Faculty Bibliography

OBJECTIVES/HYPOTHESIS:Hashimoto's Thyroiditis (HT) is a common cause of hypothyroidism. Among adults with differentiated thyroid cancer (DTC), HT appears to be associated with less severe disease burden. In the absence of information regarding HT and disease burden among children with DTC, we assessed the relationship between pediatric DTC severity and HT. STUDY DESIGN:Retrospective cohort. METHODS:Charts from 90 pediatric patients who underwent surgical removal of DTC from 2002 to 2017 at tertiary-care children's hospital were reviewed. Demographic, clinical, surgical, pathology, and outcome details were compared between patients with and without HT. Consistency among diagnostic modalities of HT was also evaluated. RESULTS:Median age at presentation was 16.0 years (range 4.2-18.9 years). Twenty-two patients were male (24%). Forty-five patients (50%) had HT based on presence of thyroid autoantibodies and/or surgical pathology findings and 45 patients did not have HT. Patients with HT had increased odds of microcalcifications (odds ratio [OR]: 3.01, P = .031) and decreased odds of palpable nodules (OR: 0.212, P = .024) and T2 lesions (vs. T1) (OR: 0.261, P = .015) compared with non-HT. No significant differences in demographics and the incidence of multifocality, extrathyroidal extension, lymphovascular invasion, lymph node or pulmonary metastases, disease recurrence, or radioactive iodine treatment were found between the two groups. Thyroglobulin/thyroid peroxidase autoantibodies and surgical pathology indicative of HT were concordant in 82.4% (κ = 0.635, P < .001). CONCLUSION:HT was present in 50% of children with DTC. Patients with DTC and HT presented with smaller tumors compared to non-HT patients. No significant differences in other markers of disease aggressiveness were found between the two groups. LEVEL OF EVIDENCE:3 Laryngoscope, 132:1668-1674, 2022.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Fibula flaps are routinely used for osseous reconstruction of head and neck defects. However, single-barrel fibula flaps may result in a height discrepancy between native mandible and grafted bone, limiting outcomes from both an aesthetic and dental standpoint. The double-barrel fibula flap aims to resolve this. We present our institution's outcomes comparing both flap designs. STUDY DESIGN/METHODS:Retrospective cohort study. METHODS:We conducted a retrospective review of all patients undergoing free fibula flap mandibular reconstruction at our institution between October 2008 and October 2020. Patients were grouped based on whether they underwent single-barrel or double-barrel reconstruction. Postoperative outcomes data were collected and compared between groups. Differences in categorical and continuous variables were assessed using a Chi-square test or Student's t-test, respectively. RESULTS:Out of 168 patients, 126 underwent single-barrel and 42 underwent double-barrel reconstruction. There was no significant difference in postoperative morbidity between approaches, including total complications (P = .37), flap-related complications (P = .62), takeback to the operating room (P = .75), flap salvage (P = .66), flap failure (P = .45), and mortality (P = .19). In addition, there was no significant difference in operative time (P = .86) or duration of hospital stay (P = .17). After adjusting for confounders, primary dental implantation was significantly higher in the double-barrel group (odds ratio, 3.02; 95% confidence interval, 1.2-7.6; P = .019). CONCLUSION/CONCLUSIONS:Double-barrel fibula flap mandibular reconstruction can be performed safely without increased postoperative morbidity or duration of hospital stay relative to single-barrel reconstruction. Moreover, the double-barrel approach is associated with higher odds of primary dental implantation and may warrant further consideration as part of an expanded toolkit for achieving early dental rehabilitation. LEVEL OF EVIDENCE/METHODS:III Laryngoscope, 2021.

Vocalizations are often elaborate, rhythmically structured behaviors. Vocal motor patterns require close coordination of neural circuits governing the muscles of the larynx, jaw, and respiratory system. In the elaborate vocalization of Alston's singing mouse (Scotinomys teguina) each note of its rapid, frequency-modulated trill is accompanied by equally rapid modulation of breath and gape. To elucidate the neural circuitry underlying this behavior, we introduced the polysynaptic retrograde neuronal tracer pseudorabies virus (PRV) into the cricothyroid and digastricus muscles, which control frequency modulation and jaw opening, respectively. Each virus singly labels ipsilateral motoneurons (nucleus ambiguus for cricothyroid, and motor trigeminal nucleus for digastricus). We find that the two isogenic viruses heavily and bilaterally colabel neurons in the gigantocellular reticular formation, a putative central pattern generator. The viruses also show strong colabeling in compartments of the midbrain including the ventrolateral periaqueductal gray and the parabrachial nucleus, two structures strongly implicated in vocalizations. In the forebrain, regions important to social cognition and energy balance both exhibit extensive colabeling. This includes the paraventricular and arcuate nuclei of the hypothalamus, the lateral hypothalamus, preoptic area, extended amygdala, central amygdala, and the bed nucleus of the stria terminalis. Finally, we find doubly labeled neurons in M1 motor cortex previously described as laryngeal, as well as in the prelimbic cortex, which indicate these cortical regions play a role in vocal production. The progress of both viruses is broadly consistent with vertebrate-general patterns of vocal circuitry, as well as with circuit models derived from primate literature.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:The aim of this study was to obtain a reliable estimate of single-sided deafness (SSD) prevalence in the adult U.S. POPULATION/METHODS/: METHODS:A cross-sectional national epidemiologic study was performed. Participants were included from the National Health and Nutrition Examination Survey (NHANES). Each cohort includes a nationally representative sample of approximately 5,000 noninstitutionalized civilians. Subjects 20 years old and over with audiometric testing were included. SSD was defined as normal hearing (pure-tone average [PTA] of ≤25 dB) in one ear and severe or worse hearing (PTA > 70 dB) in the other, using both three- and four-frequency PTA definition. Prevalence was measured as a raw number (n) and percentage (%) of the sample. Weighted estimates of prevalence were calculated based on the 2019 U.S. population census. RESULTS:An estimated 345,064 Americans (estimated prevalence of 0.14%, 95% confidence interval = 0.08-0.24) had SSD. SSD was more prevalent in individuals 60 to 79 years of age (estimated 155,917 U.S. adults, prevalence of 0.25%). A higher prevalence of SSD was noted among women compared to men (215,430 U.S. adult women, prevalence of 0.17% vs. 131,726 U.S. adult men, prevalence of 0.11%). Using a three-frequency PTA definition resulted in an estimated prevalence of 0.11%. Finally, 27% of adults with SSD reported having "good" or "excellent" hearing despite their hearing loss. CONCLUSIONS:The prevalence of SSD in the United States is estimated at 0.11%-0.14% (271,122 to 345,064 adults), depending on PTA definition used. These individuals could potentially benefit from auditory rehabilitation, including cochlear implantation. LEVEL OF EVIDENCE/METHODS:2 Laryngoscope, 2021.

BACKGROUND:Lesions of the internal auditory canal presenting with partial hearing loss are almost always vestibular schwannomas (VSs). Intracanalicular anterior inferior cerebellar artery (AICA) aneurysms are extremely rare but can mimic VS based on symptoms and imaging. The authors report the case of a flow-related intracanalicular AICA aneurysm from a pial brainstem arteriovenous malformation (AVM) masquerading as VS. OBSERVATIONS/METHODS:A 57-year-old male with partial left-sided hearing loss and an intracanalicular enhancing lesion was initially diagnosed with VS and managed conservatively at an outside institution with surveillance imaging over 3 years. When he was referred for VS follow-up, new imaging raised radiological suspicion for vascular pathology. Cerebral angiography revealed a small pial AVM located at the trigeminal root entry zone with an associated flow-related intracanalicular AICA aneurysm. The AVM was obliterated with open surgery, during which intraoperative angiography confirmed no AVM filling, preservation of the AICA, and no further aneurysm filling. LESSONS/CONCLUSIONS:Intracanalicular AICA aneurysms and other lesions, including cavernous malformations, can mimic radiographic features of VS and present with hearing loss or facial weakness. Modern vascular neurosurgical techniques such as endovascular intervention and open surgery in a hybrid operating room allowed definitive management of both lesions without untoward morbidity.

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.

Vocal communication is a critical feature of social interaction across species; however, the relation between such behavior in humans and nonhumans remains unclear. To enable comparative investigation of this topic, we review the literature pertinent to interactive language use and identify the superset of cognitive operations involved in generating communicative action. We posit these functions comprise three intersecting multistep pathways: (a) the Content Pathway, which selects the movements constituting a response; (b) the Timing Pathway, which temporally structures responses; and (c) the Affect Pathway, which modulates response parameters according to internal state. These processing streams form the basis of the Convergent Pathways for Interaction framework, which provides a conceptual model for investigating the cognitive and neural computations underlying vocal communication across species. Expected final online publication date for the Annual Review of Neuroscience, Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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.