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Objective: To determine the relationship between frequency of tonsillitis and the risk of post-tonsillectomy hemorrhage (PTH) in pediatric patients undergoing tonsillectomy for recurrent tonsillitis. Methods: After obtaining IRB approval from Nationwide Children’s Hospital, charts for all patients who underwent a total tonsillectomy in 2017 for recurrent or chronic tonsillitis were retrospectively reviewed (n = 424). Patients were divided into 2 cohorts based on the frequency of tonsillitis prior to surgery: those meeting the 1-year criteria with 7 or more infections in the past year (n = 100), and those who did not meet criteria defined as those with fewer than 7 infections in the past year (n = 324). The primary outcome of interest was PTH. Comparison of cohorts and frequency of PTH were assessed using bivariate analyses. Kaplan-Meier curves were used to compare time to onset of hemorrhage between primary vs. secondary PTH. Generalized mixed and logistic regression models were used to evaluate risk of hemorrhage following tonsillectomy. Results: Among a total cohort of 424 patients undergoing tonsillectomy, 23.58% (n = 100) met criteria while 76.42% (n = 324) did not. A total of 8.73% (n = 37) patients experienced PTH. Compared to those who did not meet criteria, those who met criteria had a higher odds of developing PTH; however, this was not significant (OR: 1.42 [95% CI: 0.67, 2.98], P = .3582). Estimated probability of developing PTH for those who met criteria was 11% [95% CI: 6.19, 18.81] compared to 8.03% [95% CI: 5.52, 11.54] for those who did not meet criteria. Among all PTH cases, 5.41% (n = 2) were primary hemorrhage while 94.59% (n = 35) were secondary hemorrhage with 50% of those with secondary PTH having experienced hemorrhage within 6 days [95% CI: 5, 7] of tonsillectomy. Patients with neuromuscular conditions had significantly higher odds of PTH (OR: 4.75 [95% CI: 1.19, 18.97], P = .0276). Conclusion: Patients who met the 1-year criteria for tonsillectomy did not have a significantly higher odds of PTH. Further research is needed to better evaluate the relationship between infection frequency and risk of PTH.

An adequate understanding of the relationships between radiographic and genomic features in diffuse intrinsic pontine glioma (DIPG) is essential, especially in the absence of universal biopsy, to further characterize the molecular heterogeneity of this disease and determine which patients are most likely to respond to biologically-driven therapies. Here, a radiogenomics analytic approach was applied to a cohort of 28 patients with DIPG. Tumor size and imaging characteristics from all available serial MRIs were evaluated by a neuro-radiologist, and patients were divided into three radiographic response groups (partial response [PR], stable disease [SD], progressive disease [PD]) based on MRI within 2 months of radiotherapy (RT) completion. Whole genome and RNA sequencing were performed on autopsy tumor specimens. We report several key, therapeutically-relevant findings: (1) Certain radiologic features on first and subsequent post-RT MRIs are associated with worse overall survival, including PD following irradiation as well as present, new, and/or increasing peripheral ring enhancement, necrosis, and diffusion restriction. (2) Upregulation of EMT-related genes and distant tumor spread at autopsy are observed in a subset of DIPG patients who exhibit poorer radiographic response to irradiation and/or higher likelihood of harboring H3F3A mutations, suggesting possible benefit of upfront craniospinal irradiation. (3) Additional genetic aberrations were identified, including DYNC1LI1 mutations in a subgroup of patients with PR on post-RT MRI; further investigation into potential roles in DIPG tumorigenesis and/or treatment sensitivity is necessary. (4) Whereas most DIPG tumors have an immunologically “cold” microenvironment, there appears to be a subset which harbor a more inflammatory genomic profile and/or higher mutational burden, with a trend toward improved overall survival and more favorable radiographic response to irradiation, in whom immunotherapy should be considered. This study has begun elucidating relationships between post-RT radiographic response with DIPG molecular profiles, revealing radiogenomically distinct subgroups with unique clinical trajectories and therapeutic targets.

Abtract Background This study describes imaging features of diffuse intrinsic pontine glioma (DIPG) and correlates with overall survival (OS) and histone mutation status in the International DIPG Registry (IDIPGR). Methods Four hundred cases submitted to the IDIPGR with a local diagnosis of DIPG and baseline MRI were evaluated by consensus review of 2 neuroradiologists; 43 cases were excluded (inadequate imaging or alternative diagnoses). Agreement between reviewers, association with histone status, and univariable and multivariable analyses relative to OS were assessed. Results On univariable analysis imaging features significantly associated with worse OS included: extrapontine extension, larger size, enhancement, necrosis, diffusion restriction, and distant disease. On central review, 9.5% of patients were considered not to have DIPG. There was moderate mean agreement of MRI features between reviewers. On multivariable analysis, chemotherapy, age, and distant disease were predictors of OS. There was no difference in OS between wild-type and H3 mutated cases. The only imaging feature associated with histone status was the presence of ill-defined signal infiltrating pontine fibers. Conclusions Baseline imaging features are assessed in the IDIPGR. There was a 9.5% discordance in DIPG diagnosis between local and central review, demonstrating need for central imaging confirmation for prospective trials. Although several imaging features were significantly associated with OS (univariable), only age and distant disease were significant on multivariable analyses. There was limited association of imaging features with histone mutation status, although numbers are small and evaluation exploratory.

The purpose of this paper is to explore the current literature on telemedicine in otolaryngology, focusing on the potential for telemedicine in the field and the major modalities available. Ultimately, the goal is to summarize telemedicine implementation in otolaryngology during the COVID-19 pandemic and potential long term applications. This paper analyzes a variety of studies that have evaluated the efficacy of different telemedicine approaches in otolaryngology, with commentary on what these results mean for the potential of telemedicine during the COVID-19 pandemic. Otolaryngology is well-suited for telemedicine, and this technology is viewed favorably by both patients and physicians. However, its application cannot be generalized to such a wide-ranging specialty. Furthermore, store and forward technology, which has been traditionally used to provide care to remote and underserved populations, and synchronous technology both have the potential to limit unnecessary in-person visits—ultimately keeping both patients and providers safe as social distancing continues.

To compare the incidence of middle ear effusion (MEE) at the time of bilateral tympanostomy tube insertion (BTI) for recurrent acute otitis media (rAOM) patients initially seen in-office or via telehealth.After obtaining IRB approval from Nationwide Children's Hospital, a total of 524 patients evaluated for rAOM were retrospectively reviewed after being divided into two cohorts: those seen via a telehealth visit from April to June of 2020 (n = 140), and those seen via an in-person visit from April to June of 2019 (n = 384). Recommendation for BTI was captured for each patient following their visit. Clinical characteristics documented at the time of the visit, such as history of intramuscular (IM) antibiotic use and hearing or speech concerns were also captured to determine whether both telehealth and in-person cohorts were similar in clinical presentation. For BTI patients, the presence or absence of MEE in either ear at the time of BTI was recorded. Patients with cleft palate or prior BTI were excluded.51.43% (72/140) of patients in the telehealth cohort were recommended for BTI. Of those recommended, 87.50% (63/72) underwent BTI. Of these, 31.75% (20/63) had a MEE at the time of BTI. In the in-office cohort, 69.01% (265/384) of patients were recommended for BTI. Of those recommended, 92.83% (246/265) underwent BTI. Of these, 69.92% (172/246) had a MEE at the time of BTI.There were significantly less middle ear effusions in the telehealth cohort compared to the in-office cohort (p 0.0001). It is well understood that telehealth is limited in its physical exam capabilities. It is possible that the use of telehealth for the surgical management of rAOM may lead to more procedures on patients without MEE.

PURPOSE To review data from DIPG Registry patients recorded to have received a second course of radiation therapy (rRT). METHODS The International DIPG Registry was searched for patients with DIPG who were treated with a known dose of rRT. Doses of rRT, timing from initial diagnosis and primary radiation therapy (pRT), radiographic response to rRT and survival from diagnosis (OS) were evaluated. RESULTS Sixty (11.2%) of 535 Registry patients underwent rRT; dose was provided for 44 patients. Median (range) data from those 44 revealed that rRT was given at 12 (2–65) months from initial diagnosis of DIPG and at 9.6 (1–61) months from completion of pRT at a dose of 26.7 (1.8–74) Gy. After completion of rRT, MRI showed response, progression, stable disease or was not available in 19, 8, 3 and 14 patients, respectively. Median PFS and OS were 11 and 18.1 months, respectively. 475 Registry patients did not undergo rRT; their ages, duration of symptoms, and primary treatment with or without chemotherapy were not significantly different from the rRT cohort. Median PFS and OS for the non-rRT patients were 6.9 and 10 months, respectively. rRT patients were more likely to have had radiographic evidence of tumor necrosis at diagnosis than non-rRT patients. CONCLUSIONS Administration of rRT to patients with DIPG has been inconsistent with respect to timing and dose. Toxicity, response and quality of life data are incomplete, but survival appears to be lengthened with rRT. Prospective clinical trials will elucidate benefits and risks of rRT.

BACKGROUND Recent discoveries have provided valuable insight into the genomic landscape of pediatric low-grade gliomas (LGGs) at diagnosis, facilitating molecularly targeted treatment. However, little is known about their temporal and therapy-related genomic heterogeneity. An adequate understanding of the evolution of pediatric LGGs’ genomic profiles over time is critically important in guiding decisions about targeted therapeutics and diagnostic biopsy at recurrence. METHODS Fluorescence in situ hybridization, mutation-specific immunohistochemistry, exome analyses, and/or targeted sequencing were performed on paired tumor samples from diagnostic and subsequent surgeries. RESULTS Ninety-four tumor samples from 45 patients (41 with two specimens, four with three specimens) from three institutions underwent testing. Conservation of BRAF fusion, BRAFV600E mutation, and FGFR1 rearrangement status was observed in 100%, 98%, and 96% of paired specimens, respectively. No loss or gain of IDH1 mutations or NTRK2, MYB, or MYBL1 rearrangements were detected over time. Histologic diagnosis remained the same in all tumors, with no acquired H3K27M mutations or malignant transformation. Changes in CDKN2A deletion status occurred in 10 patients (40%), with acquisition of CDKN2A deletion in seven (including three who received chemotherapy [two with temozolomide] and one who received radiation) and loss in three (including one who received targeted therapy and radiation). A trend toward shorter time to progression was observed among patients with acquired CDKN2A deletions compared to patients without acquisition of this alteration (median: 5.5 versus 14.0 months [p=0.078]). CONCLUSIONS Most targetable genetic aberrations in pediatric LGGs, including BRAF alterations, are conserved at recurrence and following chemotherapy or radiation. However, changes in CDKN2A deletion status over time were demonstrated. Acquisition of CDKN2A deletion may define a higher risk subgroup of pediatric LGGs with a poorer prognosis. Given the potential for targeted therapies for tumors harboring CDKN2A deletions, biopsy at recurrence may be indicated in certain patients, especially those with rapid progression.

INTRODUCTION Recent discoveries have provided valuable insight into the genomic landscape of pediatric low grade gliomas (LGGs) at diagnosis, facilitating molecularly targeted treatment. However, little is known about their temporal and therapy-related genomic heterogeneity. An adequate understanding of the evolution of pediatric LGGs’ genomic profiles over time is critically important in guiding decisions about targeted therapeutics and diagnostic biopsy at recurrence. METHODS Fluorescence in situ hybridization, mutation-specific immunohistochemistry, and exome analyses were performed on paired tumor samples from primary diagnostic and subsequent surgeries. RESULTS 101 tumor samples from 48 patients (43 with 2 specimens, 5 with 3 specimens) from 3 institutions underwent testing. BRAF fusion and BRAFV600E status were conserved in 100% and 97% of paired specimens, respectively. No loss or gain of IDH1 mutations or FGFR1, NTRK2, MYB, or MYBL1 rearrangements were detected over time. Histologic diagnosis remained the same in all tumors, with no acquired H3K27M mutations or malignant transformation. CDKN2A deletions were acquired in 7 patients (including 3 who received chemotherapy [2 with temozolomide] and 1 who received radiation), and were associated with a trend toward shorter time to progression (median: 5.5 vs. 13.0 months [p=0.08]). CONCLUSIONS Most targetable genetic alterations in pediatric LGGs, including BRAF alterations, are conserved at recurrence and following chemotherapy or radiation. However, CDKN2A deletion acquisition was demonstrated and may define a higher risk group. Given potential for targeted therapies for tumors acquiring CDKN2A deletions, performing a biopsy at recurrence may be indicated in certain patients, especially those with rapid progression.

INTRODUCTION: Pediatric low-grade gliomas (pLGG) represent the most common brain tumors in children. Though malignant transformation is rare, these tumors pose a formidable therapeutic challenge due to anatomy-limiting surgical options and local recurrence. The temporal and therapy-driven genomic evolution in pLGG is largely unknown. METHODS: To characterize the temporal genomic heterogeneity of pLGG, we performed fluorescence in situ hybridization, mutation-specific immunohistochemistry, and exome analyses on paired tumor samples from primary diagnostic and subsequent surgeries of 27 pLGG patients. RESULTS: 59 tumor samples were available for review and included pilocytic / pilomyxoid astrocytoma (PA) (67%), low grade astrocytoma (19%), ganglioglioma (11%), and pleomorphic xanthoastrocytoma (3%). BRAF duplication/rearrangement was detected in 56% of tested samples, limited to PA in all but one patient (ganglioglioma). 58% of samples harbored CDKN2A deletion, which was demonstrable across various histologies. BRAF duplication/rearrangement was found consistently conserved across primary and subsequent surgical samples, whereas CDKN2A status changed in 60% of tested temporal pairs, with deletion acquisition the most frequent finding (40%) at second surgery. Likewise, BRAF V600E mutation in one PA was lost at second surgery. Although CDKN2A status changes were seen following surgery alone, the addition of chemo-and/or radiation therapy was associated with a higher rate of temporal CDKN2A deletion acquisition (50%, versus 33% with surgery alone). CONCLUSION: Temporal genomic heterogeneity may be encountered in a significant proportion of pLGG, with some alterations potentially facilitated by therapy. Recurrence biopsy may provide improved guidance, particularly if targeted therapeutics are being considered.