OBJECTIVE:To evaluate safety and clinical course in pregnant idiopathic subglottic stenosis (iSGS) patients and to identify variables associated with operative dilation requirement during pregnancy. BACKGROUND:Pregnancy in patients with iSGS presents management challenges that may impact maternal and fetal health. Clinical studies and shared experiences are limited. METHODS:A retrospective chart review was conducted evaluating pregnant iSGS patients and an age-matched never pregnant iSGS control group. Pregnant patients were subcategorized based on whether they required surgery during pregnancy. The analyzed variables included demographics, inter-dilation intervals, time to first recurrence, intraoperative stenosis percent, and fetal and maternal safety. RESULTS:Thirty-three patients were included, 23 in the pregnancy group, and 10 in the control group. Thirteen patients required operative intervention during pregnancy. The mean age at iSGS diagnosis was 31.1 years. All pregnancies resulted in live births. No surgical or anesthesia-related complications were reported. Antinuclear antibody (ANA) positivity was more frequent in the surgical-intervention group compared to the nonintervention group (5/10 vs. 0, p < 0.05). The overall inter-dilation interval was longer in the pregnancy group compared to the control group (median: 70.9 vs. 39.6 weeks, p < 0.05) Average stenosis percentages in surgical dilations during and prior to pregnancy were comparable (60.4 ± 21.6 vs. 55.2 ± 27.8). CONCLUSION:Surgical management of iSGS patients is safe during pregnancy. Greater than 50% patients experienced exacerbation during pregnancy that required operative intervention. The only notable patient-specific factor associated with dilation during pregnancy was ANA positivity. There were no pregnancy-specific factors associated with the need for intervention. LEVEL OF EVIDENCE: 3:

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

ABSTRACT Objectives Systemic bevacizumab has been shown to reduce the surgical burden of recurrent respiratory papillomatosis (RRP). However, no previous studies have examined specific patient‐reported differences in quality‐of‐life (QoL) between systemic bevacizumab and surgical treatment. This study aimed to assess patient perspectives across two academic medical centers to inform clinical practice and shared decision‐making. Methods A cross‐institutional survey was distributed to patients who previously underwent both systemic bevacizumab and surgical treatment for RRP. Participants rated their experiences with each treatment across four domains: QoL, adverse effects, economics, and mental health. Paired responses were compared using the Wilcoxon signed‐rank test. Results Of 24 patients (mean age 48.3 years) who completed the survey, 18 (75%) were actively receiving systemic bevacizumab treatment. Mean age at RRP diagnosis was 17.1 years, and patients had undergone an average of 91.4 surgeries and 25.1 bevacizumab infusions. Compared with surgery, bevacizumab was associated with significantly improved self‐reported voice (p < 0.001), breathing (p < 0.001), and swallowing (p < 0.001), with longer‐lasting vocal improvement (p = 0.031), lower pain (p < 0.001), shorter vocal rest (p < 0.001), and fewer side effects (p = 0.002) with each treatment. Although expenditure (p = 0.649) and travel time (p = 0.288) did not differ significantly, patients reported missing fewer days of work (p < 0.001) during bevacizumab infusions. Moreover, optimism (p < 0.001) was greater with decreased fear (p = 0.002) during bevacizumab therapy. Overall, 79% wished to continue receiving bevacizumab treatment, and 83% believed it offered a better QoL. Conclusion Systemic bevacizumab improves patient QoL across multiple domains compared with surgical treatment and represents an important step toward more patient‐centered care in RRP. Level of Evidence 4.

Typical epidermodysplasia verruciformis (EV) is a rare, autosomal recessive disorder characterized by an unusual susceptibility to infection with specific skin-trophic types of human papillomavirus, principally betapapillomaviruses, and a propensity for developing malignant skin tumors in sun exposed regions. Its etiology reflects biallelic loss-of-function mutations in TMC6 (EVER1), TMC8 (EVER2) or CIB1. A TMC6-TMC8-CIB1 protein complex in the endoplasmic reticulum is hypothesized to be a restriction factor in keratinocytes for βHPV infection. However, the complex is also present in lymphocytes and its loss may compromise cellular immune control of βHPV infection. Indeed, certain primary immunodeficiencies, iatrogenic immunosuppression and AIDS are associated with the atypical form of EV. While well controlled in immunocompetent mice, murine papillomavirus MmuPV1 was first isolated from immunodeficient mice with florid skin warts, modeling atypical EV. To examine their potential as a model of typical EV, Tmc6-/-, Tmc8-/- or wildtype FVB mice were challenged with MmuPV1. At day 16 post vaginal challenge with MmuPV1, the levels of viral transcripts were similar in Tmc6-/- and Tmc8-/- mice and wildtype FVB mice, arguing against Tmc6/8 acting as intracellular restriction factors. Thereafter, greater clearance of MmuPV1 by the wildtype that the Tmc6-/- and Tmc8-/- FVB mice was evident, supporting the hypothesis that typical EV reflects a subtle cellular immune deficit. Indeed, Tmc6-/- or Tmc8-/- mice exhibit partial CD8 T cell deficits and elevated Treg. While interferon-γ production and surface CD25 were similarly elevated in CD8 T cells upon in vitro stimulation with anti-CD3/CD28, the fraction of Tmc6-/- or Tmc8-/- CD8 T cells that were dividing was lower compared to wildtype. Typical EV patients exhibit normal control of most viral infections; Tmc6-/-, Tmc8-/- and wildtype FVB mice similarly controlled vaccinia virus after skin challenge and induced neutralizing antibodies.

OBJECTIVES:Recurrent respiratory papillomatosis (RRP) is characterized by an irregular disease course, with recurrences after long periods of remission. New immunologic strategies are under investigation that aim to eliminate the chronic HPV infection. We evaluated recurrence patterns in RRP patients and sought to identify variables associated with prolonged remission periods. METHODS:Charts of all RRP patients seen since 2003 at our institution were reviewed. Surgical history and disease status in treatment-free intervals were evaluated. Patient and disease characteristics were compared using chi-squared and Fisher's exact tests in an exploratory analysis. RESULTS:Of 312 RRP patients, 71 (22.8%) experienced a treatment gap (TG) of at least 4 years between treatment and recurrence, with 43 (13.8%) having a TG over 10 years. TG patients did not differ from the remaining cohort in sex, juvenile/adult onset, or other clinical characteristics. To control for the possibility that TG patients resembled the entire cohort because of untreated occult disease, a subset was identified with prolonged (≥ 4 years) definitive remission. Compared to this remission group, TG patients were more likely to undergo surgery rather than office procedures before the gap in treatment (100% vs. 71.4% p = 0.003) and less likely to have supraglottic disease (17.5% vs. 57.1% p = 0.012). Other patient characteristics showed no significant differences. CONCLUSION:A substantial portion of RRP patients experience recurrence after prolonged treatment-free intervals, and this cohort cannot be easily predicted from available clinical characteristics. This highlights the need for effective immunologic strategies to eliminate the causative chronic infection. LEVEL OF EVIDENCE: 3:

Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV). INO-3107, DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11, was evaluated in a 52-week Phase 1/2 study for efficacy, safety, and immunogenicity (NCT04398433). Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP, requiring >= 2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation. The primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included surgical intervention frequency and change in RRP Severity Score (modified) post-INO-3107 and assessment of immune responses. 81% (26/32) of patients experienced surgery reduction following INO-3107 compared with the year prior to treatment. Blood assessments revealed HPV-6 and HPV-11 antigen-specific T-cell induction. RNA sequencing identified an inflammatory response in papillomas, inclusive of cytolytic CD8 + T-cell signatures. T-cell receptor sequencing revealed emergent T-cell clones in blood and confirmed trafficking to papillomas. Treatment-related adverse events (AEs) were reported in 13/32 (41%) patients, all low-grade. INO-3107 provides clinical benefit to HPV-6 and/or HPV-11-associated RRP adults and is well-tolerated. Importantly, treatment-induced peripheral T-cell responses traffic to airway tissue and are associated with clinical response.

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.

OBJECTIVE:Pulmonary recurrent respiratory papillomatosis (pRRP) is a rare manifestation of RRP with a paucity of data on workup and management. The objective was to develop guidance on the screening, diagnosis, and management of pRRP based on literature review and multidisciplinary expert consensus. METHODS:A pRRP expert group was assembled, comprising one representative from the RRP Foundation and 19 adult and pediatric otolaryngologists, thoracic surgeons, pulmonologists, oncologists, pathologists, and radiologists with experience in the management of pRRP. A rigorous Delphi method including video meetings and consensus surveys was used to establish consensus pertaining to screening, diagnosis, management, and treatment. RESULTS:After the literature review, the core working group created 33 statements regarding screening, diagnosis, management, and treatment. After distribution to the consensus group, three iterative surveys were performed, each followed by 90 min of live discussion. Consensus was achieved for screening (9 statements); diagnosis (6); management (4); treatment (11); and systemic treatment (3). Key statements include a recommendation for HPV typing at the time of diagnosis; chest CT to monitor disease progression; biopsy of suspected pulmonary lesions when possible; a multidisciplinary team for management; and consideration of systemic therapy. CONCLUSION:pRRP is present in up to 9% of patients with RRP and carries a 32-fold increased risk of malignant transformation. Obtaining consensus on best practices can reduce variability in the treatment of orphan diseases and guide future research efforts. This statement reflects the efforts of a national group of dedicated experts with an established history in managing this difficult disease. LEVEL OF EVIDENCE:Level V.

OBJECTIVES:The primary objective was to assess incidence and severity of acute laryngeal injury (ALgI) following intubation at time of tracheostomy using a proposed grading scale. The secondary objective was to evaluate what factors influence the rate of decannulation. METHODS:Single institution cohort study with review of prospectively maintained database including patients from October 2021 to October 2022 who underwent tracheostomy for prolonged intubation/critical illness. Severity of ALgI was graded as mild, moderate, or severe based on intraoperative endoscopic findings (laryngeal mucosal ulceration and/or granulation tissue). Rates of tracheostomy decannulation were collected as the secondary outcome measure. RESULTS:Twenty-eight patients met criteria for inclusion. About 60.7% (n = 17) patients were female. Average age was 59.0 ± 13.2 years old. Average body mass index was 32.3 ± 14.0 kg/m2. The most common endotracheal tube size was 7.5 (range = 6.0-8.0) inner diameter (ID) for men and 7.0 (range = 5.5-8.0) ID for women. Average Charlson Comorbidity Index (CCI) was 4.8 ± 2.4. Length of intubation was 15.7 ± 6.5 days (range = 5-30). Direct laryngoscopy at the time of tracheostomy demonstrated ALgI in 92.8% (n = 26) of patients. This was graded as mild (25.0%, n = 7), moderate (42.9%, n = 12), or severe (25.0%, n = 7). Severe ALgI was correlated with a reduced rate of tracheostomy decannulation compared to no/mild/moderate ALgI (28.5% vs 81.2%, P = .04). CONCLUSIONS:ALgI is highly prevalent in patients undergoing tracheostomy for prolonged intubation. Severe injury is associated with reduced rates of decannulation. Direct laryngoscopy at time of tracheostomy is warranted to diagnose ALgI and guide interventions. Determining the extent of laryngeal injury is prognostic and could help tailor follow-up and management strategies. LEVEL OF EVIDENCE:4.

OBJECTIVE:To provide detailed guidance on the administration of systemic bevacizumab in patients with recurrent respiratory papillomatosis (RRP) based on a detailed review of the scientific literature and a consensus of experts with real-world clinical experience. METHODS:A bevacizumab consensus working group (N = 10) was composed of adult and pediatric otolaryngologists, adult and pediatric oncologists, and a representative from the RRP Foundation (RRPF), all with experience administering systemic bevacizumab in patients with RRP. After extensive review of the medical literature, a modified Delphi method-based survey series was utilized to establish consensus on the following key areas: clinical and patient characteristics ideal for treatment candidacy, patient perspective in treatment decisions, treatment access, initial dosing, monitoring, guidelines for tapering and discontinuation, and reintensifying therapy. RESULTS:Seventy-nine statements were identified across nine critical domains, and 45 reached consensus [clinical benefits of bevacizumab (3), patient and disease characteristics for treatment consideration (7), contraindications for treatment (3), shared decision-making (incorporating the patient perspective) (5), treatment access (3), initial dosing and administration (8), monitoring (7), tapering and discontinuation (6), and reintensification (3)]. CONCLUSION:This consensus statement provides the necessary guidance for clinicians to initiate systemic administration of bevacizumab and represents a potential paradigm shift toward nonsurgical treatment options for patients with RRP. LEVEL OF EVIDENCE:5 Laryngoscope, 134:5041-5046, 2024.

ObjectivesMedical therapies to limit disease recurrence are critically needed for recurrent respiratory papillomatosis (RRP). Systemic bevacizumab is emerging as an exciting adjuvant therapy toward this end, but uptake has been poor due to the lack of experience and awareness of best prescribing practices. The objective of this study was to describe a single tertiary care academic medical center's experience using systemic bevacizumab for the treatment of RRP.MethodsA retrospective review was performed to identify patients with RRP on systemic bevacizumab. Demographic and clinical characteristics, findings on imaging reports, and disease response at all anatomic subsites involved in papilloma were documented.ResultsOf the 17 RRP patients on systemic bevacizumab, 9 (52.9%) were male, and 12 (70.6%) were diagnosed with juvenile‐onset RRP. The total lifetime number of surgeries was high, with more than half (n = 9; 52.9%) undergoing more than 50 surgeries. Following induction of systemic bevacizumab, a significant reduction in patients with laryngeal (n = 15; 94.1% vs. n = 7; 41.2%, p < 0.001) and tracheal (n = 11; 64.7% vs. n = 5; 29.4%, p = 0.04) RRP was noted. Surgical frequency was significantly lower following systemic bevacizumab (2.5 vs. 0.5 surgeries per year; p < 0.001). The most common complications were new‐onset hypertension (n = 4; 23.5%) and proteinuria (n = 5; 29.4%).ConclusionSystemic bevacizumab is effective in reducing the number of surgeries needed for RRP while exhibiting a relatively safe complication profile. Papillomas in the larynx and trachea are most responsive to systemic bevacizumab, while pulmonary RRP is most likely to exhibit a partial‐to‐stable response.Level of Evidence4 Laryngoscope, 134:3253–3259, 2024

Posterior glottic stenosis (PGS) has a significant impact on breathing and quality of life, and remains a challenging condition to manage. Literature does not provide a single optimal approach. In this study we aim to assess post-operative outcomes of adult patients with acquired PGS treated with open laryngotracheal reconstruction (LTR) with autologous or cadaveric rib grafting. This multicenter retrospective cohort study included adults who underwent open LTR for iatrogenic PGS (2015–2023) and were followed for 26 months on average. Data on comorbidities, surgical complications, and interventions following surgery were collected. Forty-three adult patients were included. Decannulation was successful in 76.7

OBJECTIVES:Recurrent respiratory papillomatosis (RRP) is caused by human papilloma virus (HPV) infection of the aerodigestive tract that significantly impacts quality-of-life including the ability to communicate and breathe. Treatment was traditionally limited to serial ablative procedures in the O.R. with possible local adjuvant therapy, but new systemic therapies, such as Vascular endothelial growth factor (VEGF) inhibitors, are showing significant promise. This study aims to determine whether rationale exists for combination therapeutic approaches using VEGF inhibitors and/or immune checkpoint blockade. METHODS:Using fresh specimens from the O.R., we performed flow cytometry on papilloma, normal adjacent tissue, and blood. Papilloma and surrounding tissue were examined for expression of PD-L1, PD-L2, Galectin-9, VEGFR2, and VEGFR3. CD8+ and CD4+ T cells were assayed for expression of PD-1, TIGIT, LAG3, and TIM3. RESULTS:Our data shows that papilloma tissue exhibits significantly higher levels of PD-L1 and PD-L2 compared to adjacent tissue. Elevated levels of the VEGF receptor VEGFR3 were also observed in papilloma tissue. When examining T cells within the papilloma, elevated PD-1 and TIGIT expression was observed on CD8+ T cells, while levels of PD-1, TIGIT, and TIM3 were elevated on CD4+ T cells compared to PBMCs. Heterogenous marker expression was observed between individuals. CONCLUSIONS:Our analysis shows that RRP tissue shows elevated levels of multiple immune check point targets and VEGFR3, with varied patterns unique to each papilloma patient. Some of these immune checkpoint markers already have novel immunotherapies available or in development, providing molecular rationale to offer these systemic treatments to selected patients affected by RRP alongside VEGF inhibitors. Laryngoscope, 134:2819-2825, 2024.

OBJECTIVES:Optimal vocal care for transgender patients necessitates regular follow-up. Factors associated with loss of follow-up in voice patients have never been investigated. In this study, we report a case series of transgender patients seeking vocal care at our institution and compare those who were and were not lost to follow-up. METHODS:Charts of transgender patients diagnosed with gender dysphoria who sought vocal care at our institution from January 2018 through May 2022 were reviewed. A chronological timeline of each patient's care at our vocal clinic was recorded. Loss of follow-up was defined as instances in which patients were not yet satisfied with their vocal outcomes and expressed interest in scheduling a subsequent visit but had not yet done so. Logistic regressions were performed to identify factors associated with loss of follow-up. RESULTS:Of 73 patients identified, 59 (80.8%) were assigned male at birth, and 72 (98.6%) were non-Hispanic White. Loss of follow-up occurred in 35 (47.9%) patients. Patients who received vocal surgery were significantly less likely to be lost to follow-up (OR: 0.16 (0.03, 0.79); p = 0.03). The availability of telemedicine options for vocal care was protective against loss of follow-up (OR: 0.09 (0.02, 0.44); p = 0.003). Patients who received other non-voice gender-affirming treatments concomitant to their vocal care were more likely to be lost to follow-up (OR: 4.44 (1.35, 14.59); p = 0.01). CONCLUSION:Loss of follow-up in transgender patients receiving vocal care is common. Providing telemedicine options and encouraging patients to complete vocal care prior to or after receiving other non-voice gender-affirming treatments may help increase rates of follow-up. LEVEL OF EVIDENCE:4 Laryngoscope, 133:3061-3067, 2023.

Purpose: Tracheostomy care is supply- and resource-intensive, and airway-related adverse events in community settings have high rates of readmission and mortality. Devices are often implicated in harm, but little is known about insurance coverage, gaps, and barriers to obtaining tracheostomy-related medically necessary durable medical equipment. We aimed to identify barriers patients may encounter in procuring tracheostomy-related durable medical equipment through insurance plan coverage. Materials and methods: Tracheostomy-related durable medical equipment provisions were evaluated across insurers, extracting data via structured telephone interviews and web-based searches. Each insurance company was contacted four times and queried iteratively regarding the range of coverage and co-pay policies. Outcome measures include call duration, consistency of explanation of benefits, and the number of transfers and disconnects. We also identified six qualitative themes from patient interviews. Results: Tracheostomy-related durable medical equipment coverage was offered in some form by 98.1 % (53/54) of plans across 11 insurers studied. Co-pays or deductibles were required in 42.6 % (23/54). There was significant variability in out-of-pocket expenditures. Fixed co-pays ranged from $0-30, and floating co-pays ranged from 0 to 40 %. During phone interviews, mean call duration was 19 +/- 10 min, with an average of 2 +/- 1 transfers between agents. Repeated calls revealed high information variability (mean score 2.4 +/- 1.5). Insurance sites proved challenging to navigate, scoring poorly on usability, literacy, and information quality. Conclusions: Several factors may limit access to potentially life-saving durable medical equipment for patients with tracheostomy. Barriers include out-of-pocket expenditures, lack of transparency on coverage, and lowquality information. Further research is necessary to evaluate patient outcomes.

Objectives Pulmonary papillomatosis is a rare but severe manifestation of recurrent respiratory papillomatosis (RRP). Efficacy data of systemic bevacizumab for pulmonary RRP are limited. This study's objective was to characterize disease response of pulmonary RRP to systemic bevacizumab. Methods A retrospective review was performed to identify patients with pulmonary RRP seen at three medical institutions. Clinical symptoms, CT findings, and disease response were compared before and after initiation of systemic bevacizumab therapy. Disease response was categorized as complete response, partial response, stabilization, or progression for each subsite involved by papilloma. Results Of the 12 pulmonary RRP patients treated with systemic bevacizumab, 4 (33.3%) were male, and 11 (91.7%) were juvenile‐onset RRP patients. All presented with laryngeal, tracheal, and pulmonary RRP. The median (range) age at first bevacizumab infusion was 48.1 (19.5–70.2) years. Progression to pulmonary malignancy was identified in 3 (25.0%) patients, 2 before initiation of and 1 after complete cessation of bevacizumab therapy. Clinical symptoms such as dyspnea (75.0% vs. 25.0%; p = 0.01) and dysphagia and/or odynophagia (33.3 vs. 0.0%; p = 0.03) were significantly decreased following bevacizumab therapy. Compared with pre‐treatment baseline, 9 (75.0%) patients experienced a stable‐to‐partial response in the lungs to systemic bevacizumab, and 10 (83.3%) experienced partial‐to‐complete responses in the larynx and trachea. Conclusion Systemic bevacizumab is effective in stabilizing progression in even the most severe cases of RRP, with both a dramatic reduction in laryngeal and tracheal disease as well as a stable‐to‐partial response of pulmonary involvement in a majority of patients. Level of Evidence 4 Laryngoscope , 134:577–581, 2024

OBJECTIVE:To describe iatrogenic laryngeal injury and identify its risk factors in recurrent respiratory papillomatosis (RRP) patients receiving surgical care. STUDY DESIGN:Case-control. SETTING:Tertiary care academic hospital in a metropolitan area. METHODS:Charts of patients with RRP seen at our institution from January 2002 to December 2022 were reviewed. Patients were separated into 2 cohorts based upon whether they experienced any form of iatrogenic laryngeal injury-including anterior commissure synechiae, vocal cord scar, reduced vocal fold pliability, vocal fold motion impairment, and glottic and/or subglottic stenosis. Adjusted logistic regressions were performed to identify factors associated with iatrogenic laryngeal injury. RESULTS:Of 199 RRP patients, 133 (66.8%) had identifiable iatrogenic laryngeal injury. The most common injuries were anterior commissure synechiae (n = 67; 50.4%) and reduced vocal fold pliability (n = 54; 40.6%). On a multivariate logistic regression, patients with diabetes mellitus (adjusted odds ratio [aOR] [95% confidence interval [CI]]: 2.99 [1.02, 8.79]; P = .04) and who received at least 10 surgeries lifetime (aOR [95% CI]: 14.47 [1.70, 123.19]; P = .01) were at increased risk for iatrogenic laryngeal injury, whereas receiving less than 5 surgeries (aOR [95% CI]: 0.21 [0.09, 0.51]; P < .001) was found to be protective. When treating the lifetime number of surgeries as a continuous variable, a greater number of surgeries was a significant risk factor for iatrogenic laryngeal injury (aOR [95% CI]: 1.32 [1.14, 1.53]; P < .001). CONCLUSION:These results suggest the importance of strict glucose control for diabetic patients receiving RRP surgical care, and emphasize the clinical need to identify medical therapies to decrease RRP surgical frequency for patients.

OBJECTIVE:The objective of this study was to characterize the risk factors for posterior glottic injury (PGI) in patients with coronavirus disease 2019 (COVID-19) who underwent prolonged intubation.STUDY DESIGN:This was a case-control study designed to assess the risk factors associated with development of PGI in COVID-19 patients who underwent prolonged intubation.SETTING:This single-center study was conducted at a tertiary care academic hospital in a metropolitan area.METHODS:We retrospectively reviewed patients who underwent prolonged intubation (≥7 days) for COVID-19 and compared those with PGI to those without. Patient demographics, comorbidities, and intubation characteristics were compared. Factors associated with PGI development among COVID-19 patients were assessed using multivariate regression.RESULTS:We identified 56 patients who presented with PGI following prolonged intubation for COVID-19 and 60 control patients who underwent prolonged intubation for COVID-19 but did not develop PGI. On univariate analyses, the number of reintubations due to failed extubation efforts was significantly associated with development of PGI (odds ratio [OR], 2.9; 95% CI, 1.4-6.2). On multivariate analyses, patients with cardiovascular disease (OR, 3.3; 95% CI, 1.2-9.0); non-COVID-19 respiratory illnesses, which included obstructive sleep apnea and asthma (OR, 5.9; 95% CI, 2.0-17.8); and diabetes mellitus (OR, 11.6; 95% CI, 3.7-36.6) were more likely to develop PGI.CONCLUSION:Our results represent the largest case-control study investigating risk factors for PGI in the setting of prolonged intubation specific to COVID-19. Our study suggests a significant role of comorbidities associated with poor wound healing with development of PGI.

Purpose. To study the geographic utilization of videolaryngostroboscopy (VLS) with the hypothesis that office-based voice care is unevenly distributed across the United States.Materials and Methods. This is a cross-sectional database analysis of Medicare beneficiaries. The Centers for Medicare and Medicaid Services Provider Utilization and Payment Data Physician and Other Supplier Public Use File from 2012 to 2017 was analyzed to evaluate VLS utilization. VLS distribution was assessed by calculating the density of VLS in each of the 306 hospital referral regions (HRRs) nationally. Associations between VLS density and population demographics and health system factors were assessed using Pearson correlation and multivariate regression analyses.Results. In total, 957,648 outpatient VLS were billed to Medicare part B between 2012 and 2017. The annual VLS density per HRR ranged from 0 to 38.2 per 1,000 enrollees. Pearson correlation revealed positive correlations between VLS density and number of Medicare enrollees (r = 0.2584, P < 0.001), income (r = 0.1913, P = 0.0008), education (r = 0.2089, P = 0.0002), and density of otolaryngologists (r = 0.1589, P = 0.0053) and medical specialists (r = 0.2326, P < 0.0001). A negative Pearson correlation was observed between VLS density and percent male (r =-0.1338, P = 0.0192) and Medicare mortality rate (r =-0.1628, P = 0.0043). On multivariate regression positive associations between VLS and number of Medicare enrollees (P = 0.002) and otolaryngologists (P = 0.049), and negative association with Medicare mortality rates (P = 0.032) remained significant.Conclusions. The distribution of office-based voice care varies widely across the country, even when analysis by HRR should have homogenized access to specialty care. Greater availability of VLS is seen in HRRs with more Medicare enrollees, greater density of otolaryngologists, and lower mortality rates.

OBJECTIVE:To evaluate the safety, immunogenicity, and efficacy of INO-3107, a DNA immunotherapy designed to elicit targeted T-cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433).METHODS:Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO-3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9. Patients underwent surgical debulking within 14 days prior to first dose, with office laryngoscopy and staging at screening and weeks 6, 11, 26, and 52. Primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included frequency of surgical interventions post-INO-3107 and cellular immune responses.RESULTS:An initial cohort of 21 patients was enrolled between October 2020 and August 2021. Fifteen (71.4%) patients had ≥1 TEAE; 11 (52.4%) were Grade 1, and 3 (14.3%) were Grade 3 (none treatment related). The most frequently reported TEAE was injection site or procedural pain (n = 8; 38.1%). Sixteen (76.2%) patients had fewer surgical interventions in the year following INO-3107 administration, with a median decrease of 3 interventions versus the preceding year. The RRP severity score, modified by Pransky, showed improvement from baseline to week 52. INO-3107 induced durable cellular responses against HPV-6 and HPV-11, with an increase in activated CD4 and CD8 T cells and CD8 cells with lytic potential.CONCLUSION:The data suggest that INO-3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP.LEVEL OF EVIDENCE:3 Laryngoscope, 133:3087-3093, 2023.