mm (horizontal) and 0.049 mm (vertical) with a surface roughness of 4.01 µm. Validation using a benchmark model and micro-computed tomography confirmed improved reproduction of small features under these conditions. The results demonstrate that precise control of FDM parameters enables accurate fabrication of sub-millimeter PEEK structures suitable for medical device applications.

Purpose: There are reported barriers to implementation of esophageal screening during the videofluoroscopic swallow study (VFSS) completed by the speech-language pathologist (SLP). Often, patients referred to the SLP for a VFSS have an esophageal component that may explain their complaint. In this article, authors explore roadblocks to esophageal screening and potential roadmaps to improve patient care through standardization of esophageal screening procedures. Conclusions: A strong body of literature supports physiologic, anatomic, and disease state relationships of the oropharynx and esophagus. Despite this, the assessment of the oropharynx and esophagus is dichotomized. There remain billing limitations for same-day esophagram and VFSS, and the well-documented esophageal screen provides a view of bolus flow in an upright, typical eating position with consideration of oropharyngeal function to provide a comprehensive view of the continuous process of swallowing from mouth to stomach. The continued practice of evaluating the oropharynx without consideration of the esophagus poses a threat to patient safety and may delay care. A collaborative, multidisciplinary effort among healthcare professionals to create streamlined practice parameters, update position statements, and enhance education parameters will allow for cohesive practices among professionals. Assessment of the swallow mechanism is incomplete without consideration of the entire continuum.

ABSTRACT Objective To evaluate the long‐term safety and clinical effect of INO‐3107 immunotherapy in adults with recurrent respiratory papillomatosis (RRP). Methods RRP‐002 was a retrospective, observational extension study that followed patients enrolled in the 52‐week RRP‐001 study. Patients with moderate to severe juvenile or adult‐onset RRP who had undergone ≥ 2 surgical interventions in the year preceding dosing were eligible for enrollment in RRP‐001. Participants underwent surgical debulking within 14 days prior to initial dosing and then received INO‐3107 on Day 0, Weeks 3, 6, and 9. Efficacy assessments during RRP‐002 follow‐up were the frequency of surgical interventions and alternative medication use. The safety evaluation included reported serious adverse events (SAEs). Results Twenty‐eight (28) of 32 participants from the 52‐week RRP‐001 study were enrolled in RRP‐002. The median follow‐up time for RRP‐002 was 1.8 years (range: 1.2–2.4 years) for a total median assessment time of 2.8 years (range: 1.0–3.5 years). There were no SAEs or long‐term safety concerns identified. The mean number of surgeries was reduced from 4.1 in the pre‐treatment period to 1.7 in the first year post‐INO‐3107 treatment (Year 1) to 0.9 in the second year (Year 2). The complete response rate (0 surgeries per year) increased from 28% (9/32) in Year 1 to 50% (14/28) in Year 2. Conclusion INO‐3107 is well tolerated and provides a continued clinical effect against HPV‐6 and 11 RRP that results in further reduction of the surgical burden observed in Year 1. These data support the role of INO‐3107 immunotherapy for adult patients with RRP. Level of Evidence: III.

Abstract Objective Determine relationship between frailty and hospital mortality, length of stay, cost, and medical and surgical complications in Zenker diverticulum surgery. Study Design Retrospective cross‐sectional. Setting National database. Methods Data from the National Inpatient Sample for 712 patients who underwent surgery for Zenker diverticulum 2016 to 2021 were analyzed using multivariate regressions. Frailty was defined as at least 1 frailty‐defining diagnosis from the Johns Hopkins ACG® Frailty Indicator. Elixhauser Comorbidity Index was calculated to quantify comorbidity burden. Results 12.2% of patients were identified as frail, 77.0% of whom had a weight loss or malnutrition diagnosis. Frailty predicted increased length of stay (mean, 4.09 days [95% CI: 2.98‐5.20]) and increased costs (mean, $10,500.36 [95% CI: $6885.76‐$14,114.95]). Frail patients were more likely to have medical complications compared to non‐frail patients (OR = 2.84 [95% CI: 1.66‐4.84]). Elixhauser Comorbidity Index was predictive of hospital mortality (OR = 1.78 [95% CI: 1.27‐2.51]) and likelihood of endoscopic surgical complications (OR = 1.25 [95% CI: 1.05‐1.47]), but frailty was not predictive of either. Conclusion Frailty is not associated with increased risk of surgical complications or mortality and is not an absolute contraindication to Zenker diverticulum surgery. Frailty predicts length of stay, costs, and medical complications in Zenker diverticulum surgery and should be used with comorbidity to stratify patient risk for surgery. Prospective studies involving frail patients could help develop a standardized method for assessing surgical fitness, potentially expanding treatment options and improving outcomes for this population. Level of Evidence 2.

Comparative analysis of fibrin sealant and recombinant thrombin hydrogels reveals distinct microarchitectures and cellular responses, emphasizing recombinant thrombin’s potential to enhance cellular activity and enable vesicle delivery.