Distant metastases in human papillomavirus-related oropharyngeal squamous cell carcinoma: Systematic review and meta-analysis.

The prevalence of distant metastases (DM) in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) remains unknown. A PRISMA systematic review of DM rates in patients with HPV-related OPSCC was performed. PubMed-MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched. The primary outcome was prevalence of DM. Data on demographics, tumor classification, and clinical outcomes were also collected. Meta-analysis of pooled DM rate was determined. Ten articles met inclusion criteria, representing 1860 patients with mean follow-up of 3.6 years. Overall DM rate was 7.0% (95% CI: 5.9-8.2). T3 or T4 classification disease was associated with a 4.88-fold (95% CI: 1.92-12.40) risk of DM compared to T1 or T2 classification disease. This study is the first to systematically review the prevalence of DM among patients with HPV-related OPSCC, where pooled DM rate was found to be 7%.

The Impact of Intratympanic Steroid Dosage on Hearing Recovery in Sudden Sensorineural Hearing Loss.

OBJECTIVE: To investigate how dexamethasone dosage impacts intratympanic steroid therapy (IST) for treatment of sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Retrospective review. METHODS: Inclusion criteria identified subjects who received IST between January 1, 2010 and June 1, 2020 for iSSNHL. Subjects with Meniere's disease, autoimmune inner ear disease, subjects who received injections of non-dexamethasone steroid formulations, and subjects with missing audiogram data were excluded. Subjects were stratified by dexamethasone dosage: low-dose (10 mg/ml) versus high-dose (24 mg/ml), time-to-treatment and oral corticosteroid use. Outcome measures included post-treatment improvement in 4-frequency pure tone average (4F-PTA [500, 1000, 2000,4000 Hz]), low- and high-frequency PTA (250-1000 Hz and 2000-8000 Hz, respectively). RESULTS: Of the 55 included subjects (50.9% male, mean age 48.9 ± 16.4 years), 31 received high-dose while 24 received low-dose injections. 90.9% of subjects were treated with oral steroids prior to or during IST. No significant differences in hearing outcomes were observed between low- and high-dose cohorts or when stratifying by oral steroid use. Time-to-treatment analysis comparing ≤1 month (67.3%) versus >1 month (32.7%) groups demonstrated a significant improvement in post-treatment 4F-PTA (P = .01) in the ≤1 month group. CONCLUSIONS: Hearing recovery was not significantly different between the 10 mg/ml versus 24 mg/ml doses of intratympanic dexamethasone, suggesting that steroid dose may not impact the efficacy of IST. A shorter time-to-treatment was observed to be favorable for hearing improvement.

The impact of COVID-19 on presentation and diagnosis of head and neck squamous cell carcinoma.

Objective: To analyze how the COVID-19 pandemic has influenced trends in head and neck squamous cell carcinoma (HNSCC) presentation and diagnosis-including referral patterns, stage at presentation, and time to diagnosis-over a longitudinal time course. Setting: Multicenter tertiary care academic institution. Methods: A retrospective review of patients with HNSCC presenting between January 1, 2019 and December 31, 2020 was performed. Patients were stratified into pre-COVID and COVID cohorts based upon presentation date either before or after the COVID pandemic was declared a national emergency. Data was collected on demographics, referral site, symptoms, tumor characteristics, and time to diagnosis. Results: Of 203 patients with HNSCC identified, 77.3% (157/203) were in the pre-COVID cohort and 22.7% (46/203) were in the COVID cohort. Patients in the COVID cohort were more likely to present through inpatient or ER consultation (26% vs. 11%) than outpatient setting. There was a greater than 50% decrease in new tumor board case presentations per month in the COVID cohort (4.8) relative to the pre-COVID (10.9) cohort. Cancer stage at presentation was similar between cohorts. Time from presentation to diagnosis was similar between the cohorts at approximately 30 days. Conclusions: These results suggest that patients presenting during the COVID pandemic may have unique referral patterns. A significant decrease in tumor board presentations was noted, which may contribute to more delayed presentations that have yet to be observed. Further investigation with a larger sample size is warranted. Lay Summary: The COVID-19 pandemic may have changed where and how patients with head and neck cancer initially seek care. We found that patients with newly diagnosed head and neck cancer more often were initially seen in urgent settings than before the pandemic. Level of Evidence: 3.

Increased body mass index predicts prolonged survival in patients with head and neck squamous cell carcinoma.

BACKGROUND: Higher body mass index (BMI) may have a protective effect on survival in patients with head and neck cancer. The aim of this study was to determine the effect of BMI on overall survival (OS) in veterans with head and neck squamous cell carcinoma (HNSCC). METHODS: A cohort of 702 patients diagnosed with HNSCC between 1995 and 2019 were identified at the Washington DC Veterans Affairs Medical Center, and 342 patients were included for analysis. Records were queried for clinical-demographic data, BMI, and outcomes. RESULTS: HNSCC patients categorized as overweight or obese at time of diagnosis had a lower 3-year risk of death (p = 0.033) and improved OS (p < 0.001) compared to patients who were underweight or normal weight. The majority of locoregional recurrences occurred in patients with low or normal pretreatment BMI. CONCLUSIONS: Higher BMI at diagnosis may have a protective effect on OS in veterans with HNSCC.

Utilizing Single Cell RNA-Sequencing to Implicate Cell Types and Therapeutic Targets for SSNHL in the Adult Cochlea.

OBJECTIVE: To identify genes implicated in sudden sensorineural hearing loss (SSNHL) and localize their expression in the cochlea to further explore potential pathogenic mechanisms and therapeutic targets. STUDY DESIGN: Systematic literature review and bioinformatics analysis. DATA SOURCES: The following sources were searched from inception through July 2, 2020: PubMed-NCBI, MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, OpenGrey, GreyNet, GreyLiterature Report, and European Union Clinical Trials Registry. PubMed-NCBI and MEDLINE were additionally searched for human temporal bone histopathologic studies related to SSNHL. METHODS: Literature review of candidate SSNHL genes was conducted according to PRISMA guidelines. Existing temporal bone studies from SSNHL patients were analyzed to identify the most commonly affected inner ear structures. Previously published single-cell and single-nucleus RNA-Seq datasets of the adult mouse stria vascularis, as well as postnatal day 7 and 15 mouse cochlear hair cells and supporting cells, were utilized for localization of the SSNHL-related genes curated through literature review. CONCLUSIONS: We report 92 unique single nucleotide polymorphisms (SNPs) in 76 different genes that have been investigated in relation to SSNHL in the literature. We demonstrate that a subset of these genes are expressed by cell types in the adult mouse stria vascularis and organ of Corti, consistent with findings from temporal bone studies in human subjects with SSNHL. We highlight several potential genetic targets relevant to current and possible future SSNHL treatments.

Frenotomy Revision Rate in Breastfeeding Infants: The Impact of Early Versus Late Follow-Up.

Purpose: The protocol for postoperative follow-up time after lingual frenotomy in breastfeeding infants with ankyloglossia was changed from 2 weeks to 1 week at our institution. This study examined the impact of this change in practice on frenotomy revision rate. Materials and Methods: A retrospective chart review of breastfeeding infants who underwent lingual frenotomy for ankyloglossia from January 2016 to December 2017 was performed. Subjects were divided into 1-week (1-9 days) and 2-week (10-20 days) follow-up groups. Statistical analyses were performed to investigate the relationship between revision rate and postoperative follow-up time, as well as additional patient characteristics. Results: Of the 369 patients included in the study, 34 (9.2%) underwent frenotomy revision. The individual revision rates of the 1- and 2-week follow-up cohorts were 5.2% and 12.7%, respectively. The difference in revision rate was statistically significant (p = 0.022), and logistic regression revealed the odds of revision for the 2-week cohort to be 2.67 times (95% confidence interval: 1.207-5.918) greater than the 1-week cohort (p = 0.015). Conclusion: This study demonstrates a significant association between a shorter postoperative follow-up time and decreased frenotomy revision rate. With earlier follow-up, manual adjustment can be performed sooner in the postoperative period as needed, which may prevent scarring or healing complications that usually necessitate full revision. Our findings support a shift to a shorter postoperative follow-up time as a means of improving frenotomy outcomes.

Identification of Potential Meniere's Disease Targets in the Adult Stria Vascularis.

The stria vascularis generates the endocochlear potential and is involved in processes that underlie ionic homeostasis in the cochlear endolymph, both which play essential roles in hearing. The histological hallmark of Meniere's disease (MD) is endolymphatic hydrops, which refers to the bulging or expansion of the scala media, which is the endolymph-containing compartment of the cochlea. This histologic hallmark suggests that processes that disrupt ion homeostasis or potentially endocochlear potential may underlie MD. While treatments exist for vestibular symptoms related to MD, effective therapies for hearing fluctuation and hearing loss seen in MD remain elusive. Understanding the potential cell types involved in MD may inform the creation of disease mouse models and provide insight into underlying mechanisms and potential therapeutic targets. For these reasons, we compare published datasets related to MD in humans with our previously published adult mouse stria vascularis single-cell and single-nucleus RNA-Seq datasets to implicate potentially involved stria vascularis (SV) cell types in MD. Finally, we provide support for these implicated cell types by demonstrating co-expression of select candidate genes for MD within SV cell types.

In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea.

BACKGROUND: Treatment of many types of hearing instability in humans, including sudden sensorineural hearing loss, Meniere's disease, and autoimmune inner ear disease, rely heavily on the utilization of corticosteroids delivered both by oral and transtympanic routes. Despite this use, there is heterogeneity in the response to treatment with corticosteroids in humans with these diseases. The mechanisms by which corticosteroids exert their effect and the cell types in which they exert their effects in the inner ear remain poorly characterized. In this study, we localize steroid-responsive genes to cochlear cell types using previously published transcriptome datasets from the mammalian cochlea. METHODS: Steroid-responsive genes were localized to specific cochlear cell types using existing transcriptome datasets from wild-type mammalian cochlea exposed to systemic and transtympanic steroids, as well as previously published single-cell and single-nucleus RNA-sequencing datasets from the mammalian cochlea. Gene ontology (GO) analysis of differentially expressed genes (DEGs) was performed using PANTHER to investigate cellular processes implicated in transtympanic vs. systemic steroid action in the cochlea. RESULTS: Steroid-responsive genes were localized to specific cell types and regions in the cochlea including the stria vascularis, organ of Corti, and spiral ganglion neurons (SGN). Analyses demonstrate differential prevalence of steroid-responsive genes. GO analysis demonstrated steroid-responsive DEGs in the SGN to be associated with angiogenesis, apoptosis, and cytokine-mediated anti-inflammatory pathways. CONCLUSIONS: Single-cell and single-nucleus transcriptome datasets localize steroid-responsive genes to specific regions in the cochlea. Further study of these regionally-specific steroid-responsive genes may provide insight into the mechanisms of and clinical response to corticosteroids in diseases of hearing instability.