Systematic review of neuroendocrine carcinomas of the oropharynx.

Data describing features and management of oropharyngeal neuroendocrine carcinomas (NEC) remain sparse. A systematic review was performed. Patients were stratified by treatment modality and examined for disease progression and survival outcomes. Ninety-four patients from 50 publications were included. Average age at diagnosis was 59.7 years (range 14-83). 73.4% were male. Most studies did not document HPV status. Forty patients (85.1%) were p16 positive, and 34 (85.0%) were HPV-ISH positive. Overall survival was 75.4% at 1 year, and 40.0% at 2 years. Of patients with locoregional disease, 33.8% developed distant metastasis. 12.5% of patients developed locoregional recurrence. Patients who developed distant metastases had worse overall survival (p = 0.0004). No significant difference was found between treatment modalities. Human papilloma virus may be associated with oropharyngeal NEC. Current treatments provide locoregional control, but distant metastases are common and confer low overall survival.

Caregiver Quality of Life After Cochlear Implantation in Older Adults.

OBJECTIVE: To evaluate factors affecting quality of life (QOL) in caregivers of older cochlear implant (CI) recipients. STUDY DESIGN: Cross-sectional survey. SETTING: Academic medical center. PATIENTS: Adults over age 65 receiving CI between July 13, 2000 and April 3, 2019. INTERVENTIONS: Cochlear implantation. MAIN OUTCOME MEASURES: Linear regression models for caregiver QOL measured by Significant Other Scale for Hearing Disability (SOS-HEAR), with independent variables: caregiver role, patient gender, 11 factor modified frailty index (mFI), duration of hearing loss, hearing aid use, age at surgery, time since surgery, change in pure tone average (PTA), processor input type and Nijmegen Cochlear Implant Questionnaire (NCIQ). Correlations between SOS-HEAR and patient speech recognition scores. RESULTS: Questionnaires were mailed to all 294 living CI recipients. Seventy-one caregivers completed the questionnaire. Only patient gender and mFi were significant predictors of caregiver QOL on both univariate (p ≤ 0.001, ß= -20.26 [95% confidence interval -30.21, -10.3]; 0.005, -0.72 [-1.20, -0.23], respectively) and multivariate (p = 0.005, ß = -20.09, -33.05 to -7.13; 0.003, -0.93 [-1.50, -0.37]) analysis, where caregivers of female patients with lower mFI (better health) had better QOL scores. Caregiver QOL was significantly associated with patient's change in PTA and self-reported QOL scores on univariate (p = 0.041, ß = 0.52 [0.08, 0.96]; 0.024, -0.27 [-0.52, -0.02]) but not multivariate analysis. Time since CI was significant only on multivariate analysis (0.041, -0.17 [-0.33, -0.01]). Caregiver QOL did not correlate with patient speech recognition scores. CONCLUSIONS: Higher QOL scores were found among caregivers of healthier, female CI recipients. Patient hearing measurements did not correspond with better caregiver QOL.

Frailty and Quality of Life After Cochlear Implantation in Older Adults.

OBJECTIVE: To examine the relationship among frailty index, hearing measures, and hearing-related quality of life (QOL) in older recipients of cochlear implants. STUDY DESIGN: Cross-sectional survey. SETTING: Academic medical center. METHODS: Adults aged ≥65 years at the time of receiving cochlear implants between July 13, 2000, and April 3, 2019, were asked to complete a questionnaire on hearing-related QOL. Chart review was performed to identify patients' characteristics. Correlations were calculated between frailty index and audiologic outcome measures as well as between speech recognition scores and QOL scores. Linear regression models were developed to examine the impact of clinical characteristics, frailty index, and hearing measures on hearing-related QOL. RESULTS: Data for 143 respondents were included. The mean age was 80.7 years (SD, 7.1), with a mean 27.8 years of hearing loss (SD, 17.4) before implantation. The mean frailty index was 11.1 (SD, 10.6), indicating that patients had 1 or 2 of the measured comorbidities on average. No correlation was found between lower frailty index (better health) and hearing scores, including pure tone averages (PTAs) and speech recognition scores. Lower frailty index and larger improvement in PTA after cochlear implantation predicted better QOL scores on univariate analysis (respectively, P = .002, ß = -0.42 [95% CI, -0.68 to -0.16]; P = .008, ß = -0.15 [95% CI, -0.26 to -0.04]) and multivariate analysis (P = .047, ß = -0.28 [95% CI, -0.55 to -0.01]; P = .006, ß = -0.16 [95% CI, -0.28 to -0.05]). No speech recognition scores correlated with QOL after cochlear implantation. CONCLUSIONS: Frailty index does not correlate with hearing scores after cochlear implantation in older adults. Lower frailty index and more improvement in PTA predict better QOL scores after cochlear implantation in older adults.

Does Frailty or Age Increase the Risk of Postoperative Complications Following Cochlear Implantation?

OBJECTIVE: To evaluate whether frailty or age increases the risk of postoperative complications following cochlear implant (CI) surgery. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic center. METHODS: An evaluation of all adult patients undergoing cochlear implantation between 2006 and 2020 was performed. The 5-item Modified Frailty Index (mFI-5, comprising preoperative history of pulmonary disease, heart failure, hypertension, diabetes, and partially/totally dependent functional status) was calculated for all patients included in analysis in addition to demographic characteristics. The primary outcome was postoperative complications following CI within a 3-month period. Major complications included myocardial infarction, bleeding, and cerebrospinal fluid leak, among others. Predictors of postoperative complications were examined using multivariable logistic regression reporting odds ratios (ORs) and 95% CIs. RESULTS: There were 520 patients included for review with a median age of 68 (range, 18-94) years and a slight male predominance (n = 283, 54.4%). There were 340 patients (65.4%) who were robust (nonfrail) with an mFI of 0, while 180 (34.6%) had an mFI of ≥1. There were 20 patients who experienced a postoperative complication (3.85%). There was no statistically significant association between postoperative complications as a result of preoperative frailty (OR, 1.56; 95% CI, 0.98-2.48, P = .06) or age as a continuous variable (OR, 0.99; 95% CI, 0.97-1.02, P = .51). CONCLUSIONS: CI is safe for elderly and frail patients and carries no additional risk of complications when compared to younger, healthier patients. While medical comorbidities should always be considered perioperatively, this study supports the notion that implantation is low risk in older, frail patients.

Trust in physicians among patients with head and neck cancer before and after treatment.

BACKGROUND: Little is known about physician trust in patients with head and neck cancer. This study's aim is to evaluate trust pre- and post-treatment. METHODS: A study was conducted of 50 patients with head and neck cancer at a tertiary referral center. Surveys administered before and after treatment included several validated survey tools including the Trust in Oncologist Scale Short Form. RESULTS: There was an increase in overall trust scores (p < 0.001). Female patients (p = 0.034) and those who received chemotherapy (p = 0.001) were less trusting post-treatment. Patients with more comorbidities (p = 0.045) and progression of disease (p = 0.029) had higher final trust than those without. Patients with high initial distress scores showed a decrease in trust (p = 0.023). CONCLUSIONS: Patients with head and neck cancer trust their surgeon more after completion of treatment, with specific characteristics having a variable impact on trust scores.

Penetrating Trauma Rapid Estimated Disability Scale: Assessing Facial Self-Inflicted Gunshot Wounds.

Objectives: Self-inflicted facial gunshot wounds (GSWs) result in complex but consistent injuries that are often survivable. We suggest a novel method for rapid stratification into groups that may be associated with hospital course and cost after self-inflicted facial GSWs. Methods: This is retrospective review of self-inflicted facial GSWs between January 1, 2009, and December 31, 2018, at a tertiary academic center. Patients were given a penetrating trauma rapid estimated disablity (PRED) score (1-4) based solely on radiologic imaging injury patterns. Clinicopathologic factors were then compared between groups. Results: There were 2 PRED 1 patients (15.1%), 8 PRED 2 patients (29.6%), 5 PRED 3 patients (18.5%), and 12 PRED 4 patients (44.4%). An increased PRED score was statistically associated with increasing mean days in intensive care unit (2.5 PRED 1, 4.2 PRED 2, 6 PRED 3, 11.6 PRED 4, p = 0.001), mean length of hospitalization (5.5 PRED 1, 13.1 PRED 2, 25.6 PRED 3, 39.8 PRED 4, p = 0.007), and mean cost ($) of hospitalization (22,000 PRED 1, 29,000 PRED 2, 37,000 PRED 3, 63,000 PRED 4, p = 0.01). Conclusions and Relevance: The PRED score for self-inflicted GSWs to the face is strongly associated with length of hospital stay and cost of hospitalization.

Left Ear Hearing Predicts Functional Activity in the Brains of Patients with Alzheimer's Disease Dementia.

OBJECTIVES: To determine whether central speech processing ability, as measured by hearing in noise, differs between right and left ears in adults with Alzheimer's disease related dementia (AD) as well as whether differences in central speech processing ability correlate with an fMRI-based measurement of global functional brain connectivity. METHODS: This prospective study was carried out at a tertiary referral center. Patients with an AD diagnosis and pure tone averages 40 dB HL or better were included. They were examined using resting-state fMRI and underwent central audiometric testing using the Dichotic Sentence Identification Test (DSI), the Dichotic Digits Test (DD), and the Synthetic Sentence Identification Test (SS), which test hearing in noise. DSI scores were correlated with resting-state fMRI connectivity between 361 distinct gray matter brain regions of interest (ROIs). Average global connectivity was calculated as mean functional connectivity between an ROI and the other 360 regions, a quantitative marker representing overall functional connectivity in the brain. RESULTS: Sixteen subjects had adequate fMRI and hearing data. The average age was 71.5 years old (±6.0). The average DSI score for the left ear was 40% (±34%) compared to 90% (±10%) in the right ear (P < .001). No difference between ears was noted on the DD. SS does not differentiate between ears, but worsening scores were noted with increasing background noise. Of the fMRI ROIs, 269 of the 361 had multiple comparison corrected significant correlations between global connectivity and DSI of the left ear (P = .004, r = .673), and all 269 showed higher functional connectivity for individuals with higher left DSI score. No correlations between DSI of the right ear and functional connectivity were found. CONCLUSIONS: Correlation was noted between left sided DSI and functional connectivity in patients with AD. Auditory input from the left ear was more susceptible to impairment, suggesting that side-specific auditory input may influence central auditory processing.

Changes in the Auditory Association Cortex in Dementing Illnesses.

OBJECTIVE: To evaluate the relationship between degree of cognitive impairment and gray-matter density changes in the auditory cortex. STUDY DESIGN: Retrospective case-control. PATIENTS: Six hundred sixty-three patients of a tertiary referral center cognitive disorders clinic. INTERVENTION: Magnetic resonance imaging. MAIN OUTCOME MEASURES: Ratios of gray matter density of the primary auditory cortex (A1) to whole brain and auditory association cortex (AAC) to whole brain in patients with Alzheimer's disease (AD) compared with mild cognitive impairment (MCI) and patients with a mini-mental state exam (MMSE) scores ≤25 versus >25. RESULTS: After multivariate analysis, a statistically significant difference between AAC to brain ratios for patients with a MMSE ≤25 (n = 325) compared with >25 (n = 269) was found, with values -0.03 (95% CI -0.04 to -0.02, p < 0.0001) on the left and -0.04 (95% CI -0.06 to -0.03, p < 0.0001) on the right. The adjusted average difference of left and right AAC to brain ratios between AD patients (n = 218) compared with MCI patients (n = 121) was also statistically significant, at -0.03 (95% CI -0.05 to -0.01, p = 0.004) and -0.05 (95% CI -0.07 to -0.03, p < 0.0001), respectively. There was no statistically significant difference in the left or right A1 to brain ratios between the MMSE groups or between the AD and MCI groups. CONCLUSIONS: The AAC for patients with MMSE ≤25 and for those with AD shows decreased gray matter density when compared with patients with better cognitive function. No difference was detected in A1, raising the possibility that patients may have intact neural hearing, but impaired ability to interpret sounds.

Individualized prediction of late-onset dysphagia in head and neck cancer survivors.

BACKGROUND: Limited data exist regarding which head and head and neck cancer (HNC) survivors will suffer from long-term dysphagia. METHODS: From a population-based cohort of 1901 Utah residents with HNC and ≥3 years follow-up, we determined hazard ratio for dysphagia, aspiration pneumonia, or gastrostomy associated with various risk factors. We tested prediction models with combinations of factors and then assessed discrimination of our final model. RESULTS: Cancer site in the hypopharynx, advanced tumor classification, chemoradiation, preexisting dysphagia, stroke, dementia, esophagitis, esophageal spasm, esophageal stricture, gastroesophageal reflux, thrush, or chronic obstructive pulmonary disease were associated with increased risk of long-term dysphagia. Our final prediction tool gives personalized risk calculation for diagnosis of dysphagia, aspiration pneumonia, or gastrostomy tube placement at 5, 10, and 15 years after HNC based on 18 factors. CONCLUSION: We developed a clinically useful risk prediction tool to identify HNC survivors most at risk for dysphagia.

Rates of Dysphagia-Related Diagnoses in Long-Term Survivors of Head and Neck Cancers.

OBJECTIVE: To estimate long-term prevalence of new dysphagia-related diagnoses in a large cohort of head and neck cancer survivors. STUDY DESIGN: Retrospective cohort. SETTING: Population based. SUBJECTS AND METHODS: In total, 1901 adults diagnosed with head and neck cancer between 1997 and 2012 with at least 3 years of follow-up were compared with 7796 controls matched for age, sex, and birth state. Prevalence of new dysphagia-related diagnoses and procedures and hazard ratio compared to controls were evaluated in patients 2 to 5 years and 5 years and beyond after diagnosis. Risk factors for the development of these diagnoses were analyzed. RESULTS: Prevalence of new diagnosis and hazard ratio compared to controls remained elevated for all diagnoses throughout the time periods investigated. The rate of aspiration pneumonia was 3.13% at 2 to 5 years, increasing to 6.75% at 5 or more years, with hazard ratios of 9.53 (95% confidence interval [CI], 5.08-17.87) and 12.57 (7.17-22.04), respectively. Rate of gastrostomy tube placement increased from 2.82% to 3.32% with hazard ratio remaining elevated from 51.51 (13.45-197.33) to 35.2 (7.81-158.72) over the same time period. The rate of any dysphagia-related diagnosis or procedure increased from 14.9% to 26% with hazard ratio remaining elevated from 3.32 (2.50-4.42) to 2.12 (1.63-2.75). Treatment with radiation therapy and age older than 65 years were associated with increased hazard ratio for dysphagia-related diagnoses. CONCLUSION: Our data suggest that new dysphagia-related diagnoses continue to occur at clinically meaningful levels in long-term head and neck cancer survivors beyond 5 years after diagnosis.

ACSS2 gene variant associated with cleft lip and palate in two independent Hispanic populations.

OBJECTIVES/HYPOTHESIS: A candidate variant (p.Val496Ala) of the ACSS2 gene (T > C missense, rs59088485 variant at chr20: bp37 33509608) was previously found to consistently segregate with nonsyndromic cleft lip and/or palate (NSCLP) in three Honduran families. Objectives of this study were 1) to investigate the frequency of this ACSS2 variant in Honduran unrelated NSCLP patients and unrelated unaffected controls and 2) to investigate the frequency of this variant in Colombian unrelated affected NSCLP patients and unrelated unaffected controls. STUDY DESIGN: Case-control studies. METHODS: Sanger sequencing of 99 unrelated Honduran NSCLP patients and 215 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. Sanger sequencing of 230 unrelated Colombian NSCLP patients and 146 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. RESULTS: In the Honduran population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 4.0 (P = .03), with a carrier frequency of seven of 99 (7.1%) in unrelated affected and four of 215 (1.9%) in unrelated unaffected individuals. In the Colombian population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 2.6 (P = .04), with a carrier frequency of 23 of 230 (10.0%) in unrelated affected and six of 146 (4.1%) in unrelated unaffected individuals. CONCLUSIONS: These findings support the role of ACSS2 in NSCLP in two independent Hispanic populations from Honduras and Colombia. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E336-E339, 2017.

Predictors for Permanent Medialization Laryngoplasty in Unilateral Vocal Fold Paralysis.

OBJECTIVE: Early differentiation of patients with unilateral vocal fold paralysis (VFP) who recover from those who do not and consequently require permanent medialization laryngoplasty (ML) remains a challenge. The goal of this study is to identify factors that predict the need for ML. STUDY DESIGN: Case series with chart review. SETTING: Academic center. SUBJECTS AND METHODS: A total of 507 records of patients with VFP were analyzed, of which 252 met criteria and were stratified according to whether or not they obtained ML. Demographic information and clinical features were analyzed to determine predictors of ML. A nomogram was generated according to the significance and utility of these parameters. RESULTS: Of 252 patients, 86 underwent ML, and 166 did not. No differences in age or sex were observed between the ML and non-ML patients (P = .27 and P = .35, respectively). The most common cause of VFP was iatrogenic injury (62.79%, ML; 49.40%, non-ML). ML correlated with VFP secondary to neoplastic disease (odds ratio [OR], 2.14; 95% confidence interval [95% CI], 1.01-4.53) and iatrogenic injury (OR 1.73; 95% CI 1.01-2.94). ML had an inverse correlation with idiopathic VFP (OR, 0.40; 95% CI, 0.20-0.79). Patients in the ML group were more likely to have left-sided VFP, to have a history of aspiration, and to present ≥90 days from onset and less likely to have had temporary injection augmentation. CONCLUSION: Clinical features may be used to predict the likelihood of a patient obtaining ML. Nomograms may be useful to counsel patients who would benefit from early definitive surgery.

Using Whole Exome Sequencing to Identify Candidate Genes With Rare Variants In Nonsyndromic Cleft Lip and Palate.

Studies suggest that nonsyndromic cleft lip and palate (NSCLP) is polygenic with variable penetrance, presenting a challenge in identifying all causal genetic variants. Despite relatively high prevalence of NSCLP among Amerindian populations, no large whole exome sequencing (WES) studies have been completed in this population. Our goal was to identify candidate genes with rare genetic variants for NSCLP in a Honduran population using WES. WES was performed on two to four members of 27 multiplex Honduran families. Genetic variants with a minor allele frequency > 1% in reference databases were removed. Heterozygous variants consistent with dominant disease with incomplete penetrance were ascertained, and variants with predicted functional consequence were prioritized for analysis. Pedigree-specific P-values were calculated as the probability of all affected members in the pedigree being carriers, given that at least one is a carrier. Preliminary results identified 3,727 heterozygous rare variants; 1,282 were predicted to be functionally consequential. Twenty-three genes had variants of interest in ≥3 families, where some genes had different variants in each family, giving a total of 50 variants. Variant validation via Sanger sequencing of the families and unrelated unaffected controls excluded variants that were sequencing errors or common variants not in databases, leaving four genes with candidate variants in ≥3 families. Of these, candidate variants in two genes consistently segregate with NSCLP as a dominant variant with incomplete penetrance: ACSS2 and PHYH. Rare variants found at the same gene in all affected individuals in several families are likely to be directly related to NSCLP.

Sulcus vocalis: A new clinical paradigm based on a re-evaluation of histology.

OBJECTIVES/HYPOTHESIS: Sulcus vocalis is an epithelial invagination adherent to deep tissues of the vocal fold. Traditionally, dysphonia is believed to result from attenuation or absence of lamina propria and consequent alteration of mucosal dynamics. This conception does not account for several clinical features of the lesion, most notably inflammation. The goal of this study is to elucidate the clinical nature of sulcus by re-examination of its histopathology. STUDY DESIGN: Retrospective review. METHODS: Clinical features, including stroboscopic examination, and hematoxylin and eosin sections of 19 lesions in 15 patients who underwent surgery were reviewed. RESULTS: Epithelial change was found uniformly in all specimens, consisting of parakeratosis (78.9%), epithelial thickening (77.8%), dyskeratosis (63.2%), basement membrane thickening (47%), epithelial inflammation (52.6%), and retention of keratin debris (36.8%). In contrast, submucosal findings were less prevalent. Seven patients (36.8%) had essentially normal subepithelial tissues. Submucosal inflammation was present in seven (36.8%), and other submucosal changes in four of 17 (23.5%). Clinical characteristics demonstrated general improvement after surgical intervention in most cases. CONCLUSIONS: Sulcus vocalis appears to have an important component of epithelial pathology, with especially high prevalence of parakeratosis, dyskeratosis, and epithelial thickening. Clinical changes may result from prominent perilesional inflammation related to epithelial changes instead of or in addition to any alteration of the lamina propria. Surgical treatment, when necessary, should refocus on removal of pathologic epithelium as a source of inflammation independent of reconstructive considerations. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1397-1403, 2016.