Search

Liposarcomas are the most common soft tissue sarcoma in adults, whereas liposarcomas of the head and neck, particularly the hypopharynx, are incredibly rare - with approximately 50 cases reported in the literature. We present a case of an otherwise healthy and asymptomatic 42-year-old male who presented dramatically after vomiting up a large soft tissue mass. The lesion was surgically removed via transoral approach with blue laser, and diagnosis of well-differentiated liposarcoma was made via MDM2 gene amplification by FISH. Oral extrusion is a rare feature of this disease. This is the first documented case of an orally extruded liposarcoma to present in an otherwise asymptomatic and healthy patient, demonstrating how this entity may be indolent until initial presentation. Laryngoscope, 134:4688-4690, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Hispanic/Latino adults are less likely than non-Hispanic White adults to seek treatment for hearing disability. While differential socioeconomic factors may contribute to this finding, differences in phonology and syntax in the Spanish, versus English, language may also influence patient perception of hearing disability. The objective of this study is to investigate the association between primary language spoken and participant perception of hearing disability., Design: This study represents a cross-sectional cohort study using National Health and Nutrition Examination Study cycles 2015-2016 and 2017-2020 data. Multivariable logistic regressions estimated the association between respondent-selected interview language, which was used as a proxy for primary spoken language, and participant perception of hearing disability. Models were adjusted for age, gender, highest degree of education, pure-tone average, and self-reported general health. Participants included 4687 individuals from the United States population who elected to speak English (n = 4083) or Spanish (n = 604) during the interview. Perception of hearing disability was assessed by (1) frequency of reported difficulty in following a conversation in noise, (2) frequency with which hearing caused respondents to experience frustration when talking with members of their family or friends, and (3) participants' subjective overall assessment of their hearing., Results: Speaking Spanish, versus English, as a primary language was associated with a 42% lower odds of reporting difficulty hearing and understanding in background noise (odds ratio [OR]: 0.58, 95% confidence interval [CI]: 0.48 to 0.70). Spanish speakers had 28% lower odds of reporting feeling frustrated when talking to family members or friends due to hearing (OR: 0.72, 95% CI: 0.59 to 0.88) as compared with the English-speaking cohort. Speaking Spanish additionally conferred 31% lower odds of describing their own general hearing as "a little trouble to deaf" than participants speaking English (OR: 0.69, 95% CI: 0.53 to 0.90). These observed associations were independent of age, gender, highest degree of education, better pure-tone average? and self-reported general health., Conclusions: Primary Spanish speakers may be less likely than English speakers to report hearing-related disability, an effect which may be independent of ethnicity. Patient perception of hearing-related disability is an important component of the assessment of and counseling for hearing-related disability and discussion of the need for amplification or other hearing intervention., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study investigated the comparative performance of ear, nose, and throat (ENT) physicians in correctly detecting ear abnormalities when reviewing digital otoscopy imaging using 3 different visualization methods, including computer-assisted composite images called "SelectStitch," single video frame "Still" images, and video clips. The study also explored clinicians' diagnostic confidence levels and the time to make a diagnosis., Study Design: Clinician diagnostic reader study., Setting: Online diagnostic survey of ENT physicians., Methods: Nine ENT physicians reviewed digital otoscopy examinations from 86 ears with various diagnoses (normal, perforation, retraction, middle ear effusion, tympanosclerosis). Otoscopy examinations used artificial-intelligence (AI)-based computer-aided composite image generation from a video clip (SelectStitch), manually selected best still frame from a video clip (Still), or the entire video clip. Statistical analyses included comparisons of ability to detect correct diagnosis, confidence levels, and diagnosis times., Results: The ENT physicians' ability to detect ear abnormalities (33.2%-68.7%) varied depending on the pathologies. SelectStitch and Still images were not statistically different in detecting abnormalities (P > .50), but both were different from Video (P < .01). However, the performance improvement observed with Videos came at the cost of significantly longer time to determining the diagnosis. The level of confidence in the diagnosis was positively associated with correct diagnoses, but varied by particular pathology., Conclusion: This study explores the potential of computer-assisted techniques like SelectStitch in enhancing otoscopic diagnoses and time-saving, which could benefit telemedicine settings. Comparable performance between computer-generated and manually selected images suggests the potential of AI algorithms for otoscopy applications., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Through the application of machine learning algorithms to neuroimaging data the brain age methodology was shown to provide a useful individual-level biological age prediction and identify key brain regions responsible for the prediction. In this study, we present the methodology of constructing a rhesus macaque brain age model using a machine learning algorithm and discuss the key predictive brain regions in comparison to the human brain, to shed light on cross-species primate similarities and differences. Structural information of the brain (e.g., parcellated volumes) from brain magnetic resonance imaging of 43 rhesus macaques were used to develop brain atlas-based features to build a brain age model that predicts biological age. The best-performing model used 22 selected features and achieved an R 2 of 0.72. We also identified interpretable predictive brain features including Right Fronto-orbital Cortex, Right Frontal Pole, Right Inferior Lateral Parietal Cortex, and Bilateral Posterior Central Operculum. Our findings provide converging evidence of the parallel and comparable brain regions responsible for both non-human primates and human biological age prediction., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cell migration is the major driver of invasion and metastasis during cancer progression. For cells to migrate, they utilize the actin-myosin cytoskeleton and adhesion molecules, such as integrins and CD44, to generate traction forces in their environment. CD44 primarily binds to hyaluronic acid (HA) and integrins primarily bind to extracellular matrix (ECM) proteins such as collagen. However, the role of CD44 under integrin-mediated conditions and vice versa is not well known. Here, we performed traction force microscopy (TFM) on U251 cells seeded on collagen I-coated polyacrylamide gels to assess the functional mechanical relationship between integrins and CD44. Performing TFM on integrin-mediated adhesion conditions, i.e., collagen, we found that CD44KO U251 cells exerted more traction force than wild-type (WT) U251 cells. Furthermore, untreated WT and CD44-blocked WT exhibited comparable results. Conversely, in CD44-mediated adhesive conditions, integrin-blocked WT cells exerted a higher traction force than untreated WT cells. Our data suggest that CD44 and integrins have a mutually antagonistic relationship where one receptor represses the other's ability to generate traction force on its cognate substrate., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Objective: Age-related hearing loss (ARHL) is a prevalent but often underdiagnosed and undertreated condition among individuals aged 50 and above. It is associated with various sociodemographic factors and health risks including dementia, depression, cardiovascular disease, and falls. While the causes of ARHL and its downstream effects are well defined, there is a lack of priority placed by clinicians as well as guidance regarding the identification, education, and management of this condition., Purpose: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the identification and management of ARHL. These opportunities are communicated through clear actionable statements with explanation of the support in the literature, evaluation of the quality of the evidence, and recommendations on implementation. The target patients for the guideline are any individuals aged 50 years and older. The target audience is all clinicians in all care settings. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of ARHL. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients., Action Statements: The GDG made strong recommendations for the following key action statements (KASs): (KAS 4) If screening suggests hearing loss, clinicians should obtain or refer to a clinician who can obtain an audiogram. (KAS 8) Clinicians should offer, or refer to a clinician who can offer, appropriately fit amplification to patients with ARHL. (KAS 9) Clinicians should refer patients for an evaluation of cochlear implantation candidacy when patients have appropriately fit amplification and persistent hearing difficulty with poor speech understanding. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should screen patients aged 50 years and older for hearing loss at the time of a health care encounter. (KAS 2) If screening suggests hearing loss, clinicians should examine the ear canal and tympanic membrane with otoscopy or refer to a clinician who can examine the ears for cerumen impaction, infection, or other abnormalities. (KAS 3) If screening suggests hearing loss, clinicians should identify sociodemographic factors and patient preferences that influence access to and utilization of hearing health care. (KAS 5) Clinicians should evaluate and treat or refer to a clinician who can evaluate and treat patients with significant asymmetric hearing loss, conductive or mixed hearing loss, or poor word recognition on diagnostic testing. (KAS 6) Clinicians should educate and counsel patients with hearing loss and their family/care partner(s) about the impact of hearing loss on their communication, safety, function, cognition, and quality of life (QOL). (KAS 7) Clinicians should counsel patients with hearing loss on communication strategies and assistive listening devices. (KAS 10) For patients with hearing loss, clinicians should assess if communication goals have been met and if there has been improvement in hearing-related QOL at a subsequent health care encounter or within 1 year. The GDG offered the following KAS as an option: (KAS 11) Clinicians should assess hearing at least every 3 years in patients with known hearing loss or with reported concern for changes in hearing., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: Age-related hearing loss (ARHL) is a prevalent but often underdiagnosed and undertreated condition among individuals aged 50 and above. It is associated with various sociodemographic factors and health risks including dementia, depression, cardiovascular disease, and falls. While the causes of ARHL and its downstream effects are well defined, there is a lack of priority placed by clinicians as well as guidance regarding the identification, education, and management of this condition., Purpose: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the identification and management of ARHL. These opportunities are communicated through clear actionable statements with an explanation of the support in the literature, the evaluation of the quality of the evidence, and recommendations on implementation. The target patients for the guideline are any individuals aged 50 years and older. The target audience is all clinicians in all care settings. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the Guideline Development Group (GDG). It is not intended to be a comprehensive, general guide regarding the management of ARHL. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients., Action Statements: The GDG made strong recommendations for the following key action statements (KASs): (KAS 4) If screening suggests hearing loss, clinicians should obtain or refer to a clinician who can obtain an audiogram. (KAS 8) Clinicians should offer, or refer to a clinician who can offer, appropriately fit amplification to patients with ARHL. (KAS 9) Clinicians should refer patients for an evaluation of cochlear implantation candidacy when patients have appropriately fit amplification and persistent hearing difficulty with poor speech understanding. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should screen patients aged 50 years and older for hearing loss at the time of a health care encounter. (KAS 2) If screening suggests hearing loss, clinicians should examine the ear canal and tympanic membrane with otoscopy or refer to a clinician who can examine the ears for cerumen impaction, infection, or other abnormalities. (KAS 3) If screening suggests hearing loss, clinicians should identify sociodemographic factors and patient preferences that influence access to and utilization of hearing health care. (KAS 5) Clinicians should evaluate and treat or refer to a clinician who can evaluate and treat patients with significant asymmetric hearing loss, conductive or mixed hearing loss, or poor word recognition on diagnostic testing. (KAS 6) Clinicians should educate and counsel patients with hearing loss and their family/care partner(s) about the impact of hearing loss on their communication, safety, function, cognition, and quality of life. (KAS 7) Clinicians should counsel patients with hearing loss on communication strategies and assistive listening devices. (KAS 10) For patients with hearing loss, clinicians should assess if communication goals have been met and if there has been improvement in hearing-related quality of life at a subsequent health care encounter or within 1 year. The GDG offered the following KAS as an option: (KAS 11) Clinicians should assess hearing at least every 3 years in patients with known hearing loss or with reported concern for changes in hearing., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: To examine the association between preoperative comorbidities and cochlear implant speech outcomes., Study Design: Retrospective cohort., Setting: Tertiary referral center., Patients: A total of 976 patients who underwent cochlear implantation (CI) between January 2015 and May 2022. Adult patients with follow-up, preoperative audiologic data, and a standardized anesthesia preoperative note were included., Exposure: Adult Comorbidity Evaluation 27 (ACE-27) based on standardized anesthesia preoperative notes., Main Outcome Measures: Postoperative change in consonant-nucleus-consonant (CNC) score, AzBio Sentence score in quiet, and AzBio + 10 dB signal-to-noise ratio (SNR). Sentence score of the implanted ear at 3, 6, and 12 months., Results: A total of 560 patients met inclusion criteria; 112 patients (20%) had no comorbidity, 204 patients (36.4%) had mild comorbidities, 161 patients (28.8%) had moderate comorbidities, and 83 patients (14.8%) had severe comorbidities. Mixed model analysis revealed all comorbidity groups achieved a clinically meaningful improvement in all speech outcome measures over time. This improvement was significantly different between comorbidity groups over time for AzBio Quiet ( p = 0.045) and AzBio + 10 dB SNR ( p = 0.0096). Patients with severe comorbidities had worse outcomes. From preop to 12 months, the estimated marginal mean difference values (95% confidence interval) between the no comorbidity group and the severe comorbidity group were 52.3 (45.7-58.9) and 32.5 (24.6-40.5), respectively, for AzBio Quiet; 39.5 (33.8-45.2) and 21.2 (13.6-28.7), respectively, for AzBio + 10 dB SNR; and 43.9 (38.7-49.0) and 31.1 (24.8-37.4), respectively, for CNC., Conclusions: Comorbidities as assessed by ACE-27 are associated with CI performance. Patients with more severe comorbidities have clinically meaningful improvement but have worse outcome compared to patients with no comorbidities., Competing Interests: Conflicts of interests: DK and JFP own stock options for PotentiaMetrics, but the work of the company is not related to the present article. CCW is a consultant for Stryker Corporation and Cochlear Ltd.; JAH is a consultant for Cochlear Ltd., CAB is a consultant for Advanced Bionics, Cochlear Ltd., Envoy, and IotaMotion and has equity interest in Advanced Cochlear Diagnostics, LLC.; MAS is a consultant for Cochlear Ltd., (Copyright © 2024, Otology & Neurotology, Inc.)

Artificial intelligence and machine learning applications are emerging as transformative technologies in medicine. With greater access to a diverse range of big datasets, researchers are turning to these powerful techniques for data analysis. Machine learning can reveal patterns and interactions between variables in large and complex datasets more accurately and efficiently than traditional statistical methods. Machine learning approaches open new possibilities for studying SLE, a multifactorial, highly heterogeneous and complex disease. Here, we discuss how machine learning methods are rapidly being integrated into the field of SLE research. Recent reports have focused on building prediction models and/or identifying novel biomarkers using both supervised and unsupervised techniques for understanding disease pathogenesis, early diagnosis and prognosis of disease. In this review, we will provide an overview of machine learning techniques to discuss current gaps, challenges and opportunities for SLE studies. External validation of most prediction models is still needed before clinical adoption. Utilisation of deep learning models, access to alternative sources of health data and increased awareness of the ethics, governance and regulations surrounding the use of artificial intelligence in medicine will help propel this exciting field forward., Competing Interests: Competing interests: MJF is a consultant to and has received honoraria and/or travel support from Werfen (Barcelona, Spain; San Diego, California). MJF is also Medical Director of Mitogen Diagnostics. MYC has received consulting fees from Celltrion, Mallinckrodt Pharmaceuticals, Werfen, Organon, AstraZeneca, and MitogenDx., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction  Human papillomavirus-related (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence and presents diagnostic challenges given its unique clinical presentation. Objective  The purpose of the present study is to characterize the impact of the unique clinical presentation of HPV-related OPSCC on delays in diagnosis. Methods  Retrospective review of presenting symptoms and clinical characteristics of 284 patients with OPSCC treated from 2002-2014. Delay in diagnosis was defined as the presence of any of the following: multiple non-diagnostic fine needle aspirate (FNA) biopsies; two or more courses of antibiotic therapy; surgery with incorrect preoperative diagnosis; evaluation by an otolaryngologist without further workup; or surgery without definitive postoperative diagnosis. Results  p16+ tumors demonstrated a distinct clinical presentation that more commonly involved a neck mass (85.1% versus 57.3% of p16-; p  < 0.001) and less frequently included odynophagia (24.6% versus 51.7% of p16-; p  < 0.001). Patients who experienced diagnostic delay were more likely to have p16+ tumors (77.7% delayed versus 62.8% not delayed; p  = 0.006). p16+ primary tumors were more likely to be undetectable by physical examination of the head and neck including flexible laryngoscopy (19.0% versus 6.7% of p16-; p  = 0.007) and more frequently associated with nondiagnostic FNA biopsies of a cervical nodal mass (11.8% versus 3.4% of p16-, p  = 0.03). Conclusions  Compared with non-HPV related OPSCC, the unique clinical presentation and characteristics of HPV+ OPSCC are associated with an increased incidence of diagnostic delay. Targeted education of appropriate care providers may improve time to diagnosis and treatment., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Purpose: This study utilized an automated segmentation algorithm to assess the cochlear implant electrode array within the cochlea and investigate its impact on audiologic outcomes as measured by post-operative speech perception scores. Furthermore, manual evaluations of electrode placement were compared to automatic segmentation methods to determine their accuracy in predicting post-operative audiologic outcomes., Materials and Methods: This retrospective chart review was conducted at a tertiary care referral center involving adult post-lingually deafened cochlear implant recipients implanted from 2015 to 2019. Patients with appropriate postoperative imaging and speech testing were included. Patients were excluded if non-English speaking, had a cognitive deficit, or a labyrinthine malformation. Automated and manual methods were used to analyze computed tomography (CT) scans and correlate the findings with post-operative speech perception scores and detection of electrode translocation., Results: Among the 47 patients who met inclusion criteria, 15 had electrode translocations confirmed by automatic segmentation methods. Controlling for CI usage and pre-operative AzBio scores, patients with translocation exhibited significantly lower consonant-nucleus consonant (CNC) and AzBio scores at 6-months post-implantation compared to patients with ST insertions. Moreover, the number of translocated electrode contacts was significantly associated with post-operative CNC scores. Manual evaluations of electrode location were predictive but less sensitive to electrode translocations when compared with automated 3D segmentation., Conclusions: Placement of CI electrode contacts within ST without translocation into SV, leads to improved audiologic outcomes. Manual assessment of electrode placement via temporal bone CT, without 3D reconstruction, provides a less sensitive method to determine electrode placement than automated methods., Level of Evidence: Level 4., Lay Summary: This study investigated the impact of electrode placement on speech outcomes for cochlear implant recipients. Using advanced imaging techniques, the researchers compared automated and manual methods for evaluating electrode position and examined the relationship between electrode translocation and audiologic outcomes. The findings revealed that proper placement within the cochlea without translocation into inappropriate compartments inside the cochlea improves speech understanding. Manual evaluations were somewhat accurate but less sensitive in detecting translocations compared to automated methods, which offer more precise predictions of patient outcomes. These results contribute to our understanding of factors influencing cochlear implant success and highlight the importance of optimizing electrode placement for improved speech outcomes., Competing Interests: Declaration of competing interest Oliver Adunka No other authors have any conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Compare postoperative speech outcomes in hearing preservation (HP) cochlear implantation (CI) patients with a low-frequency pure-tone average (LFPTA) ≤ 60 dB using 2 electrode array designs., Study Design: Retrospective cohort study., Setting: Large academic cochlear implant referral center., Methods: We reviewed adult HP CI cases using either the slim modiolar electrode (SME) (CI 532/CI 632) or th slim lateral wall electrode (SLWE) (CI 624). One-year speech outcomes and HP status were the primary outcomes., Results: A total of 132 implanted ears were analyzed (mean age 73.1 years, standard deviation [SD] 12.6), with 72% (N = 95) with CI 532/632 and 28% (N = 37) with CI 624. The mean preoperative LFPTA was 44.8 dB, SD 11.8. One-year functional HP was 27.2% (mean LFPTA shift 46.1 dB, SD 22.1) and was as follows: SME 23.9% and SLWE 36.4%, p = .168. The mean age at implantation was significantly younger only in SLWE patients with preserved hearing (66.9 vs 80.3 years, p = .008). At 6 months, speech measures were significantly better in all outcomes in HP patients with an SLWE than nonpreserved SLWE patients; this effect abated at 1 year as performance among nonpreserved SLWE patients became equivalent to the remaining cohort. Speech outcomes in SME patients were similar regardless of HP status. Age at implantation and datalogging was correlated with speech outcomes., Conclusion: In this cohort of HP patients, a 1-year functional HP rate of 23.9% (SME) and 36.4% (SLWE) was observed (p = 0.168). This was initially 57.1% (SME) and 70.3% (SLWE) at activation, p = .172. Datalogging and age at implantation were correlated with postoperative speech outcomes., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Monitoring the cochlear nerve during vestibular schwannoma (VS) microsurgery depends on the hearing status and surgical approach. Traditional hearing preservation VS microsurgery relies on acoustically driven auditory brainstem response (ABR) and cochlear nerve action potential. Both modalities have advantages and disadvantages that need to be understood for proper implementation. When hearing is lost or the approach violates the otic capsule, electrically evoked monitoring methods may be used. Evoked ABR (eABR) is feasible and safe but may be limited by artifact. Combining eABR with near-field measures such as electrocochleography or neural telemetry shows promise., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess the clinical application of five recently published cochlear implant (CI) candidacy evaluation (CICE) referral screening tools through external validation., Study Design: Retrospective cohort study., Setting: Tertiary otology/neurotology practice., Patients: Adults who underwent CICE between December 2020 and September 2021., Interventions: CICE referral screening tools versus CI candidacy criteria., Main Outcome Measures: CICE screening tool performance, based on the ability to identify patients who met the CI candidacy criteria, was evaluated. CI candidacy criteria were defined as best-aided AzBio sentences at +10 signal-to-noise ratio and either 60% or less accuracy to reflect traditional criteria used in clinical settings or 40% or less accuracy (only patients 65 years or older) to reflect Medicare-eligible criteria., Results: Screening criteria of proposed CICE referral tools vary widely across pure-tone average and word recognition scores. When screened by traditional criteria, the sensitivities and specificities of these referral tools varied from 40 to 77% and from 22 to 86%, respectively. When screened by Medicare-eligible criteria, sensitivities and specificities varied from 41 to 81% and from 24 to 91%, respectively. The screening tool proposed by Zwolan et al. ( Otol Neurotol 2020;41(7):895-900) demonstrated the best overall performance for traditional (Youden's J , 0.37; sensitivity, 62%; specificity, 75%) and Medicare-eligible patients (Youden's J , 0.44; sensitivity, 66%; specificity, 78%). All screening tools performed worse on the validation cohort compared with their respective development cohorts., Conclusions: Current tools for determining CICE referral have diverse screening criteria. These combinations of pure-tone average and word recognition score are modestly successful at identifying CI candidates., Competing Interests: J.A.H. is a consultant for Cochlear Ltd. J.B.F. has served on the Audiology Advisory Board for Cochlear Ltd and Advanced Bionics. C.C.W. is a consultant for Stryker and Cochlear Ltd. C.A.B. is a consultant for Advanced Bionics, Cochlear Ltd., Envoy, and IotaMotion, and has equity interest in Advanced Cochlear Diagnostics, LLC. D.S.L., A.W., K.Y.Z., N.D., and M.A.S. disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Objective: To compare the indications and efficacy of endoscopic over-under tympanoplasty versus endoscopic underlay tympanoplasty., Methods: Retrospective cohort study of patients undergoing type I endoscopic tympanoplasty via either an underlay or over-under technique by a single surgeon from 2017 to 2021. Patients were excluded if they had a concurrent mastoidectomy, ossiculoplasty, or advanced cholesteatoma defined by involvement of multiple subsites. Patient demographics, perforation size and location, middle ear status, preoperative and postoperative audiograms, and perforation closure were reviewed. Middle ear status was represented using the Ossiculoplasty Outcome Parameter Score (OOPS). The primary outcome was perforation closure at most recent follow-up and secondary outcomes were change in postoperative pure-tone average (PTA) and air-bone gap (ABG)., Results: Of 48 patients, 27 underwent endoscopic underlay tympanoplasty and 21 underwent endoscopic over-under tympanoplasty. Tragal cartilage-perichondrium graft was used in 90% of procedures. Distribution of OOPS scores was not significantly different between groups. Over- under technique addressed significantly larger perforations (mean size of 54% vs. 31%, p  < .001) and a higher rate of anterior extension (95% vs. 22%, p  < .001) than underlay technique. Perforation closure rate was not different between groups (95% vs. 96%). Patients experienced significant improvement in PTA and ABG in both groups., Conclusion: The endoscopic over-under tympanoplasty is comparable to endoscopic underlay tympanoplasty in terms of graft take and audiologic improvement. The over-under technique is effective for repairing larger perforations or those with anterior extension., Level of Evidence: IV., Competing Interests: James W. Bao–None; Kevin Y. Zhan–None; Cameron C. Wick–Consultant for Stryker and Cochlear Ltd., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objectives: Carotid blowout syndrome (CBS) is a rare, life-threatening complication for patients with head and neck cancer (HNC). The primary objective was to identify factors associated with survival following CBS., Materials and Methods: A retrospective analysis of HNC patients treated at a single tertiary care hospital with CBS between 2016 and 2020 was performed. A multivariate Cox proportional-hazards model identified independent predictors of survival. A p value of <0.05 was considered significant. Kaplan-Meier survival analysis was performed., Results: 45 patients were identified. The majority were male (80.0%) with a mean age of 64 years at time of blowout. Oropharynx was the most common primary site (48.9%) and 73.3% of patients had stage IV disease. 35 (77.7%) patients had active tumor at time of CBS. 93.3% of patients previously received RT with a mean total dose of 62.5 ± 14.8 Gy. Threatened/type I, impending/type II, and acute/type III CBS occurred in 6.7%, 62.2%, and 31.1% of cases, respectively. Patients underwent either embolization (80.0%) or endovascular stent placement (20.0%). The 30-day and 1-year OS rates were 70.1% and 32.0%, respectively. Primary oropharyngeal tumors (adjusted hazard ratio [aHR], 4.31 [1.30-15.15 95% confidence interval]), active tumor at time of CBS (aHR 8.21 [2.10-54.95]), ICA or CCA rupture (aHR 5.81 [1.63-21.50]), and acute/type III CBS (aHR 2.98 [1.08-7.98]) were independent predictors of survival., Conclusion: Primary oropharyngeal tumors, active tumor at time of CBS, ICA or CCA rupture, and acute/type III hemorrhage were independent predictors of survival. Multidisciplinary management and prompt, protocol-directed intervention may improve outcomes following CBS., (Copyright © 2022. Published by Elsevier Ltd.)

Background: During the last two decades, significant advancements in the treatment of laryngeal cancer have occurred. Although survival of head and neck cancer patients has improved over time, the temporal trend of laryngeal cancer survival is an area of controversy., Methods: From 2004 to 2016, 77,527 patients who had laryngeal cancer treated with curative intent in the United States were identified in the National Cancer Database. Relative and observed survival rates were assessed for temporal trends. Multinomial logistic regression investigated the relationship between American Joint Committee on Cancer (AJCC) stage and increasing calendar year., Results: No significant improvement in 2- or 5-year observed survival (OS) or relative survival (RS) was observed. The 5-year RS ranged from 61.72 to 63.97%, and the 5-year OS ranged from 54.26 to 56.52%. With each increasing year, the proportion of stage 4 disease increased, with risk for stage 4 disease at the time of diagnosis increasing 2.2% annually (adjusted odds ratio [aOR], 1.022; 95% confidence interval [CI], 1.017-1.028; p < 0.001). This increase was driven by a 4.7% yearly increase in N2 disease (aOR, 1.047; 95% CI, 1.041-1.053; p < 0.001), with an annual 1.2% increase in T3 disease (aOR, 1.012; 95% CI, 1.007-1.018; p < 0.001) and a 1.2% increase in T4 disease (aOR, 1.012; 95% CI, 1.005-1.018; p < 0.001)., Conclusion: Despite advances in the field, laryngeal cancer survival in the United States is not improving over time. This may be due to an increase in the proportion of stage 4 disease, driven primarily by increasing nodal disease. To achieve survival improvement commensurate with scientific and technologic advances, efforts should be made to diagnose and treat laryngeal cancer at earlier stages to prevent further stage migration., (© 2021. Society of Surgical Oncology.)

Background: The COVID-19 pandemic has required triage and delays in surgical care throughout the world. The impact of these surgical delays on survival for patients with head and neck squamous cell carcinoma (HNSCC) remains unknown., Methods: A retrospective cohort study of 37 730 patients in the National Cancer Database with HNSCC who underwent primary surgical management from 2004 to 2016 was performed. Uni- and multivariate analyses were used to identify predictors of overall survival. Bootstrapping methods were used to identify optimal time-to-surgery (TTS) thresholds at which overall survival differences were greatest. Cox proportional hazard models with or without restricted cubic splines were used to determine the association between TTS and survival., Results: The study identified TTS as an independent predictor of overall survival (OS). Bootstrapping the data to dichotomize the cohort identified the largest rise in hazard ratio (HR) at day 67, which was used as the optimal TTS cut-point in survival analysis. The patients who underwent surgical treatment longer than 67 days after diagnosis had a significantly increased risk of death (HR, 1.189; 95% confidence interval [CI], 1.122-1.261; P < 0.0001). For every 30-day delay in TTS, the hazard of death increased by 4.6%. Subsite analysis showed that the oropharynx subsite was most affected by surgical delays, followed by the oral cavity., Conclusions: Increasing TTS is an independent predictor of survival for patients with HNSCC and should be performed within 67 days after diagnosis to achieve optimal survival outcomes.

Background: Congenital hearing loss is remarkably heterogeneous, with over 130 deafness genes and thousands of variants, making for innumerable genotype/phenotype combinations. Understanding both the pathophysiology of hearing loss and molecular site of lesion along the auditory pathway permits for significantly individualized counseling. Electrophysiologic techniques such as electrocochleography (ECochG) and electrically-evoked compound action potentials (eCAP) are being studied to localize pathology and estimate residual cochlear vs. neural health. This review describes the expanding roles of genetic and electrophysiologic evaluation in the precision medicine of congenital hearing loss.The basics of genetic mutations in hearing loss and electrophysiologic testing (ECochG and eCAP) are reviewed, and how they complement each other in the diagnostics and prognostication of hearing outcomes. Used together, these measures improve the understanding of insults to the auditory system, allowing for individualized counseling for CI candidacy/outcomes or other habilitation strategies., Conclusion: Despite tremendous discovery in deafness genes, the effects of individual genes on neural function remain poorly understood. Bridging the understanding between molecular genotype and neural and functional phenotype is paramount to interpreting genetic results in clinical practice. The future hearing healthcare provider must consolidate an ever-increasing amount of genetic and phenotypic information in the precision medicine of hearing loss., Competing Interests: None., (© 2020 PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd.)

Gender and race disparities in head and neck squamous cell carcinoma (HSNCC) survival are independently well documented, but no prior studies have examined the joint effect of these factors on HSNCC outcomes. We aim to comprehensively estimate the effect of gender and race on overall survival in HNSCC. We constructed a retrospective cohort from the National Cancer Database for primary HNSCC of the larynx, hypopharynx, oral cavity, and oropharynx from 2010 to 2015. We used Kaplan-Meier curves and Cox proportional hazards regressions to calculate hazard ratios adjusting for treatment type, age, insurance, staging classifications, and comorbidities. Oral cavity cancer was significantly more common among Hispanic and White females compared to other sites. Female non-oropharyngeal HNSCC cases had better five-year overall survival than males (56.3% versus 54.4%, respectively), though Black females (52.8%) had poorer survival than both White (56.2%) and Hispanic (57.9%) males. There were significant differences in oropharyngeal cancer by HPV status. Notably, Black females with HPV-positive oropharyngeal OPSCC had far worse survival than any other race and gender group. These results persisted even when adjusting for potential mediating factors. Clearly gender is a significant prognosticator for HNSCC and has meaningful interactions with race. The distinct site distributions across gender and race reveal important insights into HNSCC among females. Taking into account these gender disparities while considering race is essential to providing appropriate care to head and neck patients and accurately counselling these individuals on prognosis and outcomes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Guideline recommendations for the treatment of early-stage glottic cancer are limited to single-modality therapy with surgery or radiation alone. We sought to investigate the clinicopathologic and treatment factors associated with the use of postoperative radiation therapy (PORT) following laser excision for patients with T1-T2N0 glottic squamous cell carcinoma (SCC)., Study Design: Retrospective observational study of the National Cancer Database., Setting: National Cancer Database review from 2004 to 2014., Patients and Methods: A total of 1338 patients with primary cT1-T2N0M0 glottic SCC undergoing primary laser excision were included. Hospitals were divided into quartiles based on yearly volume of laryngeal laser cases performed. Multivariate logistic regression was performed to identify independent predictors of PORT., Results: The overall rate of PORT was 30.0%. Predictors of PORT included treatment at lower-volume hospitals (adjusted odds ratio [aOR] for quartiles 2-4, 1.32-4.84), positive margins (aOR, 3.83 [95% CI, 2.54-5.78]), and T2 tumors (aOR, 3.58 [95% CI, 2.24-5.74]). PORT utilization demonstrated a strong inverse correlation with hospital volume. Among top-quartile hospitals, the rate of PORT was 11.2%, while rates of PORT at second-, third-, and fourth-quartile institutions were 19.2%, 32.2%, and 37.4%, respectively., Conclusions: Predictors of PORT in multivariable analysis included treatment at lower-volume facilities, positive margins, and T2 disease. This study highlights the importance of treating early-stage glottic carcinoma at high-volume institutions. In addition, there is a need to reevaluate the use of PORT and reduce the rate of dual-modality therapy for patients with early-stage glottic SCC.

Genomic instability is a hallmark of cancer, and has a central role in the initiation and development of breast cancer 1,2 . The success of poly-ADP ribose polymerase inhibitors in the treatment of breast cancers that are deficient in homologous recombination exemplifies the utility of synthetically lethal genetic interactions in the treatment of breast cancers that are driven by genomic instability 3 . Given that defects in homologous recombination are present in only a subset of breast cancers, there is a need to identify additional driver mechanisms for genomic instability and targeted strategies to exploit these defects in the treatment of cancer. Here we show that centrosome depletion induces synthetic lethality in cancer cells that contain the 17q23 amplicon, a recurrent copy number aberration that defines about 9% of all primary breast cancer tumours and is associated with high levels of genomic instability 4-6 . Specifically, inhibition of polo-like kinase 4 (PLK4) using small molecules leads to centrosome depletion, which triggers mitotic catastrophe in cells that exhibit amplicon-directed overexpression of TRIM37. To explain this effect, we identify TRIM37 as a negative regulator of centrosomal pericentriolar material. In 17q23-amplified cells that lack centrosomes, increased levels of TRIM37 block the formation of foci that comprise pericentriolar material-these foci are structures with a microtubule-nucleating capacity that are required for successful cell division in the absence of centrosomes. Finally, we find that the overexpression of TRIM37 causes genomic instability by delaying centrosome maturation and separation at mitotic entry, and thereby increases the frequency of mitotic errors. Collectively, these findings highlight TRIM37-dependent genomic instability as a putative driver event in 17q23-amplified breast cancer and provide a rationale for the use of centrosome-targeting therapeutic agents in treating these cancers.

Introduction: The clinical implications of single-sided deafness (SSD) in children has historically been underappreciated by patients and providers alike, despite a large body of literature on the wide-ranging neurocognitive, language, scholastic, and functional impairments that occur. Conventional amplification options are marked by variable results and frequent loss of follow-up., Methods: Retrospective case series for pediatric SSD from 2008 to 2018., Results: 88 children with congenital SSD were identified. Seventeen (N = 17/88, 23.9%) passed their newborn hearing screen. Median age at first otolaryngology evaluation was 0.65 years (range 0.1-16.9 years). Most common etiologies included cochlear nerve deficiency (N = 39, CND, 44.3%), unknown (N = 30, 35.2%), inner ear malformation (N = 7, 8.0%), and congenital cytomegalovirus (N = 6, 6.8%). 32.5% of patients elected for continued observation only, followed by bone conduction hearing aid (27.7%), contralateral routing of sound aid (20.5%), conventional hearing aid (13.3%), or cochlear implant (6%). Lack of follow-up at ≥1 year was common (39.8%). Of those with device use data (N = 39), 84.7% reported either discontinued or <6 h of daily use., Conclusions: Despite early diagnosis and evaluation, the pediatric SSD cohort is characterized by high rates of loss of follow-up and amplification discontinuation. Cochlear nerve deficiency is commonly seen in congenital SSD. Early specialist referral is critical for habilitation evaluation. Patients and caregivers should be educated on the significant implications of unilateral hearing loss., Competing Interests: Declaration of competing interest No relevant conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Human papillomavirus (HPV)-mediated oropharyngeal cancer (OPC) is associated with dramatically improved survival in comparison with HPV-negative OPC and can be successfully treated with surgical and nonsurgical approaches. National treatment trends for OPC were investigated with the National Cancer Data Base (NCDB)., Methods: The NCDB was reviewed for primary HPV-mediated OPC in 2010-2014. Multivariable regression was used to identify predictors of both nonsurgical therapy and receipt of adjuvant chemoradiation (CRT)., Results: There were 13,363 patients identified with a median age at diagnosis of 58 years. The incidence of triple-modality treatment (surgery with adjuvant chemotherapy) decreased from 23.7% in 2010 to 16.9% in 2014 (R 2  = 0.96), whereas the incidence of nonsurgical treatment increased from 63.9% to 68.7% (R 2  = 0.89). Hospitals in the top treatment volume quartile (quartile 1 [Q1]; n = 29) had a lower rate of positive margins (16.3%) than bottom-quartile centers (n = 741; rate of positive margins, 36.4%; P < .001); Q1 hospitals used surgical therapy significantly more. Independent predictors of nonsurgical therapy included older age, advanced disease, lower hospital volume, and living closer to the hospital or outside the Pacific United States. In surgically treated patients, younger age, lower hospital volume, nodal disease, positive surgical margins, and extranodal extension (ENE) also predicted more adjuvant CRT use., Conclusions: The use of upfront surgical treatment decreased from 2010 to 2014. Hospital volume shows a strong, inverse correlation with the rate of positive surgical margins. The upfront treatment strategy is predicted not only by staging but also by patient-, geographic-, and hospital-specific factors. Lower hospital volume remains independently associated with increased triple-modality therapy after adjustments for positive margins, ENE, and pathologic staging., (© 2019 American Cancer Society.)

Hypotheses: Significant variability in speech recognition outcomes is consistently observed in adults who receive cochlear implants (CIs), some of which may be attributable to cognitive functions. Two hypotheses were tested: 1) preoperative cognitive skills assessed visually would predict postoperative speech recognition at 6 months after CI; and 2) cochlear implantation would result in benefits to cognitive processes at 6 months., Background: Several executive functioning tasks have been identified as contributors to speech recognition in adults with hearing loss. There is also mounting evidence that cochlear implantation can improve cognitive functioning. This study examined whether preoperative cognitive functions would predict speech recognition after implantation, and whether cognitive skills would improve as a result of CI intervention., Methods: Nineteen post-lingually deafened adult CI candidates were tested preoperatively using a visual battery of tests to assess working memory (WM), processing speed, inhibition-concentration, and nonverbal reasoning. Six months post-implantation, participants were assessed with a battery of word and sentence recognition measures and cognitive tests were repeated., Results: Multiple speech measures after 6 months of CI use were correlated with preoperative visual WM (symbol span task) and inhibition ability (stroop incongruent task) with moderate-to-large effect sizes. Small-to-large effect size improvements in visual WM, concentration, and inhibition tasks were found from pre- to post-CI. Patients with lower baseline cognitive abilities improved the most after implantation., Conclusions: Findings provide evidence that preoperative cognitive factors contribute to speech recognition outcomes for adult CI users, and support the premise that implantation may lead to improvements in some cognitive domains.

Hypothesis: Intraoperative electrocochleography (ECochG) can differentiate hair cell and neural dysfunction caused by a vestibular schwannoma (VS) and help define the site of lesion as peripheral or central to the spiral ganglion., Background: Hearing loss in patients with a VS can be caused by both sensory (cochlear) and neural dysfunction., Methods: Round-window ECochG using low and high-frequency tone bursts was performed in 49 subjects with a VS. Responses were analyzed for magnitude, spectrum, and shape of the time waveform. Components examined included the cochlear microphonic, auditory nerve neurophonic, compound action potential (CAP), and summating potential (SP)., Results: Variability in the summed response magnitudes across frequency, or "total response" (ECochG-TR), varied from 0.1 to 100 μV. Responses were larger for lower frequencies. Subjective estimates revealed a wide range of neural contributions from the auditory nerve neurophonic to low frequencies and the CAP to high frequencies. Cases with larger CAPs had smaller SPs. The correlation of ECochG-TR, with word recognition score (WRS), was moderate (r = 0.67), as well as the correlation between pure-tone averages and ECochG (r = 0.63). The cochlea remained functional in two cases of sudden sensorineural hearing loss with 0% WRS., Conclusion: Reduced ECochG-TR and neural activity in many cases indicates both sensory and neural deficits. Smaller SPs when CAPs are present indicate a neural contribution to the SP. Good cochlear function with 0% WRS, and cases of sudden sensorineural hearing loss with retained cochlear function, indicate retrocochlear effects, typically proximal to the spiral ganglion cells.

A 15-year-old female presented for evaluation of progressive hearing loss over a year. Computed tomographic imaging revealed a 11 x 6 × 6 mm osseous lesion with 'groundglass' appearance within the left posterior petrous bone lateral to vestibular aqueduct suspicious for an endolymphatic sac tumor. Surgical excision revealed fibrous dysplasia on histological analysis. Fibrous dysplasia of the temporal bone is not uncommon, but few cases of extension causing sensorineural hearing loss exist in the literature. We describe the first reported case of fibrous dysplasia mimicking an endolymphatic sac tumor; interestingly, the patient also showed hearing improvement immediately following removal., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Centriole duplication occurs once in each cell cycle to maintain centrosome number. A previous genome-wide screen revealed that depletion of 14 RNA splicing factors leads to a specific defect in centriole duplication, but the cause of this deficit remains unknown. Here, we identified an additional pre-mRNA splicing factor, WBP11, as a novel protein required for centriole duplication. Loss of WBP11 results in the retention of ∼200 introns, including multiple introns in TUBGCP6, a central component of the γ-TuRC. WBP11 depletion causes centriole duplication defects, in part by causing a rapid decline in the level of TUBGCP6. Several additional splicing factors that are required for centriole duplication interact with WBP11 and are required for TUBGCP6 expression. These findings provide insight into how the loss of a subset of splicing factors leads to a failure of centriole duplication. This may have clinical implications because mutations in some spliceosome proteins cause microcephaly and/or growth retardation, phenotypes that are strongly linked to centriole defects., (© 2019 Park et al.)

Hypothesis: Objective physiologic changes measured using electrocochleography at the round window (ECOG) are observable during endolymphatic sac decompression and shunt surgery (ELS)., Background: Limited effective treatment options are available to patients with Menière's disease (MD) who have failed conservative management, experience persistent vertigo symptoms, and have substantial residual hearing. ELS is a feasible therapeutic option for these patients. However, the efficacy of this procedure has been questioned, and objective measures assessing inner ear physiologic alterations are lacking., Methods: ECOG was measured in patients with MD undergoing ELS. Stimuli consisted of tone bursts (250, 500, 1000, 2000, 4000 Hz) and 100 μs broadband clicks at various intensities (60-90 dB nHL). Cochlear microphonic (CM), summation potential (SP), compound action potential (AP), SP:AP ratio, and CM harmonic distortions were measured., Results: ECOG was completed in 18 patients. The mean SP magnitude at 500 Hz changed significantly from -7.1 μV before to -5.1 μV after ELS (p < 0.05). However, the mean SP:AP ratio in those tested (n = 13) did not significantly change after ELS. CM harmonic magnitudes remained unchanged from pre- to post-ELS (n = 12) across all frequencies., Conclusion: ECOG allows detection of acute electrophysiological changes in the cochlea. However, our results indicate only small objective changes in the low-frequency SP magnitude (500 Hz) immediately after ELS, but not in other frequencies or measures tested (CM, SP:AP, CM harmonic distortions). These results suggest minimal electrophysiological changes occur in the cochlea as a result of ELS.

Objectives: The goal of this review was to review our series of isolated malleus fixation in pediatric patients, a rare entity causing conductive hearing loss. Malleolar fixation is poorly described in this patient population., Methods: A retrospective review of pediatric tympanoplasties by the senior author over a four-year period was performed. Only cases with isolated fixation of the malleus were reviewed. Primary outcome of interest was post-operative hearing. Paired t-tests were used to calculate pre- and post-operative hearing outcomes., Results: Five cases were analyzed. Mean age at time of surgery was 9.1 years (range 4.4-16.0 years). Average follow-up after surgery was 13.9 months (range 4.4-31.2 months). Patients were otherwise healthy and typically presented after a failed school hearing test despite previously good hearing. Three out of five cases showed radiographic evidence of bony fixation (60%) on computerized tomography (CT). Otoscopy was unremarkable in all cases. Average procedure time was 41.2 min and consisted of transcanal tympanoplasty with excision of fixed bony segment. A significant improvement in both pre- and post-operative air bone gaps was observed (p = 0.005)., with average ABG of 14.75 dB., Conclusions: Isolated pediatric malleolar fixation is an uncommon cause of pediatric conductive hearing loss. CT scan is useful for identifying this abnormality, and surgical correction results in improved post-operative hearing outcomes, potentially obviating the need for hearing amplification., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The optimal timing and technique for repairing chronic tympanic membrane (TM) perforations in pediatric patients remains controversial. The objectives are to determine the surgical and hearing outcomes of pediatric lateral graft tympanoplasty at a tertiary teaching hospital., Methods: A retrospective review was conducted for pediatric lateral graft tympanoplasties performed for chronic TM perforations by a single surgeon over a four-year period. Primary and secondary outcomes were graft failure rate and hearing outcomes, respectively., Results: 78 cases were analyzed. The mean age at time of surgery was 10.3 years (range 5-18 years). Mean follow-up was 11.0 months; 27 patients had follow-up >1 yr. Most patients were non-syndromic (85.9%), had a history of bilateral Eustachian tube dysfunction (ETD) (59%) and presented with marked myringosclerosis (73.1%). Thirty-three percent of cases were revision tympanoplasties. A learner surgeon (resident or fellow) was present in 89.7% of cases. Successful closure of the TM was achieved in 97.4% (76/78) of cases and 92.6% (25/27) of cases with >1-year follow-up. No obvious difference in graft failure was noted with regards to age at time of surgery, perforation size, history of bilateral ETD, presence of a learner surgeon, myringosclerosis, presence of syndromic features, or history of prior tympanoplasty. Ninety-one percent of patients either improved hearing or preserved their conductive hearing deficit. Poorer hearing outcomes were only associated with post-operative blunting., Conclusions: Pediatric lateral graft tympanoplasty is effective in repairing chronic perforations with excellent hearing outcomes. Common quoted predictors of surgical outcome such as age at the time of surgery, syndromic features, history of previous myringoplasty, perforation size, and ETD dysfunction were not associated with graft failure in our series., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The review was carried out to inform the evaluation of the clinical pharmacists in general practice pilot scheme, a world leading initiative to improve health care delivery in England. Around 500 pharmacists are already working in general practice as part of the pilot, launched in July 2015., Objectives: The review attempts to explain the how pharmacists working in general practice is being implemented in the UK and beyond, what works well, what does not work so well and everything in-between., Methods: This realist review was conducted to the RAMESES standards. Studies were identified by searching three databases, Medline, Embase and Scopus. Additional papers were gathered from reference lists, Google searches and via the find similar citations feature., Results: A total of 83 papers and articles were initially identified from Medline (19), Embase (31) and Scopus (32). With close reading, the final review consisted of 43 papers relating to 38 studies. Most of the research was undertaken in the field of pharmacy practice and over half of the studies investigated the perspectives of different stakeholders using questionnaires or qualitative methods., Conclusion: The pharmacist working in general practice is still a relatively new concept and further more in-depth research is still required. However, from this small number of studies, the common barriers and facilitators to the implementation can be identified. The review also lists mechanisms that will be needed to ensure the effective implementation of this initiative., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive autoimmune disorder that targets peripheral nerves. It commonly presents with motor-predominant dysfunction and enlargement of cranial nerves. With regards to hearing loss, a few cases of sensorineural loss have been described. We present a novel case of conductive hearing loss caused by a mass on the tympanic segment of the facial nerve in the setting of CIDP.

Background: Nodal disease predicts survival in oral cavity squamous cell carcinoma (SCC). Currently, no large studies on predictors of occult nodal disease in cT1N0 oral cavity SCC exist., Methods: The National Cancer Database (NCDB) review for cT1N0 oral cavity SCC with surgical resection and elective neck dissection (END)., Results: The number of patients found with occult nodal disease was 2623 (15.1%). In multivariable regression, female sex and tumor differentiation predict occult nodal disease. Occult nodal disease incidence was 5.9% in well-differentiated tumors, 17.4% in moderately differentiated tumors, and 28.5% in poorly differentiated tumor (P < .001). Women with oral tongue tumors had higher occult nodal disease (19.1%) than men (12%; P = .001). Adjusted odds ratios (aORs) for occult nodal disease in women were: aOR 1.26; 95% confidence interval (CI) 1.01-1.59; P = .045; moderately differentiated aOR 3.52; 95% CI 2.47-5.01; P < .001; and poorly differentiated aOR 6.25; 95% CI 4.17-9.38; P < .001., Conclusion: Sex and tumor differentiation significantly predict occult nodal disease. END is recommended for all moderately and poorly differentiated cT1N0 oral cavity SCC, regardless of the depth of invasion. One can consider not performing END in well-differentiated tumors., (© 2018 Wiley Periodicals, Inc.)

The platinum-based DNA damaging agent cisplatin is used as a standard therapy for locally advanced head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underpinning the cytotoxic effects of this compound are not entirely elucidated. Cisplatin produces anticancer effects primarily via activation of the DNA damage response, followed by inducing BCL-2 family dependent mitochondrial apoptosis. We have previously demonstrated that cisplatin induces the expression of proapoptotic BCL-2 family protein, Noxa, that can bind to the prosurvival BCL-2 family protein, MCL-1, to inactivate its function and induce cell death. Here, we show that the upregulation of Noxa is critical for cisplatin-induced apoptosis in p53-null HNSCC cells. This induction is regulated at the transcriptional level. With a series of Noxa promoter-luciferase reporter assays, we find that the CRE (cAMP response element) in the promoter is critical for the Noxa induction by cisplatin treatment. Among the CREB/ATF transcription factors, ATF3 and ATF4 are induced by cisplatin, and downregulation of ATF3 or ATF4 reduced cisplatin-induced Noxa. ATF3 and ATF4 bind to and cooperatively activate the Noxa promoter. Furthermore, ERK1 is involved in cisplatin-induced ATF4 and Noxa induction. In conclusion, ATF3 and ATF4 are important regulators that induce Noxa by cisplatin treatment in a p53-independent manner., (© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Background: The American Joint Commission on Cancer (AJCC) recently created new staging for human papillomavirus associated oropharyngeal cancer (HPV+ OPSCC) for its 8th edition. These proposals have not yet been validated in a national registry., Methods: Review of National Cancer Database (NCDB) for surgically-treated HPV+ OPSCC for years 2010-2014 to validate the new staging system using the Kaplan Meier method to explore survival outcomes., Results: 3745 cases were analyzed. Median follow-up was 31.3months. Most patients were Caucasian males with tonsillar cancer. Distribution of stage I disease increased from 3.7% to 80.2% in AJCC 8th. pN1 disease shifted from 17.3% to 75.9%. Treatment and distribution of T-stage varied by pathologic nodal (pN) staging. Extranodal extension (ENE) was positive in 41% cases. Four-year overall survival (OS) for AJCC 8th stages I (92%), II (81%), and stage III (62%) showed excellent hazard discrimination (all pairwise p<0.001). Only 4-year OS by pN staging showed significantly different curves when comparing pN2 (79%) with others (pN0 88%; pN1 91%, p=0.01 and <0.001 respectively). Presence of ENE confers a negative effect on overall survival (92% ENE- vs. 85% ENE+, p<0.001)., Conclusion: The NCDB shows improved hazard discrimination and outcome prediction in the AJCC 8th edition staging for HPV+ OPSCC. While overall staging had excellent hazard discrimination, this accounted for poorer discrimination between pN0 and pN1. The majority of patients are reclassified as overall stage I. Presence of extranodal extension demonstrated a statistically significant but modest negative effect on overall survival. CONDENSED ABSTRACT (2 SENTENCES): Using NCDB data for validation, the AJCC 8th ed. pathologic staging system offers much improved hazard discrimination and prognostication in HPV oropharyngeal cancer, with the majority of cases reclassified as pStage I. Of note, only pN2 offered hazard discrimination within nodal staging and presence of pathologic extranodal extension has a modest negative effect on survival., (Copyright © 2017. Published by Elsevier Ltd.)

Background: The current study was conducted to determine the effect of postoperative radiotherapy (PORT) on overall survival in patients with surgically managed pT3-T4aN0 laryngeal squamous cell carcinoma (SCC)., Methods: A review of the National Cancer Data Base from 2004 through 2013 was performed. Patients with surgically managed pT3-4aN0 laryngeal SCC with negative surgical margins were included. Univariable and multivariable Cox regression analyses were used to determine factors associated with survival., Results: A total of 1460 patients were included, 46.2% of whom had pT3N0 disease (674 patients) and 53.8% of whom had pT4aN0 disease (786 patients). Approximately 72.0% of the patients with pT3N0 disease (485 patients) and 50.1% of the patients with pT4aN0 disease (394 patients) received PORT. PORT was not found to be associated with improved overall survival on univariable analysis for patients with pT3N0 disease (hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62-1.14), but was for patients with pT4aN0 disease (HR, 0.57; 95% CI, 0.45-0.71). For patients with pT3N0 SCC of the larynx, in a multivariable Cox regression analysis adjusting for age >65 years, severity of comorbidities, larynx subsite, extent of laryngectomy, and number of lymph nodes removed, PORT was not found to be associated with improved survival (adjusted HR, 0.88; 95% CI, 0.64-1.21). For patients with pT4aN0 disease, the administration of PORT was associated with improved survival on multivariable analysis adjusting for age >65 years, severity of comorbidities, larynx subsite, number of lymph nodes removed, and type of hospital (adjusted HR, 0.58; 95% CI, 0.46-0.73)., Conclusions: For patients with surgically managed pT3N0 laryngeal SCC with negative margins, PORT does not appear to be associated with improved survival. Despite a survival benefit, nearly 50% of patients with pT4aN0 laryngeal SCC and negative surgical margins do not receive standard-of-care PORT. Cancer 2017;123:2248-2257. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Objectives: We aimed to describe the presentation, treatment patterns, and survival characteristics of posterior cricoid squamous cell carcinoma (SCC) with the National Cancer Database (NCDB)., Study Design: Retrospective database review., Methods: We reviewed the NCDB from 2004 to 2013. Primary, previously untreated cases of posterior cricoid SCC were studied. Cox regression analysis was performed to look for prognostic factors., Results: Out of 14,416 hypopharyngeal malignancies, 269 (1.8%) posterior cricoid tumors were identified, of which 248 (92.2%) were SCC. Mean age at diagnosis was 65 years (range 20-90+). Most patients were Caucasian (74.7%) and male (77.1%). By presentation, 58% were classified as clinical stage tumor (cT) 3 or cT4 to cT4 disease and 57.4% were clinical node (cN) +. Radiation (RT) alone was the most common form of treatment (32.1%), followed by chemoradiation (CRT) (31.7%) and surgery plus RT (7.4%). Overall 5- and 10-year survival was 25% and 19%, respectively. Significant prognostic factors include overall clinical stage III to IV (hazard ratio [HR] 1.8 [95% confidence interval (CI) 1.15-2.82], P = 0.011), clinical nodal disease (HR 1.54 [95% CI 1.10-2.15], P = 0.012), and Charlson/Deyo comorbidity score > 1 (HR 1.94 [95% CI 1.14-3.29], P = 0.014) on univariate analysis., Conclusion: Posterior cricoid SCCs are rare hypopharyngeal malignancies with a poor prognosis. They typically present at late stage with nodal metastasis and are most commonly treated nonsurgically with primary RT or CRT. Increasing clinical stage, comorbidity, and nodal disease are associated with worse survival., Level of Evidence: 4. Laryngoscope, 127:1093-1096, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Major salivary gland large-cell undifferentiated carcinoma (LCUC) is rare and has a poor prognosis. Characterization of patient demographics, tumor characteristics, and predictors of outcome have been limited by low case numbers, as well as grouped analysis with other salivary malignancies. The objective of this study was to address these issues using large-scale national data., Study Design: Retrospective case series., Methods: Data from the National Cancer Database, including cases diagnosed from 1998 to 2012, was analyzed, identifying 247 records of LCUC. Tumor, demographic, and survival information was extracted and analyzed retrospectively., Results: Large-cell undifferentiated carcinoma comprised < 1% of all major salivary gland cancers. Seventy percent of patients presented with advanced-stage disease. The incidence of occult nodal disease was 39%. Surgery followed by radiation was the most common treatment. Five-year overall survival was 36%. Comorbidity, distant metastasis, and positive surgical margins were found to be predictors of overall survival., Conclusion: To our knowledge, this represents the largest reported case series of LCUC. The survival analysis demonstrates poorer survival in patients with positive surgical margins; therefore, efforts to complete resection are reasonable. Reported high rates of occult nodal disease also strongly support elective treatment of the neck., Level of Evidence: 4. Laryngoscope, 2016 127:372-376, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: We sought to better characterize patient, tumor, and long-term survival characteristics of parotid small cell carcinoma (SmCC) with the National Cancer Database (NCDB)., Study Design: Retrospective database review., Methods: We reviewed the NCDB (1998-2012) for all cases of parotid SmCC. Relevant demographic, tumor, and survival variables were extracted and analyzed. Cox multivariate regression was performed to identify prognosticators., Results: Out of 30,813 parotid gland cancers in the NCDB, we found 344 cases of parotid SmCC (1.11%). Age at diagnosis ranged from 23 to 91 years (mean = 73 years). Most patients (73.0%) were male. Most tumors were 2 to 4 cm in size (51.4%). Regional metastases were common (50.8% cN+ and 65.1% pN+) and distant metastasis (7.3%) was uncommon. Occult nodes were found in 14.4% of cases. Overall survival at 5 and 10 years was 37% and 20%, respectively. Although numerous variables were found to significantly impact survival on univariate regression analysis, age (hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 1.03-1.08, P < .001), tumor size of 2 to 4 cm (HR: 2.51, 95% CI: 1.83-5.11, P = .011), tumors >4 cm (HR: 3.44, 95% CI: 1.63-7.27) and distant metastasis (HR: 2.06, 95% CI: 1.02-4.14, P = .043) remained significant prognosticators in our multivariate model. Nodal disease was not a significant risk factor after adjustment (P = .055)., Conclusions: SmCC is a rare parotid malignancy with a poor prognosis. Regional metastases were common, whereas distant metastases were uncommon. Elective neck treatment should be considered due to the incidence of occult nodal disease., Level of Evidence: 4 Laryngoscope, 126:2036-2040, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Parotid adenocarcinoma not otherwise specified (PANOS) is a common parotid cancer, but studies specifically on this subject are limited., Methods: We conducted a retrospective review of the National Cancer Database., Results: Ten percent of all parotid cancers were PANOS (n = 3155). Median age was 67 years. Most patients were men (62.8%) with high-grade histology (67.2%). Regional metastasis was common (35.9%), whereas occult nodal metastasis (20.2% overall) was less frequent in non-high-grade lesions (8.5% vs 31.6%; p < .001). Distant metastasis was rare (7.9%). Five-year overall survival (OS) was 47%. In multivariate analysis, age, regional metastasis, distant metastasis, high-grade, and T classification were predictors of lower survival. Patients with stage III to IV disease receiving surgery and radiotherapy had a better OS than those receiving surgery alone (51% vs 41%; p < .001)., Conclusion: PANOS is an aggressive disease with frequent regional metastasis and low survival. Numerous variables are associated with worse survival. © 2016 Wiley Periodicals, Inc. Head Neck 38:1208-1212, 2016., (© 2016 Wiley Periodicals, Inc.)

Importance: Thirty-day unplanned readmissions are increasingly used as a measure of quality care., Objective: To describe the incidence of and risk factors for 30-day unplanned readmissions for patients undergoing treatment for cancer of the parotid gland., Design, Setting, and Participants: A retrospective cohort study was conducted using the National Cancer Database. Records on patients in the database undergoing surgery for previously untreated primary parotid cancer between 2003 and 2012 were reviewed. The data were analyzed in October 2015., Interventions: Parotidectomy with or without neck dissection., Main Outcomes and Measures: The main outcome measure was patient-, area-, and hospital-level risk factors for readmission. Secondary outcome measures were the rate of 30-day unplanned readmission and the rate of 30-day mortality., Results: We identified 11 394 cases of previously untreated parotid cancer undergoing definitive surgery. The 30-day unplanned readmission rate following parotidectomy was 2.1% (235 of 11 394 surgical procedures). Reported as odds ratios (95% CIs), factors associated with the 30-day unplanned readmission rate on multivariable analysis included advanced pathologic T category (1.59 [1.14-2.20]), uninsured status (2.27 [1.07-4.80]), and increased morbidity as measured by the Charlson/Deyo Score (CDS) (CDS 1, 1.57 [1.05-2.35]; CDS >1, 2.08 [1.06-4.08]). Thirty-day unplanned readmission was associated with an 8.4-fold (8.36 [2.04-34.30]) increased risk of 30-day mortality (1.9% vs 0.2%)., Conclusions and Relevance: Thirty-day unplanned readmission following surgery for parotid cancer is not common. Risk factors associated with 30-day unplanned readmission include pathologic T category, comorbidity, and uninsured status. Having an unplanned 30-day readmission is associated with greater risk of 30-day mortality.

Objectives/hypothesis: We sought to better characterize patient, tumor, and long-term survival characteristics of basal cell adenocarcinoma (BCAC) of the major salivary glands with the National Cancer Database (NCDB)., Study Design: Retrospective database review of the NCDB (1998-2012)., Methods: We retrospectively reviewed the NCDB for all cases of major salivary gland BCAC with histologic code 8147/3. Relevant demographic, tumor, and survival variables were extracted and analyzed. COX multivariate regression was performed to identify prognosticators., Results: Out of 36,224 major salivary gland cancers in the NCDB, we found 509 cases of BCAC (1.4%), 88% of which were in the parotid glands, 11.2% in the submandibular glands, and 0.8% in the sublingual glands. Age at diagnosis ranged from 18 to 92 years (average 64). No gender preference was found (50.7% male). Most tumors were 2 to 4 cm in size (47.3%). Regional (11.9%) and distant metastasis (1.8%) were uncommon. Overall survival at 5 and 10 years was 79% and 62%, respectively. Although numerous variables were found to significantly impact survival on univariate regression analysis, only age ≥ 65 (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.56-4.19; P < 0.001) and high primary tumor (T)-stage (HR 1.85; 95% CI, 1.16-2.95; P = 0.010) remained significant prognosticators in our multivariate model. For high T-stage disease, surgery with radiation had significantly better survival than surgery alone., Conclusion: Basal cell adenocarcinoma is a rare salivary malignancy with a good prognosis. Regional and distant metastasis were uncommon. Radiation with surgery may help for higher T-stage disease. Old age and high T-stage were significant predictors of worse survival., Level of Evidence: 4. Laryngoscope, 126:1086-1090, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To describe the clinical, demographic, and prognostic features of salivary gland mucinous adenocarcinoma, a rare head and neck malignancy., Study Design: Population-based national cancer registry analysis., Setting: Academic medical center., Subjects and Methods: A review was performed with the National Cancer Database from 1998 to 2012. Demographic, clinical, and survival characteristics were compiled and analyzed. Cox multivariate regression was used to identify predictors of survival. Log-rank tests were used to test survival differences unless otherwise specified., Results: A total of 170 cases were identified. The most common site of involvement was the parotid gland. Rates of nodal and distant metastases were 45.9% and 10.6%, respectively. High histologic grade was associated with nodal disease (P < .001) and advanced-stage disease (P = .006). Overall 5- and 10-year survival rates were 60% and 44%, respectively. Multivariate analysis found tumor size ≥2 cm (hazard ratio, 22.6; 95% confidence interval: 4.06-126.09; P < .001) and distant metastases (hazard ratio, 17.6; 95% confidence interval: 3.75-82.68; P < .001) to predict poor outcomes., Conclusions: Mucinous adenocarcinoma of the salivary gland is a rare otolaryngic cancer. Regional metastases and advanced stage are more common with high histologic grade. Tumor size and distant metastases negatively influence survival., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

This article reviews the epidemiology, embryology, risk factors, clinical presentation, diagnostic work-up, and basic management principles for the more common benign parotid neoplasms. The various histopathologies are also discussed and summarized., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Oncocytic carcinomas of the major salivary glands are extremely rare, with <100 cases reported., Methods: A retrospective review of the National Cancer Database was performed from 1998 to 2012., Results: We found 278 cases of major salivary oncocytic carcinoma. Most patients were men (61.9%), white (84.8%), with parotid disease (88.5%). Median age was 67 years (range, 16-90 years). Regional and distant metastases were found in 36.4% and 4.7% of cases. Overall survival at 5 and 10-years was 64% and 39%, respectively. Distant metastasis (hazard ratio [HR] = 13.87; 95% confidence interval [CI] = 2.98-64.52; p = .0010) and regional metastasis (HR = 3.01; 95% CI = 1.20-7.55; p = .019) are significant negative predictors, whereas positive margins approached significance (HR = 3.01; 95% CI = 1.20-7.55; p = .074)., Conclusion: Oncocytic carcinoma has a poor long-term prognosis and lymph node metastases are common. Distant and regional metastases are significant predictors of decreased survival. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1981-E1986, 2016., (© 2016 Wiley Periodicals, Inc.)

Objective: (1) To identify predictors of nodal disease in parotid malignancies using various clinical and pathologic variables. (2) To examine the effect of nodal disease on overall survival (OS) in parotid cancers, Study Design: Retrospective database review., Setting: National Cancer Data Base (1998-2012)., Subjects and Methods: We identified all cases of primary parotid malignancies in the United States between 1998 and 2012 in the National Cancer Data Base. Eight histopathologies, constituting >80% of all cases, were examined for nodal metastasis and survival., Results: We identified 22,653 cases of primary parotid cancer. Eight major histologies were studied, with mucoepidermoid carcinoma (31%), acinic cell carcinoma (18%), adenocarcinoma (14%), and adenoid cystic carcinoma (9%) being most common. Regional nodal disease incidence was 24.4% overall and varied by histopathology. Salivary ductal carcinoma had the highest incidence of both nodal metastasis and occult lymph node metastasis. Overall, N0 patients lived significantly longer than N+ (5-year OS, 79% vs 40%; P < .001). Low-grade disease had significantly better survival than high-grade (5-year OS, 88% vs 69%; P < .001). Occult nodal disease was found in 10.2% and varied by histopathology., Conclusion: Regional lymph node metastasis significantly decreases survival in many parotid malignancies. High-grade cancers had higher incidences of regional disease than did low grade. Adenocarcinoma had the highest mortality when regional disease was present. Incidence of occult disease varied by histology, but incidence was <10% for all low-grade disease. High T stage and grade are significant independent predictors of nodal disease for most histopathologies., (© American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.)

Introduction: Lymphoepithelial carcinoma (LEC) of the salivary glands is extremely rare worldwide, with studies limited to small case reports and case series from endemic areas (Southern China, Arctic Inuits) and strong association to Epstein Barr Virus (EBV). Studies on non-endemic regions are even more limited given the reality of only sporadic cases in these areas. Using the National Cancer Database (NCDB), we present the largest study on salivary LEC from a non-endemic region, the United States., Methods: A retrospective review of the NCDB from 1998-2012 for LEC of the major salivary glands was performed. Demographic and clinical variables were extracted for analysis. Multivariate COX regression was used to assess predictors of survival., Results: Two hundred and thirty-eight cases were identified (0.66% of all salivary cancers). Median age at diagnosis was 62 with peak incidence in ages 50-70. Most patients were Caucasian (81.2%), without gender preference. Regional metastasis was common (45.1%) and did not significantly impact survival. Distant metastasis was rare (2%). Overall survival (OS) at 5- and 10 years was 77% and 56%. Surgery and radiotherapy significantly showed better survival outcomes than surgery alone (p<0.001). Age >62, advanced stage, and dual modality therapy were significant predictors of survival in multivariate analysis., Conclusion: Lymphoepithelial carcinoma in the US mostly affects an older, Caucasian demographic. Regional metastasis is common and survival is fair at 5- and 10 years. Surgery and radiation are recommended for early and advanced disease stages. Age, stage, and therapy are significant predictors of survival outcomes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)