Identification of long-lived proteins reveals exceptional stability of essential cellular structures.

Intracellular proteins with long lifespans have recently been linked to age-dependent defects, ranging from decreased fertility to the functional decline of neurons. Why long-lived proteins exist in metabolically active cellular environments and how they are maintained over time remains poorly understood. Here, we provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complexes (NPCs) are maintained over a cell's life through slow but finite exchange of even its most stable subcomplexes. This maintenance is limited, however, as some nucleoporin levels decrease during aging, providing a rationale for the previously observed age-dependent deterioration of NPC function. Our identification of a long-lived proteome reveals cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process. PAPERCLIP:

Expression, purification, and structural analysis of the full-length human integral membrane protein γ-sarcoglycan.

Mutation of the gene encoding γ-sarcoglycan (SGCG), an integral membrane protein responsible for maintaining the integrity of the muscle cell sarcolemma, results in Limb-Girdle Muscular Dystrophy (LGMD), a congenital disease with no current treatment options. This member of the sarcoglycan glycoprotein family is a vital component of the Dystrophin Complex, which together facilitate normal muscle function. However, very little is known about the structure and dynamics of these proteins, and of membrane glycoproteins in general. This is due to a number of factors, including their complexity, heterogeneity and highly-specific native environments. The expression, purification, and structural study of membrane proteins is further impeded by their hydrophobic nature and consequent propensity to aggregate in aqueous solutions. Here, we report the first successful expression and purification of milligram quantities of full-length recombinant SGCG, utilizing fusion protein-guided overexpression to inclusion bodies in Escherichia coli. Purification of SGCG from the fusion protein, TrpΔLE, was facilitated using chemical cleavage. Cleavage products were then isolated by size-exclusion chromatography. Successful purification of the protein was confirmed using SDS-PAGE and mass spectroscopy. Finally, solution nuclear magnetic resonance spectroscopy of uniformly 15N-labeled SGCG in detergent environments was performed, yielding the first spectra of the full-length membrane glycoprotein, SGCG. These results represent the initial structural studies of SGCG, laying the foundation for further investigation on the interaction and dynamics of other integral membrane proteins. More specifically, this data allows for opportunities in the future for enhanced treatment modalities and cures for LGMD.

Lumbar drains: Practical understanding and application for the otolaryngologist.

INTRODUCTION: Lumbar drains are frequently used in patients with otolaryngologic concerns. These can be used therapeutically or prophylactically with the primary purpose being to modulate CSF pressure. Within otolaryngology, lumbar drains are most frequently used for cerebrospinal fluid leaks - either due to cerebrospinal fluid fistulas or in skull base surgery as these allow for potential healing of the defect. While not typically placed by otolaryngologists, a basic understanding of lumbar drains is beneficial in the context of patient management. MANAGEMENT: A lumbar drain is inserted into the intrathecal space in a patient's lumbar spine. Though considered to be a benign procedure, complications are relatively frequent, and adjustment or replacement of the drain may be required. Complications include infection, epidural bleeding, retained hardware, sequelae of relative immobility, or may relate to over-drainage, ranging from mild headache to cranial neuropathies, altered mental status, pneumocephalus, intracranial hemorrhage, and death. While in place, neurologic exams should be performed routinely and should include motor and sensory exams of the lower extremities. A patient should be monitored for fevers, nuchal rigidity, and other signs of infection or meningitis. The CSF fluid should be grossly examined to identify changes, but routine laboratory tests are not typically run on the fluid itself. Drainage rates will vary usually between 5 and 20 mL per hour and must be frequently reassessed and adjusted based upon signs of intracranial hypotension. Drains should be removed when appropriate and should not be left in more than 5 days due to the increased infectious risk. CONCLUSION: Lumbar drains are important tools used in patients with otolaryngologic pathologies. Otolaryngologists and otolaryngology residents should be familiar with these catheters to determine if they are working correctly and to identify adverse effects as early as possible.

eIF4B stimulates translation of long mRNAs with structured 5' UTRs and low closed-loop potential but weak dependence on eIF4G.

DEAD-box RNA helicases eukaryotic translation initiation factor 4A (eIF4A) and Ded1 promote translation by resolving mRNA secondary structures that impede preinitiation complex (PIC) attachment to mRNA or scanning. Eukaryotic translation initiation factor 4B (eIF4B) is a cofactor for eIF4A but also might function independently of eIF4A. Ribosome profiling of mutants lacking eIF4B or with impaired eIF4A or Ded1 activity revealed that eliminating eIF4B reduces the relative translational efficiencies of many more genes than does inactivation of eIF4A, despite comparable reductions in bulk translation, and few genes display unusually strong requirements for both factors. However, either eliminating eIF4B or inactivating eIF4A preferentially impacts mRNAs with longer, more structured 5' untranslated regions (UTRs). These findings reveal an eIF4A-independent role for eIF4B in addition to its function as eIF4A cofactor in promoting PIC attachment or scanning on structured mRNAs. eIF4B, eIF4A, and Ded1 mutations also preferentially impair translation of longer mRNAs in a fashion mitigated by the ability to form closed-loop messenger ribonucleoprotein particles (mRNPs) via eIF4F-poly(A)-binding protein 1 (Pab1) association, suggesting cooperation between closed-loop assembly and eIF4B/helicase functions. Remarkably, depleting eukaryotic translation initiation factor 4G (eIF4G), the scaffold subunit of eukaryotic translation initiation factor 4F (eIF4F), preferentially impacts short mRNAs with strong closed-loop potential and unstructured 5' UTRs, exactly the opposite features associated with hyperdependence on the eIF4B/helicases. We propose that short, highly efficient mRNAs preferentially depend on the stimulatory effects of eIF4G-dependent closed-loop assembly.

Verbal Learning and Memory After Cochlear Implantation in Postlingually Deaf Adults: Some New Findings with the CVLT-II.

OBJECTIVES: Despite the importance of verbal learning and memory in speech and language processing, this domain of cognitive functioning has been virtually ignored in clinical studies of hearing loss and cochlear implants in both adults and children. In this article, we report the results of two studies that used a newly developed visually based version of the California Verbal Learning Test-Second Edition (CVLT-II), a well-known normed neuropsychological measure of verbal learning and memory. DESIGN: The first study established the validity and feasibility of a computer-controlled visual version of the CVLT-II, which eliminates the effects of audibility of spoken stimuli, in groups of young normal-hearing and older normal-hearing (ONH) adults. A second study was then carried out using the visual CVLT-II format with a group of older postlingually deaf experienced cochlear implant (ECI) users (N = 25) and a group of ONH controls (N = 25) who were matched to ECI users for age, socioeconomic status, and nonverbal IQ. In addition to the visual CVLT-II, subjects provided data on demographics, hearing history, nonverbal IQ, reading fluency, vocabulary, and short-term memory span for visually presented digits. ECI participants were also tested for speech recognition in quiet. RESULTS: The ECI and ONH groups did not differ on most measures of verbal learning and memory obtained with the visual CVLT-II, but deficits were identified in ECI participants that were related to recency recall, the buildup of proactive interference, and retrieval-induced forgetting. Within the ECI group, nonverbal fluid IQ, reading fluency, and resistance to the buildup of proactive interference from the CVLT-II consistently predicted better speech recognition outcomes. CONCLUSIONS: Results from this study suggest that several underlying foundational neurocognitive abilities are related to core speech perception outcomes after implantation in older adults. Implications of these findings for explaining individual differences and variability and predicting speech recognition outcomes after implantation are discussed.

Reconstruction of midface defect from idiopathic destructive process using Medpor implant.

IMPORTANCE: Reconstruction of the midface remains a challenging task for even the most experienced surgeon, with a host of reconstructive options including free tissue transfer, allografts, or prosthetic implants. Presented here is a case of idiopathic bony destruction of the right midface in a 19year old female, creating a unique defect requiring repair. OBJECTIVE: Demonstrate a unique case of severe maxillary degeneration and discuss the associated reconstructive challenges and final repair with a prosthetic implant. DESIGN: Case report. RESULTS: The patient presented with a 7month history of an idiopathic progressive deformity of the right cheek. Computed tomography of the paranasal sinuses revealed extensive bone loss of the right midface and orbit. The patient underwent facial reconstruction using a customized Medpor (Stryker Corp, Kalamazoo, MI) implant. At 6month follow-up the patient and physician were both pleased with the patient's overall appearance. The patient did have some residual lower lid retraction present as well as some lateral pull at the lateral canthus outward from the orbit itself. CONCLUSIONS: Preoperative planning for midface reconstruction requires a deep understanding of the aesthetic, functional, and supportive roles this structure holds. Computer assistance allows the creation of custom made implants, providing the reconstructive surgeon with innovative options for reconstruction with minimal morbidity to the patient. As the technology around the design and creation of the custom implants continues to improve, the role of computer assistance in reconstruction will become more prominent.

Effect of Non-ablative Medical Therapy on Progression of Hearing Loss in Menière's Disease: A Systematic Review and meta-Analysis.

OBJECTIVE: To systematically review how audiometric data change over time in patients with Menière's disease (MD) undergoing non-ablative medical therapy. DATABASES REVIEWED: Medline (via PubMed), Scopus, Web of Science, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Google Scholar. METHODS: A systematic review and meta-analysis of the literature was performed. Adult patients undergoing non-ablative medical therapy and reported duration of disease or follow-up were included and pooled estimates of pure-tone average (PTA) were tabulated. Studies were excluded if they did not use established MD, did not have pure-tone average (PTA) audiometric data, underwent ear surgery or ablative therapies, and were systematic reviews or case reports. RESULTS: Out of 198 articles meeting full eligibility, 13 studies, involving 950 patients with MD, were included in the review and further analyzed. No effect on progression of PTA from initial diagnosis was seen between the different medical therapies within 2 years of non-ablative medical treatment. There was a significant worsening of PTA after 2 year, regardless of treatment used. High levels of heterogeneity among studies were noted up to 6 months from diagnosis ( I2 = 79%), likely reflecting differences in patient characteristics, treatment regimens, and study design. Overall, the risk of bias was low for the majority of included studies. CONCLUSIONS: Patients diagnosed with MD who are undergoing non-ablative medical therapy should be counseled on the likelihood of worsening of hearing loss over the course of the disease despite elected treatment.

Failure in HiRes Ultra Series Recall Devices Does Not Necessarily Lead to Decrement in Performance.

OBJECTIVE: To understand the impact on speech perception for patients experiencing Advanced Bionics V1 series Ultra and Ultra 3D cochlear implant failure. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic center. PATIENTS: Adult patients implanted with V1 series devices. INTERVENTIONS: Device integrity and speech perception testing. MAIN OUTCOME MEASURES: consonant-nucleus-consonant and AzBio in quiet speech recognition scores. RESULTS: At our institution, 116 V1 series cochlear implants were placed in 114 patients. Thirteen devices in prelingual patients were excluded, leaving 103 (89%) for final analysis. Forty-eight (46.6%) devices were considered as failed using the company provided EFI analysis tool. There were 36 (65.5%) of the remaining 55 devices that consistently tested within normal range; the remainder lost to follow-up with unknown status. Among the 48 device failures, 29 were revised and 19 patients were not revised. Among those not revised, 11 self-opted for observation (57.9%). Observed patients, despite impedance changes meeting failure criteria, had no subjective or objective changes in speech perception. Sentence testing scores for failure patients who elected observation (82.9 ± 11.4%) were significantly higher at failure compared with those opting for revision (55 ± 22.8%, p = 0.006). For those undergoing revision surgery, significant improvement in post-activation scores was noted as compared with time of failure with a mean improvement of 12.9% (p = 0.002, n = 24) for consonant-nucleus-consonant word scores and 17.2% (p = 0.001, n = 19) for AzBio in quiet scores. CONCLUSIONS: Proactive monitoring using EFI identifies a higher rate of Ultra Series V1 device failure than previously reported. However, about 20% of these patients may not have subjective change in hearing or objective decline in test scores and could be observed. Should performance worsen, reimplantation provides significant improvement in speech recognition.

Tumor biomechanical stiffness by magnetic resonance elastography predicts surgical outcomes and identifies biomarkers in vestibular schwannoma and meningioma.

Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial nerve function. Furthermore, we identify tumor microenvironment biomarkers of increased stiffness, including αSMA + myogenic fibroblasts, CD163 + macrophages, and HABP (hyaluronic acid binding protein). In a human VS cell line, a dose-dependent upregulation of HAS1-3, enzymes responsible for hyaluronan synthesis, was observed following stimulation with TNFα, a proinflammatory cytokine present in VS. Taken together, MRE is an accurate, non-invasive predictor of tumor stiffness in VS and meningiomas. VS with increased stiffness portends worse preoperative hearing and poorer postoperative outcomes. Moreover, inflammation-mediated hyaluronan deposition may lead to increased stiffness.

Digital Otoscopy With Computer-Aided Composite Image Generation: Impact on the Correct Diagnosis, Confidence, and Time.

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.

Amplitude Parameters Are Predictive of Hearing Preservation in a Randomized Controlled Trial of Intracochlear Electrocochleography During Cochlear Implant Surgery.

OBJECTIVE: To prospectively evaluate the association between hearing preservation after cochlear implantation (CI) and intracochlear electrocochleography (ECochG) amplitude parameters. STUDY DESIGN: Multi-institutional, prospective randomized clinical trial. SETTING: Ten high-volume, tertiary care CI centers. PATIENTS: Adults (n = 87) with sensorineural hearing loss meeting CI criteria (2018-2021) with audiometric thresholds of ≤80 dB HL at 500 Hz. METHODS: Participants were randomized to CI surgery with or without audible ECochG monitoring. Electrode arrays were inserted to the full-depth marker. Hearing preservation was determined by comparing pre-CI, unaided low-frequency (125-, 250-, and 500-Hz) pure-tone average (LF-PTA) to LF-PTA at CI activation. Three ECochG amplitude parameters were analyzed: 1) insertion track patterns, 2) magnitude of ECochG amplitude change, and 3) total number of ECochG amplitude drops. RESULTS: The Type CC insertion track pattern, representing corrected drops in ECochG amplitude, was seen in 76% of cases with ECochG "on," compared with 24% of cases with ECochG "off" ( p = 0.003). The magnitude of ECochG signal drop was significantly correlated with the amount of LF-PTA change pre-CI and post-CI ( p < 0.05). The mean number of amplitude drops during electrode insertion was significantly correlated with change in LF-PTA at activation and 3 months post-CI ( p ≤ 0.01). CONCLUSIONS: ECochG amplitude parameters during CI surgery have important prognostic utility. Higher incidence of Type CC in ECochG "on" suggests that monitoring may be useful for surgeons in order to recover the ECochG signal and preventing potentially traumatic electrode-cochlear interactions.

Verbal short-term memory development and spoken language outcomes in deaf children with cochlear implants.

OBJECTIVES: Cochlear implants (CIs) help many deaf children achieve near-normal speech and language (S/L) milestones. Nevertheless, high levels of unexplained variability in S/L outcomes are limiting factors in improving the effectiveness of CIs in deaf children. The objective of this study was to longitudinally assess the role of verbal short-term memory (STM) and working memory (WM) capacity as a progress-limiting source of variability in S/L outcomes after CI in children. DESIGN: Longitudinal study of 66 children with CIs for prelingual severe-to-profound hearing loss. Outcome measures included performance on digit span forward (DSF), digit span backward (DSB), and four conventional S/L measures that examined spoken-word recognition (Phonetically Balanced Kindergarten word test), receptive vocabulary (Peabody Picture Vocabulary Test ), sentence-recognition skills (Hearing in Noise Test), and receptive and expressive language functioning (Clinical Evaluation of Language Fundamentals Fourth Edition Core Language Score; CELF). RESULTS: Growth curves for DSF and DSB in the CI sample over time were comparable in slope, but consistently lagged in magnitude relative to norms for normal-hearing peers of the same age. For DSF and DSB, 50.5% and 44.0%, respectively, of the CI sample scored more than 1 SD below the normative mean for raw scores across all ages. The first (baseline) DSF score significantly predicted all endpoint scores for the four S/L measures, and DSF slope (growth) over time predicted CELF scores. DSF baseline and slope accounted for an additional 13 to 31% of variance in S/L scores after controlling for conventional predictor variables such as: chronological age at time of testing, age at time of implantation, communication mode (auditory-oral communication versus total communication), and maternal education. Only DSB baseline scores predicted endpoint language scores on Peabody Picture Vocabulary Test and CELF. DSB slopes were not significantly related to any endpoint S/L measures. DSB baseline scores and slopes taken together accounted for an additional 4 to 19% of variance in S/L endpoint measures after controlling for the conventional predictor variables. CONCLUSIONS: Verbal STM/WM scores, process measures of information capacity, develop at an average rate in the years after cochlear implantation, but were found to consistently lag in absolute magnitude behind those reported for normal-hearing peers. Baseline verbal STM/WM predicted long-term endpoint S/L outcomes, but verbal STM slopes predicted only endpoint language outcomes. Verbal STM/WM processing skills reflect important underlying core elementary neurocognitive functions and represent potential intervention targets for improving endpoint S/L outcomes in pediatric CI users.

The Sensory Auricular Branch of the Facial Nerve and its Relationship to Landmarks of the Facial Recess.

OBJECTIVE: Delineate the anatomic relationship of the sensory auricular branch (SAB) of the facial nerve to other structures of the facial recess. METHODS: Ten adult cadaveric temporal bones were randomly selected and dissected under operative microscopy. Linear and angular measurements were obtained for the following parameters: (1) the distance from the tip of the short process of the incus to the point of convergence of the SAB and the main trunk of the facial nerve; (2) the distance from the point of convergence of the SAB and the main trunk of the facial nerve to the chorda tympani (CT) division from the main trunk; (3) the distance from the bifurcation of the CT and facial nerve to the crossover point of the SAB/CT; (4) the angle at which the SAB merges with the main trunk (Y°), and (5) the angle at which the CT divides off the main trunk (X°). RESULTS: The mean distance from the tip of the short process of the incus to the SAB takeoff was 8.7 ± 1.83 mm (range 6-13 mm). The mean distance from the SAB to the CT division from the main trunk was 5.9 ± 2.41 mm (range 3-10 mm). The mean angle at which the SAB merged with the main trunk of the facial nerve was 38.5 ± 12.63° (range 25°-68°). The mean CT-main trunk angle was 16 ± 4.24° (range 8°-21°). The branching point of the SAB from the facial nerve approximately bisected the facial recess. CONCLUSION: Recognizing the SAB and knowing its relationships to surrounding anatomy provides a useful adjunctive landmark for the identification of the main trunk of the facial nerve's mastoid segment. LEVEL OF EVIDENCE: 4.

Identification Accuracy of Safety-Relevant Environmental Sounds in Adult Cochlear Implant Users.

OBJECTIVE: Examine cochlear implant (CI) users' ability to identify safety-relevant environmental sounds, imperative for safety, independence, and personal well-being. METHODS: Twenty-one experienced adult CI users completed an Environmental Sound Identification (ESI) test consisting of 42 common environmental sounds, 28 of which were relevant to personal safety, along with 14 control sounds. Prior to sound identification, participants were shown sound names and asked to rate the familiarity and, separately, relevance to safety of each corresponding sound on a 1-5 scale. RESULTS: Overall ESI accuracy was 57% correct for the safety-relevant sounds and 55% correct for control sounds. Participants rated safety-relevant sounds as more important to safety and more familiar than the non-safety sounds. ESI accuracy significantly correlated with familiarity ratings. CONCLUSION: The present findings suggest mediocre ESI accuracy in postlingual adult CI users for safety-relevant and other environmental sounds. Deficits in the identification of these sounds may put CI listeners at increased risk of accidents or injuries and may require a specific rehabilitation program to improve CI outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2388-2393, 2023.

In Vitro Glycosylation of the Membrane Protein γ-Sarcoglycan in Nanodiscs.

Membrane glycoproteins are proteins that reside in the membranes of cells and are post-translationally modified to have sugars attached to their amino acid side chains. Studies of this subset of proteins in their native states are becoming more important since they have been linked to numerous human diseases. However, these proteins are difficult to study due to their hydrophobic nature and their propensity to aggregate. Using membrane mimetics allows us to solubilize these proteins, which, in turn, allows us to perform glycosylation in vitro to study the effects of the modification on protein structure, dynamics, and interactions. Here, the membrane glycoprotein γ-sarcoglycan was incorporated into nanodiscs composed of long-chain lipids and membrane scaffold proteins to perform N-linked glycosylation in which an enzyme attaches a sugar to the asparagine side chain within the glycosylation site. We previously performed glycosylation of membrane proteins in vitro when the protein had been solubilized using different detergents and short-chain lipids. This work demonstrates successful glycosylation of a full-length membrane protein in nanodiscs providing a more biologically relevant sample to study the effects of the modification.

Contribution of Verbal Learning & Memory and Spectro-Temporal Discrimination to Speech Recognition in Cochlear Implant Users.

OBJECTIVES: Existing cochlear implant (CI) outcomes research demonstrates a high degree of variability in device effectiveness among experienced CI users. Increasing evidence suggests that verbal learning and memory (VL&M) may have an influence on speech recognition with CIs. This study examined the relations in CI users between visual measures of VL&M and speech recognition in a series of models that also incorporated spectro-temporal discrimination. Predictions were that (1) speech recognition would be associated with VL&M abilities and (2) VL&M would contribute to speech recognition outcomes above and beyond spectro-temporal discrimination in multivariable models of speech recognition. METHODS: This cross-sectional study included 30 adult postlingually deaf experienced CI users who completed a nonauditory visual version of the California Verbal Learning Test-Second Edition (v-CVLT-II) to assess VL&M, and the Spectral-Temporally Modulated Ripple Test (SMRT), an auditory measure of spectro-temporal processing. Participants also completed a battery of word and sentence recognition tasks. RESULTS: CI users showed significant correlations between some v-CVLT-II measures (short-delay free- and cued-recall, retroactive interference, and "subjective" organizational recall strategies) and speech recognition measures. Performance on the SMRT was correlated with all speech recognition measures. Hierarchical multivariable linear regression analyses showed that SMRT performance accounted for a significant degree of speech recognition outcome variance. Moreover, for all speech recognition measures, VL&M scores contributed independently in addition to SMRT. CONCLUSION: Measures of spectro-temporal discrimination and VL&M were associated with speech recognition in CI users. After accounting for spectro-temporal discrimination, VL&M contributed independently to performance on measures of speech recognition for words and sentences produced by single and multiple talkers. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:661-669, 2023.

Risk factors for cisplatin-associated ototoxicity in pediatric oncology patients.

BACKGROUND: Cisplatin is an effective chemotherapy agent against several pediatric malignancies. One of its side effects is irreversible sensorineural hearing damage that is highly variable with a reported incidence of 22-70%. The aim of this study was to evaluate the incidence and identify clinical predictors of cisplatin-related ototoxicity. PROCEDURES: We performed a retrospective chart review of 102 pediatric patients who had completed cisplatin therapy for osteosarcoma, neuroblastoma, hepatoblastoma, or germ cell tumor. Patients were diagnosed at Riley Hospital for Children between January 1995 and June 2008, were less than 18 years old at diagnosis, and had normal hearing prior to therapy. Audiograms were scored using the Brock scale (0-4), a validated grading system for cisplatin-related hearing loss. RESULTS: Forty-two percent of the patients experienced hearing loss and 28% had moderate to severe ototoxicity (Brock score ≥2). Males were at significantly greater risk for developing hearing loss than were females (P = 0.005, OR 4.812). Age at cancer diagnosis was inversely related to severity of ototoxicity. Patients who suffered Brock grade 3 ototoxicity had a mean age of 4.5 years versus 11.5 years and 7.2 years for grades 1 and 2, respectively (P = 0.02). Cumulative cisplatin dose was also identified as a risk factor for development of ototoxicity (P = 0.03). CONCLUSIONS: Gender and cumulative dose are important clinical biomarkers of cisplatin ototoxicity. Severity of ototoxicity may be inversely related to age at time of exposure, with very young patients exhibiting higher grades of hearing loss following cisplatin therapy.

Auditory skills, language development, and adaptive behavior of children with cochlear implants and additional disabilities.

OBJECTIVE: The objective of this study was to evaluate the development of functional auditory skills, language, and adaptive behavior in deaf children with cochlear implants (CI) who also have additional disabilities (AD). DESIGN: A two-group, pre-test versus post-test design was used. STUDY SAMPLE: Comparisons were made between 23 children with CIs and ADs, and an age-matched comparison group of 23 children with CIs without ADs (No-AD). Assessments were obtained pre-CI and within 12 months post-CI. RESULTS: All but two deaf children with ADs improved in auditory skills using the IT-MAIS. Most deaf children in the AD group made progress in receptive but not expressive language using the preschool language scale, but their language quotients were lower than the No-AD group. Five of eight children with ADs made progress in daily living skills and socialization skills; two made progress in motor skills. Children with ADs who did not make progress in language, did show progress in adaptive behavior. CONCLUSIONS: Children with deafness and ADs made progress in functional auditory skills, receptive language, and adaptive behavior. Expanded assessment that includes adaptive functioning and multi-center collaboration is recommended to best determine benefits of implantation in areas of expected growth in this clinical population.

Impact of Demographics and Clinical Features on Initial Treatment Pathway for Vestibular Schwannoma.

OBJECTIVE: To identify demographic and clinical features impacting initial treatment pathway for vestibular schwannoma. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care academic medical center. PATIENTS: Patients diagnosed with vestibular schwannoma between 2009 and 2019. INTERVENTIONS: Observation, stereotactic radiosurgery, or microsurgical resection. MAIN OUTCOME MEASURES: χ 2 Test, one-way analysis of variance, and multivariate logistic regression were used to correlate demographic and clinical factors with initial treatment pathway for 197 newly diagnosed vestibular schwannoma patients. RESULTS: Among 197 patients, 93 (47%) were initially treated with observation, 60 (30%) with stereotactic radiation (Gamma Knife) and 44 (22%) with surgical resection. Age univariately had no statistically significant impact on initial pathway, but those undergoing surgery trended toward a younger demographic (49.1 yr [surgery] versus 57.2 yr [observation] versus 59.0 yr [Gamma Knife]). Men were more likely to be initially observed than women ( p = 0.04). Patients initially observed were more likely to have a lower Koos classification ( p < 0.001) and have better tumor-ear hearing ( p = 0.03). Only 34.4% of patients living outside the local geographic region were initially observed compared with 53.0% living locally ( p = 0.055). Surgeon correlated with initial treatment ( p = 0.04) but did not maintain significance when adjusting for hearing level or tumor size. A multiple linear regression model found age, maximum tumor diameter, and Koos class to correlate with initial treatment pathway ( p < 0.0001, r2 = 0.42). CONCLUSION: Initial treatment pathway for newly diagnosed vestibular schwannoma is impacted by demographic factors such as age, sex, and geographic proximity to the medical center. Clinical features including hearing level and tumor size also correlated with initial treatment modality.

Standardization of Outcome Measures for Intratympanic Steroid Treatment for Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: To identify variability in reported hearing outcomes for intratympanic (IT) steroid treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) by comparing outcomes using the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guideline with other published criteria. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary otology practice. PATIENTS: Patients with ISSNHL treated with IT steroid between April 2003 and December 2020. INTERVENTIONS: IT steroid injection and audiometric evaluation. MAIN OUTCOME MEASURES: 1) Rates of full, partial, or no recovery using the AAO-HNS guideline versus other reported criteria, and 2) correlation analyses of demographic and clinical variables with response to IT steroid. RESULTS: Using AAO-HNS reporting criteria, full recovery of the pure-tone average was noted in 25.68% of patients. Applying eight other published outcomes criteria to this patient cohort classified full recovery in 14.87 to 40.54% of patients. Similarly, AAO-HNS criteria classified "no recovery" in 51.35% of our patients, whereas applying the other reported criteria showed an average rate of 62.16% no recovery and as high as 82.43% of patients without recovery. Younger age ( p = 0.003; effect size, 0.924) and IT injection within a week of onset ( p < 0.001; effect size, 1.099) positively correlated with full recovery. There was no impact of prior or concurrent oral steroids, or number of steroid injections on outcome. CONCLUSION: Great variability exists in the literature for assessment of IT steroid outcomes in ISSNHL. Standard reporting of outcomes as per the AAO-HNS SSNHL guideline is recommended to consistently characterize IT steroid efficacy and allow comparison across studies.