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Objectives: 1) Demonstrate the surgical anatomy of a fourth branchial cleft sinus relative to the superior and recurrent laryngeal nerves. 2) Review the diagnosis and management of a fourth branchial cleft sinus. Design: Case Study. Setting: Tertiary Children's Hospital. Patient: Three year old female who presented with a fever and painful right neck mass. CT scan demonstrated a right neck abscess containing air adjacent to the thyroid. Intervention: Two months after initial drainage, the patient underwent enbloc excision of the sinus including the thyroid lobe with closure of the piriform sinus defect. Main Outcome Measure: Intraoperative photo documentation of the anatomic relationship between the fourth branchial sinus and surrounding neural structures. Results: The sinus tract was shown to terminate in the piriform sinus inferior to the superior laryngeal nerve. [ABSTRACT FROM AUTHOR]

Objective: While management protocols of pediatric esophageal foreign bodies (EFBs) are well-delineated, resource utilization can be improved. This study's objectives were to explore hospital charges/costs for pediatric patients who present with EFBs and to identify patient risk factors associated with esophageal injury., Methods: A retrospective chart review of patients undergoing aerodigestive foreign body removal at a tertiary-care children's hospital from 2018 to 2021 was conducted. Data collected included demographics, medical history, presenting symptoms, EFB type, surgical findings, and hospital visit charges/costs., Results: 203 patients were included. 178 of 203 (87.7%) patients were admitted prior to operation. Unwitnessed EFB ingestion (p < 0.001, OR = 15.1, 95% CI = 5.88-38.6), experiencing symptoms for longer than a week (p < 0.001, OR = 11.4, 95% CI = 3.66-38.6) and the following presenting symptoms increased the odds of esophageal injury: dysphagia (p = 0.04, OR = 2.45, 95% CI = 1.02-5.85), respiratory distress (p = 0.005, OR = 15.5, 95% CI = 2.09-181), coughing (p < 0.001, OR = 10.1, 95% CI = 3.73-28.2), decreased oral intake (p = 0.001, OR = 6.60, 95% CI = 2.49-17.7), fever (p = 0.001, OR = 5.52, 95% CI = 1.46-19.6), and congestion (p = 0.001, OR = 8.15, 95% CI = 2.42-27.3). None of the 51 asymptomatic patients had esophageal injury. The median total charges during the encounter was $20,808 (interquartile range: $18,636-$24,252), with operating room (OR) (median: $5,396; 28.2%) and inpatient admission (median: $5,520; 26.0%) contributing the greatest percentage., Conclusions: Asymptomatic patients with EFBs did not experience esophageal injury. The OR and inpatient observation accounted for the greatest percentage of the hospital charges. These results support developing a potential algorithm to triage asymptomatic patients to be managed on a same-day outpatient basis to improve the value of care., Level of Evidence: 3 Laryngoscope, 134:4774-4782, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The objective of the study is to evaluate the outcomes of surgical management options for cholesteatoma using a national database., Study Design: Database analysis of the Pediatric Health Information System database to identify children undergoing surgical intervention for cholesteatoma from October 2015 to December 2022., Methods: Patients were categorized by initial surgical modality: tympanoplasty (TM), tympanoplasty with canal wall-up tympanomastoidectomy (TM-CWU), and tympanoplasty with canal wall-down tympanomastoidectomy (TM-CWD). Group comparisons were done on number of surgical revisions and number of patients identified with recommendations for hearing aids., Results: A total of 6304 patients were identified in the database who underwent surgery for cholesteatoma. Of these children, 3405 underwent TM (54.0%), 3116 underwent TM-CWU (49.4%), and 825 underwent TM-CWD (8.2%). The estimated difference in mean number of procedures was significantly higher in the TM-CWU group compared to TM-CWD (-0.34, 95% confidence interval [CI] -0.406,-0.279, P < .0001) and the TM group (9.352, 95% CI 0.315, 0.390, P < .0001). The rate of significant hearing loss necessitating hearing aids was significantly lower in the TM group, but there was no difference between the TM-CWU and TM-CWD groups (1.2%, P < .03, 1.9% vs 2.7%, P = .13). There was no difference in the number of speech delays/therapy diagnoses between TM and TM-CWU or TM-CWU and TM-CWD (3.5%vs 4.4% P = .07, 4.4% vs 5.2%., P = .38)., Conclusion: TM and TM-CWD had lower total surgical procedures than the TM-CWU group, and the TM group had a lesser rate of recommendation for hearing aids. The difference between number of procedures is likely due to the complexity of the disease; for instance, TM was likely chosen for small, less severe disease cases, whereas TM-CWD was chosen as more definitive treatment in aggressive cases. TM-CWD is associated with a lower rate of recidivism and recurrence, which also likely contributed to the lower number of procedures., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Purpose: Gamma knife radiosurgery (GKRS) for orbital cavernous hemangioma (OCH) has emerged as a promising method due to its significant clinical improvement and low incidence of complications. This study aimed to evaluate the safety and efficacy of GKRS for the treatment of OCH., Methods: In accordance with the PRISMA framework, we searched PubMed, Cochrane Central, and Embase for studies reporting outcomes of GKRS for OCH. Studies reporting complications, visual improvement, proptosis, tumor reduction rate, and tumor progression rate for OCH following GKRS were included., Results: Six studies, out of 1856 search results, with 100 patients were included. Among them, only 5 minor complications were related to GKRS, including 3 with orbital pain and 2 with periorbital chemosis. Thus, the complication rate was 13% (95% CI, 7-25%). Visual acuity and visual field improvement rates after GKRS were 80% (95% CI, 63-96%) and 71% (95% CI, 47-95%) respectively. Proptosis improved in 94% of cases (95% CI, 83-100%). The tumor reduction rate was 77% after GKRS (95% CI, 69-85%)., Conclusion: GKRS for OCH appears to be a safe technique, as evidenced by the rate of clinical improvement and radiological improvement. However, studies are limited by an absence of a control group. Additional studies are needed to evaluate the relative efficacy of GKRS as compared with alternative surgical modalities for OCH., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. Tonsillectomy is considered a potential treatment option. A common concept is that patients with PFAPA are more likely to have postoperative fever, which might be hard to distinguish from other etiologies such as malignant hyperthermia or drug adverse effects. For this reason, many institutions require these patients to be cared for at their main center and not at satellite centers. Our objective was to evaluate the rate of immediate postoperative fever in PFAPA patients undergoing tonsillectomy., Material and Methods: Following IRB approval (STUDY20060029), a retrospective chart review of all PFAPA patients who underwent tonsillectomy at a tertiary children's hospital between January 1st, 2013, and September 30th, 2022. The PHIS database was queried from January 1st, 2013, to June 30th, 2022, for pediatric tonsillectomy and PFAPA., Results: Sixty-one patients underwent tonsillectomy for PFAPA during the study period at our institution. Only one (1.6 %) had immediate postoperative fever. Fever episode resolution was seen in 90.25 % of patients, 41/41 (100 %) of the patients reported fever episodes pre-op, compared with 4/41 (9.75 %) post-op (McNemar's Chi-squared test, Chi2 = 37.0, p < 0.001). 481,118 pediatric tonsillectomies were recorded in the PHIS database during this period, 1197 (0.25 %) were also diagnosed with PFAPA. None of the PFAPA patients had an immediate post-operative fever., Conclusions: Our results suggest there is no increased risk of immediate postoperative fever in PFAPA patients undergoing tonsillectomy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Activated lung ILC2s produce large quantities of IL-5 and IL-13 that contribute to eosinophilic inflammation and mucus production following respiratory syncytial virus infection (RSV). The current understanding of ILC2 activation during RSV infection, is that ILC2s are activated by alarmins, including IL-33, released from airway epithelial cells in response to viral-mediated damage. Thus, high levels of RSV neutralizing maternal antibody generated from maternal immunization would be expected to reduce IL-33 production and mitigate ILC2 activation. Here we report that lung ILC2s from mice born to RSV-immunized dams become activated despite undetectable RSV replication. We also report, for the first time, expression of activating and inhibitory Fcgamma receptors on ILC2s that are differentially expressed in offspring born to immunized versus unimmunized dams. Alternatively, ex vivo IL-33-mediated activation of ILC2s was mitigated following the addition of antibody: antigen immune complexes. Further studies are needed to confirm the role of Fcgamma receptor ligation by immune complexes as an alternative mechanism of ILC2 regulation in RSV-associated eosinophilic lung inflammation., Competing Interests: SG, DB, and MY are employed by Calder Biosciences Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kosanovich, Eichinger, Lipp, Gidwani, Brahmbhatt, Yondola, Chi, Perkins and Empey.)

Objective: The objective of the current study is to perform a systematic review of the research literature to evaluate the impact of hearing loss on intelligence quotient (IQ) scores in pediatric patients., Data Sources: Ovid MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from their inception up to December 21st, 2021., Review Methods: Studies evaluating neurocognitive testing and hearing loss in children aged 21 years old or younger who had not undergone auditory rehabilitation were included in the study. Two independent reviewers evaluated titles, abstracts, and full texts for all included studies., Results: The literature search yielded 3199 studies of which 431 studies underwent full-text screening. 21 studies were ultimately selected for inclusion and contained a total of 1716 pediatric patients assessed through 13 different validated tests of intelligence. Six studies included both hearing impaired (HI) and normal hearing (NH) patients, and IQ testing results., Conclusion: The results of this large systematic review demonstrate that hearing impaired children may perform lower than their age-matched normal hearing peers on IQ testing across a battery of IQ testing modalities., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aim of the study was to investigate whether morphology (i.e. compact/diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients receiving Stereotactic Radiosurgery (SRS) for unruptured bAVMs. This retrospective study included 262 adult patients with unruptured bAVMs who underwent upfront SRS. Hemorrhagic events were defined as evidence of blood on CT or MRI. The morphology of bAVMs was evaluated using automated segmentation which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as the ratio of vessel to brain tissue, categorized bAVMs into compact and diffuse types based on the optimal cutoff. Cox proportional hazard model was used to identify the independent factors for post-SRS hemorrhage. The median clinical follow-ups was 62.1 months. Post-SRS hemorrhage occurred in 13 (5.0%) patients and one of them had two bleeds, resulting in an annual bleeding rate of 0.8%. Multivariable analysis revealed bAVM morphology (compact versus diffuse), bAVM volume, and prescribed margin dose were significant predictors. The post-SRS hemorrhage rate increased with larger bAVM volume only among the diffuse nidi (1.7 versus 14.9 versus 30.6 hemorrhage per 1000 person-years in bAVM volume < 20 cm 3 versus 20-40 cm 3 versus > 40 cm 3 ; p = 0.022). The significantly higher post-SRS hemorrhage rate of Spetzler-Martin grade IV-V compared with grade I-III bAVMs (20.0 versus 3.3 hemorrhages per 1000 person-years; p = 0.001) mainly originated from the diffuse bAVMs rather than the compact subgroup (30.9 versus 4.8 hemorrhages per 1000 person-years; p = 0.035). Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. The post-SRS hemorrhage rate exceeded 2.2% annually within the diffuse and large (> 40 cm 3 ) bAVMs and the diffuse Spetzler-Martin IV-V bAVMs. These findings may help guide patient selection of SRS for the unruptured bAVMs., (© 2024. The Author(s).)

Objective: COVID-19 (COVID) delayed access to speech and hearing services. The objective of this study was to identify interactions between socioeconomic status (SES) and cochlear implant (CI) usage during COVID., Methods: Consecutive pediatric patients (age 0-17) with CI and audiology visits between 2019 and 2022 at a tertiary care children's hospital were reviewed. Age, sex, race, insurance type, and proxy measures for SES using zip code were recorded. Hours spent with CI on and in different listening environments were compared between pre-COVID (1/1/2019-12/31/2019), COVID (4/1/2020-3/31/2021), and most recent (6/1/2021-5/31/2022) time periods., Results: Most patients were male (32/59, 54 % ears of 48 patients) and White, non-Hispanic (45/59, 76 %). Median age at implant was 2.0 years (range:0.6-12.2). There were no significant differences in hours spent with CI on during COVID compared with pre-COVID. However, children spent more time listening to louder noises (70-79 dB and ≥80 dB) recently compared with during COVID (p = 0.01 and 0.006, respectively). During COVID, children living in areas with greater educational attainment showed smaller reductions in total hours with CI on (β = 0.1, p = 0.02) and hours listening to speech in noise (β = 0.03, p = 0.005) compared with pre-COVID. In the most recent time period, children of minority race (β = -3.94 p = 0.008) and those who were older at implant (β = -0.630, p = 0.02) were more likely to experience reductions in total hours with CI on compared with during COVID., Conclusion: Interventions which mitigate barriers of implant use and promote rich listening home-environments for at risk populations should be implemented during challenging future social and environmental conditions., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives: The pathophysiology of vestibular schwannoma (VS) pseudoprogression after Gamma Knife radiosurgery (GKRS) remains unclear. Radiological features in pretreatment magnetic resonance images may help predict VS pseudoprogression. This study used VS radiological features quantified using an automated segmentation algorithm to predict pseudoprogression after GKRS treatment., Methods: This is a retrospective study comprising 330 patients with VS who received GKRS. After image preprocessing and T2W/contrast-enhanced T1-weighted image (CET1W) image generation, with fuzzy C-means clustering, VSs were segmented into solid and cystic components and classified as solid and cystic. Relevant radiological features were then extracted. The response to GKRS was classified into "nonpseudoprogression" and "pseudoprogression/fluctuation". The Z test for two proportions was used to compare solid and cystic VS for the likelihood of pseudoprogression/fluctuation. Logistic regression was used to assess the correlation between clinical variables and radiological features and response to GKRS., Results: The likelihood of pseudoprogression/fluctuation after GKRS was significantly higher for solid VS compared with cystic VS (55% vs 31%, P < .001). For the entire VS cohort, multivariable logistic regression revealed that a lower mean tumor signal intensity (SI) in T2W/CET1W images was associated with pseudoprogression/fluctuation after GKRS ( P = .001). For the solid VS subgroup, a lower mean tumor SI in T2W/CET1W images ( P = .035) was associated with pseudoprogression/fluctuation after GKRS. For the cystic VS subgroup, a lower mean SI of the cystic component in T2W/CET1W images ( P = .040) was associated with pseudoprogression/fluctuation after GKRS., Conclusion: Pseudoprogression is more likely to occur in solid VS compared with cystic VS. Quantitative radiological features in pretreatment magnetic resonance images were associated with pseudoprogression after GKRS. In T2W/CET1W images, solid VS with a lower mean tumor SI and cystic VS with a lower mean SI of cystic component were more likely to have pseudoprogression after GKRS. These radiological features can help predict the likelihood of pseudoprogression after GKRS., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: To evaluate the associations between proxy measures of socioeconomic status (SES) and usage of cochlear implants., Study Design: Retrospective case series., Methods: Usage outcomes were measured among patients with a cochlear implant and data logging at a tertiary care children's hospital between 2002 and 2017. Time per day with cochlear implant turned on, coil off, and listening to speech in noise and speech in quiet were extracted from audiology records, averaging right and left ear usage for those with bilateral implants. Associations between cochlear implant usage and demographic factors such as insurance type and median household income for zip code were assessed., Results: There were 142 total patients; 74 had bilateral usage data. Mean on air time was 10.76 hours (SD: 4.4). Those with private insurance had 1.2 hour more on air time/day ( P  = .047) and 0.9 hour more quiet time/day ( P  = .011) compared to those with public insurance. Younger age at last visit was associated with increased speech in quiet ( B  = -.08; 95% CI: -0.12-[-0.05], P  < .001) and coil off ( B  = -0.06; 95% CI: -0.11-[-0.02], P  = .006). Younger age at implant was associated with longer duration since last data logging visit ( B  = -10.46; 95% CI: -18.41-[-2.51], P  = .010), more daily use (on air; B  = -0.23; 95% CI: -0.43-[-0.03], P  = .026), and increased time spent listening to speech in noise ( B  = -0.07; 95% CI: -0.14-[-0.01], P  = .024). No other significant associations between datalogging output and each proxy SES factor were found., Conclusions: Lack of private insurance and older age at implantation decreased access to binaural hearing for children and young adults with cochlear implants., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: We compared adherence rates by attending otolaryngologists (OTOs) and advanced practice providers (APPs) to the 2013 American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guideline (CPG) for children with recurrent acute otitis media (RAOM) undergoing bilateral myringotomy and tympanostomy tube placement (BMT)., Methods: Patients aged 6 months to 12 years old undergoing BMT for RAOM who had a pre-operative visit with an independent APP or OTO were reviewed. Patients satisfied CPG criteria if middle ear effusion was identified at the pre-operative visit (pre-op) or if they did not have effusion but met exception criteria based on their risk for developmental difficulties and contraindications to medical therapy. Adherence rates between APPs and OTOs were compared. Agreement between pre-op and time-of-surgery middle ear effusion identification was assessed., Results: Nine hundred twenty-three patients were included. Six hundred one patients were seen by OTOs and 322 by APPs. Middle ear effusion was identified at pre-op in 84% of APP patients and in 76% of OTO patients ( P  = .005). Eight percent of APP patients and 11% of OTO patients met exception criteria ( P  = .138). Overall, 87% of OTO patients and 92% of APP patients met either CPG or exception criteria for BMT ( P  = .037). A logistic regression model demonstrated that pre-op provider type did not significantly impact rates of agreement between pre-op visit and time-of-surgery middle ear effusion identification., Conclusions: Independent APP-led clinics can reliably and effectively deliver evidence-based care for prevalent conditions such as RAOM at similar rates of adherence to CPGs as OTOs.

Purpose: To examine the differential effects of SRS and TKI on EGFR-mutated NSCLC patients with brain metastases (BMs) and outcomes following continuation of the same TKI agent in case of new BMs., Methods: This study included 608 NSCLC patients (2,274 BMs) while meta-analyses included 1,651 NSCLC patients (> 3,944 BMs). Overall survival (OS) and intracranial progression free survival (iPFS) were estimated using Kaplan-Meier methods. Hazard ratios (95% CI) of prognostic factors were estimated using Cox regression models., Results: The median OS/iPFS (95% CI) (months) for patients with wildtype EGFR/ALK, EGFR mutations, and ALK rearrangements were 17.7 (12.9-23.6)/12.1 (9.8-15.6), 28.9 (23.8-33.3)/17.7 (14.8-21.2), and 118.0 (not reached)/71.7 (15.1-not reached), respectively. In EGFR-mutated patients, meta-analyses combining our data showed significantly improved OS and iPFS of patients who received SRS and TKI (OS:35.1 months, iPFS:20.0 months) when compared to those who have SRS alone (OS:20.8 months, iPFS:11.8 months) or TKI alone (OS:24.3 months, iPFS:13.8 months). Having SRS for newly diagnosed BMs while keeping the existing TKI agent yielded OS (30.0 vs. 32.1 months, p = 0.200) non-inferior to patients who started combined SRS and TKI therapy for their newly diagnosed NSCLC with BMs. Multivariable analyses showed that good performance score and TKI therapy were associated with improved outcomes., Conclusions: Combined SRS and TKI resulted in favorable outcomes in EGFR-mutated NSCLC patients with newly diagnosed BMs. Continuation of the same TKI agent plus SRS in case of new brain metastases yielded good clinical outcomes and may be considered a standard-of-care treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Assess practice patterns amongst pediatric otolaryngologist for the management of children with SSNHL., Materials and Methods: A cross-sectional online survey of members of the American Society of Pediatric Otolaryngology (ASPO) was performed; 135 responded. Patterns in treatment modalities, ancillary tests, and timing of treatment and follow-up were evaluated. These patterns were compared between respondents with different characteristics (number of years in practice, clinic location, and number of pediatric SSNHL cases within the last year) using ordered logistic regression, Kruskal-Wallis, Wilcoxon rank-sum, and Fisher's exact tests., Results: Mean time from onset of hearing loss to presentation to a pediatric otolaryngologist was 10 days (range 1-60 days). The most cited reasons for delay in care were 'patient not seeking any healthcare evaluation' (65 %) and 'lack of access to obtain an audiogram' (54 %). The most ordered blood work was complete blood count (14 %) and herpes simplex testing (15 %). Complete blood count was ordered more frequently by physicians in practice for >10 years compared with those in practice 1-10 years, P = 0.03. Most respondents reported treating with systemic steroids (86/92, 93 %), including intratympanic steroids (32/92, 35 %). Treatment with systemic steroids was more common in academic compared with private practice, P = 0.03. Antivirals were the most common additional agent prescribed (14/89, 16 %). Most patients were seen in follow-up 1-4 weeks after diagnosis (63/85, 74 %)., Conclusions: Most pediatric otolaryngologists treat SSNHL with systemic steroids. The remainder of the diagnostic and management paradigm varies significantly, highlighting the need to systematically define which treatment optimizes outcomes in this population., Competing Interests: Declaration of competing interest This work was supported by University of Pittsburgh Intramural Scientific Program funding to Dr. Chi. REDCap is supported by National Institutes of Health funding to the Clinical and Translational Sciences Institute at the University of Pittsburgh (Grant Number UL1-TR-001857)., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Evaluate health-related quality of life (HR-QOL) benefits with cochlear implantation (CI) in children with unilateral sensorineural hearing loss (USNHL) versus bilateral sensorineural hearing loss (BSNHL)., Study Design: A cross-sectional survey of parents of children who underwent CI for USNHL and BSNHL., Setting: Tertiary care academic centers., Methods: The "Children with cochlear implants: parental perspectives" survey was administered. Parents rated responses on a 5-point Likert scale. Scores greater than 3.0 were considered favorable. Responses were recorded within 8 domains and groups were compared with respect to domain scores. Analysis of covariance models was used to compare groups while adjusting for age at implantation and duration of implant use., Results: There were 31 patients with USNHL and 27 patients with BSNHL. The average age of implantation in BSNHL patients was 1.9 and 6.7 years for USNHL. Parents of all children answered favorably in all domains. When adjusted for age at implantation and duration of implant use, parents of BSNHL children responded significantly more favorably only in 2 domains. When comparing patients with older age or prolonged duration of hearing loss in the USNHL cohort, there were favorable responses in all domains with no significant differences between groups., Conclusion: There are HR-QOL benefits of CI in USNHL children; less pronounced favorable results were noted only in 2 domains when compared to BSNHL children. Benefits were noted with CI in USNHL children at an older age at implantation or prolonged duration of hearing loss. Therefore, these factors should not be absolute contraindications for CI in USNHL., (© 2023 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Endocannabinoid 2-arachidonoylglycerol (2-AG) has been implicated in habituation to stress, and its augmentation reduces stress-induced anxiety-like behavior. Chronic restraint stress (CRS) changes the 2-AG levels in some gross brain areas, such as the forebrain. However, the detailed spatial distribution of 2-AG and its changes by CRS in stress processing-related anatomical structures such as the anterior cingulate cortex (ACC), caudate putamen (CP), nucleus accumbens (NAc), and piriform cortex (PIR) are still unclear. In this study, mice were restrained for 30 min in a 50 mL-centrifuge tube for eight consecutive days, followed by imaging of the coronal brain sections of control and stressed mice using desorption electrospray ionization mass spectrometry imaging (DESI-MSI). The results showed that from the forebrain to the cerebellum, 2-AG levels were highest in the hypothalamus and lowest in the hippocampal region. 2-AG levels were significantly ( p < 0.05) upregulated and 2-AG precursors levels were significantly ( p < 0.05) downregulated in the ACC, CP, NAc, and PIR of stressed mice compared with control mice. This study provided direct evidence of 2-AG expression and changes, suggesting that 2-AG levels are increased in the ACC CP, NAc, and PIR when individuals are under chronic stress.

Background: Whole brain radiation therapy (WBRT) for brain metastases (BMs) is a common cause of radiation-induced leukoencephalopathy; however the safety of alternative stereotactic radiosurgery (SRS) remains unclear. This study examined the incidence of leukoencephalopathy in patients treated with SRS alone versus WBRT plus SRS for BMs with a focus on the relationship between prognostic factors and leukoencephalopathy., Methods: Analysis was performed between 2002 and 2021. The total enrollment was 993 patients with the distribution: WBRT plus SRS (n = 291) and SRS only (n = 702). Leukoencephalopathy was graded from 0 to 3 for changes in white matter indicated by the MRI after WBRT or SRS. Patient characteristics and SRS dosimetric parameters were reviewed to identify factors that contributed to the incidence of leukoencephalopathy or overall survival., Results: The incidence of leukoencephalopathy was consistently higher in WBRT plus SRS group than in SRS alone group (p < 0.001). Leukoencephalopathy was also associated with a larger total tumor volume (≧28cm 3 ; p = 0.028) and age (> 77 years; p = 0.025). Nonetheless, the SRS integral dose to skull in the subgroup of WBRT plus SRS treatment was not demonstrated significance in development of leukoencephalopathy (p = 0.986 for integral dose 1-2 J, p = 0.776 for integral dose > 2 J)., Conclusions: This study revealed that SRS is safe for oligo-BMs in terms of leukoencephalopathy development. Patient age and total tumor volume were identified as important factors in assessing the development of leukoencephalopathy. The additional of SRS (even at an integral dose > 2 J) did not increase the incidence of leukoencephalopathy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Metastases extending to the pituitary gland and cavernous sinus are extremely rare; however, advances in neuroimaging have increased the reported incidence. Stereotactic radiosurgery (SRS) affords the precise delivery of focused radiation to minimize adverse radiation effects. This study assessed the efficacy and safety of SRS in the treatment of pituitary and cavernous sinus metastases., Methods: Analysis was performed on 23 patients with pituitary and cavernous sinus metastases who underwent treatment using SRS between 1996 and 2021. The cohort was categorized into 2 groups in terms of metastasis location: pituitary involvement (Group 1, n = 11) and cavernous sinus involvement (Group 2, n = 12). Overall survival, local tumor control, and distal tumor control rates were compared between the two groups using Kaplan-Meier analysis., Results: The median age of the cohort was 52.2 years and the median tumor volume was 4.5 mL. Overall survival rates were as follows: 1 year (72.9%), 2 years (51.8%), and 3 years (45.3%). Local tumor control rates were as follows: 1 year (82.3%), 2 years (82.3%), and 3 years (65.9%). Visual deficit and hypopituitarism were the most common presentations in Group 1, whereas cranial nerve deficit was the most common presentation in Group 2., Conclusions: SRS appears to be a safe and effective therapy for the treatment of pituitary and cavernous sinus metastases. GKRS is a relatively simple procedure, which places minimal stress on the patient, thereby facilitating further anti-cancer treatment. Considering the limited survival duration in cases of metastasis, it is very likely that post-GKRS complications (e.g., new onset cranial nerve deficit and hypopituitarism) would not become an issue before patient passes away., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To compare the mean pre-operative air-bone gaps (ABG), mean post-operative ABGs, and extrusion rates between pediatric recipients of partial ossicular reconstruction prostheses (PORPs) and pediatric recipients of total ossicular reconstruction prostheses (TORPs) via a systematic review and meta-analysis., Methods: A quantitative systematic review last updated on September 29, 2021 of PubMed, Scopus, and Embase databases was conducted for studies reporting mean post-operative ABGs or numbers of children with post-operative ABG ≤ 20 dB following PORP and TORP procedures in at least five children aged 0-18 years. Studies were excluded if they were review articles, conference abstracts, or not in English. Studies that primarily reported data on congenital aural atresia, stapedectomy/stapedotomy, congenital stapes fixation, or juvenile otosclerosis were also excluded. NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess for risk of bias. Review Manager (RevMan) version 5.4.1 was used to perform the meta-analysis and generate forest plots., Results: Out of 648 unique abstracts retrieved, 11 papers were included in this systematic review with meta-analysis. Data from 449 children (247 TORP recipients and 202 TORP recipients) are represented among the various analyses. Data from nine studies, representing 84.2 % of all children in the systematic review, demonstrated that PORP recipients presented with a pre-operative ABG 6.30 dB less than TORP recipients (mean difference: -6.30, 95 %CI: -7.4, -5.18, p < 0.01). Data from these same children demonstrated that PORP recipients had a 1.80 dB less post-operative ABG compared to TORP recipients (mean difference: -1.80 dB, 95 %CI: -2.84, -0.77, p < 0.001). Data from seven studies, representing 49.4 % of all children in the systematic review, demonstrated that PORP recipients were more likely to have a successful closure of the post-operative ABG to ≤20 dB (OR: 2.12, 95 %CI: 1.18, 3.79, p = 0.01). In these same children, 62.5 % of PORP recipients had a post-operative ABG ≤ 20 dB and 48.3 % of TORP recipients had a post-operative ABG ≤ 20 dB. There was no difference in extrusion rates between PORP recipients compared to TORP recipients (OR: 1.08, 95 %CI: 0.31, 3.78, p = 0.90) from five studies representing 45.9 % children in the systematic review., Conclusion: Children who receive a PORP have better pre-operative hearing baselines and post-operative hearing outcomes compared to those who receive TORP with similar rates of extrusion. More pediatric studies should report their mean pre- and post-operative ABGs stratifying by various material types, surgical indications, and surgical details to facilitate future meta-analyses., Competing Interests: Declaration of competing interest There are no conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Stereotactic radiosurgery (SRS) is an effective treatment for brain metastases (BMs) in patients with non-small cell lung cancer (NSCLC). However, factors associated with the development of post-SRS leptomeningeal metastasis (LM) remain unclear. The authors analyzed the incidence and risk factors of LM development in patients with NSCLC and BMs after SRS and examined the survival outcomes and prognostic factors after LM development., Methods: This retrospective study included patients with NSCLC treated with SRS for MRI-diagnosed BM from 2002 to 2021. The authors recorded various clinical and demographic data, including age, sex, tumor histology, molecular profile of tumors, extracranial disease status, previous craniotomy, Karnofsky Performance Status, systemic treatments, tumor volume, and number of BMs. The management and survival outcomes after LM diagnosis were also recorded., Results: LM developed in 13.7% of patients with NSCLC and BMs after SRS treatment. Large initial tumor volume and more than 5 BM lesions, but not EGFR mutation status and post-SRS treatment, were associated with LM development after SRS. Multivariate analysis revealed that chemotherapy and targeted therapy after LM were associated with better survival in patients with LM after SRS., Conclusions: This study is the first to evaluate the risk factors for LM in a relatively large cohort of patients with NSCLC after SRS. In patients with BMs harboring risk factors for subsequent LM, such as initial tumor volume and number of metastatic lesions, aggressive therapies with high CNS penetrating ability should be considered.

Objective: The goal of this study was to assess the safety and efficacy of single-session Gamma Knife radiosurgery (GKRS) for orbital cavernous hemangiomas (OCHs)., Methods: Patients who presented with an OCH between September 1999 and May 2022 and were treated with single-session GKRS were included in this single-center cohort study., Results: There were 23 patients (7 males and 16 females) in this study. The median margin dose was 12 Gy (range 11-13 Gy). The median clinical and radiological follow-ups were 45 months (range 5-190 months) and 45 months (range 6-190 months), respectively. Nine (69.2%) of 13 patients with visual acuity impairment had improvement in best corrected visual acuity. Of the 8 patients with visual field defects, 5 patients (62.5%) had complete resolution. Tumor regression was observed in 22 patients (95.7%). The mean relative reduction in tumor volume was 82.6% ± 23.7%. The relative reductions in tumor volume were 33%, 49%, 72%, 84%, and 89% at 6, 12, 24, 36, and 48 months, respectively. Adverse effects of radiation were not observed., Conclusions: GKRS appears to be safe and efficacious for treating OCHs over long-term follow-up. The treatment is associated with a high rate of regression in OCHs and remarkable improvement in both visual acuity and visual field deficits.

Objective: Tyrosine kinase inhibitors (TKIs) is the first-line treatment for EGFR-positive non-small cell lung cancer (NSCLC); however, its applicability to patients with wild-type NSCLC remains an issue of contention. This study compared the effects of gamma knife radiosurgery (GKRS) alone versus combining GKRS and TKIs in treating two genetic forms of NSCLC., Methods: This retrospective study examined 479 NSCLC patients with 1982 brain metastases who underwent GKRS and for whom imaging follow-up data or death records were available. All our patients were consecutive. All gene mutations were confirmed by lung biopsy. The three main endpoints in this study were overall survival (OS), local intracranial tumor control (LC), and distal intracranial tumor control (DC)., Results: There were 296 NSCLC patients with EGFR positive: TKI treatment (n = 262) and without TKI treatment (n = 34). GKRS + TKIs was more effective than GKRS alone in terms of OS (HR 0.53, p = 0.085) and DC (HR 0.51, p < 0.001). There were 150 NSCLC patients with wild-type EGFR: TKI treatment (n = 50) and without TKI treatment (n = 100). GKRS + TKIs was less effective than GKRS alone in terms of OS (HR 1.82, p = 0.049) and DC (HR: 1.40, p = 0.011). We observed no difference in terms of LC in both genetic groups., Conclusions: Combining GKRS with TKIs proved effective in EGFR positive NSCLC patients; however, we do not observe the similar results when combining GKRS with TKIs for patients with wild-type NSCLC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The goal of the study was to define and quantify brain arteriovenous malformation (bAVM) compactness and to assess its effect on outcomes after Gamma Knife radiosurgery (GKRS) for unruptured bAVMs., Methods: Unsupervised machine learning with fuzzy c-means clustering was used to differentiate the tissue constituents of bAVMs on T2-weighted MR images. The percentages of vessel, brain, and CSF were quantified. The proposed compactness index, defined as the ratio of vasculature tissue to brain tissue, categorized bAVM morphology into compact, intermediate, and diffuse types according to the tertiles of this index. The outcomes of interest were complete obliteration and radiation-induced changes (RICs)., Results: A total of 209 unruptured bAVMs treated with GKRS were retrospectively included. The median imaging and clinical follow-up periods were 49.2 and 72.3 months, respectively. One hundred seventy-three bAVMs (82.8%) achieved complete obliteration after a median latency period of 43.3 months. The rates of RIC and permanent RIC were 76.1% and 3.8%, respectively. Post-GKRS hemorrhage occurred in 14 patients (6.7%), resulting in an annual bleeding risk of 1.0%. Compact bAVM, smaller bAVM volume, and exclusively superficial venous drainage were independent predictors of complete obliteration. Diffuse bAVM morphology, larger bAVM volume, and higher margin dose were independently associated with RICs., Conclusions: The compactness index quantitatively describes the compactness of unruptured bAVMs. Moreover, compact bAVMs may have a higher obliteration rate and a smaller risk of RICs than diffuse bAVMs. This finding could help guide decision-making regarding GKRS treatment for patients with unruptured bAVMs.

Background: Maintaining bioenergetic homeostasis provides a means to reduce the risk of cardiovascular events during chronological aging. Nicotinamide adenine dinucleotide (NAD + ) acts as a signaling molecule, and its levels were used to govern several biological pathways, for example, promoting angiogenesis by SIRT1 (sirtuin 1)-mediated inhibition of Notch signaling to rejuvenate capillary density of old-aged mice. NAD + modulation shows promise in the vascular remodeling of endothelial cells. However, NAD + distribution in atherosclerotic regions remains uncharacterized. Omega-3 polyunsaturated fatty acids consumption, such as docosahexaenoic acid and eicosapentaenoic acid, might increase the abundance of cofactors in blood vessels due to omega-3 polyunsaturated fatty acids metabolism., Methods: Apolipoprotein E-deficient ( ApoE -/- ) mice were fed a Western diet, and the omega-3 polyunsaturated fatty acids-treated groups were supplemented with docosahexaenoic acid (1%, w/w) or eicosapentaenoic acid (1%, w/w) for 3 weeks. Desorption electrospray ionization mass spectrometry imaging was exploited to detect exogenous and endogenous NAD + imaging., Results: NAD + , NADH, NADP + , NADPH, FAD + , FADH, and nicotinic acid adenine dinucleotide of the aortic arches were detected higher in the omega-3 polyunsaturated fatty acids-treated mice than the nontreated control. Comparing the distribution in the outer and inner layers of the arterial walls, only NADPH was detected slightly higher in the outer part in eicosapentaenoic acid-treated mice., Conclusions: Supplementation of adding docosahexaenoic acid or eicosapentaenoic acid to the Western diet led to a higher NAD + , FAD + , and their metabolites in the aortic arch. Considering the pleiotropic roles of NAD + in biology, this result serves as a beneficial therapeutic strategy in the animal model counter to pathological conditions.

Objective: Whether combined radiation and tyrosine kinase inhibitor (TKI) therapy in non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) and epidermal growth factor receptor (EGFR) mutations confers additional benefits over TKI therapy alone remains a matter of debate. The goal of this study was to compare outcomes between combined TKI therapy with stereotactic radiosurgery (SRS) versus TKI therapy alone in NSCLC patients with BMs and EGFR mutations., Methods: Consecutive cases of NSCLC patients with EGFR mutations and BMs treated with TKIs were selected for inclusion in this study. Patients were categorized into two groups based on SRS: TKI therapy alone (group I) and combined SRS and TKI therapy (group II). Patients who had SRS or TKI as salvage therapy and those with prior radiation treatment for BMs were excluded. Tumor control (< 10% increase in tumor volume) and overall survival (OS) rates were compared using Kaplan-Meier analyses. Independent predictors of tumor control and OS were identified using multivariable Cox regression analyses., Results: The study cohort comprised 280 patients (n = 90 in group I and n = 190 in group II). Cumulative tumor control rates were higher in group II than in group I (79.8% vs 31.2% at 36 months, p < 0.0001). Cumulative OS rates were comparable between groups I and II (43.8% vs 59.4% at 36 months, p = 0.3203). Independent predictors of tumor control were older age (p < 0.01, HR 1.03), fewer BMs (p < 0.01, HR 1.09), lack of extracranial metastasis (p < 0.02, HR 0.70), and combined SRS and TKI therapy (p < 0.01, HR 0.25). Independent predictors of OS were fewer BMs (p < 0.01, HR 1.04) and a higher Karnofsky Performance Status score (p < 0.01, HR 0.97)., Conclusions: Although the OS rate did not differ between TKI therapy with and without SRS, the addition of SRS to TKI therapy resulted in improvement of intracranial tumor control. The lack of effect on survival rate with the addition of SRS may be attributable to extracranial disease progression. The addition of SRS to TKI therapy is recommended for intracranial disease control in NSCLC patients with BMs and EGFR mutations. Potential benefits may include prevention of neurological deficits and seizures. Future prospective studies may help clarify the clinical outcome benefits of SRS in these patients.

Objectives: Define aerosol and droplet risks associated with routine otolaryngology clinic procedures during the COVID-19 era., Methods: Clinical procedures were simulated in cadaveric heads whose oral and nasal cavities were coated with fluorescent tracer (vitamin B2) and breathing was manually simulated through retrograde intubation. A cascade impactor placed adjacent to the nares collected generated particles with aerodynamic diameters ≤14.1 µm. The 3D printed models and syringes were used to simulate middle and external ear suctioning as well as open suctioning, respectively. Provider's personal protective equipment (PPE) and procedural field contamination were also recorded for all trials using vitamin B2 fluorescent tracer., Results: The positive controls of nebulized vitamin B2 produced aerosol particles ≤3.30 µm and endonasal drilling of a 3D model generated particles ≤14.1 µm. As compared with positive controls, aerosols and small droplets with aerodynamic diameter ≤14.1 µm were not detected during rigid nasal endoscopy, flexible fiberoptic laryngoscopy, and rigid nasal suction of cadavers with simulated breathing. There was minimal to no field contamination in all 3 scenarios. Middle and external ear suctioning and open container suctioning did not result in any detectable droplet contamination. The clinic suction unit contained all fluorescent material without surrounding environmental contamination., Conclusion: While patients' coughing and sneezing may create a baseline risk for providers, this study demonstrates that nasal endoscopy, flexible laryngoscopy, and suctioning inherently do not pose an additional risk in terms of aerosol and small droplet generation. An overarching generalization cannot be made about endoscopy or suctioning being an aerosol generating procedure., Level of Evidence: 3.

Objectives: Evaluate health-related quality-of-life (HRQoL) measures in noncommunicative, neurologically impaired, developmentally delayed (NCNIDD) children compared to normally developing children (ND) who undergo cochlear implantation (CI)., Study Design: Cross-sectional survey of parents of NCNIDD and ND children who underwent CI., Setting: Two tertiary care medical centers., Methods: Questions comprising the Children With Cochlear Implants: Parental Perspectives survey were used in analysis. Average responses were calculated within 8 domains (communication, general functioning, self-reliance, well-being and happiness, social relationships, education, effects of implantation, and support the child). Groups were compared using Wilcoxon rank-sum test. Impact of individual and collective socioeconomic/family covariates was assessed using analysis of variance., Results: Surveys were returned from 17 of 42 (40%) patients with NCNIDD and 35 of 131 (27%) patients with ND. There were no statistically significant differences between groups in survey response rate, age, sex, age at implantation, current age, or duration of implant use. Overall, parents of children with ND responded more favorably in all domains vs children with NCNIDD. Parents of children with NCNIDD answered neutrally or favorably in all domains, except "support the child" and "self-reliance" domains. Differences between groups in mean domain scores, univariably and almost universally when adjusting for socioeconomic and family variables individually and collectively, were statistically significant., Conclusions: This study suggests that HRQoL benefits of CI are perceived in most domains by parents of children with NCNIDD, albeit less strongly than children with ND. A survey sensitive to challenges of children with NCNIDD may better capture benefits that may not be apparent in this study.

Purpose: Our purpose was to determine whether the coverage of brain parenchyma within the 12 Gy radiosurgical volume (V12) correlates with the development of radiation-induced changes (RICs) in patients with unruptured cerebral arteriovenous malformations (AVM) after undergoing stereotactic radiosurgery (SRS)., Methods and Materials: This study conducted regular follow-up examinations of 165 patients with unruptured AVMs who had previously undergone SRS. The RICs identified in T2-weighted magnetic resonance imaging (MRI) scans at any time point in the first 3 years after SRS were labeled "early RICs." The RICs identified in T2-weighted MRI scans at 5-year follow-up brain images were labeled "late RICs." Fully automated segmentation was used to analyze the MRI scans from these patients, whereupon the volume and proportion of brain parenchyma within the V12 was calculated. Logistic regression analysis was used to characterize the factors affecting the incidence of early and late RICs of any grade after SRS., Results: The median duration of follow-up was 70 months (range, 36-222). Early RICs were identified in 124 of the 165 patients with the highest grades as followed: grade 1 (103 patients), grade 2 (19 patients), and grade 3 (2 patients). Only 103 patients had more than 5 years follow-up, and late RICs were identified in 70 of 103 patients. Seventeen of 70 patients with late RICs were symptomatic. The median volume and proportion of brain parenchyma within the V12 was 22.4 cm 3 (range, 0.6-63.9) and 58.7% (range, 18.4-76.8). Univariate analysis revealed that AVM volume and the brain volume within the V12 were correlated with the incidence of both early and late RICs after SRS. Multivariable analysis revealed that only the brain volume within the V12 was significantly associated with the incidence of early and late RICs after SRS., Conclusions: In patients with unruptured AVM, the volume of brain parenchyma within the V12 was an important factor associated with the incidence of early and late RICs after SRS. Before SRS, meticulous radiosurgical planning to reduce brain parenchyma coverage within the V12 could reduce the risk of complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A bifunctional glycoside hydrolase GH78 from the ascomycete Xylaria polymorpha ( Xpo GH78) possesses catalytic versatility towards both glycosides and esters, which may be advantageous for the efficient degradation of the plant cell-wall complex that contains both diverse sugar residues and esterified structures. The contribution of Xpo GH78 to the conversion of lignocellulosic materials without any chemical pretreatment to release the water-soluble aromatic fragments, carbohydrates, and methanol was studied. The disintegrating effect of enzymatic lignocellulose treatment can be significantly improved by using different kinds of hydrolases and phenoloxidases. The considerable changes in low (3 kDa), medium (30 kDa), and high (> 200 kDa) aromatic fragments were observed after the treatment with Xpo GH78 alone or with this potent cocktail. Synergistic conversion of rape straw also resulted in a release of 17.3 mg of total carbohydrates ( e.g. , arabinose, galactose, glucose, mannose, xylose) per gram of substrate after incubating for 72 h. Moreover, the treatment of rape straw with Xpo GH78 led to a marginal methanol release of approximately 17 μg/g and improved to 270 μg/g by cooperation with the above accessory enzymes. In the case of beech wood conversion, the combined catalysis by Xpo GH78 and laccase caused an effect comparable with that of fungal strain X. polymorpha in woody cultures concerning the liberation of aromatic lignocellulose fragments.

Objective: Gamma Knife radiosurgery (GKRS) is a common treatment modality for vestibular schwannoma (VS). The ability to predict treatment response is important in patient counseling and decision-making. The authors developed an algorithm that can automatically segment and differentiate cystic and solid tumor components of VS. They also investigated associations between the quantified radiological features of each component and tumor response after GKRS., Methods: This is a retrospective study comprising 323 patients with VS treated with GKRS. After preprocessing and generation of pretreatment T2-weighted (T2W)/T1-weighted with contrast (T1WC) images, the authors segmented VSs into cystic and solid components by using fuzzy C-means clustering. Quantitative radiological features of the entire tumor and its cystic and solid components were extracted. Linear regression models were implemented to correlate clinical variables and radiological features with the specific growth rate (SGR) of VS after GKRS., Results: A multivariable linear regression model of radiological features of the entire tumor demonstrated that a higher tumor mean signal intensity (SI) on T2W/T1WC images (p < 0.001) was associated with a lower SGR after GKRS. Similarly, a multivariable linear regression model using radiological features of cystic and solid tumor components demonstrated that a higher solid component mean SI (p = 0.039) and a higher cystic component mean SI (p = 0.004) on T2W/T1WC images were associated with a lower SGR after GKRS. A larger cystic component proportion (p = 0.085) was associated with a trend toward a lower SGR after GKRS., Conclusions: Radiological features of VSs on pretreatment MRI that were quantified using fuzzy C-means were associated with tumor response after GKRS. Tumors with a higher tumor mean SI, a higher solid component mean SI, and a higher cystic component mean SI on T2W/T1WC images were more likely to regress in volume after GKRS. Those with a larger cystic component proportion also trended toward regression after GKRS. Further refinement of the algorithm may allow direct prediction of tumor response.

Objectives: Children with Down syndrome (DS) have a higher incidence of tympanostomy tube insertion (TTI) than children in the general population. As there were no studies investigating factors that are associated with multiple TTIs in children with DS, we sought to determine what factors increase or decrease the likelihood of repeat TTI in children with DS., Methods: A retrospective case-control study was performed on consecutive children with DS from 2007 to 2018 with first TTI at a large tertiary children's hospital and follow-up duration at least 27 months since first TTI., Results: 277 patients met the inclusion criteria. Repeat TTI rate was 61.4%. Having an indication of chronic otitis media with effusion (COME) at first TTI was an adjusted risk factor for increased rate of repeat TTI (OR: 2.01, 95%CI: 1.15-3.51, p = .014), while being older at first TTI was an adjusted protective factor for decreased rate of repeat TTI (OR: 0.84, 95%CI: 0.74-0.95, p = .004). Adenotonsillectomy at or before first TTI was not an adjusted protective factor for decreased rate of repeat TTI (OR: 0.915, 95%CI: 0.448-1.872, p = .809) and bilateral intra-operative fluid was not an adjusted risk factor for repeat TTI (OR: 1.97, 95%CI: 0.99-3.90, p = .054)., Conclusion: Children with DS were more likely to undergo repeat TTI if they were of younger age and if the indication for surgery was COME. The repeat TTI rate for children with DS was high at 61.4%. Prospective studies are warranted to more precisely investigate factors associated with repeat TTIs in this unique patient population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rationale: DIUTHAME (desorption ionization using through-hole alumina membrane), a recently developed matrix-free ionization-assisting substrate, was examined for reproducibility in terms of mass accuracy and intensity using standard lipid and mouse brain sections. The impregnation property of DIUTHAME significantly improved the reproducibility of mass accuracy and intensity compared with 2,5-dihydroxybenzoic acid (DHB)., Methods: Frozen tissue sections were mounted on indium tin oxide-coated glass slides. DIUTHAME and DHB were applied to individual sections. Subsequently, a solution of a phosphatidylcholine standard, PC(18:2/18:2), was poured onto the DIUTHAME and matrix. Finally, the samples were subjected to laser desorption ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry. The reproducibility was tested by calculating the mean ± standard deviation values of mass errors and intensities of individual ion species., Results: Analysis of the PC(18:2/18:2) standard showed significantly (p < 0.01) lower mass error for DIUTHAME-MS than for MALDI-MS. Endogenous PC(36:4) analysis in mouse brain section also showed significantly (p < 0.05) lower mass errors for DIUTHAME-MS. Furthermore, we investigated the mass error of some abundant lipid ions in brain sections and observed similar results. DIUTHAME-MS displayed lower signal intensity in standard PC analysis. Interestingly, it offered higher signal intensities for all the endogenous lipid ions. Lower fluctuations of both mass accuracies and signal intensities were observed in DIUTHAME-MS., Conclusions: Our results demonstrated that DIUTHAME-MS offers higher reproducibility for mass accuracies and intensities than MALDI-MS in both standard lipid and mouse brain tissue analyses. It can potentially be used instead of conventional MALDI-MS and mass spectrometry imaging analyses to achieve highly reproducible data for mass accuracy and intensity., (© 2021 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Objective: Hypothalamic obesity is common among patients with craniopharyngioma. This study examined whether precise stereotactic radiosurgery reduces the risk of hypothalamic obesity in cases of craniopharyngioma with expected long-term survival., Methods: This cohort study included 40 patients who had undergone Gamma Knife radiosurgery (GKRS; n = 22) or fractionated radiotherapy (FRT; n = 18) for residual or recurrent craniopharyngioma. Neurological presentations, tumor volume changes, and BMI values were meticulously reviewed. The median clinical follow-up durations were 9.7 years in the GKRS group and 10.8 years in the FRT group., Results: The median ages at the time of GKRS and FRT were 9.0 years and 10.0 years, respectively. The median margin dose of GKRS was 12.0 Gy (range 10.0-16.0 Gy), whereas the median dose of FRT was 50.40 Gy (range 44.1-56.3 Gy). Prior to GKRS or FRT, the median BMI values were 20.5 kg/m2 in the GKRS cohort and 20.0 kg/m2 in the FRT cohort. The median BMIs after radiation therapy at final follow-up were 21.0 kg/m2 and 24.0 kg/m2 for the GKRS and FRT cohorts, respectively. In the FRT cohort, BMI curves rapidly increased beyond the 85th percentile of the upper limit of the general population. BMI curves in the GKRS cohort increased more gradually, and many of the patients merged into the normal growth curve after adolescence. However, the observed difference was not statistically significant (p = 0.409)., Conclusions: The study compared the two adjuvant radiation modalities most commonly used for recurrent and residual craniopharyngioma. The authors' results revealed that precise radiosurgery dose planning can mediate the subsequent increase in BMI. There is every indication that meticulous GKRS treatment is an effective approach to treating craniopharyngioma while also reducing the risk of hypothalamic obesity.

Background: Official recommendations differ regarding tympanostomy-tube placement for children with recurrent acute otitis media., Methods: We randomly assigned children 6 to 35 months of age who had had at least three episodes of acute otitis media within 6 months, or at least four episodes within 12 months with at least one episode within the preceding 6 months, to either undergo tympanostomy-tube placement or receive medical management involving episodic antimicrobial treatment. The primary outcome was the mean number of episodes of acute otitis media per child-year (rate) during a 2-year period., Results: In our main, intention-to-treat analysis, the rate (±SE) of episodes of acute otitis media per child-year during a 2-year period was 1.48±0.08 in the tympanostomy-tube group and 1.56±0.08 in the medical-management group (P = 0.66). Because 10% of the children in the tympanostomy-tube group did not undergo tympanostomy-tube placement and 16% of the children in the medical-management group underwent tympanostomy-tube placement at parental request, we conducted a per-protocol analysis, which gave corresponding episode rates of 1.47±0.08 and 1.72±0.11, respectively. Among secondary outcomes in the main analysis, results were mixed. Favoring tympanostomy-tube placement were the time to a first episode of acute otitis media, various episode-related clinical findings, and the percentage of children meeting specified criteria for treatment failure. Favoring medical management was children's cumulative number of days with otorrhea. Outcomes that did not show substantial differences included the frequency distribution of episodes of acute otitis media, the percentage of episodes considered to be severe, and antimicrobial resistance among respiratory isolates. Trial-related adverse events were limited to those included among the secondary outcomes of the trial., Conclusions: Among children 6 to 35 months of age with recurrent acute otitis media, the rate of episodes of acute otitis media during a 2-year period was not significantly lower with tympanostomy-tube placement than with medical management. (Funded by the National Institute on Deafness and Other Communication Disorders and others; ClinicalTrials.gov number, NCT02567825.)., (Copyright © 2021 Massachusetts Medical Society.)

Hypothesis: Aerosols are generated during mastoidectomy and mitigation strategies may effectively reduce aerosol spread., Background: An objective understanding of aerosol generation and the effectiveness of mitigation strategies can inform interventions to reduce aerosol risk from mastoidectomy and other open surgeries involving drilling., Methods: Cadaveric and fluorescent three-dimensional printed temporal bone models were drilled under variable conditions and mitigation methods. Aerosol production was measured with a cascade impactor set to detect particle sizes under 14.1 μm. Field contamination was determined with examination under UV light., Results: Drilling of cadaveric bones and three-dimensional models resulted in strongly positive aerosol production, measuring positive in all eight impactor stages for the cadaver trials. This occurred regardless of using coarse or cutting burs, irrigation, a handheld suction, or an additional parked suction. The only mitigation factor that led to a completely negative aerosol result in all eight stages was placing an additional microscope drape to surround the field. Bone dust was scattered in all directions from the drill, including on the microscope, the surgeon, and visually suspended in the air for all but the drape trial., Conclusions: Aerosols are generated with drilling the mastoid. Using an additional microscope drape to cover the surgical field was an effective mitigation strategy to prevent fine aerosol dispersion while drilling., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2020, Otology & Neurotology, Inc.)

Objective: To determine if barriers to cochlear implantation (CI) exist with respect to Amish children and to describe unique considerations associated with CI and subsequent otologic care in the Amish population., Methods: Out of all patients who underwent CI at a tertiary care pediatric hospital from 2008 to 2019, Amish children were age-matched to the remainder of the cohort to compare demographics and care-related metrics including etiology of hearing loss, age at time of initial hearing-related appointment and at CI, total number of pre- and post-operative audiologic and otologic appointments, and post-operative complications. Social considerations that may pose barriers to care were collected for descriptive analysis., Results: Since 2008, 232 children underwent CI, of which 8 implants were performed on Amish children. Six (75%) Amish children underwent newborn hearing screening and 3(38%) were found to have syndromic etiology for hearing loss. While Amish patients had a lower number of both audiologic (15 vs 33.5, p<.001) and otologic (4.5 vs 8.5, p=.028) appointments when compared to age-matched controls, median age at the time of implantation for the whole sample was not different between groups (2.5 vs 2.0 years, p=.211). From a social standpoint, limitations in transportation, telephone communication, and ability to recharge processor batteries must be considered in the Amish population., Conclusion: Amish children undergoing CI face unique barriers to care including transportation and technologic limitations, leading to overall fewer hearing-related appointments when compared to an age-matched cohort. Understanding societal differences is important to facilitate optimal care for Amish children with hearing loss., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Although rare, orbital cavernous hemangioma (OCH) is the most common benign orbital neoplasm in adults and may cause vision disturbance or loss due to optic nerve compression. The conventional treatment is surgical excision, which carries a risk of intraoperative nerve damage, whereas gamma knife radiosurgery (GKRS) can be a safe and effective alternative. Herein, we report the results of four patients with OCH treated with GKRS, and describe the method of treatment including the optic nerve protection., Methods: This retrospective study included four consecutive patients (three women, one man; mean age: 50 ± 14.7 years) with OCH treated with single-session GKRS between 2014 and 2020. Three patients had decreased visual acuity. During GKRS, the prescription dose delivered to the tumor margin was 12 Gy at the 55-58% isodose line. The dose to the optic nerve margin was < 12 Gy. Follow-up included sequential magnetic resonance imaging (MRI) and ophthalmological examinations at 6-month intervals., Results: The median follow-up period was 29.5 ± 23 months (range, 12-63 months). After GKRS, three patients with visual dysfunction had substantial vision improvement; the fourth patient continued to have normal vision without deterioration. Radiological outcomes after GKRS indicated an average tumor shrinkage of 70% ± 10.6% at the 6-month follow-up and 83% ± 2.64% at the 1-year follow-up. No adverse radiation effects were observed., Conclusions: GKRS for OCH achieved favorable clinical outcomes, with substantial tumor volume reduction. OCH can be diagnosed based on characteristic MRI findings. GKRS may be considered a treatment option for OCH in selected cases.

Objective: During the COVID-19 era, a reliable method for tracing aerosols and droplets generated during otolaryngology procedures is needed to accurately assess contamination risk and to develop mitigation measures. Prior studies have not investigated the reliability of different fluorescent tracers for the purpose of studying aerosols and small droplets. Objectives include (1) comparing vitamin B2, fluorescein, and a commercial fluorescent green dye in terms of particle dispersion pattern, suspension into aerosols and small droplets, and fluorescence in aerosolized form and (2) determining the utility of vitamin B2 as a fluorescent tracer coating the aerodigestive tract mucosa in otolaryngology contamination models., Methods: Vitamin B2, fluorescein, and a commercial fluorescent dye were aerosolized using a nebulizer and passed through the nasal cavity from the trachea in a retrograde-intubated cadaveric head. In another scenario, vitamin B2 was irrigated to coat the nasal cavity and nasopharyngeal mucosa of a cadaveric head for assessment of aerosol and droplet generation from endonasal drilling. A cascade impactor was used to collect aerosols and small droplets ≤14.1 µm based on average aerodynamic diameter, and the collection chambers were visualized under UV light., Results: When vitamin B2 was nebulized, aerosols ≤5.4 µm were generated and the collected particles were fluorescent. When fluorescein and the commercial water tracer dye were nebulized, aerosols ≤8.61 µm and ≤2.08 µm respectively were generated, but the collected aerosols did not appear visibly fluorescent. Endonasal drilling in the nasopharynx coated with vitamin B2 irrigation yielded aerosols ≤3.30 µm that were fluorescent under UV light., Conclusion: Vitamin B2's reliability as a fluorescent tracer when suspended in aerosols and small droplets ≤14.1 µm and known mucosal safety profile make it an ideal compound compared to fluorescein and commercial water-based fluorescent dyes for use as a safe fluorescent tracer in healthcare contamination models especially with human subjects.

Objectives/hypothesis: Bilateral myringotomy and tympanostomy tube placement (BMT) is the most common pediatric surgery in the United States. Intraoperative middle ear effusion (MEE) is a risk factor for future BMTs in children with recurrent acute otitis media (RAOM). However, the impact of the type of MEE is unknown. Here, we assess otologic outcomes based on intraoperative MEE type and indication for surgery., Study Design: Case series chart review., Methods: After institutional review board approval, we performed a review of children undergoing BMTs between 2008 and 2009. Included patients had their first BMT, preoperative visit, and an operative report. Patients with cleft palate or Down syndrome were excluded. Indications for surgery included RAOM and chronic otitis media with effusion (COME). Other variables evaluated were future BMT, acquired cholesteatoma, and otorrhea. Logistic regression was used for statistical analysis., Results: Out of 1,045 patients reviewed, 680 were included and underwent their first BMT. There were 619 patients who had RAOM. Serous effusions were present in 22.2%, mucoid in 31.3%, purulent in 12.9%, undocumented or bloody in 2.3% of patients, and 31.2% of patients had dry middle ears. Moreover, 22.7% of patients underwent future BMTs. In RAOM patients, serous effusions decreased odds of perforation (odds ratio [OR]: 0.195, 95% confidence interval [CI]: 0.0438-0.867, P = .032), and purulent effusions increased the odds of in-office otorrhea suctioning (OR: 2.13, 95% CI: 1.20-3.77, P = .010) compared to dry. Mucoid effusions had no significant effect on outcomes in COME or RAOM patients., Conclusions: Intraoperative MEEs were noted in 68.7% of cases; purulent effusions increase the odds of in-office suctioning in RAOM patients., Level of Evidence: 4 Laryngoscope, 131:E993-E997, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To identify which patient characteristics and treatments are associated with hearing improvement in patients with pediatric sudden sensorineural hearing loss (SSNHL)., Methods: PubMed, Web of Science, Cochrane Library, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature were systematically searched for articles published before February 5, 2019, and references of relevant articles were screened. Original English-language case series and cohort studies were included if they addressed SSNHL in patients <20 years of age. Study characteristics, patient demographics, symptoms, treatments, and hearing outcomes were extracted. The primary outcome was hearing improvement., Results: Thirteen studies were included, totaling 605 patients (670 ears). Hearing did not improve in 46.7% of ears (95% confidence interval [CI]: 34.4% to 59.0%). Imaging (computed tomography and/or magnetic resonance imaging) results were described in three studies, and 24.2% of ears (95% CI: 7.7% to 40.6%) had abnormal findings. The most common serological finding was cytomegalovirus immunoglobulin (Ig)G or IgM (34.3% of ears tested, 95% CI: -2.9% to 71.6%). Unilateral hearing loss (odds ratio [OR]:3.85, P < .001), tinnitus (OR: 2.20, P = .003), age >12 years (OR: 2.11, P = .002), and ascending audiogram (OR: 3.66, P = .005), but not systemic or intratympanic steroids, were associated with increased odds of partial or complete improvement. In contrast, profound hearing loss (OR: 0.29, P < .001) and treatment delay of >6 days (OR: 0.27, P < .001) were associated with decreased odds of improvement., Conclusions: Despite treatment, half of patients had no improvement in hearing. Prognostic factors associated with hearing improvement were generally consistent with those established in the adult population. Further research with consistent definitions for hearing improvement is needed to improve the understanding and treatment of pediatric SSNHL., Level of Evidence: Laryngoscope, 131:425-434, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Recent cochlear implant (CI) electrodes are designed to be atraumatic to inner ear structures. Studies in adults have demonstrated improved hearing preservation rates with the CI532/632 electrode, but none have examined this in children. Our objective is to describe the hearing preservation rate with CI532/632 in pediatric patients and determine factors that influence hearing preservation., Methods: We conducted a retrospective cohort study of children undergoing CI over a three-year period. Inclusion criteria were: CI with the 532/632 electrode, presence of pre-operative low frequency hearing defined by pure tone average (PTA) of ≤80 dB at 250 Hz or at the average of 250 and 500 Hz, and post-operative unaided audiometry. Other data collected included demographics, otologic history, imaging, and surgical details., Results: A total of 13 patients and 15 ears were included. Hearing was preserved in 10/15 (66%) ears at an average follow-up of 6 months, similar to that reported in the adult literature. Patients with preserved hearing post-operatively were more likely to have a positive family history of hearing loss. There was a trend towards patients with anatomic inner ear abnormalities being more likely to lose hearing after CI, but this was not statistically significant. Pre-operative thresholds were not predictive of hearing preservation. Patients with preserved hearing had a significantly smaller shift in thresholds after cochlear implantation. Therefore, hearing preserved and non-preserved groups differed more by the magnitude of change in threshold, rather than their preoperative threshold. Other factors such as age, sex, surgeon, and surgery duration were not associated with hearing preservation., Conclusion: This study describes low frequency hearing preservation after pediatric CI532/632 implantation. The hearing preservation rate in our cohort was consistent with that reported in the adult literature. Our data suggest that preoperative thresholds do not solely determine which patients will go on to experience hearing preservation. We believe this will aid surgeons with patient-specific device selection and counseling potential pediatric CI recipients with preserved hearing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: We proposed an algorithm to automate the components within the identification of components within the nidus of cerebral arteriovenous malformations (AVMs) which may be used to analyze the relationship between its diffuseness and treatment outcomes following stereotactic radiosurgery (SRS)., Objectives: to determine the impact of the diffuseness of the AVM nidus on SRS outcomes., Methods: This study conducted regular follow-ups of 209 patients with unruptured AVMs who underwent SRS. The diffuseness of the AVM nidus was estimated by quantifying the proportions of vascular nidal component, brain parenchyma, and cerebrospinal fluid in T2-weighted MRIs. We used Cox regression analysis to characterize the association between nidal diffuseness and treatment outcomes in terms of obliteration rate and radiation-induced change (RICs) rate following SRS., Results: The median AVM volume was 20.7 cm3. The median duration of imaging follow-up was 51 months after SRS. The overall AVM obliteration rate was 68.4%. RICs were identified in 156 of the 209 patients (74.6%). The median proportions of the nidus of AVM and brain parenchyma components within the prescription isodose range were 30.2 and 52.2%, respectively. Cox regression multivariate analysis revealed that the only factor associated with AVM obliteration rate after SRS was AVM volume. However, a larger AVM volume (>20 mL) and a larger proportion of brain parenchyma (>50%) within the prescription isodose range were both correlated with a higher RIC rate following SRS., Conclusions: The diffuseness of the nidus indeed appears to affect the RIC rate following SRS in patients with unruptured AVMs., (© 2020 S. Karger AG, Basel.)

Objective: To review the otologic outcomes of infants who failed the newborn hearing screen (NBHS) and received early tympanostomy tubes for otitis media with effusion (OME)., Study Design: Retrospective case series., Setting: Tertiary care pediatric hospital., Subjects and Methods: Consecutive patients (2007-2018) who failed an NBHS and required tympanostomy tubes before 6 months of age were included. Variables including hearing loss and otitis media risk factors, episodes of acute otitis media (AOM), number of subsequent tympanostomy tubes, and posttympanostomy tube audiogram results were recorded., Results: The cohort included 171 patients. Median age at referral to otolaryngology was 2.7 months. Sensorineural hearing loss (SNHL) was subsequently identified in 22 (12.9%) of infants after resolution of the effusion. The peak incidence of AOM was during the second year of life (1-1.9 years), with a median of 1 episode. Ninety-five patients (55.6%) had replacement of tubes, 41 of 171 (24.0%) had 2 or more additional sets of tubes, and long-term tubes were eventually placed in 8 of 95 (8.4%) patients. Craniofacial anomalies were identified in 43.3% of patients. Tube replacement (hazard ratio, 3.00; 95% CI, 1.95-4.63; P < .01, log-rank) and AOM (β, 1.04; 95% CI, 0.43-1.65; P = .04, ordered logistic regression) were more common, and SNHL less common (odds ratio, 0.17; 95% CI, 0.031-0.61; P < .01, logistic regression), in children with craniofacial anomalies., Conclusion: OME is a common cause of failed NBHS. A notable proportion was subsequently found to have SNHL, reiterating the need for postoperative hearing assessments. Infants meeting indication for early tympanostomy tubes for resolution of OME have a high incidence of recurrent AOM and require subsequent tubes.

Purpose: The current loss to follow-up rate after failed newborn hearing screening (NBHS) is 34.4%. Previous studies have found that lack of parental and primary care provider (PCP) awareness of NBHS results are significant contributors to loss to follow-up. The objective of this study was to identify factors associated with parental and PCP awareness of NBHS results., Materials and Methods: Retrospective cohort study. A survey asking about demographics and knowledge of NBHS testing and results was offered to parents in the waiting room of an urban pediatric primary care office. Included were biological parents ≥18 years of age of children ≤10 years of age born in Pennsylvania. Each child's chart was reviewed for PCP documentation of NBHS results. The odds of knowing NBHS results were evaluated using logistic regression., Results: The survey was completed by 304 parents. 74.0% were aware of their child's NBHS results. Child age ≥1 year old (OR: 0.49, 95%CI[0.29, 0.82], P = 0.007) and Hispanic ethnicity (OR: 0.38, 95%CI[0.16, 0.89], P = 0.03) were associated with decreased odds of a parent knowing NBHS results. In addition, fewer fathers knew the results of their child's NBHS compared with mothers (OR: 0.33, 95%CI[0.18, 0.62], P < 0.001). However, parental awareness was not associated with birthing facility or insurance type. 222 charts were reviewed for NBHS documentation, revealing PCP awareness in 95.5% of cases and no associations with any of the factors examined., Conclusions: Factors associated with parents not knowing NBHS results included being the parent of an older child, Hispanic, or the father., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: Stereotactic radiosurgery (SRS) is a potential re-irradiation treatment for recurrent intracranial ependymoma after prior radiation therapy. The purpose of this study was to examine the efficacy and safety of repeated SRS in the treatment of recurrent intracranial ependymomas., Methods: This is a retrospective study of consecutive patients with residual or recurrent intracranial ependymomas who were treated with SRS between 1993 and 2018. Tumor progression was defined as a ≥ 10% increase in tumor volume. Tumor regression was defined as a ≥ 10% reduction in tumor volume. A tumor that remained within 10% of its original volume was defined as stable. Tumor control comprised tumor regression and stability. Time-dependent analyses were performed using two treatment failure endpoint definitions: (1) evidence of local tumor progression or distant metastasis (single SRS analysis), and (2) lack of tumor response to SRS (repeated SRS analysis). These analyses were adjusted for the competing risk of death., Results: The study comprised 37 patients (65 intracranial ependymomas) who underwent multiple SRS sessions (range: 1-7). Median age was 10.2 years (range: 0.8-53.8 years), and median tumor volume was 1.5 mL (range: 0.01-22.5 mL). The median radiation dose was 13.3 Gy (range: 7.9-22.0 Gy) at a median isodose line of 57% (range: 50-90%). Overall tumor control rates in the single SRS analysis adjusting for the competing risk of death were 53.6%, 30.5%, and 23.6% at 1, 3, and 5 years, respectively. Overall tumor control rates in the repeated SRS analysis adjusting for the competing risk of death were 70.6%, 50.4%, and 43.1% at 1, 3, and 5 years, respectively. Prior gross total resection was the only independent predictor of overall tumor control after SRS (aHR = 25.62 (1.55-422.1), p = 0.02)., Conclusions: Repeated GKRS appeared to be an effective treatment strategy for recurrent or residual intracranial ependymomas, with acceptable complication rates.

Objective: Develop a clinically relevant and reproducible endoscopic animal model for subglottic stenosis amenable to testing of minimally invasive therapeutic modalities., Study Design: Cohort study., Setting: Division of Laboratory Animals Research, University of Pittsburgh., Subjects and Methods: Subglottic stenosis was induced endoscopically via microsuspension laryngoscopy in 26 New Zealand white rabbits. A trimmed polypropylene brush connected to a novel electronic stenosis induction apparatus was used to create circumferential trauma to the subglottis. By using open source image analysis software, the cross-sectional areas of the stenotic and native airways were compared to calculate the percentage of stenosis and the Myer-Cotton classification grade., Results: Of the 26 rabbits, 24 (92%) exhibited stenosis after the first attempt. The mean percentage of airway stenosis was 57% (range, 34%-85%; SD, 15%). Five rabbits (19.2%) died on the day of stenosis induction from procedural complications. Of the 21 rabbits, 2 demonstrated no stenosis 7 days after initial injury and so underwent reinduction of airway injury, upon which they developed stenosis. Overall, 14 of the 21 rabbits (67%) exhibited moderate to severe stenosis (grade 2 or 3)., Conclusion: The stenosis induction apparatus reliably induced stenosis with a low mortality rate as compared with that of other methods in the literature. The device could be improved to generate a predetermined potentially reproducible grade of stenosis as desired by the operator. This method sets the stage for a clinically relevant and reproducible subglottic stenosis disease model that is amenable to testing of minimally invasive treatment modalities.