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OBJECTIVES: Describe the diagnosis and management of a spontaneous cerebrospinal fluid leak (sCSF-L) through the facial nerve fallopian canal and determine the role of intracranial hypertension (IH). STUDY DESIGN: Retrospective case study and systematic review of the literature. METHODS: Reviewed patient characteristics, radiographic findings, and management of the facial nerve canal CSF leak and postoperative IH. Conducted systematic literature review according to the PRISMA guidelines for surgical management and rates of IH. RESULTS: A 50-year-old female with bilateral tegmen defects and temporal encephaloceles underwent left middle cranial fossa (MCF) repair. Intraoperative CSF egressed from the temporal bone tegmen defects. Facial nerve decompression revealed CSF leak from the labyrinthine segment. A nonocclusive temporalis muscle plug was placed in the fallopian canal, and tegmen repair was completed with bone cement. A ventriculoperitoneal shunt was placed for IH. Postoperative facial nerve function and hearing were normal. A total of 20 studies met inclusion criteria with a total of 25 unique patients. Of 13 total adult cases of fallopian canal CSF leak, there is a 46% recurrence rate, and 86% of patients had documented IH when tested. CONCLUSIONS: Fallopian canal CSF leaks are rare and challenging to manage. Assessment of intracranial hypertension and CSF diversion is recommended along with MCF skull base repair to preserve facial nerve function and conductive hearing.
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Pérdida de Líquido Cefalorraquídeo , Hipertensión Intracraneal , Humanos , Femenino , Persona de Mediana Edad , Hipertensión Intracraneal/cirugía , Pérdida de Líquido Cefalorraquídeo/cirugía , Derivación Ventriculoperitoneal , Encefalocele/cirugía , Nervio Facial/cirugíaRESUMEN
Cochlear implants (CI) have revolutionized the treatment of patients with severe to profound sensory hearing loss by providing a method of bypassing normal hearing to directly stimulate the auditory nerve. A further advance in the field has been the introduction of "hearing preservation" surgery, whereby the CI electrode array (EA) is carefully inserted to spare damage to the delicate anatomy and function of the cochlea. Preserving residual function of the inner ear allows patients to receive maximal benefit from the CI and to combine CI electric stimulation with acoustic hearing, offering improved postoperative speech, hearing, and quality of life outcomes. However, under the current paradigm of implant surgery, where EAs are inserted by hand, the cochlea cannot be reliably spared from damage. Robotics-assisted EA insertion is an emerging technology that may overcome fundamental human kinetic limitations that prevent consistency in achieving steady and slow EA insertion. This review begins by describing the relationship between EA insertion speed and generation of intracochlear forces and pressures. The various mechanisms by which these intracochlear forces can damage the cochlea and lead to worsened postoperative outcomes are discussed. The constraints of manual insertion technique are compared to robotics-assisted methods, followed by an overview of the current and future state of robotics-assisted EA insertion.
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PURPOSE: Large individual differences and poor speech recognition outcomes are routinely observed in most patients who have received auditory brainstem implants (ABIs). A case report of an ABI recipient with exceptionally good speech recognition outcomes presents an opportunity to better understand the core information processing mechanisms that underlie variability and individual differences in outcomes. METHOD: A case study is reported of an adult ABI recipient (ID-006) with postlingually acquired, Neurofibromatosis Type 2 (NF2)-related hearing loss who displayed exceptional postoperative speech recognition scores. A novel battery of assessment measures was used to evaluate ID-006's auditory, cognitive, and linguistic information processing skills. RESULTS: Seventeen years following ABI activation, ID-006 scored 77.6% correct on the AzBio Sentences in quiet. On auditory processing tasks, ID-006 scored higher on tasks with meaningful sentences and much lower on tasks that relied exclusively on audibility. ID-006 also demonstrated exceptionally strong abilities on several cognitive and linguistic information processing tasks. CONCLUSIONS: Results from a novel battery of information processing tests suggest that ID-006 relies extensively on top-down predictive processing and cognitive control strategies to efficiently encode and process auditory information provided by his ABI. Results suggest that current measures of outcomes and benefits should be expanded beyond conventional speech recognition measures to include more sensitive and robust measures of speech recognition as well as neurocognitive measures such as executive function, working memory, and lexical access.
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Implantación Auditiva en el Tronco Encefálico , Pérdida Auditiva , Neurofibromatosis 2 , Percepción del Habla , Adulto , Humanos , Implantación Auditiva en el Tronco Encefálico/efectos adversos , Implantación Auditiva en el Tronco Encefálico/métodos , Habla , Percepción del Habla/fisiología , Neurofibromatosis 2/complicaciones , Neurofibromatosis 2/cirugía , Pérdida Auditiva/etiologíaRESUMEN
OBJECTIVE: The objective of the current study was to present the results of an international working group survey identifying perceived limitations of existing facial nerve grading scales to inform the development of a novel grading scale for assessing early postoperative facial paralysis that incorporates regional scoring and is anchored in recovery prognosis and risk of associated complications. STUDY DESIGN: Survey. SETTING: A working group of 48 multidisciplinary clinicians with expertise in skull base, cerebellopontine angle, temporal bone, or parotid gland surgery. RESULTS: House-Brackmann grade is the most widely used system to assess facial nerve function among working group members (81%), although more than half (54%) agreed that the system they currently use does not adequately estimate the risk of associated complications, such as corneal injury, and confidence in interrater and intrarater reliability is generally low. Simplicity was ranked as the most important attribute of a novel postoperative facial nerve grading system to increase the likelihood of adoption, followed by reliability and accuracy. There was widespread consensus (91%) that the eye is the most critical facial region to focus on in the early postoperative setting. CONCLUSIONS: Members were invited to submit proposed grading systems in alignment with the objectives of the working group for subsequent validation. From these data, we plan to develop a simple, clinically anchored, and reproducible staging system with regional scoring for assessing early postoperative facial nerve function after surgery of the skull base, cerebellopontine angle, temporal bone, or parotid gland.
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Nervio Facial , Parálisis Facial , Humanos , Nervio Facial/cirugía , Reproducibilidad de los Resultados , Parálisis Facial/diagnóstico , Parálisis Facial/etiología , Cara , Cabeza , Complicaciones Posoperatorias/diagnósticoRESUMEN
Adeno-associated virus (AAV)-mediated gene transfer has shown promise in rescuing mouse models of genetic hearing loss, but how viral capsid and promoter selection affects efficacy is poorly characterized. Here, we tested combinations of AAVs and promoters to deliver Tmprss3, mutations in which are associated with hearing loss in humans. Tmprss3tm1/tm1 mice display severe cochlear hair cell degeneration, loss of auditory brainstem responses, and delayed loss of spiral ganglion neurons. Under the ubiquitous CAG promoter and AAV-KP1 capsid, Tmprss3 overexpression caused striking cytotoxicity in vitro and in vivo and failed to rescue degeneration or dysfunction of the Tmprss3tm1/tm1 cochlea. Reducing the dosage or using AAV-DJ-CAG-Tmprss3 diminished cytotoxicity without rescue of the Tmprss3tm1/tm1 cochlea. Finally, the combination of AAV-KP1 capsid and the EF1α promoter prevented cytotoxicity and reduced hair cell degeneration, loss of spiral ganglion neurons, and improved hearing thresholds in Tmprss3tm1/tm1 mice. Together, our study illustrates toxicity of exogenous genes and factors governing rescue efficiency, and suggests that cochlear gene therapy likely requires precisely targeted transgene expression.
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OBJECTIVE: The timing for resuming continuous positive airway pressure (CPAP) postoperatively after skull base surgery remains controversial because of the risk of pneumocephalus. We determined the safety of immediate CPAP use after middle cranial fossa (MCF) spontaneous cerebrospinal fluid (sCSF) leak repair with bone cement. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary academic medical center. PATIENTS: Thirteen consecutive patients with CPAP-treated obstructive sleep apnea and temporal bone sCSF leaks who underwent skull base repair with hydroxyapatite bone cement between July 2021 and October 2022. INTERVENTIONS: CPAP use resumed on postoperative day 1 after the confirmation of skull base reconstruction with temporal bone computed tomography (CT). MAIN OUTCOME MEASURES: Postoperative skull base defects on CT, pneumocephalus, or intracranial complications. RESULTS: The average age was 55.5 ± 8.8 years (±standard deviation), and 69.2% were female with a BMI of 45.39 ± 15.1 kg/m 2 . Multiple tegmen defects were identified intraoperatively in 53.9% of patients with an average of 1.85 ± 0.99 defects and an average defect size on preoperative imaging of 6.57 ± 3.45 mm. All patients had an encephalocele identified intraoperatively. No residual skull base defects were observed on CT imaging on postoperative day 1. No postoperative complications occurred. One patient developed a contralateral sCSF leak 2 months after repair. There were no recurrent sCSF leaks 1 month postoperatively. CONCLUSION: Immediate postoperative CPAP use is safe in patients undergoing MCF sCSF leak repair with bone cement because of the robust skull base repair.
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Cementos para Huesos , Neumocéfalo , Humanos , Femenino , Persona de Mediana Edad , Masculino , Durapatita , Presión de las Vías Aéreas Positiva Contínua , Estudios Prospectivos , Estudios Retrospectivos , Base del Cráneo/diagnóstico por imagen , Base del Cráneo/cirugía , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/cirugía , Resultado del TratamientoRESUMEN
Mechanosensitive hair cells in the cochlea are responsible for hearing but are vulnerable to damage by genetic mutations and environmental insults. The paucity of human cochlear tissues makes it difficult to study cochlear hair cells. Organoids offer a compelling platform to study scarce tissues in vitro; however, derivation of cochlear cell types has proven non-trivial. Here, using 3D cultures of human pluripotent stem cells, we sought to replicate key differentiation cues of cochlear specification. We found that timed modulations of Sonic Hedgehog and WNT signaling promote ventral gene expression in otic progenitors. Ventralized otic progenitors subsequently give rise to elaborately patterned epithelia containing hair cells with morphology, marker expression, and functional properties consistent with both outer and inner hair cells in the cochlea. These results suggest that early morphogenic cues are sufficient to drive cochlear induction and establish an unprecedented system to model the human auditory organ.
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Proteínas Hedgehog , Células Madre Pluripotentes , Humanos , Proteínas Hedgehog/metabolismo , Cóclea , Células Ciliadas Auditivas Internas , Organoides , Diferenciación Celular/fisiologíaRESUMEN
Hearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, we assessed the production of the candidate protein via western blotting of lysates from fibroblasts from an affected individual and an unaffected control. Pathogenic variants in known disease genes associated with hearing loss and peripheral neuropathy were excluded. A homozygous frameshift variant in the BICD1 gene, c.1683dup (p.(Arg562Thrfs*18)), was identified in the proband and segregated with hearing loss and peripheral neuropathy in the family. The BIDC1 RNA analysis from patient fibroblasts showed a modest reduction in gene transcripts compared to the controls. In contrast, protein could not be detected in fibroblasts from a homozygous c.1683dup individual, whereas BICD1 was detected in an unaffected individual. Our findings indicate that bi-allelic loss-of-function variants in BICD1 are associated with hearing loss and peripheral neuropathy. Definitive evidence that bi-allelic loss-of-function variants in BICD1 cause peripheral neuropathy and hearing loss will require the identification of other families and individuals with similar variants with the same phenotype.
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Sordera , Pérdida Auditiva , Enfermedades del Sistema Nervioso Periférico , Humanos , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas del Citoesqueleto/genética , Sordera/genética , Pérdida Auditiva/genética , Linaje , Enfermedades del Sistema Nervioso Periférico/genética , FenotipoRESUMEN
Objective: Military veterans have high rates of noise-induced hearing loss (NIHL) which is associated with more significant spiral ganglion neuronal loss. This study explores the relationship between NIHL and cochlear implant (CI) outcomes in veterans. Study Design: Retrospective case series of veterans who underwent CI between 2019 and 2021. Setting: Veterans Health Administration hospital. Methods: AzBio Sentence Test, Consonant-Nucleus-Consonant (CNC) scores, and Speech, Spatial, and Qualities of Hearing Scale (SSQ) were measured pre- and postoperatively. Linear regression assessed relationships between outcomes and noise exposure history, etiology of hearing loss, duration of hearing loss, and Self-Administered Gerocognitive Exam (SAGE) scores. Results: Fifty-two male veterans were implanted at an average (standard deviation) age of 75.0 (9.2) years without major complications. The average duration of hearing loss was 36.0 (18.4) years. The average time of hearing aid use was 21.2 (15.4) years. Noise exposure was reported in 51.3% of patients. Objectively, AzBio and CNC scores 6 months postoperatively showed significant improvement of 48% and 39%, respectively. Subjectively, average 6-month SSQ scores showed significant improvement by 34 points (p < .0001). Younger age, SAGE score ≥17, and shorter duration of amplification were associated with higher postoperative AzBio scores. Greater improvement in AzBio and CNC scores was associated with lower preoperative scores. Noise exposure was not associated with any difference in CI performance. Conclusion: Despite high levels of noise exposure and advanced age, veterans derive substantial benefits from cochlear implantation. SAGE score ≥17 may be predictive of overall CI outcomes. Noise exposure does not impact CI outcomes. Level of Evidence: Level 4.
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The inner ear is derived from the otic placode, one of the numerous cranial sensory placodes that emerges from the pre-placodal ectoderm (PPE) along its anterior-posterior axis. However, the molecular dynamics underlying how the PPE is regionalized are poorly resolved. We used stem cell-derived organoids to investigate the effects of Wnt signaling on early PPE differentiation and found that modulating Wnt signaling significantly increased inner ear organoid induction efficiency and reproducibility. Alongside single-cell RNA sequencing, our data reveal that the canonical Wnt signaling pathway leads to PPE regionalization and, more specifically, medium Wnt levels during the early stage induce (1) expansion of the caudal neural plate border (NPB), which serves as a precursor for the posterior PPE, and (2) a caudal microenvironment that is required for otic specification. Our data further demonstrate Wnt-mediated induction of rostral and caudal cells in organoids and more broadly suggest that Wnt signaling is critical for anterior-posterior patterning in the PPE.
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Oído Interno , Vía de Señalización Wnt , Animales , Ratones , Reproducibilidad de los Resultados , Oído Interno/metabolismo , Diferenciación Celular , Ectodermo/metabolismo , Organoides , Células Madre , Regulación del Desarrollo de la Expresión GénicaRESUMEN
OBJECTIVE: To describe a tumor resection using the inferior long-axis (ILA) technique for cisternal facial nerve dissection in large vestibular schwannomas (VS). STUDY DESIGN: Retrospective case series from 2018 to 2021. SETTING: Tertiary academic medical center. PATIENTS: Patients who underwent surgical resection with ILA facial nerve dissection of VS (>2.0 cm measured parallel to the petrous ridge) and had at least 3-month follow-up. INTERVENTIONS: Cisternal facial nerve dissection during retrosigmoid or translabyrinthine approach using standardized ILA technique developed by author R.N. MAIN OUTCOME MEASURES: Immediate postoperative and last follow-up facial nerve function with House-Brackmann scores of I to II defined as "good" facial nerve function and House-Brackmann scores III to VI defined as "poor" function. Extent of resection was also assessed. RESULTS: A total of 48 patients underwent large VS resection with ILA dissection of tumor off of the facial nerve from 2018 to 2021. Mean (standard deviation) tumor size was 3.11 (0.76) cm. Mean (standard deviation) follow-up was 9.2 (9.0) months. Gross-total resection or near-total resection were achieved in 75% (radiographic estimate) to 83% (surgeon estimate) of cases. End-of-case facial nerve stimulation at 0.05 mAmp with a response of at least 240 mV was achieved in 80.4% of patients. Good facial nerve function was observed in 72% immediately postoperatively, 70% 1-month postoperatively, and 82% of patients at last follow-up. CONCLUSIONS: The ILA technique is now the method of choice of the senior surgeon (R.N.) when performing microsurgical dissection of the cisternal facial nerve, with which he has achieved high rates of total or near-total resection with excellent facial nerve preservation.
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Neuroma Acústico , Masculino , Humanos , Neuroma Acústico/cirugía , Nervio Facial/cirugía , Estudios Retrospectivos , Procedimientos Neuroquirúrgicos/métodos , Resultado del Tratamiento , Complicaciones Posoperatorias/cirugíaRESUMEN
BACKGROUND: It is well established that biallelic mutations in transmembrane protease, serine 3 (TMPRSS3) cause hearing loss. Currently, there is controversy regarding the audiological outcomes after cochlear implantation (CI) for TMPRSS3-associated hearing loss. This controversy creates confusion among healthcare providers regarding the best treatment options for individuals with TMPRSS3-related hearing loss. METHODS: A literature review was performed to identify all published cases of patients with TMPRSS3-associated hearing loss who received a CI. CI outcomes of this cohort were compared with published adult CI cohorts using postoperative consonant-nucleus-consonant (CNC) word performance. TMPRSS3 expression in mouse cochlea and human auditory nerves (HAN) was determined by using hybridisation chain reaction and single-cell RNA-sequencing analysis. RESULTS: In aggregate, 27 patients (30 total CI ears) with TMPRSS3-associated hearing loss treated with CI, and 85% of patients reported favourable outcomes. Postoperative CNC word scores in patients with TMPRSS3-associated hearing loss were not significantly different than those seen in adult CI cohorts (8 studies). Robust Tmprss3 expression occurs throughout the mouse organ of Corti, the spindle and root cells of the lateral wall and faint staining within <5% of the HAN, representing type II spiral ganglion neurons. Adult HAN express negligible levels of TMPRSS3. CONCLUSION: The clinical features after CI and physiological expression of TMPRSS3 suggest against a major role of TMPRSS3 in auditory neurons.
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Implantación Coclear , Sordera , Pérdida Auditiva , Adulto , Humanos , Ratones , Animales , Ganglio Espiral de la Cóclea/metabolismo , Serina Endopeptidasas/genética , Proteínas de la Membrana/genética , Proteínas de Neoplasias/genética , Sordera/genética , Pérdida Auditiva/genética , Neuronas/metabolismoRESUMEN
PURPOSE: Individual differences and variability in outcomes following cochlear implantation (CI) in patients with hearing loss remain significant unresolved clinical problems. Case reports of specific individuals allow for detailed examination of the information processing mechanisms underlying variability in outcomes. Two adults who displayed exceptionally good postoperative CI outcomes shortly after activation were administered a novel battery of auditory, speech recognition, and neurocognitive processing tests. METHOD: A case study of two adult CI recipients with postlingually acquired hearing loss who displayed excellent postoperative speech recognition scores within 3 months of initial activation. Preoperative City University of New York sentence testing and a postoperative battery of sensitive speech recognition tests were combined with auditory and visual neurocognitive information processing tests to uncover their strengths, weaknesses, and milestones. RESULTS: Preactivation CUNY auditory-only (A) scores were < 5% correct while the auditory + visual (A + V) scores were > 74%. Acoustically with their CIs, both participants' scores on speech recognition, environmental sound identification and speech in noise tests exceeded average CI users scores by 1-2 standard deviations. On nonacoustic visual measures of language and neurocognitive functioning, both participants achieved above average scores compared with normal hearing adults in vocabulary knowledge, rapid phonological coding of visually presented words and nonwords, verbal working memory, and executive functioning. CONCLUSIONS: Measures of multisensory (A + V) speech recognition and visual neurocognitive functioning were associated with excellent speech recognition outcomes in two postlingual adult CI recipients. These neurocognitive information processing domains may underlie the exceptional speech recognition performance of these two patients and offer new directions for research explaining variability in postimplant outcomes. Results further suggest that current clinical outcome measures should be expanded beyond the conventional speech recognition measures to include more sensitive robust tests of speech recognition as well as neurocognitive measures of working memory, vocabulary, lexical access, and executive functioning.
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Implantación Coclear , Implantes Cocleares , Sordera , Pérdida Auditiva , Percepción del Habla , Adulto , Sordera/cirugía , Pérdida Auditiva/cirugía , Humanos , Memoria a Corto Plazo/fisiología , Habla , Percepción del Habla/fisiologíaRESUMEN
OBJECTIVE: To determine root causes leading to misplaced cochlear implant (CI) electrode arrays and discuss their management using a case series and contemporary literature review. STUDY DESIGN: Retrospective case review and contemporary literature review. SETTING: Single tertiary-referral center. PATIENTS: Adult and pediatric patients who were diagnosed with a misplaced CI electrode array, excluding tip-foldover. Literature review was performed via a MEDLINE database PubMed query. All articles that described at least one case of extracochlear electrode array misplacement were included; partial insertions and extrusions were excluded. MAIN OUTCOME MEASURE: Extracochlear misplacement. RESULTS: A total of 61 cases were reviewed, including 4 new cases and 57 cases from 29 previously published articles. We discuss management of CI arrays in the carotid canal, the vestibule, and the modiolus. The rate of CI misplacement is estimated to be 0.49%. The most frequent location of misplacement CI was the vestibular system (50.8%) followed by the internal carotid canal (11.5%). Normal cochlear anatomy was noted on preoperative computer tomography (CT) in 59.0% of patients; abnormalities were noted in 27.9%. The most common technical issue was misidentification or poor visualization of the round window. CONCLUSION: CI electrode misplacement is rare but can cause postoperative complications and may result in permanently diminished CI performance and hearing outcomes, even after revision surgery. Failure to identify the round window is the most common reason for CI misplacement, despite most patients having normal cochlear anatomy. Surgical strategies to localize the round window and basal turn are imperative for proper electrode placement. LEVEL OF EVIDENCE: 4.
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Implantación Coclear , Implantes Cocleares , Adulto , Niño , Cóclea/diagnóstico por imagen , Cóclea/cirugía , Implantación Coclear/efectos adversos , Implantación Coclear/métodos , Implantes Cocleares/efectos adversos , Electrodos Implantados/efectos adversos , Humanos , Estudios RetrospectivosRESUMEN
OBJECTIVE: To compare differences in audiologic outcomes between slim modiolar electrode (SME) CI532 and slim lateral wall electrode (SLW) CI522 cochlear implant recipients. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic hospital. METHODS: Comparison of postoperative AzBio sentence scores in quiet (percentage correct) in adult cochlear implant recipients with SME or SLW matched for preoperative AzBio sentence scores in quiet and aided and unaided pure tone average. RESULTS: Patients with SLW (n = 52) and patients with SME (n = 37) had a similar mean (SD) age (62.0 [18.2] vs 62.6 [14.6] years, respectively), mean preoperative aided pure tone average (55.9 [20.4] vs 58.1 [16.4] dB; P = .59), and mean AzBio score (percentage correct, 11.1% [13.3%] vs 8.0% [11.5%]; P = .25). At last follow-up (SLW vs SME, 9.0 [2.9] vs 9.9 [2.6] months), postoperative mean AzBio scores in quiet were not significantly different (percentage correct, 70.8% [21.3%] vs 65.6% [24.5%]; P = .29), and data log usage was similar (12.9 [4.0] vs 11.3 [4.1] hours; P = .07). In patients with preoperative AzBio <10% correct, the 6-month mean AzBio scores were significantly better with SLW than SME (percentage correct, 70.6% [22.9%] vs 53.9% [30.3%]; P = .02). The intraoperative tip rollover rate was 8% for SME and 0% for SLW. CONCLUSIONS: Cochlear implantation with SLW and SME provides comparable improvement in audiologic functioning. SME does not exhibit superior speech recognition outcomes when compared with SLW.
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Implantación Coclear , Implantes Cocleares , Percepción del Habla , Adolescente , Adulto , Cóclea/cirugía , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The Centralized Otolaryngology Research Efforts (CORE) grant program coordinates research funding initiatives across the subspecialties of otolaryngology-head and neck surgery. Modeled after National Institutes of Health study sections, CORE grant review processes provide comprehensive reviews of scientific proposals. The organizational structure and grant review process support grant-writing skills, attention to study design, and other components of academic maturation toward securing external grants from the National Institutes of Health or other agencies. As a learning community and a catalyst for scientific advances, CORE evaluates clinical, translational, basic science, and health services research. Amid the societal reckoning around long-standing social injustices and health inequities, an important question is to what extent CORE engenders diversity, equity, and inclusion for the otolaryngology workforce. This commentary explores CORE's track record as a stepping-stone for promoting equity and innovation in the specialty. Such insights can help maximize opportunities for cultivating diverse leaders across the career continuum.
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Investigación Biomédica , Medicina , Otolaringología , Organización de la Financiación , Humanos , National Institutes of Health (U.S.) , Estados Unidos , Recursos HumanosRESUMEN
Sensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide significant benefit to many with SNHL, neither targets the cellular and molecular dysfunction that ultimately underlies SNHL. The successful development of more targeted approaches, such as growth factor, stem cell, and gene therapies, will require a yet deeper understanding of the underlying molecular mechanisms of human hearing and deafness. Unfortunately, the human inner ear cannot be biopsied without causing significant, irreversible damage to the hearing or balance organ. Thus, much of our current understanding of the cellular and molecular biology of human deafness, and of the human auditory system more broadly, has been inferred from observational and experimental studies in animal models, each of which has its own advantages and limitations. In 2013, researchers described a protocol for the generation of inner ear organoids from pluripotent stem cells (PSCs), which could serve as scalable, high-fidelity alternatives to animal models. Here, we discuss the advantages and limitations of conventional models of the human auditory system, describe the generation and characteristics of PSC-derived inner ear organoids, and discuss several strategies and recent attempts to model hereditary deafness in vitro. Finally, we suggest and discuss several focus areas for the further, intensive characterization of inner ear organoids and discuss the translational applications of these novel models of the human inner ear.
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Sordera , Oído Interno , Pérdida Auditiva Sensorineural , Sordera/genética , Sordera/patología , Pruebas Auditivas , Humanos , Organoides/patologíaRESUMEN
Background: Rates of spontaneous cerebrospinal fluid leak (sCSF) repairs have increased in recent decades in line with increases in obesity rates. Objectives: To determine if the national rate of sCSF leak has continued to rise in recent years and to identify associated risk factors utilizing a comprehensive national database comprising most academic medical centers. Methods: A retrospective review from 2009 to 2018 was performed using the Vizient Clinical Database (CDB) of 105 leading academic medical centers in the United States. Patients who underwent CSF leak repair in the CDB database using ICD-9 and ICD-10 diagnostic and procedure codes. Patients with epidural hematomas over the same time frame were used as a control. National rates of craniotomy for sCSF leak repair each quarter were assessed and sCSF leak patient characteristics (age, gender, obesity, hypertension, diabetes) were calculated. Results: The rate of craniotomy for all sCSF leak repairs increased by 10.2% annually from 2009 to 2015 (P < 0.0001). There was no statistically significant change in the rate of epidural hematomas over the same period. The rate of lateral sCSF leak repair increased on average by 10.4% annually from 2009 (218 cases/year) to 2018 (457 cases/year) (P < 0.0001). A statistically significant increase was observed across all regions of the United States (P ≤ 0.005). sCSF leak patients had an average (standard deviation) age of 55.0 (13.2) years and 67.2% were female. Obesity was the only demographic factors that increased significantly over time. Likely due to comorbid factors, Black patients comprise a disproportionately large percentage of lateral sCSF leak repair patients. Conclusions: The rate of craniotomy for spontaneous CSF leaks continues to rise by approximately 10% annually.
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While intraosseous cranial myxoma is a rare pathology, it is important for providers to be aware of it, as early diagnosis and treatment is imperative for prognosis. Long-term follow-up is needed as high rates of recurrence have been documented.