No abstract

The cochlear summating potential (SP) to a tone is a baseline shift that persists for the duration of the burst. It is often considered the most enigmatic of cochlear potentials because its magnitude and polarity vary across frequency and level and its origins are uncertain. In this study, we used pharmacology to isolate sources of the SP originating from the gerbil cochlea. Animals either had the full complement of outer and inner hair cells (OHCs and IHCs) and an intact auditory nerve or had systemic treatment with furosemide and kanamycin (FK) to remove the outer hair cells. Responses to tone bursts were recorded from the round window before and after the neurotoxin kainic acid (KA) was applied. IHC responses were then isolated from the post-KA responses in FK animals, neural responses were isolated from the subtraction of post-KA from pre-KA responses in NH animals, and OHC responses were isolated by subtraction of post-KA responses in FK animals from post-KA responses in normal hearing (NH) animals. All three sources contributed to the SP; OHCs with a negative polarity and IHCs and the auditory nerve with positive polarity. Thus the recorded SP in NH animals is a sum of contributions from different sources, contributing to the variety of magnitudes and polarities seen across frequency and intensity. When this information was applied to observations of the SP recorded from the round window in human cochlear implant subjects, a strong neural contribution to the SP was confirmed in humans as well as gerbils. NEW & NOTEWORTHY Of the various potentials produced by the cochlea, the summating potential (SP) is typically described as the most enigmatic. Using combinations of ototoxins and neurotoxins, we show contributions to the SP from the auditory nerve and from inner and outer hair cells, which differ in polarity and vary in size across frequency and level. This complexity of sources helps to explain the enigmatic nature of the SP.

Objective: There is considerable variation in the travel required for a patient with head and neck squamous cell carcinoma (HNSCC) to receive a diagnosis. The impact of this travel on the late diagnosis of cancer remains unexamined, even though presenting stage is the strongest predictor of mortality. Our aim is to determine whether travel time affects HNSCC stage at diagnosis independently of other risk factors, and whether this association is affected by socioeconomic status. Materials and Methods: Cases were obtained from the CHANCE database, a population-based case-control study in North Carolina (n=808). The mean age was 59.6 and 72% were male. Stage at diagnosis was categorized as early (T1-T2) or advanced (T3-T4) T stage and the presence or absence of nodal metastasis. Multivariate logistic regression models were used to estimate odds ratios for stage-at-diagnosis based on travel time, after adjustment for variables including demographics, income, insurance status, alcohol, and tobacco use.

The Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1 (MCAHS1) has been described in two families to date. We describe a 2-year-old Mexican American boy with the syndrome and additional manifestations not yet reported as part of the phenotype. The patient presented with severe hypotonia, microphallus and left cryptorchidism, and was later diagnosed with epilepsy and severe cortical visual impairment. He also had supernumerary nipples, pectus excavatum, a short upturned nose, fleshy ear lobes and a right auricular pit. Massively parallel exome sequencing and analysis revealed two novel compound heterozygous missense (Trp136Gly and Ser859Thr) variants in the PIGN gene. This report extends and further defines the phenotype of this syndrome.

These results underscore that caution is warranted in revision flap surgery, patients with prior neck operations, and patients aged ≥60 years.

Objective To determine whether the academic affiliation or surgical volume affects the overall survival (OS) of human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC) patients receiving surgery. Methods A retrospective study of 39 North Carolina Medical Centers was conducted. Treatment centers were classified as academic hospitals, community cancer centers, or community hospitals and were divided into thirds by volume. The primary outcome was 5‐year OS. Hazard ratios (HR) were determined using Cox proportional hazard models, adjusting for demographics, tumor site, stage, insurance status, tobacco use, alcohol use, stage, chemotherapy, and radiation therapy. Patients were also stratified by stage (early stage and advanced stage). Results Patients treated at community cancer centers had significantly better 5‐year OS (HR 0.68, 95% confidence interval [CI] = 0.48–0.98), and patients treated at academic hospitals trended toward better 5‐year OS (HR 0.72, 95% CI = 0.50–1.04) compared to patients treated at community hospitals. The effect for academic affiliation on survival was more pronounced for patients with advanced stage cancer at diagnosis (HR 0.60, 95% CI = 0.37–0.95). There were no significant survival differences among early stage patients by treatment center type. Top‐third (HR = 0.64, 95% CI = 0.42–0.96) centers by surgical volume had significantly better 5‐year OS, and middle‐third (HR = 0.71, 95% CI = 0.51–1.03) centers by volume trended toward better 5‐year OS when compared to the bottom‐third centers by volume. Conclusion Patients treated at academic hospitals, community cancer centers, and hospitals in the top third by case volume have favorable survival for HPV‐negative HNSCC. The effect for academic hospitals is most pronounced among advanced stage patients. Level of Evidence 4 Laryngoscope, 131:E479–E488, 2021

Despite years of progress, mutation detection in cancer samples continues to require significant manual review as a final step. Expert review is particularly challenging in cases where tumors are sequenced without matched normal control DNA. Attempts have been made to call somatic point mutations without a matched normal sample by removing well-known germline variants, utilizing unmatched normal controls, and constructing decision rules to classify sequencing errors and private germline variants. With budgetary constraints related to computational and sequencing costs, finding the appropriate number of controls is a crucial step to identifying somatic variants. Our approach utilizes public databases for canonical somatic variants as well as germline variants and leverages information gathered about nearby positions in the normal controls. Drawing from our cohort of targeted capture panel sequencing of tumor and normal samples with varying tumortypes and demographics, these served as a benchmark for our tumor-only variant calling pipeline to observe the relationship between our ability to correctly classify variants against a number of unmatched normals. With our benchmarked samples, approximately ten normal controls were needed to maintain 94% sensitivity, 99% specificity and 76% positive predictive value, far outperforming comparable methods. Our approach, called UNMASC, also serves as a supplement to traditional tumor with matched normal variant calling workflows and can potentially extend to other concerns arising from analyzing next generation sequencing data.

Objectives: Congenital midline cervical cleft (CMCC) is a rare congenital anterior neck anatomical anomaly. We present the case of two related patients (grandchild and maternal grandmother) who were both born with a congenital midline cervical cleft along with genetic analysis. Methods: Clinical examination of both patients and surgical excision of the grandchild was performed. Genetic analysis with exome sequencing (ES) was conducted for both patients. Results: Genetic analysis with exome sequencing (ES) revealed apparently novel single nucleotide variants in 66 genes present in both proband and grandmother. Five of these variants are predicted to cause frameshifting in the coding region of the respective genes and truncated proteins ( OVGP1, TYW1B, ZAN, SSPO, FOLR3). Two of these genes ( TYW1B and SSPO) have homozygous indel mutations in both patients. Conclusions: To our knowledge, this is the first case of two related patients with a congenital midline cervical cleft. The results of our genetic analysis reveal potential relevance to CMCC development.