Faculty Bibliography

OBJECTIVE:Study the prevalence of otologic disease in a pediatric post-palatoplasty population with no prior ear tube placement in resource-deprived countries and assess patient characteristics associated with these abnormal results. DESIGN/METHODS:Retrospective data review. PARTICIPANTS/METHODS:Ecuadorian and Chinese children identified during humanitarian cleft lip and palate repair trips with cleft palates undergoing palatoplasty from 2007 to 2010. INTERVENTIONS/METHODS:Tympanometry and otoacoustic emission (OAE) testing performed following palatoplasty. Patients' parents administered surveys regarding perceived hearing deficits. MAIN OUTCOME MEASURES/METHODS:Age, gender, Veau classification, follow-up time, laterality, and country of origin were evaluated for possible association with type B tympanogram, "Refer" Otoacoustic results, and presence of hearing difficulty as identified by a parent. Significant predictors were further evaluated with multivariate analysis. RESULTS:The cohorts included 237 patients (129 Ecuadorian, 108 Chinese); mean age: 3.9 years; mean follow-up: 4.2 years. Thirty-nine percent scored type B, 38% failed OAE testing, and 8% of parents noted hearing deficits. The country of origin and a younger age were identified as predictive variables regarding type B tympanogram. Follow-up time, country of origin, and bilateral OAE "Refer" results all significantly predicted parental questionnaire results. Subsequent multivariable analysis further demonstrated effect modification between the 2 variables of age at palatoplasty and country of origin when predicting type B vs type A tympanometry. CONCLUSION/CONCLUSIONS:Without otologic intervention, cleft palate children in resource-deprived settings suffer type B tympanometry and failed OAE results with similar to increased incidences to other studied cleft palate populations with otologic interventions available.

We introduce a new wavelet-based algorithm to enhance the quality of speech corrupted by multi-talker babble noise. The algorithm comprises three stages: The first stage classifies short frames of the noisy speech as speech-dominated or noise-dominated. We design this classifier specifically for multi-talker babble noise. The second stage performs preliminary de-nosing of noisy speech frames using oversampled wavelet transforms and parallel group thresholding. The final stage performs further denoising by attenuating residual high frequency components in the signal produced by the second stage. A significant improvement in intelligibility and quality was observed in evaluation tests of the algorithm with cochlear implant users.

The presence of tumor-induced systemic immune suppression, including lymphopenia, has been recognized in adult patients with glioblastoma for several decades, and pre-treatment neutrophil-to-lymphocyte count ratio (NLCR) is associated with inferior clinical outcome in patients with glioblastoma. Whether tumor-induced systemic immune suppression is also present in children with malignant brain tumors is not known. We performed a retrospective analysis of pretreatment neutrophil and lymphocyte counts in pediatric patients with medulloblastoma (MB) compared to a control group of children with posterior fossa pilocytic astrocytoma (PA). Compared to the control group, we observed statistically significantly lower absolute lymphocyte counts (ALCs) and higher NLCRs in the medulloblastoma group. Our findings suggest the presence of tumor-induced systemic immune suppression in MB patients already present at the time of diagnosis, with potential implications for the development of immune therapies in this population.

OBJECTIVES/OBJECTIVE:Clinical indications for vocal fold injection augmentation (VFI) are expanding. Prior studies demonstrate the benefit of trial VFI for select causes of glottic insufficiency. No studies have examined trial VFI for glottic insufficiency resulting from true vocal fold (TVF) scar. METHODS:Retrospective chart review of patients who underwent trial VFI for a dominant pathology of TVF scar causing dysphonia. Patients who subsequently underwent durable augmentation were identified. The primary study outcome was the difference in Voice Handicap Index-10 (VHI-10) score from pretrial VFI to post-durable augmentation. RESULTS:Twenty-eight patients underwent trial VFI for TVF scar, 22 of whom reported a positive response. Fifteen of 22 subjects who underwent durable augmentation had viable data for analysis. Mean VHI-10 improved from 26.9 to 18.6 ( P < .05), for a delta VHI-10 of 8.3, or 30.9% improvement. Twelve of the 15 (80%) showed a clinically significant improvement (delta VHI-10 >5). CONCLUSIONS:A trial VFI is a potentially useful, low-risk procedure that appears to help the patient and clinician identify when global augmentation might improve the voice when vocal fold scar is present. Patients who reported successful trial VFI often demonstrated significant improvement in their VHI-10 after subsequent durable augmentation.

OBJECTIVES:Preoperative fine needle aspiration (FNA) of parotid lesions often is used in the initial evaluation of parotid masses, but its role in guiding surgical decision making remains unclear, in part due to varying diagnostic accuracy reported. We sought to evaluate the role of preoperative FNA in detection of malignancy and impact on surgical management. STUDY DESIGN:Retrospective study. METHODS:The medical records of patients who underwent parotidectomy at a single tertiary medical center were reviewed from 2000 to 2015. Patients who had a preoperative FNA comprised the study cohort. RESULTS:A total of 1,074 consecutive patients underwent parotidectomy during the study period; of those, 477 had a preoperative FNA. FNA was nondiagnostic in 26 cases. There were 29 false positives (6.4%), 26 false negatives (5.8%), 122 true positives (27.1%), and 274 true negatives (60.8%). The sensitivity and specificity of FNA were 82.4% and 90.4%, respectively, with a positive predictive value of 80.8% and a negative predictive value of 91.3%. The overall accuracy of preoperative FNA was 87.8%. The preoperative FNA resulted in a change in the surgical plan in 85 (18.9%) cases. In 66 of these cases (78%), surgery was extended to include neck dissection at time of resection. In 10 cases, FNA led to surgical management over surveillance. In 11 cases, FNA downgraded the extent of surgery planned to an excisional biopsy. CONCLUSION:Preoperative FNA is a valuable adjunct in the surgical management of parotid lesions, with high specificity for the detection of malignant disease. LEVEL OF EVIDENCE:4. Laryngoscope, 128:398-402, 2018.

Oral cavity squamous cell carcinoma (OCSCC) is the most common nonmelanoma head and neck cancer in the world, with an estimated 405 000 new cases expected each year. Subsites of the oral cavity include the alveolar ridge, buccal mucosa, anterior tongue, tonsillar pillar, retromolar trigone, hard palate, gingiva, and floor of the mouth. In this issue of the AHNS "Do you know your guidelines?" series, we review the evidence-based approach to the management of oral cavity carcinomas based on the framework provided by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology.

While many of the basic tenants of upper lid blepharoplasty remain constant regardless of skin type, the thick-skinned eyelid patient requires special consideration. The brow may be naturally lower in the thick-skinned patient. These patients are more prone to having the brow pulled downward while attempting to remove redundant skin. There may also be more fat in the medial and central compartments. There may be fat in a lateral compartment overlying the lacrimal gland. Patient's expectations for a deep lid sulcus and complete excision of redundant skin may not be possible. They are more prone to an observable scar, a small dog ear at the lateral wound edge, and prolonged postoperative lid edema. Patients with lifelong upper lid fullness must get some input from significant others because their upper face aesthetic will change. In these patients, the eyelid surgery is not a rejuvenation, but a creation.

BACKGROUND:Oxytocin is a peptide hormone that influences the integration of social cognition with behavior and affect regulation. Oxytocin also prominently directs the transition of neuronal GABA neurotransmission from excitatory to inhibitory after birth. The oxytocin receptor (OXTR) is linked to schizophrenia, a heterogeneous syndrome. Relationships of OXTR polymorphisms with specific clinical features could aid in evaluating any role of oxytocin in the pathogenesis of schizophrenia. METHOD/METHODS:Schizophrenia cases with rare missense coding OXTR single nucleotide variants (SNVs) were identified from a well-characterized sample of cases and controls who were assessed for symptoms, cognition and early life trauma. RESULTS:Five of 48 cases showed rare OXTR variants. Compared to the other cases they had less severe negative symptoms (deficits in emotional expression and motivation) and less severe general psychopathology scores (depression and anxiety). They demonstrated lower nonverbal (performance) than verbal intelligence due to deficient perceptual organization and slow processing speed. They also reported greater early trauma exposure (physical and sexual abuse and emotional trauma). CONCLUSION/CONCLUSIONS:Cases carrying rare OXTR SNVs had less negative and affective symptoms than other cases, but similar psychotic symptoms, along with specific cognitive deficits. The clinical characterization of these cases occurred in association with environmental exposure to early trauma, especially sexual abuse, which may have influenced the expression of schizophrenia in subjects harboring specific SNVs in the OXTR.

BACKGROUND:Facial transplantation (FT) is a challenging reconstructive endeavor that requires the expertise of a multidisciplinary team. The specific role of maxillofacial prosthodontists has not yet been reported in detail. METHODS:This review considers the contributions of prosthodontists throughout the FT process, from patient selection and dental evaluation to long-term dental rehabilitation of the transplant patient postoperatively. Moreover, considerations of dental management are evaluated. RESULTS:In the almost 40 FT reported in the literature, the most consistently documented contribution by prosthodontists is the fabrication of a donor mask to maintain donor integrity. Though infrequently reported, prosthodontists have the potential to plan and perform a variety of dental procedures and follow-up plans. CONCLUSIONS:When applicable, facial transplant teams are tasked with providing optimal stomatognathic function and dental occlusion to recipients with severe facial disfigurement. The maxillofacial prosthodontist's contribution is crucial to the long-term dental restoration of the edentulous facial transplant candidate, in addition to the fabrication of the donor mask which fulfills the team's ethical responsibilities. PRACTICAL IMPLICATIONS/CONCLUSIONS:Maxillofacial prosthodontists play a pivotal role in facial transplantation, particularly when jaw segments are intended for transplantation.

Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti-PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide biomarkers for those whose tumors respond and new therapeutic approaches for those whose tumors do not. We used affinity purification mass spectrometry to uncover multiple proteins associated with PD-1. Among these proteins, signaling lymphocytic activation molecule-associated protein (SAP) was functionally and mechanistically analyzed for its contribution to PD-1 inhibitory responses. Silencing of SAP augmented and overexpression blocked PD-1 function. T cells from patients with X-linked lymphoproliferative disease (XLP), who lack functional SAP, were hyperresponsive to PD-1 signaling, confirming its inhibitory role downstream of PD-1. Strikingly, signaling downstream of PD-1 in purified T cell subsets did not correlate with PD-1 surface expression but was inversely correlated with intracellular SAP levels. Mechanistically, SAP opposed PD-1 function by acting as a molecular shield of key tyrosine residues that are targets for the tyrosine phosphatase SHP2, which mediates PD-1 inhibitory properties. Our results identify SAP as an inhibitor of PD-1 function and SHP2 as a potential therapeutic target in patients with XLP.