Faculty Bibliography

OBJECTIVE:The aim of this study was to evaluate the prevalence of comorbidities among patients with head and neck squamous cell carcinoma (HNSCC) at the time of their cancer diagnosis and during their survivorship trajectory. The second aim was to evaluate the differences in comorbidities developed according to treatment type received. STUDY DESIGN:Retrospective cross-sectional. SETTING:SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database. SUBJECTS AND METHODS:Individuals with a first-incident primary diagnosis of HNSCC from 2004 to 2011 per the SEER-Medicare database were included in analysis. The presence or absence of 30 comorbid conditions of interest was identified during distinct periods and analyzed according to treatment with surgery alone, primary (chemo)radiation, or surgery with (chemo)radiation. RESULTS:The study population consisted of 10,524 individuals diagnosed with HNSCC, with a mean age of 74.8 years. At diagnosis, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and diabetes were the most prevalent comorbidities, and they increased over time. The probability of developing treatment-related comorbidities such as pneumonia, dysphagia, weight loss, malnutrition, and dental issues rose significantly in the short and long term following treatment ( P < .05). By 5 years from cancer diagnosis, patients were most likely to have newly diagnosed hypertension, dysphagia, anemia, and weight loss. Primary surgery alone was associated with a lower risk of diagnosis with these treatment-related comorbidities, as compared with treatments involving radiation therapy and/or chemotherapy in the primary or adjuvant settings ( P < .05). CONCLUSIONS:There is a large burden of comorbidities among patients following HNSCC treatment, which warrant clinical attention during surveillance.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Various animal models have been employed to investigate vocal fold (VF) and phonatory function. However, biomechanical testing techniques to characterize vocal fold structural properties vary and have not compared critical properties across species. We adapted a nondestructive, automated indentation mapping technique to simultaneously quantify VF structural properties (VF cover layer and intact VF) in commonly used species based on the hypothesis that VF biomechanical properties are largely preserved across species. STUDY DESIGN/METHODS:Ex vivo animal model. METHODS:Canine, leporine, and swine larynges (n = 4 each) were sagittally bisected, measured, and subjected to normal indentation mapping (indentation at 0.3 mm; 1.2 mm/s) with a 2-mm spherical indenter to quantify normal force along the VF cover layer, structural stiffness, and displacement at 0.8 mN; two-dimensional maps of the free VF edge through the conus elasticus were created for these characterizations. RESULTS:Structural stiffness was 7.79 gf/mm (0.15-74.55) for leporine, 2.48 gf/mm (0.20-41.75) for canine, and 1.45 gf (0.56-4.56) for swine. For each species, the lowest values were along the free VF edge (mean ± standard deviation; leporine: 0.40 ± 0.21 gf/mm, canine: 1.14 ± 0.49 gf/mm, swine: 0.89 ± 0.28 gf/mm). Similar results were obtained for the cover layer normal force at 0.3 mm. On the free VF edge, mean (standard deviation) displacement at 0.08 gf was 0.14 mm (0.05) in leporine, 0.11 mm (0.03) in canine, and 0.10 mm (0.02) in swine. CONCLUSIONS:Automated indentation mapping yielded reproducible biomechanical property measurement of the VF cover and intact VF. Divergent VF structural properties across canine, swine, and leporine species were observed. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2018.

OBJECTIVES:/UNASSIGNED:Prognostic information about the return of vocal fold mobility in patients with iatrogenic unilateral vocal fold immobility (UVFI) can help with informed decisions about temporary and permanent treatment options. Although many variables can influence the likelihood of recovery, clinical experience suggests that cervical versus thoracic injury is a determining factor. The purpose of this study was to compare recovery rates from UVFI between cervical and thoracic injuries. METHODS:/UNASSIGNED:analyses. RESULTS:/UNASSIGNED:Overall, 15% of patients recovered vocal fold mobility at a median of 4.1 months. Patients with cervical injury (65 of 329 [20%]) were significantly more likely to recover mobility than patients with thoracic injury (11 of 173 [6.4%]) (odds ratio, 3.63). The cervical cohort contained more women (68% vs 31%) and was younger (mean age, 60.4 ± 13.8 vs 64.1 ± 16.1 years; Cohen's D = 0.25). CONCLUSIONS:/UNASSIGNED:Patients with cervical injuries resulting in UVFI are 4 times more likely to recover mobility than patients with thoracic injuries. This information can be valuable in counseling patients with UVFI and may affect clinical decision making.

Motherhood in mammals involves tremendous changes throughout the body and central nervous system, which support attention and nurturing of infants. Maternal care consists of complex behaviors, such as nursing and protection of the offspring, requiring new mothers to become highly sensitive to infant needs. Long-lasting neural plasticity in various regions of the cerebral cortex may enable the perception and recognition of infant cues, important for appropriate caregiving responses. Recent findings have demonstrated that the neuropeptide oxytocin is involved in a number of physiological processes, including parturition and lactation and dynamically shaping neuronal responses to infant stimuli as well. Here, we review experience-dependent changes within the cortex occurring throughout motherhood, focusing on plasticity of the somatosensory and auditory cortex. We outline the role of oxytocin in gating cortical plasticity and discuss potential mechanisms regulating oxytocin release in response to different sensory stimuli.

BACKGROUND:A major concern of patients who have stereotactic radiosurgery is the long-term risk of having a secondary intracranial malignancy or, in the case of patients with benign tumours treated with the technique, the risk of malignant transformation. The incidence of stereotactic radiosurgery-associated intracranial malignancy remains unknown; therefore, our aim was to estimate it in a population-based study to assess the long-term safety of this technique. METHODS:We did a population-based, multicentre, cohort study at five international radiosurgery centres (Na Homolce Hospital, Prague, Czech Republic [n=2655 patients]; Ruber International Hospital, Madrid, Spain [n=1080], University of Pittsburgh Medical Center, Pittsburgh, PA, USA [n=1027]; University of Virginia, Charlottesville, VA, USA [n=80]; and NYU Langone Health System, New York, NY, USA [n=63]). Eligible patients were of any age, and had Gamma Knife radiosurgery for arteriovenous malformation, trigeminal neuralgia, or benign intracranial tumours, which included vestibular or other benign schwannomas, WHO grade 1 meningiomas, pituitary adenomas, and haemangioblastoma. Patients were excluded if they had previously had radiotherapy or did not have a minimum follow-up time of 5 years. The primary objective of the study was to estimate the incidence of stereotactic radiosurgery-associated intracranial malignancy, including malignant transformation of a benign lesion or development of radiation-associated secondary intracranial cancer, defined as within the 2 Gy isodose line. Estimates of age-adjusted incidence of primary CNS malignancies in the USA and European countries were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer (IARC) Global Cancer statistics. FINDINGS/RESULTS:Of 14 168 patients who had Gamma Knife stereotactic radiosurgery between Aug 14, 1987, and Dec 31, 2011, in the five contributing centres, 4905 patients were eligible for the analysis (had a minimum follow-up of 5 years and no history of previous radiation therapy). Diagnostic entities included vestibular schwannomas (1011 [20·6%] of 4905 patients), meningiomas (1490 [30·4%]), arteriovenous malformations (1089 [22·2%]), trigeminal neuralgia (565 [11·5%]), pituitary adenomas (641 [13·1%]), haemangioblastoma (29 [0·6%]), and other schwannomas (80 [1·6%]). With a median follow-up of 8·1 years (IQR 6·0-10·6), two (0·0006%) of 3251 patients with benign tumours were diagnosed with suspected malignant transformation and one (0·0002%) of 4905 patients was considered a case of radiosurgery-associated intracranial malignancy, resulting in an incidence of 6·87 per 100 000 patient-years (95% CI 1·15-22·71) for malignant transformation and 2·26 per 100 000 patient-years (0·11-11·17) for radiosurgery-associated intracranial malignancy. Two (0·0004%) of 4905 patients developed intracranial malignancies, which were judged unrelated to the radiation field. Overall incidence of radiosurgery-associated malignancy was 6·80 per 100 000 patients-years (95% CI 1·73-18·50), or a cumulative incidence of 0·00045% over 10 years (95% CI 0·00-0·0034). The overall incidence of 6·8 per 100 000, which includes institutions from Europe and the USA, after stereotactic radiosurgery was found to be similar to the risk of developing a malignant CNS tumour in the general population of the USA and some European countries as estimated by the CBTRUS and IARC data, respectively. INTERPRETATION/CONCLUSIONS:These data show that the estimated risk of an intracranial secondary malignancy or malignant transformation of a benign tumour in patients treated with stereotactic radiosurgery remains low at long-term follow-up, and is similar to the risk of the general population to have a primary CNS tumour. Although prospective cohort studies with longer follow-up are warranted to support the results of this study, the available evidence suggests the long-term safety of stereotactic radiosurgery and could support physicians counselling patients on Gamma Knife stereotactic radiosurgery. FUNDING/BACKGROUND:None.

OBJECTIVE:Age-related muscle atrophy of the laryngeal muscles contributes to presbyphonia. Remodeling of the neuromuscular junction is one aspect underlying age-related muscle atrophy. Although muscle disuse has been shown to exacerbate age-related neuromuscular changes in the limb muscles, it is unknown if reduced vocal use has a similar effect in the laryngeal muscles. The objective of this study was to examine the use of social isolation as a novel method to reduce vocal use in old rats-and the impact of that reduced vocal use on ultrasonic vocalization acoustics and neuromuscular junction morphology in the thyroarytenoid muscle. STUDY DESIGN/METHODS:Animal group comparison. METHODS:Old F344/BN rats (31 months of age) were socially isolated (n = 8) or communally housed (n = 8) for 8 weeks. Effect of housing condition on ultrasonic vocalization acoustics was assessed by calculating the changes in vocalization fundamental frequency and amplitude from baseline to 8 weeks. Neuromuscular junction morphology was measured in the lateral and medial portions of the thyroarytenoid muscle at the conclusion of the experiment. RESULTS:Vocalization amplitude decreased by a mean of -4.4 dB (standard deviation [SD], 4.49) after social isolation, whereas amplitude increased by a mean of 5.7 dB (SD, 5.07) in the communally housed rats (P = 0.002). There was no significant difference in the change in fundamental frequency between groups. Furthermore, there were no group differences in any measure of neuromuscular junction morphology. CONCLUSION/CONCLUSIONS:These results suggest that neuromuscular junctions in the thyroarytenoid muscle of old rats are unaffected by 8 weeks of social isolation, despite functional changes in vocalizations. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2018.

Previous studies have shown that tumor necrosis factor alpha (TNFα) is significantly increased in complete Freund's adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFα in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNFα in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. Intra-TMJ injection of CFA (10 μl, 5 mg/ml) induced inflammatory pain in the trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present on day 1 after CFA and persisted for at least 10 days. TNFα in both TG and Sp5C of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was significantly inhibited in TNFα KO mice. The immunofluorescence staining showed that intra-TMJ CFA injection not only enhanced co-localization of TNFα with Iba1 (a marker for microglia) in both TG and Sp5C but also markedly increased the expression of TNFα in the Sp5C neurons. By the methylated DNA immunoprecipitation assay, we also found that DNA methylation at the TNF gene promoter region in the TG was dramatically diminished after CFA injection, indicating that epigenetic regulation may be involved in the CFA-enhanced TNFα expression in our model. Our results suggest that TNFα in the trigeminal nociceptive system plays a critical role in CFA-induced inflammatory TMJ pain.

Background/UNASSIGNED:Harmony is an important part of tonal music that conveys context, form and emotion. Two notes sounded simultaneously form a harmonic interval. In normal-hearing (NH) listeners, some harmonic intervals (e.g., minor 2nd, tritone, major 7th) typically sound more dissonant than others (e.g., octave, major 3rd, 4th). Because of the limited spectro-temporal resolution afforded by cochlear implants (CIs), music perception is generally poor. However, CI users may still be sensitive to relative dissonance across intervals. In this study, dissonance ratings for harmonic intervals were measured in 11 unilaterally deaf CI patients, in whom ratings from the CI could be compared to those from the normal ear. Methods/UNASSIGNED:Stimuli consisted of pairs of equal amplitude MIDI piano tones. Intervals spanned a range of two octaves relative to two root notes (F3 or C4). Dissonance was assessed in terms of subjective pleasantness ratings for intervals presented to the NH ear alone, the CI ear alone, and both ears together (NH + CI). Ratings were collected for both root notes for within- and across-octave intervals (1-12 and 13-24 semitones). Participants rated the pleasantness of each interval by clicking on a line anchored with "least pleasant" and "most pleasant." A follow-up experiment repeated the task with a smaller stimulus set. Results/UNASSIGNED:< 0.001). Ratings were similar between NH-only and NH + CI listening, with no significant binaural enhancement/interference. The follow-up tests showed that ratings were reliable for the least and most pleasant intervals. Discussion/UNASSIGNED:Although pleasantness ratings were less differentiated for the CI ear than the NH ear, there were similarities between the two listening modes. Given the lack of spectro-temporal detail needed for harmonicity-based distinctions, temporal envelope interactions (within and across channels) associated with a perception of roughness may contribute to dissonance perception for harmonic intervals with CI-only listening.