Faculty Bibliography

OBJECTIVE:To determine if metal reduction magnetic resonance imaging sequences and changes in implant placement minimize artifact from cochlear implants and improve visualization of intracranial structures. STUDY DESIGN/METHODS:Cadaveric study. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Five cadaveric heads. INTERVENTIONS/METHODS:Specimens were implanted with Advanced Bionics HiRes Ultra3D devices at nasion-external auditory canal angles of 90, 120, and 160 degrees, and distances from the external auditory canal of 9 or 12 cm. Standard brain/internal auditory canal (IAC) sequences with metal artifact reducing technique were acquired in a 1.5T scanner. MAIN OUTCOME MEASURES/METHODS:The primary outcome was visibility of 14 intracranial structures graded on a 4-point scale (1, structures <50% visible; 2, >50% visible with some areas nonvisible from artifact; 3, artifact present but adequate for diagnosis; and 4, high quality). Scores were determined by experienced head and neck radiologists and compared with one-way analysis of variance. RESULTS:Imaging sequences included axial 5-mm whole-brain turbo spin echo (TSE) T2 with right to left and anterior to posterior encoding, fluid-attenuation inversion recovery high bandwidth, axial 5-mm whole-brain slice-encoding metal artifact correction (SEMAC), axial IAC constructive interference in steady state, and axial 3-mm T1 IAC with and without fat saturation. T1 IACs in axial and coronal planes were best for ipsilateral structures overall (mean [standard deviation {SD}], 3.8 [0.6] and 3.8 [0.5]). SEMAC (mean [SD], 3.5 [0.8]) was superior to TSE with anterior to posterior encoding (mean [SD], 3.5 [0.9) for ipsilateral cortex, cerebellopontine angle, and brainstem/cerebellum, and equivalent for the inner ear. Constructive interference in steady state and T1 with fat saturation were poor for all ipsilateral structures (mean, 2.8 [ p < 0.01]; mean, 3.1 [ p < 0.01]). The 120 degrees/12 cm position was overall best, although the 120 degrees/9 cm position still afforded visualization of ipsilateral structures; other angles and distances conferred slight advantages for specific structures of interest. CONCLUSIONS:SEMAC and T2 TSE with anterior to posterior encoding sequences provide artifact suppression while retaining excellent image quality. Different placement angles did not confer improvement in visualization, although placement distances provided slight advantages for some structures.

While motor cortical circuits contain information related to specific movement parameters¹, long-range inputs also have a critical role in action execution^2,3. Thalamic projections can shape premotor activity^2-6 and have been suggested⁷ to mediate the selection of short, stereotyped actions comprising more complex behaviours⁸. However, the mechanisms by which thalamus interacts with motor cortical circuits to execute such movement sequences remain unknown. Here we find that thalamic drive engages a specific subpopulation of premotor neurons within the zebra finch song nucleus HVC (proper name) and that these inputs are critical for the progression between vocal motor elements (that is, 'syllables'). In vivo two-photon imaging of thalamic axons in HVC showed robust song-related activity, and online perturbations of thalamic function caused song to be truncated at syllable boundaries. We used thalamic stimulation to identify a sparse set of thalamically driven neurons within HVC, representing ~15% of the premotor neurons within that network. Unexpectedly, this population of putative thalamorecipient neurons is robustly active immediately preceding syllable onset, leading to the possibility that thalamic input can initiate individual song components through selectively targeting these 'starter cells'. Our findings highlight the motor thalamus as a director of cortical dynamics in the context of an ethologically relevant behavioural sequence.

BACKGROUND:There are several options for primary surgical treatment of early-stage supraglottic squamous cell carcinoma (SCC), including transoral robotic surgery (TORS). The purpose of this study was to compare outcomes of TORS to open partial laryngectomy and transoral laser microsurgery (TLM). METHODS:Patients with clinical classification T1-2 supraglottic SCC diagnosed 2010-2019, treated with TORS, open partial laryngectomy, or TLM in the National Cancer Database were selected. RESULTS:One thousand six hundred three patients were included: 17% TORS, 26.5% TLM, 56.5% open. TORS patients had the lowest rates of adjuvant treatment (28.4% vs. TLM: 45.0%, open: 38.5%, p < 0.001), and lower positive margin rates than TLM (16.9% vs. 30.5%, p < 0.001). Thirty-day and ninety-day post-operative mortality did not differ between the approaches. Five-year survival was higher following TORS compared to open surgery (77.8% vs. 66.1%, p = 0.01); this difference persisted following matched-pair analysis. CONCLUSIONS:TORS may be a safe and effective surgical approach for early-stage supraglottic SCC in appropriate patients.

PURPOSE/UNASSIGNED:Fertility discussions are an integral part of comprehensive care for pediatric, adolescent, and young adult patients newly diagnosed with cancer and are supported by national guidelines. Current institutional practices are poorly understood. METHODS/UNASSIGNED:A cross-sectional survey was distributed to 220 Children's Oncology Group member institutions regarding fertility discussion practices. Descriptive statistics were calculated for all variables. The association between specific practices and selected outcomes on the basis of sex was examined via multivariable logistic regression. RESULTS/UNASSIGNED:< .001). Program characteristics associated with fertility discussions included reproductive endocrinology and infertility on site (females odds ratio [OR], 2.1; 95% CI, 1.0 to 4.3), discussion documentation mandate (females OR, 2.3; 95% CI, 1.0 to 5.5; males OR, 3.5; 95% CI, 1.4 to 8.7), and cumulative institution-based FP infrastructure (which included [1] routine practice of documentation, [2] template for documentation, [3] mandate for documentation, and [4] availability of FP navigation; females OR, 1.6; 95% CI, 1.1 to 2.3; males OR, 2.3; 95% CI, 1.6 to 3.4). Utilization of practices unsupported by guidelines included offering sperm banking after treatment initiation (39/135 programs; 28.9%), gonadotropin-releasing hormone analogs for ovarian suppression/FP (75/144 programs; 52.1%), ovarian tissue cryopreservation at diagnosis for patients with leukemia (19/64 programs; 29.7%), and testicular tissue cryopreservation (23/138 programs; 16.7%) not part of a clinical trial. CONCLUSION/UNASSIGNED:Despite recommended guidelines, fertility discussions with patients/families before treatment initiation are not routine at Children's Oncology Group institutions. Standard criteria to determine which options should be offered to patients are more common for males than females.

OBJECTIVES/OBJECTIVE:To examine the effects of short-term and long-term engagement with structured choral singing on vocal function and quality of life outcomes in older adults. METHODS:Two groups of older adult singers over 55 years, one with fewer than 4 semesters and one with 4 or more semesters singing in a chorale, were assessed at 3 time points: baseline, after 1 semester of singing, and either after 1 semester of rest or after 1 semester of rest and 1 semester more of singing. Acoustic and aerodynamic measures, voice-related quality of life ratings, and measures of singing accuracy were obtained. Percent change between time points were calculated to determine three outcomes: improvement, lack of change, or worsening of measures across time. RESULTS:Long-term average spectrum (LTAS), difference in first and second harmonics and estimated subglottic pressure were significantly more likely to improve after a semester of singing with less experience singers, and LTAS continued to improve after a semester of rest. Flow was significantly more likely to improve with more singing experience after a semester of singing. Aerodynamic variables consistently changed in more experienced singers and improvement was maintained over the three visits. No significant changes occurred over time for singing accuracy for any singer type. Self-perception of singing voice continued to improve with more singing experience. CONCLUSIONS:This study demonstrated that for older adults in good health, regular singing provided a mechanism for maintaining speaking voice over time.

OBJECTIVES/OBJECTIVE:Hearing loss (HL) is associated with imbalance and increased fall risk. The mechanism underlying this relationship and differences across types of hearing loss remains unclear. Head mounted displays (HMD) can shed light on postural control mechanisms via an analysis of head sway. PURPOSE/OBJECTIVE:The purpose of this study was to evaluate head sway in response to sensory perturbations in individuals with bilateral (BHL) or unilateral hearing loss (UHL) and compare them to controls. MATERIALS AND METHODS/METHODS:We recruited 36 controls, 23 individuals with UHL and 14 with BHL. An HMD (HTC Vive) measured head sway while participants stood on the floor, hips-width apart. Stimuli included two levels of visuals and sound. Root Mean Square Velocity (RMSV) and Power Spectral Density (PSD) were used to quantify head sway. RESULTS:Adjusting for age, individuals with BHL had significantly higher anterior-posterior and medio-lateral RMSV than controls and individuals with UHL. Individuals with UHL demonstrated significantly lower response to visual perturbations in RMSV AP and in all 3 frequency segments of PSD compared to controls. Individuals with UHL showed significantly lower movements at high frequencies compared to controls. Sounds or severity of HL did not impact head sway. CONCLUSIONS:Individuals with BHL demonstrated increased sway with visual perturbations and should be clinically assessed for balance performance and fall risk. Individuals with UHL exhibited reduced responses to visual stimuli compared with controls, which may reflect conscious movement processing. Additional studies are needed to further understand the mechanistic relationship between hearing loss and imbalance.

OBJECTIVES/UNASSIGNED:To present a patient with the first case of NTM (nontuberculous mycobacteria) infection of the larynx extending to cervical trachea, and the first case of subglottic stenosis associated with an NTM infection. METHODS/UNASSIGNED:Case report and review of the literature. RESULTS/UNASSIGNED:laser incision, balloon dilation, and steroid injection of the subglottic stenosis. Patient remains disease free without further subglottic stenosis. CONCLUSION/UNASSIGNED:Laryngeal NTM infections are exceedingly rare. Failure to consider NTM infection in the differential diagnosis when presented with an ulcerative, exophytic mass in patients with increased risk factors (structural lung disease, Pseudomonas colonization, chronic steroid use, prior NTM positivity) may result in insufficient tissue evaluation, delayed diagnosis, and disease progression.

Epidemiological evidence suggests that kava (Piper methysticum Forst) drinks may reduce the risk of cancer in South Pacific Island smokers. However, little is known about the anti-carcinogenic effects of kava on tobacco smoking-related bladder cancer and its underlying mechanisms. Here we show that dietary feeding of kawain (a major active component in kava root extracts) to mice either before or after hydroxy butyl(butyl) nitrosamine (OH-BBN) carcinogen exposure slows down urinary bladder carcinogenesis and prolongs the survival of the OH-BBN-exposed mice. OH-BBN-induced bladder tumors exhibit significantly increased expression of lysine-specific demethylase 1 (LSD1), accompanied by decreased levels of H3K4 mono-methylation compared to normal bladder epithelium, whereas dietary kawain reverses the effects of OH-BBN on H3K4 mono-methylation. Human bladder cancer tumor tissues at different pathological grades also show significantly increased expression of LSD1 and decreased levels of H3K4 mono-methylation compared to normal urothelium. In addition, kava root extracts and the kavalactones kawain and methysticin all increase the levels of H3K4 mono- and di-methylation, leading to inhibitory effects on cell migration. Taken together, our results suggest that modification of histone lysine methylation may represent a new approach to bladder cancer prevention and treatment and that kavalactones may be promising agents for bladder cancer interception in both current and former smokers.