Faculty Bibliography

Oral cancer pain is attributed to the release from cancers of mediators that sensitize and activate sensory neurons. Intraplantar injection of conditioned media (CM) from human tongue cancer cell line HSC-3 or OSC-20 evokes nociceptive behavior. By contrast, CM from noncancer cell lines, DOK, and HaCaT are non-nociceptive. Pain mediators are carried by extracellular vesicles (EVs) released from cancer cells. Depletion of EVs from cancer cell line CM reverses mechanical allodynia and thermal hyperalgesia. CM from non-nociceptive cell lines become nociceptive when reconstituted with HSC-3 EVs. Two miRNAs (hsa-miR-21-5p and hsa-miR-221-3p) are identified that are present in increased abundance in EVs from HSC-3 and OSC-20 CM compared to HaCaT CM. The miRNA target genes suggest potential involvement in oral cancer pain of the toll like receptor 7 (TLR7) and 8 (TLR8) pathways, as well as signaling through interleukin 6 cytokine family signal transducer receptor (gp130, encoded by IL6ST) and colony stimulating factor receptor (G-CSFR, encoded by CSF3R), Janus kinase and signal transducer and activator of transcription 3 (JAK/STAT3). These studies confirm the recent discovery of the role of cancer EVs in pain and add to the repertoire of algesic and analgesic cancer pain mediators and pathways that contribute to oral cancer pain.

OBJECTIVE:To evaluate outcomes of auditory implants in children with CHARGE syndrome and describe the evolution in management of hearing loss in this complex population. METHODS:A retrospective case review was performed at a tertiary referral center. Children with CHARGE syndrome who received either a cochlear implant (CI) or auditory brainstem implant (ABI) were included. Clinical records, demographic information, CHARGE features, neuroimaging, audiology, hearing rehabilitation interventions, operative notes, and outcomes were reviewed. RESULTS:Thirteen children with CHARGE syndrome underwent a total of 19 cochlear implants between 2008 and 2020. Among the congenitally deafened children (n = 9), six underwent bilateral implantation (five simultaneous and one sequential). Bilateral implantation was performed even in the presence of diminutive-appearing cochlear nerves. The average age of implantation was 1.1 years, and the mean device use time was 9.4 hours per day. Patients showed improvements in subjective family assessment related to hearing. In this group, two patients use oral communication, five use total communication, and two use sign language exclusively. Among the children with progressive hearing loss, the mean age of hearing deterioration was 4.4 years of age, and the device use time on average was 9.8 hours per day. The highest performer in the cohort was a child who lost hearing in their only hearing ear at age 4 and had normal cochleovestibular anatomy on that side. One child received an auditory brainstem implant at age two after deriving no benefit from a CI and can detect environmental sounds but is currently a nonuser. Over time, we noted that implantation occurred earlier in life and that practice has shifted toward bilateral implantation. CONCLUSIONS:Compared to a previous institutional cohort, children evaluated in this study were often implanted at a younger age and bilaterally with significantly improved outcomes. A CI evaluation should be considered in children with CHARGE syndrome to maximize sensory input and auditory ability.

EHRs provide an opportunity to conduct research on underrepresented oncology populations with mental health and substance use disorders. However, a lack of data quality may introduce unintended bias into EHR data. The objective of this article is describe our analysis of data quality within automated comorbidity lists commonly found in EHRs. Investigators conducted a retrospective chart review of 395 oncology patients from a safety-net integrated healthcare system. Statistical analysis included κ coefficients and a condition logistic regression. Subjects were racially and ethnically diverse and predominantly used Medicaid insurance. Weak κ coefficients (κ = 0.2-0.39, P < .01) were noted for drug and alcohol use disorders indicating deficiencies in comorbidity documentation within the automated comorbidity list. Further, conditional logistic regression analyses revealed deficiencies in comorbidity documentation in patients with drug use disorders (odds ratio, 11.03; 95% confidence interval, 2.71-44.9; P = .01) and psychoses (odds ratio, 0.04; confidence interval, 0.02-0.10; P < .01). Findings suggest deficiencies in automatic comorbidity lists as compared with a review of provider narrative notes when identifying comorbidities. As healthcare systems increasingly use EHR data in clinical studies and decision making, the quality of healthcare delivery and clinical research may be affected by discrepancies in the documentation of comorbidities.

Sinonasal glomangiopericytoma is a rare vascular tumor of the respiratory epithelium. Treatment consists mainly of surgical resection, though there is no consensus regarding the use of adjuvant therapies or preoperative endovascular embolization. The postsurgical prognosis is favorable, though there is a high risk of delayed recurrence. Here, we present the case of a patient who underwent endoscopic resection of a sinonasal glomangiopericytoma and a review of the literature.

Vocal fold mucous retention cysts are an important etiology of dysphonia and have classically been treated via microsurgical excision under general anesthesia. We present four cases that were treated with a novel technique of awake potassium-titanyl-phosphate laser-assisted marsupialization under local anesthesia. Reasons for in-office treatment included older age, medical comorbidities, and desire to avoid surgery/general anesthesia. No recurrences were observed and all patients had improved vocal quality, with a mean reduction in Voice Handicap Index-10 of 12.5. Hence, awake potassium-titanyl-phosphate laser treatment exhibits potential as a modality for addressing vocal fold mucous retention cysts in select patients with favorable outcomes.

PURPOSE/OBJECTIVE:New therapies for melanoma have been associated with increasing survival expectations, as opposed to the dismal outcomes of only a decade ago. Using a prospective registry, we aimed to define current survival goals for melanoma patients with brain metastases (BM), based on state-of-the-art multimodality care. METHODS:We reviewed 171 melanoma patients with BM receiving stereotactic radiosurgery (SRS) who were followed with point-of-care data collection between 2012 and 2020. Clinical, molecular and imaging data were collected, including systemic treatment and radiosurgical parameters. RESULTS:SRS were predictors of long-term survival ([Formula: see text] 5 years) from initial SRS (p = 0.023 and p = 0.018, respectively). Five patients (16%) of the long-term survivors required no active treatment for [Formula: see text] 5 years. CONCLUSION/CONCLUSIONS:Long-term survival in patients with melanoma BM is achievable in the current era of SRS combined with immunotherapies. For those alive [Formula: see text] 5 years after first SRS, 16% had been also off systemic or local brain therapy for over 5 years. Given late recurrences of melanoma, caution is warranted, however prolonged survival off active treatment in a subset of our patients raises the potential for cure.

OBJECTIVE:Past literature indicates that vibrato measurements of singers objectively changed (i.e., vibrato rate decreased and vibrato extent increased) from 1900 to the present day; however, historical audio recording technology may distort acoustic measurements of the voice output signal, including vibrato. As such, the listener's perception of historical singing may be influenced by the limitations of historical technology. This study attempts to show how the wax cylinder phonograph system-the oldest form of mass-produced audio recording technology-alters the recorded voice output signal of modern-day singers and, thus, provides an objective lens through which to study the effect(s) of historical audio recording technology on vibrato measurements. METHODS:for female singers, three times into a flat-response omnidirectional microphone and onto an Edison Home Phonograph simultaneously. The middle 1-3 seconds (6-10 vibrato cycles) of each sample was analyzed for vibrato rate, vibrato extent, jitter (ddp), shimmer (dda), and fundamental frequency for each recording condition (wax cylinder phonograph or microphone). Steady-state and frequency-modulating sinewave test signals were also recorded under the multiple recording conditions. RESULTS:Results indicated no significant effect of recording condition on vibrato rate (mean [standard deviation], cylinder: 5.3 Hz [0.5], microphone: 5.3 Hz [0.5]) and no significant difference was found for mean fundamental frequency (cylinder: 389 Hz [137], microphone: 390 Hz [137]). A significant main effect of recording condition was found for vibrato extent (cylinder: ±103 cents [30], microphone: ±100 cents [31]). Additionally, mean jitter (ddp) (cylinder: 1.22% [1.09], microphone: 0.24% [0.12]) and mean shimmer (dda) (cylinder: 9.40% [4.90], microphone: 1.92% [0.94]) were significantly higher for the cylinder recording condition, indicating more cycle-to-cycle variability in the wax cylinder recorded signal. Analysis of test signals revealed similar patterns based on recording condition. DISCUSSION/CONCLUSIONS:This study validates past scholarly inquiry about vibrato measurements as extracted from digitized wax cylinder phonograph recordings by demonstrating that measured vibrato rate remains constant during both recording conditions. In other words, vibrato rate as measured from historical recordings can be viewed as an accurate representation of the historical singer being studied. Furthermore, it suggests that the value of prior vibrato extent measurements from these acoustic recordings may be slightly overestimated from the original voice output signals produced by singers near the beginning of the 20th century (i.e., a narrow vibrato extent might have been numerically smaller on average). Increased jitter and shimmer in the wax cylinder recording conditions may be indicative of nonlinearities in the phonograph recording or playback systems.

BACKGROUND:Molecular-level human leukocyte antigen (HLA) mismatch is a powerful biomarker of rejection; however, few studies have explored its use in heart transplant recipients, and none have attempted to use the results of separate algorithms synergistically. Here we tested the hypothesis that a combination of HLAMatchmaker and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) can be used to identify more patients at low risk of rejection. METHODS:We studied 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC) performing class I and II HLA genotyping by next-generation sequencing to determine eplet mismatch (epMM) load and PIRCHE-II score. Correlation with clinical outcomes was performed on 131 cases. RESULTS:Of the 131 patients, 100 without pre-formed donor specific antibody (DSA) were used to identify cutoffs for the Class I, HLA-DR, and HLA-DQ epMM load and PIRCHE-II score for risk of developing post-transplant DSA (epMM: Class I/DR/DQ = 9/9/6; PIRCHE-II: 141/116/111) and antibody-mediated rejection (ABMR) (epMM: 9/8/8; PIRCHE-II: 157/80/201). Patients with above cut-off epMM load appear to be less likely to develop DSA and ABMR if their PIRCHE-II score is below cut-off (high epMM/high PIRCHE-II: 12.3%-20.3% DSA and 9%-13.5% ABMR vs high epMM/low PIRCHE-II: 4%-10% DSA and 0%-2% ABMR). CONCLUSION/CONCLUSIONS:For the first time in a pediatric heart transplant cohort, immunologic risk cut-offs for DSA and ABMR have been established. When used together, epMM load and PIRCHE-II score allow us to reclassify a portion of cases with high epMM load as having a lower risk for developing DSA and ABMR.

Sinonasal undifferentiated carcinoma (SNUC) is a rapidly growing malignancy with a propensity for extensive local invasion. Multimodal therapy, including surgery, radiotherapy, and chemotherapy, is the standard approach to treatment, but the optimal sequence and combination of these modalities are uncertain. Induction chemotherapy is being increasingly utilized based on recent reports that show better outcomes for patients who respond to chemotherapy and the ability to determine further course of treatment. We present a unique case of a patient with locally advanced SNUC that did not respond to induction chemotherapy and a review of the available literature relating to the management of this rare malignancy.

PURPOSE/OBJECTIVE:Severe hearing loss is particularly prevalent among Veterans. In response, the Veterans Affairs (VA) provides hearing aids and cochlear implants as part of their comprehensive hearing loss treatment. The VA's national health care system and integrated electronic health records offer a unique opportunity to examine patterns and outcomes in the management of severe hearing loss. METHOD/METHODS:We retrospectively reviewed an urban VA center's database for all Veterans who underwent cochlear implantation between 2010 and 2019. We collected preoperative demographic and audiological data including cochlear implant outcomes. RESULTS:During the study period, 61 Veterans received a cochlear implant, totaling 70 ears implanted. Median age at implantation was 70.2 years. Over 90% of Veterans reported preoperative hearing aid use, and median preoperative four-frequency pure-tone average and aided word recognition score in the ear to be implanted were 100 dB HL and 7%, respectively. The median onset of severe hearing loss bilaterally was over 4 years prior to cochlear implant evaluation based on available audiometric data. Postoperative word recognition score was negatively correlated with self-reported duration of hearing loss. CONCLUSIONS:This study provides unique insights into how Veterans with severe hearing loss are managed at one VA center. Compared to data published on cochlear implant recipients in the civilian population, Veterans in this cohort were older and had higher rates of preoperative hearing aid use. Available VA data suggest most Veterans were appropriate candidates for cochlear implant referral years prior to undergoing an evaluation. Reasons for treatment delays in this population remain to be studied.